FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chen, KC Kim, JH Li, XM Lee, B AF Chen, Kevin C. Kim, Junho Li, Xinmei Lee, Byungkook TI Modeling recombinant immunotoxin efficacies in solid tumors SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE recombinant immunotoxin; solid tumor; binding site barriers; modeling; simulations ID SINGLE-CHAIN FV; DISULFIDE-STABILIZED FV; NONSPECIFIC ANIMAL TOXICITY; IMPROVED ANTIGEN-BINDING; MONOCLONAL-ANTIBODY K1; ANTITUMOR-ACTIVITY; DIPHTHERIA-TOXIN; PSEUDOMONAS EXOTOXIN; COMPLETE REGRESSION; CYTOTOXIC ACTIVITY AB Effectiveness of cancer therapy is improved by the use of recombinant immunotoxins (RITs) that target membrane proteins unique to malignant tumor cells. Although RIT antitumor activity in vivo can always be improved with larger doses, clinical restriction on the dose toleration makes it critical to explore how RIT antitumor activity can be maximized without resorting to dose elevation. In this work, a mathematical model was developed to explore functional correlations between the properties of several recombinant immunotoxins and their antitumor efficacies in vivo. Simulations were compared with experimental data of human tumor xenografts grown on nude mice to assess parameters critical to optimal antitumor activity. We dissected out or held constant as many parameters of the model as possible to investigate the effect of the remaining parameters on the behavior of the system as a whole. Empirical correlations between immunotoxin binding affinity and the target binding site density were obtained for several recombinant immunotoxins targeting either human A431 carcinoma or CD46 Burkitt's lymphoma. Simulations reinforced the idea of binding site barrier for drug diffusion and suggested that optimal antitumor activity was achieved when the binding affinity is logarithmically dependent on the target binding site density. C1 [Chen, Kevin C.; Kim, Junho; Li, Xinmei] Florida State Univ, FAMU FSU Coll Engn, Dept Biomed Engn, Tallahassee, FL 32310 USA. [Li, Xinmei] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Lee, Byungkook] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chen, KC (reprint author), Florida State Univ, FAMU FSU Coll Engn, Dept Biomed Engn, Tallahassee, FL 32310 USA. EM kevinchen@eng.fsu.edu NR 59 TC 7 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAR PY 2008 VL 36 IS 3 BP 486 EP 512 DI 10.1007/s10439-007-9425-4 PG 27 WC Engineering, Biomedical SC Engineering GA 261AC UT WOS:000253050500014 PM 18183487 ER PT J AU Dennis, LK Lowe, JB Lynch, CF Alavanja, MCR AF Dennis, Leslie K. Lowe, John B. Lynch, Charles F. Alavanja, Michael C. R. TI Cutaneous melanoma and obesity in the Agricultural Health Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE melanoma; sun sensitivity; obesity; farmers; body mass index; body surface area; Lentigo Maligna; Agricultural Health Study ID BODY-SURFACE AREA; MALIGNANT-MELANOMA; SUN EXPOSURE; RISK-FACTORS; UNITED-STATES; PIGMENTARY TRAITS; SUNLIGHT-EXPOSURE; WASHINGTON-STATE; WOMEN; INTERMITTENT AB PURPOSE: To describe the risk of cutaneous melanoma in the Agricultural Health Study (AHS), a cohort of pesticide applicators and their spouses, according to baseline characteristics related to obesity along with sun exposure and sun sensitivity. METHODS: The AHS cohort was enrolled in Iowa and North Carolina during 1993-1997 and followed up through 2003 for cancer incidence. We identified 315 cases of cutaneous melanoma, which reduced to 168 incident cases among subjects reporting height, weight, sun sensitivity, and sun exposure information (on the spouse questionnaire or take-home applicator questionnaire; N = 44,086). Unconditional multiple logistic regression models were used to obtain adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: The results were consistent with those of prior studies of melanoma that indicate an association with measures of sun sensitivity. The highest category of body surface area (BSA; OR = 2.6; 95% CI, 1.5-4.4) and body mass index (BMI; OR = 2.5; 95% CI, 1.5-4.3) at age 20 were significantly associated with melanoma. There was some evidence for an association with BSA, but not BMI, at enrollment. CONCLUSIONS: Obesity was associated with an increased risk of melanoma, indicating strategies to control obesity may result in risk reduction for melanoma. C1 [Dennis, Leslie K.; Lowe, John B.; Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA 52242 USA. [Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Dennis, LK (reprint author), Univ Iowa, Dept Epidemiol, Coll Publ Hlth, 200 Hawkins Dr,C21H-GH, Iowa City, IA 52242 USA. EM leslie-dennis@uiowa.edu OI Lowe, John/0000-0003-1222-2295 FU NCI NIH HHS [5K07CA104556, K07 CA104556, K07 CA104556-03] NR 45 TC 29 Z9 29 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 2008 VL 18 IS 3 BP 214 EP 221 DI 10.1016/j.annepidem.2007.09.003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 270DB UT WOS:000253699100007 PM 18280921 ER PT J AU Chaturvedi, AK Mbulaiteye, SM Engels, EA AF Chaturvedi, Anil K. Mbulaiteye, Sam M. Engels, Eric A. TI Underestimation of relative risks by standardized incidence ratios for AIDS-related cancers SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE HIV; AIDS; Kaposi sarcoma; non-Hodgkin lymphoma; cervical cancer; SIR; RR; bias ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AFRICA; SPECTRUM; POPULATION; EPIDEMIC; PEOPLE; UGANDA; VIRUS; BIAS AB PURPOSE: Registry-based studies provide valuable data regarding cancer risk among people with HIV/AIDS (PWHA). Such studies utilize the standardized incidence ratio (SIR) to estimate the relative risk (RR), an etiologically relevant measure. However, SIR may underestimate RR when HIV/AIDS prevalence in the general population or RR is high. We quantified the extent of this underestimation for 3 AIDS-related cancers: Kaposi sarcoma (KS), central nervous system non-Hodgkin lymphoma (CNS NHL) and cervical cancer. METHODS: We used data on cancer risk among PWHA from the U.S. HIV/AIDS Cancer Match Study. SIRs were compared with RRs estimated using two methods: (1) SIRs calculated using pre-AIDS era (19731979) cancer incidence rates (SIRpre-AIDS) and (2) SIRs calculated after subtraction of cancers known to be among PWHA from general population rates (SIRexclusion). RESULTS: For KS and CNS NHL, SIRs (117.8 and 133.9, respectively) calculated using overall general population rates substantially underestimated both SIRpre-AIDS (19,778 and 3,612, respectively) and SIRexclusion (657.7 and 536.4, respectively). In contrast, the extent of underestimation was negligible for cervical cancer (SIR = 4.9 vs. SIRexclusion = 5.1). For KS and CNS NHL, SIRs were higher in females than in males. However, SIRpre-AlDs and SIRexclusion estimates were more similar, indicating that SIR differences artifactually reflect differences in HIV/AIDS prevalence between males and females. For KS and CNS NHL, trends across calendar time were weaker in SIRs than in SIRpre-AlDs and SIRexclusion. CONCLUSION: For KS and CNS NHL, SIRs substantially underestimate RRs. This underestimation arises from the exceptionally high relative risk of KS and CNS NHL among PWHA. SIRs must be interpreted cautiously when HIV/AIDS prevalence is high or varies across groups of interest. C1 [Chaturvedi, Anil K.; Mbulaiteye, Sam M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD 20852 USA. RP Chaturvedi, AK (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 NR 22 TC 22 Z9 22 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 2008 VL 18 IS 3 BP 230 EP 234 DI 10.1016/j.annepidem.2007.10.005 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 270DB UT WOS:000253699100009 PM 18083545 ER PT J AU Awwad, RT Do, K Stevenson, H Fu, SW Lo-Coco, F Costello, M Campbell, CL Berg, PE AF Awwad, Rania T. Do, Khanh Stevenson, Holly Fu, Sidney W. Lo-Coco, Francesco Costello, Maura Campbell, Cassandra L. Berg, Patricia E. TI Overexpression of BP1, a homeobox gene, is associated with resistance to all-trans retinoic acid in acute promyelocytic leukemia cells SO ANNALS OF HEMATOLOGY LA English DT Article DE acute promyelocytic leukemia; all-trans retinoic acid; homeobox; BP1 ID PML-RAR-ALPHA; BETA-GLOBIN GENE; REAL-TIME PCR; DOWN-REGULATION; DIFFERENTIATION; EXPRESSION; NB4; HEMATOPOIESIS; APOPTOSIS; LINE AB BP1, a homeobox gene, is overexpressed in the bone marrow of 63% of acute myeloid leukemia patients. In this study, we compared the growth-inhibitory and cyto-differentiating activities of all-trans retinoic acid (ATRA) in NB4 (ATRA-responsive) and R4 (ATRA-resistant) acute promyelocytic leukemia (APL) cells relative to BP1 levels. Expression of two oncogenes, bcl-2 and c-myc, was also assessed. NB4 and R4 cells express BP1, bcl-2, and c-myc; the expression of all three genes was repressed after ATRA treatment of NB4 cells but not R4 cells. To determine whether BP1 overexpression affects sensitivity to ATRA, NB4 cells were transfected with a BP1-expressing plasmid and treated with ATRA. In cells overexpressing BP1: (1) proliferation was no longer inhibited; (2) differentiation was reduced two- to threefold; (3) c-myc was no longer repressed. These and other data suggest that BP1 may regulate bcl-2 and c-myc expression. Clinically, BP1 levels were elevated in all pretreatment APL patients tested, while BP1 expression was decreased in 91% of patients after combined ATRA and chemotherapy treatment. Two patients underwent disease relapse during follow-up; one patient exhibited a 42-fold increase in BP1 expression, while the other showed no change. This suggests that BP1 may be part of a pathway involved in resistance to therapy. Taken together, our data suggest that BP1 is a potential therapeutic target in APL. C1 [Awwad, Rania T.; Do, Khanh; Stevenson, Holly; Costello, Maura; Campbell, Cassandra L.; Berg, Patricia E.] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Do, Khanh] George Washington Univ, Sch Med, Washington, DC 20037 USA. [Stevenson, Holly] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lo-Coco, Francesco] Univ Roma Tor Vergata, Dept Biopathol, Rome, Italy. RP Berg, PE (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Ross Bldg,Room 533,2300 Eye St, Washington, DC 20037 USA. EM bcmpeb@gwumc.edu NR 33 TC 12 Z9 13 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 EI 1432-0584 J9 ANN HEMATOL JI Ann. Hematol. PD MAR PY 2008 VL 87 IS 3 BP 195 EP 203 DI 10.1007/s00277-007-0402-7 PG 9 WC Hematology SC Hematology GA 253SW UT WOS:000252538900004 PM 18026954 ER PT J AU Norton, JA Venzon, DJ Berna, MJ Alexander, HR Fraker, DL Libutti, SK Marx, SJ Gibril, F Jensen, RT AF Norton, Jeffrey A. Venzon, David J. Berna, Marc J. Alexander, H. R. Fraker, Douglas L. Libutti, Stephen K. Marx, Stephen J. Gibril, Fathia Jensen, Robert T. TI Prospective study of surgery for primary hyperparathyroidism (HPT) in multiple endocrine neoplasia-type 1 and Zollinger-Ellison syndrome - Long-term outcome of 6 more virulent form of HPT SO ANNALS OF SURGERY LA English DT Article ID GASTRIC-ACID SECRETION; INSTITUTES-OF-HEALTH; DUODX AFFECT RATE; SERUM GASTRIN; SURGICAL-MANAGEMENT; SUBTOTAL PARATHYROIDECTOMY; I SYNDROME; LIVER METASTASES; LIMITED DISEASE; TYPE-1 AB Background: Primary hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) patients with Zollinger-Ellison syndrome (ZES) is caused by parathyroid hyperplasia. Surgery for parathyroid hyperplasia is tricky and difficult. Long-term outcome in ZES/MEN1/HPT is not well known. Methods: Eighty-four consecutive patients (49 F/35 M) with ZES/ MEN1/HPT underwent initial parathyroidectomy (PTX) and were followed at 1- to 3-year intervals. Results: Age at PTX was 36 +/- 2 years. Mean follow-up was 17 I years. Before PTX, mean Ca = 2.8 mmol/L (normal level (nI <2.5), PTHi = 243 pg/mL (nl <65), and gastrin = 6950 pg/mL (nl < 100). Sixty-one percent had nephrolithiasis. Each patient had parathyroid hyperplasia. Fifty-eight percent of patients had 4 parathyroid glands identified. Nine of 84 (11%) had 4 glands removed with immediate autograft, 40/84 (47%) 3 to 3.5 glands, whereas 35/84 (42%) <3 glands removed. Persistent/recurrent HPT occurred in 42%/48% of patients with <3 glands, 12%/44% with 3 to 3.5 glands, and 0%/55% with 4 glands removed. Hypoparathyroidism occurred in 3%, 10%, and 22%, respectively. The disease-free interval after surgery was significantly longer if >3 glands were removed. After surgery to correct the HPT, each biochemical parameter of ZES was improved and 20% of patients no longer had laboratory evidence of ZES. Conclusions: HPT/MEN1/ZES is a severe form of parathyroid hyperplasia with a high rate of nephrolithiasis, persistent and recurrent HPT. Surgery to correct the hypercalcemia significantly ameliorates the ZES. Removal of less than 3.5 glands has an unacceptably high incidence of persistent HPT (42%), whereas 4-gland resection and transplant has a high rate of permanent hypoparathyroidism (22%). More than 3-gland resection has a longer disease-free interval. The surgical procedure of choice for patients with HPT/MEN1/ZES is 3.5-gland parathyroidectomy. Careful long-term follow-up is necessary as a significant proportion will develop recurrent HPT. C1 [Norton, Jeffrey A.] Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Berna, Marc J.; Gibril, Fathia; Jensen, Robert T.] NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA. [Alexander, H. R.] Univ Maryland, Dept Surg, Baltimore, MD 21201 USA. [Fraker, Douglas L.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Libutti, Stephen K.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Marx, Stephen J.] NIH, Metab Dis Branch, Bethesda, MD USA. RP Norton, JA (reprint author), Stanford Univ, Med Ctr, Dept Surg, 300 Pasteur Dr,Room H3591, Stanford, CA 94305 USA. EM janorton@stanford.edu FU Intramural NIH HHS [Z01 DK053200-16, Z01 DK053215-01] NR 76 TC 47 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2008 VL 247 IS 3 BP 501 EP 510 DI 10.1097/SLA.0b013e31815efda5 PG 10 WC Surgery SC Surgery GA 266LH UT WOS:000253436200016 PM 18376196 ER PT J AU Miao, N Pingpank, JF Alexander, HR Steinberg, SM Beresneva, T Quezado, ZMN AF Miao, Ning Pingpank, James F. Alexander, H. Richard Steinberg, Seth M. Beresneva, Tatiana Quezado, Zenaide M. N. TI Percutaneous hepatic perfusion in patients with metastatic liver cancer: Anesthetic, hemodynamic, and metabolic considerations SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE hepatic perfusion; liver; metastasis; regional therapy; melphalan ID PHASE-I; CHEMOTHERAPY; INFUSION AB Background: Percutaneous hepatic perfusion (PHP), a regional cancer therapy, entails insertion of percutaneous catheters to isolate hepatic vasculature and enable simultaneous hepatic venous hemofiltration of high-dose chemotherapy. PHP has been shown to be safe and to benefit some patients with liver metastases. Methods: We examined hemodynamic and metabolic changes as well as anesthetic implications during PHP in patients with metastatic liver cancer enrolled in clinical trials of escalating doses of melphalan between 2001 and 2006. Results: Fifty-one patients underwent 136 PHPs with general anesthesia. Diagnoses included neuroendocrine tumors, melanoma, and metastatic carcinomas. Based upon available data derived from all procedures, incorporating multiple procedures per patient, after occlusion of the inferior vena cava and during hepatic perfusion, there were decreases in mean arterial (-15.4 +/- 1 and -7.4 +/- 1 mmHg, respectively) and central venous pressure (-5.4 +/- 0.3 and -5.6 +/- 0.3 mmHg) and increases in heart rate (11 +/- 1 and 13.4 +/- 0.9 bpm) (all p < 0.0001) which resolved with completion of the procedure. During vascular isolation, patients received norepinephrine (13% of procedures), phenylephrine (70%), or both agents (11%). During hepatic perfusion with melphalan, compared to baseline, there were decreases in pH (-0.09 +/- 0.01) and bicarbonate (-3.3 +/- 0.6 mmol/L) (both p < 0.0001) and, upon completion of procedure, increases (2.6 +/- 0.4 mmol/L) in bicarbonate, compared to values during hepatic perfusion (p < 0.0001). Conclusions: PHP therapy can be associated with transient but significant hemodynamic and metabolic perturbations. In order to assure patient comfort and facilitate timely diagnosis and treatment of associated hemodynamic and metabolic changes, we favor administration of general anesthesia, rather than sedation, for patients undergoing PHP. C1 [Miao, Ning; Quezado, Zenaide M. N.] NIH, Ctr Clin, Dept Anesthesia & Surg Serv, Bethesda, MD 20892 USA. [Pingpank, James F.; Alexander, H. Richard; Beresneva, Tatiana] Natl Canc Inst, NIH, Surg Branch, Bethesda, MD 20892 USA. [Steinberg, Seth M.] Natl Canc Inst, NIH, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Quezado, ZMN (reprint author), NIH, Ctr Clin, Dept Anesthesia & Surg Serv, Bldg 10, Bethesda, MD 20892 USA. EM zquezado@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS NR 9 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2008 VL 15 IS 3 BP 815 EP 823 DI 10.1245/s10434-007-9781-1 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 260DJ UT WOS:000252990700022 PM 18180999 ER PT J AU Christodoulou, MI Kapsogeorgou, EK Moutsopoulos, NM Moutsopoulos, HM AF Christodoulou, M. I. Kapsogeorgou, E. K. Moutsopoulos, N. M. Moutsopoulos, H. M. TI FOXP3+T regulatory cells (Tregs) in the autoimmune lesions of Sjogren's syndrome (SS): Correlation with the number of infiltrating dendritic cells and macrophages SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 28th European Workshop for Rheumatology Research CY FEB 28-MAR 01, 2008 CL Toulouse, FRANCE C1 [Christodoulou, M. I.; Kapsogeorgou, E. K.; Moutsopoulos, H. M.] Natl Univ Athens, Sch Med, Dept Pathophysiol, Athens, Greece. [Moutsopoulos, N. M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immunity Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2008 VL 67 SU 1 MA 035 BP A12 EP A13 PG 2 WC Rheumatology SC Rheumatology GA 266NP UT WOS:000253443300036 ER PT J AU Chu, Z Chen, JS Liau, CT Wang, HM Lin, YC Yang, MH Chen, PM Gardner, ER Figg, WD Sparreboom, A AF Chu, Zyting Chen, Jen-Shi Liau, Chi-Ting Wang, Hung-Ming Lin, Yung-Chang Yang, Muh-Hwa Chen, Po-Min Gardner, Erin R. Figg, William D. Sparreboom, Alex TI Oral bioavailability of a novel paclitaxel formulation (Genetaxyl) administered with cyclosporin A in cancer patients SO ANTI-CANCER DRUGS LA English DT Article DE cremophor; cyclosporin A; formulation; oral paclitaxel; pharmacokinetics ID CELL LUNG-CANCER; CREMOPHOR-EL; CLINICAL PHARMACOKINETICS; SYSTEMIC EXPOSURE; 1ST-LINE THERAPY; P-GLYCOPROTEIN; BREAST-CANCER; HUMAN PLASMA; PHASE-II; RESISTANCE AB The formulation excipient Cremophor EL (CrEL) is known to limit the absorption of oral paclitaxel given together with cyclosporin A. We hypothesized that the use of oral Genetaxyl, a paclitaxel formulation containing only 20% CrEL would have an improved oral bioavailability. Cohorts of six patients were treated with oral Genetaxyl at a dose of 60,120, or 180 mg/m(2) and 10mg/kg of oral cyclosporin A in cycle 1. In cycle 2, patients received intravenous (i.v.) Genetaxyl (1175 mg/m(2), 3-h infusion). Three additional patients received one dose of generic i.v. paclitaxel (Genaxol, containing 50% CrEL; 175 mg/m(2), 3-h infusion). The median area under the plasma concentration-time curve (AUC) and peak concentration of total paclitaxel following i.v. Genetaxyl were lower than those for i.v. Genaxol, as a result of significantly increased clearance (P=0.017), and the AUC ratio for unbound to total paclitaxel for i.v. Genetaxyl was about two times higher than that for i.v. Genaxol (P=0.0077). After oral administration of Genetaxyl at doses of 60,120, and 180 mg/m(2), the median total paclitaxel AUCs were 1.29, 1.60, and 1.85 mu g x h/ml, respectively, suggesting a less than proportional increase in systemic exposure with increasing doses. The corresponding median values for the apparent bioavailability of oral Genetaxyl were similar when compared with i.v. Genetaxyl, when calculated either on the basis of data for total paclitaxel (30.1%) or unbound paclitaxel (30.6%). C1 [Chu, Zyting] China Med Univ, Dept Med Res, Taichung, Taiwan. [Chen, Jen-Shi; Liau, Chi-Ting; Wang, Hung-Ming; Lin, Yung-Chang] Chang Gung Mem Hosp, Div Hematol Oncol, Dept Internal Med, Taipei 10591, Taiwan. [Chen, Jen-Shi; Liau, Chi-Ting; Wang, Hung-Ming; Lin, Yung-Chang] Chang Gung Univ, Coll Med, Taipei, Taiwan. [Yang, Muh-Hwa; Chen, Po-Min] Taipei Vet Gen Hosp, Div Hematol, Dept Med, Taipei, Taiwan. [Yang, Muh-Hwa; Chen, Po-Min] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan. [Gardner, Erin R.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Figg, William D.; Sparreboom, Alex] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Sparreboom, A (reprint author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, DTRC, Mail Stop 314,RoomD1034B,332 N Lauderdale, Memphis, TN 38105 USA. EM alex.sparreboom@stjude.org RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [NIH0011335962, Z01 BC010548-02]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 30 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD MAR PY 2008 VL 19 IS 3 BP 275 EP 281 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 264ZR UT WOS:000253329400005 PM 18510173 ER PT J AU Montero, CI Stock, F Murray, PR AF Montero, Clemente I. Stock, Frida Murray, Patrick R. TI Mechanisms of resistance to daptomycin in Enterococcus faecium SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; STAPHYLOCOCCUS-AUREUS; REDUCED SUSCEPTIBILITY; VANCOMYCIN RESISTANCE; IDENTIFICATION; ENDOCARDITIS; BACTEREMIA; LEVEL; PCR AB In this study, we investigated the clonal emergence of daptomycin-resistant Enterococcus faecium, strains isolated from a patient with leukocyte adhesion deficiency syndrome. The resistance mechanism in these strains is independent of either equivalent point mutations previously described for Staphylococcus aureus or daptomycin inactivation mechanisms identified in soil bacteria. C1 [Montero, Clemente I.; Stock, Frida; Murray, Patrick R.] US Dept Hlth & Human Serv, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,NIH, Bethesda, MD 20892 USA. RP Montero, CI (reprint author), Dept Lab Med, Clin Ctr Bldg 10,Room 2C385, Bethesda, MD 20892 USA. EM monteroc@cc.nih.gov NR 26 TC 39 Z9 39 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2008 VL 52 IS 3 BP 1167 EP 1170 DI 10.1128/AAC.00774-07 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 268BS UT WOS:000253553500053 PM 18180351 ER PT J AU Mancini, AJ Lawley, LP Uzel, G AF Mancini, Anthony J. Lawley, Leslie P. Uzel, Gulbu TI X-linked ectodermal dysplasia with immunodeficiency caused by NEMO mutation - Early recognition and diagnosis SO ARCHIVES OF DERMATOLOGY LA English DT Article ID B ESSENTIAL MODULATOR; INCONTINENTIA PIGMENTI; IMMUNE-DEFICIENCY; HUMAN-DISEASE; DISORDERS; CYTOTOXICITY; ACTIVATION; GENE AB Background: X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is described in patients with hypomophic mutations in IKBKG (the inhibitory kappa B kinase gamma gene), which encodes nuclear factor kappa B essential modulator (NEMO). Features include hypohidrosis, dental anomalies, alopecia, and immunodeficiency. Boys with NEMO mutations often present with serious infections, but the NEMO mutations are rarely diagnosed early in infancy. Cutaneous features in these patients are poorly elucidated. Observations: A 12-week-old male infant presented with a recalcitrant skin eruption, intertrigo, atopiclike dermatitis, and erythroderma. Alopecia, frontal bossing, and periorbital wrinkling were present, and family history revealed incontinentia pigmenti in his mother. Laboratory evaluation revealed leukocytosis with eosinophilia, low IgG and IgM levels, and absent IgA. Flow cytometry revealed lymphocytosis with elevated CD3(+) and CD4(+) counts and low levels of natural killer cells. Amplification and sequencing of IKBKG revealed insertion of cytosine at nucleotide 1167 (1167-1168insC) in exon 10, with frameshift mutation in the zinc-finger domain. Peripheral blood stem cell transplantation led to initial engraftment and improvement in his skin findings, but his engrafted cell counts diminished, and a second stem cell transplantation was planned. Conclusions: Mutations in NEMO should be considered in male infants with recalcitrant seborrheic or atopic dermatitislike eruptions and intertrigo, especially when features of ectodermal dysplasia are present. Early recognition and diagnosis are desirable, prior to the onset of manifestations of immunodeficiency. C1 [Mancini, Anthony J.; Lawley, Leslie P.; Uzel, Gulbu] Childrens Mem Hosp, Div Dermatol, Chicago, IL 60614 USA. [Mancini, Anthony J.; Lawley, Leslie P.; Uzel, Gulbu] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA. [Mancini, Anthony J.; Lawley, Leslie P.; Uzel, Gulbu] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Uzel, Gulbu] NIAID, Natl Inst Hlth, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Mancini, AJ (reprint author), Childrens Mem Hosp, Div Dermatol, 2300 Childrens Pl 107, Chicago, IL 60614 USA. EM amancini@northwestern.edu NR 24 TC 27 Z9 28 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2008 VL 144 IS 3 BP 342 EP 346 DI 10.1001/archderm.144.3.342 PG 5 WC Dermatology SC Dermatology GA 275AU UT WOS:000254045100007 PM 18347290 ER PT J AU Farasat, S Aksentijevich, I Toro, JR AF Farasat, Sharifeh Aksentijevich, Ivona Toro, Jorge R. TI Autoinflammatory diseases - Clinical and genetic advances SO ARCHIVES OF DERMATOLOGY LA English DT Review ID FAMILIAL MEDITERRANEAN-FEVER; MULTISYSTEM INFLAMMATORY DISEASE; MUCKLE-WELLS-SYNDROME; PERIODIC SYNDROME TRAPS; HYPER-IGD SYNDROME; NF-KAPPA-B; RECURRENT HEREDITARY POLYSEROSITIS; HYPERIMMUNOGLOBULINEMIA-D SYNDROME; ENCODING MEVALONATE KINASE; PAPA SYNDROME AB We conducted a literature review to investigate the recent advances in genetics, molecular biology, clinical manifestations, and therapy of 7 inherited diseases that are characterized by seemingly unprovoked inflammation. These autoinflammatory dis eases include familial Mediterranean fever; tumor necrosis factor receptor-associated periodic syndrome; hyperimmunoglobulinemia D with periodic fever syndrome; pyogenic arthritis, pyoderma gangrenosum, and acne syndrome; and the 3 cryopyrinopathies: neonatal-onset multisystem inflammatory disease/chronic infantile neurologic cutaneous and arthropathy syndrome, familial cold autoinflammatory syndrome, and Muckle-Wells syndrome. Recent identification of the susceptibility genes for autoinflammatory diseases has broadened the clinical spectrum as well as the molecular basis of these diseases. The cryopyrinopathies represent a continuum of diseases associated with mutations in the cold-induced autoinflammatory syndrome 1 (CLAS1) gene that encodes cryopyrin. Cryopyrin and pyrin (protein mutated in familial Mediterranean fever) belong to the family of PYRIN domain-containing proteins. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome is associated with mutations in the gene that encodes for CD2-binding protein 1 (CD2BP1), which binds pyrin. Recent studies have shown that activation of the interleukin 1 beta pathway is a common mechanism in the pathogenesis of autoinflammatory diseases, further unifying these diseases. Recent advances in genetics and molecular biology have advanced our understanding of the pathogenesis of autoinflammatory diseases. Understanding autoinflammatory diseases will further our knowledge of cutaneous as well as systemic inflammation. Anakinra, a recombinant human interleukin 1 receptor antagonist, is a promising new biologic agent for the treatment of cryopyrinopathies as well other autoinflammatory diseases, such as tumor necrosis factor receptor-associated periodic syndrome and hyperimmunoglobulinemia D with periodic fever syndrome. C1 [Farasat, Sharifeh; Toro, Jorge R.] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Brach, Rockville, MD USA. [Aksentijevich, Ivona] NIAMSD, Natl Inst Hlth, Genet & Genom Branch, Bethesda, MD 20892 USA. RP Toro, JR (reprint author), NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Brach, 6120 Execut Blvd,Execut Pl S,Room 7012, Rockville, MD USA. EM toroj@mail.nih.gov FU Intramural NIH HHS NR 153 TC 66 Z9 69 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2008 VL 144 IS 3 BP 392 EP 402 PG 11 WC Dermatology SC Dermatology GA 275AU UT WOS:000254045100015 PM 18347298 ER PT J AU Hardy, J Singleton, A AF Hardy, John Singleton, Andrew TI The HapMap - Charting a course for genetic discovery in neurological diseases SO ARCHIVES OF NEUROLOGY LA English DT Review ID GENOME-WIDE ASSOCIATION; AMYOTROPHIC-LATERAL-SCLEROSIS; ONSET ALZHEIMERS-DISEASE; RISK LOCI; REVEALS; POLYMORPHISMS; HAPLOTYPE; RELEASE; APOE AB Whole-genome association analyses have begun to yield confirmed findings for genetic risk variants for complex disease. As the first reports of its application to neurological disease are described, we review this progress, explain the principles of the analysis, and discuss what the future is likely to be in this exciting area. C1 [Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London WC1 3BG, England. [Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1 3BG, England. [Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1 3BG, England. EM j.hardy@ionucl.ac.uk RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 FU Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 29 TC 3 Z9 6 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2008 VL 65 IS 3 BP 319 EP 321 DI 10.1001/archneur.65.3.319 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 272TD UT WOS:000253881900004 PM 18332243 ER PT J AU Mata, IF Samii, A Schneer, SH Roberts, JW Griffith, A Leis, BC Schellenberg, GD Sidransky, E Bird, TD Leverenz, JB Tsuang, D Zabetian, CP AF Mata, Ignacio F. Samii, Ali Schneer, Seth H. Roberts, John W. Griffith, Alida Leis, Berta C. Schellenberg, Gerard D. Sidransky, Ellen Bird, Thomas D. Leverenz, James B. Tsuang, Debby Zabetian, Cyrus P. TI Glucocerebrosidase gene mutations - A risk factor for Lewy body disorders SO ARCHIVES OF NEUROLOGY LA English DT Article ID PARKINSONS-DISEASE; GAUCHER-DISEASE; ASHKENAZI-JEWS; ASSOCIATION AB Background: Mutations in the glucocerebrosidase (GBA) gene have been reported to modify risk for Parkinson disease (PD) and dementia with Lewy bodies (DLB). However, these findings have not been consistently replicated, and most studies have had substantial methodological shortcomings. Objective: To better assess the role of GBA variants in altering risk for Lewy body disorders. Design: Case-control study. Setting: Four movement disorder clinics in the Seattle, Washington, area. Participants: Seven hundred twenty-one patients with PD, 554 healthy control subjects, and 57 patients with DLB. Main Outcome Measures: Disease status and presence or absence of the 2 most common GBA mutations (N370S and L444P). Results: We observed a significantly higher heterozygote frequency for the 2 mutations in patients with PD (2.9%; P<.001) and those with DLB (3.5%; P=.045) compared with control subjects (0.4%). Conclusion: Our findings suggest that GBA mutations exert a large effect on susceptibility for Lewy body disorders at the individual level but are associated with a modest (approximately 3%) population-attributable risk in individuals of European ancestry. C1 [Mata, Ignacio F.; Schellenberg, Gerard D.; Bird, Thomas D.; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. [Leverenz, James B.; Tsuang, Debby; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Samii, Ali; Leverenz, James B.; Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Mata, Ignacio F.; Samii, Ali; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Roberts, John W.] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Schellenberg, Gerard D.; Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA USA. [Schellenberg, Gerard D.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Leverenz, James B.; Tsuang, Debby] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Schneer, Seth H.] Oberlin Coll, Dept Biol, Oberlin, OH 44074 USA. [Griffith, Alida; Leis, Berta C.] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [U01 AG016976]; NINDS NIH HHS [K08 NS044138-05, K08 NS044138] NR 20 TC 98 Z9 101 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2008 VL 65 IS 3 BP 379 EP 382 DI 10.1001/archneurol.2007.68 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 272TD UT WOS:000253881900013 PM 18332251 ER PT J AU Brooks, BP MacDonald, IM Tumminia, SJ Smaoui, N Blain, D Nezhuvingal, AA Sieving, PA AF Brooks, Brian P. MacDonald, Ian M. Tumminia, Santa J. Smaoui, Nizar Blain, Delphine Nezhuvingal, Ajaina A. Sieving, Paul A. TI Genomics in the era of molecular ophthalmology - Reflections on the National Ophthalmic Disease Genotyping Network (eyeGENE) SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID MACULAR DEGENERATION RP Brooks, BP (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, Bldg 10,Room 10N226,MSC 1860,10 Ctr Dr, Bethesda, MD 20892 USA. EM brooksb@mail.nih.gov OI MacDonald, Ian/0000-0001-7472-8385 FU Intramural NIH HHS [Z99 EY999999] NR 14 TC 9 Z9 9 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2008 VL 126 IS 3 BP 424 EP 425 DI 10.1001/archopht.126.3.424 PG 2 WC Ophthalmology SC Ophthalmology GA 272TE UT WOS:000253882000019 PM 18332328 ER PT J AU Link, RP AF Link, Rebecca P. TI National heart, lung, and blood institute programs for deep vein thrombosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article C1 [Link, Rebecca P.] NIH, NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Link, RP (reprint author), NIH, NHLBI, Div Blood Dis & Resources, Bldg 10, Bethesda, MD 20892 USA. EM linkr@nhlbi.nih.gov NR 2 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2008 VL 28 IS 3 BP 392 EP 393 DI 10.1161/ATVBAHA.108.162461 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 266IZ UT WOS:000253429000006 PM 18296595 ER PT J AU Mellemkjaer, L Pfeiffer, RM Engels, EA Gridley, G Wheeler, W Hemminki, K Olsen, JH Dreyer, L Linet, MS Goldin, LR Landgren, O AF Mellemkjaer, Lene Pfeiffer, Ruth M. Engels, Eric A. Gridley, Gloria Wheeler, William Hemminki, Kari Olsen, Jorgen H. Dreyer, Lene Linet, Martha S. Goldin, Lynn R. Landgren, Ola TI Autoimmune disease in individuals and close family members and susceptibility to non-Hodgkin's lymphoma SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY-BOWEL-DISEASE; PRIMARY SJOGRENS-SYNDROME; POPULATION-BASED COHORT; CANCER-RISK; RHEUMATOID-ARTHRITIS; MALIGNANT-LYMPHOMAS; HEMATOPOIETIC CANCER; MEDICAL HISTORY; CROHNS-DISEASE AB Objective. Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjogren's syndrome have been consistently associated with an increased risk of non-Hodgkin's lymphoma (NHL). This study was initiated to evaluate the risks of NHL associated with a personal or family history of a wide range of autoimmune diseases. Methods. A population-based case-control study was conducted that included 24,728 NHL patients in Denmark (years 1977-1997) and Sweden (years 19641998) and 55,632 controls. Using univariate logistic and hierarchical regression models, we determined odds ratios (ORs) of NHL associated with a personal history of hospital-diagnosed autoimmune conditions. Risks of NHL associated with a family history of the same autoimmune conditions were assessed. by similar regression analyses that included 25,941 NHL patients and 58,551 controls. Results. A personal history of systemic autoimmune diseases (RA, SLE, Sjogren's syndrome, systemic sclerosis) was clearly linked with NHL risk, both for individual conditions (hierarchical odds ratios [ORh] ranged from 1.6 to 5.4) and as a group (ORh 2.64 [95% confidence interval (95% CI) 1.72-4.07]). In contrast a family history of systemic autoimmune diseases was modestly and nonsignificantly associated with NHL (ORh 1.31 [95% CI 0.85-2.03]). An increased risk of NHL was found for a personal history of 5 nonsystemic autoimmune conditions (autoimmune hemolytic anemia, Hashimoto thyroiditis, Crohn's disease, psoriasis, and sarcoidosis) (ORh ranged from 1.5 to 2.6) of 27 conditions examined. Conclusion. Overall, our results demonstrate a strong relationship of personal history of systemic autoimmune diseases with NHL risk and suggest that shared susceptibility may explain a very small fraction of this increase, at best. Positive associations were found for a personal history of some, though far from all, nonsystemic autoimmune conditions. C1 [Mellemkjaer, Lene; Olsen, Jorgen H.] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. [Pfeiffer, Ruth M.; Engels, Eric A.; Gridley, Gloria; Linet, Martha S.; Goldin, Lynn R.; Landgren, Ola] Natl Canc Inst, Bethesda, MD USA. [Wheeler, William] Informat Management Serv Inc, Rockville, MD USA. [Hemminki, Kari] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Hemminki, Kari] Karolinska Inst, Huddinge, Sweden. [Dreyer, Lene] Univ Copenhagen Hosp, Rigshosp, DK-2100 Copenhagen, Denmark. [Dreyer, Lene] Frederiksberg Univ Hosp, Frederiksberg, Denmark. RP Mellemkjaer, L (reprint author), Danish Canc Soc, Inst Canc Epidemiol, Strandblvd 49, DK-2100 Copenhagen, Denmark. EM lene@cancer.dk RI Pfeiffer, Ruth /F-4748-2011; OI Olsen, Jorgen Helge/0000-0001-9633-5662 FU Intramural NIH HHS; NCI NIH HHS [N02-CP-01309] NR 50 TC 73 Z9 76 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 2008 VL 58 IS 3 BP 657 EP 666 DI 10.1002/art.23267 PG 10 WC Rheumatology SC Rheumatology GA 272XR UT WOS:000253895500005 PM 18311836 ER PT J AU Manolio, TA Arnold, AM Post, W Bertoni, AG Schreiner, PJ Sacco, RL Saadi, ME Detrano, RL Szklo, M AF Manolio, Teri A. Arnold, Alice M. Post, Wendy Bertoni, Alain G. Schreiner, Pamela J. Sacco, Ralph L. Saadi, Mohammed F. Detrano, Robert L. Szklo, Moyses TI Ethnic differences in the relationship of carotid atherosclerosis to coronary calcification: The Multi-Ethnic Study of Atherosclerosis SO ATHEROSCLEROSIS LA English DT Article DE atherosclerosis; calcium; carotid arteries; epidemiology ID INTIMAL-MEDIAL THICKNESS; BEAM COMPUTED-TOMOGRAPHY; ARTERY WALL THICKNESS; MIDDLE-AGED ADULTS; CARDIOVASCULAR-DISEASE; OLDER-ADULTS; CALCIUM; DENSITY; RACE; DIFFERENTIATION AB Ethnic differences in non-invasive measures of atherosclerosis are increasingly being reported, but the relationship of these measures to each other has not been widely explored. Carotid ultrasonographic and computed cardiac tomographic findings were compared in 6814 participants of White, Black, Hispanic, and Chinese ethnicities free of overt cardiovascular disease. Coronary calcium and carotid atherosclerosis were strongly related to each other in all ethnic groups. Associations of coronary calcium prevalence and common carotid intimal-medial thickness (IMT) differed by ethnicity in women, being weakest among Black women (0.07 mm IMT difference between those with and without coronary calcium) compared to the other three groups (0.10-0.12 mm difference, p = 0.007). Estimated percent increments in internal carotid IMT per 10% increment in coronary calcium score were highest in Hispanics (18.5%) and lowest in Blacks (6.1 %, p < 0.01). Coronary calcium may be less strongly associated with carotid atherosclerosis in Blacks, particularly Black women, than in other ethnic groups. These differences should be pursued for relationships to coronary events to determine whether coronary calcium carries the same risk information in other ethnic groups as it does in Whites. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Manolio, Teri A.] NHGRI, Bethesda, MD 20892 USA. [Manolio, Teri A.] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Post, Wendy] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Post, Wendy; Szklo, Moyses] Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD 21205 USA. [Bertoni, Alain G.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Schreiner, Pamela J.] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. [Sacco, Ralph L.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. [Sacco, Ralph L.] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA. [Saadi, Mohammed F.] SUNY Stony Brook, Hlth Sci Ctr, Dept Prevent Med, Stony Brook, NY 11794 USA. [Detrano, Robert L.] Univ Calif Los Angeles, Harbor Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. RP Manolio, TA (reprint author), NHGRI, 31 Ctr Dr,Rm 4B-09, Bethesda, MD 20892 USA. EM manolio@nih.gov FU Intramural NIH HHS [Z99 HG999999]; NHLBI NIH HHS [N01 HC095159, N01 HC095160, N01 HC095162, N01 HC095164, N01-HC-95160, N01-HC-95162, N01-HC-95164, N01HC95159, N01-HC-95163, N01 HC095161, N01 HC095163, N01 HC095165, N01 HC095169, N01-HC-95161, N01-HC-95165, N01-HC-95169, N01HC95165, N01HC95169, N01-HC-95159] NR 30 TC 41 Z9 44 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAR PY 2008 VL 197 IS 1 BP 132 EP 138 DI 10.1016/j.atherosclerosis.2007.02.030 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 282LS UT WOS:000254569900016 PM 17412347 ER PT J AU Brummett, BH Siegler, IC Day, S Costa, PT AF Brummett, Beverly H. Siegler, Ilene C. Day, Sue Costa, Paul T. TI Personality as a predictor of dietary quality in spouses during midlife SO BEHAVIORAL MEDICINE LA English DT Article DE diet; NEO-PI-R; personality; spouses ID BODY-MASS INDEX; SOCIAL SUPPORT; 5-FACTOR MODEL; RISK-FACTORS; HEALTH; OBESITY; WOMEN; CONSCIENTIOUSNESS; MORTALITY; HOSTILITY AB The authors evaluated the NEO Personality Inventory-Revised (NEO-PI-R) as a predictor of dietary quality in 850 married couples, focusing on associations among each participant's personality as a predictor of their own dietary quality and their spouses' dietary quality. Diet was based on a modified version of the US Department of Agriculture Healthy Eating Index. Openness was associated with self-ratings of dietary quality for wives (r =.28) and husbands (r =.27). Wives' levels of the characteristic openness were also related to their spouses' ratings of dietary quality (r=.22). The primary facets of openness accounting for the domain-level findings were O2-aesthetics and O4-actions. The remaining personality domains (neuroticism, extraversion, agreeableness, and conscientiousness) were not associated with self or spousal ratings of dietary quality (rs =.08-.09). Openness was associated with healthy eating habits-findings that may affect disease prevention during midlife. C1 [Brummett, Beverly H.; Siegler, Ilene C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Med, Durham, NC 27710 USA. [Day, Sue] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Costa, Paul T.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. RP Brummett, BH (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Med, Box 2969, Durham, NC 27710 USA. EM brummett@duke.edu OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [Z01 AG000184-19]; NHLBI NIH HHS [P01HL36587, R01 HL055356, R01 HL055356-09, R01HL55356] NR 33 TC 21 Z9 22 U1 0 U2 8 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0896-4289 J9 BEHAV MED JI Behav. Med. PD SPR PY 2008 VL 34 IS 1 BP 5 EP 10 DI 10.3200/BMED.34.1.5-10 PG 6 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 285ZU UT WOS:000254815500001 PM 18400684 ER PT J AU Roberts, KJ Grusky, O Swanson, AN AF Roberts, Kathleen Johnston Grusky, Oscar Swanson, Aimee-Noelle TI Client encounters in alternative HIV testing sites: Counselors' perceptions and experiences SO BEHAVIORAL MEDICINE LA English DT Article DE HIV/AIDS counseling and testing; provider-client relationship ID DIFFICULT PATIENT; FAMILY PHYSICIANS AB In this study, the authors explored HIV test counselors' perceptions of and experiences working with "difficult" and "good" clients in alternative HIV testing sites. Trained interviewers made field observations and conducted sixteen 60-minute, semistructured interviews with counselors. Counselors reported 7 main characteristics of difficult clients: (1) uncooperative, (2) mean, (3) inebriated, (4) threatening, (5) "crazy," (6) sexually inappropriate, and (7) aesthetically unappealing/overly appealing. They also identified 3 main characteristics of good clients: (1) communicative, (2) responsive, and (3) vulnerable. In addition, HIV test counselors used 4 strategies to deal with difficult clients: (1) received help from other counselors, (2) refused to test or threatened to refuse to test, (3) verbally confronted clients, and (4) "followed the forms" (ie, asked the necessary questions on the standard risk assessment forms). Results highlight the combined importance of patient characteristics, HIV test counselor characteristics, and the testing environment in contributing to difficult and good encounters in alternative HIV testing sites and point to the need for better training and support services in this area. C1 [Grusky, Oscar] Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90095 USA. [Roberts, Kathleen Johnston; Swanson, Aimee-Noelle] Univ Calif Los Angeles, Sch Publ Affairs, Los Angeles, CA 90095 USA. [Grusky, Oscar] Univ Calif Los Angeles, NIMH, AIDS Res Training Program, Los Angeles, CA 90024 USA. RP Grusky, O (reprint author), Univ Calif Los Angeles, Dept Sociol, 264 Haines Hall,Box 951551, Los Angeles, CA 90095 USA. EM grusky@ucla.edu FU NIMH NIH HHS [T32-MH19127, R01-MH62709] NR 14 TC 1 Z9 1 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0896-4289 J9 BEHAV MED JI Behav. Med. PD SPR PY 2008 VL 34 IS 1 BP 11 EP 18 DI 10.3200/BMED.34.1.11-20 PG 8 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 285ZU UT WOS:000254815500002 PM 18400685 ER PT J AU Vergarajauregui, S Oberdickt, R Kiselyov, K Puertollano, R AF Vergarajauregui, Silvia Oberdickt, Ross Kiselyov, Kirill Puertollano, Rosa TI Mucolipin 1 channel activity is regulated by protein kinase A-mediated phosphorylation SO BIOCHEMICAL JOURNAL LA English DT Article DE lysosome; mucolipin 1 (MCOLN1); mucolipidosis IV (MLIV); protein kinase A (PKA); transient receptor potential (TRP) ID CATION CHANNEL; MEMBRANE-PROTEIN; IV; GENE; TRAFFICKING; MUTATIONS; TRANSPORT; BRAIN; IDENTIFICATION; ACHLORHYDRIA AB Mucolipins constitute a family of cation channels with homology with the transient receptor potential family. Mutations in MCOLN1 (mucolipin 1) have been linked to mucolipiclosis type IV, a recessive lysosomal storage disease characterized by severe neurological and ophthalmologic abnormalities. At present, little is known about the mechanisms that regulate MCOLN1 activity. In the present paper, we addressed whether MCOLN1 activity is regulated by phosphorylation. We identified two PKA (protein kinase A) consensus motifs in the G terminal tail of MCOLN 1, containing Ser(557) and Ser(559) Ser(557) was the principal phosphorylation site, as mutation of this residue to alanine caused a greater than 75% reduction in the total levels of phosphorylated MCOLN 1 C-terminal tail. Activation of PKA with forskolin promoted MCOLN1 phosphorylation, both in vitro and in vivo. In contrast, addition of the PKA inhibitor H89 abolished MCOLN1 phosphorylation. We also found that PKA-mediated phosphorylation regulates MCOLN1 channel activity. Forskolin treatment decreased MCOLN1 channel activity, whereas treatment with H89 increased MCOLN1 channel activity. The stimulatory effect of H89 on MCOLN1 function was not observed when Ser(557) and Ser(559) were mutated to alanine residues, indicating that these two residues are essential for PKA-mediated negative regulation of MCOLN1. This paper presents the first example of regulation of a member of the mucolipin family by phosphorylation. C1 [Vergarajauregui, Silvia; Puertollano, Rosa] NIH, NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. [Oberdickt, Ross; Kiselyov, Kirill] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. RP Puertollano, R (reprint author), NIH, NHLBI, Cell Biol Lab, Bldg 10, Bethesda, MD 20892 USA. EM puertolr@mail.nih.gov FU Intramural NIH HHS NR 51 TC 24 Z9 24 U1 1 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 2008 VL 410 BP 417 EP 425 DI 10.1042/BJ20070713 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 268ZJ UT WOS:000253618900021 PM 17988215 ER PT J AU Schumann, M Nakagawa, T Mantey, SA Howell, B Jensen, RT AF Schumann, Michael Nakagawa, Tomoo Mantey, Samuel A. Howell, Brian Jensen, Robert T. TI Function of non-visual arrestins in signaling and endocytosis of the gastrin-releasing peptide receptor (GRP receptor) SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE G protein-coupled receptor; gastrin-releasing peptide; arrestin receptor endocytosis; rab5 ID PROTEIN-COUPLED RECEPTORS; MUSCARINIC ACETYLCHOLINE-RECEPTOR; CLATHRIN-MEDIATED ENDOCYTOSIS; COATED PIT FORMATION; BETA-ARRESTIN; DOWN-REGULATION; KINASE-C; BETA(2)-ADRENERGIC RECEPTOR; BOMBESIN RECEPTORS; INTERNALIZATION AB Little is known about the role of arrestins in gastrointestinal hormone/neurotransmitter receptor endocytosis. With other G protein-coupled receptors, arrestins induce G protein-uncoupling and receptor endocytosis. In this study, we used arrestin wild-type and dominant-negative mutant constructs to analyze the arrestin dependence of endocytosis and desensitization of the gastrin-releasing peptide receptor (GRP-R). Co-expression of the GRP-R with wild-type arrestin2 and arrestin3 increased not only GRP-R endocytosis but also GRP-R desensitization in arrestin-overexpres sing cells. Co-expression of the dominant-negative mutants V53D-arrestin2 or V54D-arrestin3 reduced GRP-R endocytosis. Notably, different trafficking routes for agonist-activated GRP-R-arrestin2 and GRP-R-arrestin3 complexes were found. Arrestin3 internalizes with GRP-R to intracellular vesicles, arrestin2 splits from the GRP-R and localizes to the cell membrane. Also, the recycling pathway of the GRP-R was different if co-expressed with arrestin2 or arrestin3. Using different GRP-R mutants, the C-terminus and the 2nd intracellular loop of the GRP-R were found to be important for the GRP-R-arrestin interaction and for the difference in GRP receptor trafficking with the two arrestin subtypes. Our results show that both non-visual arrestins play an important role in GRP-R internalization and desensitization. (c) 2007 Elsevier Inc. All rights reserved. C1 [Schumann, Michael; Nakagawa, Tomoo; Mantey, Samuel A.; Jensen, Robert T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Howell, Brian] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Schumann, M (reprint author), Charite Univ Med Berlin, Dept Gastroenterol Infectiol & Rheumatol, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany. EM michael.schumann@charite.de RI Schumann, Michael/K-6426-2013 OI Howell, Brian/0000-0002-0204-0773; Schumann, Michael/0000-0001-6391-9979 FU Intramural NIH HHS [Z01 DK053100-19] NR 57 TC 6 Z9 7 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 1 PY 2008 VL 75 IS 5 BP 1170 EP 1185 DI 10.1016/j.bcp.2007.11.022 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 268XR UT WOS:000253614200016 PM 18199425 ER PT J AU Iacob, RE Keck, Z Olson, O Foung, SKH Tomer, KB AF Iacob, Roxana E. Keck, Zhenyong Olson, Oakley Foung, Steven K. H. Tomer, Kenneth B. TI Structural elucidation of critical residues involved in binding of human monoclonal antibodies to hepatitis C virus E2 envelope glycoprotein SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE hepatitis C E2 glycoprotein; human neutralizing and non-neutralizing antibodies; limited proteolysis; differential chemical modification; mass spectrometry; alanine scanning mutagenesis ID MASS-SPECTROMETRY; CONFORMATIONAL EPITOPES; ELECTROSPRAY-IONIZATION; CHEMICAL-MODIFICATION; LIMITED PROTEOLYSIS; ESCAPE MUTATIONS; SURFACE-TOPOLOGY; T-LYMPHOCYTES; CROSS-LINKING; PROTEIN AB Human monoclonal antibodies derived from B cells of HCV-infected individuals provide information on the immune response to native HCV envelope proteins as they are recognized during infection. Monoclonal antibodies have been useful in the determination of the function and structure of specific immunogenic domains of proteins and should also be useful for the structure/function characterization of HCV E1 and E2 envelope glycoproteins. The HCV E2 envelope glycoprotein has at least three immunodistinctive conformation domains, designated A, B, and C. Conformational epitopes within domain B and C are neutralizing antibody targets on HCV pseudoparticles as well as from infectious cell culture virus. In this study, a combination of differential surface modification and mass spectrometric limited proteolysis followed by alanine mutagenesis was used to provide insight into potential conformational changes within the E2 protein upon antibody binding. The arginine guanidine groups in the E2 protein were modified with CHD in both the affinity bound and free states followed by mass spectrometric analysis, and the regions showing protection upon antibody binding were identified. This protection can arise by direct contact between the residues and the monoclonal antibody, or by antibody-induced conformational changes. Based on the mass spectrometric data, site-directed mutagenesis experiments were performed which clearly identified additional amino acid residues on E2 distant from the site of antibody interaction, whose change to alanine inhibited antibody recognition by inducing conformational changes within the E2 protein. (C) 2008 Elsevier B.V. All rights reserved. C1 [Iacob, Roxana E.; Tomer, Kenneth B.] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. [Iacob, Roxana E.; Tomer, Kenneth B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Keck, Zhenyong; Olson, Oakley; Foung, Steven K. H.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA USA. RP Iacob, RE (reprint author), Northeastern Univ, Barnett Inst, 341 Mugar Life Sci Bldg, Boston, MA 02115 USA. EM R.Iacob@neu.edu RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS [Z01 ES050127-15]; NHLBI NIH HHS [HL079381, R01 HL079381, R01 HL079381-04]; NIAID NIH HHS [AI047355, R01 AI047355, R01 AI047355-05] NR 57 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD MAR PY 2008 VL 1784 IS 3 BP 530 EP 542 DI 10.1016/j.bbapap.2007.12.015 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 285MF UT WOS:000254780200012 PM 18230369 ER PT J AU Li, L Bass, RL Liang, Y AF Li, Leping Bass, Robert L. Liang, Yu TI fdrMotif: identifying cis-elements by an EM algorithm coupled with false discovery rate control SO BIOINFORMATICS LA English DT Article ID FACTOR-BINDING-SITES; HUMAN GENOME; MOTIFS AB Motivation: Most de novo motif identification methods optimize the motif model first and then separately test the statistical significance of the motif score. In the first stage, a motif abundance parameter needs to be specified or modeled. In the second stage, a Z-score or P-value is used as the test statistic. Error rates under multiple comparisons are not fully considered. Methodology: We propose a simple but novel approach, fdrMotif, that selects as many binding sites as possible while controlling a user-specified false discovery rate (FDR). Unlike existing iterative methods, fdrMotif combines model optimization [e.g. position weight matrix (PWM)] and significance testing at each step. By monitoring the proportion of binding sites selected in many sets of background sequences, fdrMotif controls the FDR in the original data. The model is then updated using an expectation (E)- and maximization (M)-like procedure. We propose a new normalization procedure in the E-step for updating the model. This process is repeated until either the model converges or the number of iterations exceeds a maximum. Results: Simulation studies suggest that our normalization procedure assigns larger weights to the binding sites than do two other commonly used normalization procedures. Furthermore, fdrMotif requires only a user-specified FDR and an initial PWM. When tested on 542 high confidence experimental p53 binding loci, fdrMotif identified 569 p53 binding sites in 505 (93.2) sequences. In comparison, MEME identified more binding sites but in fewer ChIP sequences than fdrMotif. When tested on 500 sets of simulated ChIP sequences with embedded known p53 binding sites, fdrMotif, compared to MEME, has higher sensitivity with similar positive predictive value. Furthermore, fdrMotif is robust to noise: it selected nearly identical binding sites in data adulterated with 50 added background sequences and the unadulterated data. We suggest that fdrMotif represents an improvement over MEME. C1 [Li, Leping; Liang, Yu] NIEHS, NIH, DHHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Bass, Robert L.] NIEHS, NIH, DHHS, Computat Biol Facil, Res Triangle Pk, NC 27709 USA. RP Li, L (reprint author), NIEHS, NIH, DHHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z01 ES101765-04, Z99 ES999999] NR 28 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 1 PY 2008 VL 24 IS 5 BP 629 EP 636 DI 10.1093/bioinformatics/btn009 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 270UT UT WOS:000253746400005 PM 18296465 ER PT J AU Draghici, S Tarca, AL Yu, LF Ethier, S Romero, R AF Draghici, Sorin Tarca, Adi L. Yu, Longfei Ethier, Stephen Romero, Roberto TI KUTE-BASE: storing, downloading and exporting MIAME-compliant microarray experiments in minutes rather than hours SO BIOINFORMATICS LA English DT Article AB Motivation: The BioArray Software Environment (BASE) is a very popular MIAME-compliant, web-based microarray data repository. However in BASE, like in most other microarray data repositories, the experiment annotation and raw data uploading can be very timeconsuming, especially for large microarray experiments. Results: We developed KUTE (Karmanos Universal daTabase for microarray Experiments), as a plug-in for BASE 2.0 that addresses these issues. KUTE provides an automatic experiment annotation feature and a completely redesigned data work-flow that dramatically reduce the humancomputer interaction time. For instance, in BASE 2.0 a typical Affymetrix experiment involving 100 arrays required 4 h 30 min of user interaction time forexperiment annotation, and 45 min for data upload/download. In contrast, for the same experiment, KUTE required only 28 min of user interaction time for experiment annotation, and 3.3 min for data upload/download. C1 [Draghici, Sorin; Tarca, Adi L.; Yu, Longfei] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Tarca, Adi L.; Romero, Roberto] NICHHD, NIH, Perinatol Res Branch, Detroit, MI 48201 USA. [Tarca, Adi L.; Ethier, Stephen] Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA. RP Draghici, S (reprint author), Wayne State Univ, Dept Comp Sci, 431 State Hall, Detroit, MI 48202 USA. RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Intramural NIH HHS; NCI NIH HHS [U01 CA117478-01, 2P30 CA022453, R21 CA100740, U01 CA117478, P30 CA022453, R21 CA100740-01, 1U01CA117478, 1R21CA100740]; NHGRI NIH HHS [R01 HG003491-01A1, R01 HG003491, 1R01HG003491]; NIBIB NIH HHS [5R21EB000990, R21 EB000990-01, R21 EB000990-03, R21 EB000990]; NICHD NIH HHS [R01 HD040007-01]; NINDS NIH HHS [1R01NS045207, R01 NS045207, R01 NS045207-03, R01 NS045207-02, R01 NS045207-01, R01 NS045207-04] NR 1 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 1 PY 2008 VL 24 IS 5 BP 738 EP 740 DI 10.1093/bioinformatics/btm559 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 270UT UT WOS:000253746400026 PM 18024967 ER PT J AU Abdelmohsen, K Kuwano, Y Kim, HH Gorospe, M AF Abdelmohsen, Kotb Kuwano, Yuki Kim, Hyeon Ho Gorospe, Myriarn TI Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence SO BIOLOGICAL CHEMISTRY LA English DT Review DE mRNA stability; posttranscriptional gene regulation; reactive oxygen species (ROS) signaling pathway; RNA-binding proteins; translational control ID AU-RICH ELEMENT; TUMOR-NECROSIS-FACTOR; CONTAINING MESSENGER-RNAS; ZINC-FINGER PROTEINS; DNA-DAMAGE CHECKPOINTS; STABILIZING FACTOR HUR; NF-KAPPA-B; 3'-UNTRANSLATED REGION; TRANSLATIONAL CONTROL; FACTOR-ALPHA AB To respond adequately to oxidative stress, mammalian cells elicit rapid and tightly controlled changes in gene expression patterns. Besides alterations in the subsets of transcribed genes, two posttranscriptional processes prominently influence the oxidant-triggered gene expression programs: mRNA turnover and translation. Here, we review recent progress in our knowledge of the turnover and translation regulatory (TTR) mRNA-binding proteins (RBPs) that influence gene expression in response to oxidative damage. Specifically, we identify oxidant damage-regulated mRNAs that are targets of TTR-RBPs, we review the oxidant-triggered signaling pathways that govern TTR-RBP function, and we examine emerging evidence that TTR-RBP activity is altered with senescence and aging. Given the potent influence of TTR-RBPs upon oxidant-regulated gene expression profiles, we propose that the senescence-associated changes in TTR-RBPs directly contribute to the impaired responses to oxidant damage that characterize cellular senescence and advancing age. C1 [Abdelmohsen, Kotb; Kuwano, Yuki; Kim, Hyeon Ho; Gorospe, Myriarn] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Catonsville, MD 21228 USA. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Catonsville, MD 21228 USA. EM myriam-gorospe@nih.gov OI abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural NIH HHS NR 152 TC 140 Z9 140 U1 0 U2 11 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD MAR PY 2008 VL 389 IS 3 BP 243 EP 255 DI 10.1515/BC.2008.022 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 281GS UT WOS:000254485500006 PM 18177264 ER PT J AU Honea, RA Meyer-Lindenberg, A Hobbs, KB Pezawas, L Mattay, VS Egan, MF Verchinski, B Passingham, RE Weinberger, DR Callicott, JH AF Honea, Robyn A. Meyer-Lindenberg, Andreas Hobbs, Katherine B. Pezawas, Lukas Mattay, Venkata S. Egan, Michael F. Verchinski, Beth Passingham, Richard E. Weinberger, Daniel R. Callicott, Joseph H. TI Is gray matter volume an intermediate phenotype for schizophrenia? A voxel-based morphometry study of patients with schizophrenia and their healthy siblings SO BIOLOGICAL PSYCHIATRY LA English DT Article DE brain; gray matter volume; heritability; hippocampus; MRI; schizoaffective; schizophrenia; siblings; voxel-based morphometry ID SUPERIOR TEMPORAL GYRUS; MONOZYGOTIC TWINS DISCORDANT; HIPPOCAMPAL VOLUME; HIGH-RISK; BIPOLAR DISORDER; VENTRICULAR ENLARGEMENT; GENETIC LIABILITY; BRAIN STRUCTURE; 1ST EPISODE; ABNORMALITIES AB Background: Shared neuropathological characteristics of patients with schizophrenia and their siblings might represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover previously unidentified gray matter volume differences in patients with schizophrenia and their siblings with optimized voxel-based morphometry. Methods: We studied 169 patients with schizophrenia, 213 of their unaffected siblings, and 212 healthy volunteers from the Clinical Brain Disorders Branch/National Institute of Mental Health Genetic Study of Schizophrenia with magnetic resonance imaging. Results: Patients with schizophrenia had significant regional gray matter decreases in the frontal, temporal, and parietal cortices compared with healthy volunteers. Their unaffected siblings tended to share gray matter decreases in the medial frontal, superior temporal, and insular cortices, but these decreases were not significant after correction for multiple comparisons, even when we looked at a subgroup of siblings with a past history of mood disorder. As an exploratory analysis, we estimated heritability with regions of interest from the VBM analysis as well as from the hippocampus. Hippocampal volume was significantly correlated within sibling-pairs. Conclusions: Our findings confirm and extend previous voxel-based morphometry analyses in ill subjects with schizophrenia. Furthermore, these data argue that although siblings might share some regional gray matter decreases with their affected siblings, the pattern of regional differences might be a weak intermediate phenotype for schizophrenia. C1 [Pezawas, Lukas] Univ Klin Psychiat, Vienna, Austria. [Egan, Michael F.] Merck & Co Inc, West Point, PA USA. [Honea, Robyn A.; Passingham, Richard E.] Univ Oxford, Dept Expt Psychol, Oxford Cognit Neurosci Res Grp, Oxford, England. [Honea, Robyn A.; Meyer-Lindenberg, Andreas; Hobbs, Katherine B.; Mattay, Venkata S.; Verchinski, Beth; Weinberger, Daniel R.; Callicott, Joseph H.] NIH, NIMH, Div Intramural Res, Dept Hlth & Human Serv,Genes Cognit & Psychosis P, Bethesda, MD 20892 USA. RP Callicott, JH (reprint author), Bldg 10,Ctr Dr,Rm 4C-216,MSC 1364, Bethesda, MD 20892 USA. EM callicottj@mail.nih.gov RI Callicott, Joseph/C-9102-2009; Meyer-Lindenberg, Andreas/H-1076-2011; OI Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Pezawas, Lukas/0000-0002-1329-6352 FU Intramural NIH HHS [Z01 MH002712-13, Z01 MH002716-13, Z01 MH002734-12, Z99 MH999999] NR 71 TC 125 Z9 127 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2008 VL 63 IS 5 BP 465 EP 474 DI 10.1016/j.biopsych.2007.05.027 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 263ZZ UT WOS:000253256300005 PM 17689500 ER PT J AU Goldman, AL Pezawas, L Mattay, VS Fischl, B Verchinski, BA Zoltick, B Weinberger, DR Meyer-Lindenberg, A AF Goldman, Aaron L. Pezawas, Lukas Mattay, Venkata S. Fischl, Bruce Verchinski, Beth A. Zoltick, Brad Weinberger, Daniel R. Meyer-Lindenberg, Andreas TI Heritability of brain morphology related to schizophrenia: A large-scale automated magnetic resonance imaging segmentation study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE brain volume; heritability; MRI; phenotypes; schizophrenia ID GENETICALLY COMPLEX TRAITS; BASAL GANGLIA VOLUMES; TWINS DISCORDANT; UNAFFECTED SIBLINGS; HIPPOCAMPAL VOLUME; LINKAGE STRATEGIES; NEUROLEPTIC-NAIVE; TREATED PATIENTS; MRI; ABNORMALITIES AB Background: Schizophrenia is a devastating psychiatric disorder with a strong genetic component that has been related to a number of structural brain alterations. Currently available data on the heritability of these structural changes are inconsistent. Methods: To examine heritability of morphological alterations in a large sample, we used a novel and validated fully-automated whole brain segmentation technique to study disease-related variability and heritability in anatomically defined regions of interest in 221 healthy control subjects, 169 patients with schizophrenia, and 183 unaffected siblings. Results: Compared with healthy control subjects, patients showed a bilateral decrease in hippocampal and cortical gray matter volume and increases in bilateral dorsal striatum and right lateral ventricle. No significant volumetric differences were found in unaffected siblings compared with normal control subjects in any structure. Post hoc analysis of the dorsal striatum showed the volumetric increase to be widespread, including caudate, putamen, and globus pallidus. With Risch's lambda (lambda(s)), we found strong evidence for heritability of reduced cortical volume and moderate evidence for hippocampal volume, whereas abnormal striatal and ventricle volumes showed no sign of heritability. Additional exploratory analyses were performed on amygdala, thalamus, nucleus accumbens, ventral diencephalon, and cerebral and cerebellar cortex and white matter. Of these regions, patients showed increased volume in ventral diencephalon and cerebellum. Conclusions: These findings support evidence of genetic control of brain volume even in adults, particularly of hippocampal and neocortical volume and of cortical volumetric reductions being familial, but do not support measures of subcortical volumes per se as representing intermediate biologic phenotypes. C1 [Goldman, Aaron L.; Pezawas, Lukas; Mattay, Venkata S.; Verchinski, Beth A.; Zoltick, Brad; Weinberger, Daniel R.; Meyer-Lindenberg, Andreas] Natl Inst Hlth, NIMH, Genes Cognit & Psychosis Program, Neuroimaging Core Facil, Bethesda, MD USA. [Fischl, Bruce] Harvard Med Sch, Athinoula A Martinos Ctr, Dept Radiol, MGH, Charlestown, MA USA. [Fischl, Bruce] MIT, HST, CSAIL Dept, Cambridge, MA USA. [Pezawas, Lukas] Med Univ Vienna, Univ Hosp Psychiat, Dept Gen Psychiat, Vienna, Austria. RP Meyer-Lindenberg, A (reprint author), Zentral Inst Seelische Gesundheit, D-68159 Mannheim, Germany. EM a.meyer-lindenberg@zi.mannheim.de RI Meyer-Lindenberg, Andreas/H-1076-2011; OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Pezawas, Lukas/0000-0002-1329-6352 FU Intramural NIH HHS; NCRR NIH HHS [P41-RR14075, R01 RR16594-01A1, U24 RR021382]; NIBIB NIH HHS [R01 EB001550, U54 EB005149]; NINDS NIH HHS [R01 NS052585-01] NR 44 TC 88 Z9 90 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2008 VL 63 IS 5 BP 475 EP 483 DI 10.1016/j.biopsych.2007.06.006 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 263ZZ UT WOS:000253256300006 PM 17727823 ER PT J AU Boyiadzis, M Memon, S Carson, J Allen, K Szczepaski, MR Vance, BA Dean, R Bishop, MR Gress, RE Hakint, FT AF Boyiadzis, Michael Memon, Sarfraz Carson, Jesse Allen, Kenton Szczepaski, Miroslaw R. Vance, Barbara A. Dean, Robert Bishop, Michael R. Gress, Ronald E. Hakint, Frances T. TI Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE natural killer cells; IL-15; natural cytotoxicity receptors; NKG2D; transplantation ID NATURAL-KILLER-CELLS; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; HLA CLASS-I; T-CELL; POTENTIAL ROLE; EXPRESSION; RECONSTITUTION; INTERLEUKIN-15; CYTOTOXICITY AB Because natural killer (NK) cells can be potent anti-tumor effectors after allogeneic stem cell transplantation, we investigated NK reconstitution and receptor expression in patients undergoing allogeneic hematopoietic stem cell transplantation, focusing on the activating receptors that trigger anti-tumor responses. We determined that NK levels in the peri-transplant period were inversely proportional to the dramatic rise and fall in plasma levels of the NK homeostatic cytokine IL-15, which increased more than 50-fold from pretreatment to the day of transplant during the lymphoreductive preparative regimen. Furthermore, in NK cells cultured with IL-15, we observed an up-regulation of the activating receptors NKG2D, NKp30, and NKp46, associated with an increase in anti-tumor lyric activity. Similarly, the expression of these activating receptors increased significantly during the early post-transplant period, concurrent with a rapid increase in total NK cells and a shift toward increased expression of CD56. These data suggest that the cytokine milieu of transplants, in particular elevated levels of IL-15, may contribute to anti-tumor efficacy post-transplant by enhancing the recovery of NK subsets and modulating expression of activating receptors. (C) 2008 American Society for Blood and Marrow Transplantation. C1 [Boyiadzis, Michael; Szczepaski, Miroslaw R.] Univ Pittsburgh, Sch Med, Div Hematol & Oncol, Dept Med, Pittsburgh, PA 15232 USA. [Boyiadzis, Michael; Memon, Sarfraz; Carson, Jesse; Allen, Kenton; Vance, Barbara A.; Dean, Robert; Bishop, Michael R.; Gress, Ronald E.; Hakint, Frances T.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Boyiadzis, M (reprint author), Univ Pittsburgh, Sch Med, Div Hematol & Oncol, Dept Med, UPMC Canc Pavil,5150 Ctr Ave,Suite 572, Pittsburgh, PA 15232 USA. EM boviadzism@upmc.edu RI Memon, Sarfraz/E-1198-2013; OI Memon, Sarfraz/0000-0002-0164-9739 NR 44 TC 33 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2008 VL 14 IS 3 BP 290 EP 300 DI 10.1016/j.bbmt.2007.12.490 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 265FC UT WOS:000253343500004 PM 18275895 ER PT J AU Browne, RW Bloom, MS Schisterman, EF Hovey, K Trevisan, M Xu, CQ Liu, A Wactawsyi-Wende, J AF Browne, Richard W. Bloom, Michael S. Schisterman, Enrique F. Hovey, Kathy Trevisan, Maurizio Xu, Chengqing Liu, Aiyi Wactawsyi-Wende, Jean TI Analytical and biological variation of biomarkers of oxidative stress during the menstrual cycle SO BIOMARKERS LA English DT Article DE oxidative stress; antioxidants; biological variation; menstrual cycle ID GLUTATHIONE-PEROXIDASE ACTIVITY; CLINICAL-CHEMISTRY; LIPID-PEROXIDATION; QUALITY SPECIFICATIONS; SUPEROXIDE-DISMUTASE; ANTIOXIDANT ENZYMES; ASCORBIC-ACID; HUMAN PLASMA; HUMAN HEALTH; DISEASE AB Little information is available on the intra-individual variability of oxidative stress biomarkers in healthy individuals and even less in the context of the menstrual cycle. The objective of this study was to characterize the analytical and biological variability of a panel of 21 markers of oxidative damage, antioxidant defence and micronutrients in nine healthy, regularly menstruating women aged 18-44 years. Analyses included measurement of lipid peroxidation, antioxidant enzymes and antioxidant vitamins. Blood specimens were collected, processed and stored using standardized procedures on days 2, 7, 12, 13, 14, 18, 22 and 28 in one cycle for each subject. Replicate analyses of markers were performed and two-way nested random effects ANOVA was used to describe analytical, intra-individual and inter-individual variability. No statistically significant differences at alpha = 0.05, or temporal effects across the menstrual cycle were observed. Analytical variability was the smallest component of variance for all variables. The ICC among replicates ranged from 0.80 to 0.98. Imprecision based on quality control materials ranged from I to 11%. The critical differences between serial results varied greatly between assays ranging from 6 to 216% of the mean level. These results provide important initial information on the variability of biomarkers of oxidative stress, antioxidant defence and micronutrients across the menstrual cycle. C1 [Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14214 USA. [Hovey, Kathy; Trevisan, Maurizio; Wactawsyi-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. [Bloom, Michael S.; Schisterman, Enrique F.; Xu, Chengqing; Liu, Aiyi] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Browne, RW (reprint author), SUNY Buffalo, Dept Biotech & Clin Lab Sci, 26 Cary Hall, Buffalo, NY 14214 USA. EM rwbrowne@buffalo.edu OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X; Bloom, Michael/0000-0002-0028-5494 FU Intramural NIH HHS [Z01 HD008762-05] NR 75 TC 23 Z9 23 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD MAR PY 2008 VL 13 IS 2 BP 160 EP 183 DI 10.1080/13547500701775563 PG 24 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 273BW UT WOS:000253906400002 PM 18270869 ER PT J AU Chein, BE Kramer, JL Greene, MH Rosenberg, PS AF Chein, Bingshu E. Kramer, Joan L. Greene, Mark H. Rosenberg, Philip S. TI Competing risks analysis of correlated failure time data SO BIOMETRICS LA English DT Article DE BRCA1 gene; breast neoplasm; competing risks; correlated survival data; counting processes; robust variance ID NONPARAMETRIC-INFERENCE; CUMULATIVE INCIDENCE; VARIANCE-ESTIMATION; RECURRENT EVENTS; KAPLAN-MEIER; TESTS AB We develop methods for competing risks analysis when individual event times are correlated within clusters. Clustering arises naturally in clinical genetic studies and other settings. We develop a nonparametric estimator of cumulative incidence, and obtain robust pointwise standard errors that account for within-cluster correlation. We modify the two-sample Gray and Pepe-Mori tests for correlated competing risks data, and propose a simple two-sample test of the difference in cumulative incidence at a landmark time. In simulation studies, our estimators are asymptotically unbiased, and the modified test statistics control the type I error. The power of the respective two-sample tests is differentially sensitive to the degree of correlation; the optimal test depends on the alternative hypothesis of interest and the within-cluster correlation. For purposes of illustration, we apply our methods to a family-based prospective cohort study of hereditary breast/ovarian cancer families. For women with BRCA1 mutations, we estimate the cumulative incidence of breast cancer in the presence of competing mortality from ovarian cancer, accounting for significant within-family correlation. C1 [Chein, Bingshu E.; Rosenberg, Philip S.] Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. [Kramer, Joan L.; Greene, Mark H.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA. RP Chein, BE (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. EM bingshu@chenstat.com OI Chen, Bingshu/0000-0001-6139-0696 NR 20 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD MAR PY 2008 VL 64 IS 1 BP 172 EP 179 DI 10.1111/j.1541-0420.2007.00868.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 269EL UT WOS:000253632200020 ER PT J AU Brittain, E Follmann, D Yang, S AF Brittain, Erica Follmann, Dean Yang, Song TI Dynamic comparison of Kaplan-Meier proportions: Monitoring a randomized clinical trial with a long-term binary endpoint SO BIOMETRICS LA English DT Article DE Kaplan-Meier; sequential testing ID CENSORED SURVIVAL-DATA; SEQUENTIAL DESIGNS; TESTS; STATISTICS AB The approach to early termination for efficacy in a trial where events occur over time but the primary question of interest relates to a long-term binary endpoint is not straightforward. This article considers comparison of treatment groups with Kaplan-Meier (KM) proportions evaluated at increasing times from randomization, at increasing calendar testing times. This strategy is employed to improve the ability to detect important treatment effects and provide critical treatments to patients in a timely manner. This dynamic Kaplan-Meier (DKM) approach is shown to be robust; that is, it produces high power and early termination time across a wide range of circumstances. In contrast, a fixed time KM comparison and the log-rank test are both shown to be more variable in performance. Practical considerations of implementing the DKM method are discussed. C1 [Brittain, Erica; Follmann, Dean] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Yang, Song] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Brittain, E (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ebrittain@niaid.nih.gov NR 16 TC 1 Z9 1 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2008 VL 64 IS 1 BP 189 EP 197 DI 10.1111/j.1541-0420.2007.00874.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 269EL UT WOS:000253632200022 PM 17680830 ER PT J AU Korn, EL M-Eidlin, B AF Korn, Edward L. M-Eidlin, Boris TI A note on controlling the number of false positives SO BIOMETRICS LA English DT Article DE Bonferroni; false discovery proportion; multiple testing; multivariate permutation test; permutation test ID MULTIPLE; CANCER AB Lehmann and Romano (2005, Annals of Statistics 33, 1138-1154) discuss a Bonferroni-type procedure that bounds the probability that the number of false positives is larger than a specified number. We note that this procedure will have poor power as compared to a multivariate permutation test type procedure when the experimental design accommodates a permutation test. An example is given involving gene expression microarray data of breast cancer tumors. C1 [Korn, Edward L.; M-Eidlin, Boris] NCI, Biometr Res Branch, Rockville, MD 20852 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, Rockville, MD 20852 USA. EM korne@ctep.nci.nih.gov NR 19 TC 3 Z9 3 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2008 VL 64 IS 1 BP 227 EP 231 DI 10.1111/j.1541-0420.2007.00881.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 269EL UT WOS:000253632200026 PM 17900315 ER PT J AU Midthune, D Kipnis, V Freedman, LS Carroll, RJ AF Midthune, Douglas Kipnis, Victor Freedman, Laurence S. Carroll, Raymond J. TI Binary regression in truncated samples, with application to comparing dietary instruments in a large prospective study SO BIOMETRICS LA English DT Article DE biased sampling; breast cancer; case-control studies; comparison of instruments; measurement error; misspecified models; nutritional epidemiology; truncation; Women's Health Initiative ID FOOD FREQUENCY QUESTIONNAIRE; BREAST-CANCER; MEASUREMENT ERROR; FAT; RISK; BIOMARKER; COHORT AB We examine two issues of importance in nutritional epidemiology: the relationship between dietary fat intake and breast cancer, and the comparison of different dietary assessment instruments, in our case the food frequency questionnaire (FFQ) and the multiple-day food record (FR). The data we use come from women participants in the control group of the Dietary Modification component of the Women's Health Initiative (WHI) Clinical Trial. The difficulty with the analysis of this important data set is that it comes from a truncated sample, namely those women for whom fat intake as measured by the FFQ amounted to 32% or more of total calories. We describe methods that allow estimation of logistic regression parameters in such samples, and also allow comparison of different dietary instruments. Because likelihood approaches that specify the full multivariate distribution can be difficult to implement, we develop approximate methods for both our main problems that are simple to compute and have high efficiency. Application of these approximate methods to the WHI study reveals statistically significant fat and breast cancer relationships when a FR is the instrument used, and demonstrate a marginally significant advantage of the FR over the FFQ in the local power to detect such relationships. C1 [Midthune, Douglas; Kipnis, Victor] NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. [Freedman, Laurence S.] Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Midthune, D (reprint author), NCI, Div Canc Prevent, Biometry Res Grp, Execut Plaza N,Room 3131,6130 Execut Blvd,MSC 735, Bethesda, MD 20892 USA. EM dm76q@nih.gov FU NCI NIH HHS [CA-57030, U01 CA057030, R37 CA057030, R37 CA057030-20, R01 CA057030]; NIEHS NIH HHS [P30 ES009106, P30-ES09106] NR 17 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2008 VL 64 IS 1 BP 289 EP 298 DI 10.1111/j.1541-0420.2007.00833.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 269EL UT WOS:000253632200036 PM 17651458 ER PT J AU Chakrapani, H Wilde, TC Citro, ML Goodblatt, MM Keefer, LK Saavedra, JE AF Chakrapani, Harinath Wilde, Thomas C. Citro, Michael L. Goodblatt, Michael M. Keefer, Larry K. Saavedra, Joseph E. TI Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE nitric oxide; glutathione; GST; anti-cancer; prodrugs; PABA/NO ID BIOLOGICAL EVALUATION; IN-VITRO; DONOR; DIAZENIUMDIOLATE; CHEMISTRY; MECHANISM; TRANSFERASES; RESISTANCE; NONOATES; DESIGN AB Diazeniumdiolate anions and their prodrug forms are reliable sources of nitric oxide (NO) that have generated interest as promising therapeutic agents. A number of structural analogues of O-2-(2,4-dinitro-5-(4-(N-methylamino)benzoyloxy)phenyl)-1-(N,N-dimetliylamino)diazen-1-ium-1,2-diolate (PABA/NO), an anti-cancer lead compound that is designed to release NO upon activation by glutathione, were prepared. The nitric oxide release patterns of these O-2-(2,4-dinitrophenyl) diazeniumdiolates in the presence of glutathione were tested and it was found that in the absence of competing pathways, these compounds release nearly quantitative amounts of NO. The ability of PABA/NO and its structural analogues to inhibit human leukemia cell proliferation was determined and it was found that compounds releasing elevated amounts of NO displayed superior cytotoxic effects. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Chakrapani, Harinath; Wilde, Thomas C.; Goodblatt, Michael M.; Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. [Citro, Michael L.; Saavedra, Joseph E.] NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Chakrapani, H (reprint author), NCI, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. EM chakrah@ncifcrf.gov; saavj@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural NIH HHS [, NIH0012791200]; NCI NIH HHS [N01-CO-12400, N01CO12400]; PHS HHS [NIH0012791200] NR 25 TC 19 Z9 23 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR 1 PY 2008 VL 16 IS 5 BP 2657 EP 2664 DI 10.1016/j.bmc.2007.11.035 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 288RB UT WOS:000255002400045 PM 18060792 ER PT J AU Jeong, LS Lee, HW Kim, HO Tosh, DK Pal, S Choi, WJ Gao, ZG Patel, AR Williams, W Jacobson, KA Kim, HD AF Jeong, Lak Shin Lee, Hyuk Woo Kim, Hea Ok Tosh, Dilip K. Pal, Shantanu Choi, Won Jun Gao, Zhan-Guo Patel, Amit R. Williams, Wanda Jacobson, Kenneth A. Kim, Hee-Doo TI Structure-activity relationships of 2-chloro-N-6-substituted-4 '-thioadenosine-5 '-N,N-dialkyluronamides as human A(3) adenosine receptor antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE 4 '-thionucleoside; A(3) adenosine receptor antagonist; conformational change; radioligand binding ID BIOLOGICAL-ACTIVITY; SELECTIVE AGONISTS; DERIVATIVES; EFFICACY; LIGANDS; POTENT; DETERMINANTS; MOIETY AB On the basis of potent and selective A(3) adenosine receptor (AR) antagonist, 2-chloro-N-6-(3-iodobenzyl)-4'-thioadenosine-5'-N,N-dimethyluronamide, structure-activity relationships were studied for a series of 5'-N,N-dialkyluronamide derivatives, synthesized from D-gulonic gamma-lactone. From this study, it was revealed that removal of the hydrogen bond-donating ability of the 5'-uronamide was essential for the pure A(3)AR antagonism. 5'-N,N-Dimethyluronamide derivatives exhibited higher binding affinity than larger 5'-N,N-dialkyl or 5'-N,N-cycloalkylamide derivatives, indicating that steric factors are crucial in binding to the human A(3)AR. A N-6-(3-bromobenzyl) derivative 6c (K-i = 9.32 nM) exhibited the highest binding affinity at the human A3AR with very low binding affinities to other AR subtypes. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Jeong, Lak Shin; Lee, Hyuk Woo; Kim, Hea Ok; Tosh, Dilip K.; Pal, Shantanu; Choi, Won Jun] Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. [Gao, Zhan-Guo; Patel, Amit R.; Jacobson, Kenneth A.] NIH, Bioorgan Chem Lab, Mol Recognit Sect, Bethesda, MD 20892 USA. [Williams, Wanda] NIDDKD, NIH, Chem Biol Core Lab, Bethesda, MD 20892 USA. [Kim, Hee-Doo] Sookmyung Womens Univ, Coll Pharm, Seoul 140742, South Korea. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS NR 20 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAR 1 PY 2008 VL 18 IS 5 BP 1612 EP 1616 DI 10.1016/j.bmcl.2008.01.070 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 276YS UT WOS:000254180200014 PM 18255292 ER PT J AU Cao, H Lin, R Ghosh, S Anderson, RA Urban, JF AF Cao, Heping Lin, Rui Ghosh, Sanjukta Anderson, Richard A. Urban, Joseph F., Jr. TI Production and characterization of ZFP36L1 antiserum against recombinant protein from Escherichia coli SO BIOTECHNOLOGY PROGRESS LA English DT Article ID ZINC-FINGER PROTEINS; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA TURNOVER; AU-RICH ELEMENTS; TRISTETRAPROLIN FAMILY; KINASE-B; GENE; EXPRESSION; INSULIN; DESTABILIZATION AB Tristetraprolin/zinc finger protein 36 (TTP/ZFP36) family proteins are anti-inflammatory. They bind and destabilize some AU-rich element-containing mRNAs such as tumor necrosis factor mRNA. In this study, recombinant ZFP36L1/TIS 11B (a TTP homologue) was overexpressed in E. coli, purified, and used for polyclonal antibody production in rabbits. The antiserum recognized nanograms of the antigen on immunoblots. This antiserum and another antiserum developed against recombinant mouse TTP were used to detect ZFP36L1 and TTP in mouse 3T3-L1 adipocytes and RAW264.7 macrophages. Immunoblotting showed that ZFP36L1 was stably expressed with a size corresponding to the lower mass size of ZFP36L1 expressed in transfected human embryonic kidney 293 cells, but TTP was induced by cinnamon extract and not by lipopolysaccharide (LPS) in adipocytes. In contrast, ZFP36L1 was undetectable, but TTP was strongly induced in LPS-stimulated RAW cells. Quantitative real-time polymerase chain reaction confirmed the higher levels of ZFP36L1 mRNA in adipocytes and TTP mRNA in RAW cells. Low levels of ZFP36L1 expression were also confirmed by Northern blotting in mouse embryonic fibroblasts. These results demonstrate that ZFP36L1 antiserum is useful in the detection of this protein and that TTP and ZFP36L1 are differentially expressed and regulated at the mRNA and protein levels in mouse adipocytes and macrophages. C1 [Cao, Heping; Anderson, Richard A.; Urban, Joseph F., Jr.] USDA ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. [Cao, Heping; Lin, Rui; Ghosh, Sanjukta] NIEHS, DHHS, NIH, Res Triangle Pk, NC 27709 USA. RP Cao, H (reprint author), USDA ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, Bldg 307C,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM heping.cao@ars.usda.gov OI Urban, Joseph/0000-0002-1590-8869 FU Intramural NIH HHS [Z01 ES090080-10] NR 39 TC 11 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAR-APR PY 2008 VL 24 IS 2 BP 326 EP 333 DI 10.1021/bp070269n PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 284JU UT WOS:000254703500006 PM 18302406 ER PT J AU Harwood, B Nansel, T AF Harwood, B. Nansel, T. CA Natl Inst Child Hlth Human Dev Man TI Quality of life and acceptability of medical versus surgical management of early pregnancy failure SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article; Proceedings Paper CT Joint Annual Meeting of the Association-of-Reproductive-Health-Professionals/Society-of-Family-Plann ing CY 2005 CL Washington, DC SP Assoc Reprod Hlth Profess, Soc Family Planning DE early pregnancy failure; misoprostol; quality of life. ID RANDOMIZED CONTROLLED-TRIAL; DEPRESSION-HAPPINESS SCALE; EXPECTANT MANAGEMENT; SPONTANEOUS-ABORTION; WOMENS PREFERENCES; VACUUM ASPIRATION; MISCARRIAGE; MISOPROSTOL; HEALTH; IMPACT AB Objective This study compares quality of life (QOL) and acceptability of medical versus surgical treatment of early pregnancy failure (EPF). Design A randomised clinical trial of treatment for EPF compared misoprostol vaginally versus vacuum aspiration (VA). Setting A multisite trial at four US Urban University Hospitals. Population A total of 652 women with an EPF were randomised to treatment. Methods Participants completed a daily symptom diary and a questionnaire 2 weeks after treatment. Main outcome measures The questionnaire assessment included subscales of the Short Form-36 Health Survey Revised for QOL and measures of wellbeing, recovery difficulties, and treatment acceptability. Results The two groups did not differ in mean scores for QOL except bodily pain; medical treatment was associated with higher levels of bodily pain than VA (P < 0.001). Success of treatment was not related to QOL, but acceptability of the procedure was decreased for medical therapy if unsuccessful (P = 0.003). Type of treatment was not associated with differences in recovery, and the two groups reported similar acceptability except for cramping (P = 0.02), bleeding (P < 0.001), and symptom duration (P = 0.03). Conclusions Despite reporting greater pain and lower acceptability of treatment-related symptoms, QOL and treatment acceptability were similar for medical and surgical treatment of EPF. Acceptability, but not QOL, was influenced by success or failure of medical management. C1 [Harwood, B.] Univ Illinois, Coll Med, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Nansel, T.] NICHHD, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. RP Harwood, B (reprint author), Univ Illinois, Coll Med, Dept Obstet & Gynecol, 820 S Wood St,Room 217,MC 808, Chicago, IL 60612 USA. EM brynah@uic.edu OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS [Z99 HD999999]; NCRR NIH HHS [M01 RR000056, MO1RR000056]; NICHD NIH HHS [K12 HD055892, K12 HD055892-01, N01-HD-1-3321, N01-HD-1-3322, N01-HD-1-3323, N01-HD-1-3324, N01-HD-1-3325] NR 32 TC 13 Z9 13 U1 2 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD MAR PY 2008 VL 115 IS 4 BP 501 EP 508 DI 10.1111/j.1471-0528.2007.01632.x PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 260AS UT WOS:000252982800011 PM 18271887 ER PT J AU Raponi, M Lancet, JE Fan, HT Dossey, L Lee, G Gojo, I Feldman, EJ Gotlib, J Morris, LE Greenberg, PL Wright, JJ Harousseau, JL Lowenberg, B Stone, RM De Porre, P Wang, YX Karp, JE AF Raponi, Mitch Lancet, Jeffrey E. Fan, Hongtao Dossey, Lesley Lee, Grace Gojo, Ivana Feldman, Eric J. Gotlib, Jason Morris, Lawrence E. Greenberg, Peter L. Wright, John J. Harousseau, Jean-Luc Loewenberg, Bob Stone, Richard M. De Porre, Peter Wang, Yixin Karp, Judith E. TI A 2-gene classifier for predicting response to the famesyltransferase inhibitor tipifarnib in acute myeloid leukemia SO BLOOD LA English DT Article ID ACUTE-MYELOGENOUS-LEUKEMIA; B-CELL LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; NUCLEOTIDE EXCHANGE FACTOR; BREAST-CANCER; TRANSFERASE INHIBITORS; ACTIVATING MUTATIONS; COLORECTAL-CANCER; LUNG-CANCER; IN-VITRO AB At present, there is no method available to predict response to farnesyltransferase inhibitors (FTIs). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1/APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy using a "leave one out" cross validation (LOOCV; 96%). RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair. The utility of this classifier for predicting response to tipifarnib was validated in an independent set of 58 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (1154 vs 56 days; P < .001), which was independent of other covariates, including a previously described prognostic gene expression classifier. Therefore, these data indicate that a 2-gene expression assay may have utility in categorizing a population of patients with AML who are more likely to respond to tipifarnib. C1 [Raponi, Mitch; Dossey, Lesley; Lee, Grace; Wang, Yixin] Veridex, La Jolla, CA USA. [Lancet, Jeffrey E.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Fan, Hongtao] Centocor R&D, Malvern, PA USA. [Gojo, Ivana] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Feldman, Eric J.] Cornell Univ, Weill Med Coll, New York, NY USA. [Gotlib, Jason; Greenberg, Peter L.] Stanford Canc Ctr, Stanford, CA USA. [Morris, Lawrence E.] Blood & Bone Marrow Transplant Grp Georgia, Atlanta, GA USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Natl Inst Hlth, Bethesda, MD 20892 USA. [Harousseau, Jean-Luc] CHU, Hotel Dieu, Serv Hematol Clin, Nantes, France. [Loewenberg, Bob] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Stone, Richard M.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. [De Porre, Peter] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Karp, Judith E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Raponi, M (reprint author), Johnson & Johnson Co, Veridex LLC, 3210 Merryfield Row, San Diego, CA 92121 USA. EM mraponi1@ocdus.jnj.com FU NCRR NIH HHS [M01 RR000052] NR 55 TC 73 Z9 74 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2008 VL 111 IS 5 BP 2589 EP 2596 DI 10.1182/blood-2007-09-112730 PG 8 WC Hematology SC Hematology GA 269SX UT WOS:000253671600023 PM 18160667 ER PT J AU Patel, KV Harris, TB Newman, AB Guralnik, JM AF Patel, Kushang V. Harris, Tamara B. Newman, Anne B. Guralnik, Jack M. TI Further epidemiologic research on anemia in older adults is needed SO BLOOD LA English DT Letter ID MORTALITY; COMMUNITY; WHITES C1 [Patel, Kushang V.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Patel, KV (reprint author), NIA, Lab Epidemiol Demog & Biometry, Gateway Bldg,7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. EM patelku@mail.nih.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2008 VL 111 IS 5 BP 2941 EP 2942 DI 10.1182/blood-2007-08-109140 PG 2 WC Hematology SC Hematology GA 269SX UT WOS:000253671600065 ER PT J AU Bodine, D Harrow, F Laflame, K AF Bodine, David Harrow, Faith Laflame, Karina TI Novel lentivirus vectors for safe and efficient gene therapy of hemoglobin disorders SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 [Bodine, David; Harrow, Faith; Laflame, Karina] NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 10 BP 255 EP 255 DI 10.1016/j.bcmd.2007.10.020 PG 1 WC Hematology SC Hematology GA 266YP UT WOS:000253474400029 ER PT J AU Condotti, F Kohn, DB AF Condotti, Fabio Kohn, Donald B. TI Gene therapy for adenosine deaminase deficiency in the USA SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 NHGRI, NIH, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 17 BP 258 EP 259 DI 10.1016/j.bcmd.2007.10.027 PG 2 WC Hematology SC Hematology GA 266YP UT WOS:000253474400036 ER PT J AU Davis, BR DiCola, MJ Prokopishyn, NL Rosenberg, JB Moratto, D Muul, LM Candotti, F Blaese, RM AF Davis, Brian R. DiCola, Michael J. Prokopishyn, Nicole L. Rosenberg, Jonathan B. Moratto, Daniele Muul, Linda M. Candotti, Fabio Blaese, R. Michael TI Natural gene therapy: Somatic reversion in the Wiskott-Aldrich syndrome SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 [Davis, Brian R.; DiCola, Michael J.; Prokopishyn, Nicole L.; Rosenberg, Jonathan B.; Blaese, R. Michael] Inst Inherited Dis Res, Newtown, PA USA. [Davis, Brian R.] Univ Texas Houston, Hlth Sci Ctr, Brown Fdn Inst Mol Med, Ctr Stem Cell Res, Houston, TX USA. [Moratto, Daniele; Muul, Linda M.; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 22 BP 261 EP 261 DI 10.1016/j.bcmd.2007.10.032 PG 1 WC Hematology SC Hematology GA 266YP UT WOS:000253474400041 ER PT J AU Dunbar, CE AF Dunbar, Cynthia E. TI Genotoxicity in the rhesus macaque model SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 [Dunbar, Cynthia E.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 25 BP 263 EP 263 DI 10.1016/j.bcmd.2007.10.035 PG 1 WC Hematology SC Hematology GA 266YP UT WOS:000253474400044 ER PT J AU Bauer, TR Russell, D Hickstein, DD AF Bauer, Thomas R. Russell, David Hickstein, Dennis D. TI Successful gene therapy of canine leukocyte adhesion deficiency using foamy viral vectors SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 [Bauer, Thomas R.; Russell, David; Hickstein, Dennis D.] Univ Washington, Sch Med, NCI, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 37 BP 269 EP 269 DI 10.1016/j.bcmd.2007.10.047 PG 1 WC Hematology SC Hematology GA 266YP UT WOS:000253474400056 ER PT J AU Kang, EM Linton, G Theobald, N O'Brien, SA Hilligoss, D Malech, HL AF Kang, Elizabeth M. Linton, Gilda Theobald, Narda O'Brien, Sandra Anaya Hilligoss, Dianne Malech, Harry L. TI Treatment of infections in patients with X-linked chronic granulomatous disease (CGD) with gene therapy SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 [Kang, Elizabeth M.; Linton, Gilda; Theobald, Narda; O'Brien, Sandra Anaya; Hilligoss, Dianne; Malech, Harry L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 39 BP 270 EP 271 DI 10.1016/j.bcmd.2007.10.049 PG 2 WC Hematology SC Hematology GA 266YP UT WOS:000253474400058 ER PT J AU Malech, HL Linton, GF Whiting-Theobald, N Naumann, N De Ravin, SS Choi, U Moayeri, M O'Brien, SA Hilligoss, D Ikeda, Y Kang, EM AF Malech, Harry L. Linton, Gilda F. Whiting-Theobald, Narda Naumann, Nora De Ravin, Suk See Choi, Uimook Moayeri, Morvarid O'Brien, Sandra Anaya Hilligoss, Dianne Ikeda, Yasuhiro Kang, Elizabeth M. TI Update on gene therapy for Chronic Granulomatous Disease: Current studies and future approaches SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 4th Conference on Stem Cell Gene Therapy CY SEP 13-17, 2007 CL Thessaloniki, GREECE C1 [Malech, Harry L.; Linton, Gilda F.; Whiting-Theobald, Narda; Naumann, Nora; De Ravin, Suk See; Choi, Uimook; Moayeri, Morvarid; O'Brien, Sandra Anaya; Hilligoss, Dianne; Kang, Elizabeth M.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Ikeda, Yasuhiro] Mayo Clin, Rochester, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2008 VL 40 IS 2 MA 48 BP 274 EP 275 DI 10.1016/j.bcmd.2007.10.058 PG 2 WC Hematology SC Hematology GA 266YP UT WOS:000253474400067 ER PT J AU Mak, KK Yang, YZ AF Mak, Kinglun Kingston Yang, Yingzi TI Hedgehog signaling in mature osteoblasts regulates bone formation and resorption by controlling PTHrP and RANKL expression SO BONE LA English DT Meeting Abstract CT International-Bone-and-Mineral-Society Davos Workshop on Bone Biology and Therapeutics CY MAR 09-14, 2008 CL Davos, SWITZERLAND SP Int Bone & Mineral Soc, Alliance Better Bone Hlth, Amgen, F Hoffman La Roche LTD, Hologic Inc, Novartis Oncol, Merck, Pfizer C1 [Mak, Kinglun Kingston; Yang, Yingzi] NIH, NHGRI, Genet Dis Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAR PY 2008 VL 42 SU 1 MA 22 BP S26 EP S26 DI 10.1016/j.bone.2007.12.032 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271OX UT WOS:000253799600022 ER PT J AU Childs, R AF Childs, R. TI Characterisation of GVT effects against RCC following allogeneic stem cell transplantation: identification of a new HERV-E derived tumour antigen targeted by allogeneic T-cells SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Childs, R.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S4 EP S5 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200011 ER PT J AU Le Blanc, K Remberger, M Barrett, J AF Le Blanc, K. Remberger, M. Barrett, J. TI Lymphocyte recovery is a major determinant of transplant outcome after myeloablative transplantation in patients with myeloid malignancies receiving matched unrelated grafts SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Le Blanc, K.; Remberger, M.] Karolinska Inst, Stockholm, Sweden. [Barrett, J.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S11 EP S12 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200029 ER PT J AU Mielke, S Shenoy, A Fellowes, VS Rezvani, K Savani, B Musse, L Wisch, L Kurlander, R Khuu, H Boss, C Barrett, AJ AF Mielke, S. Shenoy, A. Fellowes, V. S. Rezvani, K. Savani, B. Musse, L. Wisch, L. Kurlander, R. Khuu, H. Boss, C. Barrett, A. J. TI First clinical report of matched sibling allografts for haematologic malignancies using selectively photo-depleted T-cells and purified peripheral blood stem cells SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Mielke, S.; Shenoy, A.; Rezvani, K.; Savani, B.; Musse, L.; Wisch, L.; Boss, C.; Barrett, A. J.] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Fellowes, V. S.; Kurlander, R.; Khuu, H.] Natl Inst Hlth, CC, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S329 EP S330 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200832 ER PT J AU Rezvani, K Yong, ASM Mielke, S Eniafe, R Savani, B Price, D Gostick, E Douek, D Goldman, JM Barrett, J AF Rezvani, K. Yong, A. S. M. Mielke, S. Eniafe, R. Savani, B. Price, D. Gostick, E. Douek, D. Goldman, J. M. Barrett, J. TI CD8 T-cell responses to PR1 coincide with haematopoietic recovery following allogeneic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Rezvani, K.; Yong, A. S. M.; Mielke, S.; Eniafe, R.; Savani, B.; Price, D.; Gostick, E.; Douek, D.; Goldman, J. M.; Barrett, J.] NIH, Bethesda, MD 20892 USA. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S162 EP S162 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200404 ER PT J AU Rezvani, K Yong, AM Jafarpour, B Eniafe, R Mielke, S Barrett, J AF Rezvani, K. Yong, A. M. Jafarpour, B. Eniafe, R. Mielke, S. Barrett, J. TI Polyclonal memory CD8 T-cell responses to PRAME-specific peptides occur in patients with acute leukaemias and chronic myeloid leukaemia SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Rezvani, K.; Yong, A. M.; Jafarpour, B.; Eniafe, R.; Mielke, S.; Barrett, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S161 EP S162 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200402 ER PT J AU Sundin, M Lindblom, A Orvell, C Barrett, J Sundberg, B Watz, E Wikman, A Broliden, K Le Blanc, K AF Sundin, M. Lindblom, A. Oervell, C. Barrett, J. Sundberg, B. Watz, E. Wikman, A. Broliden, K. Le Blanc, K. TI Persistence of human parvovirus B19 in multipotent mesenchymal stromal cells expressing the erythrocyte P antigen: implications for transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Sundin, M.; Lindblom, A.; Oervell, C.; Sundberg, B.; Watz, E.; Wikman, A.; Broliden, K.; Le Blanc, K.] Karolinska Inst, Stockholm, Sweden. [Barrett, J.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S322 EP S322 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200813 ER PT J AU Weichsel, R Dix, C Wooldridge, L Clement, M Fenton-May, A Sewell, A Greiner, E Gostick, E Price, D Einsele, H Seggewiss, R AF Weichsel, R. Dix, C. Wooldridge, L. Clement, M. Fenton-May, A. Sewell, A. Greiner, E. Gostick, E. Price, D. Einsele, H. Seggewiss, R. TI Profound inhibition of antigen-specific T-cell effector functions by dasatinib SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 [Weichsel, R.; Dix, C.; Einsele, H.; Seggewiss, R.] Univ Wurzburg, Wurzburg, Germany. [Wooldridge, L.; Clement, M.; Fenton-May, A.; Sewell, A.; Price, D.] Cardiff Univ, Cardiff, Wales. [Greiner, E.] DHHS, NIH, Bethesda, MD USA. [Price, D.] Univ Oxford, Oxford, England. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2008 VL 41 SU 1 BP S271 EP S271 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 279ML UT WOS:000254359200681 ER PT J AU Leighl, NB Dent, S Clemons, M Vandenberg, TA Tozer, R Warr, DG Crump, RM Hedley, D Pond, GR Dancey, JE Moor, MJ AF Leighl, Natasha B. Dent, Susan Clemons, Mark Vandenberg, Theodore A. Tozer, Richard Warr, David G. Crump, R. Michael Hedley, David Pond, Gregory R. Dancey, Janet E. Moor, Malcolm J. TI A Phase 2 study of perifosine in advanced or metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE metastatic breast cancer; perifosine; alkylphospholipid; phase 2; taxane-refractory; anthracycline-refractory ID MILTEFOSINE SOLUTION; SOLID TUMORS; II TRIAL; EXPRESSION; CHEMOTHERAPY; CARCINOMA; PATHWAY; P21(WAF1); D-21266 AB Background First- and second-line chemotherapy with anthracyclines and taxanes in metastatic breast cancer yield a modest improvement in survival with potentially significant toxicity. Subsequent lines of chemotherapy yield response rates of 20-25%, with an unknown impact on survival. Perifosine, an oral alkylphospholipid structurally related to miltefosine, has marked activity against breast cancer cell lines and xenograft models, with broad spectrum cellular effects. Objectives To determine the efficacy and toxicity of perifosine in patients with metastatic breast cancer patients after up to 2 lines of prior chemotherapy for advanced disease. Methods 18 patients were enrolled, and 17 treated, using a loading/maintenance dose schedule, (day 1, 300 mg, maintenance 150 mg days 2-21) every 28 days, until disease progression or unacceptable toxicity. Results Median age of patients was 54 (28-69), 16/17 were female, ECOG performance status was 0/1 in 16 patients. Fifteen received at least 1 prior chemotherapy regimen for metastatic disease (maximum 2). A median of 2 cycles (range 1-13) was administered per patient. Sixteen were evaluable for response: 2 had SD for 4 cycles, 1 SD for 13 cycles, 13 progressed by cycle 2. Grade 3/4 drug-related non-hematologic toxicities include: diarrhea (2), vomiting (2), nausea (2), fatigue (2) and anorexia (1). No grade 3/4 hematologic toxicities were seen. Median time to progression was 8 weeks (7-15 weeks). Conclusion No objective responses were seen in this group of pretreated metastatic breast cancer patients. Disease stabilization was observed in 19% at 2 months. C1 [Leighl, Natasha B.; Pond, Gregory R.] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. [Dent, Susan; Clemons, Mark; Vandenberg, Theodore A.; Tozer, Richard; Warr, David G.; Crump, R. Michael; Hedley, David; Moor, Malcolm J.] Princess Margaret Hosp, Phase 2 Consortium, Toronto, ON, Canada. [Dancey, Janet E.] Natl Canc Inst Canc Therapy Evaluat Program, Bethesda, MD USA. RP Leighl, NB (reprint author), Univ Hlth Network, Princess Margaret Hosp, 5-105 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM Natasha.Leighl@uhn.on.ca FU NCI NIH HHS [N01 CM 17107] NR 31 TC 43 Z9 46 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2008 VL 108 IS 1 BP 87 EP 92 DI 10.1007/s10549-007-9584-x PG 6 WC Oncology SC Oncology GA 263DU UT WOS:000253198600009 PM 17458693 ER PT J AU Gaudet, MM Gammon, MD Bensen, JT Sagiv, SK Shantakumar, S Teitelbaum, SL Eng, SM Neugut, AI Santella, RM AF Gaudet, Mia M. Gammon, Marilie D. Bensen, Jeannette T. Sagiv, Sharon K. Shantakumar, Sumitra Teitelbaum, Susan L. Eng, Sybil M. Neugut, Alfred I. Santella, Regina M. TI Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE TP53; PAHs; smoking; breast cancer; epidemiology ID DNA-ADDUCTS; CODON-72 POLYMORPHISM; CIGARETTE-SMOKING; P53 POLYMORPHISMS; HAPLOTYPES; MUTATIONS; TISSUE; DAMAGE; CELLS AB Background p53 participates in cell cycle control, programmed cell death/apoptosis, and DNA repair, all pathways involved in carcinogenesis. TP53 variants may influence p53 function. Objective We evaluated whether three well-characterized TP53 variants-Ex4 + 119 C > G (rs#1042522, Arg72Pro), IVS6 + 62 A > G (rs#1625895), and an IVS3 16 bp insertion/ deletion (INDEL; rs#17878362)-were associated with breast cancer risk in a population-based case-control study. Methods Genotypes and haplotypes were determined using long-range PCR in a sample of 578 cases and 390 controls. Results For the Ex4 + 19 C > G SNP (rs1042522), women with the heterozygous genotype (G/C) had a 32% increase in breast cancer risk. Other variants were not associated with risk. We further examined whether these associations were modified by cigarette smoking status and detection of PAH-DNA adducts in circulating lymphocytes. Among current smokers, each copy of the minor alleles for the IVS6 + 62 A > G SNP (rs1625895) and the IVS3 INDEL polymorphism (rs17878362) was associated with lower breast cancer risk (OR = 0.49, 95% CI 0.27-0.90; OR = 0.42, 95% CI 0.22-0.78, respectively). However, among former smokers, the homozygous variant genotype for these 2 SNPs was observed among cases (4.1 and 3.2%, respectively) and not controls. Genotype associations were not modified by the presence or absence of DNA adducts in circulating lymphocytes. Three-loci haplotypes were not significantly associated with breast cancer risk. Conclusions These results should be confirmed in larger studies, but suggest that cigarette smoking may influence breast cancer risk through interaction with p53. C1 [Gaudet, Mia M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Gaudet, Mia M.; Gammon, Marilie D.; Bensen, Jeannette T.; Sagiv, Sharon K.; Shantakumar, Sumitra] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Teitelbaum, Susan L.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. [Eng, Sybil M.] Pfizer Inc, Global Epidemiol, New York, NY USA. [Neugut, Alfred I.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Neugut, Alfred I.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10027 USA. [Santella, Regina M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10027 USA. [Shantakumar, Sumitra] GlaxoSmithKline Inc, Worldwide Epidemiol, Res Triangle Pk, NC USA. RP Gaudet, MM (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20852 USA. EM gaudetm@mail.nih.gov OI Sagiv, Sharon/0000-0003-2245-1905 FU NCI NIH HHS [U01 CA/ES 66572]; NIEHS NIH HHS [P30 ES 09089, P30 ES 10126, P30 ES009089] NR 30 TC 17 Z9 17 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2008 VL 108 IS 1 BP 93 EP 99 DI 10.1007/s10549-007-9573-0 PG 7 WC Oncology SC Oncology GA 263DU UT WOS:000253198600010 PM 17624591 ER PT J AU Jansson, LM Choo, R Velez, ML Lowe, R Huestis, MA AF Jansson, Lauren M. Choo, Robin Velez, Martha L. Lowe, Ross Huestis, Marilyn A. TI Methadone Maintenance and Long-Term Lactation SO BREASTFEEDING MEDICINE LA English DT Article AB Breastfeeding among methadone-maintained women is frequently challenged because of unclear guidelines regarding this practice. Previous research has confirmed that concentrations of methadone in breastmilk in the neonatal period are low. Currently unknown are the concentrations of methadone in breastmilk among women who breastfeed for longer periods of time. The purpose of this research is to examine concentrations of methadone in the plasma and breastmilk of women who breastfeed their infants beyond the neonatal period. Four methadone-maintained women provided blood and breastmilk samples up to 6 months postpartum. The concentrations of methadone in blood and breastmilk were low, contributing to the recommendation of breastfeeding for some methadone-maintained women. C1 [Jansson, Lauren M.] Johns Hopkins Univ, Sch Med, Ctr Addict & Pregnancy, Dept Pediat, Baltimore, MD 21224 USA. [Choo, Robin; Lowe, Ross; Huestis, Marilyn A.] Natl Inst Drug Abuse, Chem & Drug Metab Intramural Res Program, Natl Inst Hlth, Baltimore, MD USA. [Choo, Robin] Univ Pittsburgh, Titusville, PA USA. RP Jansson, LM (reprint author), Johns Hopkins Univ, Sch Med, Ctr Addict & Pregnancy, Dept Pediat, 4940 Eastern Ave,D5, Baltimore, MD 21224 USA. EM ljansson@jhmi.edu FU NIH/NIDA [K08 DA00495, RO1 DA019934] FX The authors thank the subjects, without whose cooperation this work is not possible, and the staff at the Center for Addiction and Pregnancy, Baltimore, MD. This work is supported by NIH/NIDA grants K08 DA00495 and RO1 DA019934, awarded to L. M. J., and the NIH, NIDA Intramural Research Program. NR 15 TC 17 Z9 17 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1556-8253 J9 BREASTFEED MED JI Breastfeed. Med. PD MAR PY 2008 VL 3 IS 1 BP 34 EP U43 DI 10.1089/bfm.2007.0032 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA V11LZ UT WOS:000207534400006 PM 18333767 ER PT J AU Costa, PT McCrae, RR Martin, TA AF Costa, Paul T., Jr. McCrae, Robert R. Martin, Thomas A. TI Incipient adult personality: The NEO-PI-3 in middle-school-aged children SO BRITISH JOURNAL OF DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID MULTITRAIT-MULTIMETHOD ANALYSES; HIGHER-ORDER FACTORS; NEO-PI-R; 5-FACTOR MODEL; BIG 5; ADOLESCENTS PERSONALITY; DISCRIMINANT VALIDITY; SELF-REPORTS; TRAITS; PERSPECTIVE AB This study administered the NEO Personality Inventory-3 (NEO-PI-3), a more readable version of an adult measure of the Five-Factor Model, to 449 boys and girls aged 12 and 13, who described themselves or a peer. Analyses of readability, reliability, factor structure, and convergent and discriminant validity suggested that the NEO-PI-3 can be appropriately used in this age group. Personality traits in children of this age closely resemble in structure and functioning the traits of older adolescents and adults. Most gender differences known from studies of adults are found in this age group, and mean levels show continuity with older groups. The NEO-PI-3 appears to be a useful instrument for research, and potentially for clinical applications, in middle-school-aged children. C1 [Costa, Paul T., Jr.; McCrae, Robert R.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. [Martin, Thomas A.] Susquehanna Univ, Dept Psychol, Selinsgrove, PA USA. RP McCrae, RR (reprint author), NIA, Lab Personal & Cognit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov OI Costa, Paul/0000-0003-4375-1712 NR 58 TC 14 Z9 16 U1 2 U2 21 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 0261-510X J9 BRIT J DEV PSYCHOL JI Br. J. Dev. Psychol. PD MAR PY 2008 VL 26 BP 71 EP 89 DI 10.1348/026151007X196273 PN 1 PG 19 WC Psychology, Developmental SC Psychology GA 260CF UT WOS:000252987700005 ER PT J AU Franco, R Casado, V Cortes, A Mallol, J Ciruela, F Ferre, S Lluis, C Canela, E AF Franco, R. Casado, V. Cortes, A. Mallol, J. Ciruela, F. Ferre, S. Lluis, C. Canela, Ei TI G-protein-coupled receptor heteromers: function and ligand pharmacology SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article; Proceedings Paper CT Joint Life Science Meeting of the British-Pharmacological-Society/Physiological-Society/Biochemical-Societ y CY JUL, 2007 CL Glasgow, SCOTLAND SP British Pharmacol Soc, Physiol Soc, Biochem Soc DE adenosine; dopamine; opioid; fitting data; receptor dimers; receptor oligomers; allosteric regulation; cooperativity; drug targets ID ADENOSINE A(2A); ENERGY-TRANSFER; HIGH-AFFINITY; HETERODIMERIZATION; DIMERIZATION; RELEVANCE; BINDING; DIMERS; MODEL; FLUORESCENCE AB Almost all existing models for G-protein-coupled receptors ( GPCRs) are based on the occurrence of monomers. Recent studies show that many GPCRs are dimers. Therefore for some receptors dimers and not monomers are the main species interacting with hormones/neurotransmitters/drugs. There are reasons for equivocal interpretations of the data fitting to receptor dimers assuming they are monomers. Fitting data using a dimer-based model gives not only the equilibrium dissociation constants for high and low affinity binding to receptor dimers but also a 'cooperativity index' that reflects the molecular communication between monomers within the dimer. The dimer cooperativity index ( DC) is a valuable tool that enables to interpret and quantify, for instance, the effect of allosteric regulators. For different receptors heteromerization confers a specific functional property for the receptor heteromer that can be considered as a 'dimer fingerprint'. The occurrence of heteromers with different pharmacological and signalling properties opens a complete new field to search for novel drug targets useful to combat a variety of diseases and potentially with fewer side effects. Antagonists, which are quite common marketed drugs targeting GPCRs, display variable affinities when a given receptor is expressed with different heteromeric partners. This fact should be taken into account in the development of new drugs. C1 [Franco, R.; Casado, V.; Cortes, A.; Mallol, J.; Ciruela, F.; Lluis, C.; Canela, Ei] Univ Barcelona, Dept Bioquim & Biol Mol, CIBERNED, IDIBAPS, E-08028 Barcelona, Spain. [Ferre, S.] Natl Inst Drug Abuse, Dept Hlth & Human Serv, Behav Neurosci Branch, Intramural Res Program,NIH, Baltimore, MD USA. RP Franco, R (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, CIBERNED, IDIBAPS, Av Diagonal 645, E-08028 Barcelona, Spain. EM rfranco@ub.edu RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825 FU Intramural NIH HHS NR 42 TC 42 Z9 42 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 2008 VL 153 SU 1 BP S90 EP S98 DI 10.1038/sj.bjp.0707571 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 268OA UT WOS:000253587900012 PM 18037920 ER PT J AU Sahut-Barnola, I Lambert-Langlais, S Val, P Lefrancois-Martinez, AM Pointud, JC De, JC Ragazzon, B Bertherat, J Stratakis, C Martinez, A AF Sahut-Barnola, I Lambert-Langlais, S. Val, P. Lefrancois-Martinez, A. M. Pointud, J. C. De, Joussineau C. Ragazzon, B. Bertherat, J. Stratakis, C. Martinez, A. TI PKA signalization and surrenalian tumorigenesis SO BULLETIN DU CANCER LA French DT Meeting Abstract C1 CNRS, INSERM, U567, Inst Cochin,UMR8104, F-75700 Paris, France. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0007-4551 J9 B CANCER JI Bull. Cancer PD MAR PY 2008 VL 95 SI SI BP S90 EP S90 PG 1 WC Oncology SC Oncology GA 277PE UT WOS:000254225900174 ER PT J AU Yabroff, KR Harlan, LC Clegg, LX Ballard-Barbash, R Stevens, J Weaver, DL AF Yabroff, K. Robin Harlan, Linda C. Clegg, Limin X. Ballard-Barbash, Rachel Stevens, Jennifer Weaver, Donald L. TI Is mode of breast cancer detection associated with cancer treatment in the united states? SO CANCER LA English DT Article DE mammography; breast cancer detection; breast cancer/detection; tamoxifen; chemotherapy; practice guidelines ID RANDOMIZED-TRIALS; ADJUVANT THERAPY; OLDER WOMEN; MAMMOGRAPHY; SURVIVAL; PATTERNS; PREDICTORS; RECURRENCE; TAMOXIFEN; INTERVAL AB BACKGROUND. The prognosis for women who have breast cancer detected by mammography is more favorable than that for women who have breast cancer detected by other methods, even after controlling for tumor characteristics. In the current study, the authors explored whether detection by mammography was associated with greater use of guideline-consistent breast cancer treatment among patients with recently diagnosed breast cancer in the United States. METHODS. The authors evaluated the association between mode of breast cancer detection (mammography vs other) and use of guideline-consistent treatment in 1006 women aged >= 40 years who were diagnosed in 2000. These patients were sampled from the Surveillance, Epidemiology, and End Results Program as part of the Patterns of Care studies. The analyses controlled for the potential confounders of clinical, demographic, and health system characteristics in multivariate logistic regression models. RESULTS. Breast cancer patients who were diagnosed by mammography were more likely to be aged >= 55 years, to have lower stage disease, and to be treated in larger hospitals than patients who were diagnosed by other methods (P <.05). Women whose breast cancer was diagnosed by a method other than mammography were more likely to receive guideline-consistent treatment than women who were diagnosed by mammography in unadjusted (odds ratio, 1.39; 95% confidence interval, 1.07-1.80) and multivariate analyses (odds ratio, 1.43; 95% confidence interval, 1.05-1.95). CONCLUSIONS. The current results indicated that women who had breast cancer detected by methods other than mammography were slightly more likely to receive guideline-consistent therapy than women who had breast cancer detected by mammography. Future research exploring mode of detection, guideline-consistent treatment, and survival among patients with recently diagnosed breast cancer may inform understanding of factors associated with breast cancer prognosis. C1 [Yabroff, K. Robin; Harlan, Linda C.; Clegg, Limin X.; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Clegg, Limin X.] US Dept Vet Affairs, Off Healthcare Inspect, Off Inspector Gen, Washington, DC USA. [Stevens, Jennifer] Informat Management Serv Inc, Silver Spring, MD USA. [Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. RP Yabroff, KR (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM Yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 FU NCI NIH HHS [N01 PC 67000, N01 PC 65064, N01 PC 65107, N01 PC 67001, N01 PC 67005, N01 PC 67006, N01 PC 67007, N01 PC 67008, N01 PC 67009, N01 PC 67010] NR 35 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2008 VL 112 IS 5 BP 1011 EP 1019 DI 10.1002/cncr.23260 PG 9 WC Oncology SC Oncology GA 268HA UT WOS:000253569100009 PM 18189297 ER PT J AU Stetler-Stevenson, WG AF Stetler-Stevenson, William G. TI The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2 SO CANCER AND METASTASIS REVIEWS LA English DT Review DE tissue inhibitor of metalloproteinase; TIMP-2; anti-angiogenic; anti-tumorigenic; cellular differentiation; cancer therapy ID ERYTHROID-POTENTIATING ACTIVITY; BREAST EPITHELIAL-CELLS; MATRIX METALLOPROTEINASES; GROWTH-FACTOR; IN-VITRO; MAMMARY TUMORIGENESIS; EXTRACELLULAR-MATRIX; GELATINASE-A; ANGIOGENESIS; TIMP-2 AB Proteolytic remodeling of the extracellular matrix is an important component of disease progression in many chronic disease states and is the initiating event in the formation of the tumor microenvironment in cancer. It is the balance of extracellular matrix degrading enzymes, the matrix metalloproteinases (MMPs) and their endogenous inhibitors that determine the extent of tissue remodeling. Unchecked MMP activity can result in significant tissue damage, facilitate disease progression and is associated with host responses to pathologic injury such as angiogenesis and inflammation. The tissue inhibitors of metalloproteinases (TIMPs) have been shown to regulate MMP activity. However, recent findings demonstrate that the tissue inhibitor of metalloproteinases-2 (TIMP-2) inhibits the mitogenic response of human microvascular endothelial cells to growth factors, such as VEGF-A and FGF-2 in vitro and angiogenesis in vivo. The mechanism of this effect is independent of metalloproteinase inhibition. Our lab is the first to demonstrate a cell-surface signaling receptor for a member of the TIMP family and suggest that TIMP-2 functions to regulate cellular responses to growth factors. These new findings are discussed in terms of a model of TIMP-2 regulation of cellular functions in the tumor microenvironment. C1 NCI, Cell & Canc Biol Branch, Vasc Biol Fac, CCR,NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, WG (reprint author), NCI, Cell & Canc Biol Branch, Vasc Biol Fac, CCR,NIH, Bldg 10,Room 2A33,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA. EM sstevenw@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU Intramural NIH HHS [Z01 SC009179-18] NR 70 TC 78 Z9 79 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD MAR PY 2008 VL 27 IS 1 BP 57 EP 66 DI 10.1007/s10555-007-9105-8 PG 10 WC Oncology SC Oncology GA 255PX UT WOS:000252671000007 PM 18058195 ER PT J AU Danish, M Sissung, T Price, DK Figg, WD AF Danish, Matthew Sissung, Tristan Price, Douglas K. Figg, William D. TI Genetic stability of tumor microenvironment SO CANCER BIOLOGY & THERAPY LA English DT Article DE microenvironment; cancer; breast; genomic alterations; microsatellites; TP53 C1 [Danish, Matthew; Sissung, Tristan; Price, Douglas K.; Figg, William D.] NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Danish, M (reprint author), NCI, Canc Therapeut Branch, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC 1910, Bethesda, MD 20892 USA. EM Danishm@mail.nih.gov RI Figg Sr, William/M-2411-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2008 VL 7 IS 3 BP 331 EP 332 PG 2 WC Oncology SC Oncology GA 312HB UT WOS:000256658700002 PM 18362517 ER PT J AU Gardner, ER Sparreboom, A Verweij, J Figg, WD AF Gardner, Erin R. Sparreboom, Alex Verweij, Jaap Figg, William D. TI Lack of ABC transporter autoinduction in mice following long-term exposure to imatinib SO CANCER BIOLOGY & THERAPY LA English DT Article DE imatinib; ABCB1; ABCG2; pharmacokinetics ID CHRONIC MYELOID-LEUKEMIA; DOSE-ESCALATION; P-GLYCOPROTEIN; IN-VITRO; RESISTANCE; MESYLATE; PHARMACOKINETICS; STI571; MECHANISMS; INHIBITOR AB Purpose: Chronic imatinib exposure has been shown to result in upregulation of the ABCB1 ( P-glycoprotein) and ABCG2 ( BCRP) transporters in vitro, for which imatinib is a substrate. This finding, along a trend towards increasing imatinib clearance over time in patients, has resulted in the suggestion that pharmacokinetic resistance may be contributing to eventual treatment failure. Here, we sought to determine the effects of long-term imatinib exposure on apparent oral clearance and transporter expression in vivo. Results: Plasma and liver concentrations of imatinib did not change significantly ( p > 0.1) over the course of treatment, suggesting that steady-state had been reached. There was no increase in Abcb1 or Abcg2 expression in liver samples, whereas expression of these transporters in intestinal samples was highly variable, and no increase was apparent. Methods: Male BALB/ c mice were treated daily-times 5 with oral imatinib at a dose of 50 mg/ kg for 4 consecutive weeks. Imatinib concentrations were measured in plasma and liver tissue prior to treatment and following each week of dosing. Western blotting of liver and intestinal tissue lysates was performed to assess expression of Abcb1 and Abcg2. Conclusions: Imatinib does not appear to cause upregulation of ABC transporters in the hepatic and intestinal compartments in mice. These data do not support the possibility that autoinduction contributes to the development of resistance to imatinib. C1 [Sparreboom, Alex; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, Clin Pharmacol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Verweij, Jaap] Erasmus MC Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [, NIH0011335962]; NCI NIH HHS [N01-CO-12400]; PHS HHS [NIH0011335962] NR 26 TC 6 Z9 6 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2008 VL 7 IS 3 BP 412 EP 415 PG 4 WC Oncology SC Oncology GA 312HB UT WOS:000256658700017 PM 18094612 ER PT J AU Faupel-Badger, JM Kidd, LCR Albanes, D Virtamo, J Woodson, K Tangrea, JA AF Faupel-Badger, Jessica M. Kidd, La Creisi Renee Albanes, Demetrius Virtamo, Jarmo Woodson, Karen Tangrea, Joseph A. TI Association of IL-10 polymorphisms with prostate cancer risk and grade of disease SO CANCER CAUSES & CONTROL LA English DT Article DE ATBC study; interleukin-10; prostate cancer ID HEPATOCELLULAR-CARCINOMA; GENETIC POLYMORPHISMS; SERUM INTERLEUKIN-10; BETA-CAROTENE; LUNG-CANCER; PROMOTER; INHIBITION; HAPLOTYPE; ANGIOGENESIS; STIMULATION AB Animal and in vitro models of prostate cancer demonstrate high IL-10 levels result in smaller tumors, fewer metastases, and reduced angiogenesis compared to controls. We sought to examine the hypothesis that genotypes correlated with low IL-10 production may be associated with increased prostate cancer risk among Finnish male participants from the Alpha-tocopherol Beta-carotene Cancer Prevention Study. DNA from 584 prostate cancer cases and 584 controls was genotyped for four IL-10 alleles, -1082, -819, -592, and 210. DNA from more of the controls than cases failed to amplify, resulting in 509 cases and 382 controls with genotype data for -1082; 507 and 384 for -819; 511 and 386 for -592; and 491 and 362 for 210. Odds ratios for the association between the IL-10 genotypes and risk of prostate cancer or, among cases only, high-grade disease were calculated using logistic regression. In this population, the -819 TT and -592 AA low expression genotypes were highly correlated. These two genotypes also were associated with increased prostate cancer susceptibility (OR = 1.92, 95% CI 1.07-3.43 for -819) and, among cases, with high-grade tumors (OR = 2.56, 95% CI 1.26-5.20 for -819). These data demonstrate genotypes correlated with low IL-10 production are associated with increased risk of prostate cancer and with high-grade disease in this population. C1 [Faupel-Badger, Jessica M.] NCI, Natl Inst Hlth, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. [Faupel-Badger, Jessica M.] NCI, Natl Inst Hlth, Ctr Canc Res, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. [Kidd, La Creisi Renee] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Albanes, Demetrius] NCI, Natl Inst Hlth, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Woodson, Karen] NCI, Natl Inst Hlth, Ctr Canc Res, Canc Genet Branch, Bethesda, MD USA. [Tangrea, Joseph A.] Natl Inst Hlth, Div Canc Prevent, Prostate & Urol Canc Res Grp, Bethesda, MD USA. RP Faupel-Badger, JM (reprint author), NCI, Natl Inst Hlth, Canc Prevent Fellowship Program, Div Canc Prevent, 37 Convent Dr,Bldg 37,Room 1106, Bethesda, MD 20892 USA. EM badgerje@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01 RC 37004, N01 RC 45035]; Intramural NIH HHS; NCI NIH HHS [N01 CN 45165] NR 24 TC 35 Z9 36 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2008 VL 19 IS 2 BP 119 EP 124 DI 10.1007/s10552-007-9077-6 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 268MG UT WOS:000253583300001 PM 17999153 ER PT J AU Etzioni, R Tsodikov, A Mariotto, A Szabo, A Falcon, S Wegelin, J Ditommaso, D Karnofski, K Gulati, R Penson, DF Feuer, E AF Etzioni, Ruth Tsodikov, Alex Mariotto, Angela Szabo, Aniko Falcon, Seth Wegelin, Jake ditommaso, Dante Karnofski, Kent Gulati, Roman Penson, David F. Feuer, Eric TI Quantifying the role of PSA screening in the US prostate cancer mortality decline SO CANCER CAUSES & CONTROL LA English DT Article DE prostate-specific antigen; prostate cancer; public health; computer simulation ID UNITED-STATES; BIOPSY STRATEGY; TRENDS; MODEL; TRIAL; MANAGEMENT; PATTERNS; THERAPY; EUROPE; LUNG AB Objective To quantify the plausible contribution of prostate-specific antigen (PSA) screening to the nearly 30% decline in the US prostate cancer mortality rate observed during the 1990s. Methods Two mathematical modeling teams of,the US National Cancer Institute's Cancer Intervention and Surveillance Modeling Network independently projected disease mortality in the absence and presence of PSA screening. Both teams relied on Surveillance, Epidemiology, and End Results (SEER) registry data for disease incidence, used common estimates of PSA screening rates, and assumed that screening, by shifting disease from distant to local-regional clinical stage, confers a corresponding improvement in disease-specific survival. Results The teams projected similar mortality increases in the absence of screening and decreases in the presence of screening after 1985. By 2000, the models projected that 45% (Fred Hutchinson Cancer Research Center) to 70% (University of Michigan) of the observed decline in prostate cancer mortality could be plausibly attributed to the stage shift induced by screening. Conclusions PSA screening may account for much, but not all, of the observed drop in prostate cancer mortality. Other factors, such as changing treatment practices, may also have played a role in improving prostate cancer outcomes. C1 [Etzioni, Ruth; Falcon, Seth; ditommaso, Dante; Karnofski, Kent; Gulati, Roman] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Tsodikov, Alex; Wegelin, Jake] Univ Calif Davis, Dept Biostat, Davis, CA 95616 USA. [Szabo, Aniko; Feuer, Eric] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Szabo, Aniko] Huntsman Canc Inst, Salt Lake City, UT USA. [Penson, David F.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Penson, David F.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. RP Etzioni, R (reprint author), Fred Hutchinson Canc Res Ctr, 1100 fairview Ave N,M2-B230, Seattle, WA 98109 USA. EM retzioni@fhcrc.org FU NCI NIH HHS [U01 CA 88160, U01 CA088160, U01 CA097414-07, U01 CA097414-08] NR 40 TC 161 Z9 164 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2008 VL 19 IS 2 BP 175 EP 181 DI 10.1007/s10552-007-9083-8 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 268MG UT WOS:000253583300007 PM 18027095 ER PT J AU Evans, A Bates, V Troy, H Hewitt, S Holbeck, S Chung, YL Phillips, R Stubbs, M Griffiths, J Airley, R AF Evans, Andrew Bates, Victoria Troy, Helen Hewitt, Stephen Holbeck, Susan Chung, Yuen-Li Phillips, Roger Stubbs, Marion Griffiths, John Airley, Rachel TI Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent link with cell turnover is revealed through COMPARE analysis and metabolomic studies SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Glut-1; HIF-1; NCI60; COMPARE analysis; metabolomics ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; GLUCOSE-TRANSPORTER GLUT-1; POSITRON-EMISSION-TOMOGRAPHY; ENDOTHELIAL GROWTH-FACTOR; TUMOR-GROWTH; GENE-EXPRESSION; BREAST-CANCER; PHASE-I; DEFICIENCY SYNDROME; PROGNOSTIC VALUE AB The facilitative glucose transporter Glut-1 is overexpressed and confers poor prognosis in a wide range of solid tumours. The peri-necrotic pattern of expression often seen in human tumour samples is linked with its transcriptional control in hypoxic conditions by hypoxia-inducible factor HIF-1 or through a reduced rate of oxidative phosphorylation. Hypoxia-regulated genes offer promise as novel therapeutic targets as a means of preventing the proliferation and eventual metastatic spread of tissue originating from residual chemically and radio resistant hypoxic cells that have survived treatment. Inhibiting the expression or functionality of Glut-1 may be a way of specifically targeting hypoxic cells within the tumour that depend upon a high rate of glucose uptake for anaerobic glycolysis. We used an array of formalin-fixed, paraffin-embedded samples of the NCI-60 panel of cell lines to carry out immunohistochemical detection of Glut-1 and to select possible candidate lead compounds by COMPARE analysis with agents from the NCI diversity screen, which may work via inhibition of Glut-1 or Glut-1-dependent processes. "Positive" COMPARE hits were mostly conjugated Pseudomonas toxins binding the epidermal growth factor receptor (EGFR). However, correlations with standard anticancer agents were virtually all negative, indicating a link between Glut-1 and chemoresistance. MTT proliferation assays carried out using stable, Glut-1 overexpressing cell lines generated from the bladder EJ138, human fibrosarcoma HT 1080 and the hepatoma wild type Hepa and HIF-1B-deficient c4 tumour cell lines revealed a cell line-dependent increase in chemoresistance to dacarbazine, vincristine and the bioreductive agent EO9 in Glut-1 overexpressing EJ138 relative to WT and empty vector controls. Metabolomic analysis (P-31-MRS and H-1 MRS) carried out using cell lysates and xenografts generated from Glut-1 overexpressing Hepa and c4 cell lines showed higher glucose levels in Glut-1 overxpressing c4 relative to parental tumour extracts occurred in the absence of an increase in lactate levels, which were in turn significantly higher in the Glut-1 overexpressing Hepa xenografts. This implies that Glut-1 over-expression without a co-ordinate increase in HIF-1-regulated glycolytic enzymes increases glucose uptake but not the rate of glycolysis. Glut-1 overexpressing xenografts also showed higher levels of phosphodiester (PDE), which relates to the metabolite turnover of phospholipids and is involved in membrane lipid degradation, indicating a mechanism by which Glut-1 may increase cell turnover. C1 [Airley, Rachel] Albert Einstein Coll Med, Chanin Cancer Inst, Dept Dev & Mol Biol, Bronx, NY 10467 USA. [Phillips, Roger] Univ Bradford, Tom Connors Canc Res Ctr, Bradford BD7 1DP, W Yorkshire, England. [Holbeck, Susan] NCI, Informat Technol Branch, Dev Therapeut Programme, Bethesda, MD 20892 USA. [Hewitt, Stephen] NCI, TARP Lab, Bethesda, MD 20892 USA. [Troy, Helen; Chung, Yuen-Li; Stubbs, Marion; Griffiths, John] Univ London St Georges Hosp, Dept Basic Med Sci, CR UK Biomed Magnet Resonance Res Grp, London, England. [Evans, Andrew; Bates, Victoria; Airley, Rachel] Liverpool John Moores Univ, Sch Pharm & Chem, Tumour Metab & Therapeut Grp, Liverpool L3 3AF, Merseyside, England. RP Airley, R (reprint author), Albert Einstein Coll Med, Chanin Cancer Inst, Dept Dev & Mol Biol, Bronx, NY 10467 USA. EM a.r.evans@ljmu.ac.uk; V.Bates@2004.ljmu.ac.uk; htroy@sgul.ac.uk; hewitts@mail.nih.gov; holbecks@mail.nih.gov; ylchung@sgul.ac.uk; r.m.philips@brad.ac.uk; mstubbs@sgul.ac.uk; jgriffiths@sgul.ac.uk; rairleyinusa@hotmail.com RI Griffiths, John/F-2853-2010; OI Hewitt, Stephen/0000-0001-8283-1788; Phillips, Roger/0000-0003-3504-177X NR 56 TC 46 Z9 48 U1 0 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2008 VL 61 IS 3 BP 377 EP 393 DI 10.1007/s00280-007-0480-1 PG 17 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 241IF UT WOS:000251649400004 PM 17520257 ER PT J AU Jimeno, A Rudek, MA Purcell, T Laheru, DA Messersmith, WA Dancey, J Carducci, MA Baker, SD Hidalgo, M Donehower, RC AF Jimeno, Antonio Rudek, Michelle A. Purcell, Thomas Laheru, Daniel A. Messersmith, Wells A. Dancey, Janet Carducci, Michael A. Baker, Sharyn D. Hidalgo, Manuel Donehower, Ross C. TI Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in patients with solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY SEP 28-OCT 01, 2004 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR DE UCN-01; irinotecan; phase I; cell cycle; G2; M checkpoint ID PROTEIN-KINASE-C; CELL-LINES; ALPHA(1)-ACID GLYCOPROTEIN; CLINICAL-PHARMACOLOGY; SELECTIVE INHIBITOR; GROWTH-INHIBITION; BETA INHIBITOR; CANCER; CARCINOMA; VITRO AB Purpose 7-Hydroxystaurosporine (UCN-01) is a protein kinase inhibitor that inhibits several serine-threonine kinases including PKC and PDK1. Due to the preclinical synergistic effects seen with topoisomerase I inhibitors and non-overlapping toxicity, UCN-01 and irinotecan were combined in a dose-finding study designed to determine the maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of UCN-01 and irinotecan. Methods Patients with incurable solid malignancies received UCN-01 intravenously (IV) as a 3-h infusion on day 1 and irinotecan IV over 90 min on days 1 and 8 of a 21-day cycle. Doses of UCN-01 for subsequent cycles were half the starting dose. Dose level 1 (DL1) consisted of UCN-01 and irinotecan doses of 50 and 60 mg/m(2), respectively. Blood samples were collected in cycle 1 for UCN-01, irinotecan, and irinotecan metabolites. Results A total of 16 patients were enrolled on the trial at UCN-01/Irinotecan doses of 50/60 mg/m(2) (DL1; n = 1), 70/60 mg/m(2) (DL2; n = 6), 90/60 mg/m(2) (DL3; n = 4), and 70/90 mg/m(2) (DL4; n = 5). Two dose-limiting toxicities were observed each in DL3 and DL4 (2 grade 3 hypophosphatemia, 1 grade 4 hyperglycemia and grade 3 hypophosphatemia, 1 grade 4 febrile neutropenia). Fatigue, diarrhea, nausea, and anorexia were the most prevalent toxicities. No objective responses were documented, and four patients had stable disease for at least ten cycles. The long half-life (292.0 +/- 135.7 h), low clearance (0.045 +/- 0.038 l/h), and volume of distribution (14.3 +/- 5.9 l) observed for UCN-01 are consistent with prior UCN-01 data. There was a significant decrease in C-max of APC, AUC of APC and SN-38, and AUC ratio of SN-38:irinotecan when comparing days 1 and 8 PK. Conclusions APC and SN-38 exposure decreased when administered in combination with UCN-01. The MTD of the combination based on protocol criteria was defined as 70 mg/m(2) of UCN-01 on day 1 and 60 mg/m(2) of irinotecan on days 1 and 8 in a 21-day cycle. C1 [Jimeno, Antonio; Rudek, Michelle A.; Purcell, Thomas; Laheru, Daniel A.; Messersmith, Wells A.; Carducci, Michael A.; Baker, Sharyn D.; Hidalgo, Manuel; Donehower, Ross C.] Johns Hopkins Univ, Sidney Kimmel Comprehensive Canc Ctr, Baltimore, MD 21218 USA. [Dancey, Janet] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Donehower, RC (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehensive Canc Ctr, Canc Res Bldg I,1650 Orleans St,Room 186, Baltimore, MD 21218 USA. EM donehro@jhmi.edu RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU NCI NIH HHS [P30 CA006973, U01 CA 70095, U01 CA070095] NR 36 TC 28 Z9 29 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2008 VL 61 IS 3 BP 423 EP 433 DI 10.1007/s00280-007-0485-9 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 241IF UT WOS:000251649400008 PM 17429623 ER PT J AU Tucker, MA AF Tucker, Margaret A. TI Is sunlight important to melanoma causation? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID SUN EXPOSURE; CUTANEOUS MELANOMA; MELANOCYTIC NEVI; ULTRAVIOLET-RADIATION; RISK-FACTORS; CHILDREN; SKIN; SUSCEPTIBILITY; EPIDEMIOLOGY; POPULATIONS C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tucker, MA (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7122, Bethesda, MD 20892 USA. EM tuckerp@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS NR 29 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 467 EP 468 DI 10.1158/1055-9965.EPI-07-2743 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600001 PM 18319329 ER PT J AU Davis, FG Malmer, BS Aldape, K Barnholtz-Sloan, JS Bondy, ML Brannstrom, T Bruner, JM Burger, PC Collins, VP Inskip, PD Kruchko, C McCarthy, BJ McLendon, RE Sadetzki, S Tihan, T Wrensch, MR Buffler, PA AF Davis, Faith G. Malmer, Beatrice S. Aldape, Ken Barnholtz-Sloan, Jill S. Bondy, Melissa L. Brannstrom, Thomas Bruner, Janet M. Burger, Peter C. Collins, V. Peter Inskip, Peter D. Kruchko, Carol McCarthy, Bridget J. McLendon, Roger E. Sadetzki, Siegal Tihan, Tarik Wrensch, Margaret R. Buffler, Patricia A. TI Issues of diagnostic review in brain tumor studies: From the brain tumor epidemiology consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; CLASSIFICATION; GLIOMAS; CANCER; PROGNOSIS; DISEASE; 19Q; 1P AB Epidemiologists routinely conduct centralized single pathology reviews to minimize interobserver diagnostic variability, but this practice does not facilitate the combination of studies across geographic regions and institutions where diagnostic practices differ. A meeting of neuropathologists and epidemiologists focused on brain tumor classification issues in the context of protocol needs for consortial studies (http://epi.grants. cancer.gov/btec/). It resulted in recommendations relevant to brain tumors and possibly other rare disease studies. Two categories of brain tumors have enough general agreement over time, across regions, and between individual pathologists that one can consider using existing diagnostic data without further review: glioblastomas and meningiomas (as long as uniform guidelines such as those provided by the WHO are used). Prospective studies of these tumors benefit from collection of pathology reports, at a minimum recording the pathology department and classification system used in the diagnosis. Other brain tumors, such as oligodendroglioma, are less distinct and require careful histopathologic review for consistent classification across study centers. Epidemiologic study protocols must consider the study specific aims, diagnostic changes that have taken place over time, and other issues unique to the type(s) of tumor being studied. As diagnostic changes are being made rapidly, there are no readily available answers on disease classification issues. It is essential that epidemiologists and neuropathologists collaborate to develop appropriate study designs and protocols for specific hypothesis and populations. C1 [Davis, Faith G.; McCarthy, Bridget J.] Univ Illinois, Sch Publ Hlth, Div Epidemiol Biostat, Chicago, IL 60612 USA. [Malmer, Beatrice S.] Umea Univ Hosp, Dept Radiat Sci & Oncol, S-90185 Umea, Sweden. [Brannstrom, Thomas] Umea Univ, Dept Med Biosci Pathol, Umea, Sweden. [Aldape, Ken; Bruner, Janet M.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Bondy, Melissa L.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA. [Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA. [Burger, Peter C.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Collins, V. Peter] Addenbrookes Hosp, Dept Pathol, Div Mol Histopathol, Cambridge, England. [Inskip, Peter D.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kruchko, Carol; McCarthy, Bridget J.] Cent Brain Tumor Registry US, Hinsdale, IL USA. [McLendon, Roger E.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Sadetzki, Siegal] Chaim Sheba Med Ctr, Gertner Inst, Canc & Radiat Epidemiol Unit, IL-52621 Tel Hashomer, Israel. [Sadetzki, Siegal] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel. [Tihan, Tarik; Wrensch, Margaret R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Buffler, Patricia A.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. RP Davis, FG (reprint author), Univ Illinois, Sch Publ Hlth, Div Epidemiol Biostat, 1603 W Taylor,M-C 923, Chicago, IL 60612 USA. EM fayed@uic.edu RI Barnholtz-Sloan, Jill/A-4817-2011 FU Intramural NIH HHS; NINDS NIH HHS [1R13NS0554479-01] NR 24 TC 37 Z9 37 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 484 EP 489 DI 10.1158/1055-9965.EPI-07-0725 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600005 PM 18349266 ER PT J AU Andreotti, G Chen, JB Gao, YT Rashid, A Chen, BSE Rosenberg, P Sakoda, LC Deng, J Shen, MC Wang, BS Han, TQ Zhang, BH Yeager, M Welch, R Chanock, S Fraumeni, JF Hsing, AW AF Andreotti, Gabriella Chen, Jinbo Gao, Yu-Tang Rashid, Asif Chen, Bingshu E. Rosenberg, Philip Sakoda, Lori C. Deng, Jie Shen, Ming-Chang Wang, Bing-Sheng Han, Tian-Quan Zhang, Bai-He Yeager, Meredith Welch, Robert Chanock, Stephen Fraumeni, Joseph F., Jr. Hsing, Ann W. TI Polymorphisms of genes in the lipid metabolism pathway and risk of biliary tract cancers and stones: A population-based case-control study in shanghai, china SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID APOLIPOPROTEIN-E POLYMORPHISM; LOW-DENSITY-LIPOPROTEIN; GALLBLADDER-DISEASE; E GENOTYPE; ASSOCIATION; PROTEIN; HAPLOTYPES; GALLSTONES; DNA; HETEROGENEITY AB Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by Taq-Man assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% Cl), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% Cl, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% Cl, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% Cl, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct. C1 [Andreotti, Gabriella; Chen, Bingshu E.; Rosenberg, Philip; Chanock, Stephen; Fraumeni, Joseph F., Jr.; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gao, Yu-Tang; Deng, Jie] Shanghai Canc Ctr, Dept Epidemiol, Shanghai, Peoples R China. [Rashid, Asif] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Washington, DC USA. [Shen, Ming-Chang] Fudan Univ, Shanghai Tumor Hosp, Shanghai, Peoples R China. [Wang, Bing-Sheng] Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China. [Han, Tian-Quan] Second Med Univ, Ruijin Hosp, Dept Surg, Shanghai, Peoples R China. [Zhang, Bai-He] Second Mil Univ, Inst Oriental Hepatobiliary Surg, Shanghai, Peoples R China. [Yeager, Meredith; Welch, Robert; Chanock, Stephen] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chanock, Stephen] NCI, Core Genetyping Facil, NIH, Gaithersburg, MD USA. RP Andreotti, G (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8011,MSC 7240, Bethesda, MD 20892 USA. EM atidreotg@mail.nih.gov FU Intramural NIH HHS [ZIA CP010158-09] NR 52 TC 21 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 525 EP 534 DI 10.1158/1055-9965.EPI-07-2704 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600010 PM 18296645 ER PT J AU Bobe, G Weinstein, SJ Albanes, D Hirvonen, T Ashby, J Taylor, PR Virtamo, J Stolzenberg-Solomoni, RZ AF Bobe, Gerd Weinstein, Stephanie J. Albanes, Demetrius Hirvonen, Tero Ashby, Jason Taylor, Phil R. Virtamo, Jarmo Stolzenberg-Solomoni, Rachael Z. TI Flavonoid intake and risk of pancreatic cancer in male smokers (Finland) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; DIETARY FLAVONOIDS; MULTIETHNIC COHORT; UNITED-STATES; TUMOR-CELLS; PREVENTION; QUERCETIN; GROWTH; MORTALITY; FRUIT AB Extending research on the protective effect of flavonoids in cell culture and animal studies, we examined the association between consumption of flavonoids and flavonoid-rich foods and development of exocrine pancreatic cancer within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Of the 27,111 healthy male smokers (50-69 years) who completed a self-administered dietary questionnaire at baseline, 306 developed exocrine pancreatic cancer during follow-up (1985-2004; median, 16.1 years). Intakes of total flavonoids, three flavonoid subgroups, seven individual flavonoids, and flavonoid-rich foods were estimated from a validated food frequency questionnaire. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. Overall, flavonoid intake was not significantly associated with pancreatic cancer. However, in stratified analysis, greater total flavonoid intake was associated with decreased pancreatic cancer risk in participants randomized during the trial to placebo (fourth versus first quartile: hazard ratio, 0.36; 95% confidence interval, 0.17-0.78; P-trend = 0.009) and not to supplemental alpha-tocopherol (50 mg/d) and/or beta-carotene (20 mg/d; P-interaction = 0.002). Similar patterns and significant interactions were observed for flavonols, flavan-3-ols, kaempferol, quercetin, catechin, and epicatechin. Our data suggest that a flavonoid-rich diet may decrease pancreatic cancer risk in male smokers not consuming supplemental alpha-tocopherol and/or beta-carotene. C1 [Bobe, Gerd; Weinstein, Stephanie J.; Albanes, Demetrius; Stolzenberg-Solomoni, Rachael Z.] NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Taylor, Phil R.] NIH, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Ashby, Jason] Informat Management Serv Inc, Rockville, MD USA. [Bobe, Gerd] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Bobe, Gerd] NCI, Lab Canc Prevent, Canc Res Ctr, Frederick, MD 21701 USA. [Hirvonen, Tero; Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Stolzenberg-Solomoni, RZ (reprint author), NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 3022, Rockville, MD 20852 USA. EM rs221z@nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 54 TC 36 Z9 37 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 553 EP 562 DI 10.1158/1055-9965.EPI-07-2523 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600013 PM 18349272 ER PT J AU Greene, MH Piedmonte, M Alberts, D Gail, M Hensley, M Miner, Z Mai, PL Loud, J Rodriguez, G Basil, J Boggess, J Schwartz, PE Kelley, JL Wakeley, KE Minasian, L Skates, S AF Greene, Mark H. Piedmonte, Marion Alberts, Dave Gail, Mitchell Hensley, Martee Miner, Zoe Mai, Phuong L. Loud, Jennifer Rodriguez, Gustavo Basil, Jack Boggess, John Schwartz, Peter E. Kelley, Joseph L. Wakeley, Katie E. Minasian, Lori Skates, Stephen TI A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: Design and baseline characteristics: A Gynecologic oncology group study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ORAL-CONTRACEPTIVE USE; BRCA2 MUTATION CARRIERS; PROPHYLACTIC OOPHORECTOMY; TUBAL-LIGATION; BREAST-CANCER; PROSPECTIVE COHORT; HEREDITARY BREAST; FALLOPIAN-TUBE; HYSTERECTOMY; CARCINOMA AB Background: Women who are genetically predisposed to ovarian cancer are at very high risk of developing this disease. Although risk-reducing salpingo-oophorectomy (RRSO) and various screening regimens are currently recommended to reduce ovarian cancer risk, the optimal management strategy has not been established nor have multiple additional issues been adequately addressed. We developed a collaboration among the Clinical Genetics Branch (National Cancer Institute's Intramural Research Program), the Gynecologic Oncology Group (GOG), and the Cancer Genetics Network to address these issues. Methods: This is a prospective, international, two-cohort, nonrandomized study of women at genetic risk of ovarian cancer, who chose either to undergo RRSO or screening, at study enrollment. Primary study objectives include quantifying and comparing ovarian and breast cancer incidence in the two study groups, assessing feasibility and selected performance characteristics of a novel ovarian cancer screening strategy (the Risk of Ovarian Cancer Algorithm), evaluating various aspects of quality of life and nononcologic morbidity related to various interventions in at-risk women, and creating a biospecimen repository for subsequent translational research. Results: Study accrual is complete as of November 2006; 2,605 participants enrolled: 1,030 (40%) into the surgical cohort and 1,575 (60%) into the screening cohort. Five years of prospective follow-up ends in November 2011. Verification of BRCA mutation carrier status is under way, either through patient-provided reports from clinical genetic testing done before enrollment or through research-based genetic testing being conducted as part of the protocol. Patient eligibility is currently under evaluation and baseline, surgical, pathology, and outcome data are still being collected. The study design and selected baseline characteristics of cohort members are summarized. Conclusion: This National Cancer Institute intramural/extramural collaboration will provide invaluable prospectively collected observational data on women at high familial ovarian cancer risk, including substantial numbers cf women carrying BRCA1/2 mutations. These data will aid in elucidating the effect of RRSO on breast/ ovarian cancer risk and the effects of two management strategies, on quality of life and other issues that may influence patient care, as well as providing preliminary estimates of test specificity and positive predictive value of a novel ovarian cancer screening strategy. C1 [Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer] NCI, Clin Genet Branch, Rockville, MD 20852 USA. [Gail, Mitchell] NCI, Biostat Branch, Rockville, MD 20852 USA. [Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Rockville, MD 20852 USA. [Piedmonte, Marion; Miner, Zoe] New York State Dept Hlth, Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [Alberts, Dave] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85721 USA. [Hensley, Martee] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Rodriguez, Gustavo] Evanston NW Healthcare, Evanston, IL USA. [Basil, Jack] St Elizabeth Hosp, Edgewater, KY USA. [Boggess, John] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT USA. [Kelley, Joseph L.] Univ Pittsburgh, Ctr Med, Magee Womens Hosp, Pittsburgh, PA USA. [Wakeley, Katie E.] Tufts Univ New England Med Ctr, London, England. [Skates, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, MH (reprint author), NCI, Clin Genet Branch, 6120 Execut Blvd,Room EPS 7032, Rockville, MD 20852 USA. EM greenem@mail.nih.gov FU Intramural NIH HHS [ZIA CP010145-11]; NCI NIH HHS [P50 CA105009, CA 27469, CA 37517, CA086381, CA105009, U01 CA086381, U10 CA027469, U10 CA037517] NR 47 TC 47 Z9 47 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 594 EP 604 DI 10.1158/1055-9965.EPI-07-2703 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600018 PM 18349277 ER PT J AU Ronckers, CM Doody, MM Lonstein, JE Stovall, M Land, CE AF Ronckers, Cecile M. Doody, Michele M. Lonstein, John E. Stovall, Marilyn Land, Charles E. TI Multiple diagnostic x-rays for spine deformities and risk of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ATOMIC-BOMB SURVIVORS; HODGKINS-DISEASE; FAMILY-HISTORY; IDIOPATHIC SCOLIOSIS; IONIZING-RADIATION; POOLED ANALYSIS; FOLLOW-UP; EXPOSURE; WOMEN; INFANCY AB Background: Ionizing radiation is a well-established human mammary carcinogen. Women historically monitored by radiography at young ages for abnormal spinal curvature are an exposed population suitable for investigating radiation-related risk and its variation by modifying factors. In this historic cohort, 95% of daily dose increments (when exposure to the breast occurred) were under 2.4 cGy, with mean 1.1 cGy. Methods: A retrospective cohort of 3,010 women, diagnosed with spinal curvature between 1912 and 1965 in 14 U.S. pediatric orthopedic centers and who completed a questionnaire by telephone interview or mail survey in 1992, were studied for risk of breast cancer by radiation dose to the breast (mean, 12 cGy) after adjustment for established breast cancer risk factors. Results: A borderline-significant radiation dose response (excess relative risk/Gy = 2.86; P = 0.058; one-tailed P = 0.029) was observed during 118,905 woman-years of follow-up (median, 35.5 years) based on 78 cases of invasive breast cancer. The dose response was significantly greater (P = 0.03) for women who reported a family history of breast cancer in first- or second-degree relatives (excess relative risk/Gy = 8.37; 95% confidence interval, 1.50-28.16). Radiation-related risk did not vary significantly by stage of reproductive development at exposure. Conclusions: Assuming that repair of radiation-related DNA damage requires at most a few hours, our data argue against existence of a low-dose threshold on the order of 1 to 3 cGy for radiation exposure contributing to breast carcinogenesis. The possibility that a family history of breast cancer may have enhanced a carcinogenic radiation effect requires confirmation in other studies. C1 [Ronckers, Cecile M.; Doody, Michele M.; Land, Charles E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Lonstein, John E.] Twin Cities Spine Ctr, Minneapolis, MN USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. RP Land, CE (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 7046,6120 Execut Blvd,MS 7238, Bethesda, MD 20892 USA. EM landc@exchange.nih.gov FU Intramural NIH HHS NR 54 TC 61 Z9 63 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 605 EP 613 DI 10.1158/1055-9965.EPI-07-2628 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600019 PM 18349278 ER PT J AU Reid, JM Mandrekar, SJ Carlson, EC Harmsen, WS Green, EM McGovern, RM Szabo, E Ames, MM Boring, D Limburg, PJ AF Reid, Joel M. Mandrekar, Surnithra J. Carlson, Elsa C. Harmsen, W. Scott Green, Erin M. McGovern, Renee M. Szabo, Eva Ames, Matthew M. Boring, Daniel Limburg, Paul J. CA Cancer Prevention Network TI Comparative Bioavailability of sulindac in capsule and tablet formulations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; COLORECTAL ADENOMAS; CARDIOVASCULAR EVENTS; CHEMOPREVENTION; METABOLITES; BIOEQUIVALENCE; PREVENTION; CELECOXIB; TRIAL; PHARMACOKINETICS AB The cyclooxygenase (COX)-2 enzyme appears to be an important target for cancer chemoprevention. Given the recent emergence of potentially serious cardiovascular toxicity associated with selective COX-2 inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), which inhibit both COX-1 and COX-2, have received renewed attention as candidate chemoprevention agents. Sulindac has shown consistent chemopreventive potential in preclinical studies as well as in a limited number of clinical trials reported to date. For the current pharmacokinetic study, sulindac capsules were prepared to facilitate ample agent supplies for future intervention studies. Encapsulation of the parent compound (sulindac sulfoxide) can be readily accomplished, but the effects of alternate formulations on bioavailability have not been rigorously examined. In the present single-dose, two-period crossover trial, we conducted pharmacokinetic analyses of sulindac in capsule (test) versus tablet (reference) formulations. Overall, bioavailability appeared to be higher for the capsule compared with the tablet formulation based on test-to-reference pharmacokinetic variable ratios for the parent compound alone. However, additional analyses based on the sulfide and sulfone metabolites of sulindac with the same pharmacokinetic variables indicated similar chemopreventive exposures between the capsule and tablet formulations. These data support the use of sulindac capsules, which can be readily prepared with matching placebos, in future blinded chemoprevention trials. C1 [Reid, Joel M.; Mandrekar, Surnithra J.; Carlson, Elsa C.; Harmsen, W. Scott; Green, Erin M.; McGovern, Renee M.; Ames, Matthew M.; Limburg, Paul J.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Szabo, Eva; Boring, Daniel] NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Limburg, PJ (reprint author), Mayo Clin, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM limburg.paul@mayo.edu FU NCI NIH HHS [N01 CN03500, N01-CN-35000, N01CN35000, P30 CA015083, N01 CN003500, P30CA015083]; NCRR NIH HHS [M01-RR00585, M01 RR000585] NR 28 TC 10 Z9 10 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 674 EP 679 DI 10.1158/1055-9965.EPI-07-2510 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600028 PM 18349286 ER PT J AU Hudson, AG Gierach, GL Modugno, F Simpson, J Wilson, JW Evans, RW Vogel, VG Weissfeld, JL AF Hudson, Alana G. Gierach, Gretchen L. Modugno, Francesmary Simpson, Jennifer Wilson, John W. Evans, Rhobert W. Vogel, Victor G. Weissfeld, Joel L. TI Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; HORMONE-RECEPTOR STATUS; LOW-DOSE ASPIRIN; ALCOHOL-CONSUMPTION; PHYSICAL-ACTIVITY; GENE-EXPRESSION; SEX-HORMONES; AROMATASE; HEALTH; INDOMETHACIN AB Laboratory and epidemiologic evidence suggest that nonsteroidal anti-inflammatory drug (NSAID) use may be inversely related to the risk of breast cancer; however, the mechanism by which NSAIDs may protect against the development of this disease is uncertain. The objective of this observational study was to assess the relationship between current NSAID use and endogenous estradiol levels, an established breast cancer risk factor. To evaluate this aim, we conducted a cross-sectional investigation among 260 postmenopausal women who were not recently exposed to exogenous hormones. Information on current NSAID use (aspirin, cyclooxygenase-2 inhibitors, and other NSAIDs combined) was collected using a questionnaire at the time of blood draw. Estradiol was quantified in serum by radioimmunoassay. General linear models were used to evaluate the association between NSAID use and serum total estradiol. The age-adjusted and body mass index-adjusted geometric mean serum estradiol concentration among NSAID users (n = 124) was significantly lower than nonusers of NSAIDs (n = 136; 17.8 versus 21.3 pmol/L; P = 0.03). Further adjustment for additional potential confounding factors did not substantially alter estimates (17.7 versus 21.2 pmol/L; P = 0.03). To our knowledge, this report is the first to examine the relationship between NSAID use and serum estradiol in postmenopausal women. These cross-sectional findings suggest that NSAID use may be associated with lower circulating estradiol levels, potentially representing one mechanism through which NSAIDs exert protective effects on breast cancer. C1 [Hudson, Alana G.; Modugno, Francesmary; Simpson, Jennifer; Evans, Rhobert W.; Weissfeld, Joel L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Wilson, John W.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA. [Vogel, Victor G.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Vogel, Victor G.; Weissfeld, Joel L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Gierach, Gretchen L.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. RP Hudson, AG (reprint author), 516A Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM alg33@pitt.edu RI Gierach, Gretchen/E-1817-2016 OI Gierach, Gretchen/0000-0002-0165-5522 FU NCI NIH HHS [P20 CA103730-02, R21-CA95113, K07-CA80668, R25-CA57703]; NCRR NIH HHS [MO1-RR000056] NR 44 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 680 EP 687 DI 10.1158/1055-9965.EPI-07-2739 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600029 PM 18349287 ER PT J AU Chia, VM Sakoda, LC Graubard, BI Rubertone, MV Chanock, SJ Erickson, RL McGlynn, KA AF Chia, Victoria M. Sakoda, Lori C. Graubard, Barry I. Rubertone, Mark V. Chanock, Stephen J. Erickson, Ralph L. McGlynn, Katherine A. TI Risk of testicular germ cell tumors and polymorphisms in the insulin-like growth factor genes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BONE-MINERAL DENSITY; FACTOR-I; CANCER-RISK; CIRCULATING LEVELS; BINDING PROTEIN-3; BREAST-CANCER; UNITED-STATES; BODY-SIZE; VITAMIN-D; IGF-I AB Because taller men are at increased risk of developing testicular germ cell tumors (TGCT), it is conceivable that factors that influence adult height could be related to risk of TGCT. Because common genetic variation in genes of the insulin-like growth factor (IGF) pathway could influence somatic growth, 43 single nucleotide polymorphisms in four IGF genes (IGF-1, IGF-1R, IGF-2, and IGFALS) were genotyped in 577 case and 707 control participants from the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study to assess relationships with TGCT risk; additionally, associations between polymorphisms and adult height were examined. Relationships between polymorphisms and adult height were assessed using adjusted linear regression models, and associations between polymorphisms and TGCT risk were determined by adjusted logistic regression models estimating odds ratios. Although four IGF-1R polymorphisms (rs907806, rs3743258, rs229765, and rs9282714) were associated with height (P-trend < 0.05), there were no relationships with any other polymorphism. Overall, there were no associations among polymorphisms or haplotypes in the IGF genes and TGCT risk, with odds ratios ranging from 0.55 to 1.50. Similarly, there was no association among the polymorphisms and risk of specific TGCT histologies (seminoma and nonseminoma). There was a suggestion, however, that adult height may modify the relationship between an IGF-1 haplotype and TGCT risk. These results suggest that, in aggregate, genetic variation in IGF loci is not associated with TGCT risk. C1 [Chia, Victoria M.; Graubard, Barry I.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Sakoda, Lori C.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Rubertone, Mark V.] USA, Ctr Hlth Promot & Prevent Med, Washington, DC 20310 USA. [Chanock, Stephen J.] NCI, Inst Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Gaithersburg, MD USA. [Erickson, Ralph L.] Walter Reed Army Inst Res, Forest Glen, MD USA. RP Chia, VM (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, EPS,Suite 550,6120 Execut Blvd, Rockville, MD 20892 USA. EM chiav@mail.nih.gov FU Intramural NIH HHS NR 25 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2008 VL 17 IS 3 BP 721 EP 726 DI 10.1158/1055-9965.EPI-07-0768 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279RZ UT WOS:000254373600036 PM 18349294 ER PT J AU Freedman, LS Kipnis, V Schatzkin, A Potischman, N AF Freedman, Laurence S. Kipnis, Victor Schatzkin, Arthur Potischman, Nancy TI Methods of epidemiology: Evaluating the fat-breast cancer hypothesis - Comparing dietary instruments and other developments SO CANCER JOURNAL LA English DT Article DE breast cancer; dietary fat; dietary measurement error; food frequency questionnaire; multiple-day food record ID FOOD FREQUENCY QUESTIONNAIRE; NUTRITIONAL EPIDEMIOLOGY; NATIONAL-INSTITUTES; MEASUREMENT ERROR; HEALTH; COHORT; RISK; BIOMARKER; DESIGN; TRIAL AB Results from several large cohort studies that were reported 10 to 20 years ago seemed to indicate that the hypothesized link between dietary fat intake and breast cancer risk was illusory. In this article, we review several strands of more recent evidence that have emerged. These include two studies comparing the performance of dietary instruments used to investigate the dietary fat-breast cancer hypothesis, a large randomized disease prevention trial, a more recent meta-analysis of nutritional cohort studies, and a very large nutritional cohort study. Each of the studies discussed in this article suggests that a modest but real association between fat intake and breast cancer is likely. If the association is causative, it would have important implications for public health strategies in reducing breast cancer incidence. The evidence is not yet conclusive, but additional follow-up in the randomized trial, as well as efforts to improve dietary assessment methodology for cohort studies, may be sufficient to provide a convincing answer. C1 [Kipnis, Victor] Natl Canc Inst, Div Canc Prevent, Bethesda, MD USA. [Schatzkin, Arthur] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Potischman, Nancy] Natl Canc Inst, Div Canc Control & Populat Studies, Bethesda, MD USA. [Freedman, Laurence S.] Chaim Sheba Med Ctr, Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52161 Tel Hashomer, Israel. RP Freedman, LS (reprint author), Chaim Sheba Med Ctr, Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52161 Tel Hashomer, Israel. EM lsf@actcom.co.il FU Intramural NIH HHS [Z99 CA999999] NR 27 TC 10 Z9 10 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2008 VL 14 IS 2 BP 69 EP 74 DI 10.1097/PPO.0b013e31816a5e02 PG 6 WC Oncology SC Oncology GA 286BE UT WOS:000254819500001 PM 18391610 ER PT J AU Schmid, T Jansen, AP Baker, AR Hegamyer, G Hagan, JP Colburn, NH AF Schmid, Tobias Jansen, Aaron P. Baker, Alyson R. Hegamyer, Glenn Hagan, John P. Colburn, Nancy H. TI Translation inhibitor Pdcd4 is targeted for degradation during tumor promotion SO CANCER RESEARCH LA English DT Article ID INITIATION-FACTOR 4A; PROGRAMMED CELL-DEATH-4; SUPPRESSOR PDCD4; EXPRESSION; PROTEIN; CANCER; CARCINOGENESIS; TRANSFORMATION; TUMORIGENESIS; APOPTOSIS AB Inactivation of tumor suppressors is among the rate-limiting steps in carcinogenesis that occur during the tumor promotion stage. The translation inhibitor programmed cell death 4 (Pdcd4) suppresses tumorigenesis and invasion. Although Pdcd4 is not mutationatly inactivated in human cancer, the mechanisms controlling Pdcd4 inactivation during tumorigenesis remain elusive. We report that tumor promoter 12-O-tetradecanoylphorbol-13-acetate exposure decreases protein levels of Pdcd4 in mouse skin papillomas and keratinocytes as well as in human HEK293 cells. This decrease is attributable to increased proteasomal degradation of Pdcd4 and is mediated by protein kinase C-dependent activation of phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin-p70(S6K) and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK signaling. Both Akt and p70(S6K) phosphorylate Pdcd4, allowing for binding of the E3-ubiquitin ligase beta-TrCP and consequently ubiquitylation. MEK-ERK signaling on the other hand facilitates the subsequent proteasomal degradation. We further show that Pdcd4 protein levels in vivo are limiting for tumor formation, establishing Pdcd4 as a haploinsufficient tumor suppressor in Pdcd4-deficient mice. Thus, because endogenous Pdcd4 levels are limiting for tumorigenesis, inhibiting signaling to Pdcd4 degradation may prove a valid strategy for cancer prevention and intervention. C1 [Schmid, Tobias; Jansen, Aaron P.; Baker, Alyson R.; Hegamyer, Glenn; Colburn, Nancy H.] Natl Canc Inst, Lab Canc Prevent, Ft Detrick, MD 21702 USA. [Hagan, John P.] Natl Canc Inst, Canc & Dev Biol Lab, Ft Detrick, MD USA. RP Schmid, T (reprint author), Natl Canc Inst, Lab Canc Prevent, Ft Detrick, MD 21702 USA. EM tschmid@ncifcrf.gov OI Hagan, John/0000-0003-0295-4898 FU Intramural NIH HHS NR 22 TC 92 Z9 98 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2008 VL 68 IS 5 BP 1254 EP 1260 DI 10.1158/0008-5472.CAN-07-1719 PG 7 WC Oncology SC Oncology GA 271PW UT WOS:000253802200003 PM 18296647 ER PT J AU Camps, J Grade, M Nguyen, QT Hoermann, P Becker, S Hummon, AB Rodriguez, V Chandrasekharappa, S Chen, Y Difilippantonio, MJ Becker, H Ghadimi, BM Ried, T AF Camps, Jordi Grade, Marian Nguyen, Quang Tri Hoermann, Patrick Becker, Sandra Hummon, Amanda B. Rodriguez, Virginia Chandrasekharappa, Settara Chen, Yidong Difilippantonio, Michael J. Becker, Heinz Ghadimi, B. Michael Ried, Thomas TI Chromosomal breakpoints in primary colon cancer cluster at sites of structural variants in the genome SO CANCER RESEARCH LA English DT Article ID ONCOGENE-INDUCED SENESCENCE; HIGH-RESOLUTION ANALYSIS; WIDE ASSOCIATION SCAN; DNA-DAMAGE RESPONSE; COLORECTAL-CANCER; COPY-NUMBER; GENE-EXPRESSION; CELLULAR TRANSCRIPTOME; ANALYSIS REVEALS; BREAST-CANCER AB Genomic aberrations on chromosome 8 are common in colon cancer, and are associated with lymph node and distant metastases as well as with disease susceptibility. This prompted us to generate a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array consisting of a tiling path of BAC clones. This analysis confirmed the dominant role of this chromosome. Unexpectedly, the position of the breakpoints suggested colocalization with structural variants in the human genome. In order to map these sites with increased resolution and to extend the analysis to the entire genome, we analyzed a subset of these tumors (n = 32) by comparative genomic hybridization on a 185K oligonucleotide array platform. Our comprehensive map of the colon cancer genome confirmed recurrent and specific low-level copy number changes of chromosomes 7, 8, 13, 18, and 20, and unveiled additional, novel sites of genomic imbalances including amplification of a histone gene cluster on chromosome 6p21.1-21.33 and deletions on chromosome 4q34-35. The systematic comparison of segments of copy number change with gene expression profiles showed that genomic imbalances directly affect average expression levels. Strikingly, we observed a significant association of chromosomal breakpoints with structural variants in the human genome: 41% of all copy number changes occurred at sites of such copy number variants (P < 2.2e(-16)). Such an association has not been previously described and reveals a yet underappreciated plasticity of the colon cancer genome; it also points to potential mechanisms for the induction of chromosomal breakage in cancer cells. C1 [Camps, Jordi; Grade, Marian; Nguyen, Quang Tri; Hoermann, Patrick; Becker, Sandra; Hummon, Amanda B.; Chen, Yidong; Difilippantonio, Michael J.; Ried, Thomas] Natl Canc Inst NIH, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. [Rodriguez, Virginia; Chandrasekharappa, Settara] NHGRI NIH, Genome Technol Branch, Bethesda, MD USA. [Grade, Marian; Becker, Heinz] Univ Med Gottingen, Dept Gen & Visceral Surg, Gottingen, Germany. RP Ried, T (reprint author), Natl Canc Inst NIH, Ctr Canc Res, Genet Branch, Bldg 50,Room 1408,50 South Dr, Bethesda, MD 20892 USA. EM riedt@mad.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 47 TC 50 Z9 50 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2008 VL 68 IS 5 BP 1284 EP 1295 DI 10.1158/0008-5472.CAN-07-2864 PG 12 WC Oncology SC Oncology GA 271PW UT WOS:000253802200007 PM 18316590 ER PT J AU Yamashita, T Forgues, M Wang, W Kim, JW Ye, QH Jia, HL Budhu, A Zanetti, KA Chen, Y Qin, LX Tang, ZY Wang, XW AF Yamashita, Taro Forgues, Marshorma Wang, Wei Kim, Jin Woo Ye, Qinghai Jia, Huliang Budhu, Anuradha Zanetti, Krista A. Chen, Yidong Qin, Lun-Xiu Tang, Zhao-You Wang, Xin Wei TI EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma SO CANCER RESEARCH LA English DT Article ID HEPATIC STEM-CELLS; BETA-CATENIN; EP-CAM; PROGENITOR CELLS; LUNG-CANCER; B-VIRUS; LIVER; PREDICTION; TUMOR; OVEREXPRESSION AB The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. Recently, we have identified that a hepatic stem cell marker, epithelial cell adhesion molecule (EpCAM), may serve as an early biomarker of HCC because its expression is highly elevated in premalignant hepatic tissues and in a subset of HCC. In this study, we aimed to identify novel HCC subtypes that resemble certain stages of liver lineages by searching for EpCAM-coexpressed genes. A unique signature of EpCAM-positive HCCs was identified by cDNA microarray analysis of 40 HCC cases and validated by oligonucleotide microarray analysis of 238 independent HCC cases, which was further confirmed by immunohistochemical analysis of an additional 101 HCC cases. EpCAM-positive HCC displayed a distinct molecular signature with features of hepatic progenitor cells including the presence of known stem/progenitor markers such as cytokeratin 19, c-Kit, EpCAM, and activated Wnt-beta-catenin signaling, whereas EpCAM-negative HCC displayed genes with features of mature hepatocytes. Moreover, EpCAM-positive and EpCAM-negative HCC could be further subclassified into four groups with prognostic implication by determining the level of alpha-fetoprotein (AFP). These four subtypes displayed distinct gene expression patterns with features resembling certain stages of hepatic lineages. Taken together, we proposed an easy classification system defined by EpCAM and AFP to reveal HCC subtypes similar to hepatic cell maturation lineages, which may enable prognostic stratification and assessment of HCC patients with adjuvant therapy and provide new insights into the potential cellular origin of HCC and its activated molecular pathways. C1 [Yamashita, Taro; Forgues, Marshorma; Wang, Wei; Kim, Jin Woo; Budhu, Anuradha; Zanetti, Krista A.; Wang, Xin Wei] NCI, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Chen, Yidong] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. [Zanetti, Krista A.] NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. [Ye, Qinghai; Jia, Huliang; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. RP Wang, XW (reprint author), NCI, Ctr Canc Res, Human Carcinogenesis Lab, 37 Convent Dr,Room 3044A,MSC 4258, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS NR 50 TC 335 Z9 349 U1 5 U2 32 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2008 VL 68 IS 5 BP 1451 EP 1461 DI 10.1158/0008-5472.CAN-07-6013 PG 11 WC Oncology SC Oncology GA 271PW UT WOS:000253802200026 PM 18316609 ER PT J AU Zhang, QS Eaton, L Snyder, ER Houghtaling, S Mitchell, JB Finegold, M Van Waes, C Grompe, M AF Zhang, Qing-Shuo Eaton, Laura Snyder, Eric R. Houghtaling, Scott Mitchell, James B. Finegold, Milton Van Waes, Carter Grompe, Markus TI Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice SO CANCER RESEARCH LA English DT Article ID FANCD2 KNOCKOUT MICE; ATM-DEFICIENT MICE; SUPEROXIDE-DISMUTASE; CANCER CHEMOPREVENTION; ANTIOXIDANT TEMPOL; DNA-DAMAGE; STEM-CELLS; STRESS; 8-HYDROXYGUANINE; ACCUMULATION AB Fanconi anemia (FA) is a genetic disorder characterized by congenital abnormalities, bone marrow failure, and marked cancer susceptibility. FA patients have an elevated risk of developing hematologic malignancies and solid tumors. Using Faned2(-/-) knockout mice as a model of FA, we examined the potential of tempol, a nitroxide antioxidant and a superoxide dismutase mimetic, as a tumor-delaying agent for solid tumors. Dietary tempol increased the mean tumor-free survival time of Fancd2(-/-) Trp53(+/-) mice by 27% (P < 0.01), from 308 to 390 days, without changing the overall tumor spectrum. More strikingly, tempol delayed the onset of epithelial tumors and increased the mean epithelial tumor-free survival time by 38% (P < 0.0001), from 312 to 432 days, in Fancd2(-/-) Trp53(+/-) mice. These results show that tempol can significantly delay tumor formation in Fancd2(-/-) Trp53(+/-) mice. Furthermore, tempol treatment did not adversely affect the repopulating ability of FA hematopoietic stem cells. The reduction in oxidative DNA damage in tempol-treated FA fibroblasts and mice suggests that its tumor-delaying function may be attributed to its antioxidant activity. C1 [Zhang, Qing-Shuo; Eaton, Laura; Houghtaling, Scott; Grompe, Markus] Oregon Hlth & Sci Univ, Oregon Stem Cell Ctr, Portland, OR 97239 USA. [Snyder, Eric R.; Van Waes, Carter] Natl Tech Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD USA. [Mitchell, James B.] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Finegold, Milton] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA. RP Zhang, QS (reprint author), Oregon Hlth & Sci Univ, Oregon Stem Cell Ctr, 3181 SW Sam Jackson Pk, Portland, OR 97239 USA. EM zhangqi@ohsu.edu OI Zhang, Qing-shuo/0000-0002-4407-6053 FU Intramural NIH HHS; NHLBI NIH HHS [1P01HL48546] NR 39 TC 46 Z9 47 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2008 VL 68 IS 5 BP 1601 EP 1608 DI 10.1158/0008-5472.CAN-07-5186 PG 8 WC Oncology SC Oncology GA 271PW UT WOS:000253802200043 PM 18316625 ER PT J AU Simpkins, FA Devoogdt, NM Rasool, N Tchabo, NE Alejandro, EU Kamrava, MMRN Kohn, EC AF Simpkins, Fiona A. Devoogdt, Nick M. Rasool, Nabila Tchabo, Nana E. Alejandro, Emilyn U. Kamrava, Mitchell M. R. N. Kohn, Elise C. TI The alarm anti-protease, secretory leukocyte protease inhibitor, is a proliferation and survival factor for ovarian cancer cells SO CARCINOGENESIS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GRANULIN-EPITHELIN PRECURSOR; GROWTH-FACTOR; PROTEINASE-INHIBITOR; SLPI; EXPRESSION; CARCINOMAS; COMPLEX; ELAFIN; GENES AB Alarm anti-proteases are secreted locally in response to inflammation and have been shown to be elevated in cancers. Secretory leukocyte protease inhibitor (SLPI), an alarm anti-protease, is amplified in ovarian carcinoma and is induced and binds to and protects progranulin (prgn) in inflammation. We reported prgn is a survival protein in ovarian cancer and now hypothesize that SLPI/prgn would promote proliferation and survival. Neutralizing anti-SLPI antibody treatment of HEY-A8 and OVCAR3 ovarian cancer cells decreased cell number (P < 0.001), induced apoptosis and reduced prgn quantity. This was confirmed using SLPI small interfering RNA. Prgn and SLPI were co-immunoprecipitated and co-localized by confocal microscopy. Prgn is a substrate of the serine protease elastase and SLPI is an inhibitor of elastase. Elastase reduced prgn expression, inhibited proliferation in a dose-dependent manner (P <= 0.01) and was pro-apoptotic. SLPI protected prgn from elastase-mediated degradation and restored its survival and proliferative function (P <= 0.04). SLPI also reversed elastase's pro-apoptotic effects (P <= 0.03), yielding recovery of S-phase fraction (P <= 0.001) and increased cyclin D1. Treatment with a general serine protease inhibitor increased prgn, but did not reverse elastase-mediated prgn loss or apoptosis. These data demonstrate that inappropriate over-expression of the alarm anti-protease, SLPI, creates a pro-survival milieu for ovarian cancer. C1 [Simpkins, Fiona A.; Devoogdt, Nick M.; Rasool, Nabila; Tchabo, Nana E.; Alejandro, Emilyn U.; Kamrava, Mitchell M. R. N.; Kohn, Elise C.] NCI, Ctr Canc Res, Pathol Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. [Devoogdt, Nick M.] Vrije Univ Brussels, Vlaams Interuniv Inst Biotechnol, Dept Mol & Cellular Interact, Brussels, Belgium. RP Kohn, EC (reprint author), NCI, Ctr Canc Res, Pathol Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. EM ek1b@nih.gov RI Devoogdt, Nick/H-5156-2013; OI Devoogdt, Nick/0000-0001-9220-4833; Alejandro, Emilyn/0000-0002-7941-8439 FU Howard Hughes Medical Institute; Intramural NIH HHS NR 42 TC 21 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2008 VL 29 IS 3 BP 466 EP 472 DI 10.1093/carcin/bgm212 PG 7 WC Oncology SC Oncology GA 274NP UT WOS:000254008300002 PM 17916899 ER PT J AU Danforth, KN Hayes, RB Rodriguez, C Yu, K Sakoda, LC Huang, WY Chen, BE Chen, JB Andriole, GL Calle, EE Jacobs, EJ Chu, LW Figueroa, JD Yeager, M Platz, EA Michaud, DS Chanock, SJ Thun, MJ Hsing, AW AF Danforth, Kim N. Hayes, Richard B. Rodriguez, Carmen Yu, Kai Sakoda, Lori C. Huang, Wen-Yi Chen, Bingshu E. Chen, Jinbo Andriole, Gerald L. Calle, Eugenia E. Jacobs, Eric J. Chu, Lisa W. Figueroa, Jonine D. Yeager, Meredith Platz, Elizabeth A. Michaud, Dominique S. Chanock, Stephen J. Thun, Michael J. Hsing, Ann W. TI Polymorphic variants in PTGS2 and prostate cancer risk: results from two large nested case-control studies SO CARCINOGENESIS LA English DT Article ID LINKAGE PHASE; COX-2 GENE; ASSOCIATION; CARCINOGENESIS; INFLAMMATION; TESTS; HAPLOTYPES; GENOME AB Chronic inflammation has been hypothesized to increase prostate cancer risk. Prostaglandin-endoperoxide synthase 2 (PTGS2) encodes the proinflammatory cyclooxygenase 2 enzyme believed to be the rate-limiting step in the synthesis of prostaglandins, important mediators of inflammation. We investigated associations between PTGS2 polymorphisms and prostate cancer risk among 2321 prostate cancer cases and 2560 controls in two large case-control studies nested within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Cancer Prevention Study II Nutrition Cohort. Five single nucleotide polymorphisms (SNPs) (rs5277, rs20432, rs4648276, rs5275 and rs689470) were examined in SNP and haplotype analyses (five SNPs in PLCO and four SNPs in the Nutrition Cohort). In PLCO, the Ex10 +837 T > C marker (rs5275) was initially associated with prostate cancer risk (P-trend = 0.02) but became non-significant after adjustment for multiple comparisons (P = 0.08); this SNP showed no association with prostate cancer risk in the Nutrition Cohort (P-trend = 0.54) or in an analysis pooling the two cohorts (P-trend = 0.20). No other SNP was associated with prostate cancer risk in PLCO or the Nutrition Cohort individually or combined. Haplotype analyses suggested an association between PTGS2 variants in PLCO alone (global P = 0.007), but not in the Nutrition Cohort (global P = 0.78) or pooled analysis (global P = 0.18). In conclusion, despite the potential importance of inflammation in prostate carcinogenesis, results from our large study of five PTGS2 SNPs does not support a strong association between PTGS2 variants and prostate cancer risk in non-Hispanic white men. C1 [Danforth, Kim N.; Hayes, Richard B.; Yu, Kai; Huang, Wen-Yi; Figueroa, Jonine D.; Chanock, Stephen J.; Hsing, Ann W.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Rodriguez, Carmen; Calle, Eugenia E.; Jacobs, Eric J.; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Sakoda, Lori C.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Chen, Bingshu E.] Concordia Univ, Dept Mat & Stat, Montreal, PQ H3G 1M8, Canada. [Chen, Jinbo] Hosp Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Chu, Lisa W.; Figueroa, Jonine D.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Prevent,Off Prevent Oncol,Canc Prevent F, Rockville, MD 20852 USA. [Chanock, Stephen J.] NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Div Canc Epidemiol & Genet,Core Genotyping Facil, Frederick, MD 20877 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Michaud, Dominique S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chanock, Stephen J.] NCI, NIH, Dept Hlth & Human Serv, Ctr Canc Res, Bethesda, MD 20892 USA. RP Danforth, KN (reprint author), NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. EM danfortk@mail.nih.gov RI Michaud, Dominique/I-5231-2014; OI Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 22 TC 22 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2008 VL 29 IS 3 BP 568 EP 572 DI 10.1093/carcin/bgm253 PG 5 WC Oncology SC Oncology GA 274NP UT WOS:000254008300014 PM 17999989 ER PT J AU Xiong, K Chu, YP Clough, RW Bin Cai, H Luo, XG Struble, RG Kordower, JH Yan, XX AF Xiong, Kun Chu, Ya Ping Clough, Richard W. Bin Cai, Huai Luo, Xue Gang Struble, Robert G. Kordower, Jeffrey H. Yan, Xiao Xin TI beta-SECRETASE-1 (BACE1) EXPRESSION IN CEREBRAL NEOCORTEX SHOWS A MODULAR DISTRIBUTION PATTERN: INVERSE CORRELATION WITH ENDOGENOUS NEURONAL ACTIVITY SO CELL BIOLOGY INTERNATIONAL LA English DT Meeting Abstract C1 [Xiong, Kun; Luo, Xue Gang] Cent S Univ, Xiangya Med Sch, Dept Anat & Neurobiol, Changsha 410078, Hunan, Peoples R China. [Xiong, Kun; Clough, Richard W.; Yan, Xiao Xin] So Illinois Univ, Sch Med, Dept Anat, Carbondale, IL 62901 USA. [Chu, Ya Ping; Kordower, Jeffrey H.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Bin Cai, Huai] NIA, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Struble, Robert G.] So Illinois Univ, Sch Med, Dept Neurol, Springfield, IL 62794 USA. [Struble, Robert G.] So Illinois Univ, Sch Med, Ctr Alzheimer Dis, Springfield, IL 62794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD MAR PY 2008 VL 32 IS 3 BP S10 EP S11 DI 10.1016/j.cellbi.2008.01.052 PG 7 WC Cell Biology SC Cell Biology GA 369BU UT WOS:000260668800040 ER PT J AU Cho, H Kehrl, JH AF Cho, Hyeseon Kehrl, John H. TI Beyond the plasma membrane - New functions for heterotrimeric G-protein signaling in asymmetric and symmetric cell division SO CELL CYCLE LA English DT Article DE heterotrimeric G protein; RGS protein; cell division; microtubules; centrosome ID REGULATES SPINDLE ORIENTATION; BETA-GAMMA-SUBUNITS; G-ALPHA; MITOTIC SPINDLE; C-ELEGANS; CAENORHABDITIS-ELEGANS; DROSOPHILA NEUROBLASTS; CORTICAL LOCALIZATION; NUMA; RIC-8 AB Plasma membrane heterotrimeric G proteins transduce extracellular signals from seven transmembrane receptors to downstream effectors. In addition, G proteins and their regulators localize at multiple intracellular sites and play crucial roles in cell division. In model organisms such as Caenorhabditis elegans and Drosophila receptor-independent heterotrimeric G protein function is vital for the orientation of mitotic spindle, generation of microtubule pulling force, aster-induced cytokinesis and centration of the nucleus-centrosome complex. This new paradigm is now being extended to mammalian cells. Mammalian G protein signaling components localize in centrosomes and at the midbody, and altered function or expression of these proteins can cause cell division defects. Here, we highlight the role and possible mechanisms of G protein signaling in mammalian cell division in conjunction with recent findings in model organisms. Together the evidence argues for a more direct role of non-canonical heterotrimeric G protein signaling in microtubule- and actin cytoskeleton-mediated cellular processes. C1 [Cho, Hyeseon; Kehrl, John H.] LIR NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Cho, H (reprint author), LIR NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bld 10,Rm 11N214,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM hcho@niaid.nih.gov; jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 45 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 1 PY 2008 VL 7 IS 5 BP 573 EP 577 PG 5 WC Cell Biology SC Cell Biology GA 279OY UT WOS:000254365700006 PM 18239453 ER PT J AU Jeong, WI Osei-Hyiaman, D Park, O Liu, J Batkai, S Mukhopadhyay, P Horiguchi, N Harvey-White, J Marsicano, G Lutz, B Gao, B Kunos, G AF Jeong, Won-il Osei-Hyiaman, Douglas Park, Ogyi Liu, Jie Batkai, Sandor Mukhopadhyay, Partha Horiguchi, Norio Harvey-White, Judith Marsicano, Giovanni Lutz, Beat Gao, Bin Kunos, George TI Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver SO CELL METABOLISM LA English DT Article ID DIET-INDUCED OBESITY; METABOLIC SYNDROME; PROTEIN-KINASE; ACID SYNTHESIS; ABDOMINAL OBESITY; ETHANOL; MICE; STEATOSIS; FIBROSIS; RATS AB Alcohol-induced fatty liver, a major cause of morbidity, has been attributed to enhanced hepatic lipogenesis and decreased fat clearance of unknown mechanism. Here we report that the steatosis induced in mice by a low-fat, liquid ethanol diet is attenuated by concurrent blockade of cannabinoid CB1 receptors. Global or hepatocyte-specific CB1 knockout mice are resistant to ethanol-induced steatosis and increases in lipogenic gene expression and have increased carnitine palmitoyltransferase 1 activity, which, unlike in controls, is not reduced by ethanol treatment. Ethanol feeding increases the hepatic expression of CB1 receptors and upregulates the endocannabinoid 2-arachidonoylglycerol (2-AG) and its biosynthetic enzyme diacylglycerol lipase beta selectively in hepatic stellate cells. In control but not CB1 receptor-deficient hepatocytes, coculture with stellate cells from ethanol-fed mice results in upregulation of CB1 receptors and lipogenic gene expression. We conclude that paracrine activation of hepatic CB1 receptors by stellate cell-derived 2-AG mediates ethanol-induced steatosis through increasing lipogenesis and decreasing fatty acid oxidation. C1 [Jeong, Won-il; Osei-Hyiaman, Douglas; Park, Ogyi; Liu, Jie; Batkai, Sandor; Mukhopadhyay, Partha; Horiguchi, Norio; Harvey-White, Judith; Gao, Bin; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Marsicano, Giovanni] Univ Bordeaux 2, Ctr Rech, INSERM, Inst Francois Magendie,U862, F-33077 Bordeaux, France. [Lutz, Beat] Johannes Gutenberg Univ Mainz, Dept Physiol Chem, D-55099 Mainz, Germany. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Batkai, Sandor/G-3889-2010; JEONG, WON IL/B-6615-2011; Batkai, Sandor/H-7983-2014 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; FU Intramural NIH HHS NR 53 TC 157 Z9 159 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAR PY 2008 VL 7 IS 3 BP 227 EP 235 DI 10.1016/j.cmet.2007.12.007 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 270NK UT WOS:000253727300009 PM 18316028 ER PT J AU Lin, AN Liu, ZG AF Lin, Anning Liu, Zheng-gang TI Cell signaling review series SO CELL RESEARCH LA English DT Editorial Material C1 [Lin, Anning] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Liu, Zheng-gang] Natl Canc Inst, Ctr Canc Res, Cell & Canc Biol Branch, NIH, Bethesda, MD USA. RP Lin, AN (reprint author), Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. EM alin@huggins.bsd.uchicago.edu; zgliu@helix.nih.gov NR 0 TC 1 Z9 1 U1 1 U2 1 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD MAR PY 2008 VL 18 IS 3 BP 327 EP 327 DI 10.1038/cr.2008.32 PG 1 WC Cell Biology SC Cell Biology GA 290CP UT WOS:000255101000001 ER PT J AU Morgan, MJ Kim, YS Liu, ZG AF Morgan, Michael J. Kim, You-Sun Liu, Zheng-gang TI TNF alpha and reactive oxygen species in necrotic cell death SO CELL RESEARCH LA English DT Review DE TNF; necrosis; Nox1; TRADD; RIP1; ROS; INK ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; RECEPTOR-INTERACTING PROTEIN; COLONY-STIMULATING FACTOR; FAS-MEDIATED APOPTOSIS; NADPH OXIDASE; OXIDATIVE STRESS; HUMAN-NEUTROPHILS; REDOX REGULATION; SUPEROXIDE GENERATION AB Death receptors, including the TNF receptor-1 (TNF-RI), have been shown to be able to initiate caspase-independent cell death. This form of "necrotic cell death" appears to be dependent on the generation of reactive oxygen species. Recent data have indicated that superoxide generation is dependent on the activation of NADPH oxidases, which form a complex with the adaptor molecules RIP1 and TRADD. The mechanism of superoxide generation further establishes RIP1 as the central molecule in ROS production and cell death initiated by TNF alpha and other death receptors. A role for the sustained JNK activation in necrotic cell death is also suggested. The sensitization of virus-infected cells to TNF alpha indicates that necrotic cell death may represent an alternative cell death pathway for clearance of infected cells. C1 [Morgan, Michael J.; Kim, You-Sun; Liu, Zheng-gang] NCI, Ctr Canc Res, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Ctr Canc Res, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. EM zgliu@helix.nih.gov FU Intramural NIH HHS NR 75 TC 89 Z9 99 U1 2 U2 10 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD MAR PY 2008 VL 18 IS 3 BP 343 EP 349 DI 10.1038/cr.2008.31 PG 7 WC Cell Biology SC Cell Biology GA 290CP UT WOS:000255101000005 PM 18301379 ER PT J AU Roberts, DD AF Roberts, D. D. TI Thrombospondins: from structure to therapeutics SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Editorial Material DE extracellular matrix; bone development; angiogenesis; hemostasis; blood flow; inherited disorders; cancer ID NITRIC-OXIDE; ANGIOGENESIS; PROGRESSION; INHIBITION; MELANOMA C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS [Z01 SC009172-04, Z01 SC009174-04] NR 13 TC 8 Z9 8 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2008 VL 65 IS 5 BP 669 EP 671 DI 10.1007/s00018-007-7483-2 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270XN UT WOS:000253753600001 PM 18193165 ER PT J AU Posey, KL Yang, Y Veerisetty, AC Sharan, SK Hecht, JT AF Posey, K. L. Yang, Y. Veerisetty, A. C. Sharan, S. K. Hecht, J. T. TI Model systems for studying skeletal dysplasias caused by TSP-5/COMP mutations SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE TSP-5; PSACH; pseudoachondroplasia; mouse model; chondrocyte; growth plate; COMP; MED; multiple epiphyseal dysplasia ID OLIGOMERIC MATRIX PROTEIN; MULTIPLE EPIPHYSEAL DYSPLASIA; ENDOPLASMIC-RETICULUM; ARTICULAR-CARTILAGE; CELL-DEATH; PSEUDOACHONDROPLASIA CHONDROCYTES; CALCIUM-BINDING; DTDST MUTATION; MUTANT COMP; IX COLLAGEN AB Cartilage oligomeric matrix protein, also known as thrombospondin-5 (TSP-5), is an extracellular matrix protein found primarily in cartilage and musculoskeletal tissues. TSP-5 is of interest because mutations in the gene cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED/EDM1). Both PSACH and EDM1 have a characteristic chondrocyte phenotype distinguished by giant rough endoplasmic reticulum (rER) cisternae containing TSP-5 and other extracellular matrix proteins such as type IX collagen and matrilin-3. The accumulation of proteinaceous material in the rER compromises cellular function and leads to premature chondrocyte death. Both in vitro and in vivo models have been generated with varying degrees of success to study the cellular mechanisms of the disease process. Here we review and discuss in vitro and in vivo PSACH and MED model systems and describe two transgenic mouse lines expressing human mutant TSP-5 protein. These model systems have revealed several important features of the PSACH cellular pathology: unfolded protein response activation, upregulation of apoptosis and inappropriate assembly of matrix network in the rER. Some of these models are valuable reagents that may be of use in testing therapeutic interventions. C1 [Posey, K. L.; Veerisetty, A. C.; Hecht, J. T.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX 77030 USA. [Yang, Y.; Sharan, S. K.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Hecht, J. T.] Shriners Hosp Children, Houston, TX 77030 USA. RP Hecht, JT (reprint author), Univ Texas Houston, Sch Med, Dept Pediat, 6431 Fannin, Houston, TX 77030 USA. EM Jacqueline.T.Hecht@uth.tmc.edu NR 79 TC 27 Z9 27 U1 2 U2 2 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2008 VL 65 IS 5 BP 687 EP 699 DI 10.1007/s00018-007-7485-0 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270XN UT WOS:000253753600003 PM 18193163 ER PT J AU Isenberg, JS Frazier, WA Roberts, DD AF Isenberg, J. S. Frazier, W. A. Roberts, D. D. TI Thrombospondin-1: a physiological regulator of nitric oxide signaling SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE ischemic injury; tissue perfusion; angiogenesis; hemostasis; blood flow; nitric oxide; vascular smooth muscle; platelets ID INTEGRIN-ASSOCIATED PROTEIN; SMOOTH-MUSCLE-CELLS; ENDOTHELIAL GROWTH-FACTOR; ISCHEMIA-REPERFUSION INJURY; PERIPHERAL ARTERIAL-DISEASE; SKIN FLAP SURVIVAL; PLATELET-AGGREGATION; BLOOD-FLOW; L-ARGININE; IN-VIVO AB Thrombospondin-1 is a secreted protein that modulates vascular cell behavior via several cell surface receptors. In vitro, nanomolar concentrations of thrombospondin-1 are required to alter endothelial and vascular smooth muscle cell adhesion, proliferation, motility, and survival. Yet, much lower levels of thrombospondin-1 are clearly functional in vivo. This discrepancy was explained with the discovery that the potency of thrombospondin-1 increases more than 100-fold in the presence of physiological levels of nitric oxide (NO). Thrombospondin-1 binding to CD47 inhibits NO signaling by preventing cGMP synthesis and activation of its target cGMP-dependent protein kinase. This potent antagonism of NO signaling allows thrombospondin-1 to acutely constrict blood vessels, accelerate platelet aggregation, and if sustained, inhibit angiogenic responses. Acute antagonism of NO signaling by thrombospondin-1 is important for hemostasis but becomes detrimental for tissue survival of ischemic injuries. New therapeutic approaches targeting thrombospondin-1 or CD47 can improve recovery from ischemic injuries and overcome a deficit in NO-responsiveness in aging. C1 [Isenberg, J. S.; Roberts, D. D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Frazier, W. A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS [Z01 SC009172-04, Z01 SC009174-04]; NHLBI NIH HHS [HL54390]; NIGMS NIH HHS [GM57573] NR 142 TC 59 Z9 61 U1 4 U2 6 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2008 VL 65 IS 5 BP 728 EP 742 DI 10.1007/s00018-007-7488-x PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270XN UT WOS:000253753600006 PM 18193160 ER PT J AU Ungerleider, LG Galkin, TW Desimone, R Gattass, R AF Ungerleider, Leslie G. Galkin, Thelma W. Desimone, Robert Gattass, Ricardo TI Cortical connections of area V4 in the macaque SO CEREBRAL CORTEX LA English DT Review DE extrastriate cortex; inferior temporal cortex; object recognition; primates; visual system ID SUPERIOR TEMPORAL SULCUS; MONKEY VISUAL-CORTEX; FRONTAL EYE FIELD; POSTERIOR PARIETAL CORTEX; RHESUS-MONKEY; CEBUS MONKEY; VISUOTOPIC ORGANIZATION; CORTICOCORTICAL CONNECTIONS; TOPOGRAPHIC ORGANIZATION; INFEROTEMPORAL CORTEX AB To determine the locus, full extent, and topographic organization of cortical connections of area V4 (visual area 4), we injected anterograde and retrograde tracers under electrophysiological guidance into 21 sites in 9 macaques. Injection sites included representations ranging from central to far peripheral eccentricities in the upper and lower fields. Our results indicated that all parts of V4 are connected with occipital areas V2 (visual area 2), V3 (visual area 3), and V3A (visual complex V3, part A), superior temporal areas V4t (V4 transition zone), MT (medial temporal area), and FST (fundus of the superior temporal sulcus [STS] area), inferior temporal areas TEO (cytoarchitectonic area TEO in posterior inferior temporal cortex) and TE (cytoarchitectonic area TE in anterior temporal cortex), and the frontal eye field (FEF). By contrast, mainly peripheral field representations of V4 are connected with occipitoparietal areas DP (dorsal prelunate area), VIP (ventral intraparietal area), LIP (lateral intraparietal area), PIP (posterior intraparietal area), parieto-occipital area, and MST (medial STS area), and parahippocampal area TF (cytoarchitectonic area TF on the parahippocampal gyrus). Based on the distribution of labeled cells and terminals, projections from V4 to V2 and V3 are feedback, those to V3A, V4t, MT, DP, VIP, PIP, and FEF are the intermediate type, and those to FST, MST, LIP, TEO, TE, and TF are feedforward. Peripheral field projections from V4 to parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention. By contrast, the predominance of central field projections from V4 to inferior temporal areas is consistent with the need for detailed form analysis for object vision. C1 [Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Galkin, Thelma W.; Desimone, Robert] NIH, Neuropsychol Lab, NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Desimone, Robert] MIT, McGovern Inst, Cambridge, MA 02139 USA. [Gattass, Ricardo] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21941 Rio De Janeiro, Brazil. RP Ungerleider, LG (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C104, Bethesda, MD 20892 USA. EM ungerlel@mail.nih.gov NR 115 TC 120 Z9 120 U1 2 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2008 VL 18 IS 3 BP 477 EP 499 DI 10.1093/cercor/bhm061 PG 23 WC Neurosciences SC Neurosciences & Neurology GA 267DP UT WOS:000253490000001 PM 17548798 ER PT J AU Hering, S Beyl, S Stary, A Kudrnac, M Hohaus, A Guy, HR Timin, E AF Hering, Steffen Beyl, Stansilav Stary, Anna Kudrnac, Michaela Hohaus, Annette Guy, H. Robert Timin, Eugen TI Pore stability and gating in voltage-activated calcium channels SO CHANNELS LA English DT Review DE Ca(V)1.2 channel; pore structure; activation gating; patch clamp; structure activity studies ID FAMILIAL HEMIPLEGIC MIGRAINE; DEPENDENT K+ CHANNEL; CA2+ CHANNEL; ION CHANNELS; STRUCTURAL DETERMINANTS; FUNCTIONAL CONSEQUENCES; POTASSIUM CHANNEL; RETINAL DISORDER; BETA-SUBUNITS; REPEAT-I AB Calcium channel family members activate at different membrane potentials, which enables tissue specific calcium entry. Pore mutations affecting this voltage dependence are associated with channelopathies. In this review we analyze the link between voltage sensitivity and corresponding kinetic phenotypes of calcium channel activation. Systematic changes in hydrophobicity in the lower third of S6 segments gradually shift the activation curve thereby determining the voltage sensitivity. Homology modeling suggests that hydrophobic residues that are located in all four S6 segments close to the inner channel mouth might form adhesion points stabilizing the closed gate. Simulation studies support a scenario where voltage sensors and the pore are essentially independent structural units. We speculate that evolution designed the voltage sensing machinery as robust "all-or-non" device while the varietys of voltage sensitivities of different channel types was accomplished by shaping pore stability. C1 [Hering, Steffen; Beyl, Stansilav; Kudrnac, Michaela; Hohaus, Annette; Timin, Eugen] Univ Vienna, Inst Pharmacol & Toxicol, Vienna, Austria. [Stary, Anna] Univ Vienna, Inst Theoret Chem, Vienna, Austria. [Guy, H. Robert] NCI, Cell Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hering, S (reprint author), Univ Vienna, Inst Pharmacol & Toxicol, Vienna, Austria. EM steffen.hering@univie.ac.at RI Stary-Weinzinger, Anna/A-3629-2014 OI Stary-Weinzinger, Anna/0000-0002-9202-0484 FU FWF [P19614-B11]; NIH; National Cancer Institute; Center for Cancer Research FX This work was supported by FWF grant P19614-B11 (to Steffen Hering) and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (to H. Robert Guy). NR 50 TC 8 Z9 8 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1933-6950 J9 CHANNELS JI Channels PD MAR-APR PY 2008 VL 2 IS 2 BP 61 EP 69 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 344SV UT WOS:000258948500001 PM 18849656 ER PT J AU Huang, R Southall, N Cho, MF Xia, M Inglese, J Austin, CP AF Huang, Ruili Southall, Noel Cho, Ming-Fsuang Xia, Mengbang Inglese, James Austin, Christopher P. TI Characterization of diversity in toxicity mechanism using in vitro cytotoxicity assays in quantitative high throughput screening SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CLUSTER VALIDITY; CELLS; APOPTOSIS; INHIBITION; GLYCOALKALOIDS; COLCHICINE; CASPASE-3; MEMBRANE AB Assessing the potential health risks of environmental chemical compounds is an expensive undertaking that has motivated the development of new alternatives to traditional in vivo toxicological testing. One approach is to stage the evaluation, beginning with less expensive and higher throughput in vitro testing before progressing to more definitive trials. In vitro testing can be used to generate a hypothesis about a compound's mechanism of action, which can then be used to design an appropriate in vivo experiment. Here we begin to address the question of how to design such a battery of in vitro cell-based assays by combining data from two different types of assays, cell viability and caspase activation, with the aim of elucidating the mechanism of action. Because caspase activation is a transient event during apoptosis, it is not possible to design a single end-point assay protocol that would identify all instances of compound-induced caspase activation. Nevertheless, useful information about compound mechanism of action can be obtained from these assays in combination with cell viability data. Unsupervised clustering in combination with Dunn's cluster validity index is a robust method for identifying mechanisms of action without requiring any a priori knowledge about mechanisms of toxicity. The performance of this clustering method is evaluated by comparing the clustering results against literature annotations of compound mechanisms. C1 [Huang, Ruili; Southall, Noel; Cho, Ming-Fsuang; Xia, Mengbang; Inglese, James; Austin, Christopher P.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Huang, R (reprint author), NIH, Chem Genom Ctr, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM huangru@mail.nih.gov RI Southall, Noel/H-8991-2012 OI Southall, Noel/0000-0003-4500-880X FU Intramural NIH HHS [Z01 HG200319-04] NR 31 TC 37 Z9 38 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2008 VL 21 IS 3 BP 659 EP 667 DI 10.1021/tx700365e PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 275PY UT WOS:000254085300014 PM 18281954 ER PT J AU Yi-Brunozzi, HY Brinson, RG Brabazon, DI Lener, D Le Grice, SFJ Marino, JP AF Yi-Brunozzi, Hye Young Brinson, Robert G. Brabazon, Danielle Im. Lener, Daniela Le Grice, Stuart F. J. Marino, John P. TI High-resolution NMR analysis of the conformations of native and base analog substituted retroviral and LTR-retrotransposon PPT primers SO CHEMISTRY & BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; STRAND DNA-SYNTHESIS; POLYPURINE TRACT; CRYSTAL-STRUCTURE; RNA/DNA HYBRID; RNA DUPLEXES; TY3; INITIATION; STABILITY AB A purine-rich region of the plus-strand RNA genome of retroviruses and long terminal repeat (LTR)-containing retrotransposons, known as the polypurine tract (PPT), is resistant to hydrolysis by the RNase H domain of reverse transcriptase (RT) and ultimately serves as a primer for plus-strand DNA synthesis. The mechanisms underlying PPT resistance and selective processing remain largely unknown. Here, two RNA/DNA hybrids derived from the PPTs of HIV-1 and Ty3 were probed using high-resolution NMR for preexisting structural distortions in the absence of RT. The PPTs were selectively modified through base-pair changes or by incorporation of the thymine isostere, 2,4-difluoro-5-methylbenzene (dF), into the DNA strand. Although both wild-type (WT) and mutated hybrids adopted global A-form-like helical geometries, observed structural perturbations in the base-pair and dF-modified hybrids suggested that the PPT hybrids may function as structurally coupled domains. C1 [Yi-Brunozzi, Hye Young; Brinson, Robert G.; Lener, Daniela; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick Natl Inst Hlth, Frederick, MD 21702 USA. [Brinson, Robert G.; Marino, John P.] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. [Brinson, Robert G.; Marino, John P.] Univ Maryland, Natl Inst Stand & Technol, Rockville, MD 20850 USA. [Brabazon, Danielle Im.] Loyola Coll Maryland, Dept Chem, Baltimore, MD 21210 USA. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Frederick Natl Inst Hlth, Frederick, MD 21702 USA. EM slegrice@ncifcrf.gov; marino@umbi.umd.edu FU Intramural NIH HHS [Z01 BC010493-05]; NIGMS NIH HHS [R01 GM059107, GM59107] NR 37 TC 12 Z9 13 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD MAR PY 2008 VL 15 IS 3 BP 254 EP 262 DI 10.1016/j.chembiol.2008.01.012 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 282LY UT WOS:000254570500011 PM 18355725 ER PT J AU Trifonov, VA Stanyon, R Nesterenko, AI Fu, BY Perelman, PL O'Brien, PCM Stone, G Rubtsova, NV Houck, ML Robinson, TJ Ferguson-Smith, MA Dobigny, G Graphodatsky, AS Yang, FT AF Trifonov, Vladimir A. Stanyon, Roscoe Nesterenko, Anastasia I. Fu, Beiyuan Perelman, Polina L. O'Brien, Patricia C. M. Stone, Gary Rubtsova, Nadezhda V. Houck, Marlys L. Robinson, Terence J. Ferguson-Smith, Malcolm A. Dobigny, Gauthier Graphodatsky, Alexander S. Yang, Fengtang TI Multidirectional cross-species painting illuminates the history of karyotypic evolution in Perissodactyla SO CHROMOSOME RESEARCH LA English DT Article DE chromosomal evolution; chromosome painting; cladistics; Equidae; karyology; Perissodactyla ID GENE-MAPPING WORKSHOP; RADIATION HYBRID MAP; COMPARATIVE CHROMOSOME MAP; LINKAGE MAP; RHINOCEROS-UNICORNIS; ANCESTRAL KARYOTYPE; CERATOTHERIUM-SIMUM; HOMOLOGOUS REGIONS; INDIAN RHINOCEROS; GENOME EVOLUTION AB The order Perissodactyla, the group of odd-toed ungulates, includes three extant families: Equidae, Tapiridae, and Rhinocerotidae. The extremely rapid karyotypic diversification in perissodactyls has so far prevented the establishment of genome-wide homology maps between these three families by traditional cytogenetic approaches. Here we report the first genome-wide comparative chromosome maps of African rhinoceroses, four tapir species, four equine species, and humans. These maps were established by multidirectional chromosome painting, with paint probes derived from flow-sorted chromosomes of Equus grevyi, Tapirus indicus, and Ceratotherium simum as well as painting probes from horse and human. The Malayan tapir (Tapirus indicus), Baird's tapir (T. bairdii), mountain tapir (T. pinchaque), lowland tapir (T. terrestris), and onager (E. hemionus onager), were studied by cross-species chromosome painting for the first time. Our results, when integrated with previously published comparative chromosome maps of the other perissodactyl species, have enabled the reconstruction of perissodactyl, ceratomorph, and equid ancestral karyotypes, and the identification of the defining evolutionary chromosomal rearrangements along each lineage. Our results allow a more reliable estimate of the mode and tempo of evolutionary chromosomal rearrangements, revealing a striking switch between the slowly evolving ceratomorphs and extremely rapidly evolving equids. C1 [Trifonov, Vladimir A.; Nesterenko, Anastasia I.; Perelman, Polina L.; Rubtsova, Nadezhda V.; Graphodatsky, Alexander S.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. [Yang, Fengtang] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Trifonov, Vladimir A.; Fu, Beiyuan; O'Brien, Patricia C. M.; Ferguson-Smith, Malcolm A.] Cambridge Resource Ctr Comparat Genom, Dept Vet Med, Cambridge CB3 0ES, England. [Stanyon, Roscoe] Univ Florence, Dept Anim Biol & Genet, I-50122 Florence, Italy. [Perelman, Polina L.; Stone, Gary] NCI, Frederick, MD 21702 USA. [Houck, Marlys L.] Zool Soc San Diego, Conservat & Res Endangered Species, San Diego, CA USA. [Robinson, Terence J.] Univ Stellenbosch, Dept Bot & Zool, Evout Genom Grp, Matieland, South Africa. [Dobigny, Gauthier] Ctr Biol & Gest Populat, Inst Rech Dev, F-34988 Montferrier Sur Lez, France. RP Trifonov, VA (reprint author), Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. EM vlad@bionet.nsc.ru; fy1@sanger.ac.uk RI Graphodatsky, Alexander/B-4922-2010; Trifonov, Vladimir/E-4907-2012; Perelman, Polina/N-8088-2015; Kulemzina, Anastasia/N-8554-2015; OI Graphodatsky, Alexander/0000-0002-8282-1085; Trifonov, Vladimir/0000-0003-0454-8359; Perelman, Polina/0000-0002-0982-5100; Stanyon, Roscoe/0000-0002-7229-1092 FU Wellcome Trust NR 61 TC 41 Z9 45 U1 1 U2 21 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAR PY 2008 VL 16 IS 1 BP 89 EP 107 DI 10.1007/s10577-007-1201-7 PG 19 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 267RB UT WOS:000253525800007 PM 18293107 ER PT J AU Graphodatsky, AS Perelman, PL Sokolovskaya, NV Beklemisheva, VR Serdukova, NA Dobigny, G Brien, SJO Ferguson-Smith, MA Yang, FT AF Graphodatsky, Alexander S. Perelman, Polina L. Sokolovskaya, Natalya V. Beklemisheva, Violetta R. Serdukova, Natalya A. Dobigny, Gauthier Brien, Stephen J. O. Ferguson-Smith, Malcolm A. Yang, Fengtang TI Phylogenomics of the dog and fox family (Canidae, Carnivora) revealed by chromosome painting SO CHROMOSOME RESEARCH LA English DT Article DE Canidae; Carnivora; chromosome maps; chromosome painting; evolution; genome; phylogeny ID ZOO-FISH ANALYSIS; DOMESTIC DOG; SILVER FOX; PHYLOGENETIC-RELATIONSHIPS; ORDER CARNIVORA; AMERICAN MINK; RED FOX; EVOLUTION; GENOME; KARYOTYPE AB Canid species (dogs and foxes) have highly rearranged karyotypes and thus represent a challenge for conventional comparative cytogenetic studies. Among them, the domestic dog is one of the best-mapped species in mammals, constituting an ideal reference genome for comparative genomic study. Here we report the results of genome-wide comparative mapping of dog chromosome-specific probes onto chromosomes of the dhole, fennec fox, and gray fox, as well as the mapping of red fox chromosome-specific probes onto chromosomes of the corsac fox. We also present an integrated comparative chromosome map between the species studied here and all canids studied previously. The integrated map demonstrates an extensive conservation of whole chromosome arms across different canid species. In addition, we have generated a comprehensive genome phylogeny for the Canidae on the basis of the chromosome rearrangements revealed by comparative painting. This genome phylogeny has provided new insights into the karyotypic relationships among the canids. Our results, together with published data, allow the formulation of a likely Canidae ancestral karyotype (CAK, 2n=82), and reveal that at least 6-24 chromosomal fission/fusion events are needed to convert the CAK karyotype to that of the modern canids. C1 [Graphodatsky, Alexander S.; Perelman, Polina L.; Sokolovskaya, Natalya V.; Beklemisheva, Violetta R.; Serdukova, Natalya A.] SB RAS, Inst Cytol & Genet, Novosibirsk 630090, Russia. [Perelman, Polina L.; Brien, Stephen J. O.] NCI, Lab Genome Divers, Frederick, MD 21702 USA. [Dobigny, Gauthier] Ctr Biol & Gest Populat, Inst Rech Dev, F-34988 Montferrier Sur Lez, France. [Ferguson-Smith, Malcolm A.] Univ Cambridge, Dept Vet Med, Cambridge Resource Ctr Comparat Genom, Cambridge CB3 0ES, England. [Yang, Fengtang] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. RP Graphodatsky, AS (reprint author), SB RAS, Inst Cytol & Genet, Novosibirsk 630090, Russia. EM graf@bionet.nsc.ru RI Graphodatsky, Alexander/B-4922-2010; Serdyukova, Natalia/N-6476-2015; Perelman, Polina/N-8088-2015; Beklemisheva, Violetta/N-9532-2015 OI Graphodatsky, Alexander/0000-0002-8282-1085; Perelman, Polina/0000-0002-0982-5100; NR 39 TC 26 Z9 30 U1 2 U2 29 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAR PY 2008 VL 16 IS 1 BP 129 EP 143 DI 10.1007/s10577-007-1203-5 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 267RB UT WOS:000253525800009 PM 18293108 ER PT J AU Lee, JY Choi, JY Lee, KM Park, SK Han, SH Noh, DY Ahn, SH Kim, DH Hong, YC Ha, E Yoo, KY Ambrosone, CB Kang, D AF Lee, Ji-Young Choi, Ji-Yeob Lee, Kyoung-Mu Park, Sue Kyung Han, So-Hee Noh, Dong-Young Ahn, Sei-Hyun Kim, Dong-Hyun Hong, Yun-Chul Ha, Eunhee Yoo, Keun-Young Ambrosone, Christine B. Kang, Daehee TI Rare variant of hypoxia-inducible factor-1 alpha (HIF-1A) and breast cancer risk in Korean women SO CLINICA CHIMICA ACTA LA English DT Article DE HIF-1A; polymorphism; breast cancer; clinicopathologic features ID FACTOR-I; PROSTATE-CANCER; FACTOR 1-ALPHA; POLYMORPHISM; CARCINOMA; GENE; OVEREXPRESSION AB Background: Hypoxia inducible factor 1 alpha (HIF-1A) is activated by low oxygen condition tension, a key regulator of the gene involved in the cellular response to hypoxia. Tumors exhibiting extensive hypoxia are more aggressive than tumors oxygenized better. Methods: To evaluate the potential role of the polymorphisms of HIF-1A in the etiology of breast cancer, histologically confirmed incident breast cancer cases (n=1599) and control subjects (n=1536) were recruited. Results: Two selected SNPs (Ex15+197C > T and P582S) were not associated with overall breast cancer risk (TT vs. CC: OR=0.9, 95% CI=0.6 - 1.5, Ser/Ser vs. Pro/Pro: OR=5.5, 95% CI=0.7 - 45.4, respectively). However, when stratified analyses were performed, significant associations were observed between Ser/Ser genotype at codon 582 and breast cancer risk among women with larger tumor size (> 2 cm) (OR=10. 1, 95% CI=1.1 - 91.1) or without lymph node involvement (OR=9.3, 95% CI=1.1 - 79.4), although confidence intervals were wide. Conclusions: Our findings support the hypothesis that the HIF-1A P582S variant may confer susceptibility to subgroups of breast cancer in Korean women. However, further study is warranted due to low statistical power caused by very low minor allele frequencies. (c) 2007 Elsevier B.V. All rights reserved. C1 [Lee, Ji-Young; Park, Sue Kyung; Han, So-Hee; Hong, Yun-Chul; Yoo, Keun-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. [Choi, Ji-Yeob; Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. [Lee, Kyoung-Mu] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110799, South Korea. [Kim, Dong-Hyun] Hallym Univ, Coll Med, Dept Social & Prevent Med, Chunchon, South Korea. [Ahn, Sei-Hyun; Ha, Eunhee] Univ Ulsan, Coll Med, Dept Surg, Seoul 138736, South Korea. [Yoo, Keun-Young] Korea Natl Canc Ctr, Gyeonggi 410769, South Korea. [Kang, Daehee] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yongon Dong, Seoul 110799, South Korea. EM dhkang@snu.ac.kr RI Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Choi, Ji-Yeob/J-2796-2012; Hong, Yun-Chul/J-5725-2012; Yoo, Keun-Young/J-5548-2012 NR 17 TC 31 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAR PY 2008 VL 389 IS 1-2 BP 167 EP 170 DI 10.1016/j.cca.2007.12.005 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 266QB UT WOS:000253450300029 PM 18160046 ER PT J AU Booty, M Kastner, D Aksentijevich, I AF Booty, M. Kastner, D. Aksentijevich, I. TI Novel insights into the inheritance and diagnosis of familial Mediterranean fever (FMF) SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Booty, M.; Kastner, D.; Aksentijevich, I.] NIH NIAMS GGB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA C1 BP 175 EP 175 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200012 ER PT J AU Colburn, N McManigle, J Singal, P Balow, J Mogul, D Zaal, K Sun, H Barham, B Chae, J Kastner, D AF Colburn, N. McManigle, J. Singal, P. Balow, J. Mogul, D. Zaal, K. Sun, H. Barham, B. Chae, J. Kastner, D. TI Dissecting inflammatory and chemotactic pathways in Familial Mediterrean Fever SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Colburn, N.; McManigle, J.; Singal, P.; Balow, J.; Mogul, D.; Zaal, K.; Sun, H.; Barham, B.; Chae, J.; Kastner, D.] NIAMSD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA C4 BP 176 EP 176 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200015 ER PT J AU Stojanov, S Chae, J Wood, G Rivollier, A Sun, H Grivel, J Balow, J Aksentijevich, I Kelsall, B Kastner, D AF Stojanov, S. Chae, J. Wood, G. Rivollier, A. Sun, H. Grivel, J. Balow, J. Aksentijevich, I. Kelsall, B. Kastner, D. TI Altered development and function of CD11c+cells in pyrin-null mice SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Stojanov, S.; Chae, J.; Wood, G.; Balow, J.; Aksentijevich, I.; Kastner, D.] NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. [Rivollier, A.; Kelsall, B.] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, Bethesda, MD 20892 USA. [Sun, H.] NIAMS, Biodata Min & Discovery Sect, Off Sci & Technol, NIH, Bethesda, MD USA. [Grivel, J.] NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA C11 BP 177 EP 177 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200022 ER PT J AU Balow, J Sun, H Godbach-Mansky, R Kastner, D Aksentijevich, I AF Balow, Jr J. Sun, H. Godbach-Mansky, R. Kastner, D. Aksentijevich, I. TI Microarray-based gene expression studies of systemic inflammation in patients with cryopyrin-associated periodic syndromes (CAPS) SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Balow, Jr J.; Kastner, D.; Aksentijevich, I.] NIAMS, NIH, Genet & Genom Branch, Bethesda, MD USA. [Sun, H.] NIAMS, NIH, Off Sci & Technol, Bethesda, MD USA. [Godbach-Mansky, R.] NIAMS, NIH, Off Clin Director, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA D2 BP 178 EP 178 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200026 ER PT J AU Brydges, S Mueller, J Misaghi, A McGeough, M Hillman, J Boyle, D Firestein, G Kastner, D Hoffman, H AF Brydges, S. Mueller, J. Misaghi, A. McGeough, M. Hillman, J. Boyle, D. Firestein, G. Kastner, D. Hoffman, H. TI Initial characterization of a mouse model of cryopyrinopathy SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Brydges, S.; Kastner, D.] NIAMS, Bethesda, MD USA. [Mueller, J.; Misaghi, A.; McGeough, M.; Hillman, J.; Boyle, D.; Firestein, G.; Hoffman, H.] Univ Calif San Diego, Dept Pediat, Dept Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA D3 BP 179 EP 179 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200027 ER PT J AU van der Hilst, J Bodar, E Barron, K Frenkel, J Drenth, J van der Meer, J Simon, A AF van der Hilst, J. Bodar, E. Barron, K. Frenkel, J. Drenth, J. van der Meer, J. Simon, A. TI Follow-up, clinical features, and quality of life in 10.3 patients with HyperImmunoglubulin D syndrome SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [van der Hilst, J.; Bodar, E.; van der Meer, J.; Simon, A.] Radboud Univ Nijmegen Med Ctr, Dept Gen Internal Med, Nijmegen, Netherlands. [Barron, K.] NIAMSD, Bethesda, MD USA. [Drenth, J.] Radboud Univ Nijmegen Med Ctr, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands. [Frenkel, J.] Univ Med Ctr, Dept Gen Pediat, Div Pediat, Utrecht, Netherlands. [Frenkel, J.] Univ Med Ctr, Dept Pediat Immunol, Div Pediat, Utrecht, Netherlands. RI Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA F2 BP 180 EP 180 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200030 ER PT J AU Ryan, J Balow, JJ Barham, B Barron, K Kastner, D Aksentijevich, I AF Ryan, J. Balow, Jnr J. Barham, B. Barron, K. Kastner, D. Aksentijevich, I. TI Identification and analysis of gene-expression signatures in peripheral blood leukocytes of patients with TRAPS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Ryan, J.; Balow, Jnr J.; Barham, B.; Kastner, D.; Aksentijevich, I.] NIAMSD, Bethesda, MD USA. [Barron, K.] Natl Inst Allergy & Infect Dis, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA H2 BP 182 EP 182 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200039 ER PT J AU Lapidus, S Chitkara, P Feder, H Salazar, J Aksentijevich, I Barham, B Athreya, B Barron, K Kastner, D Stojanov, S AF Lapidus, S. Chitkara, P. Feder, H. Salazar, J. Aksentijevich, I Barham, B. Athreya, B. Barron, K. Kastner, D. Stojanov, S. TI Unraveling the pathogenesis of Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) Syndrome: an immunological approach SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Lapidus, S.; Chitkara, P.; Aksentijevich, I; Barham, B.; Barron, K.; Kastner, D.; Stojanov, S.] NIH, Bethesda, MD USA. [Feder, H.; Salazar, J.] Univ Connecticut, Hlth Sci Ctr, Connecticut Childrens Med Ctr, Storrs, CT 06269 USA. [Athreya, B.] Thomas Jefferson Univ, Nemours AI DuPont Hosp Children, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA X4 BP 215 EP 215 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200163 ER PT J AU Aksentijevich, I Booty, M Kastner, D AF Aksentijevich, I Booty, M. Kastner, D. TI Targeted genes sequencing and high-throughput parallel strategies for mutation screening in patients with autoinflammatory diseases SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Aksentijevich, I; Booty, M.; Kastner, D.] NIAMS, NIH, GGB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA BB1 BP 218 EP 218 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200173 ER PT J AU Masters, S Booty, M Chae, J Aksentijevich, I Kastner, D AF Masters, S. Booty, M. Chae, J. Aksentijevich, I Kastner, D. TI A variant truncation form of ASC has a reduced pro-inflammatory profile SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Masters, S.; Booty, M.; Chae, J.; Aksentijevich, I; Kastner, D.] NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA BB2 BP 218 EP 218 PG 1 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200174 ER PT J AU Lapidus, S Athreya, B Aksentijevich, I Barham, B Kastner, D Barron, K AF Lapidus, S. Athreya, B. Aksentijevich, I. Barham, B. Kastner, D. Barron, K. TI The R92Q variant: Phenotype as a reflection of genotype in tumor necrosis factor receptor-associated periodic syndrome (TRAPS) SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Lapidus, S.; Aksentijevich, I.; Barham, B.; Kastner, D.; Barron, K.] Natl Inst Hlth, Bethesda, MD USA. [Athreya, B.] Thomas Jefferson Univ, AI DuPont Hosp Children, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2008 VL 26 IS 2 MA CC6 BP 220 EP 221 PG 2 WC Rheumatology SC Rheumatology GA 296CX UT WOS:000255522200181 ER PT J AU Garbow, JR Wang, M Wang, Y Lubet, RA You, M AF Garbow, Joel R. Wang, Min Wang, Yian Lubet, Ronald A. You, Ming TI Quantitative monitoring of adenocarcinoma development in rodents by magnetic resonance imaging SO CLINICAL CANCER RESEARCH LA English DT Article ID MOUSE LUNG; MRI; CANCER; TUMOR AB Purpose: Accurately following the time course of tumor progression and response to therapy in animal models of cancer is key to the development of better chemopreventive and chemotherapeutic agents. The goal of this work was to monitor quantitatively the development and progression of adenocarcinoma in a time course study of mice treated with the carcinogen urethane using in vivo small-animal magnetic resonance imaging (MRI). Experimental Design: Mice treated with a single dose of urethane were imaged at four time points beginning 8 months after treatment. High-resolution images of mouse lung were obtained in vivo using respiratory-gated MRI methods. Individual tumors were manually segmented and their volumes calculated. At the end of the study, mice were euthanized and MRI tumor quantification was validated by histology and histopathology. Results: Tumors as small as 0.4 mm in diameter can be detected and quantitatively measured in mice by in vivo MRI. Total tumor burden increased consistently in all mice studied, whereas the growth rate of individual tumors varied widely. The positions and diameters of individual tumors as measured by MRI correlated well with histology results. Histologic study of large, rapidly growing tumors showed that these were adenocarcinomas, whereas small, slowly growing lesions were predominantly adenomas. Conclusions: Longitudinal in vivo MRI is a powerful modality that can be of great aid in elucidating the factors that control the onset of lung tumors and can serve as a platform for the development and preclinical testing of novel therapies having a high likelihood of efficacy in human clinical trials. C1 [Wang, Min; Wang, Yian; You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Garbow, Joel R.; You, Ming] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Lubet, Ronald A.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. [Garbow, Joel R.] Washington Univ, Sch Med, Dept Radiol, Biomed MR Lab, St Louis, MO 63110 USA. RP Garbow, JR (reprint author), Washington Univ, Sch Med, Dept Radiol, Biomed MR Lab, Campus Box 8227,4525 Scott Ave, St Louis, MO 63110 USA. EM garbow@wustl.edu FU NCI NIH HHS [P30 CA91842, R01 CA58554, R24 CA83060] NR 13 TC 20 Z9 20 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2008 VL 14 IS 5 BP 1363 EP 1367 DI 10.1158/1078-0432.CCR-07-1757 PG 5 WC Oncology SC Oncology GA 268FR UT WOS:000253565000014 PM 18316556 ER PT J AU Chen, JP Lam, S Pilon, A McWilliams, A MacAulay, C Szabo, E AF Chen, Jiping Lam, Stephen Pilon, Aprile McWilliams, Annette MacAulay, Calum Szabo, Eva TI Higher levels of the anti-inflammatory protein CC10 are associated with improvement in bronchial dysplasia and sputum cytometric assessment in individuals at high risk for lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CLARA CELL PROTEIN; C-REACTIVE PROTEIN; RESPIRATORY-DISTRESS-SYNDROME; SECRETORY PROTEIN; CIGARETTE-SMOKE; 10-KDA PROTEIN; SERUM; GAMMA; CHEMOPREVENTION; INFLAMMATION AB Purpose: CC10, a 10-kDa anti-inflammatory protein secreted by bronchiolar Clara cells, is infrequently expressed in non-small cell lung cancer and its overexpression in non-small cell lung cancer cell lines results in a less malignant phenotype. Several lines of evidence have shown that bronchial dysplasia and sputum atypia are predictors of lung cancer. We investigated whether changes in CC10 expression correlate with regression of bronchial dysplasia and/or improvement in sputum abnormalities as measured by image cytometry. Experimental Design: High-risk smokers enrolled in a chemoprevention trial underwent serial bronchoscopies with biopsies and bronchoalveolar lavage (BAL) collection, sputum assessment by image cytometry, and blood collection. CC10 was measured by competitive ELISA in BAL and plasma. Logistic regression analyses were done to determine the associations between CC10 levels and the improvement in bronchial dysplasia and sputum cytometric assessment. Results: The net change in the BAL CC10 levels in subjects with improved bronchial lesions or improved sputum cytometry assessment was significantly higher than in those without improvement (P < 0.05). The odds ratio (95% confidence interval) associated with 1-unit increase in CC10 was 2.72 (1.31-5.64) for regression of dysplastic lesions and 2.94 (1.22-7.05) for improvement in sputum cytometry assessment after multivariate adjustment. Plasma CC10 was not significantly associated with either outcome. Conclusions: Higher BAL CC10 levels are significantly correlated with regression of bronchial dysplasia and improvement in sputum cytometry assessment in smokers with high lung cancer risk. Whether CC10 levels can predict clinical outcomes among high-risk populations warrants further investigation. C1 [Chen, Jiping; Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. [Chen, Jiping] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Lam, Stephen; McWilliams, Annette; MacAulay, Calum] British Columbia Canc Agcy, Lung Tumor Grp, Vancouver, BC V5Z 4E6, Canada. [Lam, Stephen; McWilliams, Annette; MacAulay, Calum] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Pilon, Aprile] CC10 Sweden AB, Rockville, MD USA. RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, NIH, 6130 Execut Blvdm,Room 2132, Bethesda, MD 20892 USA. EM szaboe@mail.nih.gov RI MacAulay, Calum/K-1795-2016 FU NCI NIH HHS [N01-CN-85188] NR 41 TC 12 Z9 13 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2008 VL 14 IS 5 BP 1590 EP 1597 DI 10.1158/1078-0432.CCR-07-4066 PG 8 WC Oncology SC Oncology GA 268FR UT WOS:000253565000042 PM 18316584 ER PT J AU Lauretani, F Semba, RD Bandinelli, S Miller, ER Ruggiero, C Cherubini, A Guralnik, JM Ferrucci, L AF Lauretani, Fulvio Semba, Richard D. Bandinelli, Stefania Miller, Edgar R., III Ruggiero, Carmelinda Cherubini, Antonio Guralnik, Jack M. Ferrucci, Luigi TI Plasma polyunsaturated fatty acids and the decline of renal function SO CLINICAL CHEMISTRY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; INFLAMMATORY MARKERS; KIDNEY-FUNCTION; LINOLENIC ACID; NITRIC-OXIDE; FISH-OIL; DISEASE; ALPHA; DIET AB BACKGROUND: Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. METHODS: We performed a cross-sectional and prospective analysis of 931 adults, >= 65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. RESULTS: At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. CONCLUSION: High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the Age-associated decline in renal function among older community-dwelling women and men. (c) 2008 American Association for Clinical Chemistry. C1 [Lauretani, Fulvio; Miller, Edgar R., III; Ruggiero, Carmelinda; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, ASTRA Unit, Baltimore, MD 21225 USA. [Lauretani, Fulvio] Tuscany Reg Agcy, Florence, Italy. [Semba, Richard D.; Miller, Edgar R., III] Johns Hopkins Sch Med, Baltimore, MD USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Ruggiero, Carmelinda; Cherubini, Antonio] Univ Perugia, Sch Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, ASTRA Unit, Harbor Hosp 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, N01-AG-916413, R01 AG027012, N01-AG-5-0002] NR 33 TC 27 Z9 27 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2008 VL 54 IS 3 BP 475 EP 481 DI 10.1373/clinchem.2007.095521 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 268HI UT WOS:000253570400006 PM 18202159 ER PT J AU Remaley, AT AF Remaley, Alan T. TI An unusual case of severe hypertriglyceridemia and splenomegaly - Commentary SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NIH, Bldg 10,Rm 2C-433,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM aremaley@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2008 VL 54 IS 3 BP 610 EP 611 DI 10.1373/clinchem.2007.101881 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 268HI UT WOS:000253570400025 ER PT J AU Shamburek, R AF Shamburek, Robert TI An unusual case of severe hypertriglyceridemia and splenomegaly - Commentary SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Shamburek, R (reprint author), Natl Inst Hlth, Bldg 10 7N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM bobs@nhlbi.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2008 VL 54 IS 3 BP 611 EP 611 DI 10.1373/clinchem.2007.101899 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 268HI UT WOS:000253570400026 ER PT J AU Boasso, A Shearer, GM AF Boasso, Adriano Shearer, Gene M. TI Chronic innate immune activation as a cause of HIV-1 immunopathogenesis SO CLINICAL IMMUNOLOGY LA English DT Review DE human immunodeficiency virus; simian immunodeficiency virus; immunopathogenesis; innate immunity; adaptive immunity; T cells; plasmacitoid dendritic cells (pDC); type I interferon; indoleamine; 2,3-dioxygenase ID PLASMACYTOID DENDRITIC CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; REGULATORY T-CELLS; INTERFERON-PRODUCING CELLS; INFECTED SOOTY MANGABEYS; TRYPTOPHAN CATABOLISM; DISEASE PROGRESSION; INDOLEAMINE 2,3-DIOXYGENASE; LYMPHOID-TISSUE; UP-REGULATION AB Human immunodeficiency virus (HIV)-1 infection causes progressive impairment of the immune system in humans, characterized by depletion of CD4 T cells and toss of T cell function. Increased markers of T cell activation and lymphoid hyperplasia suggest that chronic T cell activation persists in immunocompromised hosts, and contributes to the exhaustion of immune functions. Here we propose a revision of this hypothesis, in which we suggest that chronic activation of innate immunity may negatively affect adaptive T cell-mediated responses. We hypothesize that constant exposure of the effector cells of innate immunity to HIV results in their chronic hyperactivation, with deleterious effects on T cells. In particular, plasmacytoid dendritic cells (pDC) may be highly susceptible to HIV-induced activation due to its interaction with the cellular receptor CD4, expressed by pDC. Subsequent production of type I interferon and indoleamine 2,3-dioxygenase may exert suppressive and cytotoxic effects on T cells. Published by Elsevier Inc. C1 [Boasso, Adriano; Shearer, Gene M.] NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Boasso, A (reprint author), NCI, NIH, Expt Immunol Branch, 10 Ctr Dr,Bldg 10,Room 4B36, Bethesda, MD 20892 USA. EM boassoa@mait.nih.gov OI Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS [NIH0011420077]; PHS HHS [NIH0011420077] NR 77 TC 127 Z9 133 U1 5 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2008 VL 126 IS 3 BP 235 EP 242 DI 10.1016/j.clim.2007.08.015 PG 8 WC Immunology SC Immunology GA 265MW UT WOS:000253364400001 PM 17916442 ER PT J AU Gao, SW Oliver, DK Das, N Hurst, FP Lentine, KL Agodoa, LY Sawyers, ES Abbott, KC AF Gao, Sam W. Oliver, David K. Das, Neal Hurst, Frank P. Lentine, Krista L. Agodoa, Lawrence Y. Sawyers, Eric S. Abbott, Kevin C. TI Assessment of racial disparities in chronic kidney disease stage 3 and 4 care in the Department of Defense health system SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID AFRICAN-AMERICANS; PREVALENCE; MORTALITY; GFR AB Background and objectives: Racial disparities in provision of healthcare are widespread in the United States but have not been specifically assessed in provision of chronic kidney disease (CKD) care. Design, setting, participants, & measurements: We conducted a retrospective cohort study of the clinical database used in a Department of Defense (DOD) medical system. Beneficiaries studied were DOD-eligible beneficiaries with CKD stage 3 (n = 7729) and 4 (n = 589) using the modified Modification of Diet in Renal Disease (MDRD)-estimated GFR formula but requiring manual correction for Black race. Compliance with selected Kidney Disease Outcomes Quality Initiative (KDOQI) CKD recommended targets (monitoring of recommended laboratory data, prescription of recommended medications, and referral to nephrology) was assessed over a 12-mo period, stratified by CKD stage. Logistic regression analysis was used to assess whether race (White, Black, or other) was independently associated with provider compliance with targets, adjusted for demographic factors and burden of comorbid conditions. Results: Among the targets, only monitoring of LDL cholesterol was significantly less common among Blacks. For all other measures, compliance was either not significantly different or significantly higher for Black compared with White beneficiaries. However, patients categorized as "Other" race were in general less likely to achieve targets than Whites, and at stage 3 CKD significantly less likely to achieve targets for monitoring of phosphorous, hemoglobin, and vitamin D. Conclusions: In the DOD health system, provider compliance with selected CKD stage 3 and 4 targets was not significantly lower for Black beneficiaries than for Whites, with the exception of LDL cholesterol monitoring. Patients classified as Other race were generally less likely to achieve targets than Whites, in some patients significantly so. C1 [Oliver, David K.; Das, Neal; Hurst, Frank P.; Abbott, Kevin C.] Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. [Gao, Sam W.] Natl Naval Med Ctr, Serv Nephrol, Bethesda, MD USA. [Gao, Sam W.; Oliver, David K.; Das, Neal; Hurst, Frank P.; Abbott, Kevin C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Lentine, Krista L.] St Louis Univ, Ctr Outcomes Res, St Louis, MO 63103 USA. [Sawyers, Eric S.] Natl Naval Med Ctr, San Diego, CA USA. [Agodoa, Lawrence Y.] NIDDK, Natl Inst Hlth, San Diego, CA USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@us.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 15 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2008 VL 3 IS 2 BP 442 EP 449 DI 10.2215/CJN.03940907 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 270GS UT WOS:000253709800021 PM 18199843 ER PT J AU Fadrowski, JJ Pierce, CB Cole, SR Moxey-Mims, M Warady, BA Furth, SL AF Fadrowski, Jeffrey J. Pierce, Christopher B. Cole, Stephen R. Moxey-Mims, Marva Warady, Bradley A. Furth, Susan L. TI Hemoglobin decline in children with chronic kidney disease: Baseline results from the chronic kidney disease in children prospective cohort study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ERYTHROPOIETIN; ANEMIA AB Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population. Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration. Results: Of the 340 patients studied, the mean age was 11 +/- 4 yr, the mean glomerular filtration rate was 42 +/- 14 ml/min per 1.73 m(2), and the mean hemoglobin was 12.5 +/- 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval -0.2 to -0.5) for every 5-ml/min per 1.73 m(2) decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m(2), the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m(2) decrease in glomerular filtration rate. Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m(2). Because serum creatinine-based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals. C1 [Fadrowski, Jeffrey J.; Furth, Susan L.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. [Pierce, Christopher B.; Cole, Stephen R.; Furth, Susan L.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. [Furth, Susan L.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21218 USA. [Moxey-Mims, Marva] NIDDK, Natl Inst Hlth, Bethesda, MD USA. [Warady, Bradley A.] Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. RP Fadrowski, JJ (reprint author), David M Rubenstein Child Hlth Bldg,Room 3055,200, Baltimore, MD 21287 USA. EM jfadrow1@jhmi.edu FU NIDDK NIH HHS [U01-DK-66174, K24 DK078737, U01 DK066116, U01 DK066143, U01 DK066174, U01-DK-66116, U01-DK-66143]; NIEHS NIH HHS [K23 ES016514] NR 17 TC 21 Z9 27 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2008 VL 3 IS 2 BP 457 EP 462 DI 10.2215/CJN.03020707 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 270GS UT WOS:000253709800023 PM 18235140 ER PT J AU Chandraker, A Mannon, RB AF Chandraker, Anil Mannon, Roslyn B. TI Care of the kidney transplant recipient SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 [Mannon, Roslyn B.] NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. [Chandraker, Anil] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Mannon, RB (reprint author), NIDDK, Transplantat Branch, NIH, 10 Ctr Dr,MSC 1450,CRC 5-5750, Bethesda, MD 20892 USA. EM rozm@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2008 VL 3 SU 2 BP S27 EP S28 DI 10.2215/CJN.05141107 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 271XS UT WOS:000253822600001 PM 18309000 ER PT J AU Jevnikar, AM Mannon, RB AF Jevnikar, Anthony M. Mannon, Roslyn B. TI Late kidney allograft loss: What we know about it, and what we can do about it SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID RENAL-TRANSPLANT RECIPIENTS; TUBULAR EPITHELIAL-CELLS; ANTI-HLA ANTIBODIES; CONVERTING-ENZYME-INHIBITOR; TO-MESENCHYMAL TRANSITION; TISSUE GROWTH-FACTOR; CHRONIC REJECTION; CALCINEURIN INHIBITORS; PROTOCOL BIOPSIES; RANDOMIZED-TRIAL AB Despite dramatic improvements in immunosuppression, late graft loss after kidney transplantation remains a common and difficult problem. Histologic evaluation may reveal changes related to BK polyomavirus infection, hypertension, or calcineurin inhibitor toxicity, which can help to guide therapy. The designation chronic allograft nephropathy should thus be reserved for biopsies with tubular atrophy and interstitial fibrosis without an apparent cause. Although the cause clearly includes both antigen-dependent and antigen-independent events, the approach remains largely to exclude immune mechanisms. Although this review discusses the potential contribution of antibody to chronic injury, it focuses on the basic elements of kidney injury, the role of parenchymal cells in promoting injury, and the proliferative and inflammatory responses that accompanying injury. Strategies to manage these recipients include close attention to accompanying hypertension, diabetes, and hyperlipidemia, as well as consideration for altering immunosuppression; however, therapies that limit epithelial-to-mesenchymal transition or directly block fibrosis pathways may reduce chronic allograft fibrosis and may prove to be useful. Understanding the basic pathogenesis sufficiently to allow early intervention may finally benefit patients who are at high risk for tubular atrophy and interstitial fibrosis and promote their long-term graft function. C1 [Mannon, Roslyn B.] NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. [Jevnikar, Anthony M.] Univ Western Ontario, London Hlth Sci Ctr, Lawson Hlth Res Inst, Dept Med, London, ON, Canada. [Jevnikar, Anthony M.] Univ Western Ontario, Robarts Res Inst, London Hlth Sci Ctr, London, ON, Canada. RP Mannon, RB (reprint author), NIDDK, Transplantat Branch, NIH, 10 Ctr Dr,MSC 1450,CRC 5-5750, Bethesda, MD 20892 USA. EM rozm@mail.nih.gov FU Intramural NIH HHS NR 134 TC 61 Z9 66 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2008 VL 3 SU 2 BP S56 EP S67 DI 10.2215/CJN.03040707 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 271XS UT WOS:000253822600005 PM 18309004 ER PT J AU Cao, YJ Mager, DE Simonsick, EM Hilmer, SN Ling, SM Windham, BG Crentsil, V Yasar, S Fried, LP Abernethy, DR AF Cao, Y-J Mager, D. E. Simonsick, E. M. Hilmer, S. N. Ling, S. M. Windham, B. G. Crentsil, V. Yasar, S. Fried, L. P. Abernethy, D. R. TI Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ELDERLY POPULATION; BENZODIAZEPINE USE; RISK-FACTORS; DRUG-USE; ADULTS; DISABILITY; COMMUNITY; ASSOCIATION; MEDICATIONS; PEOPLE AB Polypharmacy, common in older people, confers both risk of adverse outcomes and benefits. We assessed the relationship of commonly prescribed medications with anticholinergic and sedative effects to physical and cognitive performance in older individuals. The study population comprised 932 moderately to severely disabled community-resident women aged 65 years or older who were participants in the Women's Health and Aging Study I. A scale based on pharmacodynamic principles was developed and utilized as a measure of drug burden. This was related to measures of physical and cognitive function. After adjusting for demographics and comorbidities, anticholinergic drug burden was independently associated with greater difficulty in four physical function domains with adjusted odds ratios (95% confidence interval (CI)) of 4.9 (2.0-12.0) for balance difficulty; 3.2 (1.5-6.9) for mobility difficulty; 3.6 (1.6-8.0) for slow gait; 4.2 (2.0-8.7) for chair stands difficulty; 2.4 (1.1-5.3) for weak grip strength; 2.7 (1.3-5.4) for upper extremity limitations; 3.4 (1.7-6.9) for difficulty in activities of daily living; and 2.4 (95% CI, 1.1-5.1) for poor performance on the Mini-Mental State Examination. Sedative burden was associated only with impaired grip strength (3.3 (1.5-7.3)) and mobility difficulty (2.4 (1.1-5.3)). The burden of multiple drugs can be quantified by incorporating the recommended dose regimen and the actual dose and frequency of drug taken. Anticholinergic drug burden is strongly associated with limitations in physical and cognitive function. Sedative burden is associated with impaired functioning in more limited domains. The risk associated with exposure of vulnerable older women to drugs with anticholinergic properties, and to a lesser extent those with sedative properties, implies that such drugs should not be used in this patient group without compelling clinical indication. C1 [Cao, Y-J; Mager, D. E.; Simonsick, E. M.; Hilmer, S. N.; Ling, S. M.; Windham, B. G.; Abernethy, D. R.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Cao, Y-J; Abernethy, D. R.] Johns Hopkins Univ, Sch Med, Dept Med Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Mager, D. E.] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. [Simonsick, E. M.; Crentsil, V.; Yasar, S.; Fried, L. P.; Abernethy, D. R.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med,Ctr Aging & Hlth, Baltimore, MD 21205 USA. [Hilmer, S. N.] Univ Sydney, Sydney, NSW 2006, Australia. RP Abernethy, DR (reprint author), NIA, Intramural Res Program, Baltimore, MD 21224 USA. EM abernethyd@grc.nia.nih.gov OI Hilmer, Sarah/0000-0002-5970-1501 FU Intramural NIH HHS; NIA NIH HHS [N0-1AG-1-2112, R01 AG-19825, R37 AG-19905]; NIGMS NIH HHS [5T32GM066691-02] NR 34 TC 71 Z9 74 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 IS 3 BP 422 EP 429 DI 10.1038/sj.clpt.6100303 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 267ZN UT WOS:000253547800017 PM 17713474 ER PT J AU Gregorc, V Hidalgo, M Spreafico, A Cusatis, G Ludovini, V Ingersoll, RG Marsh, S Steinberg, SM Vigano, MG Ghio, D Villa, E Sparreboom, A Baker, SD AF Gregorc, V. Hidalgo, M. Spreafico, A. Cusatis, G. Ludovini, V. Ingersoll, R. G. Marsh, S. Steinberg, S. M. Vigano, M. G. Ghio, D. Villa, E. Sparreboom, A. Baker, S. D. TI Germline polymorphisms in EGFR and survival in patients with lung cancer receiving gefitinib SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 17th EORTC/AACR/NCI International Conference on Molecular Targets and Cancer Therapeutics CY NOV 14-18, 2005 CL Philadelphia, PA SP European Soc Comparat Endocrinol, City Manchester, Univ Manchester, AstraZeneca, Bristol Myers Squibb, Pfizer, Sanofi Aventis, Bayer Hlth Care Pharmaceut, Lilly, Genentech, GlaxoSmithKline, Johnson & Johnson, MERCK, NOVARTIS ONCOL, Centocor, OSI Oncol, Schering-Plough, BTG, Servier, RADPHARM, Cvitkovic & Associes ID GROWTH-FACTOR-RECEPTOR; CA DINUCLEOTIDE REPEAT; TYROSINE KINASE DOMAIN; PHASE-III TRIAL; GENE-TRANSCRIPTION; PROGNOSTIC-FACTOR; CLINICAL BENEFIT; RANDOMIZED-TRIAL; SKIN RASH; INTRON 1 AB The purpose of this study was to evaluate associations between germline epidermal growth factor receptor (EGFR) variants involved in transcriptional regulation and overall survival in white patients with non-small-cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor, gefitinib. Of 175 consecutive patients treated with oral gefitinib (250mg/day), 170 ( median age: 67 years; 72% men) were evaluable for genotyping and survival. Fifty-five patients (33%) had stable disease and 17 (10%) had an objective response. The most common of four haplotypes was G-C (EGFR*1) at the EGFR -216G>T and -191C>A loci (frequency, 0.45). After adjusting for performance status, previous platinum-containing chemotherapy and occurrence of skin rash or diarrhea during the first treatment cycle in patients with performance status 0 or 1 (N=139), the absence of EGFR*1 was associated with significantly better survival ( hazard ratio: 0.54; 95% confidence interval: 0.32-0.91; P=0.015). The results may help identify patients with NSCLC who can benefit from gefitinib treatment. C1 [Hidalgo, M.; Cusatis, G.; Ingersoll, R. G.; Baker, S. D.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Gregorc, V.; Spreafico, A.; Vigano, M. G.; Ghio, D.; Villa, E.] Univ Hosp San Raffaele, Inst Sci, Dept Oncol, Milan, Italy. [Ludovini, V.] Monteluce Policlin, Div Med Oncol, Perugia, Italy. [Marsh, S.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Steinberg, S. M.; Sparreboom, A.] Natl Canc Inst, Med Oncol Branch, Bethesda, MD USA. RP Baker, SD (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. EM sharyn.baker@stjude.org RI Sparreboom, Alex/B-3247-2008; Cusatis, Gianluca/G-2539-2011; HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 NR 42 TC 37 Z9 38 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 IS 3 BP 477 EP 484 DI 10.1038/sj.clpt.6100320 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 267ZN UT WOS:000253547800024 PM 17713473 ER PT J AU Brar, S Ramchandani, V Hersh, J Lee, J Kim, H George, DT Herion, D Venitz, J AF Brar, S. Ramchandani, V. Hersh, J. Lee, J. Kim, H. George, D. T. Herion, D. Venitz, J. TI Temporal influence of alcohol detoxification and smoking on plasma dopamine and R/S-salsolinol in alcoholics. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Brar, S.; Venitz, J.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Ramchandani, V.; Hersh, J.; Lee, J.; Kim, H.; George, D. T.; Herion, D.] NIH, NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S75 EP S75 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800240 ER PT J AU Gronich, N Zhang, Y Kumar, A Hucker, W Wood, W Becker, K Efimov, I Soldatov, N AF Gronich, N. Zhang, Y. Kumar, A. Hucker, W. Wood, W., III Becker, K. Efimov, I. Soldatov, N. TI Molecular remodeling of calcium channels in human cardiac myocytes affected by dilated cardiomyopathy. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Gronich, N.] NIH, NIA, ClinPrat Fellowship, Baltimore, MD USA. [Zhang, Y.; Kumar, A.; Wood, W., III; Becker, K.; Soldatov, N.] NIH, NIA, Baltimore, MD USA. [Hucker, W.; Efimov, I.] Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S82 EP S82 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800264 ER PT J AU Soule, TA Schrieber, SJ Wen, Z Wahed, A Smith, PC Fried, MW Reddy, R Navarro, VJ Afdhal, NH Belle, SH Berman, J Liu, QY Doo, E Hawkel, RL AF Soule, T. A. Schrieber, S. J. Wen, Z. Wahed, A. Smith, P. C. Fried, M. W. Reddy, R. Navarro, V. J. Afdhal, N. H. Belle, S. H. Berman, J. Liu, Q. Y. Doo, E. Hawkel, R. L. TI Single dose escalation phase I study to evaluate the pharmacokinetics (PK) of silymarin (Legalon (R)) and the effect of food in patients with chronic hepatitis C (HCV). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Soule, T. A.; Schrieber, S. J.; Wen, Z.; Smith, P. C.; Fried, M. W.; Hawkel, R. L.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Wahed, A.; Belle, S. H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Reddy, R.] Univ Penn, Philadelphia, PA 19104 USA. [Navarro, V. J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Afdhal, N. H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Berman, J.; Liu, Q. Y.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Doo, E.] NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S77 EP S77 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800248 ER PT J AU Wang, X Hamza, M Gordon, SM Wahl, SM Dionne, RA AF Wang, X. Hamza, M. Gordon, S. M. Wahl, S. M. Dionne, R. A. TI Cox inhibitors downregulate PDE4D expression in a clinical model of inflammatory pain. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Wang, X.; Hamza, M.; Dionne, R. A.] NIH, NINR, Bethesda, MD 20892 USA. [Gordon, S. M.] Univ Maryland, Sch Dent, College Pk, MD 20742 USA. [Wahl, S. M.] NIH, NIDCR, Bethesda, MD 20892 USA. RI Hamza, May/A-5053-2010 OI Hamza, May/0000-0002-7637-3060 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S71 EP S71 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800229 ER PT J AU Berry, C Zimmerli, LU Steedman, T Foster, JE Dargie, HJ Berg, GA Dominiczak, AF Delles, C AF Berry, Colin Zimmerli, Lukas U. Steedman, Tracey Foster, John E. Dargie, Henry J. Berg, Geoffrey A. Dominiczak, Anna F. Delles, Christian TI Cardiac magnetic resonance findings predict increased resource utilization in elective coronary artery bypass grafting SO CLINICAL SCIENCE LA English DT Article DE coronary artery bypass surgery (CABG); coronary artery disease; cardiac magnetic resonance (CMR); echocardiography; left ventricular function; resource utilization ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR EJECTION FRACTION; CARE-UNIT STAY; INTENSIVE-CARE; HEART-FAILURE; RISK-FACTORS; SURGERY; LENGTH; ENHANCEMENT; OUTCOMES AB Morbidity following CABG (coronary artery bypass grafting) is difficult to predict and leads to increased healthcare costs. We hypothesized that pre-operative CMR (cardiac magnetic resonance) findings would predict resource utilization in elective CABG. Over a 12-month period, patients requiring elective CABG were invited to undergo CMR I day prior to CABG. Gadolinium-enhanced CMR was performed using a trueFISP inversion recovery sequence on a 1.5 tesla, scanner (Sonata; Siemens). Clinical data were collected prospectively. Admission costs were quantified based on standardized actual cost/day. Admission cost greater than the median was defined as 'increased'. Of 458 elective CABG cases, 45 (10 %) underwent pre-operative CMR. Pre-operative characteristics [mean (S.D.) age, 64 (9) years, mortality (I %) and median (interquartile range) admission duration, 7 (6-8) days] were similar in patients who did or did not undergo CMR. In the patients undergoing CMR, eight (18 %) and 11 (24 %) patients had reduced LV (left ventricular) systolic function by CMR [LVEF (LV ejection fraction) < 55 %] and echocardiography respectively. LE (late enhancement) with gadolinium was detected in 17 (38 %) patients. The average cost/day was $2723. The median (interquartile range) admission cost was $19059 ($10891-157917). CMR LVEF {OR (odds ratio), 0.93 [95 % CI (confidence interval), 0.87-0.99]; P = 0.03} and SV (stroke volume) index [OR 1.07 (95 % CI, 1.00- 1.14); P = 0.02] predicted increased admission cost. CMR LVEF (P = 0.08) and EuroScore tended to predict actual admission cost (P = 0.09), but SV by CMR (P = 0.16) and LV function by echocardiography (P = 0.95) did not. In conclusion, in this exploratory investigation, pre-operative CMR findings predicted admission duration and increased admission cost in elective CABG surgery. The cost-effectiveness of CMR in risk stratification in elective CABG surgery merits prospective assessment. C1 [Berry, Colin; Zimmerli, Lukas U.; Steedman, Tracey; Dominiczak, Anna F.; Delles, Christian] Univ Glasgow, British Heart Fdn Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Berry, Colin; Zimmerli, Lukas U.; Steedman, Tracey; Foster, John E.; Dargie, Henry J.; Dominiczak, Anna F.; Delles, Christian] Western Infirm & Associated Hosp, Glasgow Cardiac Magnet Resonance Unit, Glasgow, Lanark, Scotland. [Dargie, Henry J.; Berg, Geoffrey A.] Western Infirm & Associated Hosp, Dept Cardiac Surg, Glasgow, Lanark, Scotland. RP Berry, C (reprint author), NHLBI, Cardiovasc Branch, Natl Inst Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM berryc@mail.nih.gov RI Dominiczak, Anna/D-2262-2009 FU Chief Scientist Office [SCD/01]; Wellcome Trust NR 35 TC 3 Z9 3 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD MAR PY 2008 VL 114 IS 5-6 BP 423 EP 430 DI 10.1042/CS20070337 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 272GX UT WOS:000253849000008 PM 17999639 ER PT J AU Sokoloff, L AF Sokoloff, Louis TI The physiological and biochemical bases of functional brain imaging SO COGNITIVE NEURODYNAMICS LA English DT Review DE Cerebral blood flow; Cerebral glucose utilization; Cerebral metabolism; Astrocytes; Glycolysis; ATPase; fMRI; Lactate shuttle ID CEREBRAL GLUCOSE-UTILIZATION; SENSORY STIMULATION; ELECTRICAL-STIMULATION; ENERGY-METABOLISM; GLUTAMATE UPTAKE; BLOOD-FLOW; RAT; ACTIVATION; DEOXYGLUCOSE; CONSUMPTION AB Functional brain imaging is based on the display of computer-derived images of changes in physiological and/or biochemical functions altered by activation or depression of local functional activities in the brain. This article reviews the physiological and biochemical mechanisms involved. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, NIH, Bldg 49,Room 1B80,49 Convent Dr MSC 4415, Bethesda, MD 20892 USA. EM louissokoloff@mail.nih.gov NR 27 TC 25 Z9 26 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1871-4080 J9 COGN NEURODYNAMICS JI Cogn. Neurodynamics PD MAR PY 2008 VL 2 IS 1 BP 1 EP 5 DI 10.1007/s11571-007-9033-x PG 5 WC Neurosciences SC Neurosciences & Neurology GA 450PH UT WOS:000266412800001 PM 19003468 ER PT J AU Della Sala, S Grafman, J AF Della Sala, Sergio Grafman, Jordan TI Letters to cortex SO CORTEX LA English DT Editorial Material C1 [Della Sala, Sergio] Univ Edinburgh, Human Cognit Neurosci Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Grafman, Jordan] NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Della Sala, S (reprint author), Univ Edinburgh, Human Cognit Neurosci Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland. OI Grafman, Jordan H./0000-0001-8645-4457 NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD MAR PY 2008 VL 44 IS 3 BP 229 EP 229 DI 10.1016/j.cortex.2007.12.006 PG 1 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 276ON UT WOS:000254152000002 ER PT J AU Carlet, J Cohen, J Calandra, T Opal, SM Masur, H AF Carlet, Jean Cohen, Jonathan Calandra, Thierry Opal, Steven M. Masur, Henry TI Sepsis: Time to reconsider the concept SO CRITICAL CARE MEDICINE LA English DT Article DE sepsis; clinical trials; severe infection; trial design ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; TUMOR-NECROSIS-FACTOR; SEPTIC SHOCK; CLINICAL-TRIALS; MORTALITY; INFECTIONS; EFFICACY; ALPHA; BLOOD AB Objective., To discuss the difficulty in using the concept of sepsis for clinical trials and propose new ways for designing future trials for severe infections. Design: Short position statement. Methods and Main Research: Using a thorough evaluation of the recent literature in the field of severe sepsis and septic shock, the authors challenge the concept of sepsis as used in the past two decades and propose new ideas for designing future trials in this setting. The two main proposals are first to use a systematic assessment of the targeted inflammatory mediators when the study intends to counteract or replace those. mediators (e.g., anti-tumor necrosis factor-et, activated protein C) and, second, to select more homogeneous populations, coming back to "precise infectious diseases," such as severe community-acquired pneumonia, severe peritonitis, or meningitis. Conclusions. The concept of sepsis has been useful to help clinicians to suspect and detect severe infections. Due to a considerable heterogeneity in the patients and type of infections included in the trials performed in the last two decades, it has not been useful in demonstrating the efficacy of new compounds. The authors propose a dramatic change in the design of future trials dealing with severe infections. C1 [Carlet, Jean] Grp Hosp Paris St Joseph, Intens Care Unit, Dept Infect Dis, Paris, France. [Cohen, Jonathan] Univ Sussex, Brighton & Sussex Med Sch, Falmer, England. [Calandra, Thierry] CHU Vaudois, Infect Dis Serv, Dept Med, Lausanne, Switzerland. [Opal, Steven M.] Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02912 USA. [Opal, Steven M.] Brown Univ, Mem Hosp Rhode Isl, Div Infect Dis, Pawtucket, RI 02860 USA. [Masur, Henry] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Carlet, J (reprint author), Grp Hosp Paris St Joseph, Intens Care Unit, Dept Infect Dis, Paris, France. EM j.cariet@has-saute.fr RI Calandra, Thierry/D-9017-2015 OI Calandra, Thierry/0000-0003-3051-1285 NR 31 TC 64 Z9 66 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2008 VL 36 IS 3 BP 964 EP 966 DI 10.1097/CCM.0B013E318165B886 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 266QD UT WOS:000253450500041 PM 18431286 ER PT J AU Rivera, J Olivera, A AF Rivera, Juan Olivera, Ana TI A current understanding of FccRI-dependent mast cell activation SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review ID FC-EPSILON-RI; NEGATIVE REGULATION; ALLERGIC RESPONSE; LYN KINASE; PHOSPHOINOSITIDE 3-KINASE; CYTOKINE PRODUCTION; SPHINGOSINE KINASE; FYN KINASE; IGE; RECEPTOR AB Mast cell activation via the high-affinity immunoglobulin (Ig) E receptor Fc epsilon RI is a topic of extensive investigation with therapeutic potential in allergic disease. The protein tyrosine kinases Fyn, Lyn, and Syk are intimately linked with the early events initiated by allergen-mediated aggregation of IgE-occupied Fc epsilon RI. Fyn and Lyn initiate signaling events that are organized by adaptor molecules, which compartmentalize and coordinate the activity of activated protein and lipid kinases and phospholipases to generate lipid products essential for signal amplification and mast cell function. Fyn and Lyn counter-regulate phosphaticlylinositol 3-OH kinase (PI3K), controlling the produced amount of phosphaticlylinositol (3,4,5)-trisphosphate (PIP3), a key regulator of mast cell degranulation. Fyn and Lyn also activate sphingosine kinases (SphK), which generate sphingosine-1-phosphate (S1P), thus contributing to mast cell chemotaxis and degranulation. Here, we summarize the current knowledge and future challenges and directions. C1 [Rivera, Juan; Olivera, Ana] NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9S205, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov FU Intramural NIH HHS NR 49 TC 30 Z9 31 U1 0 U2 4 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD MAR PY 2008 VL 8 IS 1 BP 14 EP 20 DI 10.1007/s11882-008-0004-z PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 281AT UT WOS:000254469200003 PM 18377769 ER PT J AU Feng, Y Dimitrov, DS AF Feng, Yang Dimitrov, Dimiter S. TI Monoclonal antibodies against components of the IGF system for cancer treatment SO CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT LA English DT Review DE IGF; IGF-IR; therapeutic antibody ID GROWTH-FACTOR-I; HUMAN PROSTATE-CANCER; FACTOR RECEPTOR; ANTITUMOR-ACTIVITY; BINDING-PROTEINS; TUMOR-GROWTH; INSULIN; INHIBITION; CELLS; MICE AB Insulin-like growth factor (IGF)-mediated signaling pathways have long been recognized as important targets for cancer therapy. The development of antibodies against the IGF type I receptor (IGF-IR) started in the early 1980s, although clinical studies of these antibodies were not conducted until more recent years. At least eight different anti-IGF-IR antibodies are currently in clinical trials and are reviewed in this article; each antibody was generated by a different method and has unique features. Information collected from these early clinical trials should be taken into consideration during the design of further studies and future clinical applications, as well as in the improvement of the respective antibodies. The development of antibodies against IGF ligands is also discussed. C1 [Feng, Yang; Dimitrov, Dimiter S.] NCI Frederick, NIH, CCR, Nanobiol Program,Protein Interact Grp, Frederick, MD 21702 USA. RP Feng, Y (reprint author), NCI Frederick, NIH, CCR, Nanobiol Program,Protein Interact Grp, Bldg 469,Rm 139, Frederick, MD 21702 USA. EM yfeng@ncifcrf.gov FU Intramural NIH HHS NR 41 TC 20 Z9 26 U1 0 U2 0 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1367-6733 J9 CURR OPIN DRUG DISC JI Curr. Opin. Drug Discov. Dev. PD MAR PY 2008 VL 11 IS 2 BP 178 EP 185 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 263LM UT WOS:000253218600003 PM 18283605 ER PT J AU Gutierrez, M Giaccone, G AF Gutierrez, Martin Giaccone, Giuseppe TI Antiangiogenic therapy in nonsmall cell lung cancer SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE antiangiogenesis; molecular targeted therapy; nonsmall cell lung cancer ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; FACTOR MONOCLONAL-ANTIBODY; FACTOR RECEPTOR; TUMOR ANGIOGENESIS; ANTITUMOR-ACTIVITY; PROGNOSTIC-SIGNIFICANCE; FACTOR EXPRESSION; IN-VIVO; SU11248 AB Purpose of review The use of targeted therapies, particularly those against the key mediator of angiogenesis, vascular endothelial growth factor, has the potential to improve outcomes for nonsmall cell lung cancer (NSCLC) patients. This review summarizes recent findings on targeting mediators of angiogenesis, treatment options and molecular targets in development. Recent findings Bevacizumab, a recombinant humanized monoclonal antivascular endothelial growth factor antibody, in a phase III study, showed significantly improved overall and progression-free survival when used in combination with standard first-line chemotherapy in patients with advanced NSCLC and was generally well tolerated. Adverse events, including tumor-related bleeding, have been noted in some patients, predominantly those with squamous cell histology or centrally located tumors. Summary Several small-molecule vascular endothelial growth factor receptor tyrosine kinase inhibitors have also shown promise in phase I and II trials in NSCLC. This review summarizes the most important findings on angiogenesis inhibitors in NSCLC and discusses the potential for the use of these novel agents in different settings. C1 [Gutierrez, Martin; Giaccone, Giuseppe] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10-12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 62 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAR PY 2008 VL 20 IS 2 BP 176 EP 182 PG 7 WC Oncology SC Oncology GA 273MZ UT WOS:000253936300005 PM 18300767 ER PT J AU Rich, BA Grimley, ME Schmajuk, M Blair, KS Blair, RJR Leibenlijft, E AF Rich, Brendan A. Grimley, Mary E. Schmajuk, Mariana Blair, Karina S. Blair, R. J. R. Leibenlijft, Ellen TI Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID BILATERAL AMYGDALA DAMAGE; FACIAL AFFECT RECOGNITION; VOXEL-BASED MORPHOMETRY; PSYCHOPATHIC TENDENCIES; COMMUNICATION CHECKLIST; RECOGNIZING EMOTION; NEURAL CIRCUITRY; EARLY EXPERIENCE; AUTISTIC TRAITS; JUVENILE MANIA AB Children with narrow phenotype bipolar disorder (NP-BD; i.e., history of at least one hypomanic or manic episode with euphoric mood) are deficient when labeling face emotions. It is unknown if this deficit is specific to particular emotions, or if it extends to children with severe mood dysregulation (SMD; i.e., chronic irritability and hyperarousal without episodes of mania). Thirty-nine NP-BD, 31 SMD, and 36 control subjects completed the emotional expression multimorph task, which presents gradations of facial emotions from 100% neutrality to 100% emotional expression (happiness, surprise, fear, sadness, anger, and disgust). Groups were compared in terms of intensity of emotion required before identification occurred and accuracy. Both NP-BD and SMD youth required significantly more morphs than controls to label correctly disgusted, surprised, fearful, and happy faces. Impaired face labeling correlated with deficient social reciprocity skills in NP-BD youth and dysfunctional family relationships in SMD youth. Compared to controls, patients with NP-BD or SMD require significantly more intense facial emotion before they are able to label the emotion correctly. These deficits are associated with psychosocial impairments. Understanding the neural circuitry associated with face-labeling deficits has the potential to clarify the pathophysiology of these disorders. C1 [Rich, Brendan A.; Grimley, Mary E.; Schmajuk, Mariana; Blair, Karina S.; Blair, R. J. R.; Leibenlijft, Ellen] NIMH, NIH, Bethesda, MD 20892 USA. RP Rich, BA (reprint author), NIMH, NIH, Bldg 15K,Room 204,MSC 2670, Bethesda, MD 20892 USA. EM brendanrich@mail.nih.gov FU Intramural NIH HHS [Z01 MH002778-08, Z01 MH002786-06, Z99 MH999999] NR 90 TC 71 Z9 72 U1 5 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 2008 VL 20 IS 2 BP 529 EP 546 DI 10.1017/S0954579408000266 PG 18 WC Psychology, Developmental SC Psychology GA 293HX UT WOS:000255327500008 PM 18423093 ER PT J AU Schroter, C Herrgen, L Cardona, A Brouhard, GJ Feldman, B Oates, AC AF Schroeter, Christian Herrgen, Leah Cardona, Albert Brouhard, Gary J. Feldman, Benjamin Oates, Andrew C. TI Dynamics of zebrafish somitogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE zebrafish; somitogenesis; oscillator; period; frequency; rate; time-lapse; temperature; segmentation; Clock and Wavefront model ID SOMITE SEGMENTATION CLOCK; DANIO-RERIO; EMBRYONIC-DEVELOPMENT; LOCOMOTOR MORPHOLOGY; BOUNDARY FORMATION; VERTEBRATE; TEMPERATURE; MUTANT; TIME; SPECIFICATION AB Vertebrate somitogenesis is a rhythmically repeated morphogenetic process. The dependence of somitogenesis dynamics on axial position and temperature has not been investigated systematically in any species. Here we use multiple embryo time-lapse imaging to precisely estimate somitogenesis period and somite length under various conditions in the zebrafish embryo. Somites form at a constant period along the trunk, but the period gradually increases in the tail. Somite length varies along the axis in a stereotypical manner, with tail somites decreasing in size. Therefore, our measurements prompt important modifications to the steady-state Clock and Wavefront model: somitogenesis period, somite length, and wavefront velocity all change with axial position. Finally, we show that somitogenesis period changes more than threefold across the standard developmental temperature range, whereas the axial somite length distribution is temperature invariant. This finding indicates that the temperature-induced change in somitogenesis period exactly compensates for altered axial growth. C1 [Schroeter, Christian; Herrgen, Leah; Brouhard, Gary J.; Oates, Andrew C.] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. [Cardona, Albert] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. [Feldman, Benjamin] NIH, Med Genet Branch, Bethesda, MD 20892 USA. RP Oates, AC (reprint author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany. EM oates@mpi-cbg.de OI Schroter, Christian/0000-0002-8161-7568; Feldman, Benjamin/0000-0003-4838-8641; Cardona, Albert/0000-0003-4941-6536 FU Intramural NIH HHS NR 37 TC 54 Z9 55 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD MAR PY 2008 VL 237 IS 3 BP 545 EP 553 DI 10.1002/dvdy.21458 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 277RK UT WOS:000254232200002 PM 18265021 ER PT J AU Toba, Y Tiong, JD Ma, O Wray, S AF Toba, Yoko Tiong, Jean D. Ma, Oing Wray, Susan TI CXCR4/SDF-1 system modulates development of GnRH-1 neurons and the olfactory system SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE GnRH-1; neuronal migration; axonal outgrowth; SDF-1; CXCR4 ID CHEMOKINE RECEPTOR CXCR4; HORMONE NEURONS; EMBRYONIC EXPRESSION; MIGRATORY PATHWAY; PROGENITOR CELLS; NERVOUS-SYSTEM; MESSENGER-RNA; LHRH NEURONS; IN-VITRO; BRAIN AB Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 influence neuronal migration and have been identified in nasal regions. Gonadotropin releasing hormone-1 (GnRH-1) neurons migrate from nasal regions into the developing forebrain, where postnatally they control reproduction. This study examined the role of SDF-1/CXCR4 in development of the GnRH1/olfactory systems. Migrating GnRH-1 neurons were CXCR4 immunopositive as were the fibers along which they migrate. SDF-1 transcripts were detected in olfactory epithelium and vomeronasal organ, while SDF-1 immunoreactivity highlighted the GnRH-1 migratory pathway. CXCR4-deficient mice showed a decrease in GnRH-1 cells at the nasal forebrain junction and in brain, but the overall migratory pathway remained intact, no ectopic GnRH-1 cells were detected and olfactory axons reached the olfactory bulb. To further characterize the influence of SDF-1/CXCR4 in the GnRH-1 system, nasal explants were used. CXCR4 expression in vitro was similar to that in vivo. SDF-1 was detected in a dorsal midline cell cluster as well as in migrating GnRH-1 cells. Treatment of explants with bicyclam AMD3100, a CXCR4 antagonist, attenuated GnRH-1 neuronal migration and sensory axon outgrowth. Moreover, the number of GnRH-1 neurons in the explant periphery was reduced. The effects were blocked by coin-cubation with SDF-1. Removal of midline SDF-1 cells did not alter directional outgrowth of olfactory axons. These results indicate that SDF-1/CXCR4 signaling in not necessary for olfactory axon guidance but rather influences sensory axon extension and GnRH-1 neuronal migration, and maintains GnRH-1 neuronal expression as the cells move away from nasal pit regions. (C) 2008 Wiley Periodicals, Inc. C1 [Toba, Yoko; Tiong, Jean D.; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Ma, Oing] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM swray@codon.nih.gov OI wray, susan/0000-0001-7670-3915 FU Intramural NIH HHS NR 47 TC 30 Z9 30 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8451 J9 DEV NEUROBIOL JI Dev. Neurobiol. PD MAR PY 2008 VL 68 IS 4 BP 487 EP 503 DI 10.1002/dneu.20594 PG 17 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 269OB UT WOS:000253657400006 PM 18188864 ER PT J AU Llorens, F Gil, V Iraola, S Carim-Todd, L Marti, E Estivill, X Soriano, E del Rio, JA Sumoy, L AF Llorens, Franc Gil, Vanesa Iraola, Susana Carim-Todd, Laura Marti, Eulalia Estivill, Xavier Soriano, Eduardo del Rio, Jose Antonio Sumoy, Lauro TI Developmental analysis of Lingo-1/Lern1 protein expression in the mouse brain: Interaction of its intracellular domain with Myt1l SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE Lrrn6A; lingo-1; p75; NgR1; Myt1l ID MYELIN-ASSOCIATED GLYCOPROTEIN; INHIBITOR NOGO-A; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; RECEPTOR FAMILY-MEMBER; AXONAL REGENERATION; ZINC-FINGER; VISUAL-CORTEX; MESSENGER-RNA; GENE AB Lingo-1 (also known as Lern1) is a component of the Nogo receptor complex that mediates intracellular signaling in response to myelin associated inhibitors (MAIs): NogoA, MAG, and Omgp. Signaling through Nogo receptor extends to more than its well known role in preventing axon regeneration after lesion in the CNS, being implicated in neuronal functional maturation. Using Lingo-1-deficient mice, it has been demonstrated that Lingo-1 plays relevant roles in oligodendrocyte differentiation during brain development, and that treatment with Lingo-1 antagonists can improve axon regeneration after lesion in adult mice by decreasing MAI mediated signaling. However, a detailed description of the pattern of expression of Lingo-1 protein in correlation with the other partners of Nogo receptor is missing. Here, we show that components of the Nogo receptor complex, Lingo-1, NgR1, p75, and TROY coexist in mouse brain in a defined time window only at later postnatal stages. We have also determined the Lingo-1 distribution showing expression in particular subsets of neurons, but not in myelinating mature oligodendrocytes. Surprisingly, Lingo-1 is expressed at early developmental stages without NgR1, which supports the notion that Lingo-1 may participate in other activities in developing neurons different from oligodendrocyte maturation or axon extension inhibition in the adult. Finally, we propose that the intracellular domain of Lingo-1 contributes to signaling and show that it interacts with the postmitotic neuronal specitic zinc finger protein Myt1l, suggesting that Lingo-1 may regulate Myt1l transcription factor activity by affecting its subcellular localization. (C) 2008 Wiley Periodicals, Inc. C1 [Llorens, Franc; Iraola, Susana; Carim-Todd, Laura; Sumoy, Lauro] UPF, CRG, Bioinformat & Genom Program, Barcelona 08003, Spain. [Gil, Vanesa] Univ Barcelona, Fac Biol, E-08028 Barcelona, Spain. [Gil, Vanesa; Soriano, Eduardo] CIBERNED, Barcelona, Spain. [Gil, Vanesa; Soriano, Eduardo] Univ Barcelona, Inst Rec Biomed, E-08028 Barcelona, Spain. [Gil, Vanesa; Soriano, Eduardo] Univ Barcelona, Dept Biol Celular, E-08028 Barcelona, Spain. [Carim-Todd, Laura] NCI, Mouse Canc Genet Program, Neural Dev Grp, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Marti, Eulalia; Estivill, Xavier] UPF, CRG, Genes & Dis Program, Barcelona 08003, Spain. RP Sumoy, L (reprint author), UPF, CRG, Bioinformat & Genom Program, Barcelona 08003, Spain. EM lauro.sumoy@crg.es RI Estivill, Xavier/E-2957-2012; Estivill, Xavier/A-3125-2013; gil, vanessa/N-5013-2014; Marti, Eulalia/L-2775-2014; OI Estivill, Xavier/0000-0002-0723-2256; gil, vanessa/0000-0002-7782-5575; Marti, Eulalia/0000-0002-1030-3158; Iraola-Guzman, Susana/0000-0003-3359-1241; Del Rio, Jose Antonio/0000-0002-5214-4909; , Franc/0000-0002-9756-7497 NR 61 TC 28 Z9 30 U1 0 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8451 J9 DEV NEUROBIOL JI Dev. Neurobiol. PD MAR PY 2008 VL 68 IS 4 BP 521 EP 541 DI 10.1002/dneu.20607 PG 21 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 269OB UT WOS:000253657400008 PM 18186492 ER PT J AU Rubin, RR Ma, Y Marrero, DG Peyrot, M Barrett-Connor, EL Kahn, SE Haffner, SM Price, DW Knowler, WC AF Rubin, Richard R. Ma, Yong Marrero, David G. Peyrot, Mark Barrett-Connor, Elizabeth L. Kahn, Steven E. Haffner, Steven M. Price, David W. Knowler, William C. CA Diabet Prevention Program Res Grp TI Elevated depression symptoms, antidepressant medicine use, and risk of developing diabetes during the diabetes prevention program SO DIABETES CARE LA English DT Article ID COMORBID DEPRESSION; CONTROLLED-TRIAL; MELLITUS; WEIGHT; METAANALYSIS; INDIVIDUALS; ASSOCIATION; POPULATION; DISORDERS; ADULTS AB OBJECTIVE - To assess the association between elevated depression symptoms or antidepressant medicine use on entry to the Diabetes Prevention Program (DPP) and during the study and the risk of developing diabetes during the study. RESEARCH DESIGN AND METHODS - DPP participants (n = 3,187) in three treatment arms (intensive lifestyle [ILS], metformin [MET], and placebo [PLB]) completed the Beck Depression Inventory (BDI) and reported their use of antidepressant medication at randomization and throughout the study (average duration in study 3.2 years). RESULTS - When other factors associated with the risk of developing diabetes were controlled, elevated BDI scores at baseline or during the study were not associated with diabetes risk in any arm. Baseline antidepressant use was associated with diabetes risk in the PLB (hazard ratio 2.25 [95% CI 1.38-3 66]) and ILS (3.48 [1.93-6.28]) arms. Continuous antidepressant use during the study (compared with no use) was also associated with diabetes risk in the same arms (PLB 2.60 [1.37-4.94]; ILS 3.39 [1.61-7.13]), as was intermittent antidepressant use during the study in the ILS arm (2.07 [1.18-3.62]). Among MET arm participants, antidepressant use was not associaed, with developing diabetes. CONCLUSIONS - A strong and statistically significant association between antidepressant use and diabetes risk in the PLB and ILS arms was not accounted for by measured confounders or mediators. if future research finds that antidepressant use independently predicts diabetes risk, efforts to minimize the negative effects of antidepressant agents on glycemic control should be pursued. C1 [Rubin, Richard R.; Peyrot, Mark] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Rubin, Richard R.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Ma, Yong] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Marrero, David G.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Peyrot, Mark] Loyola Coll, Dept Sociol, Baltimore, MD 21210 USA. [Barrett-Connor, Elizabeth L.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Kahn, Steven E.] Univ Washington, Dept Med, Seattle, WA USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Clin Epidemiol, San Antonio, TX 78229 USA. [Price, David W.] Univ Colorado, Sch Med, Dept Family Med, Denver, CO USA. [Knowler, William C.] NIDDKD, Phoenix, AZ USA. RP Rubin, RR (reprint author), Johns Hopkins Univ, Sch Med, 946 E Piney Hill Rd, Monkton, MD 21111 USA. EM rrubin4@jhmi.edu OI Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS; NIDDK NIH HHS [U01 DK048489-06, U01 DK048489] NR 37 TC 100 Z9 103 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2008 VL 31 IS 3 BP 420 EP 426 DI 10.2337/dc07-182T PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100008 PM 18071002 ER PT J AU Kjm, NH Pavkov, ME Looker, HC Nelson, RG Bennett, PH Hanson, RL Curtis, JM Sievers, ML Knowler, WC AF Kjm, Nan Hee Pavkov, Meda E. Looker, Helen C. Nelson, Robert G. Bennett, Peter H. Hanson, Robert L. Curtis, Jeffrey M. Sievers, Maurice L. Knowler, William C. TI Plasma glucose regulation and mortality in Pima Indian's SO DIABETES CARE LA English DT Article ID IMPAIRED FASTING GLUCOSE; CORONARY HEART-DISEASE; CARDIOVASCULAR MORTALITY; FOLLOW-UP; DIABETES-MELLITUS; RISK-FACTOR; TOLERANCE; HYPERGLYCEMIA; PREVALENCE; DIAGNOSIS AB OBJECTIVE - To evaluate whether impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are associated with increased risk of mortality and prevalent ischemic heart disease (IHD) and to analyze if the increased risk of death is dependent on subsequent development of diabetes in Pima Indians. RESEARCH DESIGN AND METHODS - A total of 2,993 Pima Indians aged >= 35 years were included. Prevalent IHD, defined by major ischemic electrocardiogram changes, was evaluated according to the following glucose/diabetes categories: normal glucose regulation (NGR), IFG and/or IGT, and diabetic groups by duration. During a median follow-up of 10.4 years, 780 subjects died from natural causes and 156 of these died from IHD. Mortality was analyzed according to the same glucose/diabetes categories at baseline and then as time-dependent variables. RESULTS - Only subjects with diabetes >= 15 years of duration have a higher prevalence of IHD (odds ratio 1.9 [95% CI 1.4-2.5]) relative to NGR. In baseline and time-dependent models, age- and sex-adjusted death rates from natural causes and from IHD were similar among the nondiabetic groups. Among diabetic subjects, natural mortality was higher in those with >= 15 years diabetes duration (death rate ratio [DRR] relative to NGR = 2.6 [95% CI 2.1-3.3]). IHD mortality was higher in subjects with long diabetes duration (DRR for diabetes 10-15 years 3.8 [1.5-9.5]; DRR for diabetes >= 15 years = 8.6 [3.8-19.4]) in the time-dependent model. CONCLUSIONS - Natural and IHD mortality are not increased in Pima Indians with IFG and/or IGT. Only after the onset of diabetes do the rates of these events increase relative to NGR. C1 [Kjm, Nan Hee; Pavkov, Meda E.; Nelson, Robert G.; Bennett, Peter H.; Hanson, Robert L.; Curtis, Jeffrey M.; Sievers, Maurice L.; Knowler, William C.] NIDDKD, NIH, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA. [Looker, Helen C.] Mt Sinai Sch Med, Div Endocrinol, New York, NY USA. RP Kjm, NH (reprint author), NIDDKD, NIH, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM kimnanhee@niddk.nih.gov RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 22 TC 2 Z9 2 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2008 VL 31 IS 3 BP 488 EP 492 DI 10.2337/dc07-1850 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100023 ER PT J AU Sosenko, JM Krisher, JP Palmer, JP Mahon, J Cowie, C Greenbaum, CJ Cuthbertson, D Lachin, JM Skyler, JS AF Sosenko, Jay M. Krisher, Jeffrey P. Palmer, Jerry P. Mahon, Jeffrey Cowie, Catherine Greenbaum, Carla J. Cuthbertson, David Lachin, John M. Skyler, Jay S. CA Diabet Prevention Trial-Type 1 Stu TI A risk score for type 1 diabetes derived from autoantibody-positive participants in the diabetes prevention trial-type-1 SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; INSULIN-RESISTANCE; ACCELERATOR HYPOTHESIS; INTERVENTION TRIAL; HOMEOSTASIS MODEL; PROGRESSION; RELATIVES; PREDICTION; SIBLINGS AB OBJECTIVE - The accurate prediction of type 1 diabetes is essential for appropriately identifying prevention trial participants. Thus, we have developed a risk score for the prediction of type 1 diabetes. RESEARCH DESIGN AND METHODS - Diabetes Prevention Trial-Type 1 (DPT-1) participants, islet cell autoantibody (ICA)-positive relatives of type 1 diabetic patients (n = 670), were randomly divided into development and validation samples. Risk score values were calculated for the validation sample from development sample model coefficients obtained through forward stepwise proportional hazards regression. RESULTS - A risk score based on a model including log-BMI, age, log-fasting C-peptide, and postchallenae glucose and C-peptide sums from 2-h oral glucose tolerance tests (OGTTs) was derived from the development sample. The baseline risk score strongly predicted type 1 diabetes in the validation sample (chi(2) = 82.3, P < 0.001). Its strength of prediction was almost the same (chi(2) = 83.3) as a risk score additionally dependent on a decreased first-phase insulin response variable from intravenous glucose tolerance tests (IVGTTs). Biochemical autoantibodies did not contribute significantly to the risk score model. A final type 1 diabetes risk score was then derived from all participants with the same variables as those in the development sample model. The change in the type 1 diabetes risk score from baseline to 1 year was in itself also highly predictive of type 1 diabetes (P < 0.001). CONCLUSIONS - A risk score based on age, BMI, and OGTT indexes, without dependence on IVGTTs or additional autoantibodies, appears to accurately predict type 1 diabetes in ICA-positive relatives. C1 [Sosenko, Jay M.; Skyler, Jay S.] Univ Miami, Div Endocrinol, Miami, FL 33101 USA. [Krisher, Jeffrey P.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Palmer, Jerry P.] Univ Washington, Div Endocrinol Metab, Seattle, WA 98195 USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 3K7, Canada. [Cowie, Catherine] NIDDK, NIH, Bethesda, MD USA. [Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, POB 016960 D110, Miami, FL 33101 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016; OI Lachin, John/0000-0001-9838-2841 NR 23 TC 52 Z9 52 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2008 VL 31 IS 3 BP 528 EP 533 DI 10.2337/dc07-1459 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100034 PM 18000175 ER PT J AU Nguyen, TT Wang, JJ Sharrett, AR Islam, FMA Klein, R Klein, BEK Cotch, MF Wong, TY AF Nguyen, Thanh Tan Wang, Jie Jin Sharrett, A. Richey Islam, F. M. Amirul Klein, Ronald Klein, Barbara E. K. Cotch, Mary Frances Wong, Tien Yin TI Relationship of retinal vascular caliber with diabetes and retinopathy - The Multi-Ethnic Study of Atherosclerosis (MESA) SO DIABETES CARE LA English DT Article ID VESSEL DIAMETERS; GLYCEMIC CONTROL; BLOOD-FLOW; RISK; MELLITUS; INFLAMMATION AB OBJECTIVE - To examine the relationship of retinal vascular caliber with diabetes, glycemia, and diabetic retinopathy. RESEARCH DESIGN AND METHODS - Population-based study using data from the Multi-Ethnic Study of Atherosclerosis (MESA), comprising 5,976 individuals (whites, blacks, Hispanics, and Chinese) residing in six U.S. communities who were free of clinical cardiovascular disease at baseline. Retinal vascular caliber was measured from digital retinal photographs. RESULTS - There were 4,585 individuals with normal fasting glucose (NFG), 499 with impaired fasting glucose (IFG), 165 with diabetes with retinopathy signs, and 727 with diabetes 00 without retinopathy signs. After multivariate analysis, retinal arteriolar caliber increased from 143.8 mu m in subjects with NFG to 144.5 mu m in IFG and 146.1 mu m in diabetes (P < 0.001 for trend). Retinal venular caliber increased from 214.4 mu m in NFG to 216.7 mu m in IFG and 218.0 mu m in diabetes (P < 0.001 for trend). Retinal venular caliber was significantly larger with increasing levels of fasting glucose and AlC. In a subgroup analysis by ethnicity, the association between wider arteriolar caliber and diabetes was evident in whites only, whereas wider venular caliber and diabetes was evident in Hispanics and Chinese only. in people with diabetes, eyes with retinopathy had larger retinal venular but not arteriolar caliber. CONCLUSIONS - Retinal arteriolar and venular calibers are larger in individuals with diabetes, but the pattern of associations appears to vary by ethnicity. Retinal venular caliber is additionally associated with retinopathy signs. These findings add further to the concept that variations in retinal vascular caliber may reflect early diabetic microvascular damage. C1 [Nguyen, Thanh Tan; Wang, Jie Jin; Islam, F. M. Amirul; Wong, Tien Yin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. [Sharrett, A. Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med, Dept Ophthalmol, Madison, WI USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Wong, Tien Yin] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117548, Singapore. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au RI Wang, Jie Jin/P-1499-2014; OI Wang, Jie Jin/0000-0001-9491-4898; Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU Intramural NIH HHS [Z99 EY999999, Z01 EY000403-06, Z01 EY000403-07, ZIA EY000403-08, ZIA EY000403-09, ZIA EY000403-10]; NHLBI NIH HHS [HL6997903, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169, R01 HL069979] NR 25 TC 82 Z9 85 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2008 VL 31 IS 3 BP 544 EP 549 DI 10.2337/dc07-1528 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100037 PM 18070990 ER PT J AU Fradkin, J Rodgers, GP AF Fradkin, Judith Rodgers, Griffin P. TI The economic imperative to conquer diabetes SO DIABETES CARE LA English DT Editorial Material ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; UNITED-STATES; HEART-ASSOCIATION; US ADULTS; MELLITUS; PREVENTION; METFORMIN; TRENDS; PEOPLE C1 [Fradkin, Judith; Rodgers, Griffin P.] NIDDK, Div Endocrinol Diabet & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Fradkin, J (reprint author), NIDDK, Div Endocrinol Diabet & Metab Dis, NIH, 3100 Ctr Dr,31-9A27, Bethesda, MD 20892 USA. EM jf58s@nih.gov NR 22 TC 6 Z9 7 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2008 VL 31 IS 3 BP 624 EP 626 DI 10.2337/dc07-0088 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271PL UT WOS:000253801100051 PM 18308686 ER PT J AU Florez, JC Jablonski, KA McAteer, J Sandhu, MS Wareham, NJ Barroso, I Franks, PW Altshuler, D Knowler, WC AF Florez, J. C. Jablonski, K. A. McAteer, J. Sandhu, M. S. Wareham, N. J. Barroso, I. Franks, P. W. Altshuler, D. Knowler, W. C. CA Diabet Prevention Program Res Grp TI Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Article DE beta cell function; diabetes prevention; genetic association study; single nucleotide polymorphism; type 2 diabetes; Wolfram syndrome ID GENOME-WIDE ASSOCIATION; TYPE-2; RISK AB Aims/hypothesis Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is caused by mutations in the WFS1 gene. Recently, single nucleotide polymorphisms (SNPs) in WFS1 have been reproducibly associated with type 2 diabetes. We therefore examined the effects of these variants on diabetes incidence and response to interventions in the Diabetes Prevention Program (DPP), in which a lifestyle intervention or metformin treatment was compared with placebo. Methods We genotyped the WFS1 SNPs rs10010131, rs752854 and rs734312 (H611R) in 3,548 DPP participants and performed Cox regression analysis using genotype, intervention and their interactions as predictors of diabetes incidence. We also evaluated the effect of these SNPs on insulin resistance and beta cell function at 1 year. Results Although none of the three SNPs was associated with diabetes incidence in the overall cohort, white homozygotes for the previously reported protective alleles appeared less likely to develop diabetes in the lifestyle arm. Examination of the publicly available Diabetes Genetics Initiative genome-wide association dataset revealed that rs10012946, which is in strong linkage disequilibrium with the three WFS1 SNPs (r(2) = 0.88-1.0), was associated with type 2 diabetes (allelic odds ratio 0.85, 95% CI 0.75-0.97, p = 0.026). In the DPP, we noted a trend towards increased insulin secretion in carriers of the protective variants, although for most SNPs this was seen as compensatory for the diminished insulin sensitivity. Conclusions/interpretation The previously reported protective effect of select WFS1 alleles may be magnified by a lifestyle intervention. These variants appear to confer an improvement in beta cell function. C1 [Florez, J. C.] George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. [Florez, J. C.; McAteer, J.; Altshuler, D.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, J. C.; Altshuler, D.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Florez, J. C.; Altshuler, D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, J. C.; Altshuler, D.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Florez, J. C.; McAteer, J.; Altshuler, D.] MIT, Cambridge, MA 02139 USA. [Jablonski, K. A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Sandhu, M. S.; Wareham, N. J.] Strangeways Res Lab, MRC, Epidemiol Unit, Cambridge CB1 4RN, England. [Sandhu, M. S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England. [Barroso, I.] Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton, England. [Franks, P. W.] Umea Univ Hosp, Inst Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. [Altshuler, D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Knowler, W. C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. RP Florez, JC (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM jcflorez@partners.org RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Franks, Paul/0000-0002-0520-7604 FU Intramural NIH HHS; Medical Research Council [MC_U106179471]; NIDDK NIH HHS [K23 DK65978-04, U01 DK048489-06, K23 DK065978, R01 DK072041, R01 DK072041-02, U01 DK048489] NR 10 TC 40 Z9 43 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2008 VL 51 IS 3 BP 451 EP 457 DI 10.1007/s00125-007-0891-x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 258RW UT WOS:000252888200011 PM 18060660 ER PT J AU Sacho, EJ Tessmer, I Diaz, M Erie, DA AF Sacho, Elizabeth J. Tessmer, Ingrid Diaz, Marilyn Erie, Dorothy A. TI Response to "Is AID a monomer in solution" SO DNA REPAIR LA English DT Letter ID ATOMIC-FORCE MICROSCOPY; ASSEMBLIES; DEAMINASE; DNA C1 [Sacho, Elizabeth J.; Erie, Dorothy A.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Erie, Dorothy A.] Univ N Carolina, Curriculum Appl & Mat Sci, Chapel Hill, NC 27599 USA. [Tessmer, Ingrid] Univ Wurzburg, Rudolf Virchow Zentrum Expt Biomed, D-97078 Wurzburg, Germany. [Diaz, Marilyn] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Erie, DA (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. EM derie@unc.edu NR 10 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAR 1 PY 2008 VL 7 IS 3 BP 351 EP 352 DI 10.1016/j.dnarep.2007.11.004 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 275MG UT WOS:000254075700002 ER PT J AU Croteau, DL DellaVecchia, MJ Perera, L Van Houten, B AF Croteau, Deborah L. DellaVecchia, Matthew J. Perera, Lalith Van Houten, Bennett TI Cooperative damage recognition by UvrA and UvrB: Identification of UvrA residues that mediate DNA binding SO DNA REPAIR LA English DT Article DE DNA binding; damage recognition; nucleotide excision repair; UvrA; UvrB ID NUCLEOTIDE EXCISION-REPAIR; ESCHERICHIA-COLI-UVRA; TERMINAL ZINC-FINGER; CRYSTAL-STRUCTURE; ATPASE ACTIVITY; HELICASE-II; THERMUS-THERMOPHILUS; STRUCTURAL INSIGHTS; PREINCISION COMPLEX; ABC EXCINUCLEASE AB Nucleotide excision repair (NER) is responsible for the recognition and removal of numerous structurally unrelated DNA lesions. in prokaryotes, the proteins UvrA, UvrB and UvrC orchestrate the recognition and excision of aberrant lesions from DNA. Despite the progress we have made in understanding the NER pathway, it remains unclear how the UvrA dimer interacts with DNA to facilitate DNA damage recognition. The purpose of this study was to define amino acid residues in UvrA that provide binding energy to DNA. Based on conservation among similar to 300 UvrA sequences and 3D-modeling, two positively charged residues, Lys680 and Arg691, were predicted to be important for DNA binding. Mutagenesis and biochemical analysis of Bacillus caldontenax UvrA variant proteins containing site directed mutations at these residues demonstrate that Lys680 and Arg691 make a significant contribution toward the DNA binding affinity of UvrA. Replacing these side chains with alanine or negatively charged residues decreased UvrA binding 3-37-fold. Survival studies indicated that these mutant proteins complemented a WP2 uvrA(-) strain of bacteria 10-100% of WT UvrA levels. Further analysis by DNase I footprinting of the double UvrA mutant revealed that the UvrA DNA binding defects caused a slower rate of transfer of DNA to UvrB. Consequently, the mutants initiated the oligonucleotide incision assay nearly as well as WT UvrA thus explaining the observed mild phenotype in the survival assay. Based on our findings we propose a model of how UvrA binds to DNA. Published by Elsevier B.V. C1 [Croteau, Deborah L.; DellaVecchia, Matthew J.; Van Houten, Bennett] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Perera, Lalith] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Van Houten, B (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM vanhout1@niehs.nih.gov RI perera, Lalith/B-6879-2012 OI perera, Lalith/0000-0003-0823-1631 FU Intramural NIH HHS [Z01 ES061060-09] NR 49 TC 20 Z9 20 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAR 1 PY 2008 VL 7 IS 3 BP 392 EP 404 DI 10.1016/j.dnarep.2007.11.013 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 275MG UT WOS:000254075700005 PM 18248777 ER PT J AU Kosarek, JN Woodruff, RV Rivera-Begeman, A Guo, CX D'Souza, S Koonin, EV Walker, GC Friedberg, EC AF Kosarek, J. Nicole Woodruff, Rachel V. Rivera-Begeman, Amanda Guo, Caixia D'Souza, Sanjay Koonin, Eugene V. Walker, Graham C. Friedberg, Errol C. TI Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts SO DNA REPAIR LA English DT Article DE Y-family of DNA polymerases; TLS; Rev1; polymerase eta; polymerase iota; polymerase kappa; protein-protein interactions ID ESCHERICHIA-COLI DINB; SACCHAROMYCES-CEREVISIAE; TRANSLESION SYNTHESIS; INTRINSIC DISORDER; MODEL ORGANISMS; COELOMATA CLADE; SOS MUTAGENESIS; UV-RADIATION; C-TERMINUS; POL-ETA AB Eukaryotes are endowed with multiple specialized DNA polymerases, some (if not all) of which are believed to play important roles in the tolerance of base damage during DNA replication. Among these DNA polymerases, Rev1 protein (a deoxycytidyl transferase) from vertebrates interacts with several other specialized polymerases via a highly conserved C-terminal region. The present studies assessed whether these interactions are retained in more experimentally tractable model systems, including yeasts, flies, and the nematode C. elegans. We observed a physical interaction between Rev1 protein and other Y-family polymerases in the fruit fly Drosophila melanogaster. However, despite the fact that the C-terminal region of Drosophila and yeast Rev1 are conserved from vertebrates to a similar extent, such interactions were not observed in Saccharomyces cerevisiae or Schizosaccharomyces pombe. with respect to regions in specialized DNA polymerases that are required for interaction with Rev1, we find predicted disorder to be an underlying structural commonality. The results of this study suggest that special consideration should be exercised when making mechanistic extrapolations regarding translesion DNA synthesis from one eukaryotic system to another. (c) 2008 Elsevier B.V. All rights reserved. C1 [Kosarek, J. Nicole; Rivera-Begeman, Amanda; Guo, Caixia; Friedberg, Errol C.] Univ Texas SW Med Ctr Dallas, Lab Mol Pathol, Dept Pathol, Dallas, TX 75390 USA. [Woodruff, Rachel V.; D'Souza, Sanjay; Walker, Graham C.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Friedberg, EC (reprint author), Univ Texas SW Med Ctr Dallas, Lab Mol Pathol, Dept Pathol, Dallas, TX 75390 USA. EM errol.friedberg@utsouthwestern.edu OI /0000-0001-7243-8261 FU NCI NIH HHS [CA21615-27, R01 CA021615, R13 CA100087, R13 CA100087-02]; NIEHS NIH HHS [R01 ES011344-12, ES015818, ES11344, R01 ES011344] NR 54 TC 27 Z9 27 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAR 1 PY 2008 VL 7 IS 3 BP 439 EP 451 DI 10.1016/j.dnarep.2007.11.016 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 275MG UT WOS:000254075700009 PM 18242152 ER PT J AU Greenwald, P AF Greenwald, P. TI Do we make optimal use of the potential of cancer prevention? SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 5th International Conference on Cancer Prevention 2008 CY MAR 06-08, 2008 CL St Gallen, SWITZERLAND SP UICC Global Canc Control, Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, European Assoc Canc Res, European Canc Prevent Org, Amer Canc Soc, Canc Res UK, Swiss Canc League C1 [Greenwald, P.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2008 VL 6 IS 3 MA S1 BP 1 EP 1 DI 10.1016/S1359-6349(08)70193-9 PG 1 WC Oncology SC Oncology GA 274UJ UT WOS:000254027300003 ER PT J AU Schiller, JT AF Schiller, J. T. TI HPV vaccination and other approaches to prevent cervical cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 5th International Conference on Cancer Prevention 2008 CY MAR 06-08, 2008 CL St Gallen, SWITZERLAND SP UICC Global Canc Control, Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, European Assoc Canc Res, European Canc Prevent Org, Amer Canc Soc, Canc Res UK, Swiss Canc League C1 [Schiller, J. T.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2008 VL 6 IS 3 MA S18 BP 18 EP 18 DI 10.1016/S1359-6349(08)70210-6 PG 1 WC Oncology SC Oncology GA 274UJ UT WOS:000254027300019 ER PT J AU Ford, LG AF Ford, L. G. TI Prevention of prostate cancer with selenium and vitamin E: SELECT-trial SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 5th International Conference on Cancer Prevention 2008 CY MAR 06-08, 2008 CL St Gallen, SWITZERLAND SP UICC Global Canc Control, Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, European Assoc Canc Res, European Canc Prevent Org, Amer Canc Soc, Canc Res UK, Swiss Canc League C1 NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2008 VL 6 IS 3 MA S31 BP 31 EP 31 DI 10.1016/S1359-6349(08)70223-4 PG 1 WC Oncology SC Oncology GA 274UJ UT WOS:000254027300031 ER PT J AU Greenwald, P AF Greenwald, P. TI Introduction into the consensus topic SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 5th International Conference on Cancer Prevention 2008 CY MAR 06-08, 2008 CL St Gallen, SWITZERLAND SP UICC Global Canc Control, Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, European Assoc Canc Res, European Canc Prevent Org, Amer Canc Soc, Canc Res UK, Swiss Canc League C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD MAR PY 2008 VL 6 IS 3 MA S35 BP 35 EP 35 DI 10.1016/S1359-6349(08)70227-1 PG 1 WC Oncology SC Oncology GA 274UJ UT WOS:000254027300035 ER PT J AU Grinev, A Daniel, S Stramer, S Rossmann, S Caglioti, S Rios, M AF Grinev, Andriyan Daniel, Sylvester Stramer, Susan Rossmann, Susan Caglioti, Sally Rios, Maria TI Genetic variability of West Nile virus in US blood donors, 2002-2005 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID 3'-TERMINAL STEM-LOOP; UNITED-STATES; PHYLOGENETIC ANALYSIS; NEW-YORK; 3'-UNTRANSLATED REGION; NORTH-AMERICA; PROTEIN; GLYCOSYLATION; ENCEPHALITIS; EPIDEMIC AB West Nile virus (WNV) was detected in the United States in 1999, has reoccurred every summer since, and has become endemic. Transfusion transmission was documented in 2002, and screening of blood donations for WNV began in 2003. We investigated genetic variation of WNV in human isolates obtained from specimens collected from 30 infected blood donors who tested positive for WNV RNA during 2002-2005. Complete genomic sequences of 8 isolates and structural gene sequences from 22 additional isolates were analyzed. We found some genetic diversity in isolates from different geographic regions and genetic divergence from reported sequences from epidemics in 1999-2001. Nucleotide divergence of structural genes showed a small increase from 2002 (0.18%) to 2005 (0.37%), suggesting absence of strong selective pressure and limited genetic evolution of WNV during that period. Nevertheless, WNV has continued to diverge from precursor isolates as geographic distribution of the virus has expanded. C1 [Grinev, Andriyan; Daniel, Sylvester; Rios, Maria] NIH, Mol Virol Lab, Div Emerging Transfus Transmitted dis, US FDA, Bethesda, MD 20892 USA. [Stramer, Susan] Amer Red Cross, Gaithersburg, MD USA. [Rossmann, Susan] Gulf Coast Reg Blood Ctr, Houston, TX USA. [Caglioti, Sally] Blood Syst Labs, Tempe, AZ USA. RP Rios, M (reprint author), NIH, Mol Virol Lab, Div Emerging Transfus Transmitted dis, US FDA, Bldg 29,Rm 131, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM maria.rios@fda.hhs.gov FU Intramural NIH HHS NR 34 TC 26 Z9 27 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR PY 2008 VL 14 IS 3 BP 436 EP 444 DI 10.3201/eid1403.070463 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 270BV UT WOS:000253695800012 PM 18325259 ER PT J AU Gill, JS Ullmann, AJ Loftis, AD Schwan, TG Raffel, SJ Schrumpf, ME Piesman, J AF Gill, James S. Ullmann, Amy J. Loftis, Amanda D. Schwan, Tom G. Raffel, Sandra J. Schrumpf, Merry E. Piesman, Joseph TI Novel relapsing fever spirochete in bat tick SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID BORRELIA-BURGDORFERI; NORTH-AMERICA; KELLEYI ACARI; ARGASIDAE; HERMSII; GENE C1 Iowa State Univ, Iowa City, IA 52245 USA. [Ullmann, Amy J.; Piesman, Joseph] Ctr Dis Control & Prevent, Ft Collins, CO USA. [Loftis, Amanda D.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Schwan, Tom G.; Raffel, Sandra J.; Schrumpf, Merry E.] Natl Inst Hlth, Rocky Mt Labs, Hamilton, MT USA. RP Gill, JS (reprint author), Iowa State Univ, 313 N Mt Vernon Dr, Iowa City, IA 52245 USA. EM bugmangill@yahoo.com FU Intramural NIH HHS NR 9 TC 8 Z9 8 U1 0 U2 4 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR PY 2008 VL 14 IS 3 BP 522 EP 523 DI 10.3201/eid1403.070766 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 270BV UT WOS:000253695800038 PM 18325285 ER PT J AU Powers, JF Picard, KL Nyska, A Tischler, AS AF Powers, James F. Picard, Kristen L. Nyska, Abraham Tischler, Arthur S. TI Adrenergic differentiation and Ret expression inn rat pheochromocytomas SO ENDOCRINE PATHOLOGY LA English DT Article DE p27kip 1; phenylethanolamine; N-methyltransferase; pheochromocytoma; Ret proto-oncogene ID NEUROFIBROMATOSIS KNOCKOUT MICE; ENDOCRINE NEOPLASIA SYNDROME; HIPPEL-LINDAU-SYNDROME; LONG-EVANS RATS; PROLIFERATIVE LESIONS; GENE-EXPRESSION; ADRENAL-MEDULLA; SPORADIC PHEOCHROMOCYTOMAS; CELL-LINES; PROTOONCOGENE AB Pheochromocytomas are catecholamine-producing tumors of the adult adrenal medulla. They are rare in humans and most other species but common in laboratory rats. However, the relevance of rat pheochromocytomas as a model for their human counterparts is uncertain. Previous studies of spontaneous and drug-induced rat pheochromocytomas and the PC12 pheochromocytoma cell line suggested a distinctive noradrenergic phenotype, possibly reflecting origin from a progenitor not present in the adult human adrenal. In this study, we studied 31 pheochromocytomas derived from test and control male and female rats in toxicologic studies for expression of the epinephrine-synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT) and the receptor tyrosine kinase Ret. PNMT, which defines adrenergic chromaffin cells, is frequently expressed in human pheochromocytomas, often in tumors that also overexpress RET. We also tested for the expression of the cell cycle checkpoint protein p27(Kip1), which recently was reported absent in pheochromocytomas from a strain of rats with a hereditary mixed multiple endocrine neoplasia (MEN)-like syndrome. Using immunoblots, we demonstrated PNMT expression in almost 50% of the 31 tumors, although often at lower levels than in normal rat adrenal medulla. The majority of tumors overexpressed Ret. There was no apparent correlation between PNMT and Ret. However, in this study, PNMT expression was strongly associated with tumors arising in female rats, while overexpression of Ret did not show a sex predilection. Robust expression of p27(Kip1) was seen in all tumors from the toxicologic studies and also in a small sample of pheochromocytomas from Long-Evans rats, which were reported to have a mixed MEN-like syndrome in the 1980s. The present results show that rat pheochromocytomas have greater phenotypic diversity than previously believed and greater similarity to their human counterparts with respect to these two important markers. Loss of p27(Kip1) does not appear to account for the high frequency of pheochromocytomas in commonly utilized rat strains. C1 [Powers, James F.; Picard, Kristen L.; Tischler, Arthur S.] Tufts Univ New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Nyska, Abraham] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Powers, JF (reprint author), Tufts Univ New England Med Ctr, Dept Pathol, 750 Washington St,POB 802, Boston, MA 02111 USA. EM jpowers1@tufts-nemc.org FU NCI NIH HHS [R01 CA48107]; NINDS NIH HHS [R01 NS37685] NR 27 TC 6 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD SPR PY 2008 VL 19 IS 1 BP 9 EP 16 DI 10.1007/s12022-008-9019-1 PG 8 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 301NF UT WOS:000255902200002 PM 18317952 ER PT J AU Shen, HCJ Rosen, JE Yang, LM Savage, SA Burns, AL Mateo, CM Agarwal, SK Chandrasekharappa, SC Spiegel, AM Collins, FS Marx, SJ Libutti, SK AF Shen, H-C Jennifer Rosen, Jennifer E. Yang, Lauren M. Savage, Sharon A. Burns, A. Lee Mateo, Carmen M. Agarwal, Sunita K. Chandrasekharappa, Settara C. Spiegel, Allen M. Collins, Francis S. Marx, Stephen J. Libutti, Steven K. TI Parathyroid tumor development involves deregulation of homeobox genes SO ENDOCRINE-RELATED CANCER LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; HISTONE METHYLTRANSFERASE COMPLEX; TYPE-1 MEN1 GENE; HOX GENES; MALIGNANT PHENOTYPE; SUPPRESSOR PROTEIN; HUMAN PROSTATE; MOUSE MODEL; EXPRESSION; CANCER AB Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome caused by mutations in the MEN1 tumor suppressor gene. Loss of the functional second copy of the MEN1 gene causes individuals to develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and pancreas. While it is clear that the protein encoded by MEN1, menin, suppresses endocrine tumors, its biochemical functions and direct downstream targets remain unclear. Recent studies have suggested that menin may act as a scaffold protein to coordinate gene transcription, and that menin is an oncogenic cofactor for homeobox (HOX) gene expression in hematopoietic cancer. The role of HOX genes in adult cell differentiation is still obscure, but growing evidence suggests that they may play important roles in the development of cancer. Therefore, we hypothesized that specific HOX genes were regulated by menin in parathyroid tumor development. Utilizing quantitative TaqMan RT-PCR, we compared expression profiles of the 39 HOX genes in human familial MEN1 (fMEN1) parathyroid tumors and sporadic parathyroid adenomas with normal samples. We identified a large set of 23 HOX genes whose deregulation is specific for fMEN1 parathyroid tumors, and only 5 HOX genes whose misexpression are specific for sporadic parathyroid tumor development. These findings provide the first evidence that loss of the MEN1 tumor suppressor gene is associated with deregulation of specific HOX gene expression in the development of familial human parathyroid tumors. Our results strongly reinforce the idea that abnormal expression of developmental HOX genes can be critical in human cancer progression. C1 [Shen, H-C Jennifer; Rosen, Jennifer E.; Yang, Lauren M.; Libutti, Steven K.] NCI, Surg Branch, Tumor Angiogenesis Sect, Bethesda, MD 20892 USA. [Burns, A. Lee; Mateo, Carmen M.; Agarwal, Sunita K.; Spiegel, Allen M.; Marx, Stephen J.] NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. [Chandrasekharappa, Settara C.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Savage, Sharon A.] NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Tumor Angiogenesis Sect, Bldg 10,Room 4W-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM steven_libutti@nih.gov RI Agarwal, Sunita/D-1428-2016; Savage, Sharon/B-9747-2015 OI Agarwal, Sunita/0000-0002-7557-3191; Savage, Sharon/0000-0001-6006-0740 FU Intramural NIH HHS [ZIA CP010142-11] NR 31 TC 24 Z9 24 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2008 VL 15 IS 1 BP 267 EP 275 DI 10.1677/ERC-07-0191 PG 9 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 276EB UT WOS:000254123000023 PM 18310293 ER PT J AU Zelinka, T Timmers, HJLM Kozupa, A Chen, CC Carrasquillo, JA Reynolds, JC Ling, A Eisenhofer, G Lazurova, I Adams, KT Whatley, MA Widimsky, J Pacak, K AF Zelinka, Tomas Timmers, Henri J. L. M. Kozupa, Anna Chen, Clara C. Carrasquillo, Jorge A. Reynolds, James C. Ling, Alexander Eisenhofer, Graeme Lazurova, Ivica Adams, Karen T. Whatley, Millie A. Widimsky, Jiri, Jr. Pacak, Karel TI Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations SO ENDOCRINE-RELATED CANCER LA English DT Article ID MALIGNANT PHEOCHROMOCYTOMA; NEUROENDOCRINE TUMORS; PET; METAIODOBENZYLGUANIDINE; LOCALIZATION; I-131-MIBG; PLASMA AB We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/-: 77% vs 63%), 39% with liver metastases (SDHB +/-: 27% vs 47%), and 32% with lung metastases (SDHB +/-: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/-: 83% vs 77%), lumbar spine (78%; SDHB +/-: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/-: 91 % vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/-: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[F-18]-fluorodopamine ([F-18]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[F-18]-fluoro-2-deOXY-D-glucose ([F-18]-FDG) PET (76%), and scintigraphy with [I-123/131]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [F-18]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [F-18]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [F-18]-FDG PET is highly recommended in SDHB mutation patients, whereas [F-18]-FDA PET is recommended in patients without the mutation. C1 [Zelinka, Tomas; Timmers, Henri J. L. M.; Kozupa, Anna; Adams, Karen T.; Pacak, Karel] NICHHD, Sect Med Neuroendocrinol Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. [Ling, Alexander] Natl Inst Neurol Disorders & Stroke, NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Chen, Clara C.; Carrasquillo, Jorge A.; Reynolds, James C.; Whatley, Millie A.] Natl Inst Neurol Disorders & Stroke, NIH, Dept Nucl Med, Bethesda, MD 20892 USA. [Zelinka, Tomas; Widimsky, Jiri, Jr.] Gen Fac Hosp, Fac Med 1, Dept Med 3, Prague 12808 2, Czech Republic. [Lazurova, Ivica] Safarik Univ, Dept Med, Kosice 04166, Slovakia. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol Reprod Biol & Med Branch, NIH, 10 Ctr Dr,Bldg 10,CRC,RM 1-E 3140,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; Zelinka, Tomas/D-4276-2017; OI Zelinka, Tomas/0000-0003-3395-8373; Carrasquillo, Jorge/0000-0002-8513-5734 FU Intramural NIH HHS NR 39 TC 35 Z9 35 U1 0 U2 2 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD MAR PY 2008 VL 15 IS 1 BP 311 EP 323 DI 10.1677/ERC-07-0217 PG 13 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 276EB UT WOS:000254123000027 PM 18310297 ER PT J AU Ladenheim, EE Hamilton, NL Behles, RR Bi, S Hampton, LL Battey, JF Moran, TH AF Ladenheim, Ellen E. Hamilton, Nahketah L. Behles, Robert R. Bi, Sheng Hampton, Lori L. Battey, James F. Moran, Timothy H. TI Factors contributing to obesity in bombesin receptor subtype-3-deficient mice SO ENDOCRINOLOGY LA English DT Article ID PITUITARY-ADRENAL AXIS; GENETICALLY-OBESE; FOOD RESTRICTION; MOLECULAR-CLONING; PEPTIDE RECEPTOR; SUBTYPE-3 BRS-3; MEAL PATTERNS; ZUCKER RATS; FACILITATION; ALYTESIN AB Mice with a targeted disruption of bombesin receptor subtype-3 (BRS-3 KO) develop hyperphagia, obesity, hypertension, and impaired glucose metabolism. However, the factors contributing to their phenotype have not been clearly established. To determine whether their obesity is a result of increased food intake or a defect in energy regulation, we matched the caloric intake of BRS-3 KO mice to wild-type (WT) ad libitum (ad lib)-fed controls over 21 wk. Although BRS-3 KO ad lib-fed mice were 29% heavier, the body weights of BRS-3 KO pair-fed mice did not differ from WT ad lib-fed mice. Pair-feeding BRS-3 KO mice normalized plasma insulin but failed to completely reverse increased adiposity and leptin levels. Hyperphagia in ad lib-fed KO mice was due to an increase in meal size without a compensatory decrease in meal frequency resulting in an increase in total daily food intake. An examination of neuropeptide Y, proopiomelanocortin, and agouti-related peptide gene expression in the arcuate nucleus revealed that BRS-3 KO mice have some deficits in their response to energy regulatory signals. An evaluation of the satiety effects of cholecystokinin, bombesin, and gastrin-releasing peptide found no differences in feeding suppression by these peptides. We conclude that hyperphagia is a major factor leading to increased body weight and hyperinsulinemia in BRS-3 KO mice. However, our finding that pair-feeding did not completely normalize fat distribution and plasma leptin levels suggests there is also a metabolic dysregulation that may contribute to, or sustain, their obese phenotype. C1 [Ladenheim, Ellen E.; Hamilton, Nahketah L.; Behles, Robert R.; Bi, Sheng; Moran, Timothy H.] Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Hampton, Lori L.; Battey, James F.] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Ladenheim, EE (reprint author), Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Ross 618,720 Rutland Ave, Baltimore, MD 21205 USA. EM laden@jhmi.edu FU NIDDK NIH HHS [R01 DK046448, DK-46448] NR 36 TC 34 Z9 34 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2008 VL 149 IS 3 BP 971 EP 978 DI 10.1210/en.2007-1319 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 266GG UT WOS:000253421900017 PM 18039774 ER PT J AU Xia, M Huang, R Witt, KL Southall, N Fostel, J Cho, MH Jadhav, A Smith, CS Inglese, J Portier, CJ Tice, RR Austin, CP AF Xia, Menghang Huang, Ruili Witt, Kristine L. Southall, Noel Fostel, Jennifer Cho, Ming-Hsuang Jadhav, Ajit Smith, Cynthia S. Inglese, James Portier, Christopher J. Tice, Raymond R. Austin, Christopher P. TI Compound cytotoxicity profiling using quantitative high-throughput screening SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE 1,536-well; cell viability; NTP 1,408 compound library; PubChem; qHTS; RT-CES ID ENVIRONMENTAL CHEMICALS; TOXICITY; CHALLENGES; APOPTOSIS; PROGRAM; GROWTH; CELLS AB BACKGROUND: The propensity of compounds to produce adverse health effects in humans is generally evaluated using animal-based test methods. Such methods can be relatively expensive, low-throughput, and associated with pain suffered by the treated animals. In addition, differences in species biology may confound extrapolation to human health effects. OBJECTIVE: The National Toxicology Program and the National Institutes of Health Chemical Genomics Center are collaborating to identify a battery of cell-based screens to prioritize compounds for further toxicologic evaluation. METHODS: A collection of 1,408 compounds previously tested in one or more traditional toxicologic assays were profiled for cytotoxicity using quantitative high-throughput screening (qHTS) in 13 human and rodent cell types derived from six common targets of xenobiotic toxicity (liver, blood, kidney, nerve, lung, skin). Selected cytotoxicants were further tested to define response kinetics. RESULTS: qHTS of these compounds produced robust and reproducible results, which allowed cross-compound, cross-cell type, and cross-species comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited species- or cell type-specific cytotoxicity. Closely related cell types and analogous cell types in human and rodent frequently showed different patterns of cytotoxicity. Some compounds inducing similar levels of cytotoxicity showed distinct time dependence in kinetic studies, consistent with known mechanisms of toxicity. CONCLUSIONS: The generation of high-quality cytotoxicity data on this large library of known compounds using qHTS demonstrates the potential of this methodology to profile a much broader array of assays and compounds, which, in aggregate, may be valuable for prioritizing compounds for further toxicologic evaluation, identifying compounds with particular mechanisms of action, and potentially predicting in vivo biological response. C1 [Xia, Menghang; Huang, Ruili; Southall, Noel; Cho, Ming-Hsuang; Jadhav, Ajit; Inglese, James; Austin, Christopher P.] NIH, NIH Chem Genom Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Witt, Kristine L.; Smith, Cynthia S.; Portier, Christopher J.; Tice, Raymond R.] NIH, Dept Hlth & Human Serv, Natl Toxicol Program, Res Triangle Pk, NC USA. [Fostel, Jennifer] NIH, Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Xia, M (reprint author), NIH, NIH Chem Genom Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Southall, Noel/H-8991-2012; Portier, Christopher/A-3160-2010 OI Southall, Noel/0000-0003-4500-880X; Portier, Christopher/0000-0002-0954-0279 FU Intramural NIH HHS NR 32 TC 124 Z9 129 U1 2 U2 24 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2008 VL 116 IS 3 BP 284 EP 291 DI 10.1289/ehp.10727 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 269SN UT WOS:000253670600022 PM 18335092 ER PT J AU Ruhlen, RL Howdeshell, KL Mao, J Taylor, JA Bronson, FH Newbold, RR Welshons, WV vom Saal, FS AF Ruhlen, Rachel L. Howdeshell, Kembra L. Mao, Jiude Taylor, Julia A. Bronson, Franklin H. Newbold, Retha R. Welshons, Wade V. vom Saal, Frederick S. TI Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the "Fetal Estrogenization Syndrome" and obesity in CD-1 mice SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE casein; estradiol; fat; glucose tolerance; leptin; metabolic syndrome; obesity; puberty; reproductive organs; soy ID BISPHENOL-A; DEVELOPMENTAL EXPOSURE; REPRODUCTIVE-ORGANS; MOUSE PROSTATE; DIETHYLSTILBESTROL; ISOFLAVONE; GENISTEIN; MECHANISMS; RECEPTORS; CHEMICALS AB BACKGROUND: Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful. OBJECTIVES: We compared reproductive and metabolic characteristics in male and female mice reared and maintained on non-soy low-phytoestrogen feed or soy-based high-phytoestrogen feed. METHODS: The low-phytoestrogen diet was non-soy PMI 5K96 (verified casein diet), and the high-phytoestrogen diet consisted of soy-based PMI 5008 during pregnancy and lactation and soy-based PMI 5001 maintenance feed after weaning. RESULTS: In fetuses whose mothers consumed the low-phytoestrogen PMI 5K96 feed, we found a paradoxical significant elevation in endogenous serum estradiol, which was associated postnatally with adverse reproductive outcomes referred to as the "fetal estrogenization syndrome (FES)". In females, this syndrome included early puberty and increased uterine responsiveness to estrogen, and in males, it included reduced testis, epididymis, and seminal vesicle size, but an enlarged prostate. The low-phytoestrogen-fed males and females were lighter at birth, but, between weaning and adulthood, they became obese and developed abnormally high serum leptin levels; these males, but not females, showed impaired glucose regulation. CONCLUSIONS: Removing phytoestrogens from mouse feed produces an obese phenotype consistent with metabolic syndrome, and the associated reproductive system abnormalities are consistent with FES due to elevated endogenous fetal estradiol. Laboratory rodents may have become adapted to high-phytoestrogen intake over many generations of being fed soy-based commercial feed; removing all phytoestrogens from feed leads to alterations that could disrupt many types of biomedical research. C1 [Ruhlen, Rachel L.; Howdeshell, Kembra L.; Mao, Jiude; Taylor, Julia A.; vom Saal, Frederick S.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. [Bronson, Franklin H.] Univ Texas Austin, Dept Zool, Austin, TX 78712 USA. [Newbold, Retha R.] Natl Inst Environm Hlth Sci, Dev Endocrinol & Endocrine Disruptor Sect, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Welshons, Wade V.] Univ Missouri, Dept Biomed Sci, Columbia, MO 65211 USA. RP vom Saal, FS (reprint author), Univ Missouri, Div Biol Sci, 105 Lefevre Hall, Columbia, MO 65211 USA. EM vomsaalf@missouri.edu FU NIEHS NIH HHS [ES11283, R01 ES011283]; NIGMS NIH HHS [T32 GM008396] NR 41 TC 52 Z9 54 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2008 VL 116 IS 3 BP 322 EP 328 DI 10.1289/ehp.10448 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 269SN UT WOS:000253670600028 PM 18335098 ER PT J AU Heindel, JJ vom Saal, FS AF Heindel, Jerrold J. Saal, Frederick S. vom TI Meeting report: Batch-to-batch variability in estrogenic activity in commercial animal diets - Importance and approaches for laboratory animal research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE animal diets; batch-to-batch variability; bioassay; estrogenic contaminants; isoflavones; phytoestrogens ID SPRAGUE-DAWLEY RATS; BISPHENOL-A; PHYTOESTROGEN CONTENT; ENDOCRINE DISRUPTOR; ISOFLAVONE LEVELS; RODENT DIETS; CD-1 MICE; GENISTEIN; DAIDZEIN; METABOLISM AB We report information from two workshops sponsored by the National Institutes of Health that were held to a) assess whether dietary estrogens could significantly impact end points in experimental animals, and b) involve program participants and feed manufacturers to address the problems associated with measuring and eliminating batch-to-batch variability in rodent diets that may lead to conflicting findings in animal experiments within and between laboratories. Data were presented at the workshops showing that there is significant batch-to-batch variability in estrogenic content of commercial animal diets, and that this variability results in differences in experimental outcomes. A combination of methods were proposed to determine levels of total estrogenic activity and levels of specific estrogenic constituents in soy-containing, casein-containing, and other soy-free rodent diets. Workshop participants recommended that researchers pay greater attention to the type of diet being used in animal studies and choose a diet whose estrogenic activity (or lack thereof) is appropriate for the experimental model and end points of interest. Information about levels of specific phytoestrogens, as well as estrogenic activity caused by other contaminants and measured by bioassay, should be disclosed in scientific publications. This will require laboratory animal diet manufacturers to provide investigators with information regarding the phytoestrogen content and other estrogenic compounds in commercial diets used in animal research. C1 [Heindel, Jerrold J.] Natl Inst Environm Hlth Sci, Cellular Organs & Syst Pathobiol Branch, Div Extramural Res & Training, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Saal, Frederick S. vom] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. RP Heindel, JJ (reprint author), Natl Inst Environm Hlth Sci, Cellular Organs & Syst Pathobiol Branch, Div Extramural Res & Training, NIH,Dept Hlth & Human Serv, POB 12233,MD 3-03, Res Triangle Pk, NC 27709 USA. EM heindelj@niehs.nih.gov NR 44 TC 31 Z9 31 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2008 VL 116 IS 3 BP 389 EP 393 DI 10.1289/ehp.10524 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 269SN UT WOS:000253670600038 PM 18335108 ER PT J AU Bernbaum, JC Umbach, DM Ragan, NB Ballard, JL Archer, JL Schmidt-Davis, H Rogan, WJ AF Bernbaum, Judy C. Umbach, David M. Ragan, N. Beth Ballard, Jeanne L. Archer, Janet L. Schmidt-Davis, Holly Rogan, Walter J. TI Pilot studies of estrogen-related physical findings in wants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE breast bud; estrogen; human milk; infant formula; testis; vaginal maturation index ID TESTICULAR VOLUME; SOY; INFANTS; FORMULA; ISOFLAVONES; DEFICIENCY; MATURATION; ENDOCRINE; HUMANS; CELLS AB BACKGROUND: Soy formula containing estrogenic isoflavones is widely used in the United States. Infants consuming soy formula exclusively have high isoflavone exposures. We wanted to study whether soy formula prolonged the physiologic estrogenization of newborns, but available quantitative descriptions of the natural history of breast and genital development are inadequate for study design. OBJECTIVE: We piloted techniques for assessing infants' responses to the withdrawal from maternal estrogen and gathered data on breast and genital development in infants at different ages. METHODS: We studied 37 boys and 35 girls, from term pregnancies with normal birth weights, who were < 48 hr to 6 months of age, and residents of Philadelphia, Pennsylvania, during 2004-2005. One-third of the children of each sex and age interval were exclusively fed breast milk, soy formula, or cow-milk formula. Our cross-sectional study measured breast adipose tissue, breast buds, and testicular volume; observed breast and genital development; and collected vaginal wall cells and information on vaginal discharge. We assessed reliability of the measures. RESULTS: Breast tissue was maximal at birth and disappeared in older children, consistent with waning maternal estrogen. Genital development did not change by age. Breast-milk secretion and withdrawal bleeding were unusual. Vaginal wall cells showed maximal estrogen effect at birth and then reverted; girls on soy appeared to show reestrogenization at 6 months. CONCLUSIONS: Examination of infants for plausible effects of estrogens is valid and repeatable. Measurement of breast tissue and characterization of vaginal wall cells could be used to evaluate exposures with estrogen-like effects. C1 [Ragan, N. Beth; Rogan, Walter J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Bernbaum, Judy C.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Umbach, David M.] NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Ballard, Jeanne L.] Univ Cincinnati, Childrens Hosp, Med Ctr, Dept Neonatol, Cincinnati, OH USA. [Archer, Janet L.] Social & Sci Syst Inc, Survey & Epidemiol Serv Div, Durham, NC USA. [Schmidt-Davis, Holly] Westat Corp, Durham, NC USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU Intramural NIH HHS; NIEHS NIH HHS [N01ES85433, N01ES55546, N01-ES-85433] NR 31 TC 31 Z9 33 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2008 VL 116 IS 3 BP 416 EP 420 DI 10.1289/chp.10409 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 269SN UT WOS:000253670600042 PM 18335112 ER PT J AU Waalkes, MP Liu, J AF Waalkes, Michael P. Liu, Jie TI Early-life arsenic exposure: Methylation capacity and beyond SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID IN-UTERO; ADULTS; MICE C1 [Waalkes, Michael P.; Liu, Jie] Natl Inst Environm Hlth Sci, NCI, NIH,Dept Hlth & Human Serv, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), Natl Inst Environm Hlth Sci, NCI, NIH,Dept Hlth & Human Serv, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov NR 10 TC 6 Z9 6 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2008 VL 116 IS 3 BP A104 EP A104 DI 10.1289/ehp.11276 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 269SN UT WOS:000253670600001 PM 18335070 ER PT J AU Basso, O AF Basso, Olga TI Birth weight is forever SO EPIDEMIOLOGY LA English DT Editorial Material ID CORONARY-HEART-DISEASE; ADULT DISEASE; DEVELOPMENTAL ORIGINS; FETAL ORIGINS; HYPOTHESIS; GROWTH; INFANT; ASSOCIATION; MORTALITY; TWINS AB Birth weight is associated not just with infant morbidity and mortality, but with outcomes occurring much later in life including adult mortality, as reported by a paper by Baker an colleagues in this issue of EPIDEMIOLOGY. While these associations are tantalizing per se, the truly interesting question concerns the mechanisms that underlie these links. The prevailing hypothesis suggests a "fetal origin" of diseases resulting from alterations in fetal nutrition that permanently program organ function. The most commonly proposed alternative is that factors, mainly genetic, that affect both fetal growth and disease risk are responsible for the observed associations. Although both mechanisms are intellectually attractive-and may well coexist-we should be cautious to not focus excessively on fetal growth. Doing this may lead us in the wrong direction, as has likely happened in the case of birth weight in relation to infant survival. C1 NIEHS, NIH, HHS, Epidemiol Branch,MD A3 05, Res Triangle Pk, NC 27709 USA. RP Basso, O (reprint author), NIEHS, NIH, HHS, Epidemiol Branch,MD A3 05, POB 12233,11 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM bassoo2@niehs.nih.gov RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 FU Intramural NIH HHS NR 20 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2008 VL 19 IS 2 BP 204 EP 205 DI 10.1097/EDE.0b013e31816379d9 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265ZU UT WOS:000253401400007 PM 18277158 ER PT J AU Peplonska, B Lissowska, J Hartman, TJ Szeszenia-Dabrowska, N Blair, A Zatonski, W Sherman, ME Garcia-Closas, M Brinton, LA AF Peplonska, Beata Lissowska, Jolanta Hartman, Terryl J. Szeszenia-Dabrowska, Neonila Blair, Aaron Zatonski, Witold Sherman, Mark E. Garcia-Closas, Montserrat Brinton, Louise A. TI Adulthood lifetime physical activity and breast cancer SO EPIDEMIOLOGY LA English DT Article ID RECREATIONAL EXERCISE ACTIVITY; RANDOMIZED CLINICAL-TRIAL; HORMONE-RECEPTOR STATUS; DOUBLY LABELED WATER; POSTMENOPAUSAL WOMEN; ENERGY-EXPENDITURE; UNITED-STATES; IN-SITU; ACTIVITY QUESTIONNAIRE; PREMENOPAUSAL WOMEN AB Background: Epidemiologic studies have shown that breast cancer risk is reduced 30% to 40% in highly physically active compared with inactive women. However, the effects of moderate activities, timing of activities, and intervening effects of other risk factors remain less clear. Methods: We analyzed data on physical activity patterns in 2176 incident breast cancer cases and 2326 controls in a population-based breast cancer case-control study in Poland conducted in 2000-2003. Using unconditional logistic regression analyses, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) associated with physical activity levels (measured by average metabolic equivalents of energy expenditure hours per week), controlling for potential confounders. Results: Total adult lifetime activity reduced risk of breast cancer, with individuals in the highest quartile having an OR of 0.80 (CI = 0.67-0.96) compared with the lowest quartile. Reduced risks were most consistent for the highest quartiles of moderate-to-vigorous activities: moderate/vigorous recreational activities (OR = 0.74; CI = 0.620.89), outdoor activities (0.8 1; 0.68-0.97), heavy physical work (0.60, 0.42-0.87), and combined high intensity (metabolic equivalent >6.0) activities (0.75; 0.63-0.90). These relations were not modified by body mass index, menopausal status, or family history of breast cancer. Reductions in risk with moderate/vigorous recreational activities were stronger for larger tumors and those with nodal involvement. Women who increased their recreational activity in their 50s had significantly reduced risk, with those in the highest tertile of change being at a 27% lower risk. Conclusions: Leisure-time moderate-to-vigorous activities reduce breast cancer risk irrespective of underlying host characteristics. C1 [Peplonska, Beata; Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, PL-91348 Lodz, Poland. [Lissowska, Jolanta; Zatonski, Witold] Canc Ctr M Sklodowska Curie Inst Oncol, Div Canc Epidemiol & Prevent, Warsaw, Poland. [Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA USA. [Blair, Aaron] Occupat & Environm Epidemiol Branch, Bethesda, MD USA. [Sherman, Mark E.; Garcia-Closas, Montserrat; Brinton, Louise A.] Natl Canc Inst, Natl Inst Hlth, Hormal & Reproduct Epidemiol Branch, Bethesda, MD USA. RP Peplonska, B (reprint author), Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, 8 Reresy St, PL-91348 Lodz, Poland. EM beatap@imp.lodz.pl RI Peplonska, Beata/F-6004-2010; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS; NCI NIH HHS [N01-CP-91013] NR 61 TC 37 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2008 VL 19 IS 2 BP 226 EP 236 DI 10.1097/EDE.0b013e3181633bfb PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265ZU UT WOS:000253401400011 PM 18277160 ER PT J AU Titus-Ernstoff, L Troisi, R Hatch, EE Hyer, M Wise, LA Palmer, JR Kaufman, R Adam, E Noller, K Herbst, AL Strohsnitter, W Cole, BF Hartge, P Hoover, RN AF Titus-Ernstoff, Linda Troisi, Rebecca Hatch, Elizabeth E. Hyer, Marianne Wise, Lauren A. Palmer, Julie R. Kaufman, Raymond Adam, Ervin Noller, Kenneth Herbst, Arthur L. Strohsnitter, William Cole, Bernard F. Hartge, Patricia Hoover, Robert N. TI Offspring of women exposed in utero to diethylstilbestrol (DES) - A preliminary report of benign and malignant pathology in the third generation SO EPIDEMIOLOGY LA English DT Article ID ESTROGEN DIETHYLSTILBESTROL; PRENATAL EXPOSURE; YOUNG WOMEN; CANCER-RISK; FOLLOW-UP; C-FOS; MICE; FERTILITY; EXPRESSION; PREGNANCY AB Background: Animal studies suggest that prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes epigenetic changes that may be transmitted to the next generation. Specifically, these studies show an elevated incidence of reproductive tumors in the female offspring of prenatally-exposed mice. Methods: We assessed cancer and benign pathology diagnoses occurring in the offspring of women whose prenatal exposure to DES (or lack of exposure) was verified by medical record. Our data arose from 2 sources: the mothers' reports of cancers occurring in 8216 sons and daughters, and pathology-confirmed cancers and benign diagnoses self-reported by a subset of 793 daughters. Results: Although statistical power is limited, our data are consistent with no overall increase of cancer in the sons or daughters of women exposed in utero to DES. Based on pathology-confirmed diagnoses reported by the daughters, we saw no association between DES and risk of benign breast disease or reproductive tract conditions. Based on 3 cases, the incidence of ovarian cancer was higher than expected in the daughters of women exposed prenatally to DES. Conclusions: Our data do not support an overall increase of cancer risk in the sons or daughters of women exposed prenatally to DES, but the number of ovarian cancer cases was greater than expected. While preliminary, this finding supports continued monitoring of these daughters. C1 [Titus-Ernstoff, Linda; Cole, Bernard F.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH 03756 USA. [Titus-Ernstoff, Linda; Cole, Bernard F.] Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Titus-Ernstoff, Linda] Dartmouth Med Sch, Dept Pediat, Lebanon, NH USA. [Titus-Ernstoff, Linda] Hood Ctr Children & Families, Lebanon, NH USA. [Troisi, Rebecca; Hartge, Patricia; Hoover, Robert N.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Hatch, Elizabeth E.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hyer, Marianne] Informat Management Serv Inc, Rockville, MD USA. [Wise, Lauren A.; Palmer, Julie R.] Boston Univ, Sch Publ Hlth, Slone Epidemiol Ctr, Boston, MA USA. [Kaufman, Raymond] Methodist Hosp, Dept Obstet & Gynecol, Houston, TX USA. [Adam, Ervin] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Noller, Kenneth; Strohsnitter, William] Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. [Herbst, Arthur L.] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Titus-Ernstoff, L (reprint author), Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH 03756 USA. EM linda.titus-ernstoff@dartmouth.edu OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928; Wise, Lauren/0000-0003-2138-3752 FU NCI NIH HHS [N01 CP 01012, N01 CP 51010, N01 CP001012] NR 44 TC 33 Z9 34 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2008 VL 19 IS 2 BP 251 EP 257 DI 10.1097/EDE.0b013e318163152a PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265ZU UT WOS:000253401400014 PM 18223485 ER PT J AU Howards, PP Schisterman, EF Heagerty, PJ AF Howards, Penelope P. Schisterman, Enrique F. Heagerty, Patrick J. TI Causal interpretation based on DAGs - Response SO EPIDEMIOLOGY LA English DT Letter C1 [Howards, Penelope P.; Schisterman, Enrique F.] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Howards, PP (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM penelope.howards@emory.edu NR 3 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2008 VL 19 IS 2 BP 361 EP 362 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265ZU UT WOS:000253401400037 ER PT J AU Klarmann, GJ Decker, A Farrar, WL AF Klarmann, George J. Decker, Amy Farrar, William L. TI Epigenetic gene silencing in the Wnt pathway in breast cancer SO EPIGENETICS LA English DT Review DE breast cancer; DNA methylation; epigenetics; Wnt signaling; beta-catenin; cancer stem cell ID ADENOMATOUS POLYPOSIS-COLI; BETA-CATENIN; CELL-LINES; APC GENE; SIGNALING PATHWAY; DNA METHYLATION; STEM-CELLS; E-CADHERIN; PROMOTER HYPERMETHYLATION; ABERRANT METHYLATION AB Breast cancer is one of the most common malignancies in women. Despite advances in treatment of endocrine-dependent tumors, the complete molecular basis of transformation is still unknown. What is clear is that a variety of genetic lesions and epigenetic modifications are present in the neoplasm. Disregulation of several signaling pathways is known to be associated with breast cancer development, among them is the wingless and integration site growth factor (Wnt) pathway. While genetic mutations of certain components of this pathway, such as APC, are significant contributing factors for colorectal cancers, they are typically not the predominate mechanism associated with breast cancer. Instead, it appears that DNA hypermethylation leads to aberrant regulation of the Wnt pathway in breast cancer, and as such, this review focuses on the epigenetic regulation of Wnt pathway components in breast cancer. C1 [Klarmann, George J.; Decker, Amy; Farrar, William L.] NCI, Ctr Canc Res, Canc Stem Cell Stn, Lab Canc Prevent, Frederick, MD 21702 USA. [Klarmann, George J.] SAIC Frederick Inc, Frederick, MD USA. [Decker, Amy] Johns Hopkins Univ, Montgomery Cty Ctr, Biotechnol Program, Rockville, MD USA. RP Farrar, WL (reprint author), NCI, Ctr Canc Res, Canc Stem Cell Stn, Lab Canc Prevent, 1050 Boyles St,Bldg 560,Room 21-81, Frederick, MD 21702 USA. EM farrar@mail.ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 58 TC 54 Z9 55 U1 1 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD MAR-APR PY 2008 VL 3 IS 2 BP 59 EP 63 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307SU UT WOS:000256339400002 PM 18398311 ER PT J AU Tomic, S Babic, SD Ivek, T Vuletic, T Krca, S Livolant, F Podgornik, R AF Tomic, S. Babic, S. Dolanski Ivek, T. Vuletic, T. Krca, S. Livolant, F. Podgornik, R. TI Short-fragment Na-DNA dilute aqueous solutions: Fundamental length scales and screening SO EPL LA English DT Article ID POLYELECTROLYTE SOLUTIONS; PHASE AB Dielectric spectroscopy is used to investigate fundamental length scales of 146 bp short-fragment ( nucleosomal) dilute Na-DNA solutions. Two relaxation modes are detected: the high-and the low-frequency mode. Dependence of the corresponding length scales on the DNA and on the (uni-valent) salt concentration is studied in detail, being different from the case of long, genomic DNA, investigated before. In low-added-salt regime, the length scale of the high-frequency mode scales as the average separation between DNAs, though it is smaller in absolute magnitude, whereas the length scale of the low-frequency mode is equal to the contour length of DNA. These fundamental length scales in low-added- salt regime do not depend on whether DNA is in a double-stranded or single-stranded form. On the other hand, with increasing added salt, the characteristic length scale of the low-frequency mode diminishes at low DNA concentrations probably due to dynamical formation of denaturation bubbles and/or fraying in the vicinity of DNA denaturation threshold. Copyright (c) EPLA, 2008 C1 [Tomic, S.; Babic, S. Dolanski; Ivek, T.; Vuletic, T.] Inst Fiziku, HR-10001 Zagreb, Croatia. [Krca, S.] Rudjer Boskovic Inst, HR-10001 Zagreb, Croatia. [Livolant, F.] Univ Paris 11, Phys Solides Lab, F-91405 Orsay, France. [Podgornik, R.] Univ Ljubljana, Dept Phys, SI-1000 Ljubljana, Slovenia. [Podgornik, R.] Jozef Stefan Inst, SI-1000 Ljubljana, Slovenia. [Podgornik, R.] NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. RP Tomic, S (reprint author), Inst Fiziku, HR-10001 Zagreb, Croatia. EM stomic@ifs.hr RI Tomic, Silvia/D-5466-2011; Ivek, Tomislav/D-5298-2011; Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 18 TC 10 Z9 10 U1 0 U2 5 PU EPL ASSOCIATION, EUROPEAN PHYSICAL SOCIETY PI MULHOUSE PA 6 RUE DES FRERES LUMIERE, MULHOUSE, 68200, FRANCE SN 0295-5075 J9 EPL-EUROPHYS LETT JI EPL PD MAR PY 2008 VL 81 IS 6 AR 68003 DI 10.1209/0295-5075/81/68003 PG 5 WC Physics, Multidisciplinary SC Physics GA 293XR UT WOS:000255369200030 ER PT J AU Park, CJ Park, JE Karpova, TS Soung, NK Yu, LR Song, S Lee, KH Xia, X Kang, E Dabanoglu, I Oh, DY Zhang, JY Kang, YH Wincovitch, S Huffaker, TC Veenstra, TD McNally, JG Lee, KS AF Park, Chong J. Park, Jung-Eun Karpova, Tatiana S. Soung, Nak-Kyun Yu, Li-Rong Song, Sukgil Lee, Kyung H. Xia, Xue Kang, Eugene Dabanoglu, Ilknur Oh, Doo-Yi Zhang, James Y. Kang, Young Hwi Wincovitch, Stephen Huffaker, Tim C. Veenstra, Timothy D. McNally, James G. Lee, Kyung S. TI Requirement for the budding yeast polo kinase Cdc5 in proper microtubule growth and dynamics SO EUKARYOTIC CELL LA English DT Article ID XENOPUS EGG EXTRACTS; COLI SHUTTLE VECTORS; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; RESTRICTION SITES; PHOSPHATASE CDC14; BIPOLAR SPINDLE; LOCALIZATION; ANAPHASE; MITOSIS AB In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of the budding yeast polo kinase Cdc5, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal noncatalytic polo box domain, a region that is critical for proper subcellular localization. One of these mutants, cdc5-11, exhibited a temperature-sensitive growth defect with an abnormal spindle morphology. Strikingly, provision of a moderate level of benomyl, a microtubule-depolymerizing drug, permitted cdc5-11 cells to grow significantly better than the isogenic CDC5 wild type in a FEAR (cdc Fourteen Early Anaphase Release)-independent manner. In addition, cdc5-11 required MAD2 for both cell growth and the benomyl-remedial phenotype. These results suggest that cdc5-11 is defective in proper spindle function. Consistent with this view, cdc5-11 exhibited abnormal spindle morphology, shorter spindle length, and delayed microtubule regrowth at the nonpermissive temperature. Overexpression of CDC5 moderately rescued the spc98-2 growth defect. Interestingly, both Cdc28 and Cdc5 were required for the proper modification of the spindle pole body components Nud1, Slk19, and Stu2 in vivo. They also phosphorylated these three proteins in vitro. Taken together, these observations suggest that concerted action of Cdc28 and Cdc5 on Nud1, Slk19, and Stu2 is important for proper spindle functions. C1 [Park, Chong J.; Park, Jung-Eun; Soung, Nak-Kyun; Song, Sukgil; Lee, Kyung H.; Kang, Eugene; Dabanoglu, Ilknur; Oh, Doo-Yi; Zhang, James Y.; Kang, Young Hwi; Lee, Kyung S.] NIH, Lab Metab, Ctr Canc Res, NCI, Bethesda, MD 20892 USA. [Karpova, Tatiana S.; McNally, James G.] NIH, Lab Receptor Biol & Gene Express, Ctr Canc Res, NCI, Bethesda, MD 20892 USA. [Wincovitch, Stephen] NIH, Expt Carcinogenesis Lab, Ctr Canc Res, NCI, Bethesda, MD 20892 USA. [Yu, Li-Rong; Veenstra, Timothy D.] SAIC Frederick Inc, NCI, Lab Proteom & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA. [Xia, Xue; Huffaker, Tim C.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. RP Lee, KS (reprint author), NIH, Lab Metab, Ctr Canc Res, NCI, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov FU NCI; NCI [N01-CO-12400, R01 GM040479] FX We are grateful to Susan Garfield for technical support and critical reading of the manuscript. This work was supported in part by NCI intramural grants ( K. S. L. and J.G.M.), an NCI fund under contract N01-CO-12400 (T.D.V.), and NIH grant R01 GM040479 (T.C.H). NR 49 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD MAR PY 2008 VL 7 IS 3 BP 444 EP 453 DI 10.1128/EC.00283-07 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 340ST UT WOS:000258666000003 PM 18178775 ER PT J AU Gregory, AM Lau, JYF Eley, TC AF Gregory, A. M. Lau, J. Y. F. Eley, T. C. TI Finding gene-environment interactions for generalised anxiety disorder SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE generalized anxiety disorder; anxiety; genes; environment ID SEROTONIN TRANSPORTER GENE; NATIONAL-COMORBIDITY-SURVEY; STRESSFUL LIFE EVENTS; MAJOR DEPRESSIVE DISORDER; HUMAN AMYGDALA; ADOLESCENT DEPRESSION; MALTREATED CHILDREN; POLYMORPHISM; TWIN; PREVALENCE AB It is becoming increasingly apparent that genetic research into psychiatric disorders would benefit from consideration of the environment because these risk mechanisms are likely to interact. Despite generalised anxiety disorder (GAD) being one of the most prevalent disorders presented in primary care, there is a paucity of published studies of gene-environment interactions (G x E) for this phenotype. This article describes how our current knowledge of GAD is useful in designing studies of G x E for GAD. To increase the chances of identifying replicable G x E for GAD further information is needed with regards to: defining and measuring GAD, difficulties co-occurring with GAD, quantitative genetic estimations for GAD, specific genes associated with GAD, and specific environmental risks for GAD. C1 [Gregory, A. M.] Univ London, Dept Psychol, Univ London Goldsmiths Coll, London SE14 6NW, England. [Gregory, A. M.; Lau, J. Y. F.; Eley, T. C.] Univ London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, Univ London Kings Coll, London SE14 6NW, England. [Lau, J. Y. F.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Gregory, AM (reprint author), Univ London, Dept Psychol, Univ London Goldsmiths Coll, Lewisham Way,New Cross, London SE14 6NW, England. EM a.gregory@gold.ac.uk RI Eley, Thalia/D-4811-2011 FU Medical Research Council [, G120/635] NR 64 TC 8 Z9 10 U1 2 U2 14 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD MAR PY 2008 VL 258 IS 2 BP 69 EP 75 DI 10.1007/s00406-007-0785-4 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 278QY UT WOS:000254302600002 PM 18297422 ER PT J AU Gregory, AM Lau, JYF Eley, TC Gregory, AM AF Gregory, A. M. Lau, J. Y. F. Eley, T. C. Gregory, A. M. TI Finding gene-environment interactions for phobias SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE gene; environment; interaction; phobia; twins ID COMORBIDITY SURVEY REPLICATION; COMMON MENTAL-DISORDERS; DSM-IV DISORDERS; ANXIETY DISORDERS; SOCIAL PHOBIA; RISK-FACTORS; DEPRESSIVE-DISORDERS; MAJOR DEPRESSION; IRRATIONAL FEARS; SUBSTANCE USE AB Phobias are common disorders causing a great deal of suffering. Studies of gene-environment interaction (G x E) have revealed much about the complex processes underlying the development of various psychiatric disorders but have told us little about phobias. This article describes what is already known about genetic and environmental influences upon phobias and suggests how this information can be used to optimise the chances of discovering G x Es for phobias. In addition to the careful conceptualisation of new studies, it is suggested that data already collected should be re-analysed in light of increased understanding of processes influencing phobias. C1 [Gregory, A. M.] Univ London, Univ London Goldsmiths Coll, Dept Psychol, London SE14 6NW, England. [Lau, J. Y. F.; Eley, T. C.; Gregory, A. M.] Univ London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, Univ London Kings Coll, London WC1E 7HU, England. [Lau, J. Y. F.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Gregory, AM (reprint author), Univ London, Univ London Goldsmiths Coll, Dept Psychol, Lewisham Way,New Cross, London SE14 6NW, England. EM a.gregory@gold.ac.uk RI Eley, Thalia/D-4811-2011 FU Medical Research Council [, G120/635] NR 44 TC 4 Z9 4 U1 2 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD MAR PY 2008 VL 258 IS 2 BP 76 EP 81 DI 10.1007/s00406-007-0786-3 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 278QY UT WOS:000254302600003 PM 18297421 ER PT J AU Lau, JYF Pine, DS AF Lau, J. Y. F. Pine, D. S. TI Elucidating risk mechanisms of gene-environment interactions on pediatric anxiety: integrating findings from neuroscience SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE child and adolescent anxiety; gene-environment interaction; risk mechanisms; neural circuitry; psychological processes ID EMOTIONAL FACIAL EXPRESSIONS; PREFRONTAL CORTEX; ANXIOUS CHILDREN; ATTENTIONAL BIAS; FEARFUL FACES; SOCIAL PHOBIA; TRAIT ANXIETY; ADOLESCENTS; DISORDERS; AMYGDALA AB Recent findings of gene-environment interaction on child and adolescent anxiety generate interest in mechanisms through which genetic risks are expressed. Current findings from neuroscience suggest avenues for exploring putative mechanisms. Specifically recent documentations of abnormality in brain function among anxious adolescents may reflect the end-result of gene expression. In turn these inherited predispositions may increase the likelihood of psychopathology in the presence of stress. The aim of the current article is to consider putative mechanisms reflecting genetic sensitivity to the environment (G x E). Thus we review data implicating biased processing of threat information and anomalies in brain circuitry in the expression of pediatric anxiety. These data suggest that links across development among genes, brain, psychological processes, and behavior are far from established. Accordingly, the article proposes strategies for examining these links. Exploring these relationships during development is crucial, given that these early life processes may potentially shape longer-term patterns of emotional behavior, and therefore life-long trajectories of anxiety. C1 [Lau, J. Y. F.; Pine, D. S.] NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. RP Lau, JYF (reprint author), NIMH, Mood & Anxiety Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM lauj@mail.nih.gov NR 49 TC 16 Z9 16 U1 1 U2 8 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD MAR PY 2008 VL 258 IS 2 BP 97 EP 106 DI 10.1007/s00406-007-0788-1 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 278QY UT WOS:000254302600005 PM 18343966 ER PT J AU Pang, PS Cleland, JGF Teerlink, JR Collins, SP Lindsell, CJ Sopko, G Peacock, WF Fonarow, GC Aldeen, AZ Kirk, JD Storrow, AB Tavares, M Mebazaa, A Roland, E Massie, BM Maisel, AS Komajda, M Filippatos, G Gheorghiade, M AF Pang, Peter S. Cleland, John G. F. Teerlink, John R. Collins, Sean P. Lindsell, Christopher J. Sopko, George Peacock, W. Frank Fonarow, Gregg C. Aldeen, Amer Z. Kirk, J. Douglas Storrow, Alan B. Tavares, Miguel Mebazaa, Alexandre Roland, Edmond Massie, Barry M. Maisel, Alan S. Komajda, Michel Filippatos, Gerasimos Gheorghiade, Mihai CA Acute Heart Failure Syndromes Int TI A proposal to standardize dyspnoea measurement in clinical trials of acute heart failure syndromes: the need for a uniform approach SO EUROPEAN HEART JOURNAL LA English DT Article DE heart failure; clinical trials; dyspnoea ID RANDOMIZED CONTROLLED-TRIALS; NATRIURETIC PEPTIDE; TEZOSENTAN; NESIRITIDE; OUTCOMES; DIAGNOSIS; DESIGN; RISK; ANTAGONIST; RATIONALE AB Dyspnoea is the most common presenting symptom amongst patients with acute heart failure syndromes (AHFS). It is distressing to patients and therefore an important target for treatment in clinical practice, clinical trials, and for regulatory approval of novel agents. Despite its importance as a treatment target, no consensus exists on how to assess dyspnoea in this setting. There is a considerable uncertainty about the reproducibility of the various instruments used to measure dyspnoea, their ability to reflect changes in symptoms and whether they accurately reflect the patient's experience. Little attempt has been made to ensure consistent implementation with respect to patients' posture during assessment or timing in relationship to therapy. There is also limited understanding of how rapidly and completely dyspnoea responds to standard therapy. A standardized method with which to assess dyspnoea is required for clinical trials of AHFS in order to ensure uniform collection of data on a key endpoint. We propose the Provocative Dyspnoea Assessment, a method of measurement that combines sequential dyspnoea provocation by positioning and walking with a dyspnoea self assessment using a five-point Likert scale, to yield a final Dyspnoea Severity Score. This proposed tool requires detailed validation but has face validity for the uniform assessment of dyspnoea. C1 [Cleland, John G. F.; Aldeen, Amer Z.] Univ Hull, Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England. [Pang, Peter S.; Aldeen, Amer Z.] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. [Teerlink, John R.; Massie, Barry M.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Collins, Sean P.; Lindsell, Christopher J.] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. [Sopko, George] Natl Inst Hlth, Bethesda, MD USA. [Peacock, W. Frank] Cleveland Clin, Dept Emergency Med, Cleveland, OH 44106 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. [Kirk, J. Douglas] Univ Calif Davis, Med Ctr, Dept Emergency Med, Sacramento, CA 95817 USA. [Storrow, Alan B.] Vanderbilt Univ, Med Ctr, Dept Emergency Med, Nashville, TN USA. [Tavares, Miguel] Hosp Geral Santo Antonio, Dept Anesthesiol & Crit Care, Oporto, Portugal. [Mebazaa, Alexandre] Hop Lariboisiere, Dept Anesthesiol & Crit Care Med, F-75475 Paris, France. [Roland, Edmond] Agcy Francaise Secur Sanit Prod Sante, Paris, France. [Maisel, Alan S.] Univ Calif San Diego, Vet Affairs San Diego Hlth Care Syst, Dept Med, Div Cardiol, San Diego, CA 92103 USA. [Komajda, Michel] Univ Paris 06, Dept Cardiol, Paris, France. [Komajda, Michel] Hop La Pitie Salpetriere, Paris, France. [Filippatos, Gerasimos] Athens Univ Hosp, Heart Failure Unit, Dept Cardiol, Attikon, Greece. [Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. RP Cleland, JGF (reprint author), Univ Hull, Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England. EM j.g.cleland@hull.ac.uk RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; OI Lindsell, Christopher/0000-0002-3297-2811; Cleland, John/0000-0002-1471-7016 NR 37 TC 75 Z9 76 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAR PY 2008 VL 29 IS 6 BP 816 EP 824 DI 10.1093/eurheartj/ehn048 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 278NL UT WOS:000254293500021 PM 18310669 ER PT J AU Rosas, AL Kasperlik-Zaluska, AA Papierska, L Bass, BL Pacak, K Eisenhofer, G AF Rosas, Alejandro L. Kasperlik-Zaluska, Anna A. Papierska, Lucyna Bass, Barbara Lee Pacak, Karel Eisenhofer, Graeme TI Pheochromocytoma crisis induced by glucocorticoids: a report of four cases and review of the literature SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Review ID ADRENAL INCIDENTALOMAS; CATECHOLAMINES; HYPERTENSION; MANAGEMENT; DIAGNOSIS; SECRETION; PATIENT; CT AB Context: Pheochromocytoma crisis (PC) is a rare life-threatening endocrine emergency that may present spontaneously or can be unmasked by 'triggers', including certain medications that provoke the release of catecholamines by tumors. Several isolated cases of PC have been reported after administration of exogenous glucocorticoids; evidence that these drugs cause adverse events in patients with pheochromocytoma is mainly anecdotal. Patients: We report four cases of PC most likely induced by glucocorticoids and review seven previous reports in the literature linking steroid administration to the development of PC. Results: In four new cases reported here, glucocorticoid administration was associated with a fatal outcome in one case, a pheochromocytoma multisystem crisis in another, and serious hypertensive crises in two others. Two patients had incidental adrenal masses and were undergoing high-dose dexamethasone suppression tests (DST). Conclusions: Exogenous glucocorticoids may unpredictably trigger PC. Pheochromocytoma should be included in the differential diagnosis of any patient who develops a hypertensive crisis, cardiac failure, tachycardial headache, and abdominal or chest pain after receiving exogenous glucocorticoids. Glucocorticoid induced PC is frequently associated with hemorrhagic pheochromocytoma. Although exogenous glucocorticoids cause serious complications unpredictably, they should be avoided or administered only if necessary and with caution in patients with known or suspected pheochromocytoma. During the investigation of incidental adrenal masses, pheochromocytoma should ideally be ruled out before administering glucocorticoids. However, no cases have been reported with 1 mg of dexamethasone when given as a DST in patients with pheochromocytoma; larger doses, as low as 2 mg of dexamethasone, may trigger a PC. A patient with pheochromocytoma presenting as an adrenal incidentaloma may also be at risk if exposed to glucocorticoids given as pre-treatment in case of allergy to contrast media. C1 [Rosas, Alejandro L.] Methodist Hosp, Dept Anesthesiol, Houston, TX 77005 USA. [Kasperlik-Zaluska, Anna A.; Papierska, Lucyna] Med Ctr Postgrad Educ, Dept Endocrinol, PL-01809 Warsaw, Poland. [Bass, Barbara Lee] Methodist Hosp, Dept Surg, Houston, TX 77030 USA. [Pacak, Karel] NCI, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. [Eisenhofer, Graeme] Tech Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Eisenhofer, Graeme] Tech Univ Dresden, Dept Med, D-01307 Dresden, Germany. RP Rosas, AL (reprint author), Methodist Hosp, Dept Anesthesiol, 6565 Fannin,MS M375, Houston, TX 77005 USA. EM arosas@tinhs.org FU Intramural NIH HHS NR 27 TC 26 Z9 27 U1 0 U2 2 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAR PY 2008 VL 158 IS 3 BP 423 EP 429 DI 10.1530/EJE-07-0778 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272JB UT WOS:000253854600020 PM 18299478 ER PT J AU Hernandez-Diaz, S Wilcox, AJ Schisterman, EF Hernan, MA AF Hernandez-Diaz, Sonia Wilcox, Allen J. Schisterman, Enrique F. Hernan, Miguel A. TI From causal diagrams to birth weight-specific curves of infant mortality SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth weight; mortality; curves; DAGs; paradox AB This report explores the low birth weight paradox using two graphical approaches: causal directed acyclic graphs (DAGs), and the empirical curves of the birth weight distribution and birth weight-specific mortality. The birth weight curves are able to represent the associations quantitatively, while the corresponding causal DAGs provide a set of plausible explanations for the findings. Taken together, these two approaches can facilitate discussion of underlying biological mechanisms. C1 [Hernandez-Diaz, Sonia; Hernan, Miguel A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wilcox, Allen J.] Natl Inst Environm Hlth Sci, Natl Inst Hlth, Epidemiol Branch, Durham, NC USA. [Schisterman, Enrique F.] NICHHD, Natl Inst Hlth, Epidemiol Branch, Bethesda, MD 20892 USA. RP Hernandez-Diaz, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM shernan@hsph.harvard.edu OI Wilcox, Allen/0000-0002-3376-1311; Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [NIH0014367067, Z01 HD008795-01]; NHLBI NIH HHS [R01 HL080644, R01-HL080644] NR 9 TC 24 Z9 24 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD MAR PY 2008 VL 23 IS 3 BP 163 EP 166 DI 10.1007/s10654-007-9220-4 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265GW UT WOS:000253348100001 PM 18224448 ER PT J AU Roth, SM Walsh, S Liu, D Metter, EJ Ferrucci, L Hurley, BF AF Roth, Stephen M. Walsh, Sean Liu, Dongmei Metter, E. Jeffrey Ferrucci, Luigi Hurley, Ben F. TI The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE skeletal muscle; polymorphism; muscle strength ID ALPHA-ACTININ; MUSCLE STRENGTH; ALPHA-ACTININ-3; BODYBUILDERS; WOMEN; PERFORMANCE; MEN; POLYMORPHISM; DEFICIENCY; PHENOTYPES AB Previous reports have shown a lower proportion of the ACTN3 X/X genotype (R577X nonsense polymorphism) in sprint-related athletes compared to the general population, possibly attributed to impairment of muscle function related to alpha-actinin-3 deficiency. In the present study, we examined the frequency of the X/X genotype in both Black and White elite-level bodybuilders and strength athletes in comparison to the general population. A reference population of 668 Whites (363 men and 305 women) and 208 Blacks (98 men and 110 women) was genotyped for the ACTN3 R577X polymorphism. Strength athletes (52 white and 23 black; 4 women) consisting predominantly of world class and locally competitive bodybuilders, and elite powerlifters were recruited and similarly genotyped. Significantly lower X/X genotype frequencies were observed in the athletes (6.7%) vs controls (16.3%; P = 0.005). The X/X genotype was significantly lower in White athletes (9.7%) vs controls (19.9%; P = 0.018). No black athletes (0%) were observed with the X/X genotype, though this finding only approached statistical significance vs controls (4.8%; P = 0.10). The results indicate that the ACTN3 R577X nonsense allele (X) is under-represented in elite strength athletes, consistent with previous reports indicating that a-actinin-3 deficiency appears to impair muscle performance. C1 [Roth, Stephen M.; Walsh, Sean; Liu, Dongmei; Hurley, Ben F.] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. [Metter, E. Jeffrey; Ferrucci, Luigi] Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD USA. RP Roth, SM (reprint author), Univ Maryland, Dept Kinesiol, 2134 HHP Bldg, College Pk, MD 20742 USA. EM sroth1@umd.edu RI Liu, Dongmei/C-1525-2012; OI Roth, Stephen/0000-0002-7841-3695 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [K01 AG022791, L30 AG024705, L30 AG024705-03, R01 AG021500, R01 AG021500-03] NR 22 TC 78 Z9 81 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAR PY 2008 VL 16 IS 3 BP 391 EP 394 DI 10.1038/sj.ejhg.5201964 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 266BS UT WOS:000253406900016 PM 18043716 ER PT J AU Cordero, DR Bendavid, C Shanske, AL Haddad, BR Muenke, M AF Cordero, Dwight R. Bendavid, Claude Shanske, Alan L. Haddad, Bassem R. Muenke, Maximilian TI Holoprosencephaly - Polydactyly syndrome: In search of an etiology SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Holoprosencephaly; polydactyly; pseudotrisomy13; Forebrain; cerebral cortex; limb anomalies; SHH; SIX3; TGIF; ZIC2; GLI3; array CGH ID MUTATIONS; FISH AB Holoprosencephaly-Polydactyly (HPS) or Pseudotrisomy 13 syndrome are names conferred to clinically categorize patients whose phenotype is congruent with Trisomy 13 in the context of a normal karyotype. The literature suggests that this entity may be secondary to submicroscopic deletions in holoprosencephaly (HPE) genes; however, a limited number of investigations have been undertaken to evaluate this hypothesis. To test this hypothesis we studied a patient with H]PE, polydactyly, and craniofacial dysmorphologies consistent with the diagnosis of Trisomy 13 whose karyotype was normal. We performed mutational analysis in the four main HPE causing genes (SHH, SIX3, TGIF, and ZIC2) and GLI3, a gene associated with polydactyly as well as fluorescent in situ hybridization (FISH) to search for micro-deletions in these genes and two candidate HPE genes (DISP1 and FOXA2). No mutations or deletions were detected. A whole genome approach utilizing array Comparative Genomic Hybridization (aCGH) to screen for copy number abnormalities was then taken. No loss or gain of DNA was noted. Although a single case, our results suggest that coding mutations in these HPE genes and copy number anomalies may not be causative in this disorder. Instead, HPS likely involves mutations in other genes integral in embryonic development of the forebrain, face and limbs. Our systematic analysis sets the framework to study other affected children and delineate the molecular etiology of this disorder. Published by Elsevier Masson SAS. C1 [Bendavid, Claude; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Cordero, Dwight R.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Cordero, Dwight R.] Harvard Univ, Sch Med, Boston, MA USA. [Bendavid, Claude] Fac Med, Inst Genet & Dev Rennes, CNRS, UMR Genet Pathol Liees Dev 6061, Rennes, France. [Shanske, Alan L.] Childrens Hosp Montefiore, Albert Einstein Coll Med, Ctr Craniofacial Disorders, Bronx, NY USA. [Bendavid, Claude; Haddad, Bassem R.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Bendavid, Claude; Haddad, Bassem R.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Bendavid, Claude; Haddad, Bassem R.] Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgfi.nih.gov FU Intramural NIH HHS [Z01 HG000209-06, Z99 HG999999]; NICHD NIH HHS [K12HD001255] NR 12 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD MAR-APR PY 2008 VL 51 IS 2 BP 106 EP 112 DI 10.1016/j.ejmg.2007.08.004 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 287TV UT WOS:000254940300002 PM 18178536 ER PT J AU Chodick, G Struewing, JP Ron, E Rutter, JL Iscovich, J AF Chodick, Gabriel Struewing, Jeffery P. Ron, Elaine Rutter, Joni L. Iscovich, Jose TI Similar prevalence of founder BRCA1 and BRCA2 mutations among Ashkenazi and non-Ashkenazi men with breast cancer: Evidence from 261 cases in Israel, 1976-1999 SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE BRCA1 mutation; BRCA2 mutation; male breast cancer; epidemiology; Israel ID FAMILY-HISTORY; OVARIAN-CANCER; GERMLINE MUTATIONS; POPULATION; FREQUENCY; MALES; JEWS; CARCINOMA; RISKS; GENE AB To evaluate the potential contribution of mutations in the BRCA1 and BRCA2 genes to male breast cancer (MBC), we expanded a previous study to screen a total of 261 Israeli men diagnosed with breast carcinoma. A total of 21 BRCA2 6174delT and 8 BRCA1 185delAG mutations were found. Similar frequencies of BRCA1 and BRCA2 mutation carriers were found among Ashkenazi (12.8%) and non-Ashkenazi Jews (9.1 %). The combined prevalence of BRCA1/BRCA2 founder mutations among Ashkenazi Jewish men is slightly higher than for women, due to a higher frequency of BRCA2 mutations. (c) 2007 Elsevier Masson SAS. All rights reserved. C1 [Chodick, Gabriel] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Struewing, Jeffery P.; Rutter, Joni L.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. [Iscovich, Jose] Selikoff Ctr Environm Hlth & Human Dev, Raanana, Israel. [Iscovich, Jose] Int Fertil Inst, Raanana, Israel. RP Chodick, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7051,MSC 7238, Bethesda, MD 20892 USA. EM hodik_g@mac.org.il RI Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Rutter, Joni/0000-0002-6502-2361 FU Intramural NIH HHS [Z01 CP010138-09] NR 31 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD MAR-APR PY 2008 VL 51 IS 2 BP 141 EP 147 DI 10.1016/j.ejmg.2007.11.001 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 287TV UT WOS:000254940300005 PM 18158280 ER PT J AU Choi, SH Jin, SE Lee, MK Lim, SJ Park, JS Kim, BG Ahn, WS Kim, CK AF Choi, Sung Hee Jin, Su-Eon Lee, Mi-Kyung Lim, Soo-Jeong Park, Jeong-Sook Kim, Byung-Gyu Ahn, Woong Shick Kim, Chong-Kook TI Novel cationic solid lipid nanoparticles enhanced p53 gene transfer to lung cancer cells SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE p53; nonviral vector; cationic SLN; lung cancer ID IN-VITRO; ANTITUMOR-ACTIVITY; PLASMID DNA; WILD-TYPE; LIPOSOMES; THERAPY; VECTOR; VIVO; FORMULATION; COMPLEXES AB Mutations in the p53 tumor suppressor gene are the most common molecular genetic abnormalities to be described in lung cancer. However, there have been few reports of nonviral vector-mediated p53 gene delivery in lung cancer. A new formulation of cationic solid lipid nanoparticles (SLNs) for gene delivery was produced by the melt homogenization method with slight modification, and the SLNs were formulated by mixing tricaprin (TC) as a core, 3 beta[N-(N', N'-dimethylaminoethane) carbarnoyl] cholesterol (DC-Chol), dioleoylphosphatidylethanolamine (DOPE) and Tween 80 in various ratios. Plasmid DNA (pp53-EGFP)/SLNs complexes were transfected into human non-small cell lung cancer cells (H1299 cells) and transfection efficiency was determined by FACS analysis. The gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. The cellular growth inhibition and apoptosis of treated cells with pp53-EGFP/SLNs complexes were assessed by trypan blue exclusion assay and annexin V staining, respectively. In vivo biodistribution of plasmid DNA was investigated by PCR and RT-PCR. The transfection efficiency of SLN1 (TC:DC-Chol:DOPE:Tween 80 = 0.3:0.3:0.3:1), which showed the highest transfection efficiency among the SLN formulations, was higher than that of commercially available Lipofectin(R). The SLNs-mediated transfection of the p53 gene resulted in efficient high levels of wild-type p53 mRNA and protein expression levels in H1299 cells. The efficient reestablishment of wild-type p53 function in lung cancer cells restored the apoptotic pathway. Taken together, our results reveal that cationic SLN-mediated p53 gene delivery may have potential for clinical application as a nonviral vector-mediated lung cancer therapy due to its effective induction of apoptosis and tumor growth inhibition. (C) 2007 Elsevier B.V. All rights reserved. C1 [Choi, Sung Hee; Jin, Su-Eon; Kim, Chong-Kook] Seoul Natl Univ, Coll Pharm, Lab Excellency Drug & Gene Delivery, Seoul 151742, South Korea. [Lee, Mi-Kyung] Woosuk Univ, Dept Pharmaceut Engn, Samrye, South Korea. [Lim, Soo-Jeong] Sejong Univ, Dept Biosci & Biotechnol, Seoul, South Korea. [Park, Jeong-Sook] Chungnam Natl Univ, Coll Pharm, Taejon, South Korea. [Kim, Byung-Gyu] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Ahn, Woong Shick] Catholic Univ, Dept Obstet & Genecol, Seoul, South Korea. RP Kim, CK (reprint author), Seoul Natl Univ, Coll Pharm, Lab Excellency Drug & Gene Delivery, San 56-1,Sillim Dong, Seoul 151742, South Korea. EM ckkim@plaza.snu.ac.kr RI Kim, Chong-Kook/F-7387-2015; OI CHOI, SUNG HEE/0000-0003-0740-8116 NR 38 TC 69 Z9 76 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD MAR PY 2008 VL 68 IS 3 BP 545 EP 554 DI 10.1016/j.ejpb.2007.07.011 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 293EJ UT WOS:000255317800009 PM 17881199 ER PT J AU Mazzola, C Medalie, J Panlilio, LV Hahn, B Goldberg, SR Yasar, S Drago, F AF Mazzola, C. Medalie, J. Panlilio, L. V. Hahn, B. Goldberg, S. R. Yasar, S. Drago, F. TI Peroxisome proliferator-activated receptors (PPARs): new target for attention and memory function SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT European-College-of-Neuropsychopharmacology Workshop on Neuropsychopharmacology for Young Scientists in Europe CY MAR 06-09, 2008 CL Nice, FRANCE SP European Coll Neuropsychopharmacol C1 [Mazzola, C.] Univ Catania, Dept Expt Clin Pharmacol, Sch Med, Catania, Italy. [Hahn, B.] NIDA, NIH,DHHS, Preclin Pharmacol Sect ,Behav Neurosci Res Branch, Intramural Res Program, Baltimore, MD USA. [Yasar, S.] Johns Hopkins Univ, Sch Med, Div Geriatr Med, Baltimore, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2008 VL 18 SU 1 BP S90 EP S91 DI 10.1016/S0924-977X(08)70103-2 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 277YL UT WOS:000254250500107 ER PT J AU Rogers, CG Singh, A Blatt, AM Linehan, WM Pinto, PA AF Rogers, Craig G. Singh, Amar Blatt, Adam M. Linehan, W. Marston Pinto, Peter A. TI Robotic partial nephrectomy for complex renal tumors: Surgical technique SO EUROPEAN UROLOGY LA English DT Article DE kidney cancer; laparoscopy; partial nephrectomy; robotics; technique ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; CHRONIC KIDNEY-DISEASE; RADICAL NEPHRECTOMY; EXPERIENCE; ISCHEMIA; OUTCOMES; TERM AB Objectives: Laparoscopic partial nephrectomy requires advanced training to accomplish tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery. We describe our technique, illustrated with video, of robotic partial nephrectomy for complex renal tumors, including hilar, endophytic, and multiple tumors. Methods: Robotic assistance was used to resect 14 tumors in eight patients (mean age: 50.3 yr; range: 30-68 yr). Three patients had hereditary kidney cancer. All patients had complex tumor features, including hilar tumors (n = 5), endophytic tumors (n = 4), and/or multiple tumors (n = 3). Results: Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was used with a mean warm ischemia time of 31 min (range: 24-45 min). Mean blood loss was 230 ml (range: 100-450 ml). Histopathology confirmed clear-cell renal cell carcinoma (n 3), hybrid oncocytic tumor (n = 2), chromophobe renal cell carcinoma (n 2), and oncocytoma (n = 1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range: 2.6-6.4 cm). Mean hospital stay was 2.6 d. At 3-mo follow-up, no patients experienced a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence. Conclusions: Robotic partial nephrectomy is safe and feasible for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate a minimally invasive, nephron-sparing approach for select patients with complex renal tumors who might otherwise require open surgery or total nephrectomy. (C) 2007 Published by Elsevier B.V. on behalf of European Association of Urology. C1 [Rogers, Craig G.; Singh, Amar; Blatt, Adam M.; Linehan, W. Marston; Pinto, Peter A.] NCI, NIH, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, NIH, Ctr Canc Res, Urol Oncol Branch, Bldg 10,Room 1W-5940, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov FU Intramural NIH HHS [Z01 SC006659-25] NR 25 TC 124 Z9 129 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD MAR PY 2008 VL 53 IS 3 BP 514 EP 523 DI 10.1016/j.eururo.2007.09.047 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 268ZR UT WOS:000253619800008 PM 17961910 ER PT J AU Wu, J Liu, J Waalkes, MP Cheng, ML Li, L Li, CX Yang, Q AF Wu, Jun Liu, Jie Waalkes, Michael P. Cheng, Ming-Liang Li, Ling Li, Cheng-Xiu Yang, Qing TI High dietary fat exacerbates arsenic-induced liver fibrosis in mice SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE inorganic arsenic; chronic exposure; fat diet; liver injury; hepatofibrogenesis; gene expression ID MATRIX METALLOPROTEINASES; INORGANIC ARSENICALS; OXIDATIVE STRESS; GENE-EXPRESSION; EXPOSURE; HEPATOCARCINOGENESIS; METASTASIS; INDUCTION; TOXICITY; GUIZHOU AB Many factors could potentially affect the process of arsenic-induced liver fibrosis. The present study was undertaken to examine the effect of high fat diet on arsenic-induced liver fibrosis and preneoplastic changes. Mice were given sodium arsenite (As3+, 200 ppm) or sodium arsenate (As5+, 200 ppm) in the drinking water for 10 months, and provided a normal diet or a diet containing 20% added fat. Serum aspartate aminotransferase (AST), indicative of liver injury, was elevated in both arsenite and arsenate groups, and a high fat diet further increased these levels. Histopathology (H&E and Masson stain) showed that liver inflammation, steatosis (fatty liver), hepatocyte degeneration, and fibrosis occurred with arsenic alone, but their severity was markedly increased with the high fat diet. Total liver RNA was isolated for real-time RT-PCR analysis. Arsenic exposure increased the expression of inflammation genes, such as TNF-alpha, IL-6, iNOS, chemokines, and macrophage inflammatory protein-2. The expression of the stress-related gene heme oxygenase-1 was increased, while metallothionein-1 and GSH S-transferase-pi were decreased when arsenic was combined with the high fat diet. Expression of genes related to liver fibrosis, such as procollagen-1 and -3, SM-actin and TGF-beta, were synergistically increased in the arsenic plus high fat diet group. The expression of genes encoding matrix metalloproteinases (MMP2, MMP9) and tissue inhibitors of metalloproteinases (TIMP1, TIMP2) was also enhanced, suggestive of early oncogenic events. In general, arsenite produced more pronounced effects than arsenate. In summary, chronic inorganic arsenic exposure in mice produces liver injury, and a high fat diet markedly increases arsenic-induced hepatofibrogenesis. C1 [Wu, Jun; Cheng, Ming-Liang; Li, Ling; Li, Cheng-Xiu; Yang, Qing] Guiyang Med Coll, Guiyang 550004, Peoples R China. [Liu, Jie; Waalkes, Michael P.] NIEHS, Natl Canc Inst, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, Res Triangle Pk, NC 27709 USA. RP Wu, J (reprint author), Guiyang Med Coll, Guiyang 550004, Peoples R China. EM jn009@tom.com; Liu6@niehs.nih.gov NR 30 TC 33 Z9 33 U1 1 U2 12 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD MAR PY 2008 VL 233 IS 3 BP 377 EP 384 DI 10.3181/0710-RM-269 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 265OH UT WOS:000253368900013 PM 18296743 ER PT J AU Lonsdorf, AS Huang, V Fang, L Cha, E Nagao, K Zaleska, M Olszewski, WL Hwang, ST AF Lonsdorf, A. S. Huang, V. Fang, L. Cha, E. Nagao, K. Zaleska, M. Olszewski, W. L. Hwang, S. T. TI Accumulation of epidermis-derived CCL27 in skin-draining lymph nodes following topical application of a contact sensitizer induces accumulation of CCR10-positive cells SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Arbeitsgemeinschaft-Dermatolog-Forschung CY FEB 28-MAR 01, 2008 CL Eriangen, GERMANY SP Arbeitsgemeinsch Dermatolog Forschung C1 [Lonsdorf, A. S.; Huang, V.; Fang, L.; Cha, E.; Nagao, K.; Hwang, S. T.] NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. [Zaleska, M.; Olszewski, W. L.] Polish Acad Sci, Med Res Ctr, PL-02106 Warsaw, Poland. RI Nagao, Keisuke/J-5116-2013 OI Nagao, Keisuke/0000-0002-7005-3138 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2008 VL 17 IS 3 BP 252 EP 252 PG 1 WC Dermatology SC Dermatology GA 258VN UT WOS:000252897700073 ER PT J AU Huter, EN Shevach, EM AF Huter, E. N. Shevach, E. M. TI TGF beta-differentiated Foxp3+T regulatory (Treg) cells protect scurfy mice SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Arbeitsgemeinschaft-Dermatolog-Forschung CY FEB 28-MAR 01, 2008 CL Eriangen, GERMANY SP Arbeitsgemeinsch Dermatolog Forschung C1 [Huter, E. N.; Shevach, E. M.] NIAID, Natl Inst Hlth, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2008 VL 17 IS 3 BP 253 EP 253 PG 1 WC Dermatology SC Dermatology GA 258VN UT WOS:000252897700077 ER PT J AU Kostka, SL Dinges, S Iwakura, Y Udey, MC von Stebut, E AF Kostka, S. Lopez Dinges, S. Iwakura, Y. Udey, M. C. von Stebut, E. TI Defects in dendritic cell (DC) function in IL-1 receptor antagonist (RA) deficient mice are responsible for progressive disease in L. major infection SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Arbeitsgemeinschaft-Dermatolog-Forschung CY FEB 28-MAR 01, 2008 CL Eriangen, GERMANY SP Arbeitsgemeinsch Dermatolog Forschung C1 [Kostka, S. Lopez; Dinges, S.; von Stebut, E.] Johannes Gutenberg Univ Mainz, Haut Klin, D-55131 Mainz, Germany. [Iwakura, Y.] Univ Tokyo, Ctr Med Expt, Tokyo, Japan. [Udey, M. C.] Natl Inst Hlth, Natl Canc Inst, Dermatol Branch, Bethesda, MD USA. RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2008 VL 17 IS 3 BP 253 EP 253 PG 1 WC Dermatology SC Dermatology GA 258VN UT WOS:000252897700080 ER PT J AU Tuettenberg, A Stoll, S Huter, EN Hubo, M Kubach, J Horn, J Knop, J Grimbacher, B Jonuleit, H AF Tuettenberg, A. Stoll, S. Huter, E. N. Hubo, M. Kubach, J. Horn, J. Knop, J. Grimbacher, B. Jonuleit, H. TI Blockade of ICOS-ICOS-ligand interaction prevents tolerance induction by immature dendritic cells SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Arbeitsgemeinschaft-Dermatolog-Forschung CY FEB 28-MAR 01, 2008 CL Eriangen, GERMANY SP Arbeitsgemeinsch Dermatolog Forschung C1 [Tuettenberg, A.; Stoll, S.; Huter, E. N.; Hubo, M.; Kubach, J.; Knop, J.] Johannes Gutenberg Univ Mainz, Dept Dermatol, D-55101 Mainz, Germany. [Horn, J.; Grimbacher, B.] Univ Freiburg, Dept Rheumatol & Clin Immunol, D-79106 Freiburg, Germany. [Huter, E. N.] NIAID, NIH, Bethesda, MD 20892 USA. [Grimbacher, B.] Univ Coll, Royal Free Hosp, London NW3 2QG, England. RI Jonuleit, Helmut/D-8059-2011 OI Jonuleit, Helmut/0000-0002-5672-9365 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2008 VL 17 IS 3 BP 255 EP 255 PG 1 WC Dermatology SC Dermatology GA 258VN UT WOS:000252897700091 ER PT J AU Brenner, M Coelho, SG Beer, JZ Miller, SA Hearing, VJ AF Brenner, M. Coelho, S. G. Beer, J. Z. Miller, S. A. Hearing, V. J. TI Persistent molecular changes after repetitive in situ uvexposures of human skin SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Arbeitsgemeinschaft-Dermatolog-Forschung CY FEB 28-MAR 01, 2008 CL Eriangen, GERMANY SP Arbeitsgemeinsch Dermatolog Forschung C1 [Brenner, M.] Univ Munich, Dept Dermatol, Munich, Germany. [Coelho, S. G.; Hearing, V. J.] NIH, Natl Canc Inst, Lab Cell Biol, Bethesda, MD 20892 USA. [Beer, J. Z.; Miller, S. A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2008 VL 17 IS 3 BP 273 EP 273 PG 1 WC Dermatology SC Dermatology GA 258VN UT WOS:000252897700201 ER PT J AU Wang, E Selleri, S Sabatino, M Monaco, A Pos, Z Worschech, A Stroncek, DF Marincola, FM AF Wang, Ena Selleri, Silvia Sabatino, Marianna Monaco, Alessandro Pos, Zoltan Worschech, Andrea Stroncek, David F. Marincola, Francesco M. TI Spontaneous and treatment-induced cancer rejection in humans SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE functional genomics; immunotherapy; melanoma; microarrays; renal cell cancer; tumor immunology ID ACTIVATED KILLER-CELLS; HEPATITIS-C VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; TUMOR-INFILTRATING LYMPHOCYTES; SOLID-ORGAN TRANSPLANTATION; METASTATIC RENAL-CANCER; MELANOMA ANTIGEN GP100; CARBONIC-ANHYDRASE-IX; IN-VITRO STIMULATION; CYTOTOXIC T-CELLS AB Background: Experimental observations suggest that human cancer cells actively interact with normal host cells and this cross-talk results, in most instances, in an increased potential of cancer cells to survive. On the other hand, it is also well documented that on rare occasions tumors can be dramatically destroyed by the host's immune response. Objective: In this review, we argue that understanding the mechanisms that bring about the immune response and lead to cancer destruction is of paramount importance for the design of future rational therapies. Methods: Here we summarize the present understanding of the phenomenology leading to cancer regression in humans and propose novel strategies for a more efficient study of human cancer under natural conditions and during therapy. Conclusion: The understanding of tumor/host interactions within the tumor microenvironment is a key component of the study of tumor immunology in humans, much can be learned by a dynamic study of such interactions at time points related to the natural history of the disease or its response to therapy. Such understanding will eventually lead to novel and more effective therapies. C1 [Wang, Ena; Sabatino, Marianna; Monaco, Alessandro; Marincola, Francesco M.] NIH, Ctr Clin, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA. [Selleri, Silvia] Univ Milan, Dept Human Morphol, Milan, Italy. [Monaco, Alessandro] Natl Canc Inst, Clin Expt Oncol Lab, Bari, Italy. [Worschech, Andrea] Genelux Corp, San Diego Sci Ctr, San Diego, CA USA. [Worschech, Andrea] Univ Wurzburg, Bioctr, Dept Biochem, Wurzburg, Germany. [Stroncek, David F.] NIH, Ctr Clin, Dept Transfus Med, Cell Proc Sect, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Ctr Clin, Dept Transfus Med, Infect Dis & Immunogenet Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Fmarincola@mail.cc.nih.gov RI Worschech, Andrea/I-3919-2012; Pos, Zoltan/C-3623-2014; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Pos, Zoltan/0000-0002-2574-7616; Monaco, Alessandro/0000-0002-9941-7003 NR 145 TC 14 Z9 14 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD MAR PY 2008 VL 8 IS 3 BP 337 EP 349 DI 10.1517/14712598.8.3.337 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 275IX UT WOS:000254066200008 PM 18294104 ER PT J AU Denduluri, N Swain, SM AF Denduluri, Neelima Swain, Sandra M. TI Ixabepilone for the treatment of solid tumors: a review of clinical data SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE breast cancer; drug resistance; epothilone; microtubule stabilizer; tubulin ID EPOTHILONE-B-ANALOG; METASTATIC BREAST-CANCER; PHASE-II TRIAL; MICROTUBULE-STABILIZING AGENTS; REFRACTORY PROSTATE-CANCER; SOUTHWEST-ONCOLOGY-GROUP; RENAL-CELL CARCINOMA; PERIPHERAL NEUROPATHY; PLUS CAPECITABINE; DAILY SCHEDULE AB Background: Microtubule stabilizing agents such as taxanes are an integral part of therapy for multiple solid tumors. However, due to limitations of these agents, newer more effective cytotoxic agents are necessary. Ixabepilone, an epothilone B analog, is a novel microtubule stabilizing agent. Objective: This review provides an updated summary of emerging clinical experience with Ixabepilone. Methods: Phase 1, 11 and III clinical trials presented in abstract form or journal articles found within a PubMed search through November 2007 are described in this review. Results/conclusion: Ixabepilone offers promising clinical activity in a variety of solid tumors. Ixabepilone is FDA-approved for the treatment of breast cancer refractory to anthracyclines and taxanes. The optimal dose and schedule are still being defined, and the predominant side effects are bone marrow suppression and neuropathy. C1 [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Denduluri, Neelima] NIH, Natl Canc Inst, Breast Canc Sect, Med Oncol Branch, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA. EM Sandra.M.Swain@medstar.net OI Swain, Sandra/0000-0002-1320-3830 NR 68 TC 17 Z9 17 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD MAR PY 2008 VL 17 IS 3 BP 423 EP 435 DI 10.1517/13543784.17.3.423 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277CH UT WOS:000254189800015 PM 18321240 ER PT J AU Lau, CY Cardinali, M Sato, PA Fix, A Flores, J AF Lau, Chuen-Yen Cardinali, Massimo Sato, Paul A. Fix, Alan Flores, Jorge TI Broadening inclusion of vulnerable populations in HIV vaccine trials SO EXPERT REVIEW OF VACCINES LA English DT Review ID IMMUNODEFICIENCY VIRUS SIV; INJECTION-DRUG USERS; HEPATITIS-B; IMMUNE-RESPONSE; RHESUS MACAQUES; ORAL CHALLENGE; RISK BEHAVIOR; TRANSMISSION; CHILDREN; IMMUNOGENICITY C1 [Lau, Chuen-Yen; Cardinali, Massimo; Fix, Alan] NIAID, Vaccine Clin Res Branch, Vaccine Res Program, Div AIDS,NIH, Bethesda, MD 20817 USA. [Cardinali, Massimo] Henry M Jackson Fdn Advancement Mil Med, Bethesda, MD 20817 USA. [Sato, Paul A.] NIAID, Int Maternal Adolescent & Pediat Branch, Therapeut Res Program, Div AIDS,NIH, Bethesda, MD 20817 USA. RP Lau, CY (reprint author), NIAID, Vaccine Clin Res Branch, Vaccine Res Program, Div AIDS,NIH, 6700 N Rockledge Dr,Room 5126, Bethesda, MD 20817 USA. EM lauc@niaid.nih.gov; mcardinali@niaid.nih.gov; satop@niaid.nih.gov; afix@niaid.nih.gov; jflores@niaid.nih.gov NR 41 TC 4 Z9 4 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD MAR PY 2008 VL 7 IS 2 BP 259 EP 268 DI 10.1586/14760584.7.2.259 PG 10 WC Immunology SC Immunology GA 289HO UT WOS:000255045800017 PM 18324894 ER PT J AU Kono, T Bird, S Sonoda, K Savan, R Secombes, CJ Sakai, M AF Kono, Tomoya Bird, Steve Sonoda, Kohei Savan, Ram Secombes, Christopher J. Sakai, Masahiro TI Characterization and expression analysis of an interleukin-7 homologue in the Japanese pufferfish, Takifugu rubripes SO FEBS JOURNAL LA English DT Article DE chromosome synteny; interleukin-7 (IL-7); quantitative real-time PCR; structural analysis; Takifugu rubripes (Fugu) ID TROUT ONCORHYNCHUS-MYKISS; T-CELL DEVELOPMENT; FUGU-RUBRIPES; LYMPHOID HOMEOSTASIS; GENES; IDENTIFICATION; CYTOKINES; CLONING; FISH; EVOLUTION AB An interleukin-7 (IL-7) gene has been cloned and sequenced within the Japanese pufferfish, Takifugu rubripes (Fugu), providing the first conclusive evidence for the existence of IL-7 in teleosts. The IL-7 cDNA was composed of 1438 bp, with a 117 bp 5'-UTR, an 826 bp 3'-UTR containing two mRNA instability motifs, and a 498 bp ORF which translates into a peptide of 166 amino acid residues. The Fugu IL-7 peptide contained a predicted signal peptide of 19 amino acid residues and the IL-7/9 family signature (Arg140-Val149). Homology analysis of Fugu IL-7 with other known IL-2 family members showed some similarity to the known mammalian IL-7 and Fugu IL-21 molecules, and phylogenetic tree analysis showed that the Fugu IL-7 clustered with the chicken and mammalian IL-7 and mammalian IL-9, away from other IL-2 family members (IL-2, IL-4, IL-15 and IL-21). The organization of the Fugu IL-7 gene was the same as in mouse, and consisted of five exons and four introns, but differed from the human gene, which is composed of six exons and five introns. Comparison of the Fugu and human genomes showed that some synteny existed around the IL-7 gene, with the presence of both the protein kinase inhibitor-alpha and chromosome 8 ORF 70 (C8orf70) genes, with IL-7 and C8orf70 having the same transcriptional orientation. The Fugu IL-7 gene was expressed within unstimulated tissues, such as the head kidney, spleen, liver, intestine, gill and muscle. Stimulation of head kidney cells with lipopolysaccharide, polyinosinic polycytidylic acid or phytohaemagglutinin increased this expression. This discovery of IL-7 in Fugu will allow a more complete analysis of fish immune responses in the future. C1 [Kono, Tomoya; Sonoda, Kohei; Sakai, Masahiro] Miyazaki Univ, Fac Agr, Dept Marine Biotechnol, Miyazaki 8892192, Japan. [Bird, Steve; Secombes, Christopher J.] Univ Aberdeen, Sch Biol Sci, Scottish Fish Immunol Res Ctr, Aberdeen AB9 1FX, Scotland. [Savan, Ram] NCI, Ctr Canc Res, Expt Immunol Lab, Frederick, MD 21701 USA. RP Sakai, M (reprint author), Miyazaki Univ, Fac Agr, Dept Marine Biotechnol, Gakuenkibanadainishi 1-1, Miyazaki 8892192, Japan. EM m.sakai@cc.miyazaki-u.ac.jp RI bird, steve/B-5339-2009; Bird, Steve/K-4822-2014 OI Bird, Steve/0000-0003-2937-8579 NR 54 TC 24 Z9 28 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD MAR PY 2008 VL 275 IS 6 BP 1213 EP 1226 DI 10.1111/j.1742-4658.2008.06281.x PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 270ZH UT WOS:000253758200015 PM 18266867 ER PT J AU Sinaii, N Plumb, K Cotton, L Lambert, A Kennedy, S Zondervan, K Stratton, P AF Sinaii, Ninet Plumb, Katherine Cotton, Louise Lambert, Ann Kennedy, Stephen Zondervan, Krina Stratton, Pamela TI Differences in characteristics among 1,000 women with endometriosis based on extent of disease SO FERTILITY AND STERILITY LA English DT Article DE endometriosis; patient characteristics; extent of disease; pelvic pain; subfertility ID CHRONIC PELVIC PAIN; MENSTRUAL CHARACTERISTICS; CANCER-RISK; INFILTRATING ENDOMETRIOSIS; OVARIAN-CANCER; INFERTILITY; DYSMENORRHEA; DIAGNOSIS; FERTILE; LESIONS AB Objective: To determine the relationship between disease severity and patient characteristics in endometriosis. Design: Cross-sectional study of self-reported survey data. Setting: Academic research setting. Patient(s): One thousand women in the Oxford Endometriosis Gene (OXEGENE) study. Intervention(S): None. Main Outcome Measure(s): Participants were assigned to one of two groups with predominantly revised AFS stage I-II (group I, n = 423) or III-IV disease (group II, n = 517). Their characteristics were compared by disease extent. Result(s): Most participants were white (96%) and of reproductive age (81%). Women in group I were significantly younger on entering the study (39.9 +/- 0.5 vs. 44.5 +/- 0.4 years). Overall time to diagnosis did not differ between groups. The most common symptoms leading to a diagnosis were dysmenorrhea (79%) and pelvic pain (69%). In group II, subfertility (21.5% vs. 30.0%) and an ovarian mass (7.3% vs. 29.4%) more commonly led to a diagnosis, whereas dyspareunia (51.1% vs. 39.5%) was significantly more common in group I. Subfertility (41.5% vs. 53.4%) remained more common in group II throughout reproductive life, although birth and miscarriage rates were similar. Conclusion(s): Pelvic pain is common to all with endometriosis and those with more extensive disease report higher rates of subfertility. Remarkably, the time to diagnosis was similar among women. C1 [Sinaii, Ninet] NICHHD, Biostat & Clin Epidemiol Serv, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Plumb, Katherine; Stratton, Pamela] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Cotton, Louise; Lambert, Ann; Kennedy, Stephen] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England. [Zondervan, Krina] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. RP Sinaii, N (reprint author), 10 Ctr Dr,Bldg 10,Room 2N-228, Bethesda, MD 20892 USA. EM sinaiin@mail.nih.gov RI Kennedy, Stephen/B-8950-2009; Zondervan, Krina/M-1143-2013 OI Zondervan, Krina/0000-0002-0275-9905 FU Intramural NIH HHS [ZIA HD008769-06] NR 31 TC 47 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2008 VL 89 IS 3 BP 538 EP 545 DI 10.1016/j.fertnstert.2007.03.069 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 274UE UT WOS:000254026700006 PM 17498711 ER PT J AU Moses-Kolko, EL Wisner, KL Price, JC Berga, SL Drevets, WC Hanusa, BH Loucks, TL Meltzer, CC AF Moses-Kolko, Eydie L. Wisner, Katherine L. Price, Julie C. Berga, Sarah L. Drevets, Wayne C. Hanusa, Barbara H. Loucks, Tammy L. Meltzer, Carolyn C. TI Serotonin 1A receptor reductions in postpartum depression: a positron emission tomography study SO FERTILITY AND STERILITY LA English DT Article DE postpartum depression; serotonin; 5HT1A receptor; PET; estradiol ID PITUITARY-ADRENAL AXIS; MAJOR DEPRESSION; BIPOLAR DISORDER; 5-HT1A RECEPTOR; SUICIDE VICTIMS; POSTNATAL DEPRESSION; TREATMENT RESPONSE; PREFRONTAL CORTEX; CEREBRAL-CORTEX; BINDING-SITES AB Objective: To measure brain serotonin-1A (5HT1A) receptor binding potential (BP) in healthy and depressed postpartum women. Design: 5HT1A receptor BP was measured with positron emission tomography by using [C-11]WAY100635 a single time. Multivariate analysis of variance was used to determine depression effects on 5HT1A receptor BP in relevant brain regions. Setting: An academic research environment. Patient(s): Seven postpartum healthy controls and nine postpartum depressed (PD) subjects with perinatal (antepartum or postpartum) depression onset. Of the nine PD subjects, five had unipolar depression, and four had bipolar disorder. Intervention(S): None. Main Outcome Measure(S): 5HT1A receptor BP. Result(S): Age, time since delivery, and reproductive hormones did not differ between groups. Postsynaptic 5HT1A receptor binding in postpartum depression was reduced 20%-28% relative to controls, with most significant reductions in anterior cingulate and mesiotemporal cortices. Conclusion(s): Postsynaptic 5HT1A receptor binding is reduced in PD women by a similar magnitude as has been shown in other depression samples. The postpartum hormonal milieu and the large proportion of bipolar spectrum subjects in the PD group may have accentuated this finding in this small sample. Recognition of this neurobiological deficit in postpartum depression may be useful in the development of treatments and prevention strategies for this disabling disorder. C1 [Moses-Kolko, Eydie L.; Wisner, Katherine L.; Drevets, Wayne C.; Hanusa, Barbara H.; Meltzer, Carolyn C.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Wisner, Katherine L.] Univ Pittsburgh, Sch Med, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Price, Julie C.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. [Meltzer, Carolyn C.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Berga, Sarah L.; Loucks, Tammy L.] Emory Univ, Sch Med, Dept Obstet & Gynecol, Atlanta, GA USA. [Meltzer, Carolyn C.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. [Meltzer, Carolyn C.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Meltzer, Carolyn C.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. RP Moses-Kolko, EL (reprint author), 410 Oxford Bldg,3811 Ohara St, Pittsburgh, PA 15213 USA. EM mosesel@upmc.edu FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [M01-RR000056, M01 RR000056]; NIMH NIH HHS [K23 MH064561, K23 MH064561-01A1, K24 MH064625, K24 MH64625, MH 53735, MH 57102, MH64561, R01 MH053735, R01 MH057102, R01 MH079164] NR 60 TC 53 Z9 57 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2008 VL 89 IS 3 BP 685 EP 692 DI 10.1016/j.fertnstert.2007.03.059 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 274UE UT WOS:000254026700028 PM 17543959 ER PT J AU Abbott, D Gea-Banacloche, J Davies, PCW Hameroff, S Zeilinger, A Eisert, J Wiseman, H Bezrukov, SM Frauenfelder, H AF Abbott, Derek Gea-Banacloche, Julio Davies, Paul C. W. Hameroff, Stuart Zeilinger, Anton Eisert, Jens Wiseman, Howard Bezrukov, Sergey M. Frauenfelder, Hans TI Plenary debate: Quantum effects in biology: trivial or not? SO FLUCTUATION AND NOISE LETTERS LA English DT Editorial Material C1 [Abbott, Derek] Univ Adelaide, CBME, Adelaide, SA 5005, Australia. [Abbott, Derek] Univ Adelaide, Dept Elect & Elect Engn, Adelaide, SA 5005, Australia. [Gea-Banacloche, Julio] Univ Arkansas, Dept Phys, Fayetteville, AR 72701 USA. [Davies, Paul C. W.] Arizona State Univ, Ctr Fdn Concepts Sci, Tempe, AZ 85287 USA. [Hameroff, Stuart] Univ Arizona, Ctr Consciousness Studies, Dept Anesthesiol & Psychol, Tucson, AZ 85721 USA. [Zeilinger, Anton] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria. [Eisert, Jens] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, QOLS, London SW7 2BW, England. [Eisert, Jens] Univ London Imperial Coll Sci Technol & Med, Inst Math Sci, London SW7 2PE, England. [Wiseman, Howard] Griffith Univ, Ctr Quantrum Dynam, Ctr Quantrum Comp Technol, Brisbane, Qld 4111, Australia. [Bezrukov, Sergey M.] NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. [Frauenfelder, Hans] Los Alamos Natl Lab, Theroy Div T10, Los Alamos, NM 87545 USA. RP Abbott, D (reprint author), Univ Adelaide, CBME, Adelaide, SA 5005, Australia. RI Zeilinger, Anton/A-1170-2011; Wiseman, Howard/A-7266-2008; Quantum, CQD at IMS/D-2115-2010; Abbott, Derek/E-8352-2011; Gea-Banacloche, Julio/J-7546-2013; Eisert, Jens/D-9640-2017 OI Wiseman, Howard/0000-0001-6815-854X; Abbott, Derek/0000-0002-0945-2674; Gea-Banacloche, Julio/0000-0001-9482-9060; Eisert, Jens/0000-0003-3033-1292 NR 0 TC 11 Z9 11 U1 0 U2 13 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0219-4775 J9 FLUCT NOISE LETT JI Fluct. Noise Lett. PD MAR PY 2008 VL 8 IS 1 BP C5 EP C26 DI 10.1142/S0219477508004301 PG 22 WC Mathematics, Interdisciplinary Applications; Physics, Applied SC Mathematics; Physics GA 281IY UT WOS:000254491300002 ER PT J AU Lardinois, OM Detweiler, CD Tomer, KB Mason, RP Deterding, LJ AF Lardinois, Olivier M. Detweiler, Charles D. Tomer, Kenneth B. Mason, Ronald P. Deterding, Leesa J. TI Identifying the site of spin trapping in proteins by a combination of liquid chromatography, ELISA, and off-line tandem mass spectrometry SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE immuno-spin trapping; DMPO; protein radical; amino acid radical; mass spectrometry; hemoglobin; myoglobin ID CYTOCHROME-C PEROXIDASE; SPERM-WHALE MYOGLOBIN; HYDROGEN-PEROXIDE; RADICAL FORMATION; ELECTRON-TRANSFER; NITRIC-OXIDE; IDENTIFICATION; OXIDATION; H2O2; METMYOGLOBIN AB An off-line mass spectrometry method that combines immuno-spin trapping and chromatographic procedures has been developed for selective detection of the nitrone spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) covalently attached to proteins, an attachment which occurs only subsequent to DMPO trapping of free radicals. In this technique, the protein-DMPO nitrone adducts are digested to peptides with proteolytic agents, peptides from the enzymatic digest are separated by HPLC, and enzyme-linked immnunosorbent assays (ELISA) using polyclonal anti-DMPO nitrone antiserum are used to detect the eluted HPLC fractions that contain DMPO nitrone adducts. The fractions showing positive ELISA signals are then concentrated and characterized by tandem mass spectrometry (MS/MS). This method, which constitutes the first liquid chromatography-ELISA-mass spectrometry (LC-ELISA-MS)-based strategy for selective identification of DMPO-trapped protein residues in complex peptide mixtures, facilitates location and preparative fractionation of DMPO nitrone adducts for further structural characterization. The strategy is demonstrated for human hemoglobin, horse heart myoglobin, and sperm whale myoglobin, three globin proteins known to form DMPO-trappable protein radicals on treatment with H2O2. The results demonstrate the power of the new experimental strategy to select DMPO-labeled peptides and identify sites of DMPO covalent attachments. Published by Elsevier Inc. C1 [Tomer, Kenneth B.; Deterding, Leesa J.] Natl Inst Environm Hlth Sci, Lab Sturct Biol, Res Triangle Pk, NC 27709 USA. [Lardinois, Olivier M.; Detweiler, Charles D.; Mason, Ronald P.] Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Deterding, LJ (reprint author), Natl Inst Environm Hlth Sci, Lab Sturct Biol, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. EM deterdi2@nichs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS [Z01 ES050153-12, Z99 ES999999] NR 40 TC 16 Z9 17 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 1 PY 2008 VL 44 IS 5 BP 893 EP 906 DI 10.1016/j.freeradbiomed.2007.11.015 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 265OI UT WOS:000253369000015 PM 18160050 ER PT J AU Morozov, V Wawrousek, EF AF Morozov, V. Wawrousek, E. F. TI Single-strand DNA-mediated targeted mutagenesis of genomic DNA in early mouse embryos is stimulated by Rad51/54 and by Ku70/86 inhibition SO GENE THERAPY LA English DT Article DE targeted mutagenesis; animal models; gene correction/modification; oligonucleotide-based therapies ID TRIPLEX-FORMING OLIGONUCLEOTIDES; GENE REPAIR; MAMMALIAN-CELLS; HOMOLOGOUS RECOMBINATION; MUTATIONS; CHIMERAPLASTY; MICE AB Low and variable efficiency is a major problem in targeted gene alteration, which is used as a primary tool in gene therapy and animal model studies. We tested several types of constructs alone, or in combination with other factors, to introduce a point mutation into the alpha B-crystallin gene in one-celled mouse embryos. We found that co-injection of ssDNA along with antibodies against Ku70/86, or supplementing the system with hRad51/hRad54, increases efficiency of targeted mutagenesis. These findings suggest that proteins in the homologous recombination DNA repair pathway contribute, and that proteins involved in the alternative non-homologous end-joining pathway inhibit, ssDNA-mediated targeted mutagenesis. This is the first successful demonstration of targeted mutation in early mouse embryos. This novel methodology of supplying protein factors to stimulate gene modification in the nucleus has not been previously reported. C1 [Morozov, V.; Wawrousek, E. F.] NEI, Natl Inst Hlth, Mol & Dev Biol Lab, DHHS, Bethesda, MD 20892 USA. RP Morozov, V (reprint author), NEI, Natl Inst Hlth, Mol & Dev Biol Lab, DHHS, Bldg 7,Room 108,7 Mem Dr,MSC 0704, Bethesda, MD 20892 USA. EM morozovv@nei.nih.gov FU Intramural NIH HHS NR 27 TC 21 Z9 22 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 2008 VL 15 IS 6 BP 468 EP 472 DI 10.1038/sj.gt.3303088 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 271UZ UT WOS:000253815500009 PM 18079752 ER PT J AU Bynote, KK Hackenberg, JM Korach, KS Lubahn, DB Lane, PH Gould, KA AF Bynote, K. K. Hackenberg, J. M. Korach, K. S. Lubahn, D. B. Lane, P. H. Gould, K. A. TI Estrogen receptor-alpha deficiency attenuates autoimmune disease in (NZB x NZW)F1 mice SO GENES AND IMMUNITY LA English DT Article DE lupus; autoimmunity; mouse; estrogen receptor alpha; immunologic tolerance ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MURINE LUPUS; KLINEFELTERS-SYNDROME; TARGETED DISRUPTION; ORAL-CONTRACEPTIVES; REPLACEMENT THERAPY; GENETIC DISSECTION; DNA ANTIBODIES; SEX-HORMONES; MOUSE MODEL AB Estrogens promote lupus in humans and some mouse models of this disease. Nonetheless, little is known about the role of estrogen receptors in lupus pathogenesis. Here, we report that in females on the lupus-prone (NZB x NZW)F-1 background, disruption of estrogen receptor-alpha (ER alpha or Esr1) attenuated glomerulonephritis and increased survival. ER alpha deficiency also retarded development of anti-histone/DNA antibodies, suggesting that ER alpha promotes loss of immunologic tolerance. Furthermore, ER alpha deficiency in (NZB x NZW)F-1 females attenuated the subsequent development of anti-double-stranded DNA (dsDNA) IgG antibodies, which are associated with glomerulonephritis in this model. We provide evidence that ER alpha may promote lupus, at least in part, by inducing interferon-gamma, an estrogen-regulated cytokine that impacts this disease. ER alpha deficiency in (NZB x NZW)F-1 males increased survival and reduced anti-dsDNA antibodies, suggesting that ER alpha also modulates lupus in males. These studies demonstrate that ER alpha, rather than ER beta, plays a major role in regulating autoimmunity in (NZB x NZW)F-1 mice. Furthermore, our results suggest for the first time that ER alpha promotes lupus, at least in part, by impacting the initial loss of tolerance. These data suggest that targeted therapy disrupting ER alpha, most likely within the immune system, may be effective in the prevention and/or treatment of lupus. C1 [Bynote, K. K.; Hackenberg, J. M.; Gould, K. A.] Univ Nebraska, Ctr Med, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA. [Bynote, K. K.; Gould, K. A.] Univ Nebraska, Ctr Med, Eppley Inst Res Canc, Omaha, NE 68198 USA. [Korach, K. S.] Natl Inst Environm Hlth Sci, Receptor Biol Sect, NIH, Res Triangle Pk, NC USA. [Lubahn, D. B.] Univ Missouri, Dept Biochem, Columbia, MO USA. [Lubahn, D. B.] Univ Missouri, Dept Child Hlth, Columbia, MO 65201 USA. [Lubahn, D. B.] Univ Missouri, Dept Anim Sci, Columbia, MO USA. [Lubahn, D. B.] Univ Missouri, MU Ctr Phytonutr & Phytochem Studies, Columbia, MO USA. [Lane, P. H.] Univ Nebraska, Med Ctr, Dept Pediat, Omaha, NE 68182 USA. RP Gould, KA (reprint author), Univ Nebraska, Ctr Med, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA. EM kagould@unmc.edu NR 65 TC 53 Z9 54 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD MAR PY 2008 VL 9 IS 2 BP 137 EP 152 DI 10.1038/sj.gene.6364458 PG 16 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 271VA UT WOS:000253815600007 PM 18200028 ER PT J AU McFarlane, HG Kusek, GK Yang, M Phoenix, JL Bolivar, VJ Crawley, JN AF McFarlane, H. G. Kusek, G. K. Yang, M. Phoenix, J. L. Bolivar, V. J. Crawley, J. N. TI Autism-like behavioral phenotypes in BTBR T+tf/J mice SO GENES BRAIN AND BEHAVIOR LA English DT Article DE anxiety; autism; gene; grooming; inbred strain; kynurenic acid; olfaction; repetitive behaviors; social behaviors; social communication; single nucleotide polymorphism ID INBRED MOUSE STRAINS; SOCIAL APPROACH BEHAVIORS; CORPUS-CALLOSUM; KYNURENIC ACID; DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; TRANSGENIC MICE; TASKS RELEVANT; KNOCKOUT MICE; GENE AB Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety-like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo. The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme-regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo, supporting further investigation into the contribution of this polymorphism to autism-like behavioral phenotypes. Robust and selective social deficits, repetitive self-grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms. C1 [McFarlane, H. G.; Yang, M.; Crawley, J. N.] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [McFarlane, H. G.] Kenyon Coll, Dept Psychol, Gambier, OH 43022 USA. [Kusek, G. K.; Phoenix, J. L.] New York State Dept Hlth, Wadsworth Ctr, Troy, NY USA. [Bolivar, V. J.] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12222 USA. [Crawley, J. N.] Univ N Carolina, Neurodev Disorders Res Ctr, Chapel Hill, NC USA. RP Crawley, JN (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bldg 35 Room 1C-903, Bethesda, MD 20892 USA. EM crawleyj@intra.nimh.nih.gov NR 81 TC 284 Z9 287 U1 5 U2 31 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD MAR PY 2008 VL 7 IS 2 BP 152 EP 163 DI 10.1111/j.1601-183X.2007.00330.x PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 270ZN UT WOS:000253758800002 PM 17559418 ER PT J AU Krasnova, IN Li, SM Wood, WH Mccoy, MT Prabhu, VV Becker, KG Katz, JL Cadet, JL AF Krasnova, I. N. Li, S. M. Wood, W. H. McCoy, M. T. Prabhu, V. V. Becker, K. G. Katz, J. L. Cadet, J. L. TI Transcriptional responses to reinforcing effects of cocaine in the rat hippocampus and cortex SO GENES BRAIN AND BEHAVIOR LA English DT Article DE cocaine; conditioned place preference; cortex; hippocampus; memory; microarray ID LONG-TERM POTENTIATION; CONDITIONED PLACE PREFERENCE; PROTEIN-KINASE-IV; SYNAPTIC PLASTICITY; DORSAL HIPPOCAMPUS; FRONTAL-CORTEX; MEMORY STORAGE; EXPRESSION; DOPAMINE; CONSOLIDATION AB The psychostimulant effects of cocaine are thought to result from its ability to block dopamine (DA) uptake and increase DA levels in ventral striatum. In addition, cocaine causes biochemical changes in the brain areas involved in learning and memory, including hippocampus and cortex, whose role in drug reinforcement is now being actively investigated. Thus, we studied molecular events in the hippocampus and frontal cortex of rats treated with cocaine conditioned place preference (CPP) paradigm. After exposure to cocaine conditioning (cocaine paired), cocaine alone (cocaine non-paired) or saline rats were tested for place conditioning. Cocaine (10 mg/kg) caused increases in time spent in the drug-paired compartment. By using microarray analyses, we examined gene expression in the hippocampi and frontal cortices of cocaine-paired rats, cocaine non-paired and saline-treated controls. Our study revealed that 214 transcripts were differentially regulated in the hippocampi of cocaine-paired rats. These include genes that play roles in protein phosphorylation, RNA processing and protein synthesis, ubiquitin-dependent protein degradation and cytoskeleton organization. In contrast, 39 genes were differently expressed in the frontal cortex. Our data support the possibility that molecular changes in the hippocampus might participate in the formation and maintenance of memory patterns induced by cocaine in the brain. Differences in the transcriptional responses in the hippocampus and cortex suggest the primary importance of the hippocampus for recent memory processing associated with cocaine-induced CPP. C1 [Krasnova, I. N.; McCoy, M. T.; Cadet, J. L.] Natl Inst Drug Abuse, Mol Neuropsychiat Branch, DHHS, NIH, Baltimore, MD 21224 USA. [Li, S. M.; Katz, J. L.] Natl Inst Drug Abuse, Medicat Dev Branch, Baltimore, MD USA. [Wood, W. H.; Prabhu, V. V.; Becker, K. G.] NIA, Gene Express & Genom Unit, DHHS, NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), Natl Inst Drug Abuse, Mol Neuropsychiat Branch, DHHS, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov OI Becker, Kevin/0000-0002-6794-6656; Katz, Jonathan/0000-0002-1068-1159 FU Intramural NIH HHS NR 63 TC 23 Z9 26 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD MAR PY 2008 VL 7 IS 2 BP 193 EP 202 DI 10.1111/j.1601-183X.2007.00338.x PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 270ZN UT WOS:000253758800007 PM 17640290 ER PT J AU Linger, R Dudakia, D Huddart, R Tucker, K Friedlander, M Phillips, KA Hogg, D Jewett, MAS Lohynska, R Daugaard, G Richard, S Chompret, A Stoppa-Lyonnet, D Bonaiti-Pellie, C Heidenreich, A Albers, P Olah, E Geczi, L Bodrogi, I Daly, PA Guilford, P Fossi, SD Heimdal, K Tjulandin, SA Liubchenko, L Stoll, H Weber, W Einhorn, L McMaster, M Korde, L Greene, MH Nathanson, KL Cortessis, V Easton, DF Bishop, DT Stratton, MR Rapley, EA AF Linger, Rachel Dudakia, Darshna Huddart, Robert Tucker, Kathy Friedlander, Michael Phillips, Kelly-Anne Hogg, David Jewett, Michael A. S. Lohynska, Radka Daugaard, Gedske Richard, Stephane Chompret, Agnes Stoppa-Lyonnet, Dominique Bonaiti-Pellie, Catherine Heidenreich, Axel Albers, Peter Olah, Edith Geczi, Lajos Bodrogi, Istvan Daly, Peter A. Guilford, Parry Fossi, Sophie D. Heimdal, Ketil Tjulandin, Sergei A. Liubchenko, Ludmila Stoll, Hans Weber, Walter Einhorn, Lawrence McMaster, Mary Korde, Larissa Greene, Mark H. Nathanson, Katherine L. Cortessis, Victoria Easton, Douglas F. Bishop, D. Timothy Stratton, Michael R. Rapley, Elizabeth A. TI Analysis of the DNDI gene in men with sporadic and familial testicular germ cell tumors SO GENES CHROMOSOMES & CANCER LA English DT Article ID SENSITIVE GEL-ELECTROPHORESIS; TER MUTATION; DEAD-END; CANCER; SUSCEPTIBILITY; TERATOMAS; RISK AB A base substitution in the mouse DndI gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a family history of TGCT and 98 without) and found a rare heterozygous variant, p. Glu86Ala, in a single case. This variant was not present in control chromosomes (0/4,132). Analysis of the variant in an additional 842 index TGCT cases (269 with a family history of TGCT and 573 without) did not reveal any additional instances. The variant, p. Glu86Ala, is within a known functional domain of DNDI and is highly conserved through evolution. Although the variant may be a rare polymorphism, a change at such a highly conserved residue is characteristic of a disease-causing variant. Whether it is disease-causing or not, mutations in DNDI make, at most, a very small contribution to TGCT susceptibility in adults and adolescents. (c) 2007 Wiley-Liss, Inc. C1 [Linger, Rachel; Dudakia, Darshna; Stratton, Michael R.; Rapley, Elizabeth A.] Inst Canc Res, Testicular Canc Genet Team, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. [Huddart, Robert] Inst Canc Res, Acad Radiotherapy Unit, Sutton SM2 5NG, Surrey, England. [Tucker, Kathy; Friedlander, Michael] Univ New S Wales, Div Med, Dept Med Oncol, Sydney, NSW, Australia. [Tucker, Kathy; Friedlander, Michael] Prince Wales Hosp Randwick, Sydney, NSW, Australia. [Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic, Australia. [Hogg, David; Jewett, Michael A. S.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hogg, David; Jewett, Michael A. S.] Univ Toronto, Toronto, ON, Canada. [Lohynska, Radka] Univ Hosp, Dept Radiotherapy & Oncol, Prague, Czech Republic. [Daugaard, Gedske] Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. [Richard, Stephane] Fac Med Paris Sud, Genet Oncol EPHE CNRS FRE 2939, Paris, France. [Richard, Stephane] CHU, Serv Urol, Le Kremlin Bicetre, France. [Richard, Stephane; Chompret, Agnes] Inst Gustave Roussy, Serv Urol, Villejuif, France. [Stoppa-Lyonnet, Dominique] Inst Curie, Dept Genet, Paris, France. [Bonaiti-Pellie, Catherine] Univ Paris Sud, INSERM U 535, F-94817 Villejuif, France. [Heidenreich, Axel] Univ Cologne, Div Oncol Urol, Dept Urol, D-5000 Cologne 41, Germany. [Albers, Peter] Klinikum Kassel GmbH, Dept Urol, D-34125 Kassel, Germany. [Olah, Edith; Geczi, Lajos; Bodrogi, Istvan] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. [Olah, Edith; Geczi, Lajos; Bodrogi, Istvan] Natl Inst Oncol, Dept Chemotherapy, Budapest, Hungary. [Daly, Peter A.] St James Hosp, Dept Med Oncol, Dublin, Ireland. [Guilford, Parry] Univ Otago, Canc Genet Lab, Dunedin, New Zealand. [Fossi, Sophie D.; Heimdal, Ketil] Rikshosp Radiumhosp, Dept Clin Canc Res, Oslo, Norway. [Fossi, Sophie D.; Heimdal, Ketil] Rikshosp Radiumhosp, Dept Med Genet, Oslo, Norway. [Tjulandin, Sergei A.; Liubchenko, Ludmila] NNBlokhin Russian Canc Res Ctr, Inst Clin Oncol, Lab Clin Genet, Moscow, Russia. [Stoll, Hans; Weber, Walter] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Einhorn, Lawrence] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46204 USA. [McMaster, Mary; Korde, Larissa; Greene, Mark H.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, Rockville, MD USA. [Nathanson, Katherine L.] Univ Penn, Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. [Cortessis, Victoria] USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Easton, Douglas F.] Strangeways Res Lab, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 4RN, England. [Bishop, D. Timothy] St James Univ Hosp, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England. RP Rapley, EA (reprint author), Inst Canc Res, Testicular Canc Genet Team, Sect Canc Genet, Brookes Lawley Bldg, Sutton SM2 5NG, Surrey, England. EM liz.rapley@icr.ac.uk RI friedlander, michael/G-3490-2013 OI friedlander, michael/0000-0002-6488-0604 FU Cancer Research UK [10118]; Intramural NIH HHS [ZIA CP010144-12]; NCI NIH HHS [R01 CA102042, 1R01 CA102042-01A1]; Wellcome Trust [068545/Z/02] NR 16 TC 24 Z9 24 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 2008 VL 47 IS 3 BP 247 EP 252 DI 10.1002/gec.20526 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 256XX UT WOS:000252764300007 PM 18069663 ER PT J AU Manceau, M Gros, J Savage, K Thome, V McPherron, A Paterson, B Marcelle, C AF Manceau, Marie Gros, Jerome Savage, Kathleen Thome, Virginie McPherron, Alexandra Paterson, Bruce Marcelle, Christophe TI Myostatin promotes the terminal differentiation of embryonic muscle progenitors SO GENES & DEVELOPMENT LA English DT Article DE myostatin; skeletal muscle; embryo; p21 ID SKELETAL-MUSCLE; MYOGENIC DIFFERENTIATION; MYOBLAST PROLIFERATION; NEGATIVE REGULATOR; SATELLITE CELLS; SOMITIC ORIGIN; EXPRESSION; MICE; POPULATION; CATTLE AB Myostatin, a TGF-beta family member, is an important regulator of adult muscle size. While extensively studied in vitro, the mechanisms by which this molecule mediates its effect in vivo are poorly understood. We addressed this question using chick and mouse embryos. We show that while myostatin overexpression in chick leads to an exhaustion of the muscle progenitor population that ultimately results in muscle hypotrophy, myostatin loss of function in chick and mouse provokes an expansion of this population. Our data demonstrate that myostatin acts in vivo to regulate the balance between proliferation and differentiation of embryonic muscle progenitors by promoting their terminal differentiation through the activation of p21 and MyoD. Previous studies have suggested that myostatin imposes quiescence on muscle progenitors. Our data suggest that myostatin's effect on muscle progenitors is more complex than previously realized and is likely to be context-dependent. We propose a novel model for myostatin mode of action in vivo, in which myostatin affects the balance between proliferation and differentiation of embryonic muscle progenitors by enhancing their differentiation. C1 [Manceau, Marie; Gros, Jerome; Thome, Virginie; Marcelle, Christophe] Univ Aix Marseille 2, CNRS, UMR 6216, IBDML, F-13288 Marseille 09, France. [Savage, Kathleen; McPherron, Alexandra] NIH, Genet Dev & Dis Bra, NIDDK, Bethesda, MD 20892 USA. [Paterson, Bruce] NIH, Biochem & Mol Biol Lab, Natl Canc Inst, Bethesda, MD 20892 USA. RP Marcelle, C (reprint author), Univ Aix Marseille 2, CNRS, UMR 6216, IBDML, Campus Luminy, F-13288 Marseille 09, France. EM marcelle@ibdm.univ-mrs.fr OI Gros, Jerome/0000-0002-2264-2851 NR 39 TC 84 Z9 95 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2008 VL 22 IS 5 BP 668 EP 681 DI 10.1101/gad.454408 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 271HK UT WOS:000253779300010 PM 18316481 ER PT J AU Sanderson, SC Wardle, J AF Sanderson, Saskia C. Wardle, Jane TI Associations between anticipated reactions to genetic test results and interest in genetic testing: Will self-selection reduce the potential for harm? SO GENETIC TESTING LA English DT Article ID HUNTINGTONS-DISEASE; COMPLEX INTERVENTIONS; DECISION-MAKING; IMPROVE HEALTH; CANCER; ATTITUDES; RISK; INFORMATION; FRAMEWORK; SMOKING AB The proliferation of genetic susceptibility tests for complex diseases away from clinic settings increases the potential for harm. This study assessed whether people are likely to self-select themselves into or out of genetic testing depending on whether they believe they could cope with the results. Associations between anticipated reactions to adverse genetic test results and interest in taking genetic tests for cancer and heart disease were examined in a community sample of English adults ( n=1024). Interest in genetic testing overall was 78% for cancer risk and 80% for heart disease risk. As predicted, there were differences by anticipated reactions. People who anticipated regret about having taken a genetic test for cancer risk expressed lower interest than those who did not anticipate regret ( 46% vs. 89%), and people who anticipated being glad to know of increased risk status ( i. e., reduced uncertainty) were more interested than those who did not look forward to reduced uncertainty ( 91% vs. 22%). Patterns were similar for heart disease ("regret'' 66% vs. 87%; "reduced uncertainty'' 87% vs. 38%). The potential for harm from future genetic susceptibility tests may be less than feared if people who anticipate adverse reactions self-select themselves out of testing. However, given that a significant proportion of people who anticipated adverse reactions also expressed interest in testing, there is still a concern about safety. It remains to be seen whether the same patterns emerge in studies that actually offer genetic tests for common gene variants in community settings. C1 [Sanderson, Saskia C.] NHGRI, NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Sanderson, Saskia C.; Wardle, Jane] UCL, Dept Epidemiol & Publ Hlth, Hlth Behav Res Ctr, London, England. RP Sanderson, SC (reprint author), NHGRI, NIH, Social & Behav Res Branch, 31 Ctr Dr,Bldg 31,Rm B1B37C, Bethesda, MD 20892 USA. EM sandersons@mail.nih.gov FU Cancer Research UK; Medical Research Council NR 22 TC 17 Z9 17 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD MAR PY 2008 VL 12 IS 1 BP 59 EP 66 DI 10.1089/gte.2007.0047 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 288XQ UT WOS:000255019900008 PM 18318647 ER PT J AU Truong, HT Solaymani-Kohal, S Baker, KR Girirajan, S Williams, SR Vlangos, CN Smith, ACM Bunyan, DJ Roffey, PE Blanchard, CL Elsea, SH AF Truong, Hoa T. Solaymani-Kohal, Sara Baker, Kevin R. Girirajan, Santhosh Williams, Stephen R. Vlangos, Christopher N. Smith, Ann C. M. Bunyan, David J. Roffey, Paul E. Blanchard, Christopher L. Elsea, Sarah H. TI Diagnosing Smith-Magenis syndrome and duplication 17p11.2 syndrome by RAI1 gene copy number variation using quantitative real-time PCR SO GENETIC TESTING LA English DT Article ID HOMOLOGOUS RECOMBINATION; HEREDITARY NEUROPATHY; RAPID DETECTION; DELETIONS; DISEASE; MUTATIONS; LIABILITY; MECHANISM AB Smith-Magenis syndrome ( SMS) and duplication 17p11.2 ( dup17p11.2) syndrome are multiple congenital anomalies/mental retardation disorders resulting from either a deletion or duplication of the 17p11.2 region, respectively. The retinoic acid induced 1 ( RAI1) gene is the causative gene for SMS and is included in the 17p11.2 region of dup17p11.2 syndrome. Currently SMS and dup17p11.2 syndrome are diagnosed using a combination of clinically recognized phenotypes and molecular cytogenetic analyses such as fluorescent in situ hybridization ( FISH). However, these methods have proven to be highly expensive, time consuming, and dependent upon the low resolving capabilities of the assay. To address the need for improved diagnostic methods for SMS and dup17p11.2 syndrome, we designed a quantitative real-time PCR ( Q-PCR) assay that measures RAI1 copy number using the comparative C-t method, Delta Delta C-t. We tested our assay with samples blinded to their previous SMS or dup17p11.2 syndrome status. In all cases, we were able to determine RAI1 copy number status and render a correct diagnosis accordingly. We validated these results by both FISH and multiplex ligation-dependent probe amplification ( MLPA). We conclude that Q-PCR is an accurate, reproducible, low- cost, and reliable assay that can be employed for routine use in SMS and dup17p11.2 diagnosis. C1 [Girirajan, Santhosh; Williams, Stephen R.; Vlangos, Christopher N.; Elsea, Sarah H.] Virginia Commonwealth Univ, Dept Pediat & Human Genet, Richmond, VA 23298 USA. [Truong, Hoa T.; Roffey, Paul E.; Blanchard, Christopher L.] Charles Sturt Univ, Fac Sci, Wagga Wagga, NSW, Australia. [Solaymani-Kohal, Sara] Univ W England, Bristol BS16 1QY, Avon, England. [Baker, Kevin R.; Bunyan, David J.] Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury, Wilts, England. [Smith, Ann C. M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Smith, Ann C. M.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Elsea, SH (reprint author), Virginia Commonwealth Univ, Dept Pediat & Human Genet, 1101 E Marshall St,12-018 Sanger Hall, Richmond, VA 23298 USA. EM selsea@vcu.edu RI Girirajan, Santhosh/A-5280-2010; OI Williams, Stephen/0000-0003-2108-2757 NR 28 TC 6 Z9 6 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD MAR PY 2008 VL 12 IS 1 BP 67 EP 73 DI 10.1089/gte.2007.0058 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 288XQ UT WOS:000255019900009 PM 18373405 ER PT J AU Gao, X Hou, Y Ebina, H Levin, HL Voytas, DF AF Gao, Xiang Hou, Yi Ebina, Hirotaka Levin, Henry L. Voytas, Daniel F. TI Chromodomains direct integration of retrotransposons to heterochromatin SO GENOME RESEARCH LA English DT Article ID TERMINAL REPEAT-RETROTRANSPOSON; POLYMERASE CHAIN-REACTION; HP1 CHROMO DOMAIN; HISTONE H3 TAIL; FISSION YEAST; GENOME SEQUENCE; SILENT CHROMATIN; RNA INTERFERENCE; SCHIZOSACCHAROMYCES-POMBE; ARABIDOPSIS-THALIANA AB The enrichment of mobile genetic elements in heterochromatin may be due, in part, to targeted integration. The chromoviruses are Ty3/gypsy retrotransposons with chromodomains at their integrase C termini. Chromodomains are logical determinants for targeting to heterochromatin, because the chromodomain of heterochromatin protein I (HPI) typically recognizes histone H3 K9 methylation, an epigenetic mark characteristic of heterochromatin. We describe three groups of chromoviruses based on amino acid sequence relationships of their integrase C termini. Genome sequence analysis indicates that representative chromoviruses from each group are enriched in gene-poor regions of the genome relative to other retrotransposons, and when fused to fluorescent marker proteins, the chromodomains target proteins to specific subnuclear foci coincident with heterochromatin. The chromodomain of the fungal element, MAGGY, interacts with histone H3 dimethyl- and trimethyl-K9, and when the MAGGY chromodomain is fused to integrase of the Schizosaccharomyces pombe Tfl retrotransposon, new Tfl insertions are directed to sites of H3 K9 methylation. Repetitive sequences such as transposable elements trigger the RNAi pathway resulting in their epigenetic modification. Our results suggest a dynamic interplay between retrotransposons and heterochromatin, wherein mobile elements recognize heterochromatin at the time of integration and then perpetuate the heterochromatic mark by triggering epigenetic modification. C1 [Gao, Xiang; Hou, Yi; Voytas, Daniel F.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA. [Ebina, Hirotaka; Levin, Henry L.] NICHHD, NIH, Lab Gene Regulat & Dev, Sect Eukaryot Transposable Elements, Bethesda, MD 20892 USA. RP Voytas, DF (reprint author), Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA. EM Voytas@iastate.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM061657, R01 GM061657] NR 99 TC 85 Z9 86 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAR PY 2008 VL 18 IS 3 BP 359 EP 369 DI 10.1101/gr.7146408 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 271CO UT WOS:000253766700002 PM 18256242 ER PT J AU Basu, MK Carmel, L Rogozin, IB Koonin, EV AF Basu, Malay Kumar Carmel, Liran Rogozin, Igor B. Koonin, Eugene V. TI Evolution of protein domain promiscuity in eukaryotes SO GENOME RESEARCH LA English DT Article ID COMPUTER-ASSISTED ANALYSIS; PHYLOGENETIC ANALYSIS; MULTIDOMAIN PROTEINS; MAXIMUM-LIKELIHOOD; GENOME EVOLUTION; INTRON EVOLUTION; DATABASE; CLASSIFICATION; COMBINATIONS; COMPLEXITY AB Numerous eukaryotic proteins contain multiple domains. Certain domains show a tendency to occur in diverse domain architectures and can be considered "promiscuous." These promiscuous domains are, typically, involved in protein-protein interactions and play crucial roles in interaction networks, particularly those that contribute to signal transduction. A systematic comparative-genomic analysis of promiscuous domains in eukaryotes is described. Two quantitative measures of domain promiscuity are introduced and applied to the analysis of 28 genomes of diverse eukaryotes. Altogether, 215 domains are identified as strongly promiscuous. The fraction of promiscuous domains in animals is shown to be significantly greater than that in fungi or plants. Evolutionary reconstructions indicate that domain promiscuity is a volatile, relatively fast-changing feature of eukaryotic proteins, with few domains remaining promiscuous throughout the evolution of eukaryotes. Some domains appear to have attained promiscuity independently in different lineages, for example, animals and plants. It is proposed that promiscuous domains persist within a relatively small pool of evolutionarily stable domain combinations from which numerous rare architectures emerge during evolution. Domain promiscuity positively correlates with the number of experimentally detected domain interactions and with the strength of purifying selection affecting a domain. Thus, evolution of promiscuous domains seems to be constrained by the diversity of their interaction partners. The set of promiscuous domains is enriched for domains mediating protein-protein interactions that are involved in various forms of signal transduction, especially in the ubiquitin system and in chromatin. Thus, a limited repertoire of promiscuous domains makes a major contribution to the diversity and evolvability of eukaryotic proteomes and signaling networks. C1 [Basu, Malay Kumar; Carmel, Liran; Rogozin, Igor B.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Carmel, Liran/A-9681-2008 FU Intramural NIH HHS NR 55 TC 96 Z9 98 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2008 VL 18 IS 3 BP 449 EP 461 DI 10.1101/gr.6943508 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 271CO UT WOS:000253766700011 PM 18230802 ER PT J AU Hochster, H Chen, TT Lu, JM Hills, D Sorich, J Escalon, J Ivy, P Liebes, L Muggia, F AF Hochster, Howard Chen, Thomas T. Lu, Janice M. Hills, Day Sorich, Joan Escalon, Juliet Ivy, Percy Liebes, Leonard Muggia, Franco TI Tolerance and activity of oxaliplatin with protracted topotecan infusion in patients with previously treated ovarian cancer. A phase I study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE topotecan; oxaliplatin; ovarian cancer ID PEGYLATED LIPOSOMAL DOXORUBICIN; SEQUENCE DEPENDENCE; CELL-LINES; CISPLATIN; CARBOPLATIN; COMBINATION; CARCINOMA; PLATINUM; TRIAL; DRUG AB Background. Topotecan 14-day infusion combined with cisplatin was highly active in ovarian cancer, but too myelosuppressive. We therefore sought to evaluate the feasibility of substituting oxaliplatin for cisplatin to improve safety. Methods. Ovarian and primary peritoneal cancer patients, pretreated with at least one prior platinum-containing regimen, performance status (PS) 0-1, without prior pelvic radiation were eligible. Topotecan was continuously infused days 1-15; oxaliplatin was given days 1 and 15; cycles were repeated every 28 days. Five dose levels were explored: topotecan (mg/m(2)/day)/oxaliplatin (mg/m(2)) doses: (1) 0.2/65; (2) 0.2/75; (3) 0.2/85; (4) 0.3/857- (5) 0.4/85. Results. Twenty-three patients (20 ovarian, 1 tubal, and 2 peritoneal) were entered: median age 56 years (range, 37-77); PS: 0=12 and 1 = 11; histology: papillary serous 7, serous 4, adenocarcinoma 8, poorly differentiated 2. Median of 4 cycles were delivered. Grade 3 neutropenia occurred in 3 of 7 patients at level 5 (with fever at levels 4 and 5), without grade 4 neutropenia or thrombocytopenia. Other toxicities were mild and reversible (mainly gastrointestinal), except one grade 3 neuropathy and one oxaliplatin-related grade 3 hypersensitivity reaction. Six objective responses (five of them complete) were documented among 22 patients spanning several dose levels. Conclusion. Topotecan continuous infusion, combined with oxaliplatin, was associated with no grade 4 hematologic toxicity and evidence of activity. The recommended phase II dose is topotecan 0.4 mg/m(2)/day continuous infusion d1-15 with oxaliplatin 85 mg/m(2) on days 1 and 15. A phase II evaluation as second-line treatment for both platinum-sensitive and -resistant ovarian cancer recurrences is ongoing. (c) 2007 Elsevier Inc. All rights reserved. C1 [Hochster, Howard; Chen, Thomas T.; Lu, Janice M.; Hills, Day; Sorich, Joan; Escalon, Juliet; Liebes, Leonard; Muggia, Franco] NYU, Ctr Canc, Sch Med, Div Med Oncol, New York, NY 10016 USA. [Ivy, Percy] NCI, Canc Treatment Evaluat Program, Bethesda, MD 20892 USA. RP Hochster, H (reprint author), NYU, Ctr Canc, Sch Med, Div Med Oncol, 160 E 34th St, New York, NY 10016 USA. EM howard.hochster@med.nyu.edu OI Muggia, Franco/0000-0003-0703-9146 FU NCI NIH HHS [U01 CA076642, CA21115(-27), U01 CA076642-05, P30 CA016087, N01 CM062204, N01 CM007003, U01 CA076642-04, N01-CM-07003-74S, CA76642, CA16087, U01 CA076642-03, U10 CA021115] NR 29 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 BP 500 EP 504 DI 10.1016/j.ygyno.2007.11.017 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 270CM UT WOS:000253697500009 PM 18191187 ER PT J AU Stroup, AM Harlan, LC Trimble, EL AF Stroup, A. M. Harlan, L. C. Trimble, E. L. TI Demographic, clinical, and treatment trends among women diagnosed with vulvar cancer in the United States SO GYNECOLOGIC ONCOLOGY LA English DT Article DE vulva; vulvar; cancer; patterns of care; treatment ID MANAGEMENT; SURGERY; CARCINOMA; STAGE; CHEMOTHERAPY; THERAPY; CERVIX AB Objective. Describe the treatment and survival patterns among a population-based sample of vulvar cancer patients diagnosed in the United States in 1999. Methods. Cases were identified for the National Cancer Institute's Patterns of Care Study (POC) using the Surveillance, Epidemiology, and End Results Program (SEER). A stratified random sample of non-Hispanic white, non-Hispanic black, and Hispanic women age 20 years and older was selected from cases reported by 11 SEER registries. Analyses of the association between vulvar cancer and key demographic, clinical, and hospital characteristics by stage were performed. Cox proportional hazards was used to estimate the odds of death due to cancer. All estimates were weighted, and analyses were conducted with SUDAAN. Results. Ninety percent of cases were diagnosed with in situ or early-stage invasive disease. Older patients were more likely to present at advanced stages. Twenty-five percent of women with Stage III-IV vulvar cancer received chemotherapy plus radiation. We noted widespread use of radical local excision among women with Stage I/II cancer, but 46-54% with invasive disease underwent a radical or total vulvectomy. Factors associated with cancer death were limited to age and stage. Women 75 years and older were at higher risk compared to women aged 20-49 years and the risk of death increased with advancing stage. Conclusions. Vulvar cancer is diagnosed at early stages. Late-stage disease is associated with a significant increase in mortality. Radical surgery was still commonly performed in 1999. Radiation was more common in women diagnosed at late stage, while the use of chemoradiation remained limited. (C) 2007 Elsevier Inc. All rights reserved. C1 [Stroup, A. M.] Univ Utah, Utah Canc Registry, Salt Lake City, UT 84108 USA. [Harlan, L. C.] NCI, Appl Res Program, Bethesda, MD 20892 USA. [Trimble, E. L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Stroup, AM (reprint author), Univ Utah, Utah Canc Registry, 650 Komas Dr,Suite 106B, Salt Lake City, UT 84108 USA. EM Nan.Stroup@hsc.utah.edu FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01PC35133, N01-PC-35133, N01-PC-35135, N01-PC-35136, N01-PC-35137, N01-PC-35138, N01-PC-35139, N01-PC-35141, N01-PC-35142, N01-PC-35143, N01-PC-35145, N01PC35135, N01PC35136, N01PC35137, N01PC35138, N01PC35139, N01PC35141, N01PC35142, N01PC35143, N01PC35145] NR 31 TC 40 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 BP 577 EP 583 DI 10.1016/j.ygyno.2007.11.011 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 270CM UT WOS:000253697500021 PM 18155274 ER PT J AU Ashworth, A Balkwill, F Bast, RC Berek, JS Kaye, A Boyd, JA Mills, G Weinstein, JN Woolley, K Workman, P AF Ashworth, Alan Balkwill, Frances Bast, Robert C. Berek, Jonathan S. Kaye, Allyson Boyd, Jeffrey A. Mills, Gordon Weinstein, John N. Woolley, Katie Workman, Paul TI Opportunities and challenges in ovarian cancer research, a perspective from the 11th Ovarian cancer action/HHMT Forum, Lake Como, March 2007 SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; genomics; drug development; early detection; risk ID BRCA2 MUTATIONS; BREAST-CANCER; RISK; CARRIERS AB Advances in surgery and chemotherapy have improved the 5-year survival for patients with epithelial ovarian cancer, but have not impacted on the ultimate rate of cure in a disease that is diagnosed in late stage and that recurs in the majority of patients. "Omic" technologies promise to define genetically driven aberrant signaling pathways in malignant cells, provided that bioinformatic expertise can be focused on a cancer that is neither common nor rare. Molecular therapeutics must be linked to molecular diagnostics to permit individualized therapy. Not only epithelial cancer cells but also stroma, vasculature and the immune response must be targeted. Closer collaboration between academic institutions, biotech and pharma will be required to facilitate this process and to interest the private sector in an orphan disease. New preclinical models may permit more efficient development of drugs and siRNA that can target dormant drug resistant stem cells. Strategies must be developed to deal with the heterogeneity of different grades and histotypes. Identification of women at increased risk will facilitate prevention and early detection in subsets of patients. BRCA1/2 might be sequenced in all ovarian cancer patients to identify new kindreds. Epidemiologic algorithms are being developed and validated. Awareness must be raised that oral contraceptives can reduce risk of developing ovarian cancer by 50%. Early detection is likely to require panels of complementary biomarkers, analyzed by sophisticated statistical techniques, to improve sensitivity while maintaining extremely high specificity. As ovarian cancer becomes a chronic disease, greater emphasis will be placed on the challenges facing survivors. C1 [Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Balkwill, Frances] Canc Res UK Clin Ctr, Barts & London, London, England. [Bast, Robert C.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Berek, Jonathan S.] Stanford Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, Stanford Canc Ctr, Stanford, CA 94305 USA. [Kaye, Allyson] Ovarian Canc Act, London, England. [Boyd, Jeffrey A.] MD Anderson Canc Ctr, Savannah, GA USA. [Mills, Gordon] MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX USA. [Weinstein, John N.] NCI, Genom & Bioinformat Grp, Ctr Canc Res, Bethesda, MD 20892 USA. [Workman, Paul] Inst Canc Res, Canc Res UK Ctr Canc Therapeut, London SW3 6JB, England. RP Ashworth, A (reprint author), Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. EM alan.ashworth@icr.ac.uk; frances.balkwill@cancer.org.uk; rbast@mdanderson.org; jberek@stanford.edu; allyson@hhmt.org; boydje1@memorialhealth.com; gmills@mdanderson.org; weinstein@dtpax2.ncifcrf.gov; katiewoolley@gmail.com; paul.workman@icr.ac.uk RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Balkwill, Frances/0000-0002-5587-9759 FU Medical Research Council [G0501974] NR 12 TC 12 Z9 13 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 BP 652 EP 657 DI 10.1016/j.ygyno.2007.11.014 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 270CM UT WOS:000253697500031 PM 18096210 ER PT J AU Azad, N Annunziata, CM Greenberg, L Minasian, L Kotz, H Sarosy, G Hespenheide, E Tiwari, S Kohn, E AF Azad, N. Annunziata, C. M. Greenberg, L. Minasian, L. Kotz, H. Sarosy, G. Hespenheide, E. Tiwari, S. Kohn, E. TI Combination therapy with sorafenib and bevacizumab is active in epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Azad, N.; Annunziata, C. M.; Greenberg, L.; Minasian, L.; Kotz, H.; Sarosy, G.; Hespenheide, E.; Tiwari, S.; Kohn, E.] Natl Canc Inst, Bethesda, MD USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 49 BP S23 EP S23 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200051 ER PT J AU Farley, JH Tian, C Rose, GS Brown, CL Birrer, M Thigpen, JT Fleming, GF Gallion, HH Maxwell, GL AF Farley, J. H. Tian, C. Rose, G. S. Brown, C. L. Birrer, M. Thigpen, J. T. Fleming, G. F. Gallion, H. H. Maxwell, G. L. TI Chemotherapy intensity and toxicity among black and white women with advanced and recurrent endometrial cancer: Experience from Gynecologic Oncology Group clinical trials SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Farley, J. H.] Uninformed Serv Univ Hlth Sci, Bethesda, MD USA. [Tian, C.] GOG Stat & Data Ctr, Buffalo, NY USA. [Rose, G. S.; Maxwell, G. L.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Brown, C. L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Birrer, M.] NCI Ctr Canc Res, Bethesda, MD USA. [Thigpen, J. T.] Univ Mississippi, Jackson, MS 39216 USA. [Fleming, G. F.] Univ Chicago, Chicago, IL 60637 USA. [Gallion, H. H.] Magee Womens Hosp, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 40 BP S19 EP S19 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200042 ER PT J AU Liao, JB Hasegawa, K Dudley, ME Riley, JL Rosenberg, SA June, CH Coukos, G AF Liao, J. B. Hasegawa, K. Dudley, M. E. Riley, J. L. Rosenberg, S. A. June, C. H. Coukos, G. TI Killing human ovarian cancer cells with human peripheral blood lymphocytes transduced with bicistronic lentiviral vectors encoding a murine anti-p53 T-cell receptor SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Liao, J. B.; Hasegawa, K.; Riley, J. L.; June, C. H.; Coukos, G.] Univ Penn, Philadelphia, PA 19104 USA. [Dudley, M. E.; Rosenberg, S. A.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 99 BP S45 EP S45 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200101 ER PT J AU Nevadunsky, NS Fleming, EL Merritt, MA Johnson, M Berkowitz, RS Birrer, MJ Mok, SC AF Nevadunsky, N. S. Fleming, E. L. Merritt, M. A. Johnson, M. Berkowitz, R. S. Birrer, M. J. Mok, S. C. TI Differential gene expression and function of ovarian epithelial cancer-associated fibroblasts versus normal ovarian cortical fibroblasts SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Nevadunsky, N. S.; Fleming, E. L.; Merritt, M. A.; Johnson, M.; Berkowitz, R. S.; Mok, S. C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Birrer, M. J.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 BP S116 EP S117 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200266 ER PT J AU Ozbun, L Vathipadiekal, V Radonovich, ME Pise-Masion, C Saxena, D Hauschka, PV Mok, SC Birrer, MJ AF Ozbun, L. Vathipadiekal, V. Radonovich, M. E. Pise-Masion, C. Saxena, D. Hauschka, P. V. Mok, S. C. Birrer, M. J. TI Cancer stem cell gene signature identified from ovarian tumor side populations SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Ozbun, L.; Vathipadiekal, V.; Radonovich, M. E.; Pise-Masion, C.; Birrer, M. J.] Natl Canc Inst, Bethesda, MD USA. [Saxena, D.; Hauschka, P. V.] Childrens Hosp, Boston, MA 02115 USA. [Mok, S. C.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 51 BP S24 EP S24 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200053 ER PT J AU Samimi, G Bonome, T Radonovich, M Pise-Maison, C Brady, J Ghosh, S Ng, S Mok, SC Birrer, MJ AF Samimi, G. Bonome, T. Radonovich, M. Pise-Maison, C. Brady, J. Ghosh, S. Ng, S. Mok, S. C. Birrer, M. J. TI Multiple ligands of integrin alpha v beta 3 are up-regulated in ovarian tumor stroma: important tumor-stroma interaction SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Samimi, G.; Bonome, T.; Radonovich, M.; Pise-Maison, C.; Brady, J.; Birrer, M. J.] Natl Canc Inst, NIH, Bethesda, MD USA. [Ghosh, S.; Ng, S.; Mok, S. C.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 109 BP S49 EP S50 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200111 ER PT J AU Stany, MP Ozbun, L Bonome, T Rose, GS Mok, S Birrer, MJ AF Stany, M. P. Ozbun, L. Bonome, T. Rose, G. S. Mok, S. Birrer, M. J. TI Expression profiling of microdissected clear cell ovarian cancers identifies pathways of therapeutic importance SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Stany, M. P.; Rose, G. S.] Walter Reed Army Med Ctr, Washington, DC USA. [Ozbun, L.; Bonome, T.; Birrer, M. J.] Natl Canc Inst, Bethesda, MD USA. [Mok, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 274 BP S121 EP S121 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200276 ER PT J AU Tung, CS Yeung, C Mok, SC Birrer, MJ Lu, KH Gershenson, DM Wong, K AF Tung, C. S. Yeung, C. Mok, S. C. Birrer, M. J. Lu, K. H. Gershenson, D. M. Wong, K. TI The role of PAX2 as a potential biomarker of low-grade serous ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Tung, C. S.; Lu, K. H.; Gershenson, D. M.; Wong, K.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Yeung, C.] Chinese Univ Hong Kong, Mol Biotechnol Program, Hong Kong, Peoples R China. [Mok, S. C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. [Birrer, M. J.] Natl Canc Inst, Cell & Canc Biol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 127 BP S57 EP S57 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200129 ER PT J AU Winterhoffl, BJ Konecny, GE Mariani, A Keeney, G Thomas, B Riehle, D Murphey, L Neuper, C Jones, M Dowdy, S Wang, H Morin, P Podratz, KC AF Winterhoffl, B. J. Konecny, G. E. Mariani, A. Keeney, G. Thomas, B. Riehle, D. Murphey, L. Neuper, C. Jones, M. Dowdy, S. Wang, H. Morin, P. Podratz, K. C. TI Claudin-3 and claudin-4 expression in serous papillary, clear cell, and endometrioid endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Konecny, G. E.; Mariani, A.; Keeney, G.; Thomas, B.; Neuper, C.; Jones, M.; Dowdy, S.; Podratz, K. C.] Mayo Clin, Rochester, MN USA. [Riehle, D.; Murphey, L.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Winterhoffl, B. J.] Natl Inst Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 61 BP S28 EP S28 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200063 ER PT J AU Wong, KK Tung, C Yeung, CS Zu, Z Tsang, YI Deavers, M Wolf, J Lu, K Birrer, M Mok, SC Gershenson, D AF Wong, K. K. Tung, C. Yeung, C. S. Zu, Z. Tsang, Y. I. Deavers, M. Wolf, J. Lu, K. Birrer, M. Mok, S. C. Gershenson, D. TI Decrease in the expression of BCMP11 during progression from low-malignant-potential to low-grade ovarian serous carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Wong, K. K.; Tung, C.; Zu, Z.; Tsang, Y. I.; Deavers, M.; Wolf, J.; Lu, K.; Gershenson, D.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Yeung, C. S.] Chinese Univ Hong Kong, Hong Kong, Peoples R China. [Birrer, M.] Natl Canc Inst, Bethesda, MD USA. [Mok, S. C.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2008 VL 108 IS 3 SU 1 MA 113 BP S51 EP S51 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 271XO UT WOS:000253822200115 ER PT J AU Nichols, WL Hultin, MB James, AH Manco-Johnson, MJ Montgomery, RR Ortel, TL Rick, ME Sadler, JE Weinstein, M Yawn, BP AF Nichols, W. L. Hultin, M. B. James, A. H. Manco-Johnson, M. J. Montgomery, R. R. Ortel, T. L. Rick, M. E. Sadler, J. E. Weinstein, M. Yawn, B. P. TI von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA) SO HAEMOPHILIA LA English DT Review DE acquired von Willebrand syndrome; bleeding disorder; clotting factor concentrate; coagulation factor VIII; desmopressin; haemorrhage; menorrhagia; platelet disorder; von Willebrand disease; von Willebrand factor ID INHERITED BLEEDING DISORDERS; IIB VONWILLEBRANDS DISEASE; 1-DESAMINO-8-D-ARGININE VASOPRESSIN DDAVP; CENTER DOCTORS ORGANIZATION; GLYCOPROTEIN-IB-ALPHA; HEMOPHILIA TREATMENT CENTERS; RISTOCETIN COFACTOR ACTIVITY; NORMAL PLATELET TRANSFUSION; INHIBITOR TRANEXAMIC ACID; CANDIDATE GENE HAPLOTYPES AB von Willebrand disease (VWD) is a commonly encountered inherited bleeding disorder affecting both males and females, causing mucous membrane and skin bleeding symptoms, and bleeding with surgical or other haemostatic challenges. VWD may be disproportionately symptomatic in women of child-bearing age. It may also occur less frequently as an acquired disorder (acquired von Willebrand syndrome). VWD is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates platelet haemostatic function and stabilizes blood coagulation factor VIII. The pathophysiology, classification, diagnosis and management of VWD are relatively complex, but understanding them is important for proper diagnosis and management of patients with VWD. These evidence-based guidelines for diagnosis and management of VWD from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel (USA) review relevant publications, summarize current understanding of VWD pathophysiology and classification, and present consensus diagnostic and management recommendations based on analysis of the literature and expert opinion. They also suggest an approach for clinical and laboratory evaluation of individuals with bleeding symptoms, history of bleeding or conditions associated with increased bleeding risk. This document summarizes needs for further research in VWF, VWD and bleeding disorders, including clinical research to obtain more objective information about bleeding symptoms, advancements in diagnostic and therapeutic tools, and enhancement in the education and training of clinicians and scientists in bleeding and thrombotic disorders. The NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd) has a more detailed document, a synopsis of these recommendations, and patient education information. C1 [Nichols, W. L.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Special Coagulat Lab,Div Hematopathol, Rochester, MN 55905 USA. [Nichols, W. L.] Mayo Clin, Coagulat Clin, Rochester, MN 55905 USA. [Nichols, W. L.] Mayo Clin, Comprehens Hemophilia Ctr, Div Hematol & Internal Med, Rochester, MN 55905 USA. [Hultin, M. B.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [James, A. H.] Duke Univ, Ctr Med, Dept Obstet & Gynecol, Durham, NC USA. [Manco-Johnson, M. J.] Univ Colorado Denver, Dept Pediat, Aurora, CO USA. [Manco-Johnson, M. J.] Childrens Hosp Denver, Ctr Canc & Blood Disorders, Denver, CO USA. [Montgomery, R. R.] Med Coll Wisconsin, Dept Pediat, Blood Res Inst, BloodCtr Wisconsin, Milwaukee, WI 53226 USA. [Montgomery, R. R.] Med Coll Wisconsin, Dept Pediat, Sect Pediat Hematol, Milwaukee, WI 53226 USA. [Ortel, T. L.] Duke Univ, Med Ctr, Dept Pathol, Clin Coagulat Lab, Durham, NC USA. [Ortel, T. L.] Duke Univ, Med Ctr, Div Hematol, Dept Med, Durham, NC USA. [Rick, M. E.] NIH, Warren Grant Magnuson Clin Ctr, Serv Hematol, Bethesda, MD 20892 USA. [Sadler, J. E.] Washington Univ, Dept Med, St Louis, MO USA. [Yawn, B. P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, B. P.] Univ Minnesota, Dept Family & Community Med, Minneapolis, MN USA. [Weinstein, M.] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA. RP Nichols, WL (reprint author), Mayo Clin, Coll Med, Dept Lab Med & Pathol, Special Coagulat Lab,Div Hematopathol, 200 SCL,Mayo Clin,200 1st St SW, Rochester, MN 55905 USA. EM nichols.william@mayo.edu RI Sadler, Evan/D-8556-2011; OI Sadler, J. Evan/0000-0001-5705-469X NR 411 TC 327 Z9 330 U1 4 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAR PY 2008 VL 14 IS 2 BP 171 EP 232 DI 10.1111/j.1365-2516.2007.01643.x PG 62 WC Hematology SC Hematology GA 269CC UT WOS:000253626100001 PM 18315614 ER PT J AU Miller, FG AF Miller, Franklin G. TI Twenty-five years of therapeutic misconception SO HASTINGS CENTER REPORT LA English DT Letter C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAR-APR PY 2008 VL 38 IS 2 BP 6 EP 6 PG 1 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 282JM UT WOS:000254563800005 PM 18457218 ER PT J AU Emanuel, EJ AF Emanuel, Ezekiel J. TI What are bioethicists doing about health care reform? SO HASTINGS CENTER REPORT LA English DT Article C1 [Emanuel, Ezekiel J.] NIH, Ctr Clin, Bioeth Dept, Bethesda, MD 20892 USA. [Emanuel, Ezekiel J.] Stanford Univ, FRESH Thinking Program Hlth Reform, Stanford, CA 94305 USA. RP Emanuel, EJ (reprint author), NIH, Ctr Clin, Bioeth Dept, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAR-APR PY 2008 VL 38 IS 2 BP 12 EP 13 DI 10.1353/hcr.2008.0017 PG 2 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 282JM UT WOS:000254563800009 PM 18457221 ER PT J AU Joffe, S Miller, FG AF Joffe, Steven Miller, Franklin G. TI Bench to bedside - Mapping the moral terrain of clinical research SO HASTINGS CENTER REPORT LA English DT Article ID PLACEBO-CONTROLLED TRIALS; THERAPEUTIC MISCONCEPTION; CARE RESPONSIBILITIES; MEDICAL RESEARCHERS; ETHICAL FRAMEWORK; RANDOMIZED-TRIAL; BREAST-CANCER; EQUIPOISE; CRITIQUE; INVESTIGATOR C1 [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Boston, MA 02115 USA. [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [K01-CA096872] NR 75 TC 55 Z9 56 U1 1 U2 3 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAR-APR PY 2008 VL 38 IS 2 BP 30 EP 42 DI 10.1353/hcr.2008.0019 PG 13 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 282JM UT WOS:000254563800015 PM 18457227 ER PT J AU Kim, KP Miller, DL Balter, S Kleinerman, RA Linet, MS Kwon, D Simon, SL AF Kim, Kwang Pyo Miller, Donald L. Balter, Stephen Kleinerman, Ruth A. Linet, Martha S. Kwon, Deukwoo Simon, Steven L. TI Occupational radiation doses to operators performing cardiac catheterization procedures SO HEALTH PHYSICS LA English DT Review DE exposure; occupational; fluoroscopy; medical radiation; occupational safety ID TRANSLUMINAL CORONARY ANGIOPLASTY; INTERVENTIONAL CARDIOLOGY PROCEDURES; CONTROLLED MECHANICAL PUMP; SUPRAVENTRICULAR TACHYCARDIA; DIAGNOSTIC CATHETERIZATION; ANGIOGRAPHIC PROCEDURES; INVASIVE CARDIOLOGY; ABLATION PROCEDURES; PERSONNEL EXPOSURE; MEDICAL PERSONNEL AB Cardiac catheterization procedures using fluoroscopy reduce patient morbidity and mortality compared to operative procedures. These diagnostic and therapeutic procedures require radiation exposure to patients and physicians. The objectives of the present investigation were to provide a systematic comprehensive summary of the reported radiation doses received by operators due to diagnostic or interventional fluoroscopically-guided procedures, to identify the primary factors influencing operator radiation dose, and to evaluate whether there have been temporal changes in the radiation doses received by operators performing these procedures. Using PubMed, we identified all English-language journal articles and other published data reporting radiation exposures to operators from diagnostic or interventional fluoroscopically-guided cardiovascular procedures from the early 1970's through the present. We abstracted the reported radiation doses, dose measurement methods, fluoroscopy system used, operational features, radiation protection features, and other relevant data. We calculated effective doses to operators in each study to facilitate comparisons. The effective doses ranged from 0.02-38.0 mu Sv for DC (diagnostic catheterizations), 0.17-31.2 mu Sv for PCI (percutaneous coronary interventions), 0.24-9.6 mu Sv for ablations, and 0.29-17.4 mu Sv for pacemaker or intracardiac defibrillator implantations. The ratios of doses between various anatomic sites and the thyroid, measured over protective shields, were 0.9 +/- 1.0 for the eye, 1.0 +/- 1.5 for the trunk, and 1.3 +/- 2.0 for the hand. Generally, radiation dose is higher on the left side of an operator's body, because the operator's left side is closer to the primary beam when standing at the patient's right side. Modest operator dose reductions over time were observed for DC and ablation, primarily due to reduction in patient doses due to decreased fluoroscopy/cineradiography time and dose rate by technology improvement. Doses were not reduced over time for PCI. The increased complexity of medical procedures appears to have offset dose reductions due to improvements in technology. The large variation in operator doses observed for the same type of procedure suggests that optimizing procedure protocols and implementing general use of the most effective types of protective devices and shields may reduce occupational radiation doses to operators. We had considerable difficulty in comparing reported dosimetry results because of significant differences in dosimetric methods used in each study and multiple factors influencing the actual doses received. Better standardization of dosimetric methods will facilitate future analyses aimed at determining how well medical radiation workers are being protected. C1 [Kim, Kwang Pyo; Kleinerman, Ruth A.; Linet, Martha S.; Kwon, Deukwoo; Simon, Steven L.] NCI, NIH, DCEG, Bethesda, MD 20892 USA. [Miller, Donald L.] Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. [Balter, Stephen] Columbia Univ, Med Ctr, Dept Radiol & Med, New York, NY USA. RP Kim, KP (reprint author), NCI, NIH, DCEG, 6120 Execut Blvd,Room 7056, Bethesda, MD 20892 USA. EM kimkwang@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 NR 104 TC 107 Z9 116 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAR PY 2008 VL 94 IS 3 BP 211 EP 227 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 263XN UT WOS:000253249900001 PM 18301095 ER PT J AU Beckjord, EB Rutten, LJF Arora, NK Moser, RP Hesse, BW AF Beckjord, Ellen Burke Rutten, Lila J. Finney Arora, Neeraj K. Moser, Richard P. Hesse, Bradford W. TI Information processing and negative affect: Evidence from the 2003 health information national trends survey SO HEALTH PSYCHOLOGY LA English DT Article DE health communication; information processing; negative affect ID CANCER-RELATED INFORMATION; LOW-INCOME WOMEN; BREAST-CANCER; ATTENTIONAL BIAS; DECISION-MAKING; SURVEY HINTS; CLINICAL ANXIETY; PERCEIVED RISK; WORRY; DEPRESSION AB Objective: Health communication can help reduce the cancer burden by increasing processing of information about health interventions. Negative affect is associated with information processing and may be a barrier to successful health communication. Design and Main Outcome Measures: We examined associations between negative affect and information processing at the population level. Symptoms of depression (6 items) and cancer worry (I item) operationalized negative affect; attention to health information (5 items) and cancer information-seeking experiences (6 items) operationalized information processing. Results: Higher cancer worry was associated with more attention to health information (p <.01) and worse cancer information-seeking experiences (p <.05). More symptoms of depression were associated with worse information-seeking experiences (p <.01), but not with attention. Conclusions: We found population-level evidence that increased cancer worry is associated with more attention to health information, and increased cancer worry and symptoms of depression are associated with worse cancer information-seeking experiences. Results suggest that affect plays a role in health information processing, and decreasing negative affect associated with cancer communication may improve experiences seeking cancer information. C1 [Beckjord, Ellen Burke] RAND Corp, Pittsburgh, PA 15213 USA. [Rutten, Lila J. Finney; Moser, Richard P.] NCI, Div Canc Prevent, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Rutten, Lila J. Finney; Hesse, Bradford W.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Commun & Informat Res Branch,NIH, Bethesda, MD 20892 USA. [Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Outcomes Res Branch,NIH, Bethesda, MD 20892 USA. RP Beckjord, EB (reprint author), RAND Corp, 4570 5th Ave,Room 4422, Pittsburgh, PA 15213 USA. EM ebeckjor@rand.org OI Hesse, Bradford/0000-0003-1142-1161 NR 75 TC 23 Z9 24 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAR PY 2008 VL 27 IS 2 BP 249 EP 257 DI 10.1037/0278-6133.27.2.249 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 283TQ UT WOS:000254659800015 PM 18377144 ER PT J AU Perna, FM Craft, L Carver, CS Antoni, MH AF Perna, Frank M. Craft, Lynette Carver, Charles S. Antoni, Michael H. TI Negative affect and barriers to exercise among early stage breast cancer patients SO HEALTH PSYCHOLOGY LA English DT Article DE exercise; breast cancer; physical activity; barriers ID QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; SURVIVORS; MODEL; DISTRESS; WALKING; WOMEN AB Objective: To assess the relative frequency of and barriers to exercise among women with breast cancer while controlling for cancer-relevant and demographic factors. Design: The present study employed concurrent samples, correlational research design. Main Outcome Measures: Exercise frequency and its association with negative affect and barriers to exercise, independent of cancer treatment, among women (N = 176) with Stage I or 11 breast cancer who were 3, 6, and 12 months postsurgery. Results: After accounting for cancer-relevant and control variables, degree of negative affect and frequency of perceived barriers were significantly inversely associated with exercise. Conclusion: These findings suggest that attention to both emotional factors and psychosocial barriers to exercise may be warranted to further understand exercise among women with early stage breast cancer. C1 [Perna, Frank M.; Craft, Lynette] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Carver, Charles S.; Antoni, Michael H.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. RP Perna, FM (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4060, Bethesda, MD 20892 USA. EM pernafm@mail.nih.gov OI carver, charles/0000-0002-3688-8545 FU NCI NIH HHS [R01-CA78801, CA-64710]; NCRR NIH HHS [M01RR005333]; NIMH NIH HHS [T32MH18917] NR 36 TC 10 Z9 11 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAR PY 2008 VL 27 IS 2 BP 275 EP 279 DI 10.1037/0278-6133.27.2.275 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA 283TQ UT WOS:000254659800018 PM 18377147 ER PT J AU Steinberg, JS Joshi, S Schron, RB Powel, J Hallstrom, A McBurnie, M AF Steinberg, Jonathan S. Joshi, Sandeep Schron, Reanor B. Powel, Judy Hallstrom, Affred McBurnie, MaryAnn CA AVID Invest TI Psychosocial status predicts mortality in patients with life-threatening ventricular arrhythmias SO HEART RHYTHM LA English DT Article DE quality of life; antiarrhythmics; antiarrhythmic versus implantable defibrillators trial; tachyarrhythmias; defibrillation; cardiac arrest ID QUALITY-OF-LIFE; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; CORONARY-ARTERY-DISEASE; ISCHEMIC-HEART-DISEASE; MENTAL STRESS; VITAL EXHAUSTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PSYCHOLOGICAL STRESS; THERAPY AB BACKGROUND Quality-of-life (QoL) instruments evaluate various aspects of physical, mental, and emotional health, but how these psychosocial characteristics impact Long-term outcome after cardiac arrest and ventricular tachycardia (VT) is unknown. OBJECTIVE The purpose of this study was to evaluate the retationship of baseline QoL scores with Long-term survival of patients enrolled in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial. METHODS Formal QoL measures included SF-36 mental and physical components, Patient Concerns Checklist, and Ferrans and Powers Quality-of-Life Index-Cardiac Version. Multivariate Cox regression was used to assess the association of survival and these measures, adjusting for index arrhythmia type, gender, race, age, ejection fraction, history of congestive heart failure; antiarrhythmic therapy, and beta-blocker use. RESULTS During mean follow-up of 546 +/- 356 days, 129 deaths occurred among 740 patients. Higher baseline SF-36 physical summary scores (P <.001), higher baseline QoL Index summary scores (P =.015), and lower baseline Patient Concerns Checklist summary scores (P =.047) were associated with longer survival, even after adjustment for clinical variables. When Col. measures were examined simultaneously, only the SF-36 physical summary score remained significant (P =.002). CONCLUSION During recovery after sustained VT or cardiac arrest, formal baseline QoL assessment provides important prognostic information independent of traditional clinical data. C1 [Steinberg, Jonathan S.; Joshi, Sandeep] St Lukes Roosevelt Hosp, Div Cardiol, New York, NY 10025 USA. [Steinberg, Jonathan S.; Joshi, Sandeep] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Schron, Reanor B.] NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. [Powel, Judy; Hallstrom, Affred] Univ Washington, Seattle, WA 98195 USA. [McBurnie, MaryAnn] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Steinberg, JS (reprint author), St Lukes Roosevelt Hosp, Div Cardiol, 1111 Amsterdam Ave, New York, NY 10025 USA. EM jss7@columbia.edu NR 38 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2008 VL 5 IS 3 BP 361 EP 365 DI 10.1016/j.hrthm.2007.11.010 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 273WE UT WOS:000253961900005 PM 18313592 ER PT J AU Arias, IM AF Arias, Irwin M. TI Perspective: Five decades of cholestasis research and the brave new world SO HEPATOLOGY LA English DT Editorial Material ID CANALICULAR MEMBRANE-VESICLES; FAMILIAL INTRAHEPATIC CHOLESTASIS; SALT EXPORT PUMP; POLARIZED HEPATIC CELLS; ATP-DEPENDENT TRANSPORT; CANINE KIDNEY-CELLS; RAT-LIVER; BILE-SALT; PHOSPHOINOSITIDE 3-KINASE; APICAL MEMBRANE C1 [Arias, Irwin M.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Arias, IM (reprint author), NICHD, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM ariasi@mail.nih.gov NR 51 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2008 VL 47 IS 3 BP 777 EP 785 DI 10.1002/bep.22210 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270CZ UT WOS:000253698900003 PM 18302286 ER PT J AU Fontana, RJ Goodman, ZD Dienstag, JL Bonkovsky, HL Naishadham, D Sterling, RK Su, GL Ghosh, M Wright, EC AF Fontana, Robert J. Goodman, Zachary D. Dienstag, Jules L. Bonkovsky, Herbert L. Naishadham, Deepa Sterling, Richard K. Su, Grace L. Ghosh, Mita Wright, Elizabeth C. CA HALT-C Trial Grp TI Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C SO HEPATOLOGY LA English DT Article ID IMAGE-ANALYSIS; HYALURONIC-ACID; VIRUS-INFECTION; CIRRHOSIS; DISEASE; EVOLUTION; QUANTIFICATION; VARIABILITY; PROGRESSION; INTERFERON AB This study determined the utility of a panel of serum fibrosis markers along with routine laboratory tests in estimating the likelihood of histological cirrhosis in a cohort of prior nonresponders with chronic hepatitis C. The relationship between serum markers and quantitative hepatic collagen content was also determined. Liver biopsy samples from 513 subjects enrolled in the HALT-C trial were assigned Ishak fibrosis scores. The collagen content of 386 sirius-red stained, nonfragmented biopsy samples was quantified using computerized morphometry. Serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), amino-terminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA), and YKL-40 levels were determined using commercially available assays. Sixty-two percent of patients had noncirrhotic fibrosis (Ishak stage 2-4) whereas 38% had cirrhosis (Ishak stage 5,6). Multivariate analysis identified a 3-variable model (HA, TIMP-1, and platelet count) that had an area under the receiver operating curve (AUROC) of 0.81 for estimating the presence of cirrhosis. This model was significantly better than that derived from the cirrhosis discriminant score (AUROC 0.70), the AST-to-platelet ratio (AUROC 0.73), and a prior model developed in HALT-C patients (AUROC 0.79). Multivariate analysis demonstrated that the serum fibrosis markers correlated substantially better with Ishak fibrosis scores than with the log hepatic collagen content (AUROC 0.84 versus 0.72). Conclusion: A 3-variable model consisting of serum HA, TIMP-1, and platelet count was better than other published models in identifying cirrhosis in HALT-C Trial subjects. The stronger correlation of the serum markers with Ishak scores suggests that serum fibrosis markers reflect the pattern of fibrosis more closely than the quantity of hepatic collagen. C1 [Fontana, Robert J.; Ghosh, Mita] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Goodman, Zachary D.] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA. [Sterling, Richard K.] Virginia Commonwealth Univ Hlth Syst, Hepatol Sect, Richmond, VA USA. [Su, Grace L.] Ann Arbor Vet Adm Hlth Ctr, Ann Arbor, MI USA. [Wright, Elizabeth C.] NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Fontana, RJ (reprint author), Univ Michigan, Sch Med, Dept Internal Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM rfontana@umich.edu FU NCRR NIH HHS [M01RR-06192, M01RR-01066, M01RR-00065]; NIDDK NIH HHS [N01-DK-9-2319, N01-DK-9-2328, N01-DK-9-2326, N01-DK-9-2323] NR 41 TC 97 Z9 100 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2008 VL 47 IS 3 BP 789 EP 798 DI 10.1002/hep.22099 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270CZ UT WOS:000253698900005 PM 18175357 ER PT J AU Goodman, ZD Makhlouf, HR Liu, L Bahstreri, W Gonzalez-Peralta, RP Haber, B Jonas, MA Mohan, P Molleston, JP Murray, KF Narkewicz, MR Rosenthal, P Smith, LJ Robuck, PR Schwarz, KB AF Goodman, Zachary D. Makhlouf, Hala R. Liu, Lea Bahstreri, William Gonzalez-Peralta, Regino P. Haber, Barbara Jonas, Maureen A. Mohan, Parvathi Molleston, Jean P. Murray, Karen F. Narkewicz, Michael R. Rosenthal, Philip Smith, Lesley J. Robuck, Patricia R. Schwarz, Kathleen B. TI Pathology of chronic hepatitis C in children: Liver biopsy findings in the Peds-C trial SO HEPATOLOGY LA English DT Article ID CHRONIC VIRAL-HEPATITIS; INITIAL TREATMENT; VIRUS-INFECTION; PEGYLATED INTERFERON-ALPHA-2B; CLINICAL SPECTRUM; RIBAVIRIN; STEATOSIS; HISTOPATHOLOGY; PEGINTERFERON; FEATURES AB There is relatively little information in the literature on the histopathology of chronic hepatitis C in children. The Peds-C Trial, designed to test the efficacy and safety of peginterferon alfa-2a and ribavirin in children, provided an opportunity to examine liver biopsies from 121 treatment-naive children, ages 2 to 16 (mean, 9.8 years) infected with the hepatitis C virus (HCV) and with no other identifiable cause for liver disease, signs of hepatic decompensation, or another significant nonhepatic disease. Liver biopsies were scored for inflammation, fibrosis, steatosis, and other histological features. Inflammation in the biopsy was minimal in 42%, mild in 17%, moderate in 38%, and severe in only 3%. Five had bridging fibrosis, and 2 had cirrhosis. Steatosis was absent in 56%, minimal in 34%, and mild in 10%. Inflammation scores correlated with fibrosis scores, serum alanine aminotransferase levels, and duration of infection, but not with age, body mass index z score, or HCV genotype. Fibrosis scores correlated with inflammation but not with age, HCV genotype, body mass index z score, or steatosis parameters. Steatosis correlated with serum alanine aminotransferase levels and body mass index z scores; overweight children had more fibrosis than the non-overweight. In conclusion, in this cohort of HCV-infected children, inflammation, fibrosis, and steatosis were milder than reported for treatment-naive adults with chronic hepatitis C, but there were several with bridging fibrosis or cirrhosis. The positive correlation of inflammation with duration of infection and fibrosis and of obesity with fibrosis suggest that children with chronic hepatitis C will be at risk for progressive liver disease as they age and possibly acquire other comorbid risk factors. C1 [Goodman, Zachary D.; Makhlouf, Hala R.] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Goodman, Zachary D.; Makhlouf, Hala R.] Vet Adm Special Reference, Pathol Lab, Washington, DC 20306 USA. [Liu, Lea] Maryland Med Res Inst, Baltimore, MD USA. [Bahstreri, William] Univ Cincinnati, Cincinnati, OH USA. [Bahstreri, William] Univ Florida, Gainesville, FL USA. [Gonzalez-Peralta, Regino P.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gonzalez-Peralta, Regino P.] Univ Penn, Philadelphia, PA 19104 USA. [Haber, Barbara] Childrens Hosp, Boston, MA 02115 USA. [Jonas, Maureen A.] George Washington Univ, Washington, DC USA. [Mohan, Parvathi] Indiana Univ, Indianapolis, IN 46204 USA. [Molleston, Jean P.] Univ Washington, Seattle, WA 98195 USA. [Murray, Karen F.] Univ Colorado, Denver, CO 80202 USA. [Narkewicz, Michael R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rosenthal, Philip] Columbia Univ, New York, NY USA. [Robuck, Patricia R.] NIH, Bethesda, MD 20892 USA. [Smith, Lesley J.] NIDDK, Bethesda, MD USA. [Schwarz, Kathleen B.] Johns Hopkins Univ, Baltimore, MD USA. RP Goodman, ZD (reprint author), Armed Forces Inst Pathol, 14th St & Alaska Ave NW, Washington, DC 20306 USA. EM Goodman@afip.osd.mil RI Liu, Li/K-1936-2012 OI Liu, Li/0000-0002-5054-2372 FU NIDDK NIH HHS [U01 DK067767] NR 24 TC 67 Z9 73 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2008 VL 47 IS 3 BP 836 EP 843 DI 10.1002/hep.22094 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270CZ UT WOS:000253698900010 PM 18167062 ER PT J AU Budhu, A Jia, HL Forgues, M Liu, CG Goldsteir, D Lam, A Zanetti, KA Ye, QH Qin, LY Croce, CM Tang, ZY Wang, XW AF Budhu, Anuradha Jia, Hu-Liang Forgues, Marshonna Liu, Chang-Gong Goldsteir, David Lam, Amy Zanetti, Krista A. Ye, Qing-Hai Qin, Lun-Yju Croce, Carlo M. Tang, Zhao-You Wang, Xin Wei TI Identification of metastasis-related microRNAs in hepatocellular carcinoma SO HEPATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN LUNG CANCERS; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; PROGNOSTIC SYSTEM; STAGING SYSTEMS; GROWTH; RNAS; CLASSIFICATION; PREDICTION AB MicroRNAs (miRNAs) have been used as cancer-related biomarkers. Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome largely due to metastasis and postsurgical recurrence. We investigated whether the expression of certain miRNAs are associated with HCC metastasis. We examined the miRNA expression profiles of 482 cancerous and noncancerous specimens from radical resection of 241 patients with HCC. Using a supervised algorithm and a clinically well-defined cohort of 131 cases, we built a unique 20-miRNA metastasis signature that could significantly predict (P < 0.001) primary HCC tissues with venous metastases from metastasis-free solitary tumors with 10-fold cross-validation. However, significant miRNAs could not be identified from the corresponding noncancerous hepatic tissues. A survival risk prediction analysis revealed that a majority of the metastasis-related miRNAs were associated with survival. Furthermore, the 20-miRNA tumor signature was validated in 110 additional cases as a significant independent predictor of survival (P = 0.009) and was significantly associated with both survival and relapse in 89 cases of early stage HCC (P = 0.022 and 0.002, respectively). These 20 miRNAs may provide a simple profiling method to assist in identifying patients with HCC who are likely to develop metastases/recurrence. In addition, functional analysis of these miRNAs may enhance our biological understanding of HCC metastasis. C1 [Budhu, Anuradha; Jia, Hu-Liang; Forgues, Marshonna; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Jia, Hu-Liang; Ye, Qing-Hai; Qin, Lun-Yju; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. [Jia, Hu-Liang; Ye, Qing-Hai; Qin, Lun-Yju; Tang, Zhao-You] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Liu, Chang-Gong; Croce, Carlo M.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Liu, Chang-Gong; Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Goldsteir, David] NCI, Off Sci & Technol Partnerships, Ctr Canc Res, Bethesda, MD 20892 USA. [Lam, Amy] EMMS Corp, Rockville, MD USA. [Zanetti, Krista A.] NCI, Mol Genet & Carcinogenesis Sect, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Zanetti, Krista A.] NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), 37 Convent Dr,Bldg 37,Room 3044, Bethesda, MD 20892 USA. EM Carlo.Croce@osumc.edu RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS NR 50 TC 413 Z9 467 U1 4 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAR PY 2008 VL 47 IS 3 BP 897 EP 907 DI 10.1002/hep.22160 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270CZ UT WOS:000253698900016 PM 18176954 ER PT J AU Nam-Cha, SH San-Millan, B Mollejo, M Garcia-Cosio, M Garijo, G Gomez, M Warnke, RA Jaffe, ES Piris, MA AF Nam-Cha, S. H. San-Millan, B. Mollejo, M. Garcia-Cosio, M. Garijo, G. Gomez, M. Warnke, R. A. Jaffe, E. S. Piris, M. A. TI Light-chain-restricted germinal centres in reactive lymphadenitis: report of eight cases SO HISTOPATHOLOGY LA English DT Article DE autoimmune disease; light chain restriction; reactive lymphadenitis ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; LYMPH-NODE LESIONS; B-CELL; SJOGRENS-SYNDROME; CASTLEMANS-DISEASE; FLOW-CYTOMETRY; PLASMA-CELLS; HYPERPLASIA; IMMUNOGLOBULIN; LAMBDA AB Aims: Light-chain-restricted germinal centres are generally associated with the existence of a neoplastic lymphoproliferative disorder. The aim was to present a series of cases with persistent lymph node enlargement that featured some germinal centres showing light chain immunoglobulin restriction. Methods and results: A series of six reactive lymphadenitis and two Castleman's disease cases was analysed by immunohistochemistry, IgH-polymerase chain reaction (PCR) and microdissected PCR. In all cases some germinal centres contained a population of plasma cells and plasmacytoid germinal centre cells showing light chain immunoglobulin restriction. In three cases the monotypic cells also showed distinct Bcl-2 expression. Two of the cases showed a predominant IgH rearrangement on a florid polyclonal background and one had an IgH monoclonal rearrangement, as revealed by PCR. Microdissected germinal centre PCR revealed a dominant repeated band in one of three cases and in another case a non-repeated clonal peak was observed. One of the patients developed a follicular lymphoma, which became evident from a subsequent biopsy. Conclusions: These findings may be a manifestation of an underlying disorder in the regulation of the immune response, or an exaggeration of the germinal centre oligoclonal nature. This should be taken into account in the differential diagnosis of follicular hyperplasia. C1 [Nam-Cha, S. H.; San-Millan, B.; Mollejo, M.; Piris, M. A.] CNIO, Mol Pathol Programme, Spanish Natl Canc Ctr, Lymphoma Grp, E-28029 Madrid, Spain. [Garcia-Cosio, M.] Hosp Univ Ramon & Cajal, Dept Pathol, Madrid, Spain. [Garijo, G.] Clin Benidorm, Dept Pathol, Benidorm, Spain. [Gomez, M.] Hosp Univ San Cecilo, Dept Pathol, Granada, Spain. [Warnke, R. A.] Stanford Univ, Med Ctr, Immunodiag Lab, Stanford, CA 94305 USA. [Jaffe, E. S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Nam-Cha, SH (reprint author), CNIO, Mol Pathol Programme, Spanish Natl Canc Ctr, Lymphoma Grp, C Melchor Fernandez Almagro 3, E-28029 Madrid, Spain. EM tnamcha@yahoo.es OI Piris, Miguel A/0000-0001-5839-3634 NR 29 TC 25 Z9 26 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD MAR PY 2008 VL 52 IS 4 BP 436 EP 444 DI 10.1111/j.1365-2559.2008.02965.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 269CG UT WOS:000253626500003 PM 18315596 ER PT J AU Kim, JS Romero, R Kim, MR Kim, YM Friel, L Espinoza, J Kim, CJ AF Kim, J-S Romero, R. Kim, M. R. Kim, Y. M. Friel, L. Espinoza, J. Kim, C. J. TI Involvement of Hofbauer cells and maternal T cells in villitis of unknown aetiology SO HISTOPATHOLOGY LA English DT Article DE allograft rejection; graft-versus-host disease; in-situ hybridization; placenta; villitis ID VERSUS-HOST-DISEASE; IN-SITU HYBRIDIZATION; ACTIVATED PARENCHYMAL MICROGLIA/MACROPHAGES; INFLAMMATORY INFILTRATE; NEUROLOGIC IMPAIRMENT; CD14 EXPRESSION; HUMAN-PLACENTA; LESIONS; TISSUE; MACROPHAGES AB Aims: The nature of villitis of unknown aetiology (VUE) is intriguing in terms of its aetiology, origin of inflammatory cells and immunophenotype of T cells involved. The aim was to determine the origin of macrophages and the immunophenotype of T lymphocytes in VUE associated with various complications of pregnancy. Methods and results: Placentas with VUE (n = 45) were studied by chromogenic in-situ hybridization (CISH) for Y chromosome (DYZ1) and immunohistochemistry for CD14, CD68, Ki67 (n = 10; all from male neonates) and a panel of T-cell antigens (CD3, CD4 and CD8) (n = 35). All of the placentas from male neonates showed CISH+ signals from Y chromosomes in the majority of macrophages, but not in lymphocytes, indicating that the macrophages were of fetal origin. Many macrophages of the affected chorionic villi were Ki67+, suggesting that they are hyperplastic Hofbauer cells. Among the lymphocytes, CD8+ T cells outnumbered CD4+ T cells in all placentas with different obstetrical conditions. Conclusions: We define primary components of VUE as maternal CD8+ T cells and hyperplastic Hofbauer cells. We propose that VUE is a unique inflammatory reaction where the leucocytes from two hosts are key partners, analogous to either allograft rejection or graft-versus-host disease. C1 [Kim, J-S; Romero, R.; Kim, M. R.; Kim, Y. M.; Friel, L.; Espinoza, J.; Kim, C. J.] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Kim, J-S; Romero, R.; Kim, M. R.; Kim, Y. M.; Friel, L.; Espinoza, J.; Kim, C. J.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 48201 USA. [Kim, J-S; Kim, Y. M.; Kim, C. J.] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Kim, J-S; Friel, L.; Espinoza, J.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. RP Kim, CJ (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R 4th Floor, Detroit, MI 48201 USA. EM cjkim@med.wayne.edu FU Intramural NIH HHS [Z01 HD002400-17] NR 35 TC 50 Z9 53 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD MAR PY 2008 VL 52 IS 4 BP 457 EP 464 DI 10.1111/j.1365-2559.2008.02964.x PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 269CG UT WOS:000253626500005 PM 18315598 ER PT J AU Collier, AC Tierney, C Downey, GF Eshleman, SH Kashuba, A Klingman, K Vergis, EN Pakes, GE Rooney, JF Rinehart, A Mellors, JW AF Collier, Ann C. Tierney, Camlin Downey, Gerald F. Eshleman, Susan H. Kashuba, Angela Klingman, Karin Vergis, Emanuel N. Pakes, Gary E. Rooney, James F. Rinehart, Alex Mellors, John W. CA AIDS Clinical Trials Grp Protocol TI Randomized study of dual versus single ritonavir-enhanced protease inhibitors for protease inhibitor-experienced patients with HIV SO HIV CLINICAL TRIALS LA English DT Article; Proceedings Paper CT 12th Conference on Retroviruses and Opportunistic Infections CY FEB 22-25, 2005 CL Boston, MA DE antiretroviral therapy; fosamprenavir; lopinavir; protease inhibitors; ritonavir ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; NAIVE HIV-1-INFECTED PATIENTS; CROSS-RESISTANCE; VIROLOGICAL FAILURE; CONTROLLED-TRIAL; LOPINAVIR-RITONAVIR; INFECTED PATIENTS; DRUG-RESISTANCE; OPEN-LABEL AB Purpose: To compare activity and safety of a regimen containing lopinavir/ritonavir (LPWr) + fosamprenavir (FPV) to regimens with LPWr or FPV + r and to test the hypothesis that a ritonavir-enhanced dual protease inhibitor (PI) regimen has better antiviral activity. Method: This study was a multicenter, open-label, randomized study. HIV-infected adults with prior PI failure were selectively randomized based on prior PI experience to either LPWr, FPV + r, or LPWr + FPV. All patients received tenofovir DF and 1 to 2 nucleoside reverse transcriptase inhibitors. Results: Baseline characteristics were similar across arms. Study enrollment and follow-up were stopped early (N = 56) because pharmacokinetic analyses showed significantly lower LPV and FPV exposures in the dual-PI arm. At Week 24, proportions achieving >1 log(10) decline in HIV RNA or <50 copies/mL in the dual-PI versus single-PI arms combined were 75% vs. 61% in intent-to-treat (ITT, p = .17) and 100% vs. 64% in as-treated (AT) analyses (p = .02), respectively. Median CD4+ T cell/mm(3) increases were 81 vs. 41 (ITT, p = .4) and 114 vs. 43 (AT, p = .08), respectively. Clinical events and toxicity rates were not different between arms. Conclusion: The trial was unable to show a difference between dual versus single PIs in ITT analyses but favored dual PIs in AT analyses. C1 [Collier, Ann C.] Univ Washington, Sch Med, Seattle, WA 98104 USA. [Collier, Ann C.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Tierney, Camlin; Downey, Gerald F.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kashuba, Angela] Univ N Carolina, Chapel Hill, NC USA. [Klingman, Karin] NIAID, Div Aids, Bethesda, MD 20892 USA. [Vergis, Emanuel N.] Univ Pittsburgh, Pittsburgh, PA USA. [Pakes, Gary E.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Rooney, James F.] Gilead Sci, Foster City, CA USA. [Rinehart, Alex] VircoLab Inc, Durham, NC USA. RP Collier, AC (reprint author), Univ Washington, Harborview Med Ctr, Box 359929,325 9th Ave, Seattle, WA 98104 USA. EM acollier@u.washington.edu RI Rodriguez, Benigno/C-3365-2009 OI Rodriguez, Benigno/0000-0001-9736-7957 FU NCRR NIH HHS [RR00046, RR00047, RR000750, RR00096]; NIAID NIH HHS [AI27673, AI 25879, AI025924, AI027665, AI027675, AI046376, AI046383, AI25859, AI25868, AI25897, AI27664, AI277664, AI32782, AI38855, AI38858, AI46370, AI463866, P30 AI027757] NR 38 TC 6 Z9 6 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAR-APR PY 2008 VL 9 IS 2 BP 91 EP 102 DI 10.1310/hct0902-91 PG 12 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 306ZF UT WOS:000256286400003 PM 18474494 ER PT J AU Bryson, YJ Mirochnick, M Stek, A Mofenson, LM Connor, J Capparelli, E Watts, DH Huang, S Hughes, MD Kaiser, K Purdue, L Asfaw, Y Keller, M Smith, E AF Bryson, Y. J. Mirochnick, M. Stek, A. Mofenson, L. M. Connor, J. Capparelli, E. Watts, D. H. Huang, S. Hughes, M. D. Kaiser, K. Purdue, L. Asfaw, Y. Keller, M. Smith, E. CA PACTG 353 Team TI Pharmacokinetics and safety of nelfinavir when used in combination with zidovudine and lamivudine in HIV-infected pregnant women: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 353 SO HIV CLINICAL TRIALS LA English DT Article DE HIV; nelfinavir; pregnant women ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; INCREASED RISK; NEVIRAPINE; TRANSMISSION; PLASMA; IDENTIFICATION; RESISTANCE; EXPOSURE AB Background: Combination antiretroviral regimens including nelfinavir (NFV) are commonly used in pregnancy. We studied the safety, antiviral effect, and pharmacokinetics of NFV and its M8 metabolite with two dosing regimens in combination with zidovudine (ZDV) and lamivudine (3TC) in HIV-infected pregnant women. Method: HIV-infected pregnant women between 14 and 34 weeks gestation received NFV (Cohort 1: 750 mg tid, n = 10; Cohort 2: 1250 mg bid, n = 23) with ZDV and 3TC. Serial blood sampling for NFV concentrations was performed antepartum (AP) and 6 weeks postpartum (PP). Maternal and cord blood samples were also obtained at delivery. NFV and M8 levels were determined by high-performance liquid chromatography. The pharmacokinetic (PK) target was an extrapolated NFV AUC(0-24) > 30 mu g . h/mL. Mothers were followed frequently for potential clinical and laboratory toxicity. Results: Overall, NFV in combination with ZDV and 3TC was well tolerated. The PK target was met in 3/8 AP and 5/7 PP in Cohort 1 and 17/21 AP and 16/17 PP in Cohort 2. When Cohort 2 NFV PK parameters AP and PP were compared, median C(max) (3.90 mu g/mL vs. 5.01 eta g/mL, p < .05) and AUC(0-24) (56.6 vs. 86.8 mu g . h/mL, p < .05) were increased PP and oral clearance (CI/F; 44.2 vs. 28.8 L/h, p < .05) was decreased PR The average M8/NFV ratio was increased PP compared to AP (0.085 vs. 0.29, p < .001). Placental transfer of NFV was low with a median cord blood:maternal plasma ratio at delivery of 0.05. Maternal mean CD4+ T cell counts increased significantly and plasma HIV-1 RNA levels decreased from entry to delivery and 6 to 12 weeks postpartum. Conclusion: NFV used, in combination with ZDV and 3TC was well tolerated in pregnant HIV-infected women and produced a significant improvement in HIV disease parameters. NFV drug exposure is inadequate in most pregnant women receiving 750 mg tid but is much improved with 1250 mg bid. NFV crosses the placenta poorly. The AP increase in NFV oral clearance and decrease in M8/NFV ratio suggest that CYP3A activity increases relative to CYP2C19 activity during pregnancy. C1 [Bryson, Y. J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mirochnick, M.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Stek, A.] Univ So Calif, Los Angeles, CA USA. [Mofenson, L. M.; Purdue, L.; Smith, E.] Natl Inst Hlth, Bethesda, MD USA. [Connor, J.; Capparelli, E.] Univ Calif San Diego, San Diego, CA 92103 USA. [Huang, S.; Hughes, M. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kaiser, K.] FSTRF, Buffalo, NY USA. [Asfaw, Y.] PACTG Ops, Rockville, MD USA. [Keller, M.] Harbor UCLA Med Ctr, Los Angeles, CA USA. RP Bryson, YJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM ybryson@mednet.ucla.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [M01 RR000865, M01 RR000533-310349, M01 RR000425, M01 RR000533, M01 RR000865-240402, M01-RR00425, M01-RR00865, M01RR0533, RR00533]; NIAID NIH HHS [U01 AI-41089, U01 AI027550, U01 AI027550-14, U01 AI041089, U01 AI041089-03, U01 AI27550] NR 32 TC 26 Z9 26 U1 0 U2 3 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAR-APR PY 2008 VL 9 IS 2 BP 115 EP 125 DI 10.1310/hct0902-115 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 306ZF UT WOS:000256286400005 PM 18474496 ER PT J AU Tsitouras, PD Gucciardo, F Salbe, AD Heward, C Harman, SM AF Tsitouras, P. D. Gucciardo, F. Salbe, A. D. Heward, C. Harman, S. M. TI High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL6, but does not affect other endocrine axes in healthy older adults SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE omega-3; diet; insulin; CRP; IL6; hormones ID HORMONE-RELEASING HORMONE; HUMAN CHORIONIC-GONADOTROPIN; AGE-RELATED ALTERATIONS; GROWTH-FACTOR-I; FISH-OIL; LUTEINIZING-HORMONE; GLUCOSE-METABOLISM; AGING MEN; REPRODUCTIVE HORMONES; RHEUMATOID-ARTHRITIS AB Aging diminishes hormone secretion and target cell responsiveness, possibly due to loss of cell membrane fluidity or alteration of membrane phospholipids affecting signal transduction. We investigated whether a high omega-3 polyunsaturated fatty acid diet would improve endocrine function in 6 men and 6 women aged over 60 years. Subjects first ate an isocaloric control diet for 6 weeks, followed by an 8-week experimental diet, which included 720 g of fatty fish weekly plus 15ml of sardine oil daily. In the last week, we measured RBC membrane fatty acids on each diet, performed pituitary, adrenal, hepatic, and Leydig cell endocrine provocative testing, and assayed selected cytokines. We also assessed insulin sensitivity utilizing octreotide insulin suppression testing and assessed free fatty acid (FFA) responses to isoproteronol. Insulin sensitivity increased significantly after 8 weeks on the omega-3 diet and FFA responses trended lower. Serum C-reactive protein was significantly reduced and a trend towards lower IL-6 was noted. No differences were found in other metabolic parameters, adiponectin levels, or hormone responses. We conclude that, in older people, high omega-3 consumption increases insulin sensitivity, may reduce FFA mobilization by catecholamines, and reduces inflammatory markers, but did not alter endocrine responsiveness after 8 weeks. C1 [Tsitouras, P. D.; Gucciardo, F.; Harman, S. M.] Kronos Longev Res Inst, Phoenix, AZ 85016 USA. [Salbe, A. D.] NIDDK, Obes & Diabetes Clin Res Sect, NIH, Phoenix, AZ USA. [Heward, C.] Kronos Sci Labs, Phoenix, AZ USA. RP Tsitouras, PD (reprint author), Kronos Longev Res Inst, 2390 E Camelback Rd,Suite 440, Phoenix, AZ 85016 USA. EM tsitouras@kronosinstitute.org FU Intramural NIH HHS; NIDDK NIH HHS [P01 DK-68829] NR 65 TC 77 Z9 80 U1 1 U2 7 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD MAR PY 2008 VL 40 IS 3 BP 199 EP 205 DI 10.1055/s-2008-1046759 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 286IY UT WOS:000254840800007 PM 18348080 ER PT J AU Samuni, Y Cawley, NX Zheng, CY Cotrim, AP Loh, YP Baum, BJ AF Samuni, Yuval Cawley, Niamh X. Zheng, Changyu Cotrim, Ana P. Loh, Y. Peng Baum, Bruce J. TI Sorting behavior of a transgenic erythropoietin - Growth hormone fusion protein in murine salivary glands SO HUMAN GENE THERAPY LA English DT Article ID REGULATED SECRETORY PATHWAY; RAT SUBMANDIBULAR-GLANDS; MEDIATED GENE-TRANSFER; GOLGI NETWORK; IN-VIVO; ENDOCRINE SECRETION; CARBOXYPEPTIDASE-E; EPITHELIAL-CELLS; ORAL MUCOSITIS; THERAPEUTICS AB Salivary glands are useful gene transfer target sites for the production of therapeutic proteins, and can secrete proteins into both saliva and the bloodstream. The mechanisms involved in this differential protein sorting are not well understood, although it is believed, at least in part, to be based on the amino acid sequence of the encoded protein. We hypothesized that a transgenic protein, human erythropoietin (hEpo), normally sorted from murine salivary glands into the bloodstream, could be redirected into saliva by fusing it with human growth hormone (hGH). After transfection, the hEpo - hGH fusion protein was expressed and glycosylated in both HEK 293 and A5 cells. When packaged in an adenovirus serotype 5 vector and delivered to murine submandibular cells in vivo via retroductal cannulation, the hEpo - hGH fusion protein was also expressed, albeit at similar to 26% of the levels of hEpo expression. Importantly, in multiple experiments with different cohorts of mice, the hEpo - hGH fusion protein was sorted more frequently into saliva, versus the bloodstream, than was the hEpo protein (p < 0.001). These studies show it is possible to redirect the secretion of a transgenic constitutive pathway protein from salivary gland cells after gene transfer in vivo, a finding that may facilitate developing novel treatments for certain upper gastrointestinal tract disorders. C1 [Samuni, Yuval; Zheng, Changyu; Cotrim, Ana P.; Baum, Bruce J.] NIDCR, GTTB, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Cawley, Niamh X.; Loh, Y. Peng] NICHHD, Cellular Neurobiol Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, Dept Hlth & Human Serv, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Intramural NIH HHS [, Z01 DE000336-27] NR 42 TC 9 Z9 9 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 2008 VL 19 IS 3 BP 279 EP 286 DI 10.1089/hum.2007.0136 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 282PI UT WOS:000254579300007 PM 18303958 ER PT J AU Gaudet, MM Lacey, JV Lissowska, J Peplonska, B Brinton, LA Chanock, S Garcia-Closas, M AF Gaudet, Mia M. Lacey, James V., Jr. Lissowska, Jolanta Peplonska, Beata Brinton, Louise A. Chanock, Stephen Garcia-Closas, Montserrat TI Genetic variation in CYP17 and endometrial cancer risk SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HORMONE-LEVELS; POLYMORPHISM; GENOTYPE; LOCUS; WOMEN; 8Q24; BIAS AB Genetic variation in CYP17 is suspected to be related to endometrial cancer risk based on its role in the regulation of steroid and non-steroid hormone biosynthesis. Reported associations between CYP17 and higher levels of estradiol in some studies suggest that the C allele of a T-to-C single nucleotide polymorphism (SNP) in the 5'UTR of CYP17 (rs743572) may be associated with an increased risk of hormone-related cancers. However, five relatively small epidemiologic studies of endometrial cancer have reported that women with the rs743572 C allele have a decreased risk of endometrial cancer. To examine this association, we genotyped rs743572 and eight other haplotype-tagging SNPs (htSNPs), which are estimated to capture > 80% of the variation in CYP17 in a population-based study of 497 endometrial cancer cases and 1,024 controls in Poland. Significant associations were not found for rs743572 (per C allele: OR = 1.12, 95%CI 0.96-1.30; P-trend = 0.15), for individual htSNPs, or for extended haplotypes (global P-value = 0.60). When we pooled data from previously published studies with our own (a total of 1,004 endometrial cases and 1,907 controls), we observed significant study heterogeneity in summary estimates of the association between rs743572 and endometrial cancer, as well as evidence of publication bias. In conclusion, our data are not consistent with a decreased endometrial cancer risk associated with rs743572, as previously reported, or with other haplotype-tagging polymorphisms. Further evaluation in consortia is necessary to confirm potential weak associations between common variation in CYP17 and endometrial cancer risk and to address the concern of publication bias. C1 [Gaudet, Mia M.] Natl Canc Inst, Rockville, MD 20852 USA. [Gaudet, Mia M.; Lacey, James V., Jr.; Lissowska, Jolanta; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat] NIH, Natl Canc Inst, Bethesda, MD 20892 USA. [Lissowska, Jolanta] Ctr Canc, Marie Curie Sklodowska Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. [Chanock, Stephen] Adv Technol Ctr, NIH, Natl Canc Inst, Dept Hlth & Human Serv,Core Genotype Facil, Bethesda, MD USA. RP Gaudet, MM (reprint author), Natl Canc Inst, 6120 Executive Blvd, Rockville, MD 20852 USA. EM gaudetm@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 29 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 2008 VL 123 IS 2 BP 155 EP 162 DI 10.1007/s00439-007-0454-8 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 263EM UT WOS:000253200400004 PM 18172694 ER PT J AU Chulada, PC Vahdat, HL Sharp, RR DeLozier, TC Watkins, PB Pusek, SN Blackshear, PJ AF Chulada, Patricia C. Vahdat, Heather L. Sharp, Richard R. DeLozier, Tracy C. Watkins, Paul B. Pusek, Susan N. Blackshear, Perry J. TI The environmental polymorphisms registry: A DNA resource to study genetic susceptibility loci SO HUMAN GENETICS LA English DT Article ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; HUMAN GENOME; GENERAL-POPULATION; SEQUENCE VARIATION; PROJECT; EXPERIENCE; CONSENT; VARIANT; HEALTH AB The National Institute of Environmental Health Sciences is establishing a DNA repository named the Environmental Polymorphisms Registry (EPR). The goal is to recruit 20,000 subjects from the greater Research Triangle Park region of North Carolina and collect a sample of each subject's DNA for genetic study. Personal information is obtained from each EPR subject and linked to their sample in coded form. Once individuals with the genotypes of interest are identified, their samples are decoded, and their names and contact information are given to scientists for follow-up studies in which genotype is important. "Recruit-by-genotype" resources such as the EPR require a transparent consent process and rigorous human subjects protection measures. Unlike the EPR, most US DNA resources are anonymous. Once scientists identify potentially significant genetic variants, they must screen new populations to find individuals with the variants of interest to study. The EPR eliminates this time consuming and expensive step. In designing the EPR, consideration was given to achieving high response rates, minimizing attrition and maximizing usefulness for future research studies. Subjects are recruited from outpatient clinics in area medical centers as well as from the general population to ascertain individuals in diverse states of health. Data are collected on race, ethnicity, gender and age, and are monitored for demographic diversity. As of November 2007, 7,788 individuals have been recruited into the EPR and their DNA samples have been used in numerous genetic studies. EPR subjects have also been solicited for several follow-up studies with high response rates (> 90%). The success of the EPR based on the number of subjects recruited and genetic studies underway, suggests that it will be a model for future DNA resources. C1 [Chulada, Patricia C.; Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Clin Res Program, Res Triangle Pk, NC 27709 USA. [Vahdat, Heather L.] Family Hlth Int, Res Triangle Pk, NC 27709 USA. [Sharp, Richard R.] Cleveland Clin, Dept Bioeth, Cleveland, OH 44195 USA. [DeLozier, Tracy C.] Integrated Lab Syst Inc, Durham, NC 27713 USA. [Watkins, Paul B.; Pusek, Susan N.] Univ N Carolina Hosp, Gen Clin Res Ctr, Chapel Hill, NC 27599 USA. RP Chulada, PC (reprint author), Natl Inst Environm Hlth Sci, Clin Res Program, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM chulada@niehs.nih.gov FU NCRR NIH HHS [RR000046] NR 34 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 2008 VL 123 IS 2 BP 207 EP 214 DI 10.1007/s00439-007-0457-5 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 263EM UT WOS:000253200400009 PM 18193459 ER PT J AU Wendland, JR Moya, PR Kruse, MR Ren-Patterson, RF Jensen, CL Timpano, KR Murphy, DL AF Wendland, Jens R. Moya, Pablo R. Kruse, Matthew R. Ren-Patterson, Renee F. Jensen, Catherine L. Timpano, Kiara R. Murphy, Dennis L. TI A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive-compulsive disorder SO HUMAN MOLECULAR GENETICS LA English DT Article ID SEROTONIN TRANSPORTER GENE; POLYMORPHISM 5-HTTLPR; REGION POLYMORPHISM; REGULATORY REGION; VARIANTS; SUSCEPTIBILITY; DISEQUILIBRIUM; EXPRESSION AB Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric illness with strong segregation data indicative of major genetic contributions. Association analyses of common functional variants of the serotonin transporter gene (SLC6A4), a long-standing OCD candidate, have so far been inconsistent. Here, we set out to investigate the role of additional functional SLC6A4 loci in OCD. We describe a common, functional C > T single nucleotide polymorphism, rs25532, located less than 150 nucleotides centromeric of the serotonin transporter-linked polymorphic region indel known as 5-HTTLPR. The minor allele of rs25532 significantly decreased luciferase reporter gene expression levels by 15-80%, depending on 5-HTTLPR allele background and cell type. Haplotype-based testing of rs25532 and all other known non-coding functional SLC6A4 variants revealed a highly significant omnibus association with OCD in a large case-control sample. Remarkably, the haplotype significantly overrepresented in probands contained the higher-expressing allele at each locus, supporting the notion of increased serotonin transporter functioning being pathogenetically involved in OCD. Conditional haplotype analyses with the software WHAP revealed that this association is primarily driven by 5-HTTLPR, rs25532 and rs16965628. Our results contribute to a better understanding of SLC6A4 expression genetics and provide a functional haplotype framework for future serotonin-related studies. C1 [Wendland, Jens R.; Moya, Pablo R.; Kruse, Matthew R.; Jensen, Catherine L.; Murphy, Dennis L.] NIMH, NIH, Clin Sci Lab, Bethesda, MD 20892 USA. [Ren-Patterson, Renee F.] NIMH, NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Timpano, Kiara R.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. RP Wendland, JR (reprint author), NIMH, NIH, Clin Sci Lab, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. EM wendlandj@mail.nih.gov RI Wendland, Jens/A-1809-2012; Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722 FU Intramural NIH HHS NR 29 TC 72 Z9 74 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2008 VL 17 IS 5 BP 717 EP 723 DI 10.1093/hmg/ddm343 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 267DV UT WOS:000253490600008 PM 18055562 ER PT J AU Cronin, S Berger, S Ding, JH Schymick, JC Washecka, N Hernandez, DG Greenway, MJ Bradley, DG Traynor, BJ Hardiman, O AF Cronin, Simon Berger, Stephen Ding, Jinhui Schymick, Jennifer C. Washecka, Nicole Hernandez, Dena G. Greenway, Matthew J. Bradley, Daniel G. Traynor, Bryan J. Hardiman, Orla TI A genome-wide association study of sporadic ALS in a homogenous Irish population SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; LINKAGE DISEQUILIBRIUM; WHOLE-GENOME; PROTEIN; GENE; SUSCEPTIBILITY; MUTATIONS; ORIGINS; FORM; LD AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive limb or bulbar weakness. Efforts to elucidate the disease-associated loci have to date produced conflicting results. One strategy to improve power in genome-wide studies is to genotype a genetically homogenous population. Such a population exhibits extended linkage disequilibrium (LD) and lower allelic heterogeneity to facilitate disease gene mapping. We sought to identify associated variants for ALS in the Irish, a stable population of relatively homogenous genetic background, and to replicate these findings in larger genetically out-bred populations. We conducted a genome-wide association study in 432 Irish individuals using Illumina HumanHap 550K single nucleotide polymorphism chips. We demonstrated extended LD and increased homogeneity in the Irish sample when compared to an out-bred population of mixed European ancestry. The Irish scan identified 35 loci associated with P-values below 0.0001. For replication, we identified seven chromosomal regions commonly associated in a joint analysis of genome-wide data on 958 ALS cases and 932 controls from Ireland and the previously published datasets from the US and The Netherlands. When pooled, the strongest association was a variant in the gene encoding DPP6, a component of type A neuronal transmembrane potassium channels. Further confirmation of the candidate loci is warranted in additional genome-wide datasets. We have made our individual genotyping data publicly available, contributing to a powerful world-wide resource to refine our understanding of the genetics of sporadic ALS. C1 [Cronin, Simon; Greenway, Matthew J.; Hardiman, Orla] Beaumont Hosp, Dept Neurol, Irish ALS Res Grp, Dublin 9, Ireland. [Greenway, Matthew J.; Hardiman, Orla] Royal Coll Surgeons Ireland, Dept Clin Neurol Sci, Dublin 2, Ireland. [Berger, Stephen; Schymick, Jennifer C.; Washecka, Nicole; Hernandez, Dena G.; Traynor, Bryan J.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Ding, Jinhui] Natl Mol Genet Unit, Neurogenet Lab, Bethesda, MD USA. [Traynor, Bryan J.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, Bethesda, MD USA. [Traynor, Bryan J.] NIH, Mol Genet Unit, Bethesda, MD 20892 USA. [Schymick, Jennifer C.] Univ Oxford, Dept Physiol Anat & Genet, Henry Wellcome Bldg Gene Funct, Oxford, England. [Traynor, Bryan J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Hardiman, Orla] Univ Dublin Trinity Coll, Inst Neurosci, Dublin 2, Ireland. RP Cronin, S (reprint author), Beaumont Hosp, Dept Neurol, Irish ALS Res Grp, Dublin 9, Ireland. EM scronin@rcsi.ie RI Bradley, Daniel/A-3240-2012; Traynor, Bryan/G-5690-2010; OI Bradley, Daniel G/0000-0001-7335-7092; Hardiman, Orla/0000-0003-2610-1291 FU Intramural NIH HHS NR 36 TC 113 Z9 118 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2008 VL 17 IS 5 BP 768 EP 774 DI 10.1093/hmg/ddm361 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 267DV UT WOS:000253490600013 PM 18057069 ER PT J AU Jiang, BM Wang, YH Saluzzo, JF Bargeron, K Frachette, MJ Glass, RI AF Jiang, Baoming Wang, Yuhuan Saluzzo, Jean-Francois Bargeron, Kristina Frachette, Marie-Joelle Glass, Roger I. TI Immunogenicity of a thermally inactivated rotavirus vaccine in mice SO HUMAN VACCINES LA English DT Article DE rotavirus; thermal inactivation; parenteral vaccine; immunogenicity ID PROTECTIVE IMMUNITY; ANTIBODY-RESPONSES; GNOTOBIOTIC PIGS; INFECTION; CHALLENGE; PARTICLES; CHILDREN; ANTIGENS AB Current approaches to the prevention of severe rotavirus diarrhea and deaths in children have all been through the use of live oral vaccines. To develop a safe and effective inactivated rotavirus vaccine ( IRV), a new simple, rapid and robust method for the inactivation is critical and essential because chemical inactivation commonly used for a number of killed vaccines has been a chal lenge and problematic for rotavirus. We have examined an array of thermal conditions and demonstrated that purified YK-1 rotavirus in diluent buffer can be completely inactivated by heat treatment, as evidenced by the lack of virus growth in two successive passages in cell culture. Unlike chemical treatment that often causes physical and biochemical damages to viruses, thermally inactivated rotavirus particles maintained their structural, biochemical and antigenic integrity. A two-dose intramuscular administration of thermally inactivated YK-1 rotavirus without adjuvant resulted in high titers of total and neutralizing antibody in serum of mice. Adjuvant Al(OH)(3) further led to enhanced antibody titers and also dramatically lowered the amount of antigens in the vaccine formulation. Our results demonstrate the potential of heat inactivation as a novel approach to the manufacture of a safe and efficacious parenteral rotavirus vaccine, which should serve as an important addition to and back up for live oral rotavirus vaccine in children. C1 [Jiang, Baoming; Wang, Yuhuan; Bargeron, Kristina; Glass, Roger I.] Ctr Dis Control & Prevent, Div Viral Dis, Gastroenteritis & Resp Virus Lab Branch, Atlanta, GA USA. [Saluzzo, Jean-Francois] Sanofi Pasteur, Lyon, France. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Jiang, BM (reprint author), Natl Ctr Immunizat & Resp Dis, Viral Gastroenteritis Team, Mailstop G04,1600 Clifton Road, Atlanta, GA 30333 USA. EM Baoming.Jiang@cdc.hhs.gov RI Clark, Kristina/G-2821-2016 OI Clark, Kristina/0000-0002-8829-9793 NR 28 TC 20 Z9 23 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8619 J9 HUM VACCINES JI Hum. Vaccines PD MAR-APR PY 2008 VL 4 IS 2 BP 143 EP 147 PG 5 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 317DY UT WOS:000257001100009 PM 18382129 ER PT J AU Wink, DA Paolocci, N AF Wink, David A. Paolocci, Nazareno TI Mother was right: Eat your vegetables and do not spit! When oral nitrate helps with high blood pressure SO HYPERTENSION LA English DT Article ID ISCHEMIA-REPERFUSION; NITRIC-OXIDE; REDUCTION C1 [Wink, David A.] NCI, Radiat Biol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Paolocci, Nazareno] Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21205 USA. [Paolocci, Nazareno] Univ Perugia, Dept Clin & Expt Med, I-06100 Perugia, Italy. [Paolocci, Nazareno] Univ Perugia, Gen Pathol & Immunol Sect, I-06100 Perugia, Italy. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Natl Inst Hlth, Bldg 10 Room B3-B35, Bethesda, MD 20892 USA. EM wink@mail.nih.gov OI Paolocci, Nazareno/0000-0001-7011-997X FU Intramural NIH HHS; NHLBI NIH HHS [HL075265] NR 11 TC 7 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2008 VL 51 IS 3 BP 617 EP 619 DI 10.1161/HYPERTENSIONAHA.107.106617 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 266IR UT WOS:000253428200007 PM 18250359 ER PT J AU Wyatt, SB Akylbekova, EL Wofford, MR Coady, SA Walker, ER Andrew, ME Keahey, WJ Taylor, HA Jones, DW AF Wyatt, Sharon B. Akylbekova, Ermeg L. Wofford, Marion R. Coady, Sean A. Walker, Evelyn R. Andrew, Michael E. Keahey, Wanda J. Taylor, Herman A. Jones, Daniel W. TI Prevalence, awareness, treatment, and control of hypertension in the Jackson Heart Study SO HYPERTENSION LA English DT Article DE hypertension; detection and control; population; epidemiology; blood pressure; ethnicity ID HIGH BLOOD-PRESSURE; UNITED-STATES; CARDIOVASCULAR-DISEASE; AFRICAN-AMERICANS; MANAGEMENT; RISK; DISPARITIES; POPULATION; PREVENTION; REDUCTION AB African Americans have higher reported hypertension prevalence and lower control rates than other ethnic groups in the United States. Hypertension prevalence, awareness, treatment, and control (outcomes) and potentially associated demographic, lifestyle, comorbidity, and health care access factors were examined in 5249 adult participants (3362 women and 1887 men) aged 21 to 94 years enrolled in the Jackson Heart Study. Hypertension prevalence (62.9%), awareness (87.3%), treatment (83.2%), and control (66.4%) were high. Control declined with advancing age; estimates for all of the outcomes were higher for women compared with men. Lower socioeconomic status was associated with prevalence and control. Smoking was negatively associated with awareness and treatment, particularly among men. Comorbidities (diabetes, chronic kidney disease, and cardiovascular disease), likely driven by the high rates of obesity, correlated with hypertension prevalence, awareness, treatment, and control. Lack of health insurance was marginally associated with poorer control, whereas use of preventive care was positively associated with prevalence, awareness, and treatment, particularly among men. In comparisons with the 1994-2004 National Health and Nutrition Examination Survey data adjusted to Jackson Heart Study sex, age, and socioeconomic status distribution, control rates among Jackson Heart Study participants appeared to be higher than in their national counterparts and similar to that of whites. These results suggest that public health efforts to increase awareness and treatment among African Americans have been relatively effective. The Jackson Heart Study data indicate that better control rates can be achieved in this high-risk population. C1 [Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. [Wyatt, Sharon B.; Wofford, Marion R.; Jones, Daniel W.] Univ Mississippi, Med Ctr, Div Hypertens, Jackson, MS 39216 USA. [Taylor, Herman A.] Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA. [Wyatt, Sharon B.; Wofford, Marion R.; Keahey, Wanda J.; Taylor, Herman A.; Jones, Daniel W.] Univ Mississippi, Med Ctr, Sch Med, Jackson Heart Study Examinat Ctr, Jackson, MS 39216 USA. [Keahey, Wanda J.] Univ Mississippi, Med Ctr, Dept Pharm Serv, Jackson, MS 39216 USA. [Akylbekova, Ermeg L.; Keahey, Wanda J.; Taylor, Herman A.] Jackson State Univ, Jackson Heart Study Coordinating Ctr, Jackson, MS USA. [Coady, Sean A.] NHLBI, Div Populat & Prevent Sci, Bethesda, MD 20892 USA. [Walker, Evelyn R.] NHLBI, Jackson Heart Study Field Ctr, Jackson, MS USA. [Andrew, Michael E.] NIOSH, Ctr Dis Control, Morgantown, WV USA. [Taylor, Herman A.] Tougaloo Coll, Jackson Heart Study Undergrad Training Ctr, Jackson, MS USA. RP Wyatt, SB (reprint author), Univ Mississippi, Med Ctr, Sch Nursing, 2500 N State St, Jackson, MS 39216 USA. EM swyatt@son.umsmed.edu FU NHLBI NIH HHS [N01-HC-95171, N01-HC-95172, N01 HC095171, N01-HC-95170] NR 35 TC 77 Z9 80 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2008 VL 51 IS 3 BP 650 EP 656 DI 10.1161/HYPERTENSIONAHA.107.100081 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 266IR UT WOS:000253428200015 PM 18268140 ER PT J AU Keator, DB Grethe, JS Marcus, D Ozyurt, B Gadde, S Murphy, S Pieper, S Greve, D Notestine, R Bockholt, HJ Papadopoulos, P AF Keator, David B. Grethe, J. S. Marcus, D. Ozyurt, B. Gadde, S. Murphy, Sean Pieper, S. Greve, D. Notestine, R. Bockholt, H. J. Papadopoulos, P. CA BIRN Funct BIRN Morphometry BIRN Coordinating TI A national human neuroimaging collaboratory enabled by the Biomedical Informatics Research Network (BIRN) SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE Biomedical Informatics Research Network (BIRN); cyberinfrastructure; database; data grid; Extensible Markup Language (XML); Extensible Markup Language (XML)-based clinical experiment data exchange schema (XCEDE); Extensible Neuroimaging Archive Toolkit (XNAT); globus; high intensity discharge (RID); informatics; magnetic resonance imaging (MRI); neuroimage; storage resources broker (SRB) AB The aggregation of imaging, clinical, and behavioral data from multiple independent institutions and researchers presents both a great opportunity for biomedical research as well as a formidable challenge. Many research groups have well-established data collection and analysis procedures, as well as data and metadata format requirements that are particular to that group. Moreover, the types of data and metadata collected are quite diverse, including image, physiological, and behavioral data, as well as descriptions of experimental design, and preprocessing and analysis methods. Each of these types of data utilizes a variety of software tools for collection, storage, and processing. Furthermore sites are reluctant to release control over the distribution and access to the data and the tools. To address these needs, the Biomedical Informatics Research Network (BIRN) has developed a federated and distributed infrastructure for the storage, retrieval, analysis, and documentation of biomedical imaging data. The infrastructure consists of distributed data collections hosted on dedicated storage and computational resources located at each participating site, a federated data management system and data integration environment, an Extensible Markup Language (XML) schema for data exchange, and analysis pipelines, designed to leverage both the distributed data management environment and the available grid computing resources. C1 [Keator, David B.] Univ Calif Irvine, Irvine, CA 92697 USA. [Grethe, J. S.; Ozyurt, B.; Notestine, R.; Papadopoulos, P.] Univ Calif San Diego, San Diego, CA 92093 USA. [Marcus, D.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Gadde, S.] Duke Univ, Durham, NC 27708 USA. [Murphy, Sean] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA 02115 USA. [Pieper, S.] Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. [Greve, D.] Massachusetts Gen Hosp, Dept Radiol, Ctr Magnet Resonance Imaging, Boston, MA 02115 USA. [Bockholt, H. J.] Med Invest Neurodev Disorders MIND Inst, Albuquerque, NM 87131 USA. NIH, Natl Ctr Res Resources, Biomed Informat Res Network, Bethesda, MD 20892 USA. RP Keator, DB (reprint author), Univ Calif Irvine, Irvine, CA 92697 USA. EM dbkeator@uci.edu; jgrethe@ncmir.ucsd.edu; dmarcus@npg.wustl.edu; iozyurt@ucsd.edu; gadde@biac.duke.edu; pieper@bwh.harvard.edu; greve@nmr.mgh.harvard.edu; RNotestine@ucsd.edu; jbockholt@themindinstitute.org; phil@sdsc.edu OI Grethe, Jeffrey/0000-0001-5212-7052 FU NCRR NIH HHS [U24 RR021992, U24 RR021992-02] NR 21 TC 59 Z9 59 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD MAR PY 2008 VL 12 IS 2 BP 162 EP 172 DI 10.1109/TITB.2008.917893 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 272DW UT WOS:000253840600005 PM 18348946 ER PT J AU Stewart, DM Tian, L Notarangelo, LD Nelson, DL AF Stewart, Donn M. Tian, Lan Notarangelo, Luigi D. Nelson, David L. TI X-linked hypogammaglobulinemia and isolated growth hormone deficiency: an update SO IMMUNOLOGIC RESEARCH LA English DT Article DE X-chromosome; hypogammaglobulinemia; growth hormone; B-cells; Bruton's tyrosine kinase; Btk; myeloid elf-1-like factor; MEF ID BRUTONS TYROSINE KINASE; TRANSCRIPTION FACTOR; GENE-CLUSTER; BTK GENE; AGAMMAGLOBULINEMIA; PATIENT; PROTEIN; MEF; EXPRESSION AB X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLH-GHD, OMIM # 307200) is a primary immunodeficiency disorder characterized by pan-hypogammaglobulinemia and isolated growth hormone deficiency. The disease, which is only known to occur in a single family, shares many features with X-linked agammaglobulinemia (XLA, OMIM # 300300). The current review summarizes the clinical, laboratory, and genetic features of the disease as they have unfolded over the past quarter-century since its description. C1 [Stewart, Donn M.; Tian, Lan; Notarangelo, Luigi D.; Nelson, David L.] NCI, Natl Inst Hlth, CCR,Metab Branch, Immunophysiol Sect, Bethesda, MD 20892 USA. [Notarangelo, Luigi D.] Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA USA. [Notarangelo, Luigi D.] Univ Brescia, Ist Med Mol Angelo Nocivelli, Pediat Clin, I-25123 Brescia, Italy. RP Nelson, DL (reprint author), NCI, Natl Inst Hlth, CCR,Metab Branch, Immunophysiol Sect, Bldg 10,Rm 4N115,MSC 1374, Bethesda, MD 20892 USA. EM dln@helix.nih.gov RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 31 TC 7 Z9 9 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PD MAR PY 2008 VL 40 IS 3 BP 262 EP 270 DI 10.1007/s12026-007-0028-9 PG 9 WC Immunology SC Immunology GA 262DK UT WOS:000253129000006 PM 18180883 ER PT J AU Bodnar, A Nizsaloczki, E Mocsar, G Szaloki, N Waldmann, TA Damjanovich, S Vamosi, G AF Bodnar, Andrea Nizsaloczki, Eniko Mocsar, Gabor Szaloki, Nikoletta Waldmann, Thomas A. Damjanovich, Sandor Vamosi, Gyoergy TI A biophysical approach to IL-2 and IL-15 receptor function: Localization, conformation and interactions SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 14th Symposium on Signals and Signal Processing in the Immune System CY SEP, 2007 CL Balatonoszod, HUNGARY SP EFIS, EJI DE IL-2 and IL-15 receptors; protein-protein interactions; receptor patterns; structure determination; X-ray crystallography; FRET; fluorescence correlation spectroscopy; near-field scanning optical microscopy; confocal microscopy ID RESONANCE ENERGY-TRANSFER; MEMORY T-CELLS; INTERLEUKIN-2 RECEPTOR; GAMMA-CHAIN; BETA-CHAIN; ALPHA-CHAIN; LIPID RAFTS; IL-15R-ALPHA CHAIN; CYTOKINE-RECEPTOR; PLASMA-MEMBRANE AB Interleukin-2 and interleukin-15 (IL-2, IL-15) are key participants in T and NK cell activation and function. Sharing the beta and gamma receptor subunits results in several common functions: e.g. the promotion of T cell proliferation. On the other hand, due to their distinct alpha receptor subunits, they also play opposing roles in immune processes such as activation induced cell death and immunological memory. Divergence of signaling pathways must ensue already at the plasma membrane where the cytokines interact with their receptors. Therefore understanding molecular details of receptor organization and mapping interactions with other membrane proteins that might influence receptor conformation and function, are of key importance. Biophysical/advanced microscopic methods (fluorescence resonance energy transfer (FRET), fluorescence crosscorrelation spectroscopy (FCCS), near-field scanning optical microscopy (NSOM), X-ray crystallography, surface plasmon resonance, NMR spectroscopy) have been instrumental in clarifying the details of receptor structure and organization from the atomic level to the assembly and dynamics of supramolecular clusters. In this short review some important contributions shaping our current view of IL-2 and IL-15 receptors are presented. (C) 2008 Elsevier B.V. All rights reserved. C1 [Bodnar, Andrea; Nizsaloczki, Eniko; Mocsar, Gabor; Szaloki, Nikoletta; Damjanovich, Sandor; Vamosi, Gyoergy] Univ Debrecen, Hungarian Acad Sci, Res Ctr Mol Med, Dept Biophys & Cell Biol,Cell Biol & Signalling R, H-4012 Debrecen, Hungary. [Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Damjanovich, S (reprint author), Univ Debrecen, Hungarian Acad Sci, Res Ctr Mol Med, Dept Biophys & Cell Biol,Cell Biol & Signalling R, Nagyerdei Krt 98, H-4012 Debrecen, Hungary. EM dami@dote.hu RI Vamosi, Gyorgy/C-9351-2009; Bodnar, Andrea/A-9286-2011; Damjanovich, Sandor/A-9284-2011 NR 108 TC 25 Z9 26 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD MAR PY 2008 VL 116 IS 2 BP 117 EP 125 DI 10.1016/j.imlet.2007.12.014 PG 9 WC Immunology SC Immunology GA 289ZK UT WOS:000255092200004 PM 18280585 ER PT J AU Gillette, JM Gibbs, CP Nielsen-Preiss, SM AF Gillette, Jennifer M. Gibbs, C. Parker Nielsen-Preiss, Sheila M. TI Establishment and characterization of OS 99-1, a cell line derived from a highly aggressive primary human osteosarcoma SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE osteosarcoma; osteoblast; mineralization; cell line; tumorigenicity ID CYTOGENETIC FINDINGS; OSTEOGENIC-SARCOMA; BONE; GENE; METASTASIS; CARCINOMA; SPECIMENS; PROTEINS; TIME AB Osteosarcoma is the most common form of primary bone cancer. In this study, we established a human osteosarcoma cell line (OS 99-1) from a highly aggressive primary tumor. G-banding karyotype analysis demonstrated a large number of clonal abnormalities, as well as extensive intercellular heterogeneity. Through the use of immunologic, molecular, and biochemical analyses, we characterized protein and gene expression profiles confirming the osteogenic nature of the cells. Further evaluation indicated that OS 99-1 cells maintain the capacity to differentiate in an in vitro mineralization assay as well as form tumors in the in vivo chicken embryo model. This cell line provides a useful tool to investigate the molecular mechanisms contributing to osteosarcoma and may have the potential to serve as a culture system for studies involving bone physiology. C1 [Nielsen-Preiss, Sheila M.] Montana State Univ, Dept Cell Biol & Neurosci, Bozeman, MT 59717 USA. [Gibbs, C. Parker] Univ Florida, Dept Orthopaed & Rehabil, Gainesville, FL 32607 USA. [Gillette, Jennifer M.] NICHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Nielsen-Preiss, SM (reprint author), Montana State Univ, Dept Cell Biol & Neurosci, POB 173148, Bozeman, MT 59717 USA. EM Sheila.nielsenpreiss@montana.edu FU NIAMS NIH HHS [R03 AR052898-01] NR 29 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAR-APR PY 2008 VL 44 IS 3-4 BP 87 EP 95 DI 10.1007/s11626-007-9075-8 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 283GE UT WOS:000254623900007 PM 18247100 ER PT J AU Elmore, E Jain, A Steele, VE Redpath, JL AF Elmore, Eugene Jain, Aarti Steele, Vernon E. Redpath, J. Leslie TI Responses of pineapple stem bromelain in a human cell screening assay for melanoma prevention SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Elmore, Eugene; Jain, Aarti; Redpath, J. Leslie] Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. [Elmore, Eugene; Redpath, J. Leslie] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA. [Steele, Vernon E.] NCI, DCP, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. EM eelmore@uci.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2008 VL 44 SU S BP S31 EP S32 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 338XL UT WOS:000258542600084 ER PT J AU Schloss, JA AF Schloss, J. A. TI Next generation sequencing technologies, their implications, and prospects for next-next gen technologies SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Schloss, J. A.] NHGRI, Div Extramural Res, NIH, Bethesda, MD 20892 USA. EM js173g@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2008 VL 44 SU S BP S2 EP S3 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 338XL UT WOS:000258542600006 ER PT J AU Venuti, P De Falco, S Giusti, Z Bornstein, MH AF Venuti, Paola De Falco, Simona Giusti, Zeno Bornstein, Marc H. TI Play and emotional availability in young children with Down syndrome SO INFANT MENTAL HEALTH JOURNAL LA English DT Article ID TYPICALLY DEVELOPING-CHILDREN; SYMBOLIC PLAY; COMMUNICATION-SKILLS; ATTACHMENT REPRESENTATIONS; NONVERBAL-COMMUNICATION; INFANT INTERACTION; JOINT ATTENTION; PRETEND PLAY; MOTHER; LANGUAGE AB This study investigates mother-child interaction and its associations with play in children with Down syndrome (DS). There is consensus that mother-child interaction during play represents an important determinant of typical children's play development. Concerning children with DS, few studies have investigated mother-child interaction in terms of the overall emotional quality of dyadic interaction and its effect on child play. A sample of 28 children with DS (M age = 3 years) took part in this study. In particular, we studied whether the presence of the mother in an interactional context affects the exploratory and symbolic play of children with DS and the interrelation between children's level of play and dyadic emotional availability. Children showed significantly more exploratory play during collaborative play with mothers than during solitary play. However, the maternal effect on child symbolic play was higher in children of highly sensitive mothers relative to children whose mothers showed lower sensitivity, the former displaying more symbolic play than the latter in collaborative play. Results offer some evidence that dyadic emotional availability and child play level are associated in children with DS, consistent with the hypothesis that dyadic interactions based on a healthy level of emotional involvement may lead to enhanced cognitive functioning. C1 [Venuti, Paola; De Falco, Simona; Giusti, Zeno] Univ Trent, Dept Cognit Sci & Educ, I-38068 Rovereto, TN, Italy. [Bornstein, Marc H.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Venuti, P (reprint author), Univ Trent, Dept Cognit Sci & Educ, Via Matteo Ben 5, I-38068 Rovereto, TN, Italy. EM venuti@form.unim.it NR 86 TC 15 Z9 15 U1 3 U2 10 PU MICHIGAN ASSOC INFANT MENTAL HEALTH PI E LANSING PA MICHIGAN STATE UNIV DEPT PSYCHOLOGY, E LANSING, MI 48824-1117 USA SN 0163-9641 J9 INFANT MENT HEALTH J JI Infant Ment. Health J. PD MAR-APR PY 2008 VL 29 IS 2 BP 133 EP 152 DI 10.1002/imhj.20168 PG 20 WC Psychology, Developmental SC Psychology GA 282YH UT WOS:000254603100004 ER PT J AU Ventura, CL Higdon, R Kolker, E Skerrett, SJ Rubens, CE AF Ventura, Christy L. Higdon, Roger Kolker, Eugene Skerrett, Shawn J. Rubens, Craig E. TI Host airway proteins interact with staphylococcus aureus during early pneumonia SO INFECTION AND IMMUNITY LA English DT Article ID FIBRONECTIN-BINDING PROTEIN; TANDEM MASS-SPECTROMETRY; ALVEOLAR MACROPHAGES; CELL-WALL; PSEUDOMONAS-AERUGINOSA; INFLAMMATORY RESPONSES; IDENTIFYING PROTEINS; NUCLEOTIDE-SEQUENCE; SURFACE-PROTEINS; HEME-IRON AB Staphylococcus aureus is a major cause of hospital-acquired pneumonia and is emerging as an important etiological agent of community-acquired pneumonia. Little is known about the specific host-pathogen interactions that occur when S. aureus first enters the airway. A shotgun proteomics approach was utilized to identify the airway proteins associated with S. aureus during the first 6 h of infection. Host proteins eluted from bacteria recovered from the airways of mice 30 min or 6 h following intranasal inoculation under anesthesia were subjected to liquid chromatography and tandem mass spectrometry. A total of 513 host proteins were associated with S. aureus 30 min and/or 6 h postinoculation. A majority of the identified proteins were host cytosolic proteins, suggesting that S. aureus was rapidly internalized by phagocytes in the airway and that significant host cell lysis occurred during early infection. In addition, extracellular matrix and secreted proteins, including fibronectin, antimicrobial peptides, and complement components, were associated with S. aureus at both time points. The interaction of 12 host proteins shown to bind to S. aureus in vitro was demonstrated in vivo for the first time. The association of hemoglobin, which is thought to be the primary staphylococcal iron source during infection, with S. aureus in the airway was validated by immunoblotting. Thus, we used our recently developed S. aureus pneumonia model and shotgun proteomics to validate previous in vitro findings and to identify nearly 500 other proteins that interact with S. aureus in vivo. The data presented here provide novel insights into the host-pathogen interactions that occur when S. aureus enters the airway. C1 [Ventura, Christy L.; Rubens, Craig E.] Seattle Childrens Hosp Res Inst, Ctr Childhood Infect & Prematur Res, Div Infect Dis, Seattle, WA 98101 USA. [Higdon, Roger; Kolker, Eugene] Seattle Childrens Hosp Res Inst, Ctr Dev Therapeut, Seattle, WA USA. [Ventura, Christy L.; Rubens, Craig E.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Kolker, Eugene] Univ Washington, Sch Med, Dept Med Educ & Biomed Informat, Seattle, WA 98195 USA. [Skerrett, Shawn J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Higdon, Roger; Kolker, Eugene] BIATECH Inst, Seattle, WA USA. [Ventura, Christy L.] NIAID, NIH, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. RP Rubens, CE (reprint author), Seattle Childrens Hosp Res Inst, Ctr Childhood Infect & Prematur Res, Div Infect Dis, 1900,9th Ave, Seattle, WA 98101 USA. EM craig.rubens@seattlechildrens.org RI Kolker, Eugene/C-6711-2008; OI Ventura, Christy/0000-0002-5084-1567 FU NHLBI NIH HHS [HL073996, P50 HL073996, P50 HL073996-050004] NR 47 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2008 VL 76 IS 3 BP 888 EP 898 DI 10.1128/IAI.01301-07 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268FC UT WOS:000253563500004 PM 18195024 ER PT J AU Sumby, P Zhang, S Whitney, AR Falugi, F Grandi, G Graviss, EA DeLeo, FR Musser, JM AF Sumby, Paul Zhang, Shizhen Whitney, Adeline R. Falugi, Fabiana Grandi, Guido Graviss, Edward A. DeLeo, Frank R. Musser, James M. TI A chemokine-degrading extracellular protease made by group A Streptococcus alters pathogenesis by enhancing evasion of the innate immune response SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN NEUTROPHILS; PYOGENES; IDENTIFICATION; PROTEINS; DISEASE; COLONIZATION; INACTIVATION; PHAGOCYTOSIS; INFECTIONS; EXPRESSION AB Circumvention of the host innate immune response is critical for bacterial pathogens to infect and cause disease. Here we demonstrate that the group A Streptococcus (GAS; Streptococcuspyogenes) protease SpyCEP (S. pyogenes cell envelope protease) cleaves granulocyte chemotactic protein 2 (GCP-2) and growth-related oncogene alpha (GRO alpha), two potent chemokines made abundantly in human tonsils. Cleavage of GCP-2 and GRO alpha by SpyCEP abrogated their abilities to prime neutrophils for activation, detrimentally altering the innate immune response. SpyCEP expression is negatively regulated by the signal transduction system CovR/S. Purified recombinant CovR bound the spyCEP gene promoter region in vitro, indicating direct regulation. Immunoreactive SpyCEP protein was present in the culture supernatants of covR/S mutant GAS strains but not in supernatants from wild-type strains. However, wild-type GAS strains do express SpyCEP, where it is localized to the cell wall. Strain MGAS2221, an organism representative of the highly virulent and globally disseminated MITI GAS clone, differed significantly from its isogenic spyCEP mutant derivative strain in a mouse soft tissue infection model. Interestingly, and in contrast to previous studies, the isogenic mutant strain generated lesions of larger size than those formed following infection with the parent strain. The data indicate that SpyCEP contributes to GAS virulence in a strain- and disease-dependent manner. C1 [Sumby, Paul; Zhang, Shizhen; Musser, James M.] Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA. [Whitney, Adeline R.; DeLeo, Frank R.] NIAID, NIH, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. [Falugi, Fabiana; Grandi, Guido] Novartis Vaccines & Diagnost, I-53100 Siena, Italy. [Graviss, Edward A.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Musser, JM (reprint author), Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, B490,6565 Fannin St, Houston, TX 77030 USA. EM jmmusser@tmhs.org OI Grandi, Guido/0000-0001-9724-2185; DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS; NIAID NIH HHS [AI-U01-060595] NR 34 TC 58 Z9 58 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2008 VL 76 IS 3 BP 978 EP 985 DI 10.1128/IAI.01354-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268FC UT WOS:000253563500014 PM 18174342 ER PT J AU Reckling, S Divanovic, S Karp, CL Wojciechowski, S Belkaid, Y Hildeman, D AF Reckling, Stacie Divanovic, Senad Karp, Christopher L. Wojciechowski, Sara Belkaid, Yasmine Hildeman, David TI Proapoptotic Bcl-2 family member Bim promotes persistent infection and limits protective immunity SO INFECTION AND IMMUNITY LA English DT Article ID REGULATORY T-CELLS; LEISHMANIA-MAJOR INFECTION; CHRONIC VIRAL-INFECTION; VIRUS-INFECTION; DEFICIENT MICE; NATURAL MODEL; CUTTING EDGE; MEMORY; ANTIGEN; HOMEOSTASIS AB Following the peak of the T-cell response, most of the activated effector T cells die by apoptosis driven by the proapoptotic Bcl-2 family member Bim (Bcl-2-interacting mediator of death). Whether the absence of Bimmediated T-cell apoptosis can affect protective immunity remains unclear. Here, we used a mouse model of Leishmania major infection, in which parasite persistence and protective immunity are controlled by an equilibrium reached between parasite-specific gamma interferon (IFN-gamma) -producing effector T cells and interleukin-10 (IL-10) -producing CD4(+) CD25(+) T regulatory cells. To further understand the role of Bimmediated apoptosis in persistent infection and protective immunity, we infected Bim(-/-) mice with L. major. We found that the initial parasite growth and lesion development were similar in Bim(-/-) and wild-type mice after primary L. major infection. However, at later times after infection, Bim(-/-) mice had significantly increased L. major-specific CD4(+) T-cell responses and were resistant to persistent infection. Interestingly, despite their resistance to primary L. major infection, Bim(-/-) mice displayed significantly enhanced protection against challenge with L. major. Increased resistance to challenge in Bim(-/-) mice was associated with a significant increase in the number of L. major-specific IFN-gamma-producing CD4(+) T cells and a lack of IL-10 production at the challenge site. Taken together, these data suggest that Bim limits protective immunity and that the absence of Bim allows the host to bypass antigen persistence for maintenance of immunity against reinfection. C1 [Belkaid, Yasmine] NIAID, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. [Reckling, Stacie; Divanovic, Senad; Karp, Christopher L.] Cincinnati Childrens Hosp, Med Ctr, Div Mol Immunol, Cincinnati, OH 45229 USA. [Wojciechowski, Sara; Hildeman, David] Cincinnati Childrens Hosp, Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA. RP Belkaid, Y (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr, Rockville, MD 20852 USA. EM ybelkaid@niaid.nih.gov; David.Hildeman@cchmc.org RI Hildeman, David/I-4884-2015; OI Hildeman, David/0000-0002-0421-8483; Karp, Christopher/0000-0002-0832-2659 FU NIAID NIH HHS [AI057753, R01 AI057992, R56 AI057753, R01 AI057753, AI057992] NR 29 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2008 VL 76 IS 3 BP 1179 EP 1185 DI 10.1128/IAI.01093-06 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268FC UT WOS:000253563500036 PM 18086806 ER PT J AU Gray, GC McCarthy, T Capuano, AW Setterquist, SF Alavanja, MC Lynch, CF AF Gray, Gregory C. McCarthy, Troy Capuano, Ana W. Setterquist, Sharon F. Alavanja, Michael C. Lynch, Charles F. TI Evidence for avian influenza A infections among Iowa's agricultural workers SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Agriculture; avian; influenza; influenza A virus; occupational exposure; seroepidemiological studies; zoonoses ID POULTRY WORKERS; SWINE WORKERS; UNITED-STATES; LOW-FREQUENCY; H5N1 VIRUS; TRANSMISSION; ANTIBODY; HUMANS; VACCINE; ASSAYS AB Background Identifying risk factors for zoonotic influenza transmission may aid public health officials in pandemic influenza planning. Objectives We sought to evaluate rural Iowan agriculture workers exposed to poultry for previous evidence of avian influenza virus infection. Methods In 2004, we enrolled 803 rural adult Iowans in a 2-year prospective study of zoonotic influenza transmission. Their enrollment data and sera were compared with those of 66 adult controls enrolled at the University of Iowa in 2006 by using proportional odds modeling. Results Of the 803 participants 58.8% were male with a mean age of 55.6 years. Forty-eight percent reported previous poultry exposure. Sera were studied by microneutralization techniques for antibodies against avian H4, H5, H6, H7 and H9 viruses. Touching live birds was associated (OR 1.2; 95% CI 1.02-1.8) with increased antibody titer against H5 virus. Similarly, participants who reported hunting wild birds had increased antibody titers against H7 virus (OR 2.8; 95% CI 1.2-6.5) and subjects who reported recent exposure to poultry had increased antibody titers against H6 (OR 3.4; 95% CI 1.4-8.5) and H7 viruses (OR 2.5, 95% CI 1.1-5.7). There was no evidence of elevated antibody against avian H4 or H9 viruses. Conclusions These data suggest that hunting and exposure to poultry may be important risk factors for avian influenza virus infection among rural US populations. Agriculture workers should be included in influenza pandemic plans. C1 [Gray, Gregory C.; McCarthy, Troy; Capuano, Ana W.; Setterquist, Sharon F.; Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Ctr Emerging Infect Dis, Iowa City, IA 52242 USA. [Alavanja, Michael C.] NCI, Bethesda, MD 20892 USA. RP Gray, GC (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Ctr Emerging Infect Dis, 200 Hawkins Dr,C21K GH, Iowa City, IA 52242 USA. EM gregory-gray@uiowa.edu FU NIAID NIH HHS [R21 AI059214, R21 AI059214-01, R21 AI059214-02] NR 28 TC 36 Z9 37 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD MAR PY 2008 VL 2 IS 2 BP 61 EP 69 DI 10.1111/j.1750-2659.2008.00041.x PG 9 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 467RZ UT WOS:000267761400003 PM 18941621 ER PT J AU Li, Y Cui, XZ Li, XM Solomon, SB Danner, RL Banks, SM Fitz, Y Annane, D Natanson, C Eichacker, PQ AF Li, Yan Cui, Xizhong Li, Xuemei Solomon, Steven B. Danner, Robert L. Banks, Steven M. Fitz, Yvonne Annane, Djillali Natanson, Charles Eichacker, Peter Q. TI Risk of death does not alter the efficacy of hydrocortisone therapy in a mouse E-coli pneumonia model SO INTENSIVE CARE MEDICINE LA English DT Article DE sepsis; risk of death; pneumonia; hydrocortisone; treatment ID NEGATIVE BACTERIAL SEPSIS; HYPERDYNAMIC SEPTIC SHOCK; LOW-DOSE HYDROCORTISONE; LETHAL TOXIN; DOUBLE-BLIND; MORTALITY; RATS; CYTOKINE; METAANALYSIS; ANTIBIOTICS AB Background: Risk of death may influence the efficacy of anti-inflammatory agents in sepsis. "Physiologic" dose corticosteroids, while improving survival in earlier trials with higher control mortality rates (> 50%), were not beneficial in the recent CORTICUS trial with lower control mortality (31%). We investigated whether risk of death altered the effects of hydrocortisone in a mouse pneumonia model. Methods: Mice (n = 637) challenged with high, medium or low intratracheal E. coli doses were randomized to receive one of three hydrocortisone doses (5, 25 or 125 mg/kg) or normal saline (NS) only (control) for 4 days. All animals were treated with similar volumes of ceftriaxone and NS support following E. coli and were observed for 168 h. Results: Decreasing E. coli doses reduced control mortality rates (from 94 to 12%). In similar patterns (not significant) each hydrocortisone dose increased the odds ratio (OR) of survival (95% confidence interval) with each E. coli dose (ORs ranging from 1.2 [0.4, 3.7] to 6.1 [0.6, 61.0]). The effect of hydrocortisone on the OR was not related to control mortality rate (r = - 0.13, p = 0.29) and overall was highly significant (2.04 [1.37, 3.03], p = 0.0004). In randomly selected animals 48 h after the highest E. coli dose, compared with the control, hydrocortisone (125 mg/kg) significantly decreased IL- 6, INF gamma, and nitric oxide levels. Conclusions: In this mouse model the beneficial effects of hydrocortisone were independent of risk of death. These findings suggest that factors other than risk of death may underlie the differing effects of corticosteroids in recent sepsis trials. C1 [Li, Yan; Cui, Xizhong; Li, Xuemei; Solomon, Steven B.; Danner, Robert L.; Banks, Steven M.; Fitz, Yvonne; Natanson, Charles; Eichacker, Peter Q.] Natl Inst Hlth, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Li, Xuemei] Peking Union Med Coll, Dept Nephrol, Beijing, Peoples R China. RP Eichacker, PQ (reprint author), Natl Inst Hlth, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D43, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov FU Intramural NIH HHS NR 34 TC 27 Z9 29 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAR PY 2008 VL 34 IS 3 BP 568 EP 577 DI 10.1007/s00134-007-0921-7 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 263EQ UT WOS:000253200800027 PM 17992512 ER PT J AU Ciolino, HP Bass, SE MacDonald, CJ Cheng, RYS Yeh, GC AF Ciolino, Henry P. Bass, Sara E. MacDonald, Christopher J. Cheng, Robert Y. S. Yeh, Grace Chao TI Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE sulindac; sulindac sulfide; cytochrome P450 1A1 (CYP1A1); NAD(P)H : quinone oxidoreductase (NQO1); aryl hydrocarbon receptor (AhR) ID ARYL-HYDROCARBON RECEPTOR; FAMILIAL ADENOMATOUS POLYPOSIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; XENOBIOTIC-RESPONSIVE ELEMENT; PLANAR AROMATIC-COMPOUNDS; IN-VITRO; TRANSCRIPTIONAL ACTIVATION; PHASE-I; PRIMARY CHEMOPREVENTION; MAMMARY CARCINOGENESIS AB Sulindac is a nonsteroidal antiinflammatory drug that has been demonstrated to be a potent chemopreventive agent against colorectal cancer in both human and animal models. In vivo, sulindac may be reversibly reduced to the active antiinflammatory compound, sulindac sulfide, or irreversibly oxidized to sulindac sulfone. Sulindac has also been shown to inhibit polycyclic aromatic hydrocarbon (PAH)-induced cancer, but the molecular mechanisms of its antitumor effect remain unclear. In this study, we investigated the effects of sulindac and its metabolites on the expression of enzymes that metabolize and detoxify PAHs in 2 human colon cancer cell lines, LS180 and Caco-2. Sulindac and sulindac sulfide induced a sustained, concentration -dependent increase in CYP enzyme activity as well as an increase in the mRNA levels of CYP1A1, CYP1A2 and CYP1B1. Sulindac and sulindac sulfide induced the transcription of the CYP1A1 gene, as measured by the level of heterogeneous nuclear CYP1A1 RNA and verified by the use of actinomycin D as a transcription inhibitor. Chromatin immunoprecipitation assays demonstrated that sulindac and sulindac sulfide also increased the nuclear level of activated aryl hydrocarbon receptor, the transcription factor which mediates CYP expression. Additionally, sulindac and both metabolites increased the activity and mRNA expression of the carcinogen detoxitication enzyme NAD(P)H:quinone oxidoreductase, as well as the expression of UDP-glucuronosyltransferase mRNA. These results show an overall upregulation of carcinogen metabolizing enzymes in colon cancer cells treated with sulindac, sulindac sulfide and sulindac sulfone that may contribute to the established chemoprotective effects of these compounds. (c) 2007 Wiley -Liss, Inc. C1 [MacDonald, Christopher J.; Cheng, Robert Y. S.; Yeh, Grace Chao] NCI, NIH, Ctr Canc Res, Lab Metab,Cellular Def & Carcinogenesis Sect, Frederick, MD USA. [Ciolino, Henry P.] Univ Texas Austin, Dept Human Ecol, Div Nutr Sci, Austin, TX 78712 USA. [Bass, Sara E.] SAIC Frederick Inc, NCI, Basic Res Program, Frederick, MD USA. RP Yeh, GC (reprint author), NCI, Frederick Canc Res & Dev Ctr, PO Box B, Frederick, MD 21702 USA. EM yeh@ncifcrf.gov OI Cheng, Robert/0000-0003-0287-6439 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 78 TC 17 Z9 17 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2008 VL 122 IS 5 BP 990 EP 998 DI 10.1002/ijc.23218 PG 9 WC Oncology SC Oncology GA 260TW UT WOS:000253034300005 PM 17985343 ER PT J AU McMaster, ML Csako, G AF McMaster, Mary L. Csako, Gyorgy TI Protein electrophoresis, immunoelectrophoresis and immunofixation electrophoresis as predictors for high-risk phenotype in familial Waldenstrom macroglobulinemia SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Waldenstrom; monoclonal gammopathy; MGUS; electrophoresis ID POPULATION-BASED REGISTRY; NON-HODGKINS-LYMPHOMA; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; M-COMPONENTS; FOLLOW-UP; IMMUNOGLOBULIN LEVELS; CELLULOSE-ACETATE; AGAROSE-GEL; LONG-TERM AB Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal gammopathy (MG) conditions such as Waldenstrom macroglobulinemia (WM). Immunofixation electrophoresis (IFE) is currently the most common method for isotyping of monoclonal gammopathy because of its superior sensitivity relative to immunoelectrophoresis (IEP). We designed a study to evaluate the clinicobiological relevance of small monoclonal bands detected by serum protein electrophoresis, IEP, and IFE. Serum protein electrophoresis, IEP, and IFE were used to evaluate possible monoclonal gammopathy in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of WM. IFE identified small monoclonal bands initially missed by IEP in 5 individuals (2 blood relatives, 3 spouses) among 46 study participants. All bands were IgM type. Twenty-three individuals, including the 2 blood relatives and 2 of 3 spouses with monoclonal gammopathy, were then followed for a median of 17 years (range, 13-25). The monoclonal gammopathy progressed in the 2 relatives but disappeared in the spouses, and new IgM MG developed in 2 additional relatives with a prior history of IgM polyclonal gammopathy. Small monoclonal bands detected by IFE in a familial context may be biologically meaningful, both as phenotypic biomarkers and possibly as predictors of high risk for WM. Polyclonal IgM may also be a marker of genetic susceptibility in WM families. Larger studies are needed to confirm these observations. (C) 2007 Wiley-Liss, Inc. C1 [McMaster, Mary L.] Natl Canc Inst, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD USA. [Csako, Gyorgy] Natl Inst Hlth, Ctr Clin, Dept Hlth & Human Serv, Dept Lab Med, Bethesda, MD USA. RP McMaster, ML (reprint author), NIH, NCI, DHHS, Genet Epidemiol Branch,DCEG, Bldg 10,6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM mcmastem@mail.nih.gov NR 37 TC 2 Z9 3 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2008 VL 122 IS 5 BP 1183 EP 1188 DI 10.1002/ijc.23229 PG 6 WC Oncology SC Oncology GA 260TW UT WOS:000253034300030 PM 17990319 ER PT J AU Hall, KD AF Hall, K. D. TI What is the required energy deficit per unit weight loss? SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body composition; weight loss; mathematical model; energy density; diet ID FAT-FREE MASS; BODY-COMPOSITION; MORBID-OBESITY; ADAPTIVE THERMOGENESIS; PROTEIN-METABOLISM; ADIPOSE-TISSUE; EXPENDITURE; EXERCISE; WATER; WOMEN AB One of the most pervasive weight loss rules is that a cumulative energy deficit of 3500 kcal is required per pound of body weight loss, or equivalently 32.2 MJ kg(-1). Under what conditions is it appropriate to use this rule of thumb and what are the factors that determine the cumulative energy deficit required per unit weight loss? Here, I examine this question using a modification of the classic Forbes equation that predicts the composition of weight loss as a function of the initial body fat and magnitude of weight loss. The resulting model predicts that a larger cumulative energy deficit is required per unit weight loss for people with greater initial body fat-a prediction supported by published weight loss data from obese and lean subjects. This may also explain why men can lose more weight than women for a given energy deficit since women typically have more body fat than men of similar body weight. Furthermore, additional weight loss is predicted to be associated with a lower average cumulative energy deficit since a greater proportion of the weight loss is predicted to result from loss of lean body mass, which has a relatively low energy density in comparison with body fat. The rule of thumb approximately matches the predicted energy density of lost weight in obese subjects with an initial body fat above 30 kg but overestimates the cumulative energy deficit required per unit weight loss for people with lower initial body fat. C1 NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Hall, KD (reprint author), NIDDK, Lab Biol Modeling, NIH, 12A South Dr,Room 4007, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Hall, Kevin/F-2383-2010 FU Intramural NIH HHS [Z01 DK013036-01] NR 41 TC 63 Z9 64 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 2008 VL 32 IS 3 BP 573 EP 576 DI 10.1038/sj.ijo.0803720 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 275PH UT WOS:000254083600023 PM 17848938 ER PT J AU Yoshida, Y Kurokawa, T Nishikawa, Y Orisa, M Kleinman, HK Kotsuji, F AF Yoshida, Yoshio Kurokawa, Tetsuji Nishikawa, Yukiko Orisa, Makoto Kleinman, Hynda K. Kotsuji, Fumikazu TI Laminin-1-derived scrambled peptide AG73T disaggregates laminin-1-induced ovarian cancer cell spheroids and improves the efficacy of cisplatin SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE laminin-1; ovarian cancer; cisplatin; cell spheroids ID LAMININ ALPHA-1 CHAIN; G-DOMAIN; SYNTHETIC PEPTIDES; INDUCED APOPTOSIS; BINDING-SITES; GROWTH; METASTASIS; BETA-1-INTEGRINS; MECHANISMS; EXPRESSION AB We found previously that the laminin-1-derived synthetic peptide AG73 (LQVQLSIR) promoted ovarian cancer cell metastasis in vivo. We have now studied the role of this metastasis-promoting peptide in vitro using TAC3 ovarian cancer cells, which display anchorage-independent growth and form multicellular spheroids. Our goal is to better understand how this peptide can regulate metastasis in vivo. We found that the exogenous addition of either laminin-1 or peptide AG73 stimulated the formation and growth of the spheroids. Western blot analysis indicated that laminin-1 enhanced the expression of integrin beta 1, and that AG73 peptide enhanced expression of syndecan-1 and downstream effectors, including mitogen-activated protein kinase (MAPK) and extracellular signal-related kinase (ERK), and also phosphatidylinositol (PI)-3 kinase/AKT activity signaling. The soluble peptide AG73T, which is a scramble peptide of AG73, was able to disaggregate the laminin-1-induced spheroids. Furthermore, the disaggregated cells were twice as sensitive to cisplatin as the intact spheroids. The AG73T peptide in the presence of laminin-1 suppressed expression of integrin beta 1 and its downstream effectors, including MAPK/ERK and PI3/AKT activity signaling. The MEK inhibitor U0126 reduced TAC3 cell growth more effectively in the presence of both laminin-1 and AG73T than in the presence of laminin-1 alone. Inhibition of the PI3-K cascade with LY294002 was also more effective in the presence of laminin-1 and AG73T. The increased sensitivity to cisplatin in the presence of AG73T may be due to the greater bioavailability of the drug to the free-floating cells over the spheroids. These findings suggest a novel function of AG73T in ovarian cancer and help to define mechanisms important in ovarian cancer spheroid formation and spread. C1 [Yoshida, Yoshio; Kurokawa, Tetsuji; Nishikawa, Yukiko; Orisa, Makoto; Kotsuji, Fumikazu] Univ Fukui, Fac Med Sci, Dept Obstet & Gynecol, Fukui 9101103, Japan. [Kleinman, Hynda K.] Natl Inst Dent & Craniofacial Res, NIH, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. RP Yoshida, Y (reprint author), Univ Fukui, Fac Med Sci, Dept Obstet & Gynecol, 23-3 Shimoaizuki,Eiheiji Cho, Fukui 9101103, Japan. EM yyoshida@u-fukui.ac.jp NR 29 TC 11 Z9 12 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 2008 VL 32 IS 3 BP 673 EP 681 PG 9 WC Oncology SC Oncology GA 267KJ UT WOS:000253507600018 PM 18292945 ER PT J AU Kim, MK Pulla, RK Kim, SY Yi, TH Soung, NK Yang, DC AF Kim, Myung Kyum Pulla, Rama Krishna Kim, Se-Young Yi, Tae-Hoo Soung, Nak-Kyun Yang, Deok-Chun TI Sanguibacter soli sp nov., isolated from soil of a ginseng field SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; BACTERIA; ACID AB A Gram-positive, non-spore-forming, rod-shaped, motile bacterium, designated strain DCY22(T), was isolated from soil of a ginseng field in South Korea and characterized in order to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain DCY22(T) belonged within the family Sanguibacteraceae, and highest levels of sequence similarity were found with Sanguibacter marinus 1-19(T) (96.8%), Sanguibacter suarezii ST-26(T) (96.0%), Sanguibacter inulinus ST-50(T) (95.9%), Sanguibacter keddieii ST-74(T) (95.5%), Terrabacter terrae PPLBT (94.0%) and Terrabacter tumescens DSM 20308(T) (93.8%). Chemotaxonomic investigations revealed that strain DCY22(T) possessed menaquinone MK-9, a common feature of members of the genus Sanguibacter. Predominant fatty acids were unknown ECL 13.961 (45.81 %), 17: 0 anteiso (23.46 %), 18: 0 iso (115.42 %) and unknown ECL 14.966 (8.70%). The results of physiological and biochemical tests clearly demonstrated that strain DCY22T represents a novel species of the genus Sanguibacter, for which the name Sanguibacter soli sp. nov. is proposed. The type strain is DCY22(T) (=KCTC 13155(T)=JCM 14841(T)). C1 [Kim, Myung Kyum; Pulla, Rama Krishna; Kim, Se-Young; Yi, Tae-Hoo; Yang, Deok-Chun] Kyung Hee Univ, Korean Ginseng Ctr, Yongin 449701, Kyunggi Do, South Korea. [Kim, Myung Kyum; Pulla, Rama Krishna; Kim, Se-Young; Yi, Tae-Hoo; Yang, Deok-Chun] Kyung Hee Univ, Ginseng Genet Resource Bank, Yongin 449701, Kyunggi Do, South Korea. [Soung, Nak-Kyun] NCI, Natl Inst Hlth, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yang, DC (reprint author), Kyung Hee Univ, Korean Ginseng Ctr, 1 Seocheon Dong, Yongin 449701, Kyunggi Do, South Korea. EM dcyang@khu.ac.kr NR 19 TC 2 Z9 2 U1 1 U2 6 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD MAR PY 2008 VL 58 BP 538 EP 541 DI 10.1099/ijs.0.65399-0 PN 3 PG 4 WC Microbiology SC Microbiology GA 282YN UT WOS:000254603700002 PM 18319451 ER PT J AU Gilbert, CE Ellwein, LB AF Gilbert, Clare E. Ellwein, Leon B. CA Refractive Error Study Children TI Prevalence and causes of functional low vision in school-age children: Results from standardized population surveys in Asia, Africa, and Latin America SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID REFRACTIVE ERROR; VISUAL IMPAIRMENT; DISTRICT; CHINA AB PURPOSE. Data on the prevalence and causes of functional low vision (FLV) in adults and children are lacking but are important for planning low-vision services. This study was conducted to determine the prevalence and causes of FLV among children recruited in eight population-based prevalence surveys of visual impairment and refractive error from six countries (India [2 locations]; China [2 locations]; Malaysia, Chile, Nepal, and South Africa). METHODS. Using the same protocol, 4082 to 6527 children aged 5 (or 7) to 15 years were examined at each site. Uncorrected and presenting visual acuities were successfully measured with retroilluminated logMAR tumbling-E charts in 3997 to 5949 children; cycloplegic autorefraction was performed and best corrected acuities assessed. All children were examined by an ophthalmologist and a cause of visual loss assigned to eyes with uncorrected acuity <= 6/12. The prevalence of FLV was determined overall and by site; associations with gender, age, parental education and urban/rural location were assessed with logistic regression. RESULTS. The prevalence of FLV ranged from 0.65 to 2.75 in 1000 children, with wide confidence intervals. The overall prevalence was 1.52 in 1000 children (95% CI 1.16-1.95). FLV was significantly associated with age (odds ratio [OR] 1.13 for each year, P = 0.01), and parental education was protective (OR 0.75 for each of five levels of education, P = 0.017). Retinal lesions and amblyopia were the commonest causes. CONCLUSIONS. More studies are needed to determine the prevalence and causes of FLV in children so that services can be planned that promote independence, improve quality of life, and increase access to education. C1 [Gilbert, Clare E.] Univ London London Sch Hyg & Trop Med, Int Ctr Eye Hlth, Clin Res Unit, London WC1E 7HT, England. [Ellwein, Leon B.] NEI, NIH, Bethesda, MD 20892 USA. RP Gilbert, CE (reprint author), Univ London London Sch Hyg & Trop Med, Int Ctr Eye Hlth, Clin Res Unit, Keppel St, London WC1E 7HT, England. EM clare.gilbert@lshtm.ac.uk FU NEI NIH HHS [N01-EY2103] NR 17 TC 29 Z9 30 U1 2 U2 10 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2008 VL 49 IS 3 BP 877 EP 881 DI 10.1167/iovs.07-0973 PG 5 WC Ophthalmology SC Ophthalmology GA 271TZ UT WOS:000253812900007 PM 18326706 ER PT J AU Rao, NA Saraswathy, S Wu, GS Katselis, GS Wawrousek, EF Bhat, S AF Rao, Narsing A. Saraswathy, Sindhu Wu, Guey Shuang Katselis, George S. Wawrousek, Eric F. Bhat, Suraj TI Elevated retina-specific expression of the small heat shock protein, alpha A-crystallin, is associated with photoreceptor protection in experimental uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; EXPERIMENTAL AUTOIMMUNE UVEITIS; LENS EPITHELIAL-CELLS; B-CRYSTALLIN; INDUCED APOPTOSIS; SIGNALING PATHWAYS; ALTERED EXPRESSION; GENE-EXPRESSION; FREE SYSTEM; ACTIVATION AB PURPOSE. During the early phase of experimental autoimmune uveitis (EAU), before macrophages infiltrate the retina and uvea, photoreceptor mitochondrial oxidative stress, nitration of photoreceptor mitochondrial proteins, and release of cytochrome c have been observed. However, no apoptosis has been detected during this phase. In this study, alpha A-crystallin upregulation in the retina and its antiapoptotic protective role were evaluated in early EAU. METHODS. Gene microarrays were first used to identify upregulated genes in retinas with early EAU. Among highly upregulated crystallins, alpha A was confirmed by real-time polymerase chain reaction and Western blot, and the site of upregulation was localized by immunohistochemistry. The association of alpha A-crystallin to nitrated cytochrome c and interaction with a procaspase-3 subunit was assayed. Photoreceptor apoptosis in alpha A knockout mice was compared with that in wild-type animals with EAU, by using the terminal transferase dUTP nickend labeling assay and polymerase chain reaction. RESULTS. In early EAU, alpha A-crystallin was increased 33-fold, and the site of increase was localized to the photoreceptor inner segments. This crystallin suppressed apoptosis by associating with the nitrated cytochrome c and p24. The association with nitrated cytochrome c, in particular, appeared to be restricted to nitrated cytochrome c, and thus, no association of non-nitrated cytochrome c was detected. The knockout mice showed signs of EAU development early and showed apoptosis in the retina; no such changes were seen in the wild-type control animals. CONCLUSIONS. alpha A-Crystallin is highly upregulated in the retina during early EAU. This upregulation is localized primarily in the photoreceptor inner segments, the site of mitochondrial oxidative stress. Further, in early EAU, the photoreceptors preferentially use alpha A-crystallin to suppress mitochondrial oxidative stress-mediated apoptosis. C1 [Rao, Narsing A.; Saraswathy, Sindhu; Wu, Guey Shuang] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. [Rao, Narsing A.; Saraswathy, Sindhu; Wu, Guey Shuang] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. [Katselis, George S.] Beckman Res Inst, Div Immunol, Duarte, CA USA. [Wawrousek, Eric F.] NIH, Bethesda, MD USA. [Bhat, Suraj] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. RP Rao, NA (reprint author), Univ So Calif, Keck Sch Med, Doheny Eye Inst, 1450 San Pablo St, Los Angeles, CA 90033 USA. EM nrao@usc.edu FU NEI NIH HHS [EY015714, EY03040] NR 63 TC 54 Z9 56 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2008 VL 49 IS 3 BP 1161 EP 1171 DI 10.1167/iovs.07-1259 PG 11 WC Ophthalmology SC Ophthalmology GA 271TZ UT WOS:000253812900047 PM 18326745 ER PT J AU Weinrich, M AF Weinrich, Michael TI Dealing with disability SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Letter C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Med Rehabil Res, Bethesda, MD USA. RP Weinrich, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Med Rehabil Res, Bethesda, MD USA. EM weinricm@mad.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD SPR PY 2008 VL 24 IS 3 BP 8 EP 10 PG 3 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA 289SN UT WOS:000255074300004 ER PT J AU Bachrach, CA Spirrel, M AF Bachrach, Christine A. Spirrel, Michael TI Racial disparities at birth SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Letter C1 [Bachrach, Christine A.; Spirrel, Michael] NICHHD, Demog & Behav Sci Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bachrach, CA (reprint author), NICHHD, Demog & Behav Sci Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM Marylandcbachrach@nih.gov; spittelm@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD SPR PY 2008 VL 24 IS 3 BP 17 EP 18 PG 2 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA 289SN UT WOS:000255074300012 ER PT J AU Mirochnick, M Nielsen-Saines, K Pilotto, JR Pinto, J Jimenez, E Veloso, VG Parsons, T Watts, H Move, J Mofenson, LM Camarca, M Bryson, Y AF Mirochnick, Mark Nielsen-Saines, Karin Pilotto, Jose Renrique Pinto, Jorge Jimenez, Eleanor Veloso, Valdilea G. Parsons, Teresa Watts, Heather Move, Jack Mofenson, Lynne M. Camarca, Margaret Bryson, Yvonne CA NICHD HPTN 040 PACTG 1043 Protocol TI Nevirapine concentrations in Newborns receiving an extended prophylactic regimen SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 13th Conference on Retroviruses and Opportunistic Infections CY FEB 05-09, 2006 CL Denver, CO DE mother-to-child HIV transmission; neonate; nevirapine; pharmacokinetics ID MOTHER-TO-CHILD; HUMAN-IMMUNODEFICIENCY-VIRUS; POSTEXPOSURE PROPHYLAXIS; RANDOMIZED-TRIAL; TRANSMISSION; HIV-1; ZIDOVUDINE; PHARMACOKINETICS; UGANDA; WOMEN AB Background: The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. Methods: As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates born to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration > 100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14.. Results: The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng,/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels < 100 ng/mL, although only 1 neonate had no detectable NVP. Conclusion: Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol. C1 [Mirochnick, Mark] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Nielsen-Saines, Karin; Bryson, Yvonne] Calif State Univ Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA USA. [Pilotto, Jose Renrique] Hosp Geral Nova Iguacu, Dept Sexually Transmitted Dis, Nova Iguacu, Brazil. [Pinto, Jorge] Univ Fed Minas Gerais, Dept Pediat, Belo Horizonte, MG, Brazil. [Jimenez, Eleanor] San Juan City Hosp, Dept Pediat, San Juan, PR USA. [Veloso, Valdilea G.] Inst Pesquisa Clin Evandro Chagas, Fdn Inst Oswaldo Cruz, Rio De Janeiro, Brazil. [Parsons, Teresa] Univ Baltimore, Div Clin Pharmacol, Baltimore, MD 21201 USA. [Watts, Heather; Move, Jack; Mofenson, Lynne M.] NICHD, Natl Inst Hlth, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. [Camarca, Margaret] Westat Corp, Rockville, MD USA. RP Mirochnick, M (reprint author), Boston Med Ctr, 91 E Concord St,6th Floor, Boston, MA 02118 USA. EM markm@bu.edu RI Goncalves Veloso, Valdilea/J-6189-2012; OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 FU NICHD NIH HHS [N01-HD33345] NR 12 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2008 VL 47 IS 3 BP 334 EP 337 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 271XD UT WOS:000253821100010 PM 18398973 ER PT J AU Walkup, J Blank, MB Gonzalez, JS Safren, S Schwartz, R Brown, L Wilson, I Knowlton, A Lombard, F Grossman, C Lyda, K Schumacher, JE AF Walkup, James Blank, Michael B. Gonzalez, Jeffrey S. Safren, Steven Schwartz, Rebecca Brown, Larry Wilson, Ira Knowlton, Amy Lombard, Frank Grossman, Cynthia Lyda, Karen Schumacher, Joseph E. TI The impact of mental health and substance abuse factors on HIV prevention and treatment SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 1st National Scientific Meeting of the Social-and-Behavioral-Science-Research-Network CY MAR 27-28, 2006 CL Atlanta, GA SP Social & Behav Sci Res Network ID INFECTED MEDICAID BENEFICIARIES; ACTIVE ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; UNITED-STATES; USE DISORDERS; PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; RISK BEHAVIORS; SEXUAL RISK; ILLNESS AB The convergence of HIV, substance abuse (SA), and mental illness (MI) represents a distinctive challenge to health care providers, policy makers, and researchers. Previous research with the mentally ill and substance-abusing populations has demonstrated high rates of psychiatric and general medical comorbidity. Additionally, persons living with HIV/AIDS have dramatically elevated rates of MI and other physical comorbidities. This pattern of co-occurring conditions has been described as a syndemic. Syndemic health problems occur when linked health problems involving 2 or more afflictions interact synergistically and contribute to the excess burden of disease in a population. Evidence for syndemics arises when health-related problems cluster by person, place, or time. This article describes a research agenda for beginning to understand the complex relations among MI, SA, and HIV and outlines a research agenda for the Social and Behavioral Science Research Network in these areas. C1 [Walkup, James] Rutgers State Univ, Inst Hlth Hlth Care Policy, New Brunswick, NJ USA. [Walkup, James] Rutgers State Univ, Grad Sch Appl & Profess Psychol, New Brunswick, NJ USA. [Blank, Michael B.] Univ Penn, Sch Med, Dept Psychiat, Ctr Mental Hlth Policy, Philadelphia, PA 19104 USA. [Blank, Michael B.] Univ Penn, Sch Med, Dept Psychiat, Res Serv, Philadelphia, PA 19104 USA. [Gonzalez, Jeffrey S.; Safren, Steven; Schwartz, Rebecca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Safren, Steven] Fenway Community Hlth, Boston, MA USA. [Schwartz, Rebecca] SUNY Stony Brook, Downstate Med Ctr, New York, NY USA. [Brown, Larry] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Bradley Hasbro Childrens Res Ctr, Providence, RI 02903 USA. [Wilson, Ira] Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Knowlton, Amy] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Lombard, Frank] Duke Univ, Ctr Hlth Policy, Durham, NC USA. [Grossman, Cynthia] NIMH, NIH, Bethesda, MD 20892 USA. [Lyda, Karen] Univ Colorado, Univ Colorado Hosp, Infect Dis Grp Practice, Denver, CO 80202 USA. [Schumacher, Joseph E.] Univ Alabama, Ctr AIDS Res, Div Prevent Med, Birmingham, AL USA. RP Walkup, J (reprint author), Rutgers State Univ, Inst Hlth Hlth Care Policy, 30 Coll Ave, New Brunswick, NJ USA. EM jamie.walkup@gmail.com RI walkup, james/E-5041-2012; Walkup, James/E-5047-2012 FU AHRQ HHS [U18-HS016097-01]; NIMH NIH HHS [R01-MH058984] NR 52 TC 50 Z9 50 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2008 VL 47 SU 1 BP S15 EP S19 DI 10.1097/QAI.0b013e3181605b26 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 271XE UT WOS:000253821200004 PM 18301129 ER PT J AU Purdy, JB Freeman, AF Martin, SC Ryder, C Elliott-DeSorbo, DK Zeichner, S Hazra, R AF Purdy, Julia Bilodeau Freeman, Alexandra F. Martin, Staci C. Ryder, Celia Elliott-DeSorbo, Deborah K. Zeichner, Steven Hazra, Rohan TI Virologic response using directly observed therapy in adolescents with HIV: An adherence tool SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE HIV/AIDS; directly observed therapy; adolescence; adherence; virologic response ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CHILDREN; INFECTION; MULTIDISCIPLINARY; NONADHERENCE; MORTALITY; HAART AB Virologic response to highly active antiretroviral therapy (HAART) treatment of HIV infection depends on viral sensitivity to antiretrovirals and excellent medication adherence. Adolescents with vertically acquired HIV may require complicated regimens because of significant treatment experience and often have poor medication adherence. A retrospective chart review identified five adolescents with vertically acquired HIV and plasma HIV viral load rebound or nonresponse on a stable HAART regimen followed by a period of directly observed therapy (DOT) in a clinic or hospital setting with serial viral load measurements. Four subjects had a virologic response (mean decline, 1.15 log(10)) after DOT A response to HAART can be seen despite antiretrovirals resistance using DOT and treatment-experienced patients seemingly unresponsive to HAART may be nonadherent even with reassuring adherence measures. A period of clinic-monitored DOT may allow diagnosis of non-adherence, discussion of medication barriers, and avoidance of unnecessary medication changes. C1 [Purdy, Julia Bilodeau; Freeman, Alexandra F.; Martin, Staci C.; Elliott-DeSorbo, Deborah K.; Hazra, Rohan] NCI, NIH, Bethesda, MD 20892 USA. [Ryder, Celia] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Zeichner, Steven] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Purdy, JB (reprint author), NCI, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 17 TC 10 Z9 11 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD MAR-APR PY 2008 VL 19 IS 2 BP 158 EP 165 DI 10.1016/j.jana.2007.08.003 PG 8 WC Nursing SC Nursing GA 277KW UT WOS:000254212400009 PM 18328966 ER PT J AU Hermos, JA Winter, MR Heeren, TC Hingson, RW AF Hermos, John A. Winter, Michael R. Heeren, Timothy C. Hingson, Ralph W. TI Early age-of-onset drinking predicts prescription drug misuse among teenagers and young adults: Results from a national survey SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE drinking age-of-onset; prescription drug misuse; teenagers; young adults; epidemiology; national survey ID ADOLESCENT SUBSTANCE USE; IV ALCOHOL-ABUSE; EPIDEMIOLOGIC SURVEY; COLLEGE-STUDENTS; NONMEDICAL USE; USE DISORDERS; COOCCURRENCE; PREVALENCE; DEPENDENCE; BEHAVIORS AB Early age-of-onset drinking is associated with alcohol problems and related, high-risk behaviors. We analyzed data from 18- to 34-year-old respondents from the 2001 to 2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC) to determine to what extent early age-of-onset. drinking increased risks for prescription drug misuse (PDM), defined as I or more positive responses to: "ever having misused sedatives, tranquilizers, painkillers or stimulants, obtained either as prescriptions or from indirect sources." Lifetime prevalence of PDM was 15.4% among 8306 "drinkers" and 3% among 4652 "nondrinkers." Unadjusted odds for PDM for both men and women increased with each successively younger drinking age-of-onset, reaching a 10-fold risk at < 14 years (odds ratio [OR], 10.7; 95% confidence interval [CI], 7.43-15.3) for men and women combined). In adjusted analyses, early age-of-onset marijuana use among drinkers reduced these odds and independently increased the risks for PDM 2-fold (adjusted OR, 2.07; 95% CI, 1.17-3.64). Lifetime alcohol dependence independently predicted PDM (adjusted OR, 2.43; 95% CI, 2-2.96) and obscured the association of early drinking, but not of early marijuana use, with PDM. This finding suggests a specific mediating effect of alcohol dependence between early drinking and PDM. Findings support the need for effective programs to prevent and reduce harm from early-onset drinking and from the associated risk of alcohol dependence and prescription drug misuse. C1 [Hermos, John A.] Va Boston Healthcare Syst 151MAV, Boston, MA 02130 USA. [Hermos, John A.; Winter, Michael R.; Heeren, Timothy C.; Hingson, Ralph W.] Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA USA. [Hermos, John A.; Hingson, Ralph W.] Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Winter, Michael R.; Heeren, Timothy C.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hingson, Ralph W.] NIAAA, Div Epidemiol & Prevent, Bethesda, MD USA. RP Hermos, JA (reprint author), Va Boston Healthcare Syst 151MAV, 150 S Huntington Ave, Boston, MA 02130 USA. EM john.hermos@med.va.gov NR 28 TC 14 Z9 14 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD MAR PY 2008 VL 2 IS 1 BP 22 EP 30 DI 10.1097/ADM.0b013e3181565e14 PG 9 WC Substance Abuse SC Substance Abuse GA 305GN UT WOS:000256166100003 PM 21768969 ER PT J AU Barr, C AF Barr, C. TI Moderating effects of 5-HTT, MAO-A and COMT polymorphisms on early life stress: Evidence from primate studies SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Meeting Abstract C1 [Barr, C.] NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2008 VL 107 SU 1 BP S29 EP S29 DI 10.1016/j.jad.2007.12.171 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 284WB UT WOS:000254736500025 ER PT J AU Salo, PM Arbes, SJ Crockett, PW Thorne, PS Cohn, RD Zeldin, DC AF Salo, Paeivi M. Arbes, Samuel J. Crockett, Patrick W. Thorne, Peter S. Cohn, Richard D. Zeldin, Darryl C. TI Exposure to multiple indoor allergens in US homes and its relationship to asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergen; indoor exposure; asthma; allergy ID HOUSE-DUST MITE; INNER-CITY CHILDREN; 1ST NATIONAL-SURVEY; ALTERNARIA-ALTERNATA; MOUSE ALLERGEN; ENVIRONMENTAL INTERVENTION; COCKROACH ALLERGEN; UNITED-STATES; DOG ALLERGEN; SENSITIZATION AB Background: The National Survey of Lead and Allergens in Housing was the first population-based study to measure indoor allergen levels in US homes. Objective: We characterized the overall burden to multiple allergens and examined whether increased allergen levels were associated with occupants' asthma status. Methods: This cross-sectional study surveyed a nationally representative sample of 831 housing units in 75 different locations throughout the United States. Information was collected by means of questionnaire and environmental assessment. Allergen concentrations in dust samples were assessed by using immunoassays. The following cutoff points were used to define increased allergen levels: 10 mu g/g for Der p 1, Der f 1, and Can f 1; 8 mu g/g for Fel d 1; 8 U/g for Bla g 1; 1.6 mu g/g for mouse urinary protein; and 7 mu g/g for Alternaria alternata antigens. Allergen burden was considered high when 4 or more allergens exceeded increased levels in any of the sampling locations. Results: Exposure to multiple allergens was common in US homes. Of the surveyed homes, 51.5% had at least 6 detectable allergens and 45.8% had at least 3 allergens exceeding increased levels. Race, income, housing type, absence of children, and presence of smokers, pets, cockroaches, rodents, and mold/moisture-related problems were independent predictors of high allergen burden. Among atopic subjects, high allergen burden increased the odds of having asthma symptoms (odds ratio, 1.81; 95% CI, 1.04-3.15). Conclusion: Increased allergen levels in the home are associated with asthma symptoms in allergic individuals. C1 [Salo, Paeivi M.; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Arbes, Samuel J.] Rho Inc, Chapel Hill, NC USA. [Crockett, Patrick W.; Cohn, Richard D.] Constella Grp LLC, Durham, NC USA. [Thorne, Peter S.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. RP Zeldin, DC (reprint author), NIEHS, NIH, 111 Alexander Dr,Mail Drop D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS [Z01 ES025041-10] NR 39 TC 85 Z9 89 U1 2 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2008 VL 121 IS 3 BP 678 EP 684 DI 10.1016/j.jaci.2007.12.1164 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 273GR UT WOS:000253918900021 PM 18255132 ER PT J AU Cohen, SG AF Cohen, Sheldon G. TI Blocking asthmatic progression and chronicity in the precorticosteroid era SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material C1 NIAID, Natl Lib Med, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, Natl Lib Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2008 VL 121 IS 3 BP 787 EP 790 DI 10.1016/j.jaci.2008.01.024 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 273GR UT WOS:000253918900052 PM 18328904 ER PT J AU Milner, JD Brenchley, J Freeman, AF Holland, SM Paul, WE Douek, DC AF Milner, J. D. Brenchley, J. Freeman, A. F. Holland, S. M. Paul, W. E. Douek, D. C. TI Dramatically impaired Th17 production in patients with stat3-mutation positive hyper-ige syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Milner, J. D.; Brenchley, J.; Freeman, A. F.; Holland, S. M.; Paul, W. E.; Douek, D. C.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2008 VL 121 IS 3 MA LB28 BP 798 EP 798 DI 10.1016/j.jaci.2008.01.064 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 273GR UT WOS:000253918900081 ER PT J AU Da Ros, VG Maldera, JA Willis, WD Cohen, DJ Goulding, EH Gelman, DM Rubinstein, M Eddy, EM Cuasnicu, PS AF Da Ros, Vanina G. Maldera, Julieta A. Willis, William D. Cohen, Debora J. Goulding, Eugenia H. Gelman, Diego M. Rubinstein, Marcelo Eddy, Edward M. Cuasnicu, Patricia S. TI Impaired sperm fertilizing ability in mice lacking epididymal protein crisp1 SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-Society-of-Andrology CY APR 12-15, 2008 CL Albuquerque, NM SP Amer Soc Androl C1 [Da Ros, Vanina G.; Maldera, Julieta A.; Cohen, Debora J.; Cuasnicu, Patricia S.] Consejo Nacl Invest Cient & Tecn, IBYME, RA-1033 Buenos Aires, DF, Argentina. [Gelman, Diego M.; Rubinstein, Marcelo] Consejo Nacl Invest Cient & Tecn, INGEBI, RA-1033 Buenos Aires, DF, Argentina. [Willis, William D.; Goulding, Eugenia H.; Eddy, Edward M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2008 SU S MA 1 BP 29 EP 29 PG 1 WC Andrology SC Endocrinology & Metabolism GA 268PN UT WOS:000253591800004 ER PT J AU Gawel, D Pham, PT Fijalkowska, WJ Jonczyk, P Schaaper, RM AF Gawel, Damian Pham, Phuong T. Fijalkowska, Wona J. Jonczyk, Piotr Schaaper, Roel M. TI Role of accessory DNA Polymerases in DNA replication in Escherichia coli: analysis of the dnaX36 mutator mutant SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ONE HOLOENZYME PARTICLE; UNIQUE C-TERMINUS; III HOLOENZYME; LAGGING-STRAND; TAU-BINDS; DISTINCT DOMAINS; GAMMA-SUBUNIT; WILD-TYPE; POL-IV; MUTATIONAL SPECIFICITY AB The dnaX36(TS) mutant of Escherichia coli confers a distinct mutator phenotype characterized by enhancement of transversion base substitutions and certain (-1) frameshift mutations. Here, we have further investigated the possible mechanism(s) underlying this mutator effect, focusing in particular on the role of the various E. coli DNA polymerases. The dnaX gene encodes the tau subunit of DNA polymerase III (Pol III) holoenzyme, the enzyme responsible for replication of the bacterial chromosome. The dnaX36 defect resides in the C-terminal domain V of tau, essential for interaction of tau with the alpha (polymerase) subunit, suggesting that the mutator phenotype is caused by an impaired or altered alpha-tau interaction. We previously proposed that the mutator activity results from aberrant processing of terminal mismatches created by Pol III insertion errors. The present results, including lack of interaction of dnaX36 with mutM, mutY, and recA defects, support our assumption that dnaX36-mediated mutations originate as errors of replication rather than DNA damage-related events. Second, an important role is described for DNA Pol II and Pol IV in preventing and producing, respectively, the mutations. In the system used, a high fraction of the mutations is dependent on the action of Pol IV in a (dinB) gene dosage-dependent manner. However, an even larger but opposing role is deduced for Pol II, revealing Pol II to be a major editor of Pol III mediated replication errors. Overall, the results provide insight into the interplay of the various DNA polymerases, and of T subunit, in securing a high fidelity of replication. C1 [Gawel, Damian; Pham, Phuong T.; Schaaper, Roel M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Fijalkowska, Wona J.; Jonczyk, Piotr] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov RI Fijalkowska, Iwona/I-7796-2016 FU Intramural NIH HHS NR 93 TC 20 Z9 21 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2008 VL 190 IS 5 BP 1730 EP 1742 DI 10.1128/JB.01463-07 PG 13 WC Microbiology SC Microbiology GA 268CA UT WOS:000253554300028 PM 18156258 ER PT J AU Liu, ML Li, YX Zhou, XM Zhao, DM AF Liu, Mei-li Li, Yu-xing Zhou, Xiang-mei Zhao, De-ming TI Copper(II) inhibits in vitro conformational conversion of ovine prion protein triggered by low pH SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE circular dichroism spectra; conformational conversion; copper; ovine prion protein; pH; protease K ID BINDING; RECOMBINANT; FRAGMENT; PRP; PEPTIDE-106-126; NEUROTOXICITY; OCTAPEPTIDE; EXPRESSION; DEPENDENCE; REDUCTION AB To gain insight into the conformational conversion of ovine prion protein (OvPrP(C)) at different pH values and/or in the presence of CuCl(2), the secondary structure of OvPrP(C) was analysed by circular dichroism (CD) spectroscopy. Copper treatment of OvPrP(C) under moderately acidic conditions (pH similar to 5.0-6.0) as well as physiological conditions (pH 7.4) also makes OvPrP(C) adopt protease-resistant and P-sheet-rich conformation. However, under lower pH conditions (2.0-4.5) with copper treatment, OvPrP(C) gained higher alpha-helix structure. This study demonstrated that Cu(2+) can significantly modulate conformational conversion triggered by acidic pH, and this will provide therapeutic intervention approaches for prion diseases. C1 [Liu, Mei-li; Zhou, Xiang-mei; Zhao, De-ming] China Agr Univ, Coll Vet Med, Natl Anim TSE Lab, Beijing 100094, Peoples R China. [Li, Yu-xing] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Zhao, DM (reprint author), China Agr Univ, Coll Vet Med, Natl Anim TSE Lab, Beijing 100094, Peoples R China. EM zhaodm@cau.edu.cn RI Zhou, Xiangmei/H-6380-2011 NR 28 TC 8 Z9 9 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0021-924X J9 J BIOCHEM JI J. Biochem. PD MAR PY 2008 VL 143 IS 3 BP 333 EP 337 DI 10.1093/jb/mvm224 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 286IX UT WOS:000254840700007 PM 18039688 ER PT J AU Chernomordik, V Hassan, M Amyot, F Riley, J Gandjbakhche, A AF Chernomordik, Victor Hassan, Moinuddin Amyot, Franck Riley, Jason Gandjbakhche, Amir TI Use of scaling relations to extract intrinsic fluorescence lifetime of targets embedded in turbid media SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE biomedical optics; fluorescence; light propagation; biological tissues ID IN-VIVO; LOCALIZATION; REFLECTANCE; TOMOGRAPHY; INCLUSION; TISSUE AB We present a novel method for estimating the intrinsic fluorescence lifetime of deeply embedded localized fluorophores. It is based on scaling relations, characteristic for turbid media. The approach is experimentally substantiated by successfully reconstructing lifetimes for targets at depths up to 14.5 mm. A derived correction factor was determined from the product of the transport-corrected scattering coefficient mu(s)' and the index of refraction n(r). In addition, data from an array of detectors (>= 2) can be used to estimate mu(s)'n(r). The suggested algorithm is a promising tool for diagnostic fluorescence, since lifetime can be a sensitive indicator of the fluorophore environment. (C) 2008 Society of Photo-Optical Instrumentation Engineers. C1 [Chernomordik, Victor; Hassan, Moinuddin; Amyot, Franck; Riley, Jason; Gandjbakhche, Amir] NICHHD, NIH, Bethesda, MD 20892 USA. RP Chernomordik, V (reprint author), NICHHD, NIH, Bldg 9 Rm B1E11 Bldg 9 Rm B1E01, Bethesda, MD 20892 USA. EM vchern@helix.nih.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2008 VL 13 IS 2 AR 024025 DI 10.1117/1.2904660 PG 4 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 309CM UT WOS:000256438300043 PM 18465988 ER PT J AU Guo, ZJ Tsai, MH Shiao, YH Chen, LH Wei, ML Lv, X Gius, D Little, JB Mitchell, JB Chuang, EY AF Guo, Zhanjun Tsai, Mong-Hsun Shiao, Yih-Horng Chen, Li-Han Wei, Mei-Ling Lv, Xing Gius, David Little, John B. Mitchell, James B. Chuang, Eric Y. TI DNA (cytosine-5)-methyltransferase 1 as a mediator of mutant p53-determined p16(ink4A) down-regulation SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE DNMT1; p53; Small interfering RNA; Chromatin immunoprecipitation; Methylation-specific polymerase chain reaction ID P53; METHYLTRANSFERASE; METHYLATION; CELLS; EXPRESSION; BINDING; MUTATIONS; COMPLEX; CANCER AB In cancer, gene silencing via hypermethylation is as common as genetic mutations in p53. Understanding the relationship between mutant p53 and hypermethylation of other tumor suppressor genes is essential when elucidate mechanisms of tumor development. In this study, two isogenic human B lymphoblast cell lines with different p53 status include TK6 containing wild-type p53 and WTK1 with mutant p53 were used and contrasted. Lower levels of p16(ink4A) protein were detected in WTK1 cells than in TK6 cells, which were accompanied by increased DNA (cytosine-5)-methyltransferase 1 (DNMT1) gene expression as well as hypermethylation of the p16(ink4A) promoter. siRNA experiments to transiently knock down wild-type p53 in TK6 cells resulted in increase of DNMT1 expression as well as decrease of p16(ink4A) protein. Conversely, siRNA knockdown of mutant p53 in WTK1 cells did not alter either DNMT1 or p16(ink4A) protein levels. Furthermore, loss of suppression function of mutant p53 to DNMT1 in WTK1 was caused by the attenuation of its binding ability to the DNMT1 promoter. In summary, we provide evidences to elucidate the relationship between mutant p53 and DNMT1. Our results indicate that mutant p53 loses its ability to suppress DNMT1 expression, and thus enhances methylation levels of the p16(ink4A) promoter and subsequently down-regulates p16(ink4A) protein. C1 [Chen, Li-Han; Chuang, Eric Y.] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan. [Guo, Zhanjun; Tsai, Mong-Hsun; Lv, Xing; Gius, David; Mitchell, James B.; Chuang, Eric Y.] NCI, Radiat Biol & Oncol Branches, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Guo, Zhanjun] Hebei Med Univ, Hosp 4, Dept Gastroenterol & Hepatol, Shijiazhuang, Peoples R China. [Tsai, Mong-Hsun] Natl Taiwan Univ, Inst Biotechnol, Coll Bioesources & Agr, Taipei 10764, Taiwan. [Shiao, Yih-Horng] NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. [Chen, Li-Han; Chuang, Eric Y.] Natl Taiwan Univ, Dept Elect Engn, Grad Inst Epidemiol, Taipei 10764, Taiwan. [Chen, Li-Han; Chuang, Eric Y.] Natl Taiwan Univ, Dept Life Sci, Grad Inst Epidemiol, Taipei 10764, Taiwan. [Chen, Li-Han; Chuang, Eric Y.] Natl Taiwan Univ, Res Ctr Med Excellence, Taipei 10764, Taiwan. [Wei, Mei-Ling] Walter Reed Army Inst Res, Div Neurosci, Silver Spring, MD 20910 USA. [Mitchell, James B.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. RP Chuang, EY (reprint author), Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, 1 Sect,4Roosevelt Rd, Taipei 10764, Taiwan. EM chuangey@ntu.edu.tw FU Intramural NIH HHS NR 19 TC 5 Z9 5 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 EI 1423-0127 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAR PY 2008 VL 15 IS 2 BP 163 EP 168 DI 10.1007/s11373-007-9222-y PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 267RV UT WOS:000253527800003 PM 18038118 ER PT J AU Sasiela, CA Stewart, DH Kitagaki, J Safiran, YJ Yang, YL Weissman, AM Oberoi, P Davydov, IV Goncharova, E Beutler, JA McMahon, JB O'Keefe, BR AF Sasiela, Christy A. Stewart, David H. Kitagaki, Jirouta Safiran, Yassamin J. Yang, Yili Weissman, Allan M. Oberoi, Pankaj Davydov, Ilia V. Goncharova, Ekaterina Beutler, John A. McMahon, James B. O'Keefe, Barry R. TI Identification of inhibitors for MDM2 ubiquitin ligase activity from natural product extracts by a novel high-throughput electrochemiluminescent screen SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE high-throughput screening; MDM2; ubiquitin; electrochemiluminescent screen; natural product extracts ID P53 PATHWAY; CELLS; ENZYMES; ASSAYS; DRUGS; HDM2 AB High-throughput screening technologies have revolutionized the manner in which potential therapeutics are identified. Although they are the source of lead compounds for similar to 65% of anticancer and antimicrobial drugs approved by the Food and Drug Administration between 1981 and 2002, natural products have largely been excluded from modern screening programs. This is due, at least in part, to the inherent difficulties in testing complex extract mixtures, which often contain nuisance compounds, in modern bioassay systems. In this article, the authors present a novel electrochemiluminescent assay system for inhibition of MDM2 activity that is suitable for testing natural product extracts in high-throughput screening systems. The assay was used to screen more than 144,000 natural product extracts. The authors identified 1 natural product, sempervirine, that inhibited MDM2 auto-ubiquitination, MDM2-mediated p53 degradation, and led to accumulation of p53 in cells. Sempervirine preferentially induced apoptosis in transformed cells expressing wild-type p53, suggesting that it could be a potential lead for anticancer therapeutics. C1 [Sasiela, Christy A.; Goncharova, Ekaterina; Beutler, John A.; McMahon, James B.; O'Keefe, Barry R.] NCI, MTDP, CCR, Mol Target Dev Program, Ft Detrick, MD 21702 USA. [Stewart, David H.; Safiran, Yassamin J.; Oberoi, Pankaj; Davydov, Ilia V.] Meso Scale Discovery, Gaithersburg, MD USA. [Kitagaki, Jirouta; Yang, Yili; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP O'Keefe, BR (reprint author), NCI, MTDP, CCR, Mol Target Dev Program, Bldg 562,Room 201, Ft Detrick, MD 21702 USA. EM okeefe@ncifcrf.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU Intramural NIH HHS NR 23 TC 39 Z9 40 U1 3 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 EI 1552-454X J9 J BIOMOL SCREEN JI J. Biomol. Screen PD MAR PY 2008 VL 13 IS 3 BP 229 EP 237 DI 10.1177/1087057108315038 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 282OF UT WOS:000254576400006 PM 18270365 ER PT J AU Birmingham, P Helm, JM Manner, PA Tuan, RS AF Birmingham, Patrick Helm, Jeannine M. Manner, Paul A. Tuan, Rocky S. TI Simulated joint infection assessment by rapid detection of live bacteria with real-time reverse transcription polymerase chain reaction SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL HIP-ARTHROPLASTY; INTRAOPERATIVE FROZEN-SECTIONS; REVISION ARTHROPLASTY; ESCHERICHIA-COLI; PERIPROSTHETIC INFECTION; ANTIBIOTIC-TREATMENT; KNEE ARTHROPLASTY; MESSENGER-RNA; PCR ASSAY; DIAGNOSIS AB Background: Although microbiological bacterial culture is currently considered the gold standard for diagnosis of septic arthritis, many studies have documented substantial false-negative and false-positive rates. The objective of this study was to determine whether real-time quantitative reverse transcription polymerase chain reaction can be used to detect bacterial messenger RNA (mRNA) in synovial fluid as a way to distinguish live and dead bacteria as an indicator of active infection. Methods: Synovial fluid samples were obtained from twelve consecutive patients who presented with knee pain and effusion but no evidence of infection. Following assurance of sterility with plate cultures, each sample was inoculated with clinically relevant bacteria and incubated for twenty-four hours to simulate septic arthritis. Bacterial viability and load were assessed with cultures. Selected samples were also treated with a single dose of a combination of two antibiotics, vancomycin and gentamicin, and sampled at several time points. Total RNA isolated from each sample was analyzed in triplicate with one-step real-time quantitative reverse transcription polymerase chain reaction to detect mRNA encoding for the genes groEL or femC. Controls included sterile, uninoculated samples and inoculated samples analyzed with quantitative polymerase chain reaction without reverse transcription. mRNA content was estimated on the basis of detection limits as a function of serial dilutions and was expressed as a function of colony number in bacterial cultures and RNA content as determined spectrophotometrically. Results: All synovial fluid samples that had been inoculated with one of the four bacterial species, and analyzed in triplicate, were identified (distinguished from aseptic synovial fluid) with real-time quantitative reverse transcription polymerase chain reaction; there were no false-negative results. All inoculated samples produced bacterial colonies on culture plates, while cultures of the aseptic samples were negative for growth. The detection limit of the one-step bacterial mRNA-based real-time quantitative reverse transcription polymerase chain reaction varied depending on the bacterial species. A time-dependent decrease in the concentration of detectable bacterial mRNA was seen after incubation of bacteria with antibiotics. Conclusions: The direct quantification of the concentration of viable bacterial mRNA with real-time quantitative reverse transcription polymerase chain reaction allows identification of both culture-positive bacterial infection and so-called unculturable bacterial infection in a simulated septic arthritis model. In contrast to conventional polymerase chain reaction, real-time quantitative reverse transcription polymerase chain reaction minimizes false-positive detection of nonviable bacteria and thus provides relevant information on the success or failure of antibiotic therapy. Clinical Relevance: Because real-time quantitative reverse transcription polymerase chain reaction detects live bacteria, its application in combination with other polymerase chain reaction-based methods for speciation could dramatically improve the way that joint infections are diagnosed and treated. C1 [Birmingham, Patrick; Helm, Jeannine M.; Manner, Paul A.; Tuan, Rocky S.] NIAMSD, Natl Inst Hlth, Cartilage Biol & Orthopead Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Birmingham, P (reprint author), 925 26th St NW,Apartment 410, Washington, DC 20037 USA. EM patrickbirmingham@gmail.com NR 44 TC 25 Z9 28 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2008 VL 90A IS 3 BP 602 EP 608 DI 10.2106/JBJS.G.00348 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 273QJ UT WOS:000253946500018 PM 18310711 ER PT J AU Lauretani, F Bandinelli, S Griswold, ME Maggio, M Semba, R Guralnik, JM Ferrucci, L AF Lauretani, Fulvio Bandinelli, Stefania Griswold, Michael E. Maggio, Marcello Semba, Richard Guralnik, Jack M. Ferrucci, Luigi TI Longitudinal changes in BMD and bone geometry in a population-based study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE longitudinal study; osteoporosis; periosteal apposition; endocortical resorption; BMD; bone geometry ID POSTMENOPAUSAL WOMEN; MINERAL DENSITY; AGE; FRACTURE; SIZE; FRAGILITY; STRENGTH; OUTCOMES; QUALITY; DECLINE AB We prospectively examined vBMD and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up. Periosteal apposition occurred both in men and women. Endocortical resorption causes bone loss in older women despite periosteal apposition. Introduction: To address the hypothesis that age-related changes in BMD and bone geometry may be different in men and women, we prospectively examined volumetric BMD (vBMD) and structural. bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up. Materials and Methods: Three hundred forty-five men and 464 women 21-102 yr of age from the InCHIANTI study, a population-based study in Tuscany, Italy, were included. Tibial QCT bone parameters were measured at enrollment (1998-2000) and at 3- (2001-2003) and 6-yr (2004-2006) follow-ups. Results: Periosteal apposition occurred both in men and women. The annual rate of bone periosteal apposition was higher in younger than in older men, whereas in women, the rate of apposition was homogenous across age groups. The age-related medullary expansion, expression of endocortical resorption, was significantly higher in women compared with men. In women, but not in men, accelerated endocortical resorption not sufficiently balanced by periosteal apposition caused accelerated loss in cortical bone mass. The cross-sectional moment of inertia decreased progressively over the life span in both sexes. Conclusions: Endocortical resorption causes bone loss in older women despite periosteal apposition. Obtaining a balance between endocortical resorption and perlosteal apposition should be the target for interventions aimed to decrease bone loss and prevent osteoporosis in older women. C1 [Lauretani, Fulvio; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD USA. [Lauretani, Fulvio] Tuscany Reg Hlth Agcy, Florence, Italy. [Bandinelli, Stefania] Geriatr Unit, Florence, Italy. [Griswold, Michael E.; Semba, Richard] Johns Hopkins Sch Med, Baltimore, MD USA. [Maggio, Marcello] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. RP Ferrucci, L (reprint author), Harbor Hosp, ASTRA Unit, NIA, Longitudinal Studies Sect,Clin Res Branch, 5th Floor 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-5-0002, N01-AG-821336, N01-AG-916413, R01 AG027012] NR 22 TC 51 Z9 51 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2008 VL 23 IS 3 BP 400 EP 408 DI 10.1359/JBMR.071103 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 265VV UT WOS:000253390700010 PM 17997708 ER PT J AU Hossain, MA Tsujita, M Gonzalez, FJ Yokoyama, S AF Hossain, Mohammad Anwar Tsujita, Maki Gonzalez, Frank J. Yokoyama, Shinji TI Effects of fibrate drugs on expression of ABCA1 and HDL biogenesis in hepatocytes SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE fibrates; PPAR; LXR; ABCA1; HDL; hepatocytes; cholesterol ID PROLIFERATOR-ACTIVATED-RECEPTOR; HIGH-DENSITY-LIPOPROTEIN; LIVER-X-RECEPTOR; REVERSE CHOLESTEROL TRANSPORT; GENE-EXPRESSION; PPAR-ALPHA; PEROXISOME PROLIFERATORS; SECONDARY PREVENTION; TARGETED DISRUPTION; TRANSFER PROTEIN AB Fibric acid-shaped drugs raise high-density lipoprotein (HDL) cholesterol by upregulating the HDL-related genes through activating peroxisome proliferater activated receptor (PPAR)-alpha. We investigated the effects of fibrates to induce expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and increase HDL biogenesis in hepatocytes. Fenofibrate, bezafibrate, gemfibrozil, and LY518674 were tested for HepG2 cells and primary-cultured mouse hepatocytes. All the compounds examined increased ABCA1 expression and HDL biogenesis dependent on PPAR alpha in association with the liver X receptor alpha upregulation. While fenofibrate and LY518674 showed exclusive dependency on PPARa for these activities, bezafibrate and gemfibrozil exhibited dependency on PPAR beta/delta and PPAR gamma as well. On the other hand, cholesterol-enrichment of HDL may involve PPAR gamma for fenofibrate and bezafibrate, and PPAR beta/delta for the fibrates examined except for bezafibrate. We concluded that fibrates enhance expression of ABCA1 in hepatocytes to contribute to increase of the HDL biogenesis in a PPAR-dependent manner, whether exclusively or nonexclusively on PPAR alpha. C1 [Hossain, Mohammad Anwar; Tsujita, Maki; Yokoyama, Shinji] Nagoya City Univ, Grad Sch Med Sci, Dept Biochem, Mizuho Ku, Nagoya, Aichi 4678601, Japan. [Gonzalez, Frank J.] NCI, NIH, Bethesda, MD 20892 USA. RP Yokoyama, S (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Biochem, Mizuho Ku, Kawasumi 1,Mizuho Cho, Nagoya, Aichi 4678601, Japan. EM syokoyam@med.nagoya-cu.ac.jp OI Hossain, Md. Anwar/0000-0002-3929-6211; TSUJITA, MAKI/0000-0003-1108-621X NR 44 TC 27 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAR PY 2008 VL 51 IS 3 BP 258 EP 266 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 284CY UT WOS:000254684100007 PM 18356690 ER PT J AU de Bakker, BI Bodnar, A van Dijk, EMHP Vamosi, G Damjanovich, S Waldmann, TA van Hulst, NF Jenei, A Garcia-Parajo, MF AF de Bakker, Barbel I. Bodnar, Andrea van Dijk, Erik M. H. P. Vamosi, Gyorgy Damjanovich, Sandor Waldmann, Thomas A. van Hulst, Niek F. Jenei, Attila Garcia-Parajo, Maria F. TI Nanometer-scale organization of the alpha subunits of the receptors for IL2 and IL15 in human T lymphoma cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE near-field scanning optical microscopy (NSOM); Interleukin receptors IL2R; IL15R; single-molecule detection; nanometer-scale membrane organization ID SCANNING OPTICAL MICROSCOPY; INTERLEUKIN-2 RECEPTOR; IL-2 RECEPTOR; GAMMA-CHAIN; LIPID RAFTS; BETA-CHAIN; CYTOKINE; SURFACE; ASSOCIATION; IL-2R-ALPHA AB Interleukin 2 and interleukin 15 (IL2 and IL15, respectively) provide quite distinct contributions to T-cell-mediated immunity, despite having similar receptor composition and signaling machinery. As most of the proposed mechanisms underlying this apparent paradox attribute key significance to the individual alpha-chains of IL2 and IL15 receptors, we investigated the spatial organization of the receptors IL2R alpha and IL15R alpha at the nanometer scale expressed on a human CD4(+) leukemia T cell line using single-molecule-sensitive near-field scanning optical microscopy (NSOM). In agreement with previous findings, we here confirm clustering of IL2R alpha and IL15R alpha at the submicron scale. In addition to clustering, our single-molecule data reveal that a non-negligible percentage of the receptors are organized as monomers. Only a minor fraction of IL2R alpha molecules reside outside the clustered domains, whereas similar to 30% of IL15R alpha molecules organize as monomers or small clusters, excluded from the main domain regions. Interestingly, we also found that the packing densities per unit area of both IL2R alpha and IL15R alpha domains remained constant, suggesting a 'building block' type of assembly involving repeated structures and composition. Finally, dual-color NSOM demonstrated co-clustering of the two alpha-chains. Our results should aid understanding the action of the IL2R-IL15R system in T cell function and also might contribute to the more rationale design of IL2R- or IL15R-targeted immunotherapy agents for treating human leukemia. C1 Univ Twente, Fac Sci & Technol, MESA Res Inst Nanotechnol, Appl Opt Grp, NL-7500 AE Enschede, Netherlands. Univ Debrecen, Hungarian Acad Sci, Res Ctr Mol Med, Cell Biol & Signaling Res Grp, H-4032 Debrecen, Hungary. Univ Debrecen, Med & Hlth Sci Ctr, Res Ctr Mol Med, Dept Biophys & Cell Biol, H-4012 Debrecen, Hungary. NIH, NCI, Metab Branch, Bethesda, MD 20892 USA. ICFO Inst Ciencies Fotoniques, Barcelona 08860, Spain. ICREA Inst Catalana Recerca Estudis Avancats, Barcelona 08010, Spain. IBEC Inst Bioengn Catalunya & CIBER BNN, Barcelona 08028, Spain. RP Garcia-Parajo, MF (reprint author), Univ Twente, Fac Sci & Technol, MESA Res Inst Nanotechnol, Appl Opt Grp, POB 217, NL-7500 AE Enschede, Netherlands. EM mgarcia@pcb.ub.es RI Vamosi, Gyorgy/C-9351-2009; Bodnar, Andrea/A-9286-2011; Damjanovich, Sandor/A-9284-2011; van Hulst, Niek/J-2121-2012; Garcia-Parajo, Maria/I-4610-2015 OI van Hulst, Niek/0000-0003-4630-1776; Garcia-Parajo, Maria/0000-0001-6618-3944 NR 36 TC 50 Z9 50 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD MAR 1 PY 2008 VL 121 IS 5 BP 627 EP 633 DI 10.1242/jcs.019513 PG 7 WC Cell Biology SC Cell Biology GA 266HU UT WOS:000253425900010 PM 18287585 ER PT J AU Li, LZ Lundkvist, A Andersson, D Wilhelmsson, U Nagai, N Pardo, AC Nodin, C Stahlberg, A Aprico, K Larsson, K Yabe, T Moons, L Fotheringham, A Davies, I Carmeliet, P Schwartz, JP Pekna, M Kubista, M Blomstrand, F Maragakis, N Nilsson, M Pekny, M AF Li, Lizhen Lundkvist, Andrea Andersson, Daniel Wilhelmsson, Ulrika Nagai, Nobuo Pardo, Andrea C. Nodin, Christina Stahlberg, Anders Aprico, Karina Larsson, Kerstin Yabe, Takeshi Moons, Lieve Fotheringham, Andrew Davies, Ioan Carmeliet, Peter Schwartz, Joan P. Pekna, Marcela Kubista, Mikael Blomstrand, Fredrik Maragakis, Nicholas Nilsson, Michael Pekny, Milos TI Protective role of reactive astrocytes in brain ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE astrocytes; GFAP; intermediate filaments; reactive gliosis (astrogliosis); vimentin ID FIBRILLARY ACIDIC PROTEIN; SPINAL-CORD-INJURY; CENTRAL-NERVOUS-SYSTEM; INTERMEDIATE-FILAMENTS; MICE DEFICIENT; PLASMINOGEN-ACTIVATOR; NEURONAL DEGENERATION; CONDITIONAL ABLATION; CEREBRAL-ISCHEMIA; HYPOTONIC STRESS AB Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament ( IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP(-/-) Vim(-/-) mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery ( MCA) transection, infarct volume was 210 to 350% higher in GFAP(-/-) Vim(-/-) than in wild-type (WT) mice; GFAP(-/-), Vim(-/-) and WT mice had the same infarct volume. Endothelin B receptor (ETBR) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP(-/-) Vim(-/-) astrocytes. In WT astrocytes, ETBR colocalized extensively with bundles of IFs. GFAP(-/-) Vim(-/-) astrocytes showed attenuated endothelin-3-induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1)-mediated glutamate transport was lower in GFAP(-/-) Vim(-/-) than in WT mice. DNA array analysis and quantitative real-time PCR showed down-regulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ETBR-mediated control of gap junctions, and PAI-1 expression. C1 [Li, Lizhen; Lundkvist, Andrea; Andersson, Daniel; Wilhelmsson, Ulrika; Nodin, Christina; Aprico, Karina; Blomstrand, Fredrik; Nilsson, Michael; Pekny, Milos] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil,Ctr Brain Repair & R, SE-40530 Gothenburg, Sweden. [Nagai, Nobuo; Moons, Lieve; Carmeliet, Peter] KU Leuven VIB, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. [Pardo, Andrea C.; Maragakis, Nicholas] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Stahlberg, Anders; Kubista, Mikael] Chalmers, Dept Chem & Biosci, S-41296 Gothenburg, Sweden. [Stahlberg, Anders; Kubista, Mikael] TATAA Bioctr, Gothenburg, Sweden. [Larsson, Kerstin; Pekna, Marcela] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Chem & Cell Biol, SE-40530 Gothenburg, Sweden. [Yabe, Takeshi; Schwartz, Joan P.] Natl Inst Neurol Disorders & Stroke, Neurotroph Factors Sect, NIH, Bethesda, MD USA. [Fotheringham, Andrew; Davies, Ioan] Univ Manchester, Sch Med, Manchester, Lancs, England. [Fotheringham, Andrew; Davies, Ioan] Univ Manchester, Sch Biol Sci, Manchester, Lancs, England. RP Pekny, M (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil,Ctr Brain Repair & R, SE-40530 Gothenburg, Sweden. EM Milos.Pekny@neuro.gu.se RI Kubista, Mikael/A-5689-2008; OI Kubista, Mikael/0000-0002-2940-352X; Pekna, Marcela/0000-0003-2734-8237; Moons, Lieve (Godelieve)/0000-0003-0186-1411; Pardo, Andrea/0000-0001-7767-8539; Stahlberg, Anders/0000-0003-4243-0191 NR 43 TC 231 Z9 238 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2008 VL 28 IS 3 BP 468 EP 481 DI 10.1038/sj.jcbfm.9600546 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 266DA UT WOS:000253410400005 PM 17726492 ER PT J AU Schatlo, B Henning, EC Pluta, RM Latour, LL Golpayegani, N Merrill, MJ Lewin, N Chen, Y Oldfield, EH AF Schatlo, Bawarjan Henning, Erica C. Pluta, Ryszard M. Latour, Lawrence L. Golpayegani, Nahal Merrill, Marsha J. Lewin, Naomi Chen, Yong Oldfield, Edward H. TI Nitrite does not provide additional protection to thrombolysis in a rat model of stroke with delayed reperfusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE nitrite; stroke; magnetic resonance imaging; nitric oxide; reperfusion injury ID TISSUE-PLASMINOGEN ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; OXYGEN SPECIES PRODUCTION; HEMORRHAGIC TRANSFORMATION; ARTERY OCCLUSION; EMBOLIC STROKE; SODIUM-NITRITE; INJURY; OXIDE AB An adjuvant therapy to prolong the therapeutic window for stroke patients is urgently needed. This randomized, blinded, placebo-controlled study investigated adjuvant intravenous sodium nitrite with recombinant tissue plasminogen activator (rtPA) in middle cerebral artery occlusion (MCAO) with 6 and 2 h of ischemia followed by reperfusion in Sprague-Dawley rats (n = 59). Quantitative diffusion, T-1-,T-2- weighted, and semiquantitative perfusion imaging were performed before and after reperfusion and at 48 h after ischemia to determine the spatiotemporal evolution of stroke. After 48 h animals were killed and examined to evaluate infarct size and evidence of hemorrhagic transformation. Factor VIII immunostaining was performed to assess vessel morphology. Nitrite treatment (6 h group: 37.5 mu mol for more than 90 mins; 2h group: 26.25 and 1.75 mu mol for more than 60 mins) did not reduce infarct volume 48 h after MCAO compared with saline-treated placebo groups after 6 or 2h of MCAO. Stroke progression from baseline to 48h, based on the apparent diffusion coefficient and relative cerebral blood flow deficits before and after reperfusion and T2- weighted hyperintensity at 48 h, did not differ between treated and control animals. These results suggest that nitrite is not a protective adjuvant therapy to delayed rtPA administration after ischemic stroke in rats. C1 [Henning, Erica C.; Latour, Lawrence L.; Lewin, Naomi; Chen, Yong] Natl Inst Neurol Disorders & Stroke, Stroke Branch, NIH, Bethesda, MD USA. [Schatlo, Bawarjan; Pluta, Ryszard M.; Golpayegani, Nahal; Merrill, Marsha J.; Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,5D37, Bethesda, MD 20892 USA. EM rysiek@ninds.nih.gov RI SCHATLO, Bawarjan/F-4285-2010; Henning, Erica/E-8542-2010 FU Intramural NIH HHS NR 33 TC 10 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2008 VL 28 IS 3 BP 482 EP 489 DI 10.1038/sj.jcbfm.9600542 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 266DA UT WOS:000253410400006 PM 17684515 ER PT J AU Zappe, AC Pfeuffer, J Merkle, H Logothetis, NK Goense, JBM AF Zappe, Anne C. Pfeuffer, Josef Merkle, Hellmut Logothetis, Nikos K. Goense, Jozien B. M. TI The effect of labeling parameters on perfusion-based fMRI in nonhuman primates SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE arterial transit time; cerebral blood flow (CBF); monkey brain; specificity; spin tagging (ASL) ID CEREBRAL-BLOOD-FLOW; BRAIN PERFUSION; TRANSIT-TIME; ARTERIAL WATER; FUNCTIONAL MRI; GRADIENT-ECHO; SPIN; SIGNAL; BOLD; CAPILLARY AB The blood oxygenation level-dependent (BOLD) signal is the most commonly used modality of functional magnetic resonance imaging (fMRI) today. Although easy to implement, it is an ambiguous signal since it results from a combination of several hemodynamic factors. Functional cerebral blood flow changes, as measured by using arterial spin labeling (ASL), typically occur in the parenchyma and have been demonstrated to be more closely coupled to neural activation compared with BOLD. However, the intrinsically low signals from ASL techniques have hindered its widespread application to fMRI for basic research and even more so for clinical applications. Here, we report the first implementation of continuous ASL in the anaesthetized macaque at high magnetic field of 7 T. The technique was optimized to permit maximum signal-to-noise ratio of functional perfusion-based images at high spatial resolution. The effect of labeling parameters, such as label time and post-label delay (PLD), on functional cerebral blood flow (fCBF) in the visual cortex was evaluated. Functional cerebral blood flow maps did not change with increasing label time after 2,000ms, indicating that a label time of 2,000 ms is sufficient for reliable mapping of fCBF. The percent changes obtained using fCBF were better localized to gray matter, than those obtained with BOLD. A short PLD of 200 ms revealed significantly higher fCBF changes at the cortical surface, indicating large-vessel contamination, than a long PLD of 800 ms. However, the effect of the PLD on fCBF was smaller than on baseline CBF. These results are of importance for high-resolution applications, and when accurate quantification is required for studies in monkeys as well as in humans. C1 [Zappe, Anne C.; Pfeuffer, Josef; Logothetis, Nikos K.; Goense, Jozien B. M.] Max Planck Inst Biol Cybernet, Dept Physiol & Cognit Proc, D-72076 Tubingen, Germany. [Pfeuffer, Josef] MR Applicat Dev, Siemens Med Solut, Erlangen, Germany. [Merkle, Hellmut] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Logothetis, Nikos K.] Univ Manchester, Manchester, Lancs, England. RP Zappe, AC (reprint author), Max Planck Inst Biol Cybernet, Dept Physiol & Cognit Proc, Spemannstr 38, D-72076 Tubingen, Germany. EM aczappe@tuebingen.mpg.de FU Intramural NIH HHS NR 42 TC 17 Z9 18 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2008 VL 28 IS 3 BP 640 EP 652 DI 10.1038/sj.jcbfm.9600564 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 266DA UT WOS:000253410400020 PM 17960143 ER PT J AU Merke, DP AF Merke, Deborah P. TI Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; DECREASED EPINEPHRINE RESERVE; GENDER-RELATED BEHAVIOR; QUALITY-OF-LIFE; FEMALE-PATIENTS; GLUCOCORTICOID REPLACEMENT; DISEASE MANIFESTATION; INTENSITY EXERCISE; MOLECULAR GENOTYPE; POLYCYSTIC OVARIES AB Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders where there is impairment of cortisol biosynthesis. CAH due to 21-hydroxylase deficiency accounts for 95% of cases and shows a wide range of clinical severity. Treatment of the classic or severe form of CAH is targeted at replacing cortisol and aldosterone and effectively controlling excess androgen symptoms by using the lowest possible glucocorticoid dose. Treatment of the mild or nonclassic form is targeted at controlling excess androgen symptoms and may or may not involve glucocorticoid therapy. Hydrocortisone is the treatment of choice for children, but there is no consensus on how patients should be treated as adults. Current glucocorticoid therapy is suboptimal because it is often difficult to reduce excess androgen without giving excess glucocorticoid, and patients may experience hypercortisolism, androgen excess, or a combination of these states. Treatment of CAH, especially in the adult patient, remains controversial given the lack of prospective randomized controlled trials comparing treatment regimens. Nevertheless, patients benefit from careful individualized therapy with avoidance of Cushingoid side effects and optimization of reproductive, sexual, and bone health. C1 [Merke, Deborah P.] NICHHD, NIH, Clin Ctr & Reprod Biol, Bethesda, MD 20892 USA. [Merke, Deborah P.] NICHHD, Med Branch, NIH, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), NICHHD, NIH, Clin Ctr & Reprod Biol, Bethesda, MD 20892 USA. NR 60 TC 40 Z9 44 U1 4 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2008 VL 93 IS 3 BP 653 EP 660 DI 10.1210/jc.2007-2417 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700002 PM 18326005 ER PT J AU Legro, RS Barnhart, HX Schlaff, WD Carr, BR Diamond, MP Carson, SA Steinkampf, MP Coutifaris, C McGovern, PG Cataldo, NA Gosman, GG Nestler, JE Giudice, LC Ewens, KG Spielman, RS Leppert, PC Myers, ER AF Legro, Richard S. Barnhart, Huiman X. Schlaff, William D. Carr, Bruce R. Diamond, Michael P. Carson, Sandra A. Steinkampf, Michael P. Coutifaris, Christos McGovern, Peter G. Cataldo, Nicholas A. Gosman, Gabriella G. Nestler, John E. Giudice, Linda C. Ewens, Kathryn G. Spielman, Richard S. Leppert, Phyllis C. Myers, Evan R. TI Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE REPLACEMENT THERAPY; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; METABOLIC FACTORS; METFORMIN; WOMEN; PREVALENCE; PREGNANCY; FEATURES; OUTCOMES AB Context: Clomiphene and insulin sensitizers such as metformin are used to induce ovulation in polycystic ovary syndrome ( PCOS), but the ovulatory response is variable, and the causes of this variation are poorly understood. Objective: Our objective was to identify predictive genetic polymorphisms and other determinants of ovulatory response. Design: This was a substudy of a multicenter randomized clinical trial. Setting: This study was performed at academic medical centers and their affiliates. Participants: A total of 312 women with PCOS were included in the study. Main Outcome Measures: Historical, biometric, biochemical, and genetic parameters were performed. Results: We found that the C allele of a single nucleotide polymorphism in the STK11 gene ( expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin. In an analysis of ovulation per cycle, the adjusted odds ratio ( OR) comparing the C/C genotype to the G/G genotype was 0.30[95% confidence interval (CI) 0.14, 0.66], and the OR for the C/C genotype vs. the G/G genotype was also 0.30 ( 95% CI 0.14, 0.66). In an analysis of metformin-treated subjects, we found that the percentage of women who ovulated increased with the number of G alleles present: 48% ( 10 of 21) of C/C women, 67% ( 32 of 48) of C/G women, and 79% ( 15 of 19) of G/G women ovulated. We also found that increased frequency of ovulation was associated with lower body mass index (BMI) [adjusted OR of 2.36(95% CI 1.65, 3.36) and 2.05 ( 95% CI 1.46, 2.88), respectively, for comparisons of BMI less than 30 vs. BMI equal to or more than 35, BMI 30-34 vs. BMI equal to or more than 35, in the analysis of ovulation per cycle], a lower free androgen index (FAI) [adjusted OR of 1.59 ( 95% CI 1.17, 2.18) for FAI < 10 vs. FAI >= 10], and a shorter duration of attempting conception [adjusted OR of 1.63 ( 95% CI 1.20, 2.21) for < 1.5 vs. >= 1.5 yr]. Conclusions: We have demonstrated that a polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action, is associated with ovulatory response to treatment with met formin alone in a prospective randomized trial. The interaction with the effects of changes in modifiable factors (e. g. BMI or FAI) requires further study. C1 [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. [Barnhart, Huiman X.; Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Barnhart, Huiman X.; Myers, Evan R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Schlaff, William D.] Univ Colorado, Denver, CO 80202 USA. [Carr, Bruce R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Diamond, Michael P.] Wayne State Univ, Dept Obstet, Detroit, MI USA. [Diamond, Michael P.] Wayne State Univ, Dept Gynecol, Detroit, MI USA. [Carson, Sandra A.] Baylor Coll Med, Houston, TX 77030 USA. [Steinkampf, Michael P.] Univ Alabama, Birmingham, AL USA. [Coutifaris, Christos; Ewens, Kathryn G.; Spielman, Richard S.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [McGovern, Peter G.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Cataldo, Nicholas A.] Stanford Univ, Stanford, CA 94305 USA. [Gosman, Gabriella G.] Univ Pittsburgh, Pittsburgh, PA USA. [Nestler, John E.] Virginia Commonwealth Univ, Sch Med, Dept Med, Richmond, VA USA. [Giudice, Linda C.] Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA. [Leppert, Phyllis C.] NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Legro, RS (reprint author), Penn State Univ, Dept Obstet & Gynecol, Milton S Hershey Med Ctr, Coll Med, 500 Univ Dr,H103, Hershey, PA 17033 USA. EM RSL1@psu.edu OI Diamond, Michael/0000-0001-6353-4489 FU NCRR NIH HHS [C06 RR016499, M01 RR000056, M01RR10732, M01RR00056, M01 RR010732]; NICHD NIH HHS [U54-HD29834, U10 HD39005, U10 HD38999, U10 HD27011, U10 HD038988, U01 HD38997, U54 HD034449, U10 HD038999, U54 HD34449, U10 HD039005, U10 HD27049, U10 HD38998, U10 HD027011, U10 HD38992, U10 HD038992, R01 HD029834, U10 HD027049, U10 HD033172, U10 HD38988, U10 HD038998, U10 HD33172, U01 HD038997] NR 20 TC 54 Z9 59 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2008 VL 93 IS 3 BP 792 EP 800 DI 10.1210/jc.2007-1736 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700023 PM 18000088 ER PT J AU Pearce, EN Wilson, PWF Yang, Q Vasan, RS Braverman, LE AF Pearce, Elizabeth N. Wilson, Peter W. F. Yang, Qiong Vasan, Ramachandran S. Braverman, Lewis E. TI Thyroid function and lipid subparticle sizes in patients with short-term hypothyroidism and a population-based cohort SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; MAGNETIC-RESONANCE-SPECTROSCOPY; CORONARY-HEART-DISEASE; ESTER TRANSFER PROTEIN; SUBCLINICAL HYPOTHYROIDISM; CARDIOVASCULAR RISK; ALL-CAUSE; REPLACEMENT THERAPY; ARTERY-DISEASE; HEPATIC LIPASE AB Context: Relations between thyroid function and lipids remain incompletely understood. Objective: Our objective was to determine whether lipoprotein subparticle concentrations are associated with thyroid status. Design and Setting: We conducted a prospective clinical study and cross-sectional cohort analysis at a university endocrine clinic and the Framingham Heart Study. Subjects: Subjects included 28 thyroidectomized patients with short-term overt hypothyroidism and 2944 Framingham Offspring cohort participants. Main Outcome Measures: Fasting subclass concentrations of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) particles were measured by nuclear magnetic resonance spectroscopy. TSH values were also measured. Results: Total cholesterol and LDL-C were increased during short-term overt hypothyroidism. Large LDL subparticle concentrations increased during hypothyroidism (917 +/- 294 vs. 491 +/- 183 nmol/liter; P < 0.001), but more atherogenic small LDL was unchanged. Triglycerides marginally increased during hypothyroidism, small VLDL particles significantly increased (P < 0.001), whereas more atherogenic large VLDL was unchanged. Total HDL-C increased during hypothyroidism (76 +/- 13 mg/dl vs. 58 +/- 15 mg/dl; P < 0.001). There was no change in large HDL-C particle concentrations, whereas small (P < 0.001) and medium (P = 0.002) HDL-C particle concentrations decreased. Among Framingham women, adjusted total cholesterol and LDL-C were positively related to TSH categories (P <= 0.003). This was due to a positive correlation between adjusted large LDL subparticle concentrations and log-TSH (P < 0.0001); log small LDL subparticle concentrations decreased slightly as log-TSH increased (P = 0.045). Among Framingham men, the only significant association was a positive association between log-TSH and log large HDL subparticle concentrations (P = 0.04). Conclusions: There is a shift toward less atherogenic large LDL, small VLDL, and large HDL subparticle sizes in hypothyroid women. C1 [Pearce, Elizabeth N.; Braverman, Lewis E.] Boston Univ, Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Div Cardiol, Dept Med, Atlanta, GA 30306 USA. [Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. RP Pearce, EN (reprint author), Boston Univ, Med Ctr, Sect Endocrinol Diabet & Nutr, 88 E Newton St,Evans 201, Boston, MA 02118 USA. EM elizabeth.pearce@bmc.org RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Ramachandran, Vasan/0000-0001-7357-5970; Braverman, Lewis/0000-0003-1263-1099 FU NHLBI NIH HHS [2K24HL04334, K24 HL004334]; NIDDK NIH HHS [5K23DK4611] NR 42 TC 26 Z9 29 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2008 VL 93 IS 3 BP 888 EP 894 DI 10.1210/jc.2007-1987 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700036 PM 18073305 ER PT J AU Robinson-White, AJ Hsiao, HP Leitner, WW Greene, E Bauer, A Krett, NL Nesterova, M Stratakis, CA AF Robinson-White, Audrey J. Hsiao, Hui-Pin Leitner, Wolfgang W. Greene, Elizabeth Bauer, Andrew Krett, Nancy L. Nesterova, Maria Stratakis, Constantine A. TI Protein kinase A-independent inhibition of proliferation and induction of apoptosis in human thyroid cancer cells by 8-Cl-adenosine SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MULTIPLE-MYELOMA CELLS; ACTIVE METABOLITE; GROWTH-INHIBITION; CYCLIC-AMP; SELECTIVE MODULATION; DOWN-REGULATION; LEUKEMIA-CELLS; ANNEXIN-V; IN-VITRO; 8-CHLORO-ADENOSINE AB Purpose: Protein kinaseA(PKA) affects cell proliferation in many cell types and is a potential target for cancer treatment. PKA activity is stimulated by cAMP and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl-adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however, their mechanism of action is controversial. We have investigated the antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells and determined PKA's involvement. Experimental Design: We employed proliferation and apoptosis assays and PKA activity and cell cycle analysis to understand the effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines. Results: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and 3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8-Cl-ADO induced cell accumulation in G1/S or G2/M cell cycle phases and differentially altered PKA activity and subunit levels. PKA stimulation or inhibition and adenosine receptor agonists or antagonists did not significantly affect proliferation. Conclusions: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation, induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA does not appear to have direct involvement in the inhibition of proliferation by 8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive thyroid cancer. C1 [Robinson-White, Audrey J.; Hsiao, Hui-Pin; Greene, Elizabeth; Bauer, Andrew; Nesterova, Maria; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Leitner, Wolfgang W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Krett, Nancy L.] Northwestern Univ, Dept Med, Div Hematol & Oncol, Chicago, IL 60611 USA. [Hsiao, Hui-Pin] Kaohsiung Med Univ, Kaohsiung Municipal Hsiao Kang Hosp, Dept Pediat, Kaohsiung 812, Taiwan. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Hsiao, Hui-Pin/B-3892-2010; Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 FU Intramural NIH HHS; NCI NIH HHS [R01 CA085915]; NICHD NIH HHS [Z01 HD000642] NR 40 TC 19 Z9 19 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2008 VL 93 IS 3 BP 1020 EP 1029 DI 10.1210/jc.2007-2331 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271XT UT WOS:000253822700056 PM 18073299 ER PT J AU Klitzman, R Marhefka, S Mellins, C Wiener, L AF Klitzman, Robert Marhefka, Stephanie Mellins, Claude Wiener, Lori TI Ethical issues concerning disclosures of HIV diagnoses to perinatally infected children and adolescents SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID ADHERENCE; ILLNESS; FAMILY C1 [Klitzman, Robert; Mellins, Claude] Columbia Univ, New York, NY 10027 USA. [Marhefka, Stephanie] Univ S Florida, Tampa, FL USA. [Wiener, Lori] NIH, Bethesda, MD 20892 USA. RP Klitzman, R (reprint author), Columbia Univ, New York, NY 10027 USA. EM rlk2@columbia.edu FU Intramural NIH HHS [Z99 CA999999]; NIMH NIH HHS [P30-MH43520, T32MH19139] NR 42 TC 8 Z9 9 U1 1 U2 4 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SPR PY 2008 VL 19 IS 1 BP 31 EP 42 PG 12 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 306LE UT WOS:000256248900006 PM 18552051 ER PT J AU Jesus, AA Silva, CA Segundo, GR Aksentijevich, I Fujihira, E Watanabe, M Carneiro-Sampaio, M Duarte, AJS Oliveira, JB AF Jesus, Adriana A. Silva, Clovis A. Segundo, Gesmar R. Aksentijevich, Ivona Fujihira, Erika Watanabe, Monica Carneiro-Sampaio, Magda Duarte, Alberto J. S. Oliveira, Joao B. TI Phenotype-genotype analysis of cryopyrin-associated periodic syndromes (CAPS): Description of a rare non-exon 3 and a novel CIAS1 missense mutation SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE cryopyrin; periodic fever; NOMID; CINCA; CIAS1 ID AUTOINFLAMMATORY DISEASES; PATHOGENESIS; DISORDERS; PYRIN AB We describe in this paper the phenotype-genotype analysis of a Brazilian cohort of patients with cryopyrin-associated periodic syndromes (CAPS). Patient 1 presented with an urticarial rash and recurrent fever exacerbated by cold weather, arthritis, and anterior uveitis, thus, receiving a clinical diagnosis of familial cold autoinflammatory syndrome. CIAS1 sequencing identified the T436I mutation, previously associated to a clinical phenotype of chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease. Patient 2 developed a papular exanthema with daily fever shortly after birth, frontal bossing, patellae enlargement, and cognitive and motor impairments. Sequencing identified the exceedingly rare G755R CIAS1 mutation in exon 4. Patient 3 developed skin rash and articular symptoms 6 h after birth, followed by aseptic meningitis. He was found to have the novel C148Y missense mutation in CIAS1. This report expands the spectrum of CIAS1 mutations associated to clinical disease, suggests that the same mutation can be associated with different clinical syndromes, and supports the evidence that CAPS patients should always be screened for mutations outside exon 3. C1 [Duarte, Alberto J. S.; Oliveira, Joao B.] Hosp Coracao, Res Inst, Sao Paulo, Brazil. [Jesus, Adriana A.; Silva, Clovis A.] Univ Sao Paulo, Pediat Rheumatol Unit, Sao Paulo, Brazil. [Carneiro-Sampaio, Magda] Univ Sao Paulo, Dept Pediat, Sao Paulo, Brazil. [Segundo, Gesmar R.] Univ Fed Uberlandia, BR-38400 Uberlandia, MG, Brazil. [Aksentijevich, Ivona] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. [Fujihira, Erika; Watanabe, Monica; Oliveira, Joao B.] Univ Sao Paulo, Mol Immunol & Genet Sect, Lab Med Invest 56, Dept Dermatol, BR-05403000 Sao Paulo, Brazil. RP Oliveira, JB (reprint author), Hosp Coracao, Res Inst, Sao Paulo, Brazil. EM oliveirajb@lim56.fm.sup.br RI Duarte, Alberto/D-4382-2012; Segundo, Gesmar/E-3635-2013; OI Segundo, Gesmar/0000-0001-6310-1739; Oliveira, Joao/0000-0001-9388-8173 NR 13 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAR PY 2008 VL 28 IS 2 BP 134 EP 138 DI 10.1007/s10875-007-9150-7 PG 5 WC Immunology SC Immunology GA 269WU UT WOS:000253682300006 PM 18080732 ER PT J AU Li, Y Zhang, F Nagai, NB Tang, ZS Zhang, SH Scotney, P Lennartsson, J Zhu, CY Qu, Y Fang, CG Hua, JY Matsuo, O Fong, GH Ding, H Cao, YH Becker, KG Nash, A Heldin, CH Li, XR AF Li, Yang Zhang, Fan Nagai, Nobuo Tang, Zhongshu Zhang, Shuihua Scotney, Pierre Lennartsson, Johan Zhu, Chaoyong Qu, Yi Fang, Changge Hua, Jianyuan Matsuo, Osamu Fong, Guo-Hua Ding, Hao Cao, Yihai Becker, Kevin G. Nash, Andrew Heldin, Carl-Henrik Li, Xuri TI VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ENDOTHELIAL-GROWTH-FACTOR; HYPOXIC PULMONARY-HYPERTENSION; MCA-OCCLUSION MODEL; IN-VIVO; PLASMINOGEN-ACTIVATOR; ISCHEMIC-INJURY; FAMILY-MEMBERS; DEFICIENT MICE; ANGIOGENESIS; SURVIVAL AB Despite its early discovery and high sequence homology to the other VEGF family members, the biological functions of VEGF-B remain poorly understood. We revealed here a novel function for VEGF-B as a potent inhibitor of apoptosis. Using gene expression profiling of mouse primary aortic smooth muscle cells, and confirming the results by real-time PCR using mouse and rat cell fines, we showed that VEGF-B inhibited the expression of genes encoding the proapoptotic BH3-only proteins and other apoptosis- and cell death-related proteins, including p53 and members of the caspase family, via activation of VEGFR-1. Consistent with this, VEGF-B treatment rescued neurons from apoptosis in the retina and brain in mouse models of ocular neurodegenerative disorders and stroke, respectively. Interestingly, VEGF-B treatment at the dose effective for neuronal survival did not cause retinal neovascularization, suggesting that VEGF-B is the first member of the VEGF family that has a potent antiapoptotic effect while lacking a general angiogenic activity. These findings indicate that VEGF-B may potentially offer a new therapeutic option for the treatment of neurodegenerative diseases. C1 [Li, Yang; Zhang, Fan; Tang, Zhongshu; Zhang, Shuihua; Zhu, Chaoyong; Qu, Yi; Fang, Changge; Hua, Jianyuan; Li, Xuri] NEI, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Nagai, Nobuo; Matsuo, Osamu] Kinki Univ, Sch Med, Dept Physiol, Osaka 589, Japan. [Scotney, Pierre; Nash, Andrew] CSL Ltd, Parkville, Vic, Australia. [Lennartsson, Johan; Heldin, Carl-Henrik] Uppsala Univ, Ludwig Inst Canc Res, Uppsala, Sweden. [Fong, Guo-Hua] Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Farmington, CT USA. [Ding, Hao] Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB, Canada. [Cao, Yihai] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Becker, Kevin G.] NIA, NIH, TRIAD Technol Ctr, Baltimore, MD 21224 USA. RP Li, XR (reprint author), NEI, NIH, Porter Neurosci Res Ctr, Bldg 35,35 Convent Dr MSC 3731, Bethesda, MD 20892 USA. EM lixur@nei.nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU Intramural NIH HHS NR 51 TC 90 Z9 100 U1 2 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2008 VL 118 IS 3 BP 913 EP 923 DI 10.1172/JCI33673 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400016 PM 18259607 ER PT J AU Liu, FL Kunter, G Krem, MM Eades, WC Cain, JA Tomasson, MH Hennighausen, L Link, DC AF Liu, Fulu Kunter, Ghada Krem, Maxwell M. Eades, William C. Cain, Jennifer A. Tomasson, Michael H. Hennighausen, Lothar Link, Daniel C. TI Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COLONY-STIMULATING-FACTOR; HEMATOPOIETIC STEM-CELLS; SEVERE CONGENITAL NEUTROPENIA; ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL; FACTOR-RECEPTOR; GENE-EXPRESSION; GRANULOCYTIC DIFFERENTIATION; BLAST-CRISIS; BONE-MARROW AB A fundamental property of leukemic stem cells is clonal dominance of the bone marrow microenvironment. Truncation mutations of CSF3R, which encodes the G-CSF receptor (G-CSFR), are implicated in leukemic progression in patients with severe congenital neutropenia. Here we show that expression of a truncated mutant Csf3r in mice confers a strong clonal advantage at the HSC level that is dependent upon exogenous G-CSF. G-CSF-induced proliferation, phosphorylation of Stat5, and transcription of Stat5 target genes were increased in HSCs isolated from mice expressing the mutant Csf3r. Conversely, the proliferative advantage conferred by the mutant Csf3r was abrogated in myeloid progenitors lacking both Stat5A and Stat5B, and HSC function was reduced in mice expressing a truncated mutant Csf3r engineered to have impaired Stat5 activation. These data indicate that in mice, inappropriate Stat5 activation plays a key role in establishing clonal dominance by stem cells expressing mutant Csf3r. C1 [Liu, Fulu; Kunter, Ghada; Krem, Maxwell M.; Eades, William C.; Cain, Jennifer A.; Tomasson, Michael H.; Link, Daniel C.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Hennighausen, Lothar] NIDDK, NIH, Lab Genet & Physiol, Bethesda, MD USA. RP Link, DC (reprint author), Washington Univ, Sch Med, Dept Med, Div Oncol, 660 S Euclid Ave,Campus Box 8007, St Louis, MO 63110 USA. EM dlink@im.wustl.edu FU Intramural NIH HHS; NCI NIH HHS [CA101937, P01 CA101937] NR 62 TC 42 Z9 44 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2008 VL 118 IS 3 BP 946 EP 955 DI 10.1172/JCI32704 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400019 PM 18292815 ER PT J AU Ahlenstiel, G Martin, MP Gao, XJ Carrington, M Rehermann, B AF Ahlenstiel, Golo Martin, Maureen P. Gao, Xiaojiang Carrington, Mary Rehermann, Barbara TI Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INFLUENZA-A VIRUS; MHC CLASS-I; IMMUNOGLOBULIN-LIKE RECEPTOR; BARE LYMPHOCYTE SYNDROME; HUMAN NK CELLS; HLA-C LIGANDS; INHIBITORY RECEPTORS; PSORIATIC-ARTHRITIS; DIRECT BINDING; FUNCTIONAL TRANSFER AB Genetic studies suggest a role for killer cell immunoglobulin-like receptor/HLA (KIR/HLA) compound genotypes in the outcome of viral infections, but functional data to explain these epidemiological observations have not been reported. Using an in vitro model of infection with influenza A virus (IAV), we attribute functional differences in human NK cell activity to distinct KIR/HLA genotypes. Multicolor flow cytometry revealed that the HLA-C-inhibited NK cell subset in HLA-C1 homozygous subjects was larger and responded more rapidly in IFN-gamma secretion and CD107a degranulation assays than its counterpart in HLA-C2 homozygous subjects. The differential IFN-gamma response was also observed at the level of bulk NK cells and was independent of KIR3DL1/HLA-Bw4 interactions. Moreover, the differential response was not caused by differences in NK cell maturation status and phenotype, nor by differences in the type IIFN response of IAV-infected accessory cells between HLA-C1 and HLA-C2 homozygous subjects. These results provide functional evidence for differential NK cell responsiveness depending on KIR/HLA genotype and may provide useful insights into differential innate immune responsiveness to viral infections such as IAV. C1 [Ahlenstiel, Golo; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Martin, Maureen P.; Gao, Xiaojiang; Carrington, Mary] Sci Applicat Int Corp Frederick Inc, Natl Canc Inst Frederick, Lab Genom Divers, Frederick, MD USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16C, Bethesda, MD 20892 USA. EM rehermann@nih.gov OI Ahlenstiel, Golo/0000-0003-0026-1457 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 81 TC 90 Z9 92 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2008 VL 118 IS 3 BP 1017 EP 1026 DI 10.1172/JCI32400 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400026 PM 18246204 ER PT J AU Wang, WH McNatt, LG Pang, IH Millar, C Hellberg, PE Hellberg, MH Steely, HT Rubin, JS Fingert, JH Sheffield, VC Stone, EM Clark, AF AF Wang, Wan-Heng McNatt, Loretta G. Pang, Iok-Hou Millar, Cameron Hellberg, Peggy E. Hellberg, Mark H. Steely, H. Thomas Rubin, Jeffrey S. Fingert, John H. Sheffield, Val C. Stone, Edwin M. Clark, Abbot F. TI Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OPEN-ANGLE GLAUCOMA; HUMAN TRABECULAR MESHWORK; GROWTH-FACTOR-BETA; OCULAR HYPERTENSION TREATMENT; FRIZZLED-RELATED PROTEIN-1; PERFUSION ORGAN-CULTURE; AQUEOUS-HUMOR; SIGNALING PATHWAYS; STEM-CELLS; IN-VITRO AB Elevated intraocular pressure (IOP) is the principal risk factor for glaucoma and results from excessive impedance of the fluid outflow from the eye. This abnormality likely originates from outflow pathway tissues such as the trabecular meshwork (TM), but the associated molecular etiology is poorly understood. We discovered what we believe to be a novel role for secreted frizzled-related protein-1 (sFRP-1), an antagonist of Writ signaling, in regulating IOP. sFPP1 was overexpressed in human glaucomatous TM cells. Genes involved in the Wnt signaling pathway were expressed in cultured TM cells and human TM tissues. Addition of recombinant sFRP-1 to ex vivo perfusion-cultured human eyes decreased outflow facility, concomitant with reduced levels of beta-catenin, the Writ signaling mediator, in the TM. Intravitreal injection of an adenoviral vector encoding sFRP1 in mice produced a titer-dependent increase in IOP. Five days after vector injection, IOP increased 2 fold, which was significantly reduced by topical ocular administration of an inhibitor of a downstream suppressor of Writ signaling. Thus, these data indicate that increased expression of sFPP1 in the TM appears to be responsible for elevated IOP in glaucoma and restoring Writ signaling in the TM may be a novel disease intervention strategy for treating glaucoma. C1 [Wang, Wan-Heng; McNatt, Loretta G.; Pang, Iok-Hou; Millar, Cameron; Hellberg, Peggy E.; Hellberg, Mark H.; Steely, H. Thomas; Clark, Abbot F.] Alcon Res Ltd, Glaucoma Res, Ft Worth, TX 76134 USA. [Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Fingert, John H.; Stone, Edwin M.] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Sheffield, Val C.; Stone, Edwin M.] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. [Sheffield, Val C.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. RP Clark, AF (reprint author), Alcon Res Ltd, Glaucoma Res, 6201 S Freeway, Ft Worth, TX 76134 USA. EM abe.clark@alconlabs.com RI Fingert, John/F-8787-2012 OI Fingert, John/0000-0002-0377-0479 FU Intramural NIH HHS NR 58 TC 76 Z9 78 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2008 VL 118 IS 3 BP 1056 EP 1064 DI 10.1172/JCI33871 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400030 PM 18274669 ER PT J AU Takahashi, Y Harashima, N Kajigaya, S Yokoyama, H Cherkasova, E Mccoy, JP Hanada, K Mena, O Kurlander, R Abdul, T Srinivasan, R Lundqvist, A Malinzak, E Geller, N Lerman, MI Childs, RW AF Takahashi, Yoshiyuki Harashima, Nanae Kajigaya, Sachiko Yokoyama, Hisayuki Cherkasova, Elena McCoy, J. Philip Hanada, Ken-ichi Mena, Othon Kurlander, Roger Abdul, Tawab Srinivasan, Ramaprasad Lundqvist, Andreas Malinzak, Elizabeth Geller, Nancy Lerman, Michael I. Childs, Richard W. TI Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-ENDOGENOUS-RETROVIRUS; CARCINOMA; EXPRESSION; MELANOMA; LYMPHOCYTES AB Transplanted donor lymphocytes infused during hematopoietic stem cell transplantation (HSCT) have been shown to cure patients with hematological malignancies. However, less is known about the effects of HSCT on metastatic solid tumors. Thus, a better understanding of the immune cells and their target antigens that mediate tumor regression is urgently needed to develop more effective HSCT approaches for solid tumors. Here we report regression of metastatic renal cell carcinoma (RCC) in patients following nonmyeloablative HSCT consistent with a graft-versus-tumor effect. We detected RCC-reactive donor-derived CD8(+) T cells in the blood of patients following nonmyeloablative HSCT. Using cDNA expression cloning, we identified a 10-mer peptide (CT-RCC-1) as a target antigen of RCC-specific CD8(+) T cells. The genes encoding this antigen were found to be derived from human endogenous retrovirus (HERV) type E and were expressed in RCC cell lines and fresh RCC tissue but not in normal kidney or other tissues. We believe this to be the first solid tumor antigen identified using allogeneic T cells from a patient undergoing HSCT. These data suggest that HERV-E is activated in RCC and that it encodes an overexpressed immunogenic antigen, therefore providing a potential target for cellular immunity. C1 [Takahashi, Yoshiyuki; Harashima, Nanae; Kajigaya, Sachiko; Yokoyama, Hisayuki; Cherkasova, Elena; Mena, Othon; Srinivasan, Ramaprasad; Lundqvist, Andreas; Malinzak, Elizabeth; Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Hanada, Ken-ichi] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Kurlander, Roger; Abdul, Tawab] NHLBI, Dept Clin Pathol, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Geller, Nancy] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Lerman, Michael I.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, Hematol Branch, NIH, 10 CRC, Bethesda, MD 20892 USA. EM childsr@mail.nih.gov RI Hanada, Ken-ichi/A-4642-2008; Takahashi, Yoshiyuki/I-1929-2012; Hanada, Ken-ichi/L-2481-2013; OI Hanada, Ken-ichi/0000-0003-2959-1257; Lundqvist, Andreas/0000-0002-9709-2970 FU Intramural NIH HHS NR 20 TC 83 Z9 84 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2008 VL 118 IS 3 BP 1099 EP 1109 DI 10.1172/JCI34409 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400034 PM 18292810 ER PT J AU Persad, GC Little, RF Grady, C AF Persad, Govind C. Little, Richard F. Grady, Christine TI Including persons with HIV infection in cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; AIDS-DEFINING CANCERS; KIDNEY-TRANSPLANTATION; ERA; MALIGNANCIES; LYMPHOMA; SURVIVAL; US; CHEMOTHERAPY C1 [Persad, Govind C.; Little, Richard F.; Grady, Christine] NCI, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Persad, Govind C.; Little, Richard F.; Grady, Christine] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Therapy & Diagnosis,Natl Inst Hlth, Bethesda, MD 20892 USA. RP Persad, GC (reprint author), NCI, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. NR 50 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2008 VL 26 IS 7 BP 1027 EP 1032 DI 10.1200/JCO.2007.14.5532 PG 6 WC Oncology SC Oncology GA 276XX UT WOS:000254178100004 PM 18309938 ER PT J AU Scher, HI Halabi, S Tannock, I Morris, M Sternberg, CN Carducci, MA Eisenberger, MA Higano, C Bubley, GJ Dreicer, R Petrylak, D Kantoff, P Basch, E Kelly, WK Figg, WD Small, EJ Beer, TM Wilding, G Martin, A Hussain, M AF Scher, Howard I. Halabi, Susan Tannock, Ian Morris, Michael Sternberg, Cora N. Carducci, Michael A. Eisenberger, Mario A. Higano, Celestia Bubley, Glenn J. Dreicer, Robert Petrylak, Daniel Kantoff, Philip Basch, Ethan Kelly, William Kevin Figg, William D. Small, Eric J. Beer, Tomasz M. Wilding, George Martin, Alison Hussain, Maha TI Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the prostate cancer clinical trials working group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II; ANTIGEN EXPRESSION; NATURAL-HISTORY; HORMONE; MEN; DOCETAXEL; THERAPY; MODEL; ESTRAMUSTINE; MITOXANTRONE AB Purpose To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or " no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit. C1 Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urolog Canc, New York, NY 10065 USA. Duke Univ, Med Ctr, Durham, NC USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Sam Camillo Forlanini Hosp, Rome, Italy. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Cleveland Clin, Cleveland, OH 44106 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Yale Canc Ctr, New Haven, CT USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Scher, HI (reprint author), Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urolog Canc, 1275 York Ave, New York, NY 10065 USA. EM byczekb@mskcc.org RI Figg Sr, William/M-2411-2016; OI Martin, Anne/0000-0002-8536-3550; Morris, Michael J./0000-0002-9454-0096 FU NCI NIH HHS [P50 CA092629, P50 CA092629-01, P50 CA92629] NR 40 TC 910 Z9 923 U1 4 U2 25 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2008 VL 26 IS 7 BP 1148 EP 1159 DI 10.1200/JCO.2007.12.4487 PG 12 WC Oncology SC Oncology GA 276XX UT WOS:000254178100021 PM 18309951 ER PT J AU Goldstein, RB Dawson, DA Chou, SP Ruan, WJ Saha, TD Pickering, RP Stinson, FS Grant, BF AF Goldstein, Rise B. Dawson, Deborah A. Chou, S. Patricia Ruan, W. June Saha, Tulshi D. Pickering, Roger P. Stinson, Frederick S. Grant, Bridget F. TI Antisocial behavioral syndromes and past-year physical health among adults in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID DRUG-USE DISORDERS; INTERVIEW SCHEDULE AUDADIS; FATTY LIVER-DISEASE; GENERAL-POPULATION SAMPLE; PERSONALITY-DISORDER; CONDUCT DISORDER; RISK-FACTORS; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; CARDIOVASCULAR-DISEASE AB Objective: To describe associations of DSM-IV antisocial personality disorder (ASPD), DSM-IV conduct disorder without progression to ASPD (CD-only), and syndromal antisocial behavior in adulthood without conduct disorder before age 15 years (AABS, not a DSM-IV diagnosis) with past-year physical health status and hospital care utilization in the general U.S. adult population. Method: This report is based on the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093, response rate = 81 Respondents were classified according to whether they met criteria for ASPD, AABS, CD-only, or no antisocial syndrome. Associations of antisocial syndromes with physical health status and care utilization were examined using normal theory and logistic regression. Results: ASPD and AABS were significantly but modestly associated with total past-year medical conditions, coronary heart and gastrointestinal diseases, and numbers of inpatient hospitalizations, inpatient days. emergency department visits, and clinically significant injuries (all p < .05). ASPD was also associated with liver disease, arthritis, and lower scores on the Medical Outcomes Study 12-Item Short-Form Health Survey, version 2 (SF-12v2) physical component summary, role physical, and bodily pain scales (all p < .05). AABS was associated with noncoronary heart disease, lower scores on the SF-12v2 general health and vitality scales, and, among men, arthritis (all p < .05). CD-only was associated with single but not multiple inpatient hospitalizations, emergency department visits, and clinically significant injuries (all p < .05). Conclusions: Estimates of burden related to antisocial behavioral syndromes need to consider associated physical health problems. Prevention and treatment Guidelines for injuries and common chronic diseases may need to address comorbid antisociality, and interventions targeting antisociality may need to consider general health status, including prevention and management of injuries and chronic diseases. C1 [Goldstein, Rise B.; Dawson, Deborah A.; Chou, S. Patricia; Ruan, W. June; Saha, Tulshi D.; Pickering, Roger P.; Stinson, Frederick S.; Grant, Bridget F.] NIAAA, Div Intramural Clin & Biol Res, Natl Inst Hlth, Dept Hlth & Human Serv,Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. RP Goldstein, RB (reprint author), NIAAA, Div Intramural Clin & Biol Res, Natl Inst Hlth, Dept Hlth & Human Serv,Lab Epidemiol & Biometry, M S 9304 5635 Fisher Ln, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS [Z01 AA000449-05] NR 108 TC 22 Z9 22 U1 5 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2008 VL 69 IS 3 BP 368 EP 380 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 283LL UT WOS:000254637600005 PM 18348594 ER PT J AU Nagayama, M Iwamoto, M Hargett, A Kamiya, N Tamamura, Y Young, B Morrison, T Takeuchi, H Pacifici, M Enomoto-Iwamoto, M Koyama, E AF Nagayama, M. Iwamoto, M. Hargett, A. Kamiya, N. Tamamura, Y. Young, B. Morrison, T. Takeuchi, H. Pacifici, M. Enomoto-Iwamoto, M. Koyama, E. TI Wnt/beta-catenin signaling regulates cranial base development and growth SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE cranial base synchondrosis; Wnt/beta-catenin; sFRP-1; PTHrP; hedgehog signalling ID CHONDROCYTE DIFFERENTIATION; JOINT FORMATION; WNT; HEDGEHOG; BONE; OSTEOBLAST; SKELETOGENESIS; ROLES; PLATE; PROLIFERATION AB Wnt proteins and beta-catenin signaling regulate major processes during embryonic development, and we hypothesized that they regulate cranial base synchondrosis development and growth. To address this issue, we analyzed cartilage-specific beta-catenin-deficient mice. Mutant synchondroses lacked typical growth plate zones, and endochondral ossification was delayed. In reciprocal transgenic experiments, cartilage overexpression of a constitutive active Lef1, a transcriptional mediator of Wnt/beta-catenin signaling, caused precocious chondrocyte hypertrophy and intermingling of immature and mature chondrocytes. The developmental changes seen in beta-catenin-deficient synchondroses were accompanied by marked reductions in Ihh and PTHrP as well as sFRP-1, an endogenous Wnt signaling antagonist and a potential Ihh signaling target. Thus, Wnt/beta-catenin signaling is essential for cranial base development and synchondrosis growth plate function. This pathway promotes chondrocyte maturation and ossification events, and may exert this important role by dampening the effects of Ihh- PTHrP together with sFRP-1. C1 [Nagayama, M.; Iwamoto, M.; Hargett, A.; Tamamura, Y.; Young, B.; Morrison, T.; Pacifici, M.; Enomoto-Iwamoto, M.; Koyama, E.] Thomas Jefferson Univ, Coll Med, Dept Paediat Orthopaed, Philadelphia, PA 19107 USA. [Nagayama, M.; Takeuchi, H.] Asahi Univ, Sch Dent, Dept Oral Pathol, Gifu 5010296, Japan. [Kamiya, N.] Natl Inst Environm Hlth Sci, NIH, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Koyama, E (reprint author), Thomas Jefferson Univ, Coll Med, Dept Paediat Orthopaed, Philadelphia, PA 19107 USA. EM moto@dent.asahi-u.ac.jp; eiki.koyama@jefferson.edu NR 36 TC 24 Z9 26 U1 1 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 2008 VL 87 IS 3 BP 244 EP 249 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 292ZA UT WOS:000255303400010 PM 18296608 ER PT J AU Henquin, JC Nenquin, M Szollosi, A Kubosaki, A Notkins, AL AF Henquin, Jean-Claude Nenquin, Myriarn Szollosi, Andras Kubosaki, Atsutaka Notkins, Abner Louis TI Insulin secretion in islets from mice with a double knockout for the dense core vesicle proteins islet antigen-2 (IA-2) and IA-2 beta SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID TYROSINE-PHOSPHATASE HOMOLOG; PANCREATIC BETA-CELLS; SECRETAGOGUE-DEPENDENT PHOSPHORYLATION; MEMBRANE-PROTEIN; MOLECULAR-CLONING; CYTOPLASMIC CA2+; TARGETED DISRUPTION; GLUCOSE; AUTOANTIGEN; PHOGRIN AB Islet antigen-2 (IA-2 or ICA 512) and IA-2 beta (or phogrin) are major autoantigens in type I diabetes. They are located in dense core secretory vesicles including insulin granules, but their role in beta-cell function is unclear. Targeted disruption of either IA-2 or IA-2, or both, impaired glucose tolerance, an effect attributed to diminution of insulin secretion. In this study, we therefore characterized the dynamic changes in cytosolic Ca2+([Ca2+](c)) and insulin secretion in islets from IA-2/IA-2 beta double knockout (KO) mice. High glucose (15 mM) induced biphasic insulin secretion in IA-2/IA-2 beta KO islets, with a similar first phase and smaller second phase compared with controls. Since the insulin content of IA-2/IA-2 beta KO islets was similar to 45% less than that of controls, fractional insulin secretion (relative to content) was thus increased during first phase and unaffected during second phase. This peculiar response occurred in spite of a slightly smaller rise in [Cat(2+)](c), could not be attributed to an alteration of glucose metabolism (NADPH fluorescence) and also was observed with tolbutamide. The dual control of insulin secretion via the K-ATP, channel-dependent triggering pathway and K-ATP channel-independent amplifying pathway was unaltered in IA-2/IA-2 beta KO islets,and so were the potentiations by acetylcholine or cAMP (forskolin). Intriguingly, amino acids, in particular the cationic arginine and lysine, induced larger fractional insulin secretion in IA-2/IA-2 beta KO than control islets. In conclusion, IA-2 and IA-2 beta are dispensable for exocytosis of insulin granules, but are probably more important for cargo loading and/or stability of dense core vesicles. C1 [Henquin, Jean-Claude; Nenquin, Myriarn; Szollosi, Andras] Univ Louvain, Fac Med, Unit Endocrinol & Metab, B-1200 Brussels, Belgium. [Kubosaki, Atsutaka; Notkins, Abner Louis] Natl Inst Dent & Cranofacial Res, Expt Med Sect, Oral Infect & Immun Branch, Natl Inst Hlth, Bethesda, MD 20891 USA. RP Henquin, JC (reprint author), Univ Louvain, Fac Med, Unit Endocrinol & Metab, UCL 55 30 Ave Hippocrate 55, B-1200 Brussels, Belgium. EM jean-claude.henquin@uclouvain.be RI Szollosi, Andras/J-5097-2013; OI Szollosi, Andras/0000-0002-5570-4609 NR 41 TC 23 Z9 25 U1 0 U2 3 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAR PY 2008 VL 196 IS 3 BP 573 EP 581 DI 10.1677/JOE-07-0496 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 278PC UT WOS:000254297800014 PM 18310453 ER PT J AU Jeong, WI Gao, B AF Jeong, Won-Il Gao, Bin TI Innate immunity and alcoholic liver fibrosis SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis CY OCT 18-19, 2007 CL Kobe, JAPAN SP Japanese Soc Gastroenterol, Japan Soc Hepatol DE alcohol; hepatic stellate cell; innate immunity; liver fibrosis; natural killer cell ID CHRONIC HEPATITIS-C; KILLER T-CELLS; PRIMARY BILIARY-CIRRHOSIS; INDUCED PULMONARY-FIBROSIS; ACTIVATED STELLATE CELLS; RAT KUPFFER CELLS; B-VIRUS INFECTION; INTERFERON-GAMMA; CELLS/INTERFERON-GAMMA; MOLECULAR-MECHANISMS AB The hepatic innate immune system consists of predominant innate immunity, which plays an important role in innate defense against infection and tumor transformation. Emerging evidence suggests that innate immunity also contributes to liver injury, repair, and fibrosis. The present review summarizes the recent findings on the role of innate immunity in liver fibrosis. In general, Kupffer cells stimulate liver fibrosis via production of reactive oxygen species and pro-inflammatory cytokines, whereas natural killer (NK) cells inhibit liver fibrosis by directly killing activated hepatic stellate cells and production of gamma-interferon (IFN-gamma). Complement components, interferons, and Toll-like receptors have also been shown to regulate liver fibrosis. Recent evidence also suggests that modulation of innate immunity by alcohol plays an important role in the pathogenesis of alcoholic liver fibrosis. These include alcohol amplification of the profibrotic effects of Kupffer cells and suppression of the antifibrotic effects of NK/IFN-gamma. C1 [Jeong, Won-Il; Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA. RI JEONG, WON IL/B-6615-2011 FU Intramural NIH HHS [Z01 AA000369-06] NR 84 TC 30 Z9 32 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2008 VL 23 SU 1 BP S112 EP S118 DI 10.1111/j.1440-1746.2007.05274.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284VT UT WOS:000254735700023 PM 18336653 ER PT J AU Li, TK AF Li, Ting-Kai TI Quantifying the risk for alcohol-use and alcohol-attributable health disorders: Present findings and future research needs SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis CY OCT 18-19, 2007 CL Kobe, JAPAN SP Japanese Soc Gastroenterol, Japan Soc Hepatol DE alcohol; alcohol organ damage; alcohol-use disorder; alcoholic liver disease; binge drinking ID CHRONIC HEPATITIS-C; UNITED-STATES; LIVER-DISEASE; CONSUMPTION; DRINKING; METAANALYSIS; PROGRESSION; MORTALITY; IMPACT; HIV AB The aim of the present review was to: (i) highlight epidemiological and other studies that have generated important data on the harmful patterns of drinking that increase the risk for chronic diseases, including alcohol dependence, and on the mechanisms by which alcohol produces and, in some instances, may protect against damage; and (ii) discuss a conceptual basis for quantifying risk criteria for alcohol-induced chronic disease based on the quantity, frequency, and pattern of drinking. The relationship between heavy drinking and risk for adverse health conditions such as alcoholic liver disease (ALD), dementia, and alcohol dependence is well known. However, not everyone who drinks chronically develops ALD or dementia, and the major risk factors for disease development and the mechanisms by which this occurs have remained unclear. Large-scale, general population-based studies have provided the evidence by which quantifying the frequency of a pattern of high-risk drinking can be related directly to risk and the severity of alcohol dependence. Cellular and molecular biology studies have identified the major pathways of alcohol metabolism and how genetics and the environment can interact in some individuals to further increase the risk of organ damage. Extant databases should allow scientists and clinicians jointly to develop the framework for quantifying the drinking patterns that increase the risk of alcohol-induced organ pathologies, to develop clinical practice guidelines, such as those used to diagnose other common complex diseases (e.g. diabetes and hypertension), and to propose future studies for refining such guidelines. Attention must be paid to comorbid conditions such as hepatitis B and C infections, HIV, obesity, and environmental exposures other than alcohol. Developing trait and state biomarkers is critical to the process of discovery and to fulfilling the promise of personalized medicine. C1 NIAAA, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Li, TK (reprint author), NIAAA, NIH, US Dept Hlth & Human Serv, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM tkli@mail.nih.gov NR 28 TC 50 Z9 53 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2008 VL 23 SU 1 BP S2 EP S8 DI 10.1111/j-1440-1746.2007.05298.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 284VT UT WOS:000254735700002 PM 18336658 ER PT J AU Ogawa, R Lee, S Kagiya, G Hirano, H Fukuda, S Kondol, T Kodaki, T AF Ogawa, Ryohei Lee, Sung-il Kagiya, Go Hirano, Hisao Fukuda, Shigekazu Kondol, Takashi Kodaki, Tsutornu TI Construction of X-ray-inducible promoters through cis-acting element elongation and error-prone polymerase chain reaction SO JOURNAL OF GENE MEDICINE LA English DT Article DE promoter; error prone PCR; cis-acting element; gene expression; radiation ID IONIZING-RADIATION; GENE-EXPRESSION; SYNTHETIC PROMOTERS; BINDING-SITES; THERAPY; TRANSCRIPTION; IRRADIATION; ACTIVATION; GENERATION; SEQUENCES AB Background A promoter that is activated by ionizing radiation may be a useful tool for cancer therapy since, with such a promoter, the therapeutic gene can be expressed only in cancer tissues by irradiation. An artificially constructed promoter is advantageous as natural promoters may have physiological limitations. However, reasonably designing a promoter is hampered by shortage of information about the relationship between the structure and properties of a promoter DNA. Materials and methods Binding sites of four transcription factors that were activated by radiation were randomly ligated and linked to a TATA-box sequence to control the luciferase gene located downstream. Transiently transfected cancer cells with such a vector were exposed to X-ray irradiation and enhancement of luciferase expression was assessed. To improve promoter sensitivity, mutations were randomly introduced into a constructed promoter by error-prone polymerase chain reaction (epPCR). Results Of the 11 promoters constructed, the clone 11 promoter (clone 11 + TATA-box) showed a 5-fold enhancement 6 h after the 10 GyX-ray irradiation in HeLa cells. A mutant designated the clone 11-9-37 promoter generated through two steps of epPCR showed a sensitivity 4.8 times higher than the clone 11 promoter to the 10 Gy X-rays, showing 21.6-fold enhancement of luciferase expression. Clone 11 was composed of 16 cis-acting elements, and the clone 11-9-37 promoter carried six point mutations. Conclusion A sensitively responsive promoter to radiation could be constructed using this method, possibly leading to the construction of a promoter of interest that could be applied for clinical use. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Ogawa, Ryohei; Kondol, Takashi] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Radiol Sci, Toyama 9300194, Japan. [Ogawa, Ryohei; Kagiya, Go; Fukuda, Shigekazu] Wakasa Wan Energy Res Ctr, Div Med, Tsurga 9140192, Japan. [Lee, Sung-il] Toyama Univ, Life Sci Res Ctr, Div Anim Resources & Dev, Toyama 9300194, Japan. [Kagiya, Go] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Hirano, Hisao] Nippon Gene Co, Div Res, Toyama 9300834, Japan. [Kodaki, Tsutornu] Kyoto Univ, Bioenergy Res Sect, Inst Adv Energy, Kyoto 6110011, Japan. [Lee, Sung-il] Kansai Med Univ, Inst Biomed Sci, Moriguchi, Osaka 5708506, Japan. RP Ogawa, R (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Radiol Sci, Toyama 9300194, Japan. EM ogawa@med.u-toyama.ac.jp NR 28 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR PY 2008 VL 10 IS 3 BP 316 EP 324 DI 10.1002/jgm.1154 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 283YP UT WOS:000254672700010 PM 18161064 ER PT J AU Arora, NK Hesse, BW Rimer, BK Viswanath, K Clayman, ML Croyle, RT AF Arora, Neeraj K. Hesse, Bradford W. Rimer, Barbara K. Viswanath, K. Clayman, Marla L. Croyle, Robert T. TI Frustrated and confused: The American public rates its cancer-related information-seeking experiences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE information seeking; cancer; national survey; health information; information needs ID NATIONAL TRENDS SURVEY; HEALTH INFORMATION; DECISION-MAKING; INTERNET; CARE; QUALITY; PARTICIPATE; PREFERENCES; KNOWLEDGE; NEEDS AB BACKGROUND: Ensuring access to high-quality cancer-related information is important for the success of cancer prevention and control efforts. OBJECTIVE: We conducted a population-based assessment of the barriers faced by people searching for cancer information. DESIGN: Cross-sectional data from the National Cancer Institute's 2003 Health Information National Trends Survey. PARTICIPANTS: A nationally representative sample of individuals in the USA (n=6,369). MEASUREMENTS: We assessed whether respondents had ever sought cancer-related information and examined ratings of their information-seeking experiences and beliefs regarding causes of cancer and its prevention. Linear and logistic regression models were estimated to determine predictors of negative experiences and associations between experiences and cancer beliefs. RESULTS:Nearly one half (44.9%) of Americans had searched for cancer information. Many reported negative experiences, including the search process requiring a lot of effort (47.7%), expressing frustration (41.3%), and concerns about the quality of the information found (57.7%). Respondents lacking health insurance or a high school education experienced the greatest difficulty. Compared to those reporting the most positive experiences, information seekers reporting more negative experiences were more likely to report that almost everything caused cancer [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.5-2.6], that not much can be done to prevent cancer (OR 2.7, 95% CI 1.9-3.8), and that it is hard to know which cancer prevention recommendations to follow (OR 3.2, 95% CI 2.3-4.5). CONCLUSIONS: While a significant proportion of the American public searches for cancer information, suboptimal experiences are common. Facilitation of information seeking will be critical for promoting informed decision making in cancer prevention and control. C1 [Arora, Neeraj K.; Hesse, Bradford W.; Croyle, Robert T.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Rimer, Barbara K.] Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. [Rimer, Barbara K.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Viswanath, K.] Harvard Univ, Dept Soc Human Dev, Boston, MA 02115 USA. [Viswanath, K.] Dana Faber Canc Inst, Boston, MA 02115 USA. [Clayman, Marla L.] Northwestern Univ, Ctr Commun & Med, Chicago, IL USA. Northwestern Univ, Dept Gen Med, Chicago, IL USA. [Clayman, Marla L.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. RP Arora, NK (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. OI Clayman, Marla/0000-0001-8491-3672; Hesse, Bradford/0000-0003-1142-1161 FU NCI NIH HHS [N02-PC-15003] NR 28 TC 67 Z9 68 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 IS 3 BP 223 EP 228 DI 10.1007/s11606-007-0406-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 263JS UT WOS:000253214000001 PM 17922166 ER PT J AU Keating, NL Landrum, M Arora, NK Malin, JL Ganz, PA Van Ryn, M Weeks, JC AF Keating, N. L. Landrum, M. Arora, N. K. Malin, J. L. Ganz, P. A. Van Ryn, M. Weeks, J. C. TI Cancer patients' role in treatment decision making: Are they influenced by type of treatment or strength of evidence supporting a treatment? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Keating, N. L.; Landrum, M.] Harvard Univ, Sch Med, Boston, MA USA. [Arora, N. K.] NCI, Rockville, MD USA. [Malin, J. L.] W Los Angeles Vet Affairs Healthcare Ctr, Los Angeles, CA USA. [Ganz, P. A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Van Ryn, M.] Univ Minnesota, Minneapolis, MN USA. [Weeks, J. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 260 EP 260 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100470 ER PT J AU Tilburt, J Curlin, FA Emanuel, E Kaptchuk, TJ Miller, FG AF Tilburt, J. Curlin, F. A. Emanuel, E. Kaptchuk, T. J. Miller, F. G. TI Does clinical trial evidence on CAM translate into clinical practice: A national survey of physicians and CAM practitioners SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Tilburt, J.] Mayo Clin, Rochester, MN USA. [Curlin, F. A.] Univ Chicago, Chicago, IL 60637 USA. [Emanuel, E.; Miller, F. G.] NIH, Bethesda, MD 20892 USA. [Kaptchuk, T. J.] Harvard Univ, Sch Med, Osher Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 288 EP 289 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100542 ER PT J AU Chander, G Himelhoch, S Fleishman, J Hellinger, J Gaist, P Kelly, G AF Chander, G. Himelhoch, S. Fleishman, J. Hellinger, J. Gaist, P. Kelly, G. TI HAART use and viral response among HIV-infected patients with co-occurring mental illness and injection drug use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Chander, G.; Kelly, G.] Johns Hopkins Univ, Baltimore, MD USA. [Himelhoch, S.] Univ Maryland, Baltimore, MD 21201 USA. [Fleishman, J.] Agcy Healthcare Res & Qualit, Rockville, MD USA. [Hellinger, J.] Community Med Alliance, Boston, MA USA. [Gaist, P.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 309 EP 309 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100598 ER PT J AU Haggstrom, D Taplin, S Clauser, S AF Haggstrom, D. Taplin, S. Clauser, S. TI Implementation of the chronic care model in the HRSA health disparities cancer collaborative SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Haggstrom, D.] VA HSR&D Indianapolis Ctr Excellence, Indianapolis, IN USA. [Taplin, S.] NCI, Appl Screening Res Program, Bethesda, MD 20892 USA. [Clauser, S.] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 324 EP 324 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100640 ER PT J AU Rodondi, N Marques-Vidal, P Butler, J Cornuz, J Sutton-Tyrrell, K Satterfield, S Ferrucci, L Harris, TB Vittinghoff, E Bauer, DC Newman, A AF Rodondi, N. Marques-Vidal, P. Butler, J. Cornuz, J. Sutton-Tyrrell, K. Satterfield, S. Ferrucci, L. Harris, T. B. Vittinghoff, E. Bauer, D. C. Newman, A. TI Markers of atherosclerosis and of inflammation for prediction of coronary heart disease in older adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Rodondi, N.; Marques-Vidal, P.; Cornuz, J.] Univ Lausanne, Lausanne, Switzerland. [Butler, J.] Emory Univ, Atlanta, GA 30322 USA. [Sutton-Tyrrell, K.; Newman, A.] Univ Pittsburgh, Pittsburgh, PA USA. [Satterfield, S.] Univ Tennessee, Memphis, TN USA. [Ferrucci, L.] NIA, Bethesda, MD 20892 USA. [Vittinghoff, E.] Natl Inst Hlth, Chevy Chase, MD USA. [Bauer, D. C.; Newman, A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 343 EP 343 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100692 ER PT J AU Tilburt, J Emanuel, E Kaptchuk, TJ Curlin, FA Miller, FG AF Tilburt, J. Emanuel, E. Kaptchuk, T. J. Curlin, F. A. Miller, F. G. TI Placebo prescribing among US physicians: Results of a national survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Tilburt, J.] Mayo Clin, Rochester, MN USA. [Emanuel, E.; Miller, F. G.] NIH, Bethesda, MD 20892 USA. [Kaptchuk, T. J.] Harvard Univ, Sch Med, Osher Ctr, Boston, MA 02115 USA. [Curlin, F. A.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 369 EP 370 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100763 ER PT J AU Yazdanyar, A Bost, JE Wasko, MC Kraemer, KL Ward, MM AF Yazdanyar, A. Bost, J. E. Wasko, M. C. Kraemer, K. L. Ward, M. M. TI Rheumatoid arthritis increases risk of all-cause mortality during elective hospitalizations with surgical procedures: An analysis using the national inpatient sample of healthcare cost and utilization project SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Yazdanyar, A.; Bost, J. E.; Wasko, M. C.; Kraemer, K. L.] Univ Pittsburgh, Pittsburgh, PA USA. [Ward, M. M.] NIAMS, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 396 EP 396 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100835 ER PT J AU Phillips, KA Olsen, YK Keruly, JC Moore, RD AF Phillips, K. A. Olsen, Y. K. Keruly, J. C. Moore, R. D. TI The impact of HIV-care appointment adherence on HIV outcomes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Phillips, K. A.] Natl Inst Hlth, Baltimore, MD USA. [Olsen, Y. K.] Harford Cty Dept Hlth, Bel Air, MD USA. [Keruly, J. C.; Moore, R. D.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 414 EP 415 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100887 ER PT J AU Tilburt, J Emanuel, E Miller, FG AF Tilburt, J. Emanuel, E. Miller, F. G. TI Trends in annual us sales of herbs, vitamins, and supplements before and after publication of research results: Does the evidence translate? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med C1 [Tilburt, J.] Mayo Clin, Rochester, MN USA. [Emanuel, E.; Miller, F. G.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2008 VL 23 SU 2 BP 427 EP 427 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 277TH UT WOS:000254237100920 ER PT J AU Sullivan, J Petronella, S Brooks, E Murillo, M Primeau, L Ward, J AF Sullivan, John Petronella, Sharon Brooks, Edward Murillo, Maria Primeau, Loree Ward, Jonathan TI Theatre of the oppressed and environmental justice communities: a transformational therapy for the body politic SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE Augusto Boal; Community-Based Participatory Research (CBPR); drama therapy; environmental justice (EJ); project COAL; theatre of the oppressed AB Community Environmental Forum Theatre at UTMB-NIEHS Center in Environmental Toxicology uses Augusto Boat's Theatre of the Oppressed (TO) to promote involvement of citizens, scientists, and health professionals in deconstructing toxic exposures, risk factors, and cumulative stressors that impact the well-being of communities. The TO process encourages collective empowerment of communities by disseminating information and elaborating support networks. TO also elicits transformation and growth on a personal level via a dramaturgical system that restores spontaneity through image-making and improvisation. An NIEHS Environmental Justice Project, Communities Organized against Asthma & Lead, illustrates this interplay of personal and collective change in Houston, Texas. C1 [Sullivan, John; Petronella, Sharon; Brooks, Edward; Murillo, Maria; Primeau, Loree; Ward, Jonathan] Univ Texas Galveston, Sealy Ctr Environm Hlth & Med, NIEHS Ctr Environm Toxicol, Med Branch, Galveston, TX 77555 USA. RP Sullivan, J (reprint author), Univ Texas Galveston, Sealy Ctr Environm Hlth & Med, NIEHS Ctr Environm Toxicol, Med Branch, 301 Univ Blvd, Galveston, TX 77555 USA. EM josuiliv@utmb.edu NR 31 TC 5 Z9 5 U1 1 U2 17 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD MAR PY 2008 VL 13 IS 2 BP 166 EP 179 DI 10.1177/1359105307086710 PG 14 WC Psychology, Clinical SC Psychology GA 291BL UT WOS:000255167200003 PM 18375623 ER PT J AU Kim, SY Weinstein, DA Starost, MF Mansfield, BC Chou, JY AF Kim, So Youn Weinstein, David A. Starost, Matthew F. Mansfield, Brian C. Chou, Janice Y. TI Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia SO JOURNAL OF HEPATOLOGY LA English DT Article DE glycogen storage disease type Ia; hepatic necrosis; hepatic neutrophil infiltration; chemokines; hepatocellular adenoma; glucose homeostasis ID CHRONIC HEPATITIS-C; HEPATOCELLULAR-CARCINOMA; AST/ALT RATIO; SERUM-LEVELS; INTERLEUKIN-8; INFLAMMATION; ADENOMAS; CYTOKINE; PATHOPHYSIOLOGY; HOMEOSTASIS AB Background/Aims: Glycogen storage disease type la (GSD-Ia) patients manifest the long-term complication of hepatocellular adenoma (HCA) of unknown etiology. We showed previously that GSD-Ia mice exhibit neutrophilia and elevated serum cytokine levels. This study was conducted to evaluate whether human GSD-Ia patients exhibit analogous increases and whether in GSD-Ia mice a correlation exists between immune abnormalities and, biochemical and histological alterations in the liver. Methods: Differential leukocyte counts and cytokine levels were investigated in GSD-Ia patients. Hepatic chemokine production, neutrophil infiltration, and histological abnormalities were investigated in GSD-Ia mice. Results: We show that GSD-Ia patients exhibit increased peripheral neutrophil counts and serum interleukin-8 (IL-8). Compared to normal subjects, HCA-bearing GSD-Ia patients have a 2.8-fold higher serum IL-8 concentration, while GSD-Ia patients without HCA have a 1.4-fold higher concentration. Hepatic injury in GSD-Ia mice is evidenced by necrotic foci, markedly elevated infiltrating neutrophils, and increased hepatic production of chemokines. Conclusions: Peripheral neutrophilia and elevated serum chemokines are characteristic of GSD-Ia with HCA-bearing GSD-Ia patients having the highest serum IL-8. In GSD-Ia mice these elevations correlate with elevated hepatic chemokine levels, neutrophil infiltration, and necrosis. Taken together, peripheral neutrophilia and increased serum chemokines may indicate hepatic injuries in GSD-Ia. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Kim, So Youn; Mansfield, Brian C.; Chou, Janice Y.] NICHHD, Sect Cellular Differentiat, NIH, Bethesda, MD 20892 USA. [Weinstein, David A.] Univ Florida, Coll Med, Div Pediat Endocrinol, Glycogen Storage Dis Program, Gainesville, FL 32610 USA. [Starost, Matthew F.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural NIH HHS [Z01 HD000912-28]; NCRR NIH HHS [K23 RR 017560, K23 RR017560, M01 RR 00082, M01 RR000082] NR 41 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2008 VL 48 IS 3 BP 479 EP 485 DI 10.1016/j.jhep.2007.11.014 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 275TI UT WOS:000254094100013 PM 18191274 ER PT J AU Purcell, RH Emerson, SU AF Purcell, R. H. Emerson, S. U. TI Hepatitis E: An emerging awareness of an old disease SO JOURNAL OF HEPATOLOGY LA English DT Review DE water-borne; zoonosis; acute hepatitis ID E VIRUS HEV; NON-B-HEPATITIS; ACUTE VIRAL-HEPATITIS; CELL-CULTURE SYSTEM; SPORADIC ACUTE; UNITED-STATES; NON-A; WIDESPREAD INFECTION; RHESUS-MONKEYS; RISK-FACTORS AB Although hepatitis E was recognized as a new disease in 1980, the virus was first visualized in 1983 and its genome was cloned and characterized in 1991, the disease is probably ancient but not recognized until modern times. Hepatitis E is the most important or the second most important cause of acute clinical hepatitis in adults throughout Asia, the Middle East and Africa. In contrast, hepatitis E is rare in industrialized countries, but antibody (anti-HEV) is found worldwide. HEV is a small round RNA-containing virus that is the only member of the genus Hepevirus in the family Hepeviridae. Although similar to hepatitis A virus in appearance, there are significant differences between the two viruses. Hepatitis E is principally the result of a water-borne infection in developing countries and is thought to be spread zoonotically (principally from swine) in industrialized countries. Because diagnostic tests vary greatly in specificity, sensitivity and availability, hepatitis E is probably underdiagnosed. At present, control depends upon improved hygiene; a highly efficacious vaccine has been developed and tested, but it is not presently available. Published by Elsevier B.V on behalf of the European Association for the Study of the Liver. C1 [Purcell, R. H.; Emerson, S. U.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Purcell, RH (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Dr MSC 8009, Bethesda, MD 20892 USA. EM rpurcell@niaid.nih.gov NR 68 TC 333 Z9 364 U1 4 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2008 VL 48 IS 3 BP 494 EP 503 DI 10.1016/j.jhep.2007.12.008 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 275TI UT WOS:000254094100015 PM 18192058 ER PT J AU Asano, N Watanabe, T Kitani, A Fuss, IJ Strober, W AF Asano, Naoki Watanabe, Tomohiro Kitani, Atsushi Fuss, Ivan J. Strober, Warren TI Notch1 signaling and regulatory T cell function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; BOUND TGF-BETA; DENDRITIC CELLS; IN-VIVO; GAMMA-SECRETASE; UP-REGULATION; CUTTING EDGE; DIFFERENTIATION; ACTIVATION; EXPRESSION AB Previous studies have shown that the Notch1 and TGF-beta signaling pathways are mutually re-enforcing. Given recent evidence that regulatory T cell (Treg) effector function is mediated by TGF-beta signaling, we investigated whether Notch1 signaling also participated in Treg effector function. Initial studies showed that Notch1 ligands, particularly Jagged1, are present on Tregs and that, indeed, blockade of Notch1 signaling with an anti-jagged1 or a blocking anti-Notch1 Ab inhibits Treg suppressor function in vitro. We then showed that a signaling component generated by Notch1 activation (Notch1 intracellular domain) of dendritic cells physically interacts with a signaling component generated by TGF-beta signaling (pSmad3). Furthermore, this interaction has functional downstream effects because over-expression of Notch1 intracellular domain facilitates pSmad3 translocation to the nucleus and enhances pSmad3 transcriptional activity of a Smad-sensitive promoter linked to a luciferase reporter. Finally, we showed that blockade of TGF-beta signaling and Notch signaling did not have additive inhibitory effects on Treg suppressor function. These results are consistent with the conclusion that Notch1 signaling facilitates TGF-beta-mediated effector function of Tregs. C1 [Asano, Naoki; Watanabe, Tomohiro; Kitani, Atsushi; Fuss, Ivan J.; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Watanabe, Tomohiro] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bldg 10 Clin Res Ctr,Mail Stop Code 1890,10 Ctr D, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov OI Asano, Naoki/0000-0003-4452-8459 NR 51 TC 51 Z9 55 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2008 VL 180 IS 5 BP 2796 EP 2804 PG 9 WC Immunology SC Immunology GA 313GV UT WOS:000256730000015 PM 18292500 ER PT J AU Haring, JS Jing, XF Bollenbacher-Reilley, J Xue, HH Leonard, WJ Harty, JT AF Haring, Jodie S. Jing, Xuefang Bollenbacher-Reilley, Julie Xue, Hai-Hui Leonard, Warren J. Harty, John T. TI Constitutive expression of IL-7 receptor alpha does not support increased expansion or prevent contraction of antigen-specific CD4 or CD8 T cells following Listeria monocytogenes infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-7 RECEPTOR; IFN-GAMMA; HOMEOSTATIC PROLIFERATION; DYNAMIC REGULATION; GENE-EXPRESSION; VIRAL-INFECTION; CUTTING EDGE; MEMORY CELLS; IN-VIVO; GENERATION AB Expression of IL-7R alpha (CD127) has been suggested as a major determinant in the survival of memory T cell precursors. We investigated whether constitutive expression of IL-7R alpha on T cells increased expansion and/or decreased contraction of endogenous Ag-specific CD4 and CD8 T cells following infection with Listeria monocytogenes. The results indicate that constitutive expression of IL-7Ra alone was not enough to impart an expansion or survival advantage to CD8 T cells responding to infection, and did not increase memory CD8 T cell numbers over those observed in wild-type controls. Constitutive expression of IL-7R alpha did allow for slightly prolonged expansion of Ag-specific CD4 T cells; however, it did not alter the contraction phase or protect against the waning of memory T cell numbers at later times after infection. Memory CD4 and CD8 T cells generated in IL-7R alpha transgenic mice expanded similarly to wild-type T cells after secondary infection, and immunized IL-7Ra transgenic mice were fully protected against lethal bacterial challenge demonstrating that constitutive expression of IL-7R alpha does not impair, or markedly improve memory/secondary effect-or T cell function. These results indicate that expression of IL-7R alpha alone does not support increased survival of effector Ag-specific CD4 or CD8 T cells into the memory phase following bacterial infection. C1 [Haring, Jodie S.; Jing, Xuefang; Xue, Hai-Hui; Harty, John T.] Univ Iowa, Carver Sch Med, Dept Microbiol, Iowa City, IA 52242 USA. [Harty, John T.] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA. [Bollenbacher-Reilley, Julie; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20824 USA. RP Harty, JT (reprint author), Univ Iowa, Carver Sch Med, Dept Microbiol, 3-512 Bowen Sci Bldg,51 Newton Rd, Iowa City, IA 52242 USA. EM john-harty@uiowa.edu FU NIAID NIH HHS [AI46653, AI42767, AI50073] NR 38 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2008 VL 180 IS 5 BP 2855 EP 2862 PG 8 WC Immunology SC Immunology GA 313GV UT WOS:000256730000022 PM 18292507 ER PT J AU Alderson, KL Zhou, Q Berner, V Wilkins, DEC Weiss, JM Blazar, BR Welniak, LA Wiltrout, RH Redelman, D Murphy, WJ AF Alderson, Kory L. Zhou, Qing Berner, Vanessa Wilkins, Danice E. C. Weiss, Jonathan M. Blazar, Bruce R. Welniak, Lisbeth A. Wiltrout, Robert H. Redelman, Doug Murphy, William J. TI Regulatory and conventional CD4(+) T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELL; ANTITUMOR RESPONSES; CD8-T-CELL MEMORY; CD4-T-CELL HELP; MECHANISM; DEATH; AUTOIMMUNITY; ACTIVATION; ENGAGEMENT; TOLERANCE AB Recently, our laboratory reported that secondary CD8(+) T cell-mediated antitumor responses were impaired following successful initial antitumor responses using various immunotherapeutic approaches. Although immunotherapy stimulated significant increases in CD8(+) T cell numbers, the number of CD4(+) T cells remained unchanged. The current investigation revealed a marked differential expansion of CD4(+) T cell subsets. Successful immunotherapy surprisingly resulted in an expansion of CD4(+)Foxp3(+) regulatory T (Treg) cells concurrent with a reduction of conventional CD4(+) T (Tconv) cells, despite the marked antitumor responses. Following immunotherapy, we observed differential up-regulation of PD-1 on the surface of CD4(+)Foxp3(+) Treg cells and CD4(+)Foxp3(-) Tconv cells. Interestingly, it was the ligand for PD-1, B7-H1 (PDL-1), that correlated with Tconv cell loss after treatment. Furthermore, IFN-gamma knockout (IFN-gamma(-/-)) and IFN-gamma receptor knockout (IFN-gamma R(-/-)) animals lost up-regulation of surface B7-H1 even though PD-1 expression of Tconv cells was not changed, and this correlated with CD4+ Tconv cell increases. These results suggest that subset-specific expansion may contribute to marked shifts in the composition of the T cell compartment, potentially influencing the effectiveness of some immunotherapeutic approaches that rely on IFN-gamma. C1 [Alderson, Kory L.; Zhou, Qing; Berner, Vanessa; Wilkins, Danice E. C.; Welniak, Lisbeth A.; Murphy, William J.] Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA. [Redelman, Doug] Univ Nevada, Dept Physiol & Cell Biol, Reno, NV 89557 USA. [Weiss, Jonathan M.; Wiltrout, Robert H.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Blazar, Bruce R.] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. [Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. RP Murphy, WJ (reprint author), Univ Nevada, Dept Microbiol & Immunol, ARF Room 342,Mail Stop 199, Reno, NV 89557 USA. EM wmurphy@medicine.nevada.edu FU Intramural NIH HHS [Z99 CA999999, Z01 BC009262-24]; NCI NIH HHS [R01 CA72669, R01 CA095572, R01 CA072669, R01 CA095572-06]; NCRR NIH HHS [P20 RR-016464, P20 RR016464]; NHLBI NIH HHS [R37 HL56067, R37 HL056067, R01 HL056067]; NIAID NIH HHS [P01 AI0562991, R01 AI34495] NR 36 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2008 VL 180 IS 5 BP 2981 EP 2988 PG 8 WC Immunology SC Immunology GA 313GV UT WOS:000256730000035 PM 18292520 ER PT J AU Smoak, K Madenspacher, J Jeyaseelan, S Williams, B Dixon, D Poch, KR Nick, JA Worthen, GS Fessler, MB AF Smoak, Kathleen Madenspacher, Jennifer Jeyaseelan, Samithamby Williams, Belinda Dixon, Darlene Poch, Katie R. Nick, Jerry A. Worthen, G. Scott Fessler, Michael B. TI Effects of liver X receptor agonist treatment on pulmonary inflammation and host defense SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROLIFERATOR-ACTIVATED-RECEPTOR; INDUCED LUNG INFLAMMATION; NUCLEAR RECEPTOR; HUMAN NEUTROPHIL; PROTEIN-KINASE; LXR-ALPHA; OXYSTEROL RECEPTOR; CHOLESTENOIC ACID; RESPONSE PATHWAY; EPITHELIAL-CELLS AB Liver X receptor (LXR) alpha and beta are members of the nuclear receptor superfamily of ligand-activated transcription factors. Best known for triggering "reverse cholesterol transport" gene programs upon their activation by endogenous oxysterols, LXRs have recently also been implicated in regulation of innate immunity. In this study, we define a role for LXRs in regulation of pulmonary inflammation and host defense and identify the lung and neutrophil as novel in vivo targets for pharmacologic LXR activation. LXR is expressed in murine alveolar macrophages, alveolar epithelial type II cells, and neutrophils. Treatment of mice with TO-901317, a synthetic LXR agonist, reduces influx of neutrophils to the lung triggered by inhaled LPS, intratracheal KC chemokine, and intratracheal Klebsiella pneumoniae and impairs pulmonary host defense against this bacterium. Pharmacologic LXR activation selectively modulates airspace cytokine expression induced by both LPS and K. pneumoniae. Moreover, we report for the first time that LXR activation impairs neutrophil motility and identify inhibition of chemokine-induced RhoA activation as a putative underlying mechanism. Taken together, these data define a novel role for LXR in lung pathophysiology and neutrophil biology and identify pharmacologic activation of LXR as a potential tool for modulation of innate immunity in the lung. C1 [Smoak, Kathleen; Madenspacher, Jennifer; Fessler, Michael B.] Natl Inst Environm Hlth Sci, Lab Resp Program, Res Triangle Pk, NC 27709 USA. [Dixon, Darlene] Natl Inst Environm Hlth Sci, Dept Hlth & Human Sci, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Jeyaseelan, Samithamby; Williams, Belinda; Poch, Katie R.; Nick, Jerry A.; Worthen, G. Scott] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA. RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Program, 111 TW Alexander Dr,POB 12233,Maildrop D2-01, Res Triangle Pk, NC 27709 USA. EM worthen@email.chop.edu; fesslerm@niehs.nih.gov FU Intramural NIH HHS [Z01 ES102005-02, Z99 ES999999]; NHLBI NIH HHS [5P01HL68743-04, 5R01HL061407-08, P01 HL068743, P01 HL068743-040002, R01 HL061407, R01 HL061407-08] NR 69 TC 44 Z9 49 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2008 VL 180 IS 5 BP 3305 EP 3312 PG 8 WC Immunology SC Immunology GA 313GV UT WOS:000256730000070 PM 18292555 ER PT J AU Kiwanuka, N Laeyendecker, O Robb, M Kigozi, G Arroyo, M McCutchan, F Eller, LA Eller, M Makumbi, F Birx, D Wabwire-Mangen, F Serwadda, D Sewankambo, NK Quinn, TC Wawer, M Gray, R AF Kiwanuka, Noah Laeyendecker, Oliver Robb, Merlin Kigozi, Godfrey Arroyo, Miguel McCutchan, Francine Eller, Leigh Anne Eller, Michael Makumbi, Fred Birx, Deborah Wabwire-Mangen, Fred Serwadda, David Sewankambo, Nelson K. Quinn, Thomas C. Wawer, Maria Gray, Ronald TI Effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 13th Conference on Retroviruses and Opportunistic Infections CY FEB 05-09, 2006 CL Denver, CO ID GENETIC DIVERSITY; GROUP-O; COHORT; TRANSMISSION; RECOMBINANTS; TANZANIA; DISTINCT; VACCINE; AFRICA; AIDS AB Background. Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity. Methods. We determined the HIV-1 subtype-specific rates of disease progression among 350 HIV-1 seroconverters. Subtype, viral load, and CD4(+) cell count were determined. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4(+) cell count of <= 250 cells/mm(3)) and to AIDS-associated death. Results. A total of 59.1% of study subjects had subtype D strains, 15.1% had subtype A, 21.1% had intersubtype recombinant subtypes, 4.3% had multiple subtypes, and 0.3% had subtype C. Of the 350 subjects, 129 (37%) progressed to AIDS, and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D(6.5 years), recombinant subtypes (5.6 years), or multiple subtypes (5.8 years), compared with persons with subtype A (8.0 years; P = .022). Relative to subtype A, adjusted HRs of progression to AIDS were 2.13 [ 95% confidence interval {CI}, 1.10-4.11] for subtype D, 2.16 [ 95% CI, 1.05-4.45] for recombinant subtypes, and 4.40 [ 95% CI, 1.71-11.3] for multiple subtypes. The risk of progression to death was significantly higher for subtype D(adjusted HR, 5.65; 95% CI, 1.37-23.4), recombinant subtypes (adjusted HR, 6.70; 95% CI, 1.56-28.8), and multiple subtypes (adjusted HR, 7.67; 95% CI, 1.27-46.3), compared with subtype A. Conclusions. HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression. C1 [Kiwanuka, Noah; Kigozi, Godfrey] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda. [Makumbi, Fred; Wabwire-Mangen, Fred; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Sewankambo, Nelson K.] Makerere Univ, Dept Med, Kampala, Uganda. [Sewankambo, Nelson K.] Makerere Univ, Clin Epidemiol Unit, Kampala, Uganda. [Kiwanuka, Noah] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Wawer, Maria; Gray, Ronald] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA. [Robb, Merlin; Eller, Leigh Anne; Eller, Michael; Birx, Deborah] Henry M Jackson Fdn, Rockville, MD USA. [Arroyo, Miguel; McCutchan, Francine] Walter Reed Army Inst Res, Silver Spring, MD USA. RP Kiwanuka, N (reprint author), Uganda Virus Res Inst, Rakai Hlth Sci Program, POB 49, Entebbe, Uganda. EM nkiwanuka@rhsp.org RI Laeyendecker, Oliver/B-9331-2009; OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker, Oliver/0000-0002-6429-4760; Arroyo, Miguel/0000-0001-7416-8867 FU FIC NIH HHS [5D43TW00010]; PHS HHS [2DTW000010-19] NR 30 TC 149 Z9 156 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2008 VL 197 IS 5 BP 707 EP 713 DI 10.1086/527416 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FD UT WOS:000253773400015 PM 18266607 ER PT J AU Chun, TW Nickle, DC Justement, JS Meyers, JH Roby, G Hallahan, CW Kottilil, S Moir, S Mican, JM Mullins, JI Ward, DJ Kovacs, JA Mannon, PJ Fauci, AS AF Chun, Tae-Wook Nickle, David C. Justement, Jesse S. Meyers, Jennifer H. Roby, Gregg Hallahan, Claire W. Kottilil, Shyam Moir, Susan Mican, Joann M. Mullins, James I. Ward, Douglas J. Kovacs, Joseph A. Mannon, Peter J. Fauci, Anthony S. TI Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CD4(+) T-CELLS; GASTROINTESTINAL-TRACT; LATENT RESERVOIR; SIV INFECTION; REPLICATION; VIRUS; DEPLETION; RESTORATION; INDIVIDUALS; LYMPHOCYTES AB Human immunodeficiency virus (HIV) persists in peripheral blood mononuclear cells despite sustained, undetectable plasma viremia resulting from long-term antiretroviral therapy. However, the source of persistent HIV in such infected individuals remains unclear. Given recent data suggesting high levels of viral replication and profound depletion of CD4(+) T cells in gut-associated lymphoid tissue (GALT) of animals infected with simian immunodeficiency virus and HIV-infected humans, we sought to determine the level of CD4(+) T cell depletion as well as the degree and extent of HIV persistence in the GALT of infected individuals who had been receiving effective antiviral therapy for prolonged periods of time. We demonstrate incomplete recoveries of CD4(+) T cells in the GALT of aviremic, HIV-infected individuals who had received up to 9.9 years of effective antiretroviral therapy. In addition, we demonstrate higher frequencies of HIV infection in GALT, compared with PBMCs, in these aviremic individuals and provide evidence for cross-infection between these 2 cellular compartments. Together, these data provide a possible mechanism for the maintenance of viral reservoirs revolving around the GALT of HIV-infected individuals despite long-term viral suppression and suggest that the GALT may play a major role in the persistence of HIV in such individuals. C1 [Chun, Tae-Wook; Justement, Jesse S.; Meyers, Jennifer H.; Roby, Gregg; Kottilil, Shyam; Moir, Susan; Fauci, Anthony S.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Hallahan, Claire W.] NIAID, Biol Resources Branch, Bethesda, MD 20892 USA. [Mannon, Peter J.] NIAID, Host Def Lab, Bethesda, MD 20892 USA. [Mican, Joann M.] NIAID, Div Clin Res, Bethesda, MD 20892 USA. [Kovacs, Joseph A.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. [Nickle, David C.; Mullins, James I.] Univ Washington, Dept Microbiol, Washington, DC USA. [Ward, Douglas J.] Dupont Circle Physcians Grp, Washington, DC USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A32,9000 Rockville Pike, Bethesda, MD 20892 USA. EM twchun@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [P30 AI27757] NR 29 TC 247 Z9 254 U1 8 U2 19 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2008 VL 197 IS 5 BP 714 EP 720 DI 10.1086/527324 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FD UT WOS:000253773400016 PM 18260759 ER PT J AU Castle, PE AF Castle, Philip E. TI Human papillomavirus (HPV) genotype 84 infection of the male genitalia: Further evidence for HPV tissue tropism? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID VAGINAL HUMAN-PAPILLOMAVIRUS; RISK-FACTORS; MEN; DETERMINANTS; PERSISTENCE; POPULATION; PREVALENCE; SITES; WOMEN; SELF C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2008 VL 197 IS 5 BP 776 EP 778 DI 10.1086/527398 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FD UT WOS:000253773400027 PM 18419356 ER PT J AU Cohen, JI AF Cohen, Jeffrey I. TI Strategies for herpes zoster vaccination of immunocompromised patients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INACTIVATED VARICELLA VACCINE; HIV-INFECTED CHILDREN; POSTHERPETIC NEURALGIA; TRANSPLANT RECIPIENTS; VIRUS-VACCINE; LIVE; IMMUNIZATION; IMMUNOGENICITY; IMMUNITY; SAFETY AB A vaccine to prevent herpes zoster ( HZ) in adults >= 60 years of age with healthy immune systems was recently approved by the US Food and Drug Administration. This vaccine is contraindicated in persons with certain immunodeficiency states or who are receiving immunosuppressive therapy. On the basis of studies of the varicella vaccine in healthy and immunosuppressed children and studies of HZ vaccine in healthy adults before its licensure, a series of strategies are proposed for evaluating the live HZ vaccine in immunosuppressed persons. In addition, the use of other vaccines, including heat-inactivated or replication-defective varicella-zoster virus to prevent HZ in immunocompromised persons, is also discussed. C1 NIAID, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, Bldg 10,Rm 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000978-02] NR 25 TC 19 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 1 PY 2008 VL 197 SU 2 BP S237 EP S241 DI 10.1086/522129 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FF UT WOS:000253773600036 PM 18419403 ER PT J AU Fischer, P Ai, AL AF Fischer, Peter Ai, Amy L. TI International terrorism and mental health - Recent research and future directions SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE international terrorism; mental health; posttraumatic stress; posttraumatic growth in adversity ID POSTTRAUMATIC-STRESS-DISORDER; DISASTER VICTIMS SPEAK; WORLD-TRADE-CENTER; POSITIVE EMOTIONS; SEPTEMBER 11; ATTACKS; TRAUMA; GROWTH; RELIABILITY; SYMPTOMS AB International terrorism has become a major global concern. Several studies conducted in North America and Europe in the aftermath of terrorist attacks reveal that international terrorism represents a significant short-term and long-term threat to mental health. In the present article, the authors clarify the concept and categories of terrorism and then present central findings from studies conducted in the United States and Europe, which mainly focus on negative impacts on mental health, such as emotional stress and PTSD. Furthermore, the authors outline experiments that focus on social interaction processes thought to be triggered by international terrorism and which are assumed to be related indirectly to mental health processes. Next, they highlight the potential positive outcomes on the resilience side, in line with the current theory on posttraumatic growth in adversity. Finally, theoretical and practical implications as well as limitations and future directions are discussed. C1 [Fischer, Peter] Univ Exeter, Exeter EX4 4QJ, Devon, England. [Ai, Amy L.] Univ Washington, Seattle, WA 98195 USA. [Ai, Amy L.] NIH, Bethesda, MD 20892 USA. RP Fischer, P (reprint author), Univ Exeter, Exeter EX4 4QJ, Devon, England. NR 61 TC 11 Z9 11 U1 4 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD MAR PY 2008 VL 23 IS 3 BP 339 EP 361 DI 10.1177/0886260507312292 PG 23 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 261EW UT WOS:000253062900004 PM 18245572 ER PT J AU Jozic, J Orford, J Steinhubl, S Berger, P Hsu, A Topol, E AF Jozic, Joseph Orford, James Steinhubl, Steven Berger, Peter Hsu, Amy Topol, Eric TI Timing and Correlates of Very Early Major Adverse Clinical Events following Percutaneous Coronary Intervention SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article AB We attempted to determine the incidence, timing and correlates of very early (< 24 hours) major adverse clinical events in patients undergoing contemporary percutaneous coronary intervention (PCI). Early discharge following PCI may offer significant advantages to patient and practitioner, but the timing of, and risk factors for, very early (< 24 hours) major adverse clinical events following PCI are not well characterized. A retrospective analysis of the CREDO trial was performed. A total of 1,815 patient:: underwent a PCI procedure and 139 patients (7.7%) experienced a major adverse clinical event (death, myocardial infarction or urgent target vessel revascularization) within the first 28 days. The majority of these events (111 patients) occurred within the first 24 hours, with the greatest risk of an event within the first 6 hrs. Multivariable predictors of very early events were age, AHA lesion grade, history of peripheral vascular disease, preprocedural TIMI flow grade and no. of vessels with stenosis > 50%. These data show a very low and constant risk of adverse events 6 hours following PCI. C1 [Steinhubl, Steven] Univ Kentucky, Gill Heart Inst, Lexington, KY 40536 USA. [Jozic, Joseph] Univ Hosp, Case Med Ctr, Cleveland, OH USA. [Orford, James] Mayday Univ Hosp, Croydon, England. [Berger, Peter] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. [Hsu, Amy] NHGRI, NIH, Bethesda, MD 20892 USA. [Topol, Eric] Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA. RP Steinhubl, S (reprint author), Univ Kentucky, Gill Heart Inst, 900 S Limestone Ave,326 Charles T Wethington Bldg, Lexington, KY 40536 USA. EM srstei2@email.uky.edu OI Topol, Eric/0000-0002-1478-4729 FU Sanofi-Aventis; Bristol-Myers Squibb FX Dr. Steinhubl discloses that he is a paid consultant to Eli Lilly & Co., Medeo, Bristol-Myers Squibb, AstraZeneca International, and Daiichi Sankyo. Dr. Topol discloses that he has received research grants from Sanofi-Aventis and Bristol-Myers Squibb. Dr. Berger discloses that he has been a faculty member of sicentific symposia supported by Bristol-Myers Squibb, Sanofi-Aventis, The Medicines Company, AstraZenica, Medtronic Inc., Schering Plough, and Lilly/Daiichi Sankyo. He has also served as a consultant to PlaCor, Lilly/Daiichi Sankyo, Molecular Insight Pharmaceuticals, and CV Therapeutics. Dr. Berger also has equity ownership in Lumen Biomedical, Inc. NR 13 TC 2 Z9 2 U1 0 U2 3 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD MAR PY 2008 VL 20 IS 3 BP 113 EP 118 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V14MN UT WOS:000207738600006 PM 18316826 ER PT J AU Persad, GC Elder, L Sedig, L Flores, L Emanuel, EJ AF Persad, Govind C. Elder, Linden Sedig, Laura Flores, Leonardo Emanuel, Ezekiel J. TI The current state of medical school education in bioethics, health law, and health economics SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID ETHICS EDUCATION; US; CURRICULUM; STUDENTS; LEGAL AB Current challenges in medical practice, research, and administration demand physicians who are familiar with bioethics, health law, and health economics. Curriculum directors at American Association of Medical Colleges-affiliated medical schools were sent confidential surveys requesting the number of required hours of the above subjects and the years in which they were taught, as well as instructor names. The number of relevant publications since 1990 for each named instructor was assessed by a PubMed search. In sum, teaching in all three subjects combined comprises less than two percent of the total hours in the American medical curriculum, and most instructors have not recently published articles in the fields they teach. This suggests that medical schools should reevaluate their curricula and instructors in bioethics, health law, and health economics. C1 [Emanuel, Ezekiel J.] Natl Inst Hlth, Dept Bioeth, Bethesda, MD 20892 USA. NR 17 TC 18 Z9 18 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2008 VL 36 IS 1 BP 89 EP + DI 10.1111/j.1748-720X.2008.00240.x PG 7 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 270HH UT WOS:000253711400012 PM 18315764 ER PT J AU Hasko, G Pacher, P AF Hasko, Gyoergy Pacher, Pal TI A(2A) receptors in inflammation and injury: lessons learned from transgenic animals SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 7th World Congress on Trauma, Shock, Inflammation and Sepsis CY MAR 13-17, 2007 CL Munich, GERMANY DE macrophage; lymphocyte; neutrophil; cytokine; autoimmune; infection ID ISCHEMIA-REPERFUSION INJURY; MARROW-DERIVED CELLS; ADENOSINE-DEAMINASE DEFICIENCY; BRONCHIAL EPITHELIAL-CELLS; HUMAN DENDRITIC CELLS; TUMOR-NECROSIS-FACTOR; INDUCED LUNG INJURY; IN-VIVO MODEL; NITRIC-OXIDE; TNF-ALPHA AB Adenosine regulates the function of the innate and adaptive immune systems through targeting virtually every cell type that is involved in orchestrating an immune/inflammatory response. Of the four adenosine receptors (A(1), A(2A), A(2B), A(3)), A(2A) receptors have taken center stage as the primary anti-inflammatory effectors of extracellular adenosine. This broad, anti-inflammatory effect of A(2A) receptor activation is a result of the predominant expression of A(2A) receptors on monocytes/macrophages, dendritic cells, mast cells, neutrophils, endothelial cells, eosinophils, epithelial cells, as well as lymphocytes, NK cells, and NKT cells. A(2A) receptor activation inhibits early and late events occurring during an immune response, which include antigen presentation, costimulation, immune cell trafficking, immune cell proliferation, proinflammatory cytokine production, and cytotoxicity. In addition to limiting inflammation, A(2A) receptors participate in tissue remodeling and reparation. Consistent with their multifaceted, immunoregulatory action on immune cells, A(2A) receptors have been shown to impact the course of a wide spectrum of ischemic, autoimmune, infectious, and allergic diseases. Here, we review the regulatory roles of A(2A) receptors in immune/inflammatory diseases of various organs, including heart, lung, gut, liver, kidney, joints, and brain, as well as the role of A(2A) receptors in regulating multiple organ failure and sepsis. C1 [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Hasko, Gyoergy] Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, Budapest, Hungary. [Pacher, Pal] Natl Inst Alcohol Abuse & Alcoholism, Lab Phys Studies, Sect Oxidat Stress & Tissue Injury, Bethesda, MD USA. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave,Univ Heights, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02]; NIGMS NIH HHS [R01 GM 66189, R01 GM066189, R01 GM066189-01, R01 GM066189-02] NR 114 TC 121 Z9 126 U1 0 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR 1 PY 2008 VL 83 IS 3 BP 447 EP 455 DI 10.1189/jlb.0607359 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 331NM UT WOS:000258018900002 PM 18160539 ER PT J AU Achuthan, S Asbury, T Hu, J Bertram, R Cross, TA Quine, JR AF Achuthan, S. Asbury, T. Hu, J. Bertram, R. Cross, T. A. Quine, J. R. TI Continuity conditions and torsion angles from ssNMR orientational restraints SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE solid state NMR; torsion angles; peptide planes; diplanes; degeneracies; PISEMA; PIPATH ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; TRANS-MEMBRANE DOMAIN; INFLUENZA-A VIRUS; PROTEIN-STRUCTURE; POLYPEPTIDE STRUCTURE; ANISOTROPIC ENVIRONMENTS; BACKBONE STRUCTURE; SPIN-EXCHANGE; LIPID-BILAYER AB The backbone torsion angle pair (phi, psi) at each amino acid of a polypeptide is a descriptor of its conformation. One can use chemical shift and dipolar coupling data from solid-state NMR PISEMA experiments to directly calculate the torsion angles for the membrane-spanning portion of a protein. However, degeneracies inherent in the data give rise to multiple potential torsion angles between two adjacent peptide planes (a diplane). The molecular backbone structure can be determined by gluing together the consecutive diplanes, as in the PIPATH algorithm [T. Asbury, J.R. Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross, R. Bertram, PIPATH: an optimized alogrithm for generating alpha-helical structures from PISEMA data, J. Magn. Reson. 183 (2006) 87-95.]. The multiplicities in torsion angles translate to multiplicities in diplane orientations. In this paper, we show that adjacent diplanes can be glued together to form a permissible structure only if they satisfy continuity conditions, described quantitatively here. These restrict the number of potential torsion angle pairs. We rewrite the torsion angle formulas from [J.R. Quine, M.T. Brenneman, T.A. Cross, Protein structural analysis from solid-state NMR-drived orientational constraints, Biophys. J. 72 (1997) 2342-2348.] so that they automatically satisfy the continuity conditions. The reformulated torsion angle formulas have been applied recently in the PIPATH algorithm [T. Asbury, J.R. Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross, R. Bertram, PIPATH: an optimized alogrithm for generating alpha-helical structures from PISEMA data, J. Magn. Reson. 183 (2006) 87-95.] and will be helpful in other applications in which diplane gluing is used to construct a protein backbone model. Published by Elsevier Inc. C1 [Achuthan, S.; Bertram, R.; Quine, J. R.] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. [Cross, T. A.; Quine, J. R.] Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Asbury, T.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Tallahassee, FL 32306 USA. [Bertram, R.] Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. [Cross, T. A.] Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. [Hu, J.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Achuthan, S (reprint author), Louisiana State Univ, Hlth Sci Ctr, Sch Med, Neurosci Ctr Excellence, New Orleans, LA 70112 USA. EM sachut@lsuhse.edu FU NIAID NIH HHS [R01 AI023007-18, R01 AI023007, R01-AI23007]; NIGMS NIH HHS [P01 GM064676-05, P01-GM64676, P01 GM064676] NR 30 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 2008 VL 191 IS 1 BP 24 EP 30 DI 10.1016/j.jmr.2007.11.018 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 267HS UT WOS:000253500700004 PM 18093855 ER PT J AU Baker, EH Basso, G Barker, PB Smith, MA Bonekamp, D Horska, A AF Baker, Eva H. Basso, Gianpaolo Barker, Peter B. Smith, Mari A. Bonekamp, David Horska, Alena TI Regional apparent metabolite concentrations in young adult brain measured by H-1 MR spectroscopy at 3 tesla SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance spectroscopy; normal adult; brain metabolites; LCModel; 3T ID MAGNETIC-RESONANCE-SPECTROSCOPY; LOCALIZED PROTON MRS; IN-VIVO; NMR-SPECTRA; QUANTIFICATION; WATER; QUANTITATION; GLUTAMATE; INVIVO; LOBE AB Purpose: To quantify and examine the distribution of brain metabolites in normal young adults using single voxel MR spectroscopy at 3 Tesla M. Materials and Methods: Short-echo time single-voxel PRESS technique was used to measure the apparent concentration of five metabolites at nine locations in the brains of young adults. Concentrations were estimated by means of an automated fitting method (LCModel) with reference to an unsuppressed water signal and were corrected for T, relaxation, T2 relaxation, and cerebrospinal fluid partial volume. Analysis of variance with Tukey post hoc test was used to evaluate regional variations. Results: Statistically significant differences in regional concentrations were detected for each of the metabolites. The number of significant differences was greatest for total choline, whereas myo-inositol and the sum of glutamine and glutamate had the fewest. Magnitude of variation was greatest for total choline and least for the sum of N-acetyl aspartate and N-acetylaspartylglutamate. Conclusion: In agreement with previous studies at other field strengths, we found heterogeneous distribution of the major spectroscopically measurable brain metabolites. Although the most distinct differences are between tissue types, there is appreciable variation within a tissue type at different locations. The spectra and metabolite concentrations presented should provide a useful reference for both clinical and research MR spectroscopy studies performed at 3T. C1 [Baker, Eva H.] Natl Inst Hlth, Dept Diagnost Radiol, Bethesda, MD USA. [Baker, Eva H.; Basso, Gianpaolo; Barker, Peter B.; Smith, Mari A.; Bonekamp, David; Horska, Alena] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Basso, Gianpaolo] Univ Trent, Ctr Interdipartimentale Mente Cervello, Trento, Italy. [Barker, Peter B.; Smith, Mari A.] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA. [Smith, Mari A.] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. RP Horska, A (reprint author), Dept Radiol, Traylor 217,720 Rutland Ave, Baltimore, MD 21205 USA. EM ahorska@jhmi.edu RI Basso, Gianpaolo/A-9208-2012 OI Basso, Gianpaolo/0000-0002-6245-9402 FU NCRR NIH HHS [P41 RR 15241, P41 RR015241, P41 RR015241-040002]; NINDS NIH HHS [R01 NS042851, R01 NS 042851] NR 31 TC 46 Z9 46 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAR PY 2008 VL 27 IS 3 BP 489 EP 499 DI 10.1002/jmri.21285 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 273RL UT WOS:000253949300008 PM 18307197 ER PT J AU Trott, JF Vonderhaar, BK Hovey, RC AF Trott, Josephine F. Vonderhaar, Barbara K. Hovey, Russell C. TI Historical perspectives of prolactin and growth hormone as mammogens, lactogens and galactagogues - Agog for the future! SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE prolactin; growth hormone; receptor; mammary gland ID MAMMARY EPITHELIAL-CELLS; HUMAN BREAST-CARCINOMA; ANTERIOR-PITUITARY; MESSENGER-RNA; CLEAVED PROLACTIN; ENDOCRINE CONTROL; GENE-EXPRESSION; STRUCTURAL GENE; TRANSGENIC MICE; DAIRY-COWS AB Around 80 years ago researchers first established that the pituitary gland regulates mammary gland function as demonstrated by the ability of its extracts to promote both mammogenesis and lactogenesis in animal models. Little did they realize that in fact two hormones, prolactin (PRL) and growth hormone (GH), were contributing to these effects. By the mid 1930s PRL had been purified as a distinct lactogen, while the galactopoietic effect of GH was confirmed after its purification in the 1940s. Interest in these hormones initially centered about their potential for increasing milk production, while in the latter half of the twentieth century it became obvious that these hormones also had the potential to influence mammary cancer development. During the past 50 years large strides have been made into understanding how these hormones signal to, and within, cells of the mammary gland, paralleling rapid developments in the fields of cellular and molecular biology. In compiling this review we have summarized the progress that has been made to date regarding roles for these hormones in the mammary gland, with a goal of ensuring that some of the seminal literature is not diluted or forgotten. In doing so it is clear that there are lessons to be learned from past experiences, where new methods and technologies will continue to present exciting new opportunities to revisit lingering questions regarding these fascinating hormones and this fascinating organ. C1 [Trott, Josephine F.; Hovey, Russell C.] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. [Vonderhaar, Barbara K.] NIH, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. RP Hovey, RC (reprint author), Univ Calif Davis, Dept Anim Sci, 2145 Meyer Hall,1 Shields Ave, Davis, CA 95616 USA. EM rchovey@ucdavis.edu NR 80 TC 20 Z9 21 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD MAR PY 2008 VL 13 IS 1 BP 3 EP 11 DI 10.1007/s10911-008-9064-x PG 9 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 269CF UT WOS:000253626400002 PM 18204889 ER PT J AU Dharmaraj, CD Krishna, MC Murugesan, R AF Dharmaraj, Christopher D. Krishna, Murali C. Murugesan, R. TI A feature identification system for electron magnetic resonance tomography: Fusion of principal components transform, color quantization and boundary information SO JOURNAL OF MATHEMATICAL IMAGING AND VISION LA English DT Article DE electron magnetic resonance tomography; color image segmentation; principal components transform; color quantization; feature identification ID IN-VIVO DETECTION; KARHUNEN-LOEVE TRANSFORM; PARAMAGNETIC-RESONANCE; IMAGE SEGMENTATION; FREE-RADICALS; REGION; TIME; SPECTROMETER; SPECTROSCOPY; ALGORITHM AB A windows-based, object-oriented, feature identification system for electron magnetic resonance imaging (EMRI) is presented. Identification of region of interest (ROI) is achieved by fusing the standard principal component transform (PCT) and a color quantization method. The performance of the system is evaluated using renal and a series of murine RIF tumor data imaged on different days after the implantation of the tumor. The integrated ROI identification system clearly brings out the capability of EMRI to detect changes in the tumor redox status when thiol levels are lowered. Prior application of PCT reduces the computation load on the color quantization process, enabling the system to be twice faster than an earlier technique reported by the authors. The system is implemented in Visual C++ using Micro Soft Foundation Classes (MFC). Both visual evaluation as well as quantitative metrics shows the performance of the system to be optimal for 8-color quantization. C1 [Murugesan, R.] Madurai Kamaraj Univ, Madurai 625021, Tamil Nadu, India. [Dharmaraj, Christopher D.] VHNSN Coll, Dept Comp Sci, Virudunagar, India. [Krishna, Murali C.] NCI, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Murugesan, R (reprint author), Madurai Kamaraj Univ, Madurai 625021, Tamil Nadu, India. EM rammku@eth.net NR 37 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0924-9907 J9 J MATH IMAGING VIS JI J. Math. Imaging Vis. PD MAR PY 2008 VL 30 IS 3 BP 284 EP 297 DI 10.1007/s10851-007-0056-z PG 14 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 258SD UT WOS:000252888900005 ER PT J AU Miller, FG Wendler, D AF Miller, F. G. Wendler, D. TI Is it ethical to keep interim findings of randomised controlled trials confidential? SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID MONITORING CLINICAL-TRIALS AB Data monitoring committees often are employed to review interim findings of randomised controlled trials. Interim findings are kept confidential until the data monitoring committee finds that they provide sufficiently compelling evidence regarding efficacy, typically because they have crossed the pre-defined statistical boundaries, or they raise serious concerns about safety. While this practice is vital to maintaining the scientific integrity of controlled trials and thereby ensuring their social value, it has been criticised as unethical. Commentators argue that withholding interim findings from research participants is deceptive, inconsistent with valid informed consent, and a violation of respect for participants' autonomy. The present article examines these arguments, focusing specifically on confidential data monitoring for efficacy. This practice need not be deceptive provided its use is disclosed to prospective research participants. In addition, confidential data monitoring does not make research participants worse off than they would be in the clinical setting and represents an acceptable limitation on the options available to prospective research participants. Taken together, these considerations suggest confidential data monitoring, subject to adequate safeguards, is ethically acceptable. C1 [Miller, F. G.; Wendler, D.] NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 10 TC 6 Z9 6 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD MAR 1 PY 2008 VL 34 IS 3 BP 198 EP 201 DI 10.1136/jme.2006.019109 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 271GN UT WOS:000253777000016 PM 18316463 ER PT J AU Rudd, E Bryceson, YT Zheng, C Edner, J Wood, SM Ramme, K Gavhed, S Gurgey, A Hellebostad, M Bechensteen, AG Ljunggren, HG Fadeel, B Nordenskjold, M Henter, JI AF Rudd, E. Bryceson, Y. T. Zheng, C. Edner, J. Wood, S. M. Ramme, K. Gavhed, S. Gurgey, A. Hellebostad, M. Bechensteen, A. G. Ljunggren, H-G Fadeel, B. Nordenskjold, M. Henter, J-I TI Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MUNC13-4 MUTATIONS; GENETIC SUBTYPES; SYNTAXIN-11; EXPRESSION; IDENTIFICATION; LYMPHOCYTES; DISORDERS; DEFECTS; DISEASE; FHL AB Objective: Familial haemophagocytic lymphohistiocytosis (FHL) is a fatal disorder of immune dysregulation with defective cytotoxic lymphocyte function. Disease-causing mutations have been identified in the genes encoding perforin (PRF1), syntaxin-11 (STX11), and Munc13-4 (UNC13D). We screened for UNC13D mutations and studied clinical and functional implications of such mutations in a well defined patient cohort. Methods: Sequencing of UNC13D was performed in 38 FHL patients from 34 FHL families in which PRF1 and STX11 mutations had been excluded. Results: We identified six different mutations affecting altogether 9/38 individuals (24%) in 6/34 (18%) unrelated PRF1/STX11-negative families. Four novel mutations were revealed; two homozygous nonsense mutations (R83X and W382X), one splice mutation (exon 28), and one missense mutation (R928P). In addition, two known mutations were identified (R214X and a deletion resulting in a frame-shift starting at codon 782). There was considerable variation in the age at diagnosis, ranging from time of birth to 14 years ( median 69 days). Three of nine patients (33%) developed central nervous system (CNS) symptoms. Natural killer (NK) cell activity was impaired in all four patients studied. Defective cytotoxic lymphocyte degranulation was evident in the two patients investigated, more pronounced in the patient with onset during infancy than in the patient with adolescent onset. Conclusions: Biallelic UNC13D mutations were found in 18% of the PRF1/STX11-negative FHL families. Impairment of NK cell degranulation was less pronounced in a patient with adolescent onset. FHL should be considered not only in infants but also in adolescents, and possibly young adults, presenting with fever, splenomegaly, cytopenia, hyperferritinaemia, and/or CNS symptoms. C1 [Rudd, E.; Zheng, C.; Edner, J.; Ramme, K.; Gavhed, S.; Henter, J-I] Karolinska Univ Hosp, Karolinska Inst, Dept Women & Chil Hlth, Chilhood Canc Res Unit, Stockholm, Sweden. [Rudd, E.; Zheng, C.; Edner, J.; Ramme, K.; Gavhed, S.; Nordenskjold, M.] Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Clin Genet Unit, Stockholm, Sweden. [Bryceson, Y. T.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Bryceson, Y. T.; Wood, S. M.; Ljunggren, H-G] Karolinska Univ Hosp, Karolinska Inst, Ctr Infect Med, Dept Med, Stockholm, Sweden. [Gurgey, A.] Hacettepe Univ, Dept Pediat Hematol, Ankara, Turkey. [Hellebostad, M.] Natl Hosp Norway, Univ Hosp, Dept Pediat, Oslo, Norway. [Bechensteen, A. G.] Ullevaal Univ Hosp, Dept Pediat, Oslo, Norway. [Fadeel, B.] Karolinska Inst, Inst Environm Med, Div Biomed Toxicol, S-10401 Stockholm, Sweden. RP Rudd, E (reprint author), Karolinska Hosp, CMM L8 02, SE-17176 Stockholm, Sweden. EM Eva.Rudd@ki.se RI Wood, Stephanie/D-3528-2012; OI Wood, Stephanie/0000-0003-4224-759X; Nordenskjold, Magnus/0000-0002-4974-425X; Bryceson, Yenan/0000-0002-7783-9934 NR 30 TC 28 Z9 29 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAR PY 2008 VL 45 IS 3 BP 134 EP 141 DI 10.1136/jmg.2007.054288 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 271GL UT WOS:000253776800002 PM 17993578 ER PT J AU Worrillow, LJ Smith, AG Scott, K Andersson, M Ashcroft, AJ Dores, GM Glimelius, B Holowaty, E Jackson, GH Jones, GL Lynch, CF Morgan, G Pukkala, E Scott, D Storm, HH Taylor, PR Vyberg, M Willett, E Travis, LB Allan, JM AF Worrillow, L. J. Smith, A. G. Scott, K. Andersson, M. Ashcroft, A. J. Dores, G. M. Glimelius, B. Holowaty, E. Jackson, G. H. Jones, G. L. Lynch, C. F. Morgan, G. Pukkala, E. Scott, D. Storm, H. H. Taylor, P. R. Vyberg, M. Willett, E. Travis, L. B. Allan, J. M. TI Polymorphic MLH1 and risk of cancer after methylating chemotherapy for Hodgkin lymphoma SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MYELOID-LEUKEMIA; LUNG-CANCER; DISEASE; O-6-METHYLGUANINE; SUSCEPTIBILITY; RADIOTHERAPY; SURVIVORS; EXTRACTS; PROMOTER; HMLH1 AB Background and objective: Methylating agents are effective chemotherapy agents for Hodgkin lymphoma, but are associated with the development of second primary cancers. Cytotoxicity of methylating agents is mediated primarily by the DNA mismatch repair (MMR) system. Loss of MLH1, a major component of DNA MMR, results in tolerance to the cytotoxic effects of methylating agents and persistence of mutagenised cells at high risk of malignant transformation. We hypothesised that a common substitution in the basal promoter of MLH1 (position-93, rs1800734) modifies the risk of cancer after methylating chemotherapy. Methods: 133 patients who developed cancer following chemotherapy and/or radiotherapy (n = 133), 420 patients diagnosed with de novo myeloid leukaemia, 242 patients diagnosed with primary Hodgkin lymphoma, and 1177 healthy controls were genotyped for the MLH1 -93 polymorphism by allelic discrimination polymerase chain reaction (PCR) and restriction fragment length polymorphism assay. Odds ratios and 95% confidence intervals for cancer risk by MLH1 -93 polymorphism status, and stratified by previous exposure to methylating chemotherapy, were calculated using unconditional logistic regression. Results: Carrier frequency of the MLH1 -93 variant was higher in patients who developed therapy related acute myeloid leukaemia (t-AML) (75.0%, n = 12) or breast cancer (53.3%. n = 15) after methylating chemotherapy for Hodgkin lymphoma compared to patients without previous methylating exposure (t-AML, 30.4%, n = 69; breast cancer patients, 27.2%, n = 22). The MLH1 -93 variant allele was also over-represented in t-AML cases when compared to de novo AML cases (36.9%, n = 420) and healthy controls (36.3%, n = 952), and was associated with a significantly increased risk of developing t-AML (odds ratio 5.31, 95% confidence interval 1.40 to 20.15), but only in patients previously treated with a methylating agent. Conclusions: These data support the hypothesis that the common polymorphism at position - 93 in the core promoter of MLH1 defines a risk allele for the development of cancer after methylating chemotherapy for Hodgkin lymphoma. However, replication of this finding in larger studies is suggested. C1 [Allan, J. M.] Univ Newcastle Upon Tyne, Sch Med, N Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Worrillow, L. J.; Scott, K.] Univ York, Dept Biol, York YO10 5DD, N Yorkshire, England. [Smith, A. G.; Willett, E.] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Andersson, M.; Storm, H. H.] Danish Canc Soc, Copenhagen, Denmark. [Ashcroft, A. J.] Mid Yorkshire Hosp, Pinderfields Hosp, NHS Trust, Wakefield, England. [Dores, G. M.] Ctr Vet Med, Med Serv Dept, Oklahoma City, OK USA. [Dores, G. M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Glimelius, B.] Uppsala Univ, Uppsala, Sweden. [Holowaty, E.] Canc Care Ontario, Toronto, ON, Canada. [Jackson, G. H.; Jones, G. L.; Taylor, P. R.] Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Lynch, C. F.] Univ Iowa, Iowa City, IA USA. [Morgan, G.] Inst Canc Res, Dept Hematol Oncol, Sutton, Surrey, England. [Pukkala, E.] Finnish Canc Registry, FIN-00170 Helsinki, Finland. [Scott, D.] Harrogate & Dist NHS Fdn Trust, Dept Histopathol, Harrogate, England. [Vyberg, M.] Aalborg Hosp, Dept Pathol, DK-9000 Aalborg, Denmark. [Travis, L. B.] Natl Canc Inst, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Allan, JM (reprint author), Univ Newcastle Upon Tyne, Sch Med, N Inst Canc Res, Paul OGorman Bldg,Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM Allan@ncl.ac.uk RI Kane, Eleanor/B-4349-2009; Allan, James/B-4448-2009; Vyberg, Mogens/E-7576-2016 OI Vyberg, Mogens/0000-0002-6392-9517 FU Intramural NIH HHS [ZIA CP010131-18] NR 23 TC 20 Z9 20 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAR PY 2008 VL 45 IS 3 BP 142 EP 146 DI 10.1136/jmg.2007.053850 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 271GL UT WOS:000253776800003 PM 17959715 ER PT J AU Moscarelli, M Rupp, A AF Moscarelli, Massimo Rupp, Agnes TI Untitled SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Editorial Material C1 [Moscarelli, Massimo] Mental Hlth Policy & Econ, Int Ctr, Milan, Italy. [Rupp, Agnes] NIMH, Div Epidemiol & Serv Res, Ecol Programme, Rockville, MD 20857 USA. RP Moscarelli, M (reprint author), Mental Hlth Policy & Econ, Int Ctr, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2008 VL 11 IS 1 BP 1 EP 2 PG 2 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 277MY UT WOS:000254218200001 PM 18540131 ER PT J AU Cockrell, DC Beare, PA Fischer, ER Howe, D Heinzen, RA AF Cockrell, Diane C. Beare, Paul A. Fischer, Elizabeth R. Howe, Dale Heinzen, Robert. A. TI A method for purifying obligate intracellular Coxiella burnetii that employs digitonin lysis of host cells SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE digitonin; Coxiella; Q fever; cell lysis; purification; vacuole; infectivity; sonication; intracellular parasite ID PHASE-I; Q-FEVER; CHOLESTEROL; FIBROBLASTS; COMPONENTS; INFECTION AB Purification of the obligate intracellular bacterium Coxiella burnetii requires physical disruption of infected cells. Here we describe a gentle and safe digitonin lysis procedure to release C. burnetii from infected cells. The purity, yield, and infectivity of digitonin-prepped organisms are comparable to that of organisms purified using cell lysis by sonication. Published by Elsevier B.V. C1 [Cockrell, Diane C.; Beare, Paul A.; Howe, Dale; Heinzen, Robert. A.] Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Rocky Mt Labs, Intracellular Parasites Lab,Coxiella Pathogenesis, Hamilton, MT 59840 USA. [Fischer, Elizabeth R.] Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Rocky Mt Labs, Res Technol Branch,Microscopy Unit,Res Technol Br, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Rocky Mt Labs, Intracellular Parasites Lab,Coxiella Pathogenesis, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000931-05] NR 22 TC 25 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD MAR PY 2008 VL 72 IS 3 BP 321 EP 325 DI 10.1016/j.mimet.2007.12.015 PG 5 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 282SP UT WOS:000254587800015 PM 18242746 ER PT J AU Romano, CM Zanotto, PMDA Holmes, EC AF Romano, Camila M. Zanotto, Paolo M. de A. Holmes, Edward C. TI Bayesian coalescent analysis reveals a high rate of molecular evolution in GB virus C SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE GB virus C; molecular clock; substitution rate; codivergence; phylogeny; coalescent theory ID HEPATITIS-G VIRUS; C/HEPATITIS-G VIRUS; C/HGV INFECTION; PHYLOGENY; DIVERSITY; SEQUENCES; SUBSTITUTION; FLAVIVIRIDAE; ORIGIN; GENOME AB GB virus C/hepatitis G (GBV-C) is an RNA virus of the family Flaviviridae. Despite replicating with an RNA-dependent RNA polymerase, some previous estimates of rates of evolutionary change in GBV-C suggest that it fixes mutations at the anomalously low rate of similar to 100(-7) nucleotide substitution per site, per year. However, these estimates were largely based on the assumption that GBV-C and its close relative GBV-A (New World monkey GB viruses) codiverged with their primate hosts over millions of years. Herein, we estimated the substitution rate of GBV-C using the largest set of dated GBV-C isolates compiled to date and a Bayesian coalescent approach that utilizes the year of sampling and so is independent of the assumption of codivergence. This revealed a rate of evolutionary change approximately four orders of magnitude higher than that estimated previously, in the range of 10(-2) to 10(-3) sub/site/year, and hence in line with those previously determined for RNA viruses in general and the Flaviviridae in particular. In addition, we tested the assumption of host-virus codivergence in GBV-A by performing a reconciliation analysis of host and virus phylogenies. Strikingly, we found no statistical evidence for host-virus codivergence in GBV-A, indicating that substitution rates in the GB viruses should not be estimated from host divergence times. C1 [Romano, Camila M.; Holmes, Edward C.] Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Romano, Camila M.; Zanotto, Paolo M. de A.] Univ Sao Paulo, ICBII, Inst Biomed Sci, Dept Microbiol,Lab Mol Evolut & Bioinformat, Sao Paulo, Brazil. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM ech15@psu.edu RI Romano, Camila/C-8185-2013; OI Holmes, Edward/0000-0001-9596-3552 FU NIGMS NIH HHS [GM080533-01, R01 GM080533, R01 GM080533-02] NR 35 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD MAR PY 2008 VL 66 IS 3 BP 292 EP 297 DI 10.1007/s00239-008-9087-3 PG 6 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 297PW UT WOS:000255629600009 PM 18320258 ER PT J AU Roy, SW Irimia, M AF Roy, Scott William Irimia, Manuel TI Rare genomic characters do not support Coelomata: RGC_CAMs SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Letter ID AMINO-ACID REPLACEMENTS; INTRON CONSERVATION; CLADE; ECDYSOZOA; ANIMALS; NEMATODE; PATTERN AB Recently there has been a lively debate about a new class of rare genomic characters, RGC_CAMs, and their implications for deep bilaterian phylogeny. Most recently, nine bilaterian species were analyzed along with subsets of six outgroups (Rogozin et al. 2007b), and support for a coelomate clade reported. The authors suggested that our previously reported support for an ecdysozoan clade (Irimia et al. 2007) reflected (i) one outgroup, Nematostella vectensis, being too closely related to bilaterians and (ii) lack of "rigorous statistical analysis." Here, we report further studies of these characters. First, we discuss general issues of outgroup choice. Second, we point out that an argument used by Rogozin et al. against backmutation is not statistically significant. Third, we point out that the statistical method of Rogozin et al. fails to incorporate backmutations, leading to systematic placement of the long-branch taxon as the outgroup. A simple modification of the method yields very different results: 51 of 63 outgroup combinations favor Ecdysozoa, inlcuding 51 of 52 with at least eight phylogenetically informative characters, and all 19 with statistically significant signal. These results indicate that the Coelomata signal is a long-branch artifact. C1 [Roy, Scott William] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. [Irimia, Manuel] Univ Barcelona, Dept Genet, E-08028 Barcelona, Spain. RP Roy, SW (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. EM scottwroy@gmail.com RI Irimia, Manuel/E-3040-2010; OI Irimia, Manuel/0000-0002-2179-2567 NR 17 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD MAR PY 2008 VL 66 IS 3 BP 308 EP 315 DI 10.1007/s00239-008-9077-5 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 297PW UT WOS:000255629600011 PM 18320261 ER PT J AU Kourentzi, K Srinivasan, M Smith-Gill, SJ Willson, RC AF Kourentzi, Katerina Srinivasan, Mohan Smith-Gill, Sandra J. Willson, Richard C. TI Conformational flexibility and kinetic complexity in antibody-antigen interaction SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Article DE antibody-antigen interactions; fluorescence anisotropy; docking; dissociation kinetics ID EGG-WHITE LYSOZYME; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; CROSS-REACTIVITY; WATER-MOLECULES; PROTEIN ANTIGEN; BINDING-SITES; ASSOCIATION; HYHEL-5; FAB AB The kinetics of dissociation of three structurally characterized anti-hen egg white lysozyme antibodies (H8, H10, and H26), with hen egg white lysozyme (HEL) and the avian variant Japanese quail lysozyme (JQL) were examined. These antibodies share over 90% sequence identity and recognize the same epitope, but differ in their degree of cross-reactivity and predicted combining site rigidity. Competitive dissociation induced by the addition of excess unlabeled HEL after varied periods of antibody-antigen association was followed in real time using fluorescence anisotropy. Dissociation was in many cases non-single-exponential, and the observed off-rates became slower as the complex age increased, suggesting multi-step association kinetics consistent with an encounter-docking view of protein-protein interactions. The fully docked fraction of the complexes just prior to inducing dissociation was high for the HEL complexes but was dramatically reduced for JQL complexes, that is final docking was antigen-sensitive. Variations among the systems can be understood in terms of the complexes' differing conformational flexibilities, based on the encounter-docking model of protein-protein associations. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Kourentzi, Katerina; Srinivasan, Mohan; Willson, Richard C.] Univ Houston, Dept Chem & Biomol Engn, Houston, TX 77204 USA. [Willson, Richard C.] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA. [Smith-Gill, Sandra J.] NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Willson, RC (reprint author), Univ Houston, Dept Chem & Biomol Engn, 4800 Calhoun Rd, Houston, TX 77204 USA. EM willson@uh.edu NR 19 TC 9 Z9 9 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD MAR-APR PY 2008 VL 21 IS 2 BP 114 EP 121 DI 10.1002/jmr.874 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 290EJ UT WOS:000255105800005 PM 18383102 ER PT J AU Cragg, GM Powell, RG Singh, SB AF Cragg, Gordon M. Powell, Richard G. Singh, Shen B. TI Special issue in honor of professor George Robert Pettit SO JOURNAL OF NATURAL PRODUCTS LA English DT Biographical-Item C1 [Cragg, Gordon M.] NCI, Nat Prod Branch, Frederick, MD 21701 USA. [Powell, Richard G.] USDA, Natl Canc Agr Utilizat Res, Peoria, IL USA. [Singh, Shen B.] Merck Res Labs, Rahway, NJ USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Frederick, MD 21701 USA. NR 1 TC 1 Z9 1 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2008 VL 71 IS 3 BP 297 EP 299 DI 10.1021/np700714j PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 282CJ UT WOS:000254544900001 ER PT J AU Bai, R Vanderwal, CD Diaz, JF Hamel, E AF Bai, Ruoli Vanderwal, Christopher D. Diaz, J. Fernando Hamel, Ernest TI Interaction of a cyclostreptin analogue with the microtubule taxoid site: The covalent reaction rapidly follows binding SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ANTIMITOTIC SUBSTANCE; FR182877; INHIBITOR; PROTEINS; AFFINITY; TUBULIN; POTENT AB The natural product cyclostreptin reacts covalently and stoichiometrically with microtubules, at either of two amino acid residues of beta-tubulin, Thr-218 or Asn-226, but much less extensively and only at Thr-218 in unpolymerized tubulin. It was found that 8-acetylcyclostreptin (8AcCS) induces tubulin assembly in a manner almost identical with that of cyclostreptin. We therefore synthesized [C-14-acetyl]8AcCS and studied the kinetics of its interaction with glutaraldehyde-stabilized microtubules and with unassembled tubulin. With the microtubules, we found that 8AcCS bound rapidly, with a minimal (unmeasurable with the radiolabeled analogue) lag prior to the occurrence of the covalent reaction. Apparent reaction rate constants for the overall reaction ranged from 6.2 x 10(2) M-1 s(-1) at 0 degrees C to 5.6 x 10(3) M-1 s(-1) at 20 degrees C. The rate constants obtained at 0 and 10 degrees C indicate an activation energy for the reaction of about 27 kcal/mol, while those obtained at 10 and 20 degrees C indicate an activation energy of about 7.7 kcal/mol. With the unpolymerized tubulin, we did find a minimal covalent reaction occurred without apparent microtubule assembly, but a substantial reaction only occurred following assembly. In conclusion, the radiolabeled 8AcCS shows that an extensive covalent interaction of ligand with tubulin requires microtubule assembly and that the covalent reaction occurs rapidly after the initial binding interaction. C1 [Bai, Ruoli; Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Vanderwal, Christopher D.] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA. [Diaz, J. Fernando] CSIC, Ctr Invest Biol, Madrid 28040, Spain. RP Hamel, E (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. EM hamele@mail.nih.gov OI Diaz, J. Fernando/0000-0003-2743-3319 NR 16 TC 10 Z9 10 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 EI 1520-6025 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2008 VL 71 IS 3 BP 370 EP 374 DI 10.1021/np800056m PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 282CJ UT WOS:000254544900014 PM 18298077 ER PT J AU Pettit, GR Hogan, F Xu, JP Tan, R Nogawa, T Cichacz, Z Pettit, RK Du, J Ye, QH Cragg, GM Herald, CL Hoard, MS Goswami, A Searcy, J Tackett, L Doubek, DL Williams, L Hooper, JNA Schmidt, JM Chapuis, JC Tackett, DN Craciunescu, F AF Pettit, George R. Hogan, Fiona Xu, Jun-Ping Tan, Rui Nogawa, Toshihiko Cichacz, Zbigniew Pettit, Robin K. Du, Jiang Ye, Qing-Hua Cragg, Gordon M. Herald, Cherry L. Hoard, Michael S. Goswami, Animesh Searcy, Justin Tackett, Larry Doubek, Dennis L. Williams, Lee Hooper, John N. A. Schmidt, Jean M. Chapuis, Jean-Charles Tackett, Denise N. Craciunescu, Felicia TI Antineoplastic agents. 536. New sources of naturally occurring cancer cell growth inhibitors from marine organisms, terrestrial plants, and microorganisms SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID MANZAMINE-A; ALPHA-GALACTOSYLCERAMIDES; ABSOLUTE-CONFIGURATION; STRUCTURE ELUCIDATION; ARYLTETRALIN LIGNANS; MYCOPHENOLIC-ACID; LYNGBYA-MAJUSCULA; JASPIS-JOHNSTONI; PROSTATE-CANCER; BREFELDIN-A AB Bioassay-guided fractionation of extracts of various plants, marine organisms, and microorganisms has led to the discovery of new natural sources of a number of known compounds that have significant biological activity. The isolation of interesting and valuable cancer cell growth inhibitors including majusculamide C (1), axinastatin 5 (5), bergazoles A (6), B (7), and E (8), manzamine A (10), jaspamide (11), and neoechinulin A (19) has been summarized. C1 [Pettit, George R.; Hogan, Fiona; Xu, Jun-Ping; Tan, Rui; Nogawa, Toshihiko; Cichacz, Zbigniew; Pettit, Robin K.; Du, Jiang; Ye, Qing-Hua; Herald, Cherry L.; Hoard, Michael S.; Goswami, Animesh; Searcy, Justin; Tackett, Larry; Doubek, Dennis L.; Williams, Lee; Schmidt, Jean M.; Chapuis, Jean-Charles; Tackett, Denise N.; Craciunescu, Felicia] Arizona State Univ, Canc Res Inst, Dept Chem & Biochem, Tempe, AZ 85287 USA. [Cragg, Gordon M.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. [Hooper, John N. A.] Queensland Museum, Brisbane, Qld 4101, Australia. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, Dept Chem & Biochem, POB 872404, Tempe, AZ 85287 USA. EM bpettit@asu.edu OI Hooper, John/0000-0003-1722-5954 FU NCI NIH HHS [2R56 CA090441-06A1, CA44344-01-12, CA90441-01-05] NR 87 TC 22 Z9 24 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2008 VL 71 IS 3 BP 438 EP 444 DI 10.1021/np700738k PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 282CJ UT WOS:000254544900025 PM 18327911 ER PT J AU Leet, JE Liu, X Drexler, DM Cantone, JL Huang, S Mamber, SW Fairchild, CR Hussain, R Newman, DJ Kingston, DGI AF Leet, John E. Liu, Xiaohong Drexler, Dieter M. Cantone, Joseph L. Huang, Stella Mamber, Stephen W. Fairchild, Craig R. Hussain, Raouf Newman, David J. Kingston, David G. I. TI Cytotoxic xanthones from Psorospermum molluscum from the Madagascar rain forest SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID SITE-DIRECTED ALKYLATION; ESCHERICHIA-COLI K-12; SOS CHROMOTEST; DNA; STEREOCHEMISTRY; FEBRIFUGUM; ASSAY AB Two new cytotoxic xanthones were isolated from extracts of the Madagascar rain forest plant Psorospermunt cf. molluscum using bioassay-guided fractionation with the Escherichia coli SOS chromotest. The structures of the new dihydrofuran-oxanthones, designated 3',4'-deoxy-4'-chloropsoroxanthin-(3',5'-diol) (1) and psoroxanthin (4), were determined on the basis of 2D-NMR, MS, and UV spectroscopic data and are structurally related to the psorospermins, a known class of plant antitumor agents. A new hydroxyprenylated xanthone (5) is also described. Xanthones 1 and 4 showed selective in vitro cytotoxicity against ABAE cells (bovine endothelial cell line). C1 [Leet, John E.; Liu, Xiaohong; Drexler, Dieter M.; Cantone, Joseph L.; Huang, Stella; Mamber, Stephen W.; Hussain, Raouf] Bristol Myers Squibb Co, Res & Dev, Wallingford, CT 06492 USA. [Newman, David J.] NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Nat Prod Branch, Bethesda, MD 20892 USA. [Kingston, David G. I.] Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. [Fairchild, Craig R.] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Leet, JE (reprint author), Bristol Myers Squibb Co, Res & Dev, 5 Res Pkwy, Wallingford, CT 06492 USA. EM leetj@bms.com OI Kingston, David/0000-0001-8944-246X FU FIC NIH HHS [U01 TW000313, TW 00313, U01 TW000313-07, U01 TW000313-08, U01 TW000313-09, U01 TW000313-10] NR 18 TC 10 Z9 12 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2008 VL 71 IS 3 BP 460 EP 463 DI 10.1021/np0705231 PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 282CJ UT WOS:000254544900031 PM 18247570 ER PT J AU Plaza, A Baker, HL Bewley, CA AF Plaza, Alberto Baker, Heather L. Bewley, Carole A. TI Mirabilin, an antitumor macrolide lactam from the marine sponge Siliqualiaspongia mirabilis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CYTOTOXIC DIMERIC MACROLIDE; THEONELLA-SWINHOEI; NEOSIPHONIA-SUPERSTES; NATURAL-PRODUCTS; ABSOLUTE STEREOSTRUCTURE; NMR; CONFIGURATION; CHONDROPSINS; ASSIGNMENT AB A new highly unsaturated macrolide lactam, termed mirabilin (1), was isolated from the aqueous extract of the marine sponge Siliquariaspongia mirabilis. Mirabilin is characterized by the presence of a 35-membered macrolide lactam ring bearing a pentadiene conjugated system and a tetrasubstituted tetrahydropyran ring. A linear polyketide moiety is attached to the macrocyclic ring through an amide linkage. The structure of mirabilin was determined using extensive 2D NMR and ESIMS and tandem MS techniques. Mirabilin inhibits the growth of the tumor cell line HCT-116 with an IC(50) value of 0.27 +/- 0.09 mu M and is noncytotoxic to several other cell lines. C1 [Plaza, Alberto; Baker, Heather L.; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU Intramural NIH HHS NR 27 TC 17 Z9 17 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2008 VL 71 IS 3 BP 473 EP 477 DI 10.1021/np070603p PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 282CJ UT WOS:000254544900034 PM 18271553 ER PT J AU Bai, O Lin, P Vorbach, S Floeter, MK Hattori, N Hallett, M AF Bai, Ou Lin, Peter Vorbach, Sherry Floeter, Mary Kay Hattori, Noriaki Hallett, Mark TI A high performance sensorimotor beta rhythm-based brain-computer interface associated with human natural motor behavior SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID EVENT-RELATED DESYNCHRONIZATION; AMYOTROPHIC-LATERAL-SCLEROSIS; SLOW CORTICAL POTENTIALS; PARALYZED PATIENTS; FINGER MOVEMENTS; EEG; COMMUNICATION; SIGNALS; IMAGERY; CORTEX AB To explore the reliability of a high performance brain-computer interface (130) using non-invasive EEG signals associated with human natural motor behavior does not require extensive training. We propose a new BCI method, where users perform either sustaining or stopping a motor task with time locking to a predefined time window. Nine healthy volunteers, one stroke survivor with right-sided hemiparesis and one patient with amyotrophic lateral sclerosis (ALS) participated in this study. Subjects did not receive BCI training before participating in this study. We investigated tasks of both physical movement and motor imagery. The surface Laplacian derivation was used for enhancing EEG spatial resolution. A model-free threshold setting method was used for the classification of motor intentions. The performance of the proposed BCI was validated by an online sequential binary-cursor-control game for two-dimensional cursor movement. Event-related desynchronization and synchronization were observed when subjects sustained or stopped either motor execution or motor imagery. Feature analysis showed that EEG beta band activity over sensorimotor area provided the largest discrimination. With simple model-free classification of beta band EEG activity from a single electrode (with surface Laplacian derivation), the online classifications of the EEG activity with motor execution/motor imagery were: >90%/similar to 80% for six healthy volunteers, >80%/similar to 80% for the stroke patient and -90%/similar to 80% for the ALS patient. The EEG activities of the other three healthy volunteers were not classifiable. The sensorimotor beta rhythm of EEG associated with human natural motor behavior can be used for a reliable and high performance BCI for both healthy subjects and patients with neurological disorders. Significance: The proposed new non-invasive BCI method highlights a practical 130 for clinical applications, where the user does not require extensive training. C1 [Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, Richmond, VA 23284 USA. [Bai, Ou; Lin, Peter; Vorbach, Sherry; Hattori, Noriaki; Hallett, Mark] Natl Inst Neurol Disorders, NIH, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA. [Floeter, Mary Kay] Natl Inst Neurol Disorders, NIH, Electromyo Sect, Bethesda, MD 20892 USA. RP Bai, O (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, 701 W Grace St,Room 2405, Richmond, VA 23284 USA. EM obai@vcu.edu FU Intramural NIH HHS NR 48 TC 69 Z9 70 U1 2 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD MAR PY 2008 VL 5 IS 1 BP 24 EP 35 DI 10.1088/1741-2560/5/1/003 PG 12 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 290FJ UT WOS:000255108400006 PM 18310808 ER PT J AU Csordas, G Renken, C Varnai, P Walter, L Weaver, D Buttle, KF Balla, T Mannella, CA Hajnoczky, G AF Csordas, G. Renken, C. Varnai, P. Walter, L. Weaver, D. Buttle, K. F. Balla, T. Mannella, C. A. Hajnoczky, G. TI Structural and functional features and significance of the physical linkage between ER and mitochondria SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Csordas, G.; Walter, L.; Weaver, D.; Hajnoczky, G.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Renken, C.; Weaver, D.; Buttle, K. F.; Mannella, C. A.] Wadsworth Ctr, Resourse Visualizat Biol Complexity, Albany, NY USA. [Varnai, P.; Balla, T.] NICHHD, NIH, Endocrinol & Reprod Res Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 6 EP 6 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800012 ER PT J AU Golovko, MY Nussbaum, RL Ellis, CE Mitchell, DC Scaglia, F Barcelo-Coblijn, GC Murphy, EJ AF Golovko, M. Y. Nussbaum, R. L. Ellis, C. E. Mitchell, D. C. Scaglia, F. Barcelo-Coblijn, G. C. Murphy, E. J. TI Alpha-synuclein modulates mitochondrial membrane properties and functions SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Golovko, M. Y.; Barcelo-Coblijn, G. C.; Murphy, E. J.] Univ N Dakota, Dept Pharm Phys & Therapy, Grand Forks, ND 58201 USA. [Nussbaum, R. L.; Ellis, C. E.] NHGRI, NIH, Bethesda, MD USA. [Mitchell, D. C.] NIAAA, NIH, Bethesda, MD USA. [Scaglia, F.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 6 EP 7 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800013 ER PT J AU Bosetti, F Aid, S Choi, SH AF Bosetti, F. Aid, S. Choi, S. H. TI Differential roles of cyclooxygenase-1 and-2 in lipopolysaccharide-induced neuroinflammation SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Bosetti, F.; Aid, S.; Choi, S. H.] Natl Inst Hlth, NIA, Brain Physiol Sect, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 13 EP 13 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800029 ER PT J AU Marini, AM Jiang, X Tian, F Du, D Egan, S Kenney, H Lipsky, RH AF Marini, A. M. Jiang, X. Tian, F. Du, D. Egan, S. Kenney, H. Lipsky, R. H. TI Activity-dependent BDNF transcription involves relief of BHLHB2-mediated repression SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Jiang, X.; Tian, F.; Kenney, H.; Lipsky, R. H.] NIH, NIAAA, Rockville, MD USA. [Marini, A. M.; Du, D.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Egan, S.] Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 32 EP 33 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800079 ER PT J AU Aschrafi, A Schwechter, A Natera, O Gioio, A Kaplan, BB AF Aschrafi, A. Schwechter, A. Natera, O. Gioio, A. Kaplan, B. B. TI Brain-specific microrna-338 regulates oxidative phosphorylation in the axons of sympathetic neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Aschrafi, A.; Schwechter, A.; Natera, O.; Gioio, A.; Kaplan, B. B.] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RI Aschrafi, Armaz/E-2202-2012 NR 0 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 34 EP 34 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800083 ER PT J AU Yamada, M Mishina, Y Araya, R AF Yamada, M. Mishina, Y. Araya, R. TI BMP signaling is involved in the control of growth and differentiation of glial cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Yamada, M.; Araya, R.] RIKEN, Brain Sci Inst, Wako, Saitama, Japan. [Mishina, Y.] NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 54 EP 54 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800134 ER PT J AU Mattson, MP Cutler, RG Norman, ED AF Mattson, M. P. Cutler, R. G. Norman, E. D. TI Sphingomyelin and ceramide metabolism in neuronal plasticity and aging SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Mattson, M. P.; Cutler, R. G.; Norman, E. D.] NIA, Baltimore, MD USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 61 EP 61 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800149 ER PT J AU Rosi, S Ferguson, RA Fishman, K Andres-Mach, M Tweedie, D Greig, N Fike, JR AF Rosi, S. Ferguson, R. A. Fishman, K. Andres-Mach, M. Tweedie, D. Greig, N. Fike, J. R. TI Neuroinflammation and pharmacological approaches to restore neuronal-microglia communication SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Rosi, S.; Ferguson, R. A.; Fishman, K.; Andres-Mach, M.; Fike, J. R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tweedie, D.; Greig, N.] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 65 EP 66 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800159 ER PT J AU Harry, GJ Wine, RN McPherson, CA Aoyama, M AF Harry, G. J. Wine, R. N. McPherson, C. A. Aoyama, M. TI Injury-induced neurogenesis: Can microglia offer support to new neurons in the subgranular zone SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Harry, G. J.; Wine, R. N.; McPherson, C. A.; Aoyama, M.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Aoyama, M.] Nagoya City Univ, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 66 EP 66 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800160 ER PT J AU Quarles, RH AF Quarles, R. H. TI Milestones in the myelin-associated glycoprotein journey SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Quarles, R. H.] NIH, NINDS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 90 EP 90 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800214 ER PT J AU Cookson, MR AF Cookson, M. R. TI How mutations in LRRK2 affect kinase activity, and why it matters SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Cookson, M. R.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 91 EP 91 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800215 ER PT J AU Loulier, K Lathia, JD Rao, MS Mattson, MP Ffrench Constant, C Haydar, TF AF Loulier, K. Lathia, J. D. Rao, M. S. Mattson, M. P. Ffrench Constant, C. Haydar, T. F. TI Beta 1 integrin signaling is necessary for anchorage of neural progenitors at the murine ventricular surface SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Loulier, K.; Haydar, T. F.] Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC USA. [Lathia, J. D.; Ffrench Constant, C.] Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 1TN, England. [Lathia, J. D.; Rao, M. S.; Mattson, M. P.] NIA, Baltimore, MD USA. RI Mattson, Mark/F-6038-2012; Loulier, Karine/E-5529-2017 OI Loulier, Karine/0000-0001-6216-2708 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 98 EP 99 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800231 ER PT J AU Jablonska, B Aguirre, A Vandenbosch, R Belachew, S Berthet, C Kaidis, P Gallo, V AF Jablonska, B. Aguirre, A. Vandenbosch, R. Belachew, S. Berthet, C. Kaidis, P. Gallo, V TI Cyclin-dependent kinase 2 is critical for proliferation and self-renewal of neural progenitors in the adult subventricular zone SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Jablonska, B.; Aguirre, A.; Gallo, V] CNMC, Ctr Res Neurosci, Washington, DC USA. [Vandenbosch, R.; Belachew, S.] Univ Liege, B-4000 Liege, Belgium. [Berthet, C.; Kaidis, P.] Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 99 EP 99 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800232 ER PT J AU Marini, AM Jiang, X Tian, F Du, D Egan, S Kenney, H Lipsky, RH AF Marini, A. M. Jiang, X. Tian, F. Du, D. Egan, S. Kenney, H. Lipsky, R. H. TI Identification of a novel mechanism regulating brain BDNF levels: BHLHB2 controls promoter 4 activity and neuronal excitability SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Jiang, X.; Tian, F.; Kenney, H.; Lipsky, R. H.] NIAAA, NIH, Rockville, MD 20852 USA. [Marini, A. M.; Du, D.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Egan, S.] Univ Toronto, Toronto, ON, Canada. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 129 EP 129 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800316 ER PT J AU Kapadia, RS Tureyen, K Bowen, KK Yan, Y Johnson, PF Vemuganti, R AF Kapadia, R. S. Tureyen, K. Bowen, K. K. Yan, Y. Johnson, P. F. Vemuganti, R. TI Role of C/EBP beta in mediating post-ischemic inflammation and neurogenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 39th Annual Meeting of the American-Society-for-Neurochemistry CY MAR 01-05, 2008 CL San Antonio, TX SP Amer Soc Neurochem C1 [Kapadia, R. S.; Vemuganti, R.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [Kapadia, R. S.; Tureyen, K.; Bowen, K. K.; Yan, Y.; Vemuganti, R.] Univ Wisconsin, Dept Neurol Surg, Madison, WI 53706 USA. [Johnson, P. F.] NCI, Frederick, MD USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 SU 1 BP 133 EP 134 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 257RI UT WOS:000252815800326 ER PT J AU Calderon, F Kim, HY AF Calderon, Frances Kim, Hee-Yong TI Detection of intracellular phosphatidylserine in living cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AnnexinV; green fluorescence protein; hippocampal; neuroblastoma; neuronal cells; phosphatidylserine; recycling endosome ID PROTEIN-KINASE-C; DOCOSAHEXAENOIC ACID; ANNEXIN-V; HIPPOCAMPAL-NEURONS; RAT-LIVER; MEMBRANES; ASYMMETRY; BINDING; APOPTOSIS; CALCIUM AB To demonstrate the intracellular phosphatidylserine (PS) distribution in neuronal cells, neuroblastoma cells and hippocampal neurons expressing green fluorescence protein (GFP)-AnnexinV were stimulated with a calcium ionophore and localization of GFP-AnnexinV was monitored by fluorescence microscopy. Initially, GFP-AnnexinV distributed evenly in the cytosol and nucleus. Raising the intracellular calcium level with ionomycin-induced translocation of cytoplasmic GFP-AnnexinV to the plasma membrane but not to the nuclear membrane, indicating that PS distributes in the cytoplasmic side of the plasma membrane. Nuclear GFP-AnnexinV subsequently translocated to the nuclear membrane, indicating PS localization in the nuclear envelope. GFP-AnnexinV also localized in a juxtanuclear organelle that was identified as the recycling endosome. However, minimal fluorescence was detected in any other subcellular organelles including mitochondria, endoplasmic reticulum, Golgi complex, and lysosomes, strongly suggesting that PS distribution in the cytoplasmic face in these organelles is negligible. Similarly, in hippocampal primary neurons PS distributed in the inner leaflet of plasma membranes of cell body and dendrites, and in the nuclear envelope. To our knowledge, this is the first demonstration of intracellular PS localization in living cells, providing an insight for specific sites of PS interaction with soluble proteins involved in signaling processes. C1 [Calderon, Frances; Kim, Hee-Yong] NIAAA, Mol Signalling Lab, NIH, Bethesda, MD 20892 USA. RP Kim, HY (reprint author), NIAAA, Mol Signalling Lab, NIH, 5625 Fishers Lane,3N-07, Bethesda, MD 20892 USA. EM hykim@mail.nih.gov FU Intramural NIH HHS NR 35 TC 11 Z9 12 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 IS 5 BP 1271 EP 1279 DI 10.1111/j.1471-4159.2007.05079.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 264AI UT WOS:000253257200011 PM 18028336 ER PT J AU Pivovarova, NB Stanika, RI Watts, CA Brantner, CA Smith, CL Andrews, SB AF Pivovarova, Natalia B. Stanika, Ruslan I. Watts, Charlotte A. Brantner, Christine A. Smith, Carolyn L. Andrews, S. Brian TI Reduced calcium-dependent mitochondrial damage underlies the reduced vulnerability of excitotoxicity-tolerant hippocampal neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calcium signaling; ischemia; ischemic preconditioning; neurodegeneration; neuroprotection; NMDA ID OXYGEN-GLUCOSE DEPRIVATION; CEREBELLAR GRANULE CELLS; CYTOCHROME-C RELEASE; METHYL-D-ASPARTATE; PERMEABILITY TRANSITION; BRAIN MITOCHONDRIA; GLUTAMATE EXCITOTOXICITY; CULTURED NEURONS; CASPASE-3 ACTIVATION; SURFACE EXPRESSION AB In central neurons, over-stimulation of NMDA receptors leads to excessive mitochondrial calcium accumulation and damage, which is a critical step in excitotoxic death. This raises the possibility that low susceptibility to calcium overload-induced mitochondrial damage might characterize excitotoxicity-resistant neurons. In this study, we have exploited two complementary models of preconditioning-induced excitotoxicity resistance to demonstrate reduced calcium-dependent mitochondrial damage in NMDA-tolerant hippocampal neurons. We have further identified adaptations in mitochondrial calcium handling that account for enhanced mitochondrial integrity. In both models, enhanced tolerance was associated with improved preservation of mitochondrial membrane potential and structure. In the first model, which exhibited modest neuroprotection, mitochondria-dependent calcium deregulation was delayed, even though cytosolic and mitochondrial calcium loads were quantitatively unchanged, indicating that enhanced mitochondrial calcium capacity accounts for reduced injury. In contrast, the second model, which exhibited strong neuroprotection, displayed further delayed calcium deregulation and reduced mitochondrial damage because downregulation of NMDA receptor surface expression depressed calcium loading. Reducing calcium entry also modified the chemical composition of the calcium-buffering precipitates that form in calcium-loaded mitochondria. It thus appears that reduced mitochondrial calcium loading is a major factor underlying the robust neuroprotection seen in highly tolerant cells. C1 [Pivovarova, Natalia B.; Stanika, Ruslan I.; Watts, Charlotte A.; Brantner, Christine A.; Andrews, S. Brian] NIH, Natl Inst Neurolog Disorders & Stroke, Lab Neurobiol, Bethesda, MD 20892 USA. [Smith, Carolyn L.] NIH, Natl Inst Neurolog Disorders & Stroke, Light Imaging Facil, Bethesda, MD 20892 USA. RP Andrews, SB (reprint author), NIH, Natl Inst Neurolog Disorders & Stroke, Lab Neurobiol, 49-3A62,49 Convent Dr, Bethesda, MD 20892 USA. EM sba@helix.nih.gov OI Brantner, Christine/0000-0001-8172-901X FU Intramural NIH HHS NR 55 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2008 VL 104 IS 6 BP 1686 EP 1699 DI 10.1111/j.1471-4159.2007.05080.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 269DC UT WOS:000253628700022 PM 18036152 ER PT J AU Kawamoto, EM Lepsch, LB Boaventura, MFC Munhoz, CD Lima, LS Yshii, LM Avellar, MCW Curi, R Mattson, MP Scavone, C AF Kawamoto, E. M. Lepsch, L. B. Boaventura, M. F. C. Munhoz, C. D. Lima, L. S. Yshii, L. M. Avellar, M. C. W. Curi, R. Mattson, M. P. Scavone, C. TI Amyloid beta-peptide activates nuclear factor-kappa B through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE amyloid-beta; NMDA; cultured cerebellar cells; NF-kappa B ID ALZHEIMERS-DISEASE; NITRIC-OXIDE; HIPPOCAMPAL-NEURONS; NEURODEGENERATIVE DISORDERS; TRANSCRIPTION FACTOR; CORTICAL-NEURONS; OXIDATIVE STRESS; SYNAPTIC PLASTICITY; INDUCED APOPTOSIS; STRIATAL NEURONS AB Amyloid P-peptide (A beta) likely causes functional alterations in neurons well prior to their death. Nuclear factor-kappa B (NF-kappa B), a transcription factor that is known to play important roles in cell survival and apoptosis, has been shown to be modulated by A beta in neurons and glia, but the mechanism is unknown. Because A beta has also been shown to enhance activation of N-methyl-D-aspartate (NMDA) receptors, we investigated the role of NMDA receptor-mediated intracellular signaling pathways in A beta-induced NF-kappa B activation in primary cultured rat cerebellar cells. Cells were treated with different concentrations of A beta 1-40 (1 or 2 mu M) for different periods (6, 12, or 24 hr). MK-801 (NMDA antagonist), manumycin A and FTase inhibitor 1 (farnesyltransferase inhibitors), PP1 (Src-family tyrosine kinase inhibitor), PD98059 [mitogen-activated protein kinase (MAPK) inhibitor], and LY294002 [phosphatidylinositol 3-kinase (PI3-k) inhibitor] were added 20 min before A beta treatment of the cells. A beta induced a time- and concentration-dependent activation of NF-kappa B (1 mu M, 12 hr); both p50/p65 and p50/p50 NF-kappa B dimers were involved. This activation was abolished by MK-801 and attenuated by manumycin A, FTase inhibitor 1, PP1, PD98059, and LY294002. AP at 1 mu M increased the expression of inhibitory protein I kappa B, brain-derived neurotrophic factor, inducible nitric oxide synthase, tumor necrosis factor-alpha, and interleukin-1 beta as shown by RTPCR assays. Collectively, these findings suggest that AP activates NF-kappa B by an NMDA-Src-Ras-like protein through MAPK and PI3-k pathways in cultured cerebellar cells. This pathway may mediate an adaptive, neuroprotective response to A beta. (c) 2007 Wiley-Liss, Inc. C1 [Kawamoto, E. M.; Lepsch, L. B.; Munhoz, C. D.; Lima, L. S.; Yshii, L. M.; Scavone, C.] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508 Sao Paulo, Brazil. [Boaventura, M. F. C.; Curi, R.] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, Brazil. [Avellar, M. C. W.] Univ Fed Sao Paulo, Dept Pharmacol, Sect Expt Endocrinol, Sao Paulo, Brazil. [Mattson, M. P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Scavone, C (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Avenida Lineu Prestes 1524, BR-05508 Sao Paulo, Brazil. EM criscavone@usp.br RI Kawamoto, Elisa/E-3485-2012; Mattson, Mark/F-6038-2012; Munhoz, Carolina/I-2118-2012; Avellar, Maria Christina W./E-2865-2013; Munhoz, Carolina/N-7219-2014; Cury-Boaventura, Maria Fernanda/B-3945-2012; Curi , Rui/C-9351-2012; YSHII, Lidia/I-6039-2013; OI Kawamoto, Elisa/0000-0001-8637-414X; Avellar, Maria Christina W./0000-0003-4392-7554; Munhoz, Carolina/0000-0002-8656-5234; YSHII, Lidia/0000-0002-1988-6855; Scavone, Cristoforo/0000-0002-1206-0882 FU Intramural NIH HHS NR 62 TC 19 Z9 21 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR PY 2008 VL 86 IS 4 BP 845 EP 860 DI 10.1002/jnr.21548 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 273WC UT WOS:000253961700011 PM 17969100 ER PT J AU Takashima, K Ito, Y Gonzalez, FJ Nakajima, T AF Takashima, Kayoko Ito, Yuki Gonzalez, Frank J. Nakajima, Tamie TI Different mechanisms of DEHP-induced hepatocellular adenoma tumorigenesis in wild-type and Ppar alpha-null mice SO JOURNAL OF OCCUPATIONAL HEALTH LA English DT Article DE di (2-ethylhexyl) phthalate; peroxisome proliferator-activated receptor alpha; tumorigenesis; apoptotic peptidase activating factor 1; DNA-damage-inducible 45 alpha ID ACTIVATED-RECEPTOR-ALPHA; CELL-CYCLE CONTROL; NONGENOTOXIC HEPATOCARCINOGEN; PEROXISOME PROLIFERATORS; RETINOBLASTOMA PROTEIN; CLOFIBRIC ACID; BCL-2 FAMILY; MOUSE-LIVER; APOPTOSIS; PATHWAY AB Di (2-ethylhexyl) phthalate (DEHP) exposure is thought to lead to hepatocellular hypertrophy and hyperplasia in rodents mediated via peroxisome proliferator-activated receptor alpha (PPAR(x). A recent study revealed that long-term exposure to relatively low-dose DEHP (0.05%) caused liver tumors including hepatocellular carcinomas, hepatocellular adenomas, and chologiocellular carcinomas at a higher incidence in Ppar alpha-null mice (25.8%) than in wild-type mice (10.0%). Using tissues with hepatocellular adenoma, microarray (Affymetrix MOE430A) as well as, in part, real-time quantitative PCR analysis was conducted to elucidate the mechanisms of the adenoma formation resulting from DEHP exposure in both genotyped mice. The microarray profiles showed that the up- or down-regulated genes were quite different between hepatocellular adenoma tissues of wild-type and Ppar alpha-null mice exposed to DEHR The gene expressions of apoptotic peptidase activating factor 1 (Apaf1) and DNA-damage-inducible 45 alpha (Gadd45a) were increased in the hepatocellular adenoma tissues of wild-type mice exposed to DEHP, whereas they were unchanged in corresponding tissues of Ppara-null mice. On the other hand, the expressions of cyclin B2 and myeloid cell leukemia sequence 1 were increased only in the hepatocellular adenoma tissues of Ppara-null mice. Taken together, DEHP may induce hepatocellular adenomas, in part, via suppression of G2/M arrest regulated by Gadd45a and caspase 3-dependent apoptosis in Ppara-null mice, but these genes may not be involved in tumorigenesis in the wild-type mice. In contrast, the expression level of Met was notably increased in the liver adenoma tissue of wild-type mice, which may suggest the involvement of Met in DEHP-induced tumorigenesis in wild-type mice. C1 [Ito, Yuki; Nakajima, Tamie] Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, Nagoya, Aichi 4668550, Japan. [Takashima, Kayoko] Shinshu Univ, Grad Sch Med, Dept Prevent Med, Nagano, Japan. [Takashima, Kayoko] Shinshu Univ, Grad Sch Med, Inst Organ Transplants Reconstruct Med & Tissue E, Nagano, Japan. [Gonzalez, Frank J.] Natl Canc Inst, Natl Inst Hlth, Lab Metab, Bethesda, MD USA. RP Nakajima, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. EM tnasu23@med.nagoya-u.ac.jp RI Ito, Yuki/C-3698-2008 NR 38 TC 38 Z9 44 U1 0 U2 2 PU JAPAN SOC OCCUPATIONAL HEALTH PI TOKYO PA 1-29-8 SHINJUKU, SHINJUKU-KU, TOKYO, 160, JAPAN SN 1341-9145 J9 J OCCUP HEALTH JI J. Occup. Health PD MAR PY 2008 VL 50 IS 2 BP 169 EP 180 DI 10.1539/joh.L7105 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286ZC UT WOS:000254884500010 PM 18403868 ER PT J AU Chou, WYS Stokes, SC Citko, J Davies, B AF Chou, Wen-Ying Sylvia Stokes, Sandy Chen Citko, Judy Davies, Betty TI Improving end-of-life care through community-based grassroots collaboration: Development of the Chinese-American coalition for compassionate care SO JOURNAL OF PALLIATIVE CARE LA English DT Article ID PARTICIPATORY RESEARCH AB As a volunteer-formed, community-based organization devoted to improving the quality of end-of-life care for Chinese Americans, the new Chinese-American Coalition for Compassionate Care (CACCC) is a unique and promising venture. This article has several aims: 1) to describe the history and development of the recently founded CACCC; 2) to introduce and critically evaluate one of CACCC's first public programs, a volunteer and caregiver training on end-of-life care, which prompted subsequent programs and activities; 3) to report on CACCC's current projects and short- and long-term goals; and 4) to discuss the implications for other similar community-based organizations devoted to the health and quality of life of a targeted population. C1 [Chou, Wen-Ying Sylvia] NCI, Natl Inst Hlth, Off Prevent Oncol, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Stokes, Sandy Chen] El Dorado Cty Publ Hlth Dept, Placerville, CA USA. [Citko, Judy] Calif Coalit Compassionate Care, Sacramento, CA USA. [Davies, Betty] Univ Calif San Francisco, Dept Family Hlth Care Nursing, San Francisco, CA 94143 USA. RP Chou, WYS (reprint author), NCI, Natl Inst Hlth, Off Prevent Oncol, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NR 19 TC 4 Z9 4 U1 0 U2 3 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL, QUEBEC H2W 1R7, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD SPR PY 2008 VL 24 IS 1 BP 31 EP 40 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 280SF UT WOS:000254445800005 PM 18459595 ER PT J AU Bloch, M Haverkos, L Jobe, JB AF Bloch, Michele Haverkos, Lynne Jobe, Jared B. TI Tobacco use and secondhand smoke exposure of children and youth with serious chronic illness: Establishing an agenda for research and action SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Editorial Material C1 NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Haverkos, Lynne] NICHHD, Ctr Res Mothers & Childrens, Child Dev & Behav Branch, Bethesda, MD 20892 USA. [Jobe, Jared B.] Natl Heart Lung & Blood Inst, Clin Applicat & Prevent Branch, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. RP Bloch, M (reprint author), NCI, Tobacco Control Res Branch, Execut Plaza N Room 4036,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. EM blochm@mail.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD MAR PY 2008 VL 33 IS 2 BP 111 EP 112 DI 10.1093/jpepsy/jsl057 PG 2 WC Psychology, Developmental SC Psychology GA 258XG UT WOS:000252903100001 PM 17329319 ER PT J AU Robinson, LA Emmons, KM Moolchan, ET Ostroff, JS AF Robinson, Leslie A. Emmons, Karen M. Moolchan, Eric T. Ostroff, Jamie S. TI Developing smoking cessation programs for chronically ill teens: Lessons learned from research with healthy adolescent smokers SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article; Proceedings Paper CT Conference on Tobacco Control Strategies for Medically At-Risk Youth CY OCT 06-08, 2005 CL St Jude Childrens Res Hosp, Memphis, TN HO St Jude Childrens Res Hosp DE adolescents; chronic illness; pediatric; smoking cessation; tobacco use ID RANDOMIZED CLINICAL-TRIAL; NICOTINE PATCH; CANCER SURVIVORS; CHILDHOOD-CANCER; USE TOBACCO; PREDICTORS; PREVENTION; BEHAVIOR; RISK; INTERVENTION AB Objective Medically fragile teens who smoke need access to smoking cessation programs, because they are at even higher risk than their healthy peers for smoking-related complications. Methods To date, no studies on the outcome of smoking cessation programs for medically ill teens have been conducted. To suggest directions for future research, we turn to the literature on smoking cessation in the general population of teens and occasionally to the literature on adult smokers. Results Four areas are explored: (a) the prevalence of unaided cessation in healthy teens; (b) the outcomes of various treatments for smoking cessation in healthy adolescents; (c) special issues that should be considered when designing programs for medically ill teens; and (d) lessons learned from previous research. Conclusions Medically ill teens face a number of medical, emotional, social, and developmental challenges that can affect the quitting process. Research is sorely needed to address the unique needs of this population. C1 Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Moolchan, Eric T.] Natl Inst Hlth, Natl Inst Drug Abuse, Intramural Res Program, Bethesda, MD 20892 USA. [Ostroff, Jamie S.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. RP Robinson, LA (reprint author), Univ Memphis, Dept Psychol, 202 Psychol, Memphis, TN 38152 USA. EM Robinson@mail.psyc.memphis.edu OI Ostroff, Jamie/0000-0003-2671-5680 FU NCI NIH HHS [CA117417] NR 68 TC 5 Z9 5 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD MAR PY 2008 VL 33 IS 2 BP 133 EP 144 DI 10.1093/jpepsy/jsm112 PG 12 WC Psychology, Developmental SC Psychology GA 258XG UT WOS:000252903100004 PM 18056143 ER PT J AU Poursharif, B Korst, LM Fejzo, MS MacGibbon, KW Romero, R Goodwin, TM AF Poursharif, B. Korst, L. M. Fejzo, M. S. MacGibbon, K. W. Romero, R. Goodwin, T. M. TI The psychosocial burden of hyperemesis gravidarum SO JOURNAL OF PERINATOLOGY LA English DT Article DE hyperemesis gravidarum; nausea; vomiting; pregnancy; psychosocial aspects ID PREGNANCY; NAUSEA; ASSOCIATION; OUTCOMES AB Objective: To describe the psychosocial burden of hyperemesis gravidarum (HG) in a large cohort of affected women, focusing on previously unreported problems. Study Design: Women with HG described their pregnancy history in an open-ended survey administered internationally through an HG website during 2003 to 2005. Result: Of the 808 participants, 626 (77.5%) were American. A large majority (82.8%) reported that HG caused negative psychosocial changes, consisting of (1) socioeconomic changes, for example, job loss or difficulties, (2) attitude changes including fear regarding future pregnancies and (3) psychiatric sequelae, for example, feelings of depression and anxiety, which for some continued postpartum. Women who reported that their health-care provider was uncaring or unaware of the severity of their symptoms were nearly twice as likely to report these psychiatric sequelae (odds ratio 1.86, 95% confidence interval 1.06 to 3.29, P = 0.032). Conclusion: Over 80% of a large cohort of women with HG reported that HG caused a negative psychosocial impact. C1 [Poursharif, B.; Korst, L. M.; Fejzo, M. S.; Goodwin, T. M.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, LAC & USC Womens & Childrens Hosp, Los Angeles, CA 90033 USA. [MacGibbon, K. W.] Hyperemesis Educ & Res Fdn, Leesburg, VA USA. [Romero, R.] NICHD, NIH, DHHS, Detroit, MI USA. RP Korst, LM (reprint author), Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, LAC & USC Womens & Childrens Hosp, 1240 N Mission Rd,5K40, Los Angeles, CA 90033 USA. EM korst@usc.edu OI MacGibbon, Kimber/0000-0002-6534-3114 FU Intramural NIH HHS NR 25 TC 36 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD MAR PY 2008 VL 28 IS 3 BP 176 EP 181 DI 10.1038/sj.jp.7211906 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 280HD UT WOS:000254415600003 PM 18059463 ER PT J AU McCrae, RR AF McCrae, Robert R. TI A note on some measures of profile agreement SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID IV PERSONALITY-DISORDERS; CORRELATION-COEFFICIENTS; 5-FACTOR MODEL; CULTURES; ADOLESCENTS; CONSENSUS; RATINGS AB Profile similarity or agreement is increasingly used in personality research and clinical practice and has potential applications in many other fields of psychology. I compared 4 measures of profile agreement-the Pearson r, Cattell's (1949) r(p), McCrae's (1993) r(pa), and an intraclass correlation coefficient (double entry), ICCDE-using both broad factor and specific facet profiles. Matched versus mismatched self-ratings/other ratings on the NEO Personality Inventory-3 (McCrae, Costa, & Martin, 2005) were used as criteria. At the factor level, rp, and ICCDE were comparable, and both were superior to r(p) in distinguishing matched versus mismatched profiles. At the facet level, ICCDE was superior to the other coefficients. The Pearson r performed better than expected. C1 [McCrae, Robert R.] NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. RP McCrae, RR (reprint author), NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM jeffm@lpc.grc.nia.nih.gov FU Intramural NIH HHS NR 29 TC 68 Z9 69 U1 1 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD MAR-APR PY 2008 VL 90 IS 2 BP 105 EP 109 DI 10.1080/00223890701845104 PG 5 WC Psychology, Clinical; Psychology, Social SC Psychology GA 279YN UT WOS:000254392200001 PM 18444102 ER PT J AU Yabroff, KR Troiano, RP Berrigan, D AF Yabroff, K. Robin Troiano, Richard P. Berrigan, David TI Walking the Dog: Is Pet Ownership Associated With Physical Activity in California? SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE walking/statistics and numerical data; dogs; cats AB Background: Several studies have reported positive associations between pet ownership and a variety of health outcomes. In this study, we explored associations between pet ownership and physical activity in a large, ethnically diverse population-based sample in California. Method: Data from the California Health Interview Survey (CHIS) were used to assess the associations between pet ownership (ie, dog, dog and cat, cat, and non-pet owners) and transportation and leisure walking in a sample of 41,514 adults. Logistic regression was used to assess associations between pet ownership and type of walking, and linear regression was used to assess associations between pet ownership and total minutes walking per week. Results: Dog owners were slightly less likely to walk for transportation than were non-pet owners (OR = 0.91; 95% CI: 0.85 to 0.99) but more likely to walk for leisure than non-pet owners (OR = 1.6; 95% CI: 1.5 to 1.8) in multivariate analyses. Overall, dog owners walked 18.9 (95% CI: 11.4 to 26.4) minutes more per week than non-pet owners. Walking behaviors of cat owners were similar to non-pet owners. Conclusion: Our findings support the moderate association between dog ownership and higher levels of physical activity. C1 [Yabroff, K. Robin; Berrigan, David] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Troiano, Richard P.] NCI, Risk Factor Monitoring & Methods Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Yabroff, KR (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. OI Troiano, Richard/0000-0002-6807-989X; Yabroff, K. Robin/0000-0003-0644-5572 NR 34 TC 30 Z9 30 U1 0 U2 8 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAR PY 2008 VL 5 IS 2 BP 216 EP 228 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V18OX UT WOS:000208015200002 PM 18382031 ER PT J AU Poisik, OV Shen, JX Jones, S Yakel, JL AF Poisik, Olga V. Shen, Jian-xin Jones, Susan Yakel, Jerrel L. TI Functional alpha 7-containing nicotinic acetylcholine receptors localize to cell bodies and proximal dendrites in the rat substantia nigra pars reticulata SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID PEDUNCULOPONTINE TEGMENTAL NUCLEUS; LONG-TERM POTENTIATION; SUBUNIT MESSENGER-RNA; DOPAMINERGIC-NEURONS; BASAL GANGLIA; IN-VITRO; GLUTAMATE RECEPTORS; PARKINSONS-DISEASE; BRAIN; COMPACTA AB The substantia nigra pars reticulata (SNr) is the primary output nucleus for the basal ganglia (BG) in the rat. The SNr is reciprocally connected with the pedunculopontine tegmental nucleus (PPN) in the brainstem, which provides cholinergic innervation to most BG nuclei. The cholinergic input into the BG is considered to be important because PPN activity is altered in Parkinson's disease (PD), a neurological disorder involving the BG, and cholinergic pharmacotherapy is beneficial in alleviating some of its symptoms. In order to better understand the role of cholinergic input to the BG, we examined the effects of nicotinic acetylcholine receptor (nAChR) activation in the GABAergic neurons in slices through juvenile rat SNr. With the aide of subtype selective antagonists, we found that SNr neurons express the alpha 7 subtype of nAChRs, the function of which we assessed using the whole cell patch-clamp recording technique. Besides alpha 7 nAChRs, GABAergic SNr neurons also contained functional non-alpha 7 nAChRs. Using local photolysis of caged carbachol, a broad-spectrum cholinergic agonist, we mapped alpha 7 nAChR-mediated currents along the visible extent of filled SNr neurons and found that alpha 7 nAChRs can be functionally detected as far as 60 mu m away from the soma. Our data are paving the way to a better understanding of the physiological roles of nAChRs in the BG. C1 [Poisik, Olga V.; Shen, Jian-xin; Yakel, Jerrel L.] NIEHS, NIH, Dept Hlth & Human Serv, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. [Jones, Susan] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England. RP Yakel, JL (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, Neurobiol Lab, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU Intramural NIH HHS NR 68 TC 11 Z9 11 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 1 PY 2008 VL 586 IS 5 BP 1365 EP 1378 DI 10.1113/jphysiol.2008.149963 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 269HC UT WOS:000253639100021 PM 18310132 ER PT J AU Lockwich, T Pant, J Makusky, A Jankowska-Stephens, E Kowalak, JA Markey, SP Ambudkar, IS AF Lockwich, Timothy Pant, Jaya Makusky, Anthony Jankowska-Stephens, Ewa Kowalak, Jeffrey A. Markey, Sanford P. Ambudkar, Indu S. TI Analysis of TRPC3-interacting proteins by tandem mass spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomic analysis; TRPC3; protein complex; signaling ID SIGNALING COMPLEX; PLASMA-MEMBRANE; TRPC3 CHANNELS; CA2+ INFLUX; GROWTH CONES; NERVE GROWTH; KINASE-C; CELLS; STORE; PHOSPHORYLATION AB Mammalian transient receptor potential canonical (TRPC) channels are a family of nonspecific cation channels that are activated in response to stimulation of phospholipase C (PLC)-dependent hydrolysis of the membrane lipid phosphatidylinositol 4,5-bisphosphate. Despite extensive studies, the mechanism(s) involved in regulation of mammalian TRPC channels remains unknown. Presence of various protein-interacting domains in TRPC channels have led to the suggestion that they associate with proteins that are involved in their function and regulation. This study was directed toward identifying the proteins associated with native TRPC3 using a shotgun proteomic approach. Anti-TRPC3 antibody was used to immunoprecipitate TRPC3 from solubilized rat brain crude membranes under conditions that allow retention of TRPC3 function. Proteins in the TRPC3 (using anti-TRPC3 antibody) and control (using rabbit IgG) immunoprecipitates were separated by SDS-PAGE, the gel was sectioned, and the resolved proteins were digested by trypsin in situ. After extraction of the peptides, the peptides were separated by HPLC and sequences derived by MS/MS. Analysis of the data revealed 64 specific TRPC3-associated proteins which can be grouped in terms of their cellular location and involvement in specific cellular function. Many of the proteins identified have been previously reported as TRPC3-regulatory proteins, such as IP(3)Rs and vesicle trafficking proteins. In addition, we report novel putative TRPC3-interacting proteins, including those involved in protein endocytosis and neuronal growth. To our knowledge, this is the first comprehensive proteomic analysis of a native TRPC channel. These data reveal potential TRPC3 regulatory proteins and provide novel insights of the mechanism(s) regulating TRPC3 channels as well as the possible cellular functions where the channel might be involved. C1 [Lockwich, Timothy; Ambudkar, Indu S.] NIH, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIDCR, Bethesda, MD 20892 USA. [Pant, Jaya; Makusky, Anthony; Jankowska-Stephens, Ewa; Kowalak, Jeffrey A.; Markey, Sanford P.] NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. RP Markey, SP (reprint author), 10 Ctr Dr,Bldg 10,Room 3D42, Bethesda, MD 20892 USA. EM mirkeys@mail.nih.gov; indu.ambudkar@nih.gov NR 44 TC 14 Z9 14 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAR PY 2008 VL 7 IS 3 BP 979 EP 989 DI 10.1021/pr070496k PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 271YR UT WOS:000253825100013 PM 18205297 ER PT J AU Lotrich, FE Pollock, BG Kirshner, M Ferrell, RF Reynolds, CF AF Lotrich, Francis E. Pollock, Bruce G. Kirshner, Margaret Ferrell, Robert F. Reynolds, Charles F. TI Serotonin transporter genotype interacts with paroxetine plasma levels to influence depression treatment response in geriatric patients SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article; Proceedings Paper CT 25th Congress of the Collegium-Internationale-Neuro-Psychopharmacologicum (CINP)/29th Annual Meeting of the Canadian-College-of-Neuropsychopharmacology CY JUL 09-13, 2006 CL Chicago, IL SP Collegium Int Neuro Psychopharmacol, Canadian Coll Neuro Psychopharmacol DE serotonin; paroxetine; depression; aged ID MAJOR DEPRESSION; REUPTAKE INHIBITORS; PROMOTER POLYMORPHISM; SERUM CONCENTRATIONS; INITIAL CONDITIONS; CLINICAL-RESPONSE; GENE; FLUVOXAMINE; CITALOPRAM; FLUOXETINE AB Objective: To investigate whether variable antidepressant response may be influenced by an interaction between the serotonin transporter promoter polymorphism (5-HTTLPR) and antidepressant concentration. Methods: Elderly subjects with depression treated with paroxetine (n = 110) were genotyped and assessed with the Hamilton Rating Scale for Depression (HAMD). A mixed-effect analysis of repeated measures was used. Results: There was an interaction between early paroxetine concentration and 5-HTTLPR genotype on symptomatic improvement over 12 weeks (F-18,F-59.5 = 1.8, p< 0.05), as well as main effects of both paroxetine concentration (F-68,F-55.3 = 2.4, p< 0.005) and genotype (F-2,F-74.2 = 5.7, p< 0.005). Paroxetine concentrations were correlated with change in HAMD scores after 2 weeks of treatment in subjects with the short (s) allele (r= 0.31, p< 0.05) but not in subjects homozygous for the long ( l) allele. Conclusion: The results demonstrate a concentration-response relation for paroxetine in late-life depression and support the hypothesis for both a direct main effect and a moderating influence of 5-HTTLPR alleles on this concentration-response relation. C1 [Lotrich, Francis E.; Pollock, Bruce G.; Kirshner, Margaret; Reynolds, Charles F.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin,Dept Psychiat, John A Harford Fdn Ctr Excellence Geriatr Psychia, Pittsburgh, PA 15260 USA. [Lotrich, Francis E.; Pollock, Bruce G.; Kirshner, Margaret; Reynolds, Charles F.] NIMH, Adv Ctr Intervent, Bethesda, MD USA. [Ferrell, Robert F.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Pollock, Bruce G.] Univ Toronto, Rotman Res Inst, Baycrest Ctr Geriatr Care, Toronto, ON, Canada. RP Lotrich, FE (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM lotrichfe@upmc.edu FU NCATS NIH HHS [UL1 TR000005]; NIMH NIH HHS [P30 MH071944, K24MH065416, P30MH071944, K24 MH065416, R01MH043832, R01 MH043832, K23MH074012, K23 MH074012] NR 55 TC 28 Z9 29 U1 0 U2 2 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD MAR PY 2008 VL 33 IS 2 BP 123 EP 130 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 271AN UT WOS:000253761400005 PM 18330458 ER PT J AU Colditz, GA Emmons, KM Vishwanath, K Kerner, JF AF Colditz, Graham A. Emmons, Karen M. Vishwanath, K. Kerner, Jon F. TI Translating science to practice: Community and academic perspectives SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE barriers to change; behavior change; dissemination ID WORKPLACE SMOKING; HEALTH-PROMOTION; PARTICIPATORY RESEARCH; PHYSICAL-ACTIVITY; SOCIAL ECOLOGY; PUBLIC-HEALTH; CARE; RESTRICTIONS; METAANALYSIS; HOUSEHOLD AB While evidence reviews inform practice and policy guidelines, the gap between guidelines and implementation may be growing. We place dissemination and implementation research in the context of other changes needed to drive research into practice. Multilevel approaches to research and dissemination are needed as are metrics to inform academic appointment and promotions. Moving beyond funding that stops and starts with grant cycles is a key issue from the community perspective to ensure continuity and improved health. Transdisciplinary approaches that cut across disciplinary boundaries to develop shared conceptual frameworks may help speed the integration of research with practice. Identifying and implementing structural changes to develop and support transdisciplinary teams may further facilitate this process. Changes in the approaches used to structure and implement scientific advances into practice will help achieve the enormous potential to advance the health of the population. C1 Washington Univ, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, Dept Prevent & Control, St Louis, MO USA. [Emmons, Karen M.; Vishwanath, K.] Dana Faber Cancer Inst, Soc Human Dev & Hlth, Boston, MA USA. [Emmons, Karen M.; Vishwanath, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Emmons, Karen M.] Dana Faber Harvard Cnc Ctr, Initiat Eliminate Canc Ctr, Boston, MA 02115 USA. [Kerner, Jon F.] Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Colditz, GA (reprint author), Washington Univ, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM colditzg@wustl.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 35 TC 30 Z9 30 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD MAR-APR PY 2008 VL 14 IS 2 BP 144 EP 149 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265DY UT WOS:000253340500011 PM 18287920 ER PT J AU Kreuter, MW Alcaraz, KI Pfeiffer, D Christopher, K AF Kreuter, Matthew W. Alcaraz, Kassandra I. Pfeiffer, Debra Christopher, Kara TI Using dissemination research to identify optimal community settings for tailored breast cancer information kiosks SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE African American; breast cancer; community health; computer kiosks; dissemination; health promotion; mammography ID AFRICAN-AMERICAN WOMEN; RE-AIM FRAMEWORK; HEALTH; IMPACT; PROGRAMS; CHANNELS; ISSUES AB Objective: Selecting appropriate community channels or settings for delivering evidence-based health promotion programs can be critical to successful dissemination. This article describes how five criteria-accessibility, opportunity, appropriateness, reach, and specificity-were applied in identifying and comparing seven community settings as host sites for a tailored breast cancer education computer kiosk for African American women. Met hods: Data were gathered from 10 306 kiosk uses in 92 beauty salons, churches, neighborhood health centers, Laundromats, social service agencies, health fairs, and public libraries between June 2003 and March 2007. Findings: Of the seven settings, only Laundromats were found to provide both high reach (ie, frequent kiosk use) and high specificity (ie, a large proportion of users with no health insurance, unaware of where to get a mammogram, reporting no recent mammogram and barriers to getting one, and having little knowledge about breast cancer and mammography). Conclusions: Systematic, data-based evaluations of potential dissemination channels can help identify optimal settings for cancer control interventions. C1 St Louis Univ, Sch Publ Hlth, Hlth Commun Res Lab, St Louis, MO 63104 USA. [Kreuter, Matthew W.; Alcaraz, Kassandra I.] St Louis Univ, Sch Publ Hlth, St Louis, MO 63104 USA. [Kreuter, Matthew W.] Natl Canc Inst, Ctrs Excellence Canc Commun Res, St Louis, MO 63104 USA. RP Kreuter, MW (reprint author), St Louis Univ, Sch Publ Hlth, Hlth Commun Res Lab, St Louis, MO 63104 USA. EM kreuter@slu.edu FU NCCDPHP CDC HHS [US48 DP000060]; NCI NIH HHS [CA-P50-95815] NR 21 TC 19 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD MAR-APR PY 2008 VL 14 IS 2 BP 160 EP 169 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265DY UT WOS:000253340500014 PM 18287923 ER PT J AU Weaver, NL Williams, J Jacobsen, HA Botello-Harbaum, M Glasheen, C Noelcke, E Nansel, TR AF Weaver, Nancy L. Williams, Janice Jacobsen, Heather A. Botello-Harbaum, Maria Glasheen, Cristie Noelcke, Elizabeth Nansel, Tonja R. TI Translation of an evidence-based tailored childhood injury prevention program SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE anticipatory guidance; childhood injury; injury prevention; translation ID PRIMARY-CARE PRACTICE; COMPETING DEMANDS; DISSEMINATION; INTERVENTIONS; EDUCATION; SETTINGS; COMPUTER AB This article describes the process of translating Safe n' Sound, a computer-based program for parents of young children, for a general clinic environment. Safe n' Sound is designed to reduce the risk of unintentional childhood injuries, the leading cause of death among children older than 1 year in the United States. The evidence-based program produces tailored information for parents and their healthcare provider about burns, falls, poisoning, drowning, suffocations, choking prevention, and car safety. To offer Safe n' Sound to a broader audience, we translated the program from the form used for efficacy testing to a stand-alone application. Notable steps in this translation included (1) conducting an organizational assessment to determine the needs of the clinic staff and feasibility of implementation, (2) modifying the program to reduce length, prioritize risk areas, and update content, (3) repackaging the program to minimize cost and space requirements, and (4) developing promotional and instructional materials. Factors contributing to the success of this effort include strong collaborative partnerships, the relative advantage of Safe n' Sound over traditional materials, the modifiable design of the program, and the support of the clinic staff and providers. Challenges and areas for future work are discussed. C1 St Louis Univ, Sch Publ Hlth, Dept Community Hlth, St Louis, MO 63104 USA. [Weaver, Nancy L.] St Louis Univ, Sch Publ Hlth, Hlth Community Res Lab, St Louis, MO 63104 USA. [Williams, Janice] Carolinas Med Ctr, Carolinas Ctr Injury Prevent, Charlotte, NC 28203 USA. [Jacobsen, Heather A.] St Louis Univ, Sch Publ Hlth, Hlth Commun Res Lab, St Louis, MO 63103 USA. [Botello-Harbaum, Maria; Noelcke, Elizabeth; Nansel, Tonja R.] NICHHD, Natl Inst Hlth, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Glasheen, Cristie] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Weaver, NL (reprint author), St Louis Univ, Sch Publ Hlth, Dept Community Hlth, 3545 Lafayette Ave, St Louis, MO 63104 USA. EM weavernl@slu.edu OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS [Z01 HD002402-09] NR 29 TC 11 Z9 11 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD MAR-APR PY 2008 VL 14 IS 2 BP 177 EP 184 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265DY UT WOS:000253340500016 PM 18287925 ER PT J AU Kerner, JF AF Kerner, Jon F. TI Integrating research, practice, and policy: What we see depends on where we stand SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE knowledge translation; research-practice-policy integration ID CANCER CONTROL; DISSEMINATION; TRANSLATION; DIFFUSION AB In this special issue of the Journal of Public Health Management and Practice, the editors have taken on the important challenge of characterizing the current landscape of knowledge translation research and practice in public health. This includes the diffusion of scientific and program evaluation evidence into public health practice and policy, the dissemination and implementation of evidence-based interventions in public health practice, and the complex issues associated with the meaning and methods of dissemination and implementation research. Three of the most important challenges for moving the field of dissemination and implementation science and research dissemination and implementation practice forward are the confusion of terminology, the meaning of evidence, and partnerships across the research, practice, and policy divides. Because many in the research, practice, and policy-making sectors do not see their role in closing the gap among research, practice, and policy, new and expanded incentives need to be put in place to encourage these collaborations. Partnerships between research, practice, and policy can help inform decisions in all three sectors to help achieve a better balance between evidence based on science and evidence based on personal experience. C1 NCI, Natl Inst Hlth, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Kerner, JF (reprint author), NCI, Natl Inst Hlth, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 6142, Bethesda, MD 20892 USA. EM erj@mail.nih.gov NR 14 TC 32 Z9 32 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD MAR-APR PY 2008 VL 14 IS 2 BP 193 EP 198 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 265DY UT WOS:000253340500018 PM 18287927 ER PT J AU Harsh, V McGarvey, EL Clayton, AH AF Harsh, Veronica McGarvey, Elizabeth Lloyd Clayton, Anita H. TI Physician attitudes regarding hypoactive sexual desire disorder in a primary care clinic: A pilot study SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE sexual dysfunction; women; physical examination ID DYSFUNCTION; HISTORY AB Introduction. Female sexual dysfunction (FSD), in particular, complaints of low desire, affects many American women. Despite the impact FSD may have on these women, many do not present their symptoms to their physicians. Aim. To determine physician attitudes and practices regarding hypoactive sexual desire disorder (HSDD) in the primary care setting. Main Outcome Measures. A 10-item questionnaire regarding HSDD. Methods. All residents and faculty in an academic primary care clinic were invited to participate in a web-based survey regarding HSDD. Return of the questionnaire was considered consent. Responses were downloaded into Excel and converted into an spssdatabase. Results. In total, 53 of 155 physicians responded (46% response rate-41.5% women, 58.5% men). Of respondents, 90% reported little confidence in making the diagnosis of HSDD, 90% of physicians had not screened a patient for HSDD, and 98% of the physicians had not prescribed medication for patients with HSDD. No significant gender differences among physicians were identified, but faculty providers had more confidence in diagnosing and treating HSDD than resident physicians. Conclusions. These results indicate there is an opportunity to improve patient care and life satisfaction by offering physicians training on diagnosis and management of HSDD. C1 [Clayton, Anita H.] Univ Virginia, Sch Med, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22903 USA. [Harsh, Veronica] NIMH, Bethesda, MD 20892 USA. [McGarvey, Elizabeth Lloyd] Univ Virginia, Sch Med, Dept Publ Hlth, Charlottesville, VA 22903 USA. RP Clayton, AH (reprint author), Univ Virginia, Sch Med, Dept Psychiat & Neurobehav Sci, Northridge Bldg,Suite 210,2955 Ivy Rd, Charlottesville, VA 22903 USA. EM ahc8v@virginia.edu NR 9 TC 23 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD MAR PY 2008 VL 5 IS 3 BP 640 EP 645 DI 10.1111/j.1743-6109.2007.00746.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 269DW UT WOS:000253630700026 PM 18194180 ER PT J AU Heymann, JB Cardone, G Winkler, DC Steven, AC AF Heymann, J. Bernard Cardone, Giovanni Winkler, Dennis C. Steven, Alasdair. C. TI Computational resources for cryo-electron tomography in Bsoft SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Conference on Electron Tomography CY NOV 05-08, 2006 CL San Diego, CA DE electron microscopy; image processing workflow; distributed processing; micrograph alignment; fiducial markers ID HERPES-SIMPLEX-VIRUS; 3-DIMENSIONAL ELECTRON-MICROSCOPY; TILT-SERIES; NOISE-REDUCTION; RECONSTRUCTION; IMAGE; RESOLUTION; ALIGNMENT; VISUALIZATION; ACQUISITION AB The Bsoft package [Heymann, J.B., Belnap, D.M., 2007. Bsoft: image processing and molecular modeling for electron microscopy. J. Struct. Biol. 157, 3-18] has been enhanced by adding utilities for processing electron tomographic (ET) data; in particular, cryo-ET data characterized by low contrast and high noise. To handle the high computational load efficiently, a workflow was developed, based on the database-like parameter handling in Bsoft, aimed at minimizing user interaction and facilitating automation. To the same end, scripting elements distribute the processing among multiple processors on the same or different computers. The resolution of a tomogram depends on the precision of projection alignment, which is usually based on pinpointing fiducial markers (electron-dense gold particles). Alignment requires accurate specification of the tilt axis, and our protocol includes a procedure for determining it to adequate accuracy. Refinement of projection alignment provides information that allows assessment of its precision, as well as projection quality control. We implemented a reciprocal space algorithm that affords an alternative to back-projection or real space algorithms for calculating tomograms. Resources are also included that allow resolution assessment by cross-validation (NLOO2D); denoising and interpretation; and the extraction, mutual alignment, and averaging of tomographic sub-volumes. Published by Elsevier Inc. C1 [Heymann, J. Bernard; Cardone, Giovanni; Winkler, Dennis C.; Steven, Alasdair. C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Heymann, JB (reprint author), NIAMSD, Struct Biol Lab, NIH, Bldg 50,Room 1515,50 S Dr MSC 8025, Bethesda, MD 20892 USA. EM Bernard_Heymann@nih.gov RI Heymann, Bernard/F-6825-2011; OI Heymann, Bernard/0000-0002-8872-5326 FU Intramural NIH HHS [Z99 AR999999] NR 34 TC 76 Z9 78 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAR PY 2008 VL 161 IS 3 BP 232 EP 242 DI 10.1016/j.jsb.2007.08.002 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 279IO UT WOS:000254349100003 PM 17869539 ER PT J AU Hingson, RW Heeren, T Edwards, EM AF Hingson, Ralph W. Heeren, Timothy Edwards, Erika M. TI Age at drinking onset, alcohol dependence, and their relation to drug use and dependence, driving under the influence of drugs, and motor-vehicle crash involvement because of drugs SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID BRIEF MOTIVATIONAL INTERVENTION; INITIATION; RISK; EMERGENCY AB Objective: We explored among people who ever consumed alcohol whether early age at drinking onset and alcohol dependence predicted drug use and dependence. We also examined among drinkers who have used drugs whether they also predict driving under the influence of drugs and motor-vehicle crash involvement because of drugs. Method: A US. national sample of 42,867 persons age 18 and older was surveyed in 1991-1992 (response rate = 90%). Logistic regression examined these potential associations among 27,616 respondents who ever drank alcohol, controlling for numerous demographic and personal characteristics. Results: Among "ever" drinkers, 22% used drugs, 10% had driven under the influence of drugs, and nearly 1% was in a motor-vehicle crash because of drug use, the equivalent of 1 million people. The younger the age of respondents when they first began drinking and whether they ever experienced alcohol dependence were independently associated with greater odds of ever using drugs and experiencing drug dependence. Among persons who consumed alcohol and drugs, having ever experienced drug dependence was the strongest predictor of driving under the influence of drugs and motor-vehicle crash involvement because of drug use. After controlling for drug dependence and age at first drug use, having experienced alcohol dependence was also independently associated with both outcomes. Conclusions: Efforts to prevent drug-related crashes should include drug use prevention and treatment, as well as prevention of early alcohol use and treatment of alcohol dependence. C1 [Hingson, Ralph W.; Heeren, Timothy; Edwards, Erika M.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. [Heeren, Timothy; Edwards, Erika M.] Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA 02215 USA. RP Hingson, RW (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fisheres Lane,Room 2077, Bethesda, MD 20892 USA. EM rhingson@mail.nih.gov FU NIAAA NIH HHS [P60-AA013759] NR 32 TC 51 Z9 52 U1 2 U2 5 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAR PY 2008 VL 69 IS 2 BP 192 EP 201 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 269KN UT WOS:000253648000003 PM 18299759 ER PT J AU Abram, KM Choe, JY Washburn, JJ Teplin, LA King, DC Dulcan, MK AF Abram, Karen M. Choe, Jeanne Y. Washburn, Jason J. Teplin, Linda A. King, Devon C. Dulcan, Mina K. TI Suicidal ideation and behaviors among youths in juvenile detention SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE juvenile detainee; suicidal ideation; suicide; psychiatric disorder ID DIAGNOSTIC INTERVIEW SCHEDULE; VERSION DISC-R; RISK-FACTORS; DELINQUENT POPULATION; PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; CHILDREN; ADOLESCENTS; PREVALENCE; FACILITIES AB Objective: To examine suicidal ideation, suicide attempts, lethality of suicide attempts, and the relationship between. psychiatric disorder and recent attempts in newly detained juveniles. Method: The sample included 1,829 juveniles, ages 10 to 18 years, sampled after intake to a detention center in Chicago. Interviewers administered the Diagnostic Interview Schedule for Children to assess for thoughts of death, suicidal ideation, suicide plans, lifetime suicide attempts, number of attempts, age at first attempt, attempts within the past 6 months, method of suicide attempts, and psychiatric disorder. Results: More than one third of juvenile detainees and nearly half of females had felt hopeless or thought about death in the 6 months before detention. Approximately 1 in 10 (10.3%, 95% confidence interval: 7.7%-12.8%) juvenile detainees had thought about committing suicide in the past 6 months, and 1 in 10 (11.0%, 95% confidence interval: 8.3%-13.7%) had ever attempted suicide. Recent suicide attempts were most prevalent in females and youths with major depression and generalized anxiety disorder. Conclusions: Fewer than half of detainees with recent thoughts of suicide had told anyone about their ideation. Identifying youths at risk for suicide, especially those suffering from depressive and anxiety disorders, is a crucial step in preventing suicide. C1 [Abram, Karen M.; Choe, Jeanne Y.; Washburn, Jason J.; Teplin, Linda A.; Dulcan, Mina K.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Psycholegal Studies Program, Chicago, IL 60611 USA. [King, Devon C.] NIMH, Bethesda, MD 20892 USA. RP Abram, KM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Psycholegal Studies Program, 710 N Lake Shore Dr,Suite 900, Chicago, IL 60611 USA. EM psycho-legal@northwestern.edu FU NIDA NIH HHS [R01 DA028763, R01 DA019380]; NIMH NIH HHS [R01 MH054197, R01 MH054197-05, R01 MH059463, R01 MH059463-05, R01MH54197, R01MH59463] NR 67 TC 41 Z9 41 U1 9 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2008 VL 47 IS 3 BP 291 EP 300 DI 10.1097/chi.0b013e318160bce PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 265EV UT WOS:000253342800012 PM 18216737 ER PT J AU O'Malley, J Dambrosia, JM Davis, JA AF O'Malley, James Dambrosia, James M. Davis, Judith A. TI Effect of housing density on reproductive parameters and corticosterone levels in nursing mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID CAGE FLOOR SPACE; POPULATION-DENSITY; LABORATORY MICE; MOUSE-POPULATION; BODY-WEIGHT; ENVIRONMENT; AGGRESSION; STRAINS; WELFARE; STRESS AB The Guide for the Care and Use of Laboratory Animals (Guide) recommends minimum floor space per mouse based on weight, with no other factors considered. We conducted a randomized experiment to evaluate the effect of housing density on reproductive indices and corticosterone levels in lactating mice. Female mice matched for age, strain, and date-of-pregnancy were housed individually. At parturition the dams were randomly allocated to have litters culled or remain intact. The experimental group had litters culled to meet the Guide's space density requirement. Litters of the second group were maintained as the numbers born to each dam. Fecal corticosterone levels (first-generation mice only), growth, and weaning weights were measured for mice in all cages; in addition, the reproductive behavior of progeny generated under both housing conditions was assessed to determine whether a space x litter size interaction affected subsequent reproduction. The growth rates for pups from culled litters were significantly greater than those from intact litters. The first-generation pups showed no statistically significant differences in fecal corticosterone or reproductive parameters. The second-generation pups showed no statistically significant differences in growth rates. The results of the study suggest that a strict interpretation of space requirements as listed in Table 2.1 of the Guide is not warranted for lactating dams with litters. C1 [O'Malley, James; Dambrosia, James M.] NINDS, Bethesda, MD 20892 USA. [Davis, Judith A.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. RP O'Malley, J (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM omalleyj@ninds.nih.gov FU Intramural NIH HHS NR 38 TC 11 Z9 11 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAR PY 2008 VL 47 IS 2 BP 9 EP 15 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 279OJ UT WOS:000254364200002 PM 18351716 ER PT J AU Yanetz, R Carroll, RJ Dodd, KW Subar, AF Schatzkin, A Freedman, LS AF Yanetz, Rivka Carroll, Raymond J. Dodd, Kevin W. Subar, Amy F. Schatzkin, Arthur Freedman, Laurence S. TI Using biomarker data to adjust estimates of the distribution of usual intakes for misreporting: Application to energy intake in the US population SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NUTRIENT INTAKE DISTRIBUTIONS; DIETARY; VALIDATION; OBESITY; CHOLESTEROL; PROTEIN; TRIALS; ERROR; FOODS AB Objective It is now well-established that individuals misreport their dietary intake. We propose a new method (National Research Council-Biomarker [NRC-B]) for estimating population distributions of usual dietary intake from national survey 24-hour recall data, using additional biomarker data from an external study to adjust for such dietary misreporting. Statistical analyses performed NRC-B is an extension of the NRC method, and is based upon two developed assumptions: the ratio of the mean of true intake to that of reported intake is equal in the survey and external biomarker study; and the ratio of the variance of true intake to that of reported intake is equal in these two studies. NRC-B adjusts the usual intake distribution both for within-person variation and for bias (underreporting) that occur with 24-hour recall reports. Using doubly labeled water ((H2O)-H-2-O-18) measurements from the Observing Protein and Energy Nutrition study, we applied NRC-B to data on energy intake for adults aged 40 to 69 years from two national surveys, the Continuing Survey of Food Intakes by Individuals and National Health and Nutrition Examination Survey. We compared the results with the NRC and traditional methods that used only the survey data to estimate dietary intake distributions. Results Estimated distributions from NRC-B and NRC were much narrower and less skewed than from the traditional method. However, unlike NRC, the median of the NRC-B based distribution was higher by 8% to 16% than the traditional method in our examples. Conclusions The proposed method adjusts for the well-documented problem of underreporting of energy intake. C1 [Freedman, Laurence S.] Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52161 Tel Hashomer, Israel. [Yanetz, Rivka] Bar Ilan Univ, Dept Math, Ramat Gan, Israel. [Subar, Amy F.] NCI, Bethesda, MD 20892 USA. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Schatzkin, Arthur] Div Canc Epidemiol & Gent, Nutr Epidemiol Branch, Bethesda, MD USA. RP Freedman, LS (reprint author), Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52161 Tel Hashomer, Israel. EM lsf@actcom.co.il FU NCI NIH HHS [CA-57030]; NIEHS NIH HHS [P30-ES09106] NR 34 TC 8 Z9 8 U1 0 U2 6 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2008 VL 108 IS 3 BP 455 EP 464 DI 10.1016/j.jada.2007.12.004 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 270NN UT WOS:000253727600014 PM 18313427 ER PT J AU Miller, MF Bellizzi, KM Sufian, M Ambs, AH Goldstein, MS Ballard-Bareash, R AF Miller, Melissa Farmer Bellizzi, Keith M. Sufian, Meryl Ambs, Anita H. Goldstein, Michael S. Ballard-Bareash, Rachel TI Dietary supplement use in individuals living with cancer and other chronic conditions: A population-based study SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID ALTERNATIVE MEDICINE USE; HEALTH INTERVIEW SURVEY; THE-SCIENCE CONFERENCE; UNITED-STATES; NATIONAL-HEALTH; LIFE-STYLE; PROSTATE-CANCER; MINERAL SUPPLEMENTS; ADULT-POPULATION; CHRONIC DISEASE AB Objective Cancer survivors are increasingly turning to complementary and alternative medicine (CAM) to manage short- and long-term treatment sequelae. Population-based data on relative use of dietary supplements among cancer survivors compared to those without a cancer history is lacking. Our objective was to compare supplement use among those with and without cancer and among those with and without other chronic conditions, and to identify correlates of supplement use by cancer status. Design Cross-sectional, population-based survey of participants in the 2003 CAM supplement to the 2001 California Health Interview Survey. Subjects Participants reporting a cancer diagnosis on the 2001 California Health Interview Survey or newly reported diagnosis on the 2003 survey (n=1,844) plus a random oversampling of racial/ethnic minorities (n=7,343). Measures Self-reported use of a multivitamin and 27 vitamins, minerals, herbs, and other natural products during the preceding 12 months. Statistical analyses Logistic regression analyses were performed with control for potential confounders. Results Adults with cancer or other chronic conditions had higher prevalence of supplement use than those reporting no illness. The independent effect of cancer was associated with vitamin use, whereas living with other chronic conditions was associated with all types of supplement use, except multivitamins. Correlates of supplement use were similar between cancer survivors and cancer-free individuals-being a woman, advancing age, and greater physical activity, fruit and vegetable intake, and other CAM use. Among cancer survivors, non-Hispanic whites had the lowest prevalence of herbal supplement use. Conclusions These results indicate that having a chronic medical condition is the major factor associated with supplement use. A diagnosis of cancer, by itself, does not have an independent effect on supplement use. This suggests that most supplement use among cancer survivors is directed at dealing with or preventing the exacerbation of a comorbid condition. Consumers and health professionals should be aware that there is limited information on the effects of dietary supplements taken concurrently with prescription and other over-the-counter medications. C1 [Miller, Melissa Farmer; Bellizzi, Keith M.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Miller, Melissa Farmer] Wellness Community, Washington, DC USA. [Miller, Melissa Farmer; Bellizzi, Keith M.; Sufian, Meryl] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. [Sufian, Meryl] NIH, Off Portfolio Anal & Strateg Initiat, Bethesda, MD 20892 USA. [Ambs, Anita H.; Ballard-Bareash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Goldstein, Michael S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. RP Miller, MF (reprint author), NCI, Canc Prevent Fellowship Program, 6116 Execut Blvd,Ste 404,MSC 8336, Bethesda, MD 20892 USA. EM millermeli@mail.nih.gov FU NCI NIH HHS [N02-PC-95057] NR 53 TC 37 Z9 37 U1 5 U2 11 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2008 VL 108 IS 3 BP 483 EP 494 DI 10.1016/j.jada.2007.12.005 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 270NN UT WOS:000253727600018 PM 18313431 ER PT J AU Reedy, J Krebs-Smith, SM AF Reedy, Jill Krebs-Smith, Susan M. TI A comparison of food-based recommendations and nutrient values of three food guides: USDA's MyPyramid, NHLBI's dietary approaches to stop hypertension eating plan, and Harvard's healthy eating pyramid SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID GUIDANCE-SYSTEM; PATTERNS; TRIAL AB The purpose of this research was to compare food-based recommendations and nutrient values of three food guides: the US Department of Agriculture's MyPyramid; the National Heart, Lung, and Blood Institute's Dietary Approaches to Stop Hypertension Eating Plan, and Harvard University's Healthy Eating Pyramid. Estimates of nutrient values associated with following each of the food guides at the 2,000-calorie level were made using a composite approach. This approach calculates population-weighted nutrient composites for each food group and subgroup, assuming average choices within food groups. Nutrient estimates were compared to the Dietary Reference Intakes and other goals and limits. Recommendations were similar regarding almost all food groups for both the type and amount of foods. Primary differences were seen in the types of vegetables and protein sources recommended and the amount of dairy products and total oil recommended. Overall nutrient values were also similar for most nutrients, except vitamin A, vitamin E, and calcium. These food guides were derived from different types of nutrition research, yet they share consistent messages: eat more fruits, vegetables, legumes, and whole grains; eat less added sugar and saturated fat; and emphasize plant oils. C1 [Reedy, Jill; Krebs-Smith, Susan M.] NCI, Div Canc Control & Populat Sci, App Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. RP Reedy, J (reprint author), NCI, Div Canc Control & Populat Sci, App Res Program, Risk Factor Monitoring & Methods Branch, 6130 Execut Blvd,EPN 4005,MSC 7344, Bethesda, MD 20892 USA. EM reedyj@mail.nih.gov NR 13 TC 33 Z9 34 U1 0 U2 11 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2008 VL 108 IS 3 BP 522 EP 528 DI 10.1016/j.jada.2007.12.014 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 270NN UT WOS:000253727600021 PM 18313434 ER PT J AU Ciol, MA Shumway-Cook, A Hoffman, JM Yorkston, KM Dudgeon, BJ Chan, L AF Ciol, Marcia A. Shumway-Cook, Anne Hoffman, Jeanne M. Yorkston, Kathryn M. Dudgeon, Brian J. Chan, Leighton TI Minority disparities in disability between medicare beneficiaries SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE minority disparities; disability; Medicare ID HEALTH-STATUS; OLD-AGE; POPULATION; BLACK; PREVALENCE; LIMITATIONS; PERSISTENT; MORTALITY; ADULTS; TRENDS AB OBJECTIVES: To examine racial and ethnic disparities in mobility limitation, activities of daily living (ADLs), and instrumental activities of daily living (IADLs) in older adults enrolled in Medicare. DESIGN: Longitudinal national survey. PARTICIPANTS: Community-dwelling respondents in the Medicare Current Beneficiaries Survey from 1992 to 2004 (10,180-16,788 respondents per year). MEASUREMENTS: Disability-related outcomes included mobility limitation, difficulty in six ADLs and six IADLs. Explanatory variables included age, sex, racial or ethnic group, living situation, and income level. RESULTS: From 1992 to 2004, proportions of Medicare beneficiaries with mobility limitations were stable across racial and ethnic groups, improving slightly for ADLs and IADLs. Blacks reported more limitations in all three disability-related measures. In a longitudinal analysis, the probability of developing mobility limitation was consistently higher for blacks, followed by white Hispanics, white non-Hispanics, and Asians, after adjusting for age, sex, socioeconomic status, and living situation. For ADL and IADL difficulties, the number of reported difficulties increased with age for all ethnic and racial groups. At approximately age 75, Asians and white Hispanics reported difficulties with much higher numbers of ADLs and IADLs than the other groups. CONCLUSION: Across all ethnic and racial groups, self-reported disability has declined in the past decade, but even after adjusting for age, sex, socioeconomic status, and living situation, racial and ethnic disparities in disability outcomes persist. Race and ethnicity may influence the reporting of disability, potentially affecting measures of prevalence. Further research is needed to understand whether these differences are a result of perceptions related to disablement or true differences in disability between racial and ethnic groups. C1 [Ciol, Marcia A.; Shumway-Cook, Anne; Hoffman, Jeanne M.; Yorkston, Kathryn M.; Dudgeon, Brian J.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Chan, Leighton] Natl Inst Hlth, Clin Res Ctr, Dept Rehabil Med, Bethesda, MD USA. RP Ciol, MA (reprint author), Univ Washington, Dept Rehabil Med, Box 356490, Seattle, WA 98195 USA. EM marciac@u.washington.edu FU Intramural NIH HHS [ZIA CL060072-03]; PHS HHS [MM-0625-04/04] NR 28 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2008 VL 56 IS 3 BP 444 EP 453 DI 10.1111/j.1532-5415.2007.01570.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 269CX UT WOS:000253628200008 PM 18179505 ER PT J AU Fridsma, DB Evans, J Hastak, S Mead, CN AF Fridsma, Douglas B. Evans, Julie Hastak, Smita Mead, Charles N. TI The BRIDG project: A technical report SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB Objectives: The Biomedical Research Integrated Domain Group (BRlDG) project is a collaborative initiative between the National Cancer Institute (NCI), the Clinical Data Interchange Standards Consortium (CDISC), the Regulated Clinical Research Information Management Technical Committee (RCRIM TC) of Health Level 7 (HL7), and the Food and Drug Administration (FDA) to develop a model of the shared understanding of the semantics of clinical research. Design: The BRIDG project is based on open-source collaborative principles and an implementation-independent, use-case driven approach to model development. In the BRIDG model, declarative and procedural knowledge are represented using the Unified Modeling Language (UML) class, activity and state diagrams. Measurements: The BRIDG model currently contains harmonized semantics from four project use cases: the caXchange project and the patient study calendar project from caBIG (TM); the standard data tabular model (SDTM) from CDISC; and the regulated products submission model (RPS) from HL7. Scalable harmonization processes have been developed to expand the model with content from additional use cases. Results: The first official release of the BRIDG model was published in June 2007. Use of the BRIDG model by the NCI has supported the rapid development of semantic interoperability across applications within the caBIG (TM) program. Conclusions: The BRIDG project has brought together different standards communities to clarify the semantics of clinical research across pharmaceutical, regulatory, and research organizations. Currently, the NCI uses the BRIDG model to support interoperable application development in the caBIG (TM), and CDISC and HL7 are using the BRIDG model to support standards development. C1 [Fridsma, Douglas B.] Arizona State Univ W, Dept Biomed Informat, Phoenix, AZ 85004 USA. [Evans, Julie] Clin Data Interchange Stand Consortium, Washington, DC USA. [Hastak, Smita] ScePro Inc, Washington, DC USA. [Mead, Charles N.] Booz Allen Hamilton Natl Canc Inst, Washington, DC USA. RP Fridsma, DB (reprint author), Arizona State Univ W, Dept Biomed Informat, 425 N 5th St, Phoenix, AZ 85004 USA. EM fridsma@asu.edu NR 24 TC 53 Z9 54 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 2008 VL 15 IS 2 BP 130 EP 137 DI 10.1197/jamia.M2556 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 273UL UT WOS:000253957100002 PM 18096907 ER PT J AU Oster, S Langella, S Hastings, S Ervin, D Madduri, R Phillips, J Kurc, T Siebenlist, F Covitz, P Shanbhag, K Foster, I Saltz, J AF Oster, Scott Langella, Stephen Hastings, Shannon Ervin, David Madduri, Ravi Phillips, Joshua Kurc, Tahsin Siebenlist, Frank Covitz, Peter Shanbhag, Krishnakant Foster, Ian Saltz, Joel TI caGrid 1.0: An enterprise Grid infrastructure for biomedical research SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID INFORMATICS AB Objective: To develop software infrastructure that will provide support for discovery, characterization, integrated access, and management of diverse and disparate collections of information sources, analysis methods, and applications in biomedical research. Design: An enterprise Grid software infrastructure, called caGrid version 1.0 (caGrid 1.0), has been developed as the core Grid architecture of the NCI-sponsored cancer Biomedical Informatics Grid (caBIG (TM)) program. It is designed to support a wide range of use cases in basic, translational, and clinical research, including 1) discovery, 2) integrated and large-scale data analysis, and 3) coordinated study. Measurements: The caGrid is built as a Grid software infrastructure and leverages Grid computing technologies and the Web Services Resource Framework standards. It provides a set of core services, toolkits for the development and deployment of new community provided services, and application programming interfaces for building client applications. Results: The caGrid 1.0 was released to the caBIG community in December 2006. It is built on open source components and caGrid source code is publicly and freely available under a liberal open source license. The core software, associated tools, and documentation can be downloaded from the following URL: https://cabig.nci.nih. gov/workspaces/Architecture/caGrid. Conclusions: While caGrid 1.0 is designed to address use cases in cancer research, the requirements associated with discovery, analysis and integration of large scale data, and coordinated studies are common in other biomedical fields. In this respect, caGrid 1.0 is the realization of a framework that can benefit the entire biomedical community. C1 [Oster, Scott; Langella, Stephen; Hastings, Shannon; Ervin, David; Kurc, Tahsin; Saltz, Joel] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. [Madduri, Ravi; Siebenlist, Frank; Foster, Ian] Argonne Natl Lab, Div Math & Comp Sci, Argonne, IL 60439 USA. [Covitz, Peter; Shanbhag, Krishnakant] NCI, Ctr Bioinformat, Rockville, MD USA. [Phillips, Joshua] SemanticsBits, Reston, VA USA. RP Kurc, T (reprint author), Ohio State Univ, Dept Biomed Informat, 3184 Graves Hall,333 W 10th Ave, Columbus, OH 43210 USA. EM kurc@bmi.osu.edu FU NHLBI NIH HHS [R01 HL105239, R24 HL085343]; NIBIB NIH HHS [P20 EB000591]; NLM NIH HHS [R01 LM009239]; PHS HHS [79077CBS10] NR 37 TC 59 Z9 59 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 2008 VL 15 IS 2 BP 138 EP 149 DI 10.1197/jamia.M2522 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 273UL UT WOS:000253957100003 PM 18096909 ER PT J AU Bouhaddou, O Warnekar, P Parrish, F Do, N Mandel, J Kilbourne, J Lincoln, MJ AF Bouhaddou, Omar Warnekar, Pradinya Parrish, Fola Do, Nhan Mandel, Jack Kilbourne, John Lincoln, Michael J. TI Exchange of computable patient data between the Department of Veterans Affairs (VA) and the Department of Defense (DoD): Terminology mediation strategy SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID HEALTH INFORMATION INFRASTRUCTURE; CARE AB Complete patient health information that is available where and when it is needed is essential to providers and patients and improves healthcare quality and patient safety. VA and DoD have built on their previous experience in patient data exchange to establish data standards and terminology services to enable real-time bi-directional computable (i.e., encoded) data exchange and achieve semantic interoperability in compliance with recommended national standards and the eGov initiative. The project uses RxNorm, UMLS, and SNOMED CT terminology standards to mediate codified pharmacy and allergy data with greater than 92 and 60 percent success rates respectively. Implementation of the project has been well received by users and is being expanded to multiple joint care sites. Stable and mature standards' mediation strategies, and a close relationship between healthcare institutions and Standards Development Organizations are recommended to achieve and maintain semantic interoperability in a clinical setting. C1 [Bouhaddou, Omar; Warnekar, Pradinya; Do, Nhan; Kilbourne, John] VA Salt Lake City Off Informat, Dept Vet Affairs, Salt Lake City, UT 84113 USA. [Kilbourne, John] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA. [Parrish, Fola; Do, Nhan] Tricare Management Activ, Dept Def, Falls Church, VA USA. [Mandel, Jack] Natl Lib Med, Bethesda, MD USA. RP Bouhaddou, O (reprint author), VA Salt Lake City Off Informat, Dept Vet Affairs, 550 Foothill Dr, Salt Lake City, UT 84113 USA. EM omar.bouhaddou@va.gov NR 26 TC 23 Z9 23 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 2008 VL 15 IS 2 BP 174 EP 183 DI 10.1197/jamia.M2498 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 273UL UT WOS:000253957100007 PM 18096911 ER PT J AU Friends, J Augustine, E Danoff, J AF Friends, John Augustine, Elizabeth Danoff, Jerome TI A comparison of different assessment techniques for measuring foot and ankle volume in healthy adults SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID FIGURE-OF-8 METHOD; RELIABILITY; LIMB; PEROMETER(R); EDEMA AB Background: Foot and ankle volume may be an important measurement for conditions such as lower-extremity trauma or pathologic abnormalities. Water volumetry, often used for this measure, is accurate but not always convenient. We used figure-of-eight tape measurement, prism approximation, foot size measurement (Brannock device), and optoelectric measurement (Perometer) with the standard of water volumetry to compare foot and ankle volumes. Methods: All five techniques were used to measure both the feet and ankles of ten asymptomatic men and women. Reliability was determined by repeating several trials, and validity was determined by comparing all of the techniques with water volumetry (the established standard). Regression equations were found that related each technique to water volumetry. Results: All of the techniques were reliable (intraclass correlation coefficient[3,1] 0.96-0.99). The figure-of-eight technique showed the highest agreement with water Volumetry (R-2 = 0.96), and the prism method, the lowest (R-2 = 0.73). Conclusions: Although any of these techniques should be acceptable for monitoring foot and ankle volume in normal limbs, the figure-of-eight method comes closest to reproducing the results of water volumetry. We believe that this technique would also be best in the presence of foot deformities, but this remains to be studied. C1 [Danoff, Jerome] NIH, Phys Therapy Sect, Dept Rehabil Med, Bethesda, MD 20892 USA. [Friends, John] Providence St Vincent Med Ctr, Rehabil Serv, Portland, OR USA. [Augustine, Elizabeth] Pima Med Inst, Phys Therapy Assistant Program, Tucson, AZ USA. [Danoff, Jerome] George Washington Univ, Washington, DC USA. RP Danoff, J (reprint author), NIH, Phys Therapy Sect, Dept Rehabil Med, Bldg 10-CRC,Room 1-1469,10 Ctr Dr,MSC-1604, Bethesda, MD 20892 USA. EM jdanoff@nih.gov NR 21 TC 8 Z9 9 U1 0 U2 2 PU AMER PODIATRIC MED ASSOC PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD MAR-APR PY 2008 VL 98 IS 2 BP 85 EP 94 PG 10 WC Orthopedics SC Orthopedics GA 278ZC UT WOS:000254323800001 PM 18347115 ER PT J AU Olson, MT Blank, PS Sackett, DL Yergey, AL AF Olson, Matthew T. Blank, Paul S. Sackett, Dan L. Yergey, Alfred L. TI Evaluating reproducibility and similarity of mass and intensity data in complex spectra - Applications to tubulin SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID CANCER-CELL LINES; ALPHA-TUBULIN; SPECTROMETRY; IDENTIFICATION; EXPRESSION; PROTEOMICS; TISSUE; MS/MS AB We present a data processing approach based on the spectral dot product for evaluating spectral similarity and reproducibility. The method introduces 95% confidence intervals on the spectral dot product to evaluate the strength of spectral correlation; it is the only calculation described to date that accounts for both the non-normal sampling distribution of the dot product and the number of peaks the spectra have in common. These measures of spectral similarity allow for the recursive generation of a consensus spectrum, which incorporates the most consistent features from statistically similar replicate spectra. Taking the spectral dot product and 95% confidence intervals between consensus spectra from different samples yields the similarity between these samples. Applying the data analysis scheme to replicates of brain tubulin CNBr peptides enables a robust comparison of tubulin isotype expression and post-translational modification patterns in rat and cow brains. C1 [Olson, Matthew T.; Blank, Paul S.; Yergey, Alfred L.] NICHHD, NIH, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Yergey, AL (reprint author), NICHHD, NIH, Lab Cellular & Mol Biophys, Bldg 10,Room 9D52, Bethesda, MD 20892 USA. EM aly@helix.nih.gov FU Intramural NIH HHS NR 19 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAR PY 2008 VL 19 IS 3 BP 367 EP 374 DI 10.1016/j.jasms.2007.11.012 PG 8 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 278EI UT WOS:000254266400006 PM 18207417 ER PT J AU Iacob, RE Perdivara, I Przybylski, M Tomer, KB AF Iacob, Roxana E. Perdivara, Irina Przybylski, Michael Tomer, Kenneth B. TI Mass spectrometric characterization of glycosylation of hepatitis C virus E2 envelope glycoprotein reveals extended microheterogeneity of N-glycans SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID ELECTROSPRAY-IONIZATION; LINKED OLIGOSACCHARIDES; RECOMBINANT VACCINIA; COMPLEXES; PROTEINS; CELLS; IDENTIFICATION; GLYCOPEPTIDES; LOCALIZATION; CONFORMATION AB Hepatitis C virus (HCV) causes acute and chronic liver disease in humans, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The polyprotein encoded in the HCV genome is co- and post-translationally processed by host and viral peptidases, generating the structural proteins Core, E1, E2, and p7, and five nonstructural proteins. The two envelope proteins E1 and E2 are heavily glycosylated. Studying the glycan moieties attached to the envelope E2 glycoprotein is important because the N-linked glycans on E2 envelope protein are involved in the interaction with some human neutralizing antibodies, and may also have a direct or indirect effect on protein folding. In the present study, we report the mass spectrometric characterization of the glycan moieties attached to the E2 glycoprotein. The mass spectrometric analysis clearly identified the nature, composition, and microheterogeneity of the sugars attached to the E2 glycopeptides. All 11 sites of glycosylation on E2 protein were characterized, and the majority of these sites proved to be occupied by high mannose glycans. However, complex type oligosaccharides, which have not been previously identified, were exclusively observed at two N-linked sites, and their identity and heterogeneity were determined. C1 [Iacob, Roxana E.; Perdivara, Irina; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Perdivara, Irina; Przybylski, Michael] Univ Konstanz, Dept Chem, Analyt Chem Lab, Constance, Germany. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233,MD-F-0-04, Res Triangle Pk, NC 27709 USA. EM tomer@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS [Z01 ES050171-08] NR 53 TC 30 Z9 30 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAR PY 2008 VL 19 IS 3 BP 428 EP 444 DI 10.1016/j.jasms.2007.11.022 PG 17 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 278EI UT WOS:000254266400013 PM 18187336 ER PT J AU Dunson, DB AF Dunson, David B. TI Bivariate binomial spatial modeling of Loa loa prevalence in tropical Africa - Comment SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material ID HIERARCHICAL-MODELS; VARIANCE C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2008 VL 103 IS 481 BP 40 EP 41 DI 10.1198/016214507000001436 PG 2 WC Statistics & Probability SC Mathematics GA 278UJ UT WOS:000254311500010 ER PT J AU Albert, PS Dodd, LE AF Albert, Paul S. Dodd, Lori E. TI On estimating diagnostic accuracy from studies with multiple raters and partial gold standard evaluation SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE diagnostic error; latent class models; misclassification; semilatent class models ID PARTIAL VERIFICATION; BINARY DATA; TESTS; MODELS; SPECIFICITY; SENSITIVITY; ROBUSTNESS; ERROR; BIAS AB We are often interested in estimating sensitivity and specificity of a group of raters or a set of new diagnostic tests in situations in which gold standard evaluation is expensive or invasive. Numerous authors have proposed latent modeling approaches for estimating diagnostic error without a gold standard. Albert and Dodd showed that, when modeling without a gold standard, estimates of diagnostic error can be biased when the dependence structure between tests is misspecified. In addition, they showed that choosing between different models for this dependence structure is difficult in most practical situations. While these results caution against using these latent class models, the difficulties of obtaining gold standard verification remain a practical reality. We extend two classes of models to provide a compromise that collects gold standard information on a subset of subjects but incorporates information from both the verified and nonverified subjects during estimation. We examine the robustness of diagnostic error estimation with this approach and show that choosing between competing models is easier in this context. In our analytic work and simulations, we consider situations in which verification is completely at random as well as settings in which the probability of verification depends on the actual test results. We apply our methodological work to a study designed to estimate the diagnostic error of digital radiography for gastric cancer. C1 [Albert, Paul S.; Dodd, Lori E.] NCI, Div Canc Treatment & Diag, Biometr Branch, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Div Canc Treatment & Diag, Biometr Branch, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov; doddl@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 22 TC 19 Z9 19 U1 0 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2008 VL 103 IS 481 BP 61 EP 73 DI 10.1198/016214507000000329 PG 13 WC Statistics & Probability SC Mathematics GA 278UJ UT WOS:000254311500014 PM 19802353 ER PT J AU Inoue, LYT Etzioni, R Morrell, C Muller, P AF Inoue, Lurdes Y. T. Etzioni, Ruth Morrell, Christopher Mueller, Peter TI Modeling disease progression with longitudinal markers SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE disease progression; latent variables; longitudinal response; Markov chain Monte Carlo methods; natural history model; prostate-specific antigen ID PROSTATE-SPECIFIC ANTIGEN; HIV-INFECTION; NATURAL-HISTORY; COLORECTAL-CANCER; MARKOV-MODELS; AIDS EPIDEMIC; UNITED-STATES; CARCINOGENESIS; PROGRAMS; SURVIVAL AB In this article we propose a Bayesian natural history model for disease progression based on the joint modeling of longitudinal biomarker levels, age at clinical detection of disease, and disease status at diagnosis. We establish a link between the longitudinal responses and the natural history of the disease by using an underlying latent disease process that describes the onset of the disease and models the transition to an advanced stage of the disease as dependent on the biomarker levels. We apply our model to data from the Baltimore Longitudinal Study of Aging on prostate-specific antigen to investigate the natural history of prostate cancer. C1 [Inoue, Lurdes Y. T.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Etzioni, Ruth] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Morrell, Christopher] Loyola Coll, Dept Math Sci, Baltimore, MD 21201 USA. [Morrell, Christopher] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Mueller, Peter] Univ Texas Dallas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Inoue, LYT (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM linoue@u.washington.edu FU NCI NIH HHS [R01 CA100778, U01 CA088160] NR 44 TC 8 Z9 9 U1 1 U2 6 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2008 VL 103 IS 481 BP 259 EP 270 DI 10.1198/016214507000000356 PG 12 WC Statistics & Probability SC Mathematics GA 278UJ UT WOS:000254311500030 PM 24453387 ER PT J AU Dunson, DB Xue, Y Carin, L AF Dunson, David B. Xue, Ya Carin, Lawrence TI The matrix stick-breaking process: Flexible Bayes meta-analysis SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE dependent partition; Dirichlet process; hierarchical model; local clustering; mixture model; nonparametric Bayes; random effects ID DIRICHLET PROCESSES; MODELS; PRIORS; DISTRIBUTIONS AB In analyzing data from multiple related studies, it often is of interest to borrow information across studies and to cluster similar studies. Although parametric hierarchical models are commonly used, of concern is sensitivity to the form chosen for the random-effects distribution. A Dirichlet process (DP) prior can allow the distribution to be unknown, while clustering studies; however, the DP does not allow local clustering of studies with respect to a subset of the coefficients without making independence assumptions. Motivated by this problem, we propose a matrix stick-breaking process (MSBP) as a prior for a matrix of random probability measures. Properties of the MSBP are considered, and methods are developed for posterior computation using Markov chain Monte Carlo. Using the MSBP as a prior for a matrix of study-specific regression coefficients, we demonstrate advantages over parametric modeling in simulated examples. The methods are further illustrated using a multinational uterotrophic bioassay study. C1 [Dunson, David B.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Xue, Ya] GE Global Res, Ind Artificial Intelligence Lab, Niskayuna, NY 12309 USA. [Carin, Lawrence] Duke Univ, Pratt Sch Engn, Dept Elect & Comp Engn, Durham, NC 27708 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson@stat.duke.edu; yx10@ee.duke.edu; Icarin@ee.duke.edu NR 31 TC 33 Z9 33 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2008 VL 103 IS 481 BP 317 EP 327 DI 10.1198/016214507000001364 PG 11 WC Statistics & Probability SC Mathematics GA 278UJ UT WOS:000254311500036 ER PT J AU Silberberg, A Roma, PG Huntsberry, ME Warren-Boulton, FR Sakagam, T Ruggiero, AM Suomi, SJ AF Silberberg, Alan Roma, Peter G. Huntsberry, Mary E. Warren-Boulton, Frederick R. Sakagam, Takayuki Ruggiero, Angela M. Suomi, Stephen J. TI On loss aversion in Capuchin monkeys SO JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR LA English DT Article DE loss aversion; token exchange; reversed contingency; delay of reinforcement; prospect theory; choice; monkeys; humans ID CHOICE; RISK; REINFORCEMENT; RESPONSES; BEHAVIOR AB Chen, Lakshminarayanan, and Santos (2006) claim to show in three choice experiments that monkeys react rationally to price and wealth shocks, but, when faced with gambles, display hallmark, human-like biases that include loss aversion. We present three experiments with monkeys and humans consistent with a reinterpretation of their data that attributes their results not to loss aversion, but to differences between choice alternatives in delay of reinforcement. C1 [Silberberg, Alan; Roma, Peter G.; Huntsberry, Mary E.] American Univ, Dept Psychol, Washington, DC 20016 USA. [Sakagam, Takayuki] Keio Univ, Tokyo 108, Japan. [Ruggiero, Angela M.; Suomi, Stephen J.] NICHHD, Bethesda, MD 20892 USA. RP Silberberg, A (reprint author), American Univ, Dept Psychol, Washington, DC 20016 USA. EM asilber@ametican.edu FU Intramural NIH HHS NR 20 TC 18 Z9 19 U1 0 U2 5 PU SOC EXP ANALYSIS BEHAVIOR INC PI BLOOMINGTON PA INDIANA UNIV DEPT PSYCHOLOGY, BLOOMINGTON, IN 47405 USA SN 0022-5002 J9 J EXP ANAL BEHAV JI J. Exp. Anal. Behav. PD MAR PY 2008 VL 89 IS 2 BP 145 EP 155 DI 10.1901/jeab.2008-89-145 PG 11 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental SC Psychology; Behavioral Sciences GA 273LK UT WOS:000253931900001 PM 18422015 ER PT J AU Pinsky, PF Ford, M Gamito, E Higgins, D Jenkins, V Lamerato, L Tenorio, S Marcus, PM Gohagan, JK AF Pinsky, Paul F. Ford, Marvella Gamito, Eduard Higgins, Darlene Jenkins, Victoria Lamerato, Lois Tenorio, Sally Marcus, Pamela M. Gohagan, John K. TI Enrollment of racial and ethnic minorities in the prostate, lung, colorectal and ovarian cancer screening trial SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE African Americans; Lathes; cancer; clinical investigation; screening ID AFRICAN-AMERICAN MEN; PREVENTION TRIAL; RECRUITMENT; DISEASE AB Background: minority populations in the United States, especially blacks and Hispanics, are generally underrepresented among participants in clinical trials. Here, we report the experience of enrolling ethnic minorities in a large cancer screening trial. Methods: The Prostate, Colorectal, Lung and Ovarian (PLCO) Cancer Screening Trial is a multicenter randomized trial designed to evaluate the effectiveness of screening for the PLCO cancers. Subjects were recruited at 10 U.S. centers between 1993 and 2001. One screening center had a major special recruitment effort for blacks and another center had a major special recruitment effort for Hispanics. Results: Among almost 155,000 subjects enrolled in PLCO, minority enrollment was as follows: black (5.0%), Hispanic (1.8%) and Asian (3.6%). This compares to an age-eligible population in the combined catchment areas of the PLCO centers that was 14.0% black, 2.9% Hispanic and 5.4% Asian, and an age-eligible population across the U.S. that was 9.5% black, 6.5% Hispanic and 3.0% Asian. About half (45%) of Hispanics were recruited at the center with the special Hispanic recruitment effort. Seventy percent of blacks were recruited at two centers; the one with the major special recruitment effort and a center in Detroit whose catchment area was 20% black among age-eligibles. Blacks, Hispanics and (non-Hispanic) whites were all more highly educated, less likely to currently smoke and more likely to get regular exercise than their counterparts in the general population. Conclusion: Significant efforts were made to recruit racial/ethnic minorities into PLCO, and these efforts resulted in enrollment levels that were comparable to those seen in many recent cancer screening or prevention trials. Blacks and Hispanics were nonetheless underrepresented in PLCO compared to their levels among age-eligibles in the overall U.S. population or in the aggregate PLCO catchment areas. C1 [Ford, Marvella; Lamerato, Lois] Henry Ford Hlth Syst, Detroit, MI USA. [Pinsky, Paul F.; Marcus, Pamela M.; Gohagan, John K.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. [Gamito, Eduard; Tenorio, Sally] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Higgins, Darlene] Univ Alabama, Birmingham, AL USA. [Jenkins, Victoria] Pacific Hlth Res Inst, Honolulu, HI USA. RP Pinsky, PF (reprint author), 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 15 TC 34 Z9 34 U1 0 U2 3 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD MAR PY 2008 VL 100 IS 3 BP 291 EP 298 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 282ED UT WOS:000254549500003 PM 18390022 ER PT J AU Feldman, EL Cornblath, DR Porter, J Dworkin, R Scherer, S AF Feldman, Eva L. Cornblath, David R. Porter, John Dworkin, Robert Scherer, Steven CA Attendeese NIH Peripheral Neuropat TI National Institute of Neurological Disorders and Stroke (NINDS): Advances in understanding and treating neuropathy, 24-25 October 2006; Bethesda, Maryland - Meeting summary SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Article DE biomarkers; clinical trials; demyelination; electrophysiology; intraepidermal nerve fiber density; Schwann cell; pain; Wallerian degeneration AB National Institute of Neurological Disorders and Stroke sponsored a meeting to explore the current status of basic and clinical research in peripheral neurobiology and clinical neuropathy. The goal of the workshop was to identify areas where additional research could lead to the development of new therapeutics in the next 5 years. Participants discussed the current understanding of disease mechanisms of axonal and demyelinating neuropathies, existing techniques in research, disease biomarkers, and assessment of neuropathy. Painful neuropathies were discussed at the basic scientific and clinical levels in relation to new insights into etiology and treatment. The meeting concluded with a discussion on therapeutic development in neuropathy and the need for a unified approach to multicenter trials. Short-term goals of the workshop were to form a working group for neuropathy, the Peripheral Neuropathy Study Group, and to translate new scientific findings into therapies and complete clinical trials. C1 [Feldman, Eva L.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Cornblath, David R.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Porter, John] NINDS, NIH, Rockville, MD USA. [Dworkin, Robert] Univ Rochester, Dept Anesthesiol, Rochester, NY USA. [Scherer, Steven] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Feldman, EL (reprint author), Univ Michigan, Dept Neurol, 5017 Basic Sci Res Bldg,109 Zina Pitcher Rd, Ann Arbor, MI 48109 USA. EM efeldman@umich.edu FU NINDS NIH HHS [R01 NS055284-02, R01 NS055284, R01 NS043174-07, R01 NS043174] NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD MAR PY 2008 VL 13 IS 1 BP 1 EP 6 DI 10.1111/j.1529-8027.2008.00154.x PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 285TA UT WOS:000254797900001 PM 18346227 ER PT J AU Collins, PL Graham, BS AF Collins, Peter L. Graham, Barney S. TI Viral and host factors in human respiratory syncytial virus pathogenesis SO JOURNAL OF VIROLOGY LA English DT Review ID SMALL HYDROPHOBIC PROTEIN; CELL-MEDIATED-IMMUNITY; OBSTRUCTIVE PULMONARY-DISEASE; ATTACHMENT G GLYCOPROTEIN; FORMALIN-INACTIVATED RSV; MYELOID DENDRITIC CELLS; AIRWAY EPITHELIAL-CELLS; CYSTEINE-RICH REGION; TOLL-LIKE RECEPTOR-4; CD4 T-CELLS C1 [Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. [Graham, Barney S.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, NIH, 50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov FU Intramural NIH HHS NR 167 TC 199 Z9 203 U1 4 U2 29 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 5 BP 2040 EP 2055 DI 10.1128/JVI.01625-07 PG 16 WC Virology SC Virology GA 267AR UT WOS:000253481000001 PM 17928346 ER PT J AU Luttge, BG Shehu-Xhilaga, M Demirov, DG Adamson, CS Soheilian, F Nagashima, K Stephen, AG Fisher, RJ Freed, EO AF Luttge, Benjamin G. Shehu-Xhilaga, Miranda Demirov, Dimiter G. Adamson, Catherine S. Soheilian, Ferri Nagashima, Kunio Stephen, Andrew G. Fisher, Robert J. Freed, Eric O. TI 3 molecular characterization of feline immunodeficiency virus budding SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS-ANEMIA VIRUS; ROUS-SARCOMA-VIRUS; PROTEIN-SORTING PATHWAY; TSG101 UEV DOMAIN; GAG PROTEIN; MULTIVESICULAR BODY; PARTICLE RELEASE; ESCRT-I; TRANSGENE EXPRESSION; ASSEMBLY DOMAIN AB Infection of domestic cats with feline immunodeficiency virus (FIV) is an important model system for studying human immunodeficiency virus type 1 (HIV-1) infection due to numerous similarities in pathogenesis induced by these two lentiviruses. However, many molecular aspects of FIV replication remain poorly understood. It is well established that retroviruses use short peptide motifs in Gag, known as late domains, to usurp cellular endosomal sorting machinery and promote virus release from infected cells. For example, the Pro-Thr/Ser-Ala-Pro [P(T/S)AP] motif of HIV-1 Gag interacts directly with Tsg101, a component of the endosomal sorting complex required for transport I (ESCRT-I). A Tyr-Pro-Asp-Leu (YPDL) motif in equine infectious anemia virus (EIAV), and a related sequence in HIV-1, bind the endosomal sorting factor Alix. In this study we sought to identify and characterize FIV late domain(s) and elucidate cellular machinery involved in FIV release. We determined that mutagenesis of a PSAP motif in FIV Gag, small interfering RNA-mediated knockdown of Tsg101 expression, and overexpression of a P(T/S)AP-binding fragment of Tsg101 (TSG-5') each inhibited FIV release. We also observed direct binding of FIV Gag peptides to Tsg101. In contrast, mutagenesis of a potential Alix-binding motif in FIV Gag did not affect FIV release. Similarly, expression of the HIV-1/EIAV Gag-binding domain of Alix (Alix-V) did not disrupt FIV budding, and FIV Gag peptides showed no affinity for Alix-V. Our data demonstrate that FIV relies predominantly on a Tsg101-binding PSAP motif in the C terminus of Gag to promote virus release in HeLa cells, and this budding mechanism is highly conserved in feline cells. C1 [Luttge, Benjamin G.; Shehu-Xhilaga, Miranda; Demirov, Dimiter G.; Adamson, Catherine S.; Freed, Eric O.] NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. [Soheilian, Ferri; Nagashima, Kunio] NCI, SAIC Frederick, Image Anal Lab, Adv Technol Program, Frederick, MD 21702 USA. [Stephen, Andrew G.; Fisher, Robert J.] NCI, SAIC Frederick, Prot Chem Lab, Adv Technol Program, Frederick, MD 21702 USA. RP Freed, EO (reprint author), NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Bldg 535,Rm 108, Frederick, MD 21702 USA. EM efreed@mail.nih.gov RI Fisher, Robert/B-1431-2009 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 76 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 5 BP 2106 EP 2119 DI 10.1128/JVI.02337-07 PG 14 WC Virology SC Virology GA 267AR UT WOS:000253481000007 PM 18094166 ER PT J AU Lilja, AE Chang, WLW Barry, PA Becerra, SP Shenkl, TE AF Lilja, Anders E. Chang, W. L. William Barry, Peter A. Becerra, S. Patricia Shenkl, Thomas E. TI Functional genetic analysis of rhesus cytomegalovirus: Rh01 is an epithelial cell tropism factor SO JOURNAL OF VIROLOGY LA English DT Article ID RIBONUCLEOTIDE REDUCTASE HOMOLOG; BACTERIAL ARTIFICIAL CHROMOSOME; MURINE CYTOMEGALOVIRUS; MUTATIONAL ANALYSIS; ENDOTHELIAL-CELLS; UL131-128 GENES; GENOME; REPLICATION; INFECTION; PROTEIN AB Rhesus cytomegalovirus (RhCMV) is an emerging model for human cytomegalovirus (HCMV) pathogenesis that facilitates experimental CMV infection of a natural primate host closely related to humans. We have generated a library of RhCMV mutants with lesions in genes whose HCMV orthologues have been characterized as nonessential for replication in human fibroblasts, and we characterized their replication in rhesus fibroblasts and epithelial cells. The RhCMV mutants grew well in fibroblasts, as predicted by earlier studies with HCMV. However, mutations in four genes caused replication defects in rhesus retinal pigment epithelial cells: Rh01 (an HCMV TRL1 orthologue), Rh159 (HCMV UL148), Rh160 (HCMV UL132), and Rh203 (HCMV US22). Growth of the Rh01-deficient mutant was examined in detail. After entry into epithelial cells, the mutant expressed representative viral proteins, accumulated viral DNA, and generated infectious virus, but it failed to spread efficiently. We conclude that Rh01 is a cell tropism determinant that has the potential to dramatically affect virus spread and pathogenesis. C1 [Lilja, Anders E.; Shenkl, Thomas E.] Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA. [Chang, W. L. William; Barry, Peter A.] Univ Calif Davis, Ctr Comprat Med, Davis, CA 95616 USA. [Barry, Peter A.] Univ Calif Davis, Dept Med Pathol, Davis, CA 95616 USA. [Becerra, S. Patricia] NEI, NIH, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. RP Lilja, AE (reprint author), Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA. EM alilja@grinceton.edu FU Intramural NIH HHS; NCI NIH HHS [R01 CA082396, CA-082396]; NIAID NIH HHS [R01 AI054430, AI-54430] NR 42 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 5 BP 2170 EP 2181 DI 10.1128/JVI.02316-07 PG 12 WC Virology SC Virology GA 267AR UT WOS:000253481000013 PM 18094178 ER PT J AU Chukkapalli, V Hogue, IB Boyko, V Hu, WS Ono, A AF Chukkapalli, Vineela Hogue, Ian B. Boyko, Vitaly Hu, Wei-Shau Ono, Akira TI Interaction between the human immunodeficiency virus type 1 Gag matrix domain and phosphatidylinositol-(4,5)-bisphosphate is essential for efficient Gag membrane binding SO JOURNAL OF VIROLOGY LA English DT Article ID N-TERMINAL REGION; CELL-FREE SYSTEM; PLASMA-MEMBRANE; HIV-1 GAG; HUMAN-ERYTHROCYTES; MYRISTYL SWITCH; LIPID RAFTS; PHOSPHOINOSITIDE METABOLISM; ELECTROSTATIC INTERACTIONS; FLUORESCENT PROTEIN AB Human immunodeficiency virus type 1 (HIV-1) particle assembly mediated by the viral structural protein Gag occurs predominantly on the plasma membrane (PM). Although it is known that the matrix (MA) domain of Gag plays a major role in PM localization, molecular mechanisms that determine the location of assembly remain to be elucidated. We observed previously that overexpression of polyphosphoinositide 5-phosphatase IV (5ptaseIV) that depletes PM phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P-2] impairs virus particle production and redirects processed Gag to intracellular compartments. In this study, we examined the impact of PI(4,5)P-2 depletion on the subcellular localization of the entire Gag population using Gag-fluorescent protein chimeras. Upon 5ptaseIV overexpression, in addition to perinuclear localization, Gag also showed a hazy cytosolic signal, suggesting that PI(4,5)P-2 depletion impairs Gag membrane binding. Indeed, Gag was less membrane bound in PI(4,5)P-2-depleted cells, as assessed by biochemical analysis. These observations are consistent with the hypothesis that Gag interacts with PI(4,5)P2. To examine a putative Gag interaction with PI(4,5)P-2, we developed an in vitro binding assay using full-length myristoylated Gag and liposome-associated PI(4,5)P-2. Using this assay, we observed that PI(4,5)P-2 significantly enhances liposome binding of wild-type Gag. In contrast, a Gag derivative lacking MA did not require PI(4,5)P-2 for efficient liposome binding. To analyze the involvement of MA in PI(4,5)P-2 binding further, we examined MA basic amino acid substitution mutants. These mutants, previously shown to localize in perinuclear compartments, bound PI(4,5)P-2-containing liposomes weakly. Altogether, these results indicate that HIV-1 Gag binds PI(4,5)P-2 on the membrane and that the MA basic domain mediates this interaction. C1 [Chukkapalli, Vineela; Hogue, Ian B.; Ono, Akira] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Boyko, Vitaly; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Ono, A (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, 1150 W Med Ctr Dr,Room 5736A, Ann Arbor, MI 48109 USA. EM akiraono@umich.edu OI Ono, Akira/0000-0001-7841-851X FU Intramural NIH HHS; NIAID NIH HHS [R01 AI071727]; NIGMS NIH HHS [T32 GM007544] NR 94 TC 130 Z9 131 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 5 BP 2405 EP 2417 DI 10.1128/JVI.01614-07 PG 13 WC Virology SC Virology GA 267AR UT WOS:000253481000036 PM 18094158 ER PT J AU Wong, S Zhi, N Filippone, C Keyvanfar, K Kajigaya, S Brown, KE Young, NS AF Wong, Susan Zhi, Ning Filippone, Claudia Keyvanfar, Keyvan Kajigaya, Sachiko Brown, Kevin E. Young, Neal S. TI Ex vivo-generated CD36(+) erythroid progenitors are highly permissive to human parvovirus B19 replication SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-BONE-MARROW; IN-VITRO; CELL-LINE; PERIPHERAL-BLOOD; HEMATOPOIETIC-CELLS; ANTIGEN-EXPRESSION; FETAL LIVER; P-ANTIGEN; INVITRO; DIFFERENTIATION AB The pathogenic parvovirus B19 (B19V) has an extreme tropism for human erythroid progenitor cells. In vitro, only a few erythroid leukemic cell lines (JK-1 and KU812Ep6) or megakaryoblastoid cell lines (UT7/Epo and UT7/Epo-S1) with erythroid characteristics support B19V replication, but these cells are only semipermissive. By using recent advances in generating large numbers of human erythroid progenitor cells (EPCs) ex vivo from hematopoietic stem cells (HSCs), we produced a pure population of CD36(+) EPCs expanded and differentiated from CD34(+) HSCs and assessed the CD36(+) EPCs for their permissiveness to B19V infection. Over more than 3 weeks, cells grown in serum-free medium expanded more than 800,000-fold, and 87 to 96% of the CD36+ EPCs were positive for globoside, the cellular receptor for B19V. Immunofluorescence (IF) staining showed that about 77% of the CD36(+) EPCs were positive for B19V infection, while about 9% of UT7/Epo-S1 cells were B19V positive. Viral DNA detected by real-time PCR increased by more than 3 logs in CD36(+) EPCs; the increase was 1 log in UT7/Epo-S1 cells. Due to the extensive permissivity of CD36(+) EPCs, we significantly improved the sensitivity of detection of infectious B19V by real-time reverse transcription-PCR and IF staining 100- and 1,000-fold, respectively, which is greater than the sensitivity of UT7/Epo-S1 cell-based methods. This is the first description of an ex vivo method to produce large numbers of EPCs that are highly permissive to B19V infection and replication, offering a cellular system that mimics in vivo infection with this pathogenic human virus. C1 [Wong, Susan; Zhi, Ning; Filippone, Claudia; Keyvanfar, Keyvan; Kajigaya, Sachiko; Brown, Kevin E.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Zhi, N (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-CRC,Rm 3E-5216,10 Ctr Dr, Bethesda, MD 20892 USA. EM zhin@nhlbi.nih.gov FU Intramural NIH HHS NR 41 TC 43 Z9 45 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 5 BP 2470 EP 2476 DI 10.1128/JVI.02247-07 PG 7 WC Virology SC Virology GA 267AR UT WOS:000253481000042 PM 18160440 ER PT J AU Larsen, LSZ Beliakova-Bethell, N Bilanchone, V Zhang, M Lamsa, A DaSilva, R Hatfield, GW Nagashima, K Sandmeyer, S AF Larsen, Liza S. Z. Beliakova-Bethell, Nadejda Bilanchone, Virginia Zhang, Min Lamsa, Anne DaSilva, Rhonda Hatfield, G. Wesley Nagashima, Kunio Sandmeyer, Suzanne TI Ty3 nucleocapsid controls localization of particle assembly SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA-VIRUS; REPEAT-CONTAINING RETROTRANSPOSON; NUCLEIC-ACID BINDING; SYNTHESIS IN-VIVO; CYS-HIS MOTIF; HIV-1 GAG; BASIC RESIDUES; ZINC-FINGER; INTRACELLULAR TRAFFICKING AB Expression of the budding yeast retrotransposon Ty3 results in production of viruslike particles (VLPs) and retrotransposition. The Ty3 major structural protein, Gaga, similar to retrovirus Gag, is processed into capsid, spacer, and nucleocapsid (NC) during VLP maturation. The 57-amino-acid Ty3 NC protein has 17 basic amino acids and contains one copy of the CX2CX4HX4C zinc-binding motif found in retrovirus NC proteins. Ty3 RNA, protein, and VLPs accumulate in clusters associated with RNA processing bodies (P bodies). This study investigated the role of the NC domain in Ty3-P body clustering and VLP assembly. Fifteen Ty3 NC Ala substitution and deletion mutants were examined using transposition, immunoblot, RNA protection, cDNA synthesis, and multimerization assays. Localization of Ty3 proteins and VLPs was characterized microscopically. Substitutions of each of the conserved residues of the zinc-binding motif resulted in the loss of Ty3 RNA packaging. Substitution of the first two of four conserved residues in this motif caused the loss of Ty3 RNA and protein clustering with P bodies and disrupted particle formation. NC was shown to be a mediator of formation of Ty3 RNA foci and association of Ty3 RNA and protein with P bodies. Mutations that disrupted these NC functions resulted in various degrees of Gaga nuclear localization and a spectrum of different particle states. Our findings are consistent with the model that Ty3 assembly is associated with P-body components. We hypothesize that the NC domain acts as a molecular switch to control Gaga conformational states that affect both assembly and localization. C1 [Larsen, Liza S. Z.; Beliakova-Bethell, Nadejda; Bilanchone, Virginia; Zhang, Min; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. [Larsen, Liza S. Z.; Hatfield, G. Wesley; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. [Larsen, Liza S. Z.; Hatfield, G. Wesley; Sandmeyer, Suzanne] Univ Calif Irvine, Inst Genom & Bioinformat, Irvine, CA 92697 USA. [DaSilva, Rhonda; Nagashima, Kunio] SAIC Frederick Inc, NCI, Image Anal Lab, Frederick, MD USA. [Hatfield, G. Wesley] CODA Genom Inc, Laguna Hills, CA USA. RP Sandmeyer, S (reprint author), Univ Calif Irvine, Dept Biol Chem, D240 Med Sci 1, Irvine, CA 92697 USA. EM sbsandme@uci.edu RI zhang, min/C-6300-2011 FU NCI NIH HHS [N01CO12400, N01-CO-12400, P30 CA062203]; NIAID NIH HHS [T32 AI007319, T32 AI07319]; NIGMS NIH HHS [GM68903, R01 GM033281, R01 GM068903, GM33281] NR 78 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 5 BP 2501 EP 2514 DI 10.1128/JVI.01814-07 PG 14 WC Virology SC Virology GA 267AR UT WOS:000253481000046 PM 18094177 ER PT J AU McDonald, SM Patton, JT AF McDonald, Sarah M. Patton, John T. TI Molecular characterization of a subgroup specificity associated with the rotavirus inner capsid protein VP2 SO JOURNAL OF VIROLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; MONOCLONAL-ANTIBODIES; ENZYME-IMMUNOASSAY; RNA; NEUTRALIZATION; ANTIGENS; CORE; IDENTIFICATION; VISUALIZATION; EPIDEMIOLOGY AB Group A rotaviruses are classified into serotypes, based on the reactivity pattern of neutralizing antibodies to VP4 and VP7, as well as into subgroups (SGs), based on non-neutralizing antibodies directed against VP6. The inner capsid protein (VP2) has also been described as a SG antigen; however, little is known regarding the molecular determinants of VP2 SG specificity. In this study, we characterize VP2 SGs by correlating genetic markers with the immunoreactivity of the SG-specific monoclonal antibody (YO-60). Our results show that VP2 proteins similar in sequence to that of the prototypic human strain Wa are recognized by YO-60, classifying them as VP2 SG-II. In contrast, proteins not bound by YO-60 are similar to those of human strains DS-1 or AU-1 and represent VP2 SG-I. Using a mutagenesis approach, we identified residues that determine recognition by either YO-60 or the group A-specific VP2 monoclonal antibody (6E8). We found that YO-60 binds to a conformationally dependent epitope that includes Wa VP2 residue M328. The epitope for 6E8 is also contingent upon VP2 conformation and resides within a single region of the protein (Wa VP2 residues A440 to T530). Using a high-resolution structure of bovine rotavirus double-layered particles, we predicted these epitopes to be spatially distinct from each other and located on opposite surfaces of VP2. This study reveals the extent of genetic variation among group A rotavirus VP2 proteins and illuminates the molecular basis for a previously described SG specificity associated with the rotavirus inner capsid protein. C1 [McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, Natl Inst Hlth, 50 S Dr,MSC 8026,Rm 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 FU Intramural NIH HHS NR 37 TC 15 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 6 BP 2752 EP 2764 DI 10.1128/JVI.02492-07 PG 13 WC Virology SC Virology GA 270AB UT WOS:000253691000016 PM 18216104 ER PT J AU Majerciak, V Yamanegi, K Allemand, E Kruhlak, M Krainer, AR Zheng, ZM AF Majerciak, Vladimir Yamanegi, Koji Allemand, Eric Kruhlak, Michael Krainer, Adrian R. Zheng, Zhi-Ming TI Kaposi's sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing SO JOURNAL OF VIROLOGY LA English DT Article ID PRE-MESSENGER-RNA; PRIMARY EFFUSION LYMPHOMA; BINDING PROTEIN-ALPHA; VIRUS SM PROTEIN; MULTICENTRIC CASTLEMANS-DISEASE; REPLICATION-ASSOCIATED PROTEIN; NUCLEAR EXPORT SIGNAL; CELL-CYCLE ARREST; K-BZIP; TRANSCRIPTIONAL ACTIVATION AB Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 facilitates the expression of both intronless viral ORF59 genes and intron-containing viral K8 and K8.1 genes (V. Majerciak, N. Pripuzova, J. P. McCoy, S. J. Gao, and Z. M. Zheng, J. Virol. 81:1062-1071, 2007). In this study, we showed that disruption of ORF57 in a KSHV genome led to increased accumulation of ORF50 and K8 pre-mRNAs and reduced expression of ORF50 and K-bZIP proteins but had no effect on latency-associated nuclear antigen (LANA). Cotransfection of ORF57 and K8 beta cDNA, which retains a suboptimal intron of K8 pre-mRNA due to alternative splicing, promoted RNA splicing of K8 beta and production of K8(x (K-bZIP). Although Epstein-Barr virus EB2, a closely related homolog of ORF57, had a similar activity in the cotransfection assays, herpes simplex virus type 1 ICP27 was inactive. This enhancement of RNA splicing by ORF57 correlates with the intact N-terminal nuclear localization signal motifs of ORF57 and takes place in the absence of other viral proteins. In activated KSHV-infected B cells, KSHV ORF57 partially colocalizes with splicing factors in nuclear speckles and assembles into spliceosomal complexes in association with low-abundance viral ORF50 and K8 pre-mRNAs and essential splicing components. The association of ORF57 with snRNAs occurs by ORF57-Sm protein interaction. We also found that ORF57 binds K8 beta pre-mRNAs in vitro in the presence of nuclear extracts. Collectively our data indicate that KSHV ORF57 functions as a novel splicing factor in the spliceosome-mediated splicing of viral RNA transcripts. C1 [Majerciak, Vladimir; Yamanegi, Koji; Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kruhlak, Michael] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Allemand, Eric; Krainer, Adrian R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Rm 6N106,MSC 1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov RI allemand, 131271/G-7303-2011; OI Krainer, Adrian/0000-0001-9024-9501 FU Intramural NIH HHS; NCI NIH HHS [CA13106, P01 CA013106] NR 75 TC 38 Z9 38 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 6 BP 2792 EP 2801 DI 10.1128/JVI.01856-07 PG 10 WC Virology SC Virology GA 270AB UT WOS:000253691000020 PM 18184716 ER PT J AU Pierro, DJ Powers, EL Olson, KE AF Pierro, Dennis J. Powers, Erik L. Olson, Ken E. TI Genetic determinants of sindbis virus mosquito infection are associated with a highly conserved alphavirus and flavivirus envelope sequence SO JOURNAL OF VIROLOGY LA English DT Article ID YELLOW-FEVER VIRUS; GREEN FLUORESCENT PROTEIN; BORNE ENCEPHALITIS-VIRUS; SINGLE NUCLEOTIDE CHANGE; AMINO-ACID SUBSTITUTION; PER-OS INFECTION; AEDES-AEGYPTI; E2 GLYCOPROTEIN; MUTATIONAL ANALYSIS; ANTIGENIC SITE AB Wild-type Sindbis virus (SINV) strain MRE16 efficiently infects Aedes aegypti midgut epithelia] cells (MEC), but laboratory-derived neurovirulent SINV strain TE/5'2J infects MEC poorly. SINV determinants for MEC infection have been localized to the E2 glycoprotein. The E2 amino acid sequences of MRE16 and TE/5'2J differ at 60 residue sites. To identify the genetic determinants of MEC infection of MRE16, the TE/5'2J virus genome was altered to contain either domain chimeras or more focused nucleotide substitutions of MRE16. The growth patterns of derived viruses in cell culture were determined, as were the midgut infection rates (MIR) in A. aegypti mosquitoes. The results showed that substitutions of MRE16 E2 aa 95 to 96 and 116 to 119 into the TE/5'2J virus increased MIR both independently and in combination with each other. In addition, a unique PPF/.GDS amino acid motif was located between these two sites that was found to be a highly conserved sequence among alphaviruses and flaviviruses but not other arboviruses. C1 [Pierro, Dennis J.; Powers, Erik L.; Olson, Ken E.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Arthropod Borne & Infect Dis Lab, Ft Collins, CO 80523 USA. RP Pierro, DJ (reprint author), NIAID, NIH, Infect Dis Lab, Room 6132,50 S Dr, Bethesda, MD 20892 USA. EM pierrod@niaid.nih.gov FU NIAID NIH HHS [AI046435, R01 AI046435-06, R01 AI046435, R01 AI046435-04A1, R01 AI046435-05] NR 57 TC 17 Z9 17 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2008 VL 82 IS 6 BP 2966 EP 2974 DI 10.1128/JVI.02060-07 PG 9 WC Virology SC Virology GA 270AB UT WOS:000253691000035 PM 18160430 ER PT J AU Wieland, D Ferrucci, L AF Wieland, Darryl Ferrucci, Luigi TI Multidimensional geriatric assessment: Back to the future SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID LONG-TERM-CARE; HOME-CARE; MANAGEMENT; COMMUNITY; TRIAL; IMPACT; MODEL C1 [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Wieland, Darryl] Palmetto Hlth Richland, Geriatr Serv, Columbia, SC 29203 USA. RP Wieland, D (reprint author), Palmetto Hlth Richland, Geriatr Serv, 3010 Farrow Rd,300, Columbia, SC 29203 USA. EM darryl.wieland@palmettohealth.org FU Intramural NIH HHS [Z99 AG999999] NR 20 TC 13 Z9 15 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2008 VL 63 IS 3 BP 272 EP 274 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 301FX UT WOS:000255882900006 PM 18375875 ER PT J AU Lockenhoff, CE Costa, PT Lane, RD AF Loeckenhoff, Corinna E. Costa, Paul T., Jr. Lane, Richard D. TI Age differences in descriptions of emotional experiences in oneself and others SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Age-related differences; Emotional aging; emotional experience ID ADULT LIFE-SPAN; SOCIOEMOTIONAL SELECTIVITY; CHINESE-AMERICANS; NEGATIVE AFFECT; ALEXITHYMIA; MEMORY; RECOGNITION; COMPLEXITY; HETEROGENEITY; OPTIMIZATION AB We analyzed language use to examine age differences in people's representations of their own emotions as compared with those of others. Participants (N = 365, aged 18-85 years, M = 42.8, SD = 19.2) read hypothetical emotion-eliciting scenarios and described how they themselves and the social partners involved in the scenarios would feel. Compared with those of younger adults, older adults' descriptions involved a higher frequency of positive and a lower frequency of negative emotions. Older adults were also more likely to describe a co-occurrence of positive and negative emotions, but less likely to describe the simultaneous experience of multiple negative emotions. Age effects showed similar patterns for participants' descriptions of their own emotions as compared with those of others. We discuss the implications for theoretical accounts of emotional aging. C1 [Loeckenhoff, Corinna E.; Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. [Lane, Richard D.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. RP Lockenhoff, CE (reprint author), Biomed Res Ctr, 251 Bayview Blvd,Suite 100 Room 4B323, Baltimore, MD 21224 USA. EM LoeckenhoffC@grc.nia.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [RR 05675-23] NR 55 TC 9 Z9 9 U1 1 U2 7 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAR PY 2008 VL 63 IS 2 BP P92 EP P99 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 295BK UT WOS:000255449800005 PM 18441270 ER PT J AU Lockenhoff, CE Carstensen, LL AF Loeckenhoff, Corinna E. Carstensen, Laura L. TI Decision strategies in health care choices for self and others: Older but not younger adults make adjustments for the age of the decision target SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE age differences; health care choices; socioemotional selectivity theory ID EMOTION; MEMORY AB Participants (N = 142 younger and older adults) made health care choices for themselves, a social partner of similar age, or a social partner substantially younger or older than themselves. Using computer-based decision scenarios, participants reviewed positive, negative, or neutral choice criteria before choosing. Older adults who chose for themselves reviewed a greater proportion of positive choice criteria, recalled their choices more positively, and showed more positive emotional responses than did younger adults. Comparable results were found when participants chose for another person of similar age. Older adults who were asked to choose for a young person, however, showed a reduced focus on positive information; in addition, their emotional experience during the review process was less positive. Younger adults' performance was not influenced by the decision target. C1 [Loeckenhoff, Corinna E.; Carstensen, Laura L.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Lockenhoff, CE (reprint author), Biomed Res Ctr, 251 Bayview Blvd,Suite 100 Room 4B323, Baltimore, MD 21224 USA. EM LoeckenhoffC@grc.nia.nih.gov FU Intramural NIH HHS; NIA NIH HHS [R01 AG 8816, R01 AG008816, R01 AG008816-12] NR 9 TC 18 Z9 19 U1 0 U2 13 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAR PY 2008 VL 63 IS 2 BP P106 EP P109 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 295BK UT WOS:000255449800007 PM 18441264 ER PT J AU Yiu, WH Pan, CJ Ruef, RA Peng, WT Starost, MF Mansfield, BC Chou, JY AF Yiu, W. H. Pan, C-J Ruef, R. A. Peng, W-T Starost, M. F. Mansfield, B. C. Chou, J. Y. TI Angiotensin mediates renal fibrosis in the nephropathy of glycogen storage disease type la SO KIDNEY INTERNATIONAL LA English DT Article DE angiotensin; connective tissue growth factor; glycogen storage disease type la; renal fibrosis; transforming growth factor-beta 1 ID TISSUE GROWTH-FACTOR; PROXIMAL TUBULAR CELLS; FACTOR-BETA; DIABETIC-NEPHROPATHY; URIC-ACID; TGF-BETA; RAT; GLOMERULOSCLEROSIS; EXPRESSION; SYSTEM AB Patients with glycogen storage disease type la (GSD-la) develop renal disease of unknown etiology despite intensive dietary therapies. This renal disease shares many clinical and pathological similarities to diabetic nephropathy. We studied the expression of angiotensinogen, angiotensin type 1 receptor, transforming growth factor-beta 1, and connective tissue growth factor in mice with GSD-la and found them to be elevated compared to controls. While increased renal expression of angiotensinogen was evident in 2-week-old mice with GSD-la, the renal expression of transforming growth factor-beta and connective tissue growth factor did not increase for another week; consistent with upregulation of these factors by angiotensin II. The expression of fibronectin and collagens I, III, and IV was also elevated in the kidneys of mice with GSD-la, compared to controls. Renal fibrosis was characterized by a marked increase in the synthesis and deposition of extracellular matrix proteins in the renal cortex and histological abnormalities including tubular basement membrane thickening, tubular atrophy, tubular dilation, and multifocal interstitial fibrosis. Our results suggest that activation of the angiotensin system has an important role in the pathophysiology of renal disease in patients with GSD-la. C1 [Yiu, W. H.; Pan, C-J; Ruef, R. A.; Peng, W-T; Mansfield, B. C.; Chou, J. Y.] NICHHD, NIH, Sect Cellular Differentiat, Bethesda, MD 20892 USA. [Starost, M. F.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Mansfield, B. C.] Correlog Syst Inc, Rockville, MD USA. RP Chou, JY (reprint author), NICHHD, NIH, Sect Cellular Differentiat, Bldg 10,Room 9D42,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov FU Intramural NIH HHS [Z01 HD000912-28] NR 48 TC 21 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2008 VL 73 IS 6 BP 716 EP 723 DI 10.1038/sj.ki.5002718 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 271GX UT WOS:000253778000011 PM 18075499 ER PT J AU Mantovani, A Romero, P Palucka, AK Marincola, FM AF Mantovani, Alberto Romero, Pedro Palucka, A. Karolina Marincola, Francesco M. TI Tumour immunity: effector response to tumour and role of the microenvironment SO LANCET LA English DT Review ID REGULATORY T-CELLS; HEPATITIS-C VIRUS; NF-KAPPA-B; ALTERNATIVELY ACTIVATED MACROPHAGES; HUMAN METASTATIC MELANOMA; ANTIGEN-PRESENTING CELLS; PULSED DENDRITIC CELLS; CANCER-IMMUNOTHERAPY; IN-VIVO; HIGH-FREQUENCY AB Substantial evidence shows that inflammation promotes oncogenesis and, occasionally, participates in cancer rejection. This paradox can be accounted for by a dynamic switch from chronic smouldering inflammation promoting cancer-cell survival to florid, tissue-disruptive inflammatory reactions that trigger cancer-cell destruction. Clinical and experimental observations suggest that the mechanism of this switch recapitulates the events associated with pathogen infection, which stimulate immune cells to recognise danger signals and activate immune effector functions. Generally, cancers do not have danger signals and, therefore, they cannot elicit strong immune reactions. Synthetic molecules have been developed that mimic pathogen invasion at the tumour site. These compounds activate dendritic cells to produce proinflammatory cytokines, which in turn trigger cytotoxic mechanisms leading to cancer death. Simultaneously, dendritic cells capture antigen shed by dying cancer cells, undergo activation, and stimulate antigen-specific T and B cells. This process results in massive amplification of the antineoplastic inflammatory process. Thus, although anti-inflammatory drugs can prevent onset of some malignant diseases, induction of T cells specific for tumour antigen by active immunisation, combined with powerful activation signals within the cancer microenvironment, might yield the best strategy for treatment of established cancers. C1 [Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Mantovani, Alberto] Univ Milan, Ist Clin Humanitas, Milan, Italy. [Mantovani, Alberto] Univ Milan, Inst Pathol, Milan, Italy. [Romero, Pedro] Ludwig Inst Canc Res, Lausanne Branch, Lausanne, Switzerland. [Palucka, A. Karolina] Baylor Inst Immunol Res, Dallas, TX USA. RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM FMarincola@cc.nih.gov OI Mantovani, Alberto/0000-0001-5578-236X FU NCI NIH HHS [CA085540, CA78846, CA89440, P01 CA84512]; PHS HHS [U19 AIO57234]; Associazione Italiana per la Ricerca sul Cancro NR 178 TC 271 Z9 291 U1 7 U2 55 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 1 PY 2008 VL 371 IS 9614 BP 771 EP 783 DI 10.1016/S0140-6736(08)60241-X PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 268RI UT WOS:000253596700031 PM 18275997 ER PT J AU Camargos, S Scholz, S Simon-Sanchez, J Paisan-Ruiz, C Lewis, P Hernandez, D Ding, J Gibbs, JR Cookson, MR Bras, J Guerreiro, R Oliveira, CR Lees, A Hardy, J Cardoso, F Singleton, AB AF Camargos, Sarah Scholz, Sonja Simon-Sanchez, Javier Paisan-Ruiz, Coro Lewis, Patrick Hernandez, Dena Ding, Jinhui Gibbs, J. Raphael Cookson, Mark R. Bras, Jose Guerreiro, Rita Oliveira, Catarina Resende Lees, Andrew Hardy, John Cardoso, Francisco Singleton, Andrew B. TI DYT16, a novel young-onset dystonia-parkinson ism disorder: identification of a segregating mutation in the stress-response protein PRKRA SO LANCET NEUROLOGY LA English DT Article ID GENE; DISEASE; PACT AB Background Dystonia and parkinsonism may present as part of the same genetic disorder. Identification of the genetic mutations that underlie these diseases may help to shed light on the aetiological processes involved. Methods We identified two unrelated families with members with an apparent autosomal recessive, novel, young-onset, generalised form of dystonia parkinsonism. We did autozygosity mapping and candidate gene sequencing in these families. Findings High-density genome-wide SNP genotyping revealed a disease-segregating region containing 277homozygous markers identical by state across all affected members from both families. This novel disease locus, designated DYT16, covers 1.2 Mb at chromosome 2q31.2. The crucial interval contains 11 genes or predicted transcripts. Sequence analysis of every exon of all of these transcripts revealed a single disease-segregating mutation, c.665C>T (P222L), in the stress-response gene PRKRA, which encodes the protein kinase, interferon-inducible double-stranded RNA-dependent activator. Interpretation We describe a mutation within the gene PRKRA that segregates with a novel, autosomal recessive, dystonia parkinsonism syndrome. These patients have progressive, generalised, early-onset dystonia with axial muscle involvement, oromandibular (sardonic smile), laryngeal dystonia and, in some cases, parkinsonian features, and do not respond to levodopa therapy. C1 [Camargos, Sarah; Scholz, Sonja; Simon-Sanchez, Javier; Paisan-Ruiz, Coro; Lewis, Patrick; Hernandez, Dena; Ding, Jinhui; Gibbs, J. Raphael; Cookson, Mark R.; Bras, Jose; Guerreiro, Rita; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Camargos, Sarah; Cardoso, Francisco] Univ Fed Minas Gerais, Fac Med, Dept Internal Med, Belo Horizonte, MG, Brazil. [Camargos, Sarah; Cardoso, Francisco] Hosp Clin, Neurol Serv, Movement Disorders Clin, Belo Horizonte, MG, Brazil. [Scholz, Sonja; Paisan-Ruiz, Coro; Lewis, Patrick; Gibbs, J. Raphael; Lees, Andrew; Hardy, John] Inst Neurol, London WC1N 3BG, England. [Bras, Jose; Guerreiro, Rita; Oliveira, Catarina Resende] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Paisan-Ruiz, Coro/C-2912-2009; Lewis , Patrick/C-3674-2009; Bras, Jose/D-3366-2009; Oliveira, Catarina/F-3685-2010; Bras, Jose/A-1428-2011; Gibbs, J. Raphael/A-3984-2010; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Lees, Andrew/A-6605-2009; Guerreiro, Rita/A-1327-2011; Cardoso, Francisco/A-2285-2014; CAMARGOS, SARAH/O-4670-2014; OI Oliveira, Catarina/0000-0001-6942-4328; Cardoso, Francisco/0000-0003-0808-0116; CAMARGOS, SARAH/0000-0001-9829-6783; Lewis, Patrick/0000-0003-4537-0489; Scholz, Sonja/0000-0002-6623-0429 FU Intramural NIH HHS; Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 19 TC 91 Z9 94 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAR PY 2008 VL 7 IS 3 BP 207 EP 215 DI 10.1016/S1474-4422(08)70022-X PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 268KZ UT WOS:000253580000012 PM 18243799 ER PT J AU Lehrnbecher, T Koehl, U Wittekindt, B Bochennek, K Tramsen, L Klingebiel, T Chanock, SJ AF Lehrnbecher, Thomas Koehl, Ulrike Wittekindt, Boris Bochennek, Konrad Tramsen, Lars Klingebiel, Thomas Chanock, Stephen J. TI Changes in host defence induced by malignancies and antineoplastic treatment: implication for immunotherapeutic strategies SO LANCET ONCOLOGY LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; REGULATORY T-CELLS; ANTI-CD52 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER PATIENTS; NATURAL-KILLER-CELLS; GROWTH-FACTOR KGF AB Changes of the immune system can be a consequence of an underlying malignancy or induced by antineoplastic treatment. Both influence the risk for infectious complications and relapse. Over the past decade, there have been a series of major developments in the laboratory assessment of immune dysfunction, particularly as it relates to the complex interactions of the distinct components of the immune system. in addition, several new therapeutic strategies that modulate the immune system have been introduced. We review new findings that can affect clinical decision making. Better insights into the impairment of host response could provide the rationale for the development of new therapeutic strategies, for both supportive care and anticancer treatment. C1 [Lehrnbecher, Thomas; Koehl, Ulrike; Wittekindt, Boris; Bochennek, Konrad; Tramsen, Lars; Klingebiel, Thomas] Univ Frankfurt, Childrens Hosp 3, D-60590 Frankfurt, Germany. [Chanock, Stephen J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Lehrnbecher, T (reprint author), Univ Frankfurt, Childrens Hosp 3, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM thomas.lehrnbecher@kgu.de NR 85 TC 23 Z9 24 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2008 VL 9 IS 3 BP 269 EP 278 DI 10.1016/S1470-2045(08)70071-8 PG 10 WC Oncology SC Oncology GA 269AS UT WOS:000253622500036 PM 18308252 ER PT J AU Rapp, BA AF Rapp, Barbara A. TI Excellence in evaluation: Early landmarks at the National Library of Medicine SO LIBRARY TRENDS LA English DT Article ID INTERACTIVE SYSTEMS; INFORMATION-SYSTEMS; RETRIEVAL SYSTEM; USER-INTERFACE; MEDLARS; DESIGN; EFFICIENCY; ECONOMICS; SERVICES; PROGRAM AB F. Wilfrid Lancaster has earned a reputation for greatness in the evaluation of information storage and retrieval systems. Many of his extensive contributions stern from his early experience with the National Library of Medicine (NI-M) MEDLARS system. His evaluation of the MEDLARS Demand Search Service in 1966 and 1967 was all important landmark as one of the earliest evaluations of a computer-based retrieval system and as the first application of recall and precision measures in a large, operational database setting. In 1971, his evaluation of die MEDLARS AIM-TWX system was an important study of early online systems and their direct use by end users. This paper summarizes Lancaster's two major evaluations of the MEDLARS system, including the information environment at the time and their impact in the field of information science. Examples of Lancaster's other evaluation work with information retrieval systems are provided, followed by discussion of the textbooks that grew out of his evaluation experience and expertise. The article closes with comments from current and former NLM staff regarding Lancaster's time at NLM Or his influence on their own career. C1 [Rapp, Barbara A.] Natl Lib Med, Off Planning & Anal, Postgrad Associate Fellowship Program, Bethesda, MD 20894 USA. [Rapp, Barbara A.] Natl Lib Med, Natl Ctr Biotechnol Informat, User Serv, Bethesda, MD 20894 USA. [Rapp, Barbara A.] Catholic Univ Amer, Fac Sch Library & Informat, Program Hlth Sci Librarianship, Washington, DC 20064 USA. RP Rapp, BA (reprint author), Natl Lib Med, Off Planning & Anal, Postgrad Associate Fellowship Program, Bethesda, MD 20894 USA. NR 66 TC 0 Z9 0 U1 1 U2 5 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0024-2594 EI 1559-0682 J9 LIBR TRENDS JI Libr. Trends PD SPR PY 2008 VL 56 IS 4 BP 859 EP 887 PG 29 WC Information Science & Library Science SC Information Science & Library Science GA 345HW UT WOS:000258988100011 ER PT J AU Harrington, D Gail, MH AF Harrington, David Gail, Mitchell H. TI Harry S. (Sam) Wieand SO LIFETIME DATA ANALYSIS LA English DT Biographical-Item C1 [Harrington, David] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Harrington, D (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2008 VL 14 IS 1 BP 1 EP 5 DI 10.1007/s10985-008-9081-5 PG 5 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 259ND UT WOS:000252945100001 PM 18219575 ER PT J AU Gail, MH AF Gail, Mitchell H. TI Estimation and interpretation of models of absolute risk from epidemiologic data, including family-based studies SO LIFETIME DATA ANALYSIS LA English DT Article DE absolute risk; calibration; cumulative incidence; discriminatory accuracy; family-based design ID BREAST-CANCER RISK; AUTOSOMAL-DOMINANT MUTATION; GENOME-WIDE ASSOCIATION; OVARIAN-CANCER; KIN-COHORT; ESTIMATING PENETRANCE; GENE-CHARACTERIZATION; SUSCEPTIBILITY GENES; COMPETING RISK; BRCA1 AB Absolute risk is the chance that a person with given risk factors and free of the disease of interest at age a will be diagnosed with that disease in the interval (a, a + tau]. Absolute risk is sometimes called cumulative incidence. Absolute risk is a "crude" risk because it is reduced by the chance that the person will die of competing causes of death before developing the disease of interest. Cohort studies admit flexibility in modeling absolute risk, either by allowing covariates to affect the cause-specific relative hazards or to affect the absolute risk itself. An advantage of cause-specific relative risk models is that various data sources can be used to fit the required components. For example, case-control data can be used to estimate relative risk and attributable risk, and these can be combined with registry data on age-specific composite hazard rates for the disease of interest and with national data on competing hazards of mortality to estimate absolute risk. Family-based designs, such as the kin-cohort design and collections of pedigrees with multiple affected individuals can be used to estimate the genotype-specific hazard of disease. Such analyses must be adjusted for ascertainment, and failure to take into account residual familial risk, such as might be induced by unmeasured genetic variants or by unmeasured behavioral or environmental exposures that are correlated within families, can lead to overestimates of mutation-specific absolute risk in the general population. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov NR 53 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2008 VL 14 IS 1 BP 18 EP 36 DI 10.1007/s10985-007-9070-0 PG 19 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 259ND UT WOS:000252945100006 PM 18058231 ER PT J AU Burzykowski, T Buyse, M Yothers, G Sakamoto, J Sargent, D AF Burzykowski, Tomasz Buyse, Marc Yothers, Greg Sakamoto, Junichi Sargent, Dan TI Exploring and validating surrogate endpoints in colorectal cancer SO LIFETIME DATA ANALYSIS LA English DT Article DE surrogate endpoint; colorectal cancer; surrogate threshold effect ID TRIALS AB Sargent et al (J Clin Oncol 23: 8664-8670, 2005) concluded that 3-year disease-free survival (DFS) can be considered a valid surrogate (replacement) endpoint for 5-year overall survival (OS) in clinical trials of adjuvant chemotherapy for colorectal cancer. We address the question whether the conclusion holds for trials involving other classes of treatments than those considered by Sargent et al. Additionally, we assess if the 3-year cutpoint is an optimal one. To this aim, we investigate whether the results reported by Sargent et al. could have been used to predict treatment effects in three centrally randomized adjuvant colorectal cancer trials performed by the Japanese Foundation for Multidisciplinary Treatment for Cancer (JFMTC) (Sakamoto et al. J Clin Oncol 22:484-492, 2004). Our analysis supports the conclusion of Sargent et al. and shows that using DFS at 2 or 3 years would be the best option for the prediction of OS at 5 years. C1 [Burzykowski, Tomasz; Buyse, Marc] Hasselt Univ, Ctr Stat, B-3590 Diepenbeek, Belgium. [Burzykowski, Tomasz] MSOURCE Med Dev, Warsaw, Poland. [Buyse, Marc] IDDI, Louvain, Belgium. [Yothers, Greg] NSABP, Ctr Biostat, Pittsburgh, PA USA. [Sakamoto, Junichi] Nagoya Univ, Grad Sch Med, Nagoya, Aichi, Japan. [Sargent, Dan] Mayo Clin, Coll Med, Rochester, MN USA. RP Burzykowski, T (reprint author), Hasselt Univ, Ctr Stat, Agoralaan D, B-3590 Diepenbeek, Belgium. EM tomasz.burzykowski@uhasselt.be OI Yothers, Greg/0000-0002-7965-7333; Sargent, Daniel/0000-0002-2684-4741 NR 10 TC 22 Z9 22 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2008 VL 14 IS 1 BP 54 EP 64 DI 10.1007/s10985-007-9079-4 PG 11 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 259ND UT WOS:000252945100008 PM 18205045 ER PT J AU Watashi, K Metselaar, HJ van der Laan, LJW AF Watashi, Koichi Metselaar, Herold J. van der Laan, Luc J. W. TI Interfering with interferon: Re-igniting the debate on calcineurin inhibitor choice and antiviral therapy for hepatitis C virus recurrence SO LIVER TRANSPLANTATION LA English DT Editorial Material ID LIVER-TRANSPLANT RECIPIENTS; CYCLOSPORINE-A SUPPRESSES; IN-VITRO; REPLICATION; TRIAL C1 [van der Laan, Luc J. W.] Erasmus MC Univ, Med Ctr, Dept Surg, NL-3015 CE Rotterdam, Netherlands. [Watashi, Koichi] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Watashi, Koichi] Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Kyoto 606, Japan. [Metselaar, Herold J.] Erasmus MC Univ, Med Ctr, Dept Gastroenterol & Hepatol, NL-3015 CE Rotterdam, Netherlands. RP van der Laan, LJW (reprint author), Erasmus MC Univ, Med Ctr, Dept Surg, Room L458,sGravendijkwal 230, NL-3015 CE Rotterdam, Netherlands. EM l.vanderlaan@erasmusmc.nl OI van der Laan, Luc/0000-0002-0651-5334 NR 19 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD MAR PY 2008 VL 14 IS 3 BP 265 EP 267 DI 10.1002/lt.21363 PG 3 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 270WC UT WOS:000253749900001 PM 18306373 ER PT J AU Yang, J Singh, S Shen, J AF Yang, Jehoon Singh, Sujata Shen, Jun TI C-13 saturation transfer effect of carbon dioxide-bicarbonate exchange catalyzed by carbonic anhydrase in vivo SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE carbonic anhydrase; magnetic resonance spectroscopy; magnetization transfer; carbon-13 ID RENAL TUBULAR-ACIDOSIS; MAGNETIZATION-TRANSFER; CEREBRAL CALCIFICATION; DEHYDROGENASE REACTION; II DEFICIENCY; RAT-BRAIN; NMR; SPECTROSCOPY; MECHANISM; OSTEOPETROSIS AB Carbonic anhydrase catalyzes reversible hydration of carbon dioxide and dehydration of bicarbonate. In this article we report that the rapid exchange catalyzed by carbonic anhydrase causes a large magnetization (saturation) transfer effect on the C-13 signal of bicarbonate at 160.7 ppm in vivo when the resonance of the undetectable carbon dioxide at 125.0 ppm is irradiated with RF pulses. In isoflurane-anesthetized adult rat brain the unidirectional, pseudo first-order rate constant of this exchange in the dehydration direction was determined to be 0.47 +/- 0.05 sec(-1) following intravenous infusion of uniformly C-13-labeled glucose for labeling bicarbonate. Intralateral ventricular administration of the highly specific carbonic anhydrase inhibitor acetazolamide, which is a drug used for treating glaucoma and epilepsy, was also shown to significantly attenuate the observed C-13 magnetization transfer effect of the carbon dioxide-bicarbonate exchange in the rat brain. C1 [Yang, Jehoon; Singh, Sujata; Shen, Jun] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sheni@intra.nimh.nih.gov FU Intramural NIH HHS NR 41 TC 3 Z9 3 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2008 VL 59 IS 3 BP 492 EP 498 DI 10.1002/mrm.21501 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272SX UT WOS:000253881200008 PM 18224701 ER PT J AU Kerwin, WS Oikawa, M Yuan, C Jarvik, GP Hatsukami, TS AF Kerwin, W. S. Oikawa, M. Yuan, C. Jarvik, G. P. Hatsukami, T. S. TI MR imaging of adventitial vasa vasorum in carotid atherosclerosis SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE dynamic contrast-enhanced MRI; atherosclerosis; vasa vasorum; kinetic model; carotid artery ID CONTRAST-ENHANCED MRI; IN-VIVO; KINETIC-PARAMETERS; PLAQUE MORPHOLOGY; HIGH-RESOLUTION; FIBROUS-CAP; NEOVASCULARIZATION; ANGIOGENESIS; INFLAMMATION; LESIONS AB Vasa vasorum in the adventitia of atherosclerotic arteries may play a role in plaque progression. In this investigation, a method for characterizing vasa vasorum in the carotid artery is proposed, in which the perfusion properties of the adventitia are probed via dynamic contrast-enhanced (DCE) MRI. A parametric "vasa vasorum image" is automatically generated that depicts the plasma volume (v(p)) and transfer constant (K-trans). The average K-trans within the adventitia is proposed as a quantitative measurement related to the extent of the vasa vasorum. In 25 subjects with lesions meeting the requirements for carotid endarterectomy (CEA) significantly higher adventitial K-trans of 0.155 +/- 0.045 min(-1) was observed, compared to 0.122 +/- 0.029 min(-1) in the remaining 20 subjects with moderate disease (P < 0.01). In the 25 subjects with endarterectomy specimens, histological evaluation showed that adventitial K-trans was significantly correlated with the amount of neovasculature (R = 0.41; P = 0.04) and macrophages (R = 0.49; P = 0.01) in the excised plaque. In the remaining 20 subjects without histology, elevated adventitial Ktrans was significantly correlated with the log of C-reactive protein (CRP) levels (R = 0.57, P = 0.01) and was elevated in active smokers compared to nonsmokers (0.141 +/- 0.036 vs. 0.111 +/- 0.017 min(-1); P = 0.02). Because these factors are all associated with higher risk of atherosclerotic complications, these results suggest that adventitial K-trans may be a marker of risk as well. C1 [Kerwin, W. S.; Oikawa, M.; Yuan, C.] Univ Washington, Dept Radiol, Seattle, WA 98109 USA. [Jarvik, G. P.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Hatsukami, T. S.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Hatsukami, T. S.] NIH, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kerwin, WS (reprint author), Univ Washington, Dept Radiol, 815 Mercer St,Box 358050, Seattle, WA 98109 USA. EM bkerwin@u.washington.edu RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 FU NHLBI NIH HHS [R01 HL067406, P01 HL072262, R01 HL073401] NR 40 TC 95 Z9 101 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2008 VL 59 IS 3 BP 507 EP 514 DI 10.1002/mrm.21532 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272SX UT WOS:000253881200010 PM 18306402 ER PT J AU Hernando, D Haldar, JP Sutton, BP Ma, J Kellman, P Liang, ZP AF Hernando, D. Haldar, J. P. Sutton, B. P. Ma, J. Kellman, P. Liang, Z. -P. TI Joint estimation of water/fat images and field inhomogeneity map SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE dixon imaging; linear prediction; variable projection; field map estimation; IDEAL ID LEAST-SQUARES; FAT DECOMPOSITION; PHASED-ARRAY; RECONSTRUCTION AB Water/fat separation in the presence of B-0 field inhomogeneity is a problem of considerable practical importance in MRI. This article describes two complementary methods for estimating the water/fat images and the field inhomogeneity map from Dixon-type acquisitions. One is based on variable projection (VARPRO) and the other on linear prediction (LIP). The VARPRO method is very robust and can be used in low signal-to-noise ratio conditions because of its ability to achieve the maximum-likelihood solution. The LIP method is computationally more efficient, and is shown to perform well under moderate levels of noise and field inhomogeneity. These methods have been extended to handle multicoil acquisitions by jointly solving the estimation problem for all the coils. Both methods are analyzed and compared and results from several experiments are included to demonstrate their performance. C1 [Hernando, D.; Haldar, J. P.; Sutton, B. P.; Liang, Z. -P.] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Hernando, D.; Haldar, J. P.; Liang, Z. -P.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Sutton, B. P.] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. [Ma, J.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX USA. [Kellman, P.] Natl Inst Hlth, NHLBI, Cardiac Energet Lab, Bethesda, MD USA. RP Hernando, D (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, 405 N Mathews Ave, Urbana, IL 61801 USA. EM dhernan2@uiuc.edu RI Sutton, Bradley/A-4801-2008; Haldar, Justin/B-4983-2008 OI Sutton, Bradley/0000-0002-8443-0408; Haldar, Justin/0000-0002-1838-0211 FU NCI NIH HHS [R01 CA098717, R01-CA098717]; NIBIB NIH HHS [P41-EB03631-16] NR 25 TC 71 Z9 71 U1 1 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2008 VL 59 IS 3 BP 571 EP 580 DI 10.1002/mrm.21522 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272SX UT WOS:000253881200017 PM 18306409 ER PT J AU Matsumoto, S Espey, MG Utsumi, H Devasahayam, N Matsumoto, KI Matsumoto, A Hirata, H Wink, DA Kuppusamy, P Subramanian, S Mitchell, JB Krishna, MC AF Matsumoto, Shingo Espey, Michael Graham Utsumi, Hideo Devasahayam, Nallathamby Matsumoto, Ken-Ichiro Matsumoto, Atsuko Hirata, Hiroshi Wink, David A. Kuppusamy, Periarman Subramanian, Sankaran Mitchell, James B. Krishna, Murali C. TI Dynamic monitoring of localized tumor oxygenation changes using RF pulsed electron paramagnetic resonance in conscious mice SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE pulsed EPR; lithium phthalocyanine; oximetry; tumor hypoxia ID IN-VIVO EPR; LITHIUM PHTHALOCYANINE; MAGNETIC-RESONANCE; NECK-CANCER; CONTINUOUS-WAVE; SURFACE-COIL; HEAD; HYPOXIA; OXIMETRY; HETEROGENEITY AB Oxygenation status is a key determinant in both tumor growth and responses to therapeutic interventions. The oxygen partial pressure (1302) was assessed using a novel pulsed electron paramagnetic resonance (EPR) spectroscopy at 750 MHz. Crystals of lithium phthalocyanine (LiPc) implanted into either squamous cell carcinoma (SCC) tumor or femoral muscle on opposing legs of mice were tested by pulsed EPR. The results showed pO(2) of SCC tumor was 2.7 +/- 0.4 mmHg, while in the femoral muscle it was 6.1 +/- 0.9 mmHg. A major advantage of pulsed EPR oximetry over conventional continuous-wave (CW) EPR oximetry is the lack of influence from subject motion, while avoiding artifacts associated with modulation or power saturation. Resonators in pulsed EPR are overcoupled to minimize recovery time. This makes changes in coupling associated with object motion minimal without influencing spectral quality. Consequently, pulsed EPR oximetry enables approximately a temporal resolution of similar to one second in pO(2) monitoring in conscious subjects, avoiding significant influence of anesthetics on the physiology being studied. The pO(2) in SCC tumor and muscle was found to be higher without anesthesia (3.9 +/- 0.5 mmHg for tumor, 8.8 +/- 1.2 mmHg for muscle). These results support the advantage of pulsed EPR in examining pO(2) in conscious animals with LiPc chronically implanted in predetermined regions. C1 [Matsumoto, Shingo; Espey, Michael Graham; Devasahayam, Nallathamby; Matsumoto, Ken-Ichiro; Matsumoto, Atsuko; Wink, David A.; Subramanian, Sankaran; Mitchell, James B.; Krishna, Murali C.] NIH, Natl Canc Inst, Canc Res Ctr, Radiat Biol Branch, Bethesda, MD 20892 USA. [Matsumoto, Shingo; Utsumi, Hideo] Kyushu Univ, Grad Sch Pharmaceut Sci, Fukuoka, Japan. [Hirata, Hiroshi] Yamagata Univ, Dept Elect Engn, Yamagata 990, Japan. [Kuppusamy, Periarman] Ohio State Univ, Sch Med, Davis Heart Lung Res Ctr, Columbus, OH USA. RP Krishna, MC (reprint author), NIH, Natl Canc Inst, Canc Res Ctr, Radiat Biol Branch, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 40 TC 13 Z9 13 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD MAR PY 2008 VL 59 IS 3 BP 619 EP 625 DI 10.1002/mrm.21500 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 272SX UT WOS:000253881200022 PM 18224698 ER PT J AU Gordon, RR Hunter, KW Sorensen, P Pomp, D AF Gordon, Ryan R. Hunter, Kent W. Sorensen, Peter Pomp, Daniel TI Genotype x diet interactions in mice predisposed to mammary cancer. I. Body weight and fat SO MAMMALIAN GENOME LA English DT Article ID QUANTITATIVE TRAIT LOCI; INBRED MOUSE STRAINS; LARGE-SAMPLE QTL; METASTATIC-DISEASE; TRANSGENIC MODEL; GENE-EXPRESSION; OBESITY QTLS; TUMOR; CACHEXIA; GROWTH AB High dietary fat intake and obesity may increase susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F-2 mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F-2 mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe development of the F-2 population (n = 615) which resulted from a cross between the polygenic obesity model M16i and FVB/NJ-TgN (MMTV-PyMT)(634Mul), effects of diet on growth and body composition, and QTL and QTL x diet and/or gender interaction effects for growth and obesity-related phenotypes. We identified 38 QTL for body composition traits that were significant at the genome-wide 0.05 level, likely representing nine distinct loci after accounting for pleiotropic effects. QTL x diet and/or gender interactions were present at 15 of these QTL, indicating that such interactions play a significant role in defining the genetic architecture of complex traits such as body weight and obesity. C1 [Gordon, Ryan R.; Pomp, Daniel] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Hunter, Kent W.] NCI, Natl Inst Hlth, Canc Res Ctr, Bethesda, MD 20892 USA. [Sorensen, Peter] Aarhus Univ, Fac Agr Sci, Aarhus, Denmark. RP Pomp, D (reprint author), Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. EM dpomp@unc.edu FU Intramural NIH HHS; NCI NIH HHS [U01CA105417]; NIDDK NIH HHS [DK076050] NR 60 TC 10 Z9 11 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAR PY 2008 VL 19 IS 3 BP 163 EP 178 DI 10.1007/s00335-008-9095-z PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 276AB UT WOS:000254112400003 PM 18286334 ER PT J AU Gordon, RR Hunter, KW La Merrill, M Sorensen, P Threadgill, DW Pomp, D AF Gordon, Ryan R. Hunter, Kent W. La Merrill, Michele Sorensen, Peter Threadgill, David W. Pomp, Daniel TI Genotype x diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis SO MAMMALIAN GENOME LA English DT Article ID QUANTITATIVE TRAIT LOCI; BREAST-CANCER; FATTY-ACIDS; RISK; GROWTH; COHORT; PROGRESSION; MUTATIONS; DISEASE; BRCA2 AB High dietary fat intake and obesity may increase the risk of susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F-2 mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F-2 mice either a very high-fat or a matched-control-fat diet, and we measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL x diet interaction effects. Here we describe effects of diet on mammary tumor and metastases phenotypes, mapping of tumor/metastasis modifier genes, and the interaction between dietary fat levels and effects of cancer modifiers. Results demonstrate that animals fed a high-fat diet are not only more likely to experience decreased mammary cancer latency but increased tumor growth and pulmonary metastases occurrence over an equivalent time. We identified 25 modifier loci for mammary cancer and pulmonary metastasis, likely representing 13 unique loci after accounting for pleiotropy, and novel QTL x diet interactions at a majority of these loci. These findings highlight the importance of accurately modeling not only the human cancer characteristics in mice but also the environmental exposures of human populations. C1 [Pomp, Daniel] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. [Gordon, Ryan R.; Pomp, Daniel] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Hunter, Kent W.] NCI, Dept Genet, Canc Res Ctr, Bethesda, MD 20892 USA. [La Merrill, Michele; Threadgill, David W.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Sorensen, Peter] Aarhus Univ, Fac Agr Sci, Aarhus, Denmark. [Threadgill, David W.; Pomp, Daniel] Univ N Carolina, Ctr Environm Hlth & Susceptibil, Clin Nutr Res Unit, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA. [Threadgill, David W.; Pomp, Daniel] Univ N Carolina, Carolina Genome Sci Ctr, Chapel Hill, NC 27599 USA. RP Pomp, D (reprint author), Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. EM dpomp@unc.edu RI Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 FU Intramural NIH HHS; NCI NIH HHS [U01CA105417]; NIDDK NIH HHS [DK076050] NR 40 TC 11 Z9 12 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAR PY 2008 VL 19 IS 3 BP 179 EP 189 DI 10.1007/s00335-008-9096-y PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 276AB UT WOS:000254112400004 PM 18288525 ER PT J AU Mendelson, J Rawson, R Newton, T Galloway, G de Wit, H Dewey, SL Hart, CL Epstein, DH AF Mendelson, John Rawson, Rick Newton, Thomas Galloway, Gantt de Wit, Harriet Dewey, Stephen L. Hart, Carl L. Epstein, David H. TI Treatment of methamphetamine dependence SO MAYO CLINIC PROCEEDINGS LA English DT Letter C1 [Mendelson, John; Galloway, Gantt] Univ Calif San Francisco, St Lukes Hosp, Addict Pharmacol Res Lab, Calif Pacific Med Ctr,Res Inst, San Francisco, CA 94143 USA. [Rawson, Rick; Newton, Thomas] Univ Calif Los Angeles, Geffen Sch Med, Semel Inst, UCLA Integrated Substance Abuse Programs, Los Angeles, CA 90024 USA. [de Wit, Harriet] Univ Chicago, Human Behav Pharmacol Lab, Chicago, IL 60637 USA. [Dewey, Stephen L.] NYU, Sch Med, Brookhaven Natl Lab, New York, NY USA. [Hart, Carl L.] Columbia Univ, New York, NY USA. [Epstein, David H.] NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Baltimore, MD USA. RP Mendelson, J (reprint author), Univ Calif San Francisco, St Lukes Hosp, Addict Pharmacol Res Lab, Calif Pacific Med Ctr,Res Inst, San Francisco, CA 94143 USA. OI newton, thomas/0000-0002-3198-5901; de Wit, Harriet/0000-0002-7211-8994 NR 2 TC 0 Z9 0 U1 0 U2 3 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2008 VL 83 IS 3 BP 369 EP 370 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 267MJ UT WOS:000253512800022 PM 18316008 ER PT J AU Song, JK Giniger, E Desai, CJ AF Song, Jeong K. Giniger, Edward Desai, Chand J. TI The receptor protein tyrosine phosphatase PTP69D antagonizes Abl tyrosine kinase to guide axons in Drosophila SO MECHANISMS OF DEVELOPMENT LA English DT Article DE axon guidance; RPTP; Src; signal transduction; tyrosine kinase; tyrosine phosphatase ID CELL-ADHESION MOLECULE; GROWTH CONE GUIDANCE; NEURITE OUTGROWTH; ABELSON KINASE; ACTIN CYTOSKELETON; NEURAL DEVELOPMENT; ENA/VASP PROTEINS; NEURONS; EMBRYO; MORPHOGENESIS AB During Drosophila embryogenesis, both the cytoplasmic Abelson tyrosine kinase (Abl) and the membrane bound tyrosine phosphatase PTP69D are required for proper guidance of CNS and motor axons. We provide evidence that PTP69D modulates signaling by Abl and its antagonist, Ena. An Abl loss-of function mutation dominantly suppresses most Ptp69D mutant phenotypes including larval/pupal lethality and CNS and motor axon defects, while increased Abl and decreased Ena expression dramatically increase the expressivity of Ptp69D axonal defects. In contrast, Ptp69D mutations do not affect AN mutant phenotypes. These results support the hypothesis that PTP69D antagonizes the Abl/Ena genetic pathway, perhaps as an upstream regulator. We also find that mutation of the gene encoding the cytoplasmic Src64B tyrosine kinase exacerbates Ptp69D phenotypes, suggesting that two different cytoplasmic tyrosine kinases, Abl and Src64B, modify PTP69D-mediated axon patterning in quite different ways. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Song, Jeong K.; Giniger, Edward] NINDS, Axon Guidance & Neural Connect Unit, NIH, Bethesda, MD 20892 USA. [Song, Jeong K.; Desai, Chand J.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Desai, Chand J.] Martin Luther King Acad Magnet High Sch, Dept Sci, Nashville, TN 37203 USA. RP Giniger, E (reprint author), NINDS, Axon Guidance & Neural Connect Unit, NIH, Bldg 37,Room 1016,37 Convent Dr, Bethesda, MD 20892 USA. EM ginigere@ninds.nih.gov RI Giniger, Edward/C-1764-2015 OI Giniger, Edward/0000-0002-8340-6158 FU Intramural NIH HHS [Z01 NS003013-03]; NINDS NIH HHS [R01 NS038141-01, R01 NS038141-03, R01 NS038141-05, Z01 NS003013, R01 NS038141-04, R01 NS038141-02]; PHS HHS [NSHD38141] NR 47 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAR-APR PY 2008 VL 125 IS 3-4 BP 247 EP 256 DI 10.1016/j.mod.2007.11.005 PG 10 WC Developmental Biology SC Developmental Biology GA 278RK UT WOS:000254303800006 PM 18160268 ER PT J AU Gutierrez, LF Ozturk, C McVeigh, ER Lederman, RJ AF Gutierrez, Luis F. Ozturk, Cengizhan McVeigh, Elliot R. Lederman, Robert J. TI A practical global distortion correction method for an image intensifier based x-ray fluoroscopy system SO MEDICAL PHYSICS LA English DT Article DE x-ray image intensifier; x-ray fluoroscopy; angle dependent distortion correction ID GEOMETRIC DISTORTION; CHAIN; ANGIOGRAPHY; ALGORITHM; ACCURATE; XRII AB X-ray images acquired on systems with image intensifiers (II) exhibit characteristic distortion which is due to both external and internal factors. The distortion is dependent on the orientation of the II, a fact particularly relevant to II's mounted on C arms which have several degrees of freedom of motion. Previous descriptions of distortion correction strategies have relied on a dense sampling of the C-arm orientation space, and as such have been limited mostly to a single arc of the primary angle, alpha. We present a new method which smooths the trajectories of the segmented vertices of the grid phantom as a function of alpha prior to solving the two-dimensional warping problem. It also shows that the same residual errors of distortion correction could be achieved without fitting the trajectories of the grid vertices, but instead applying the previously described global method of distortion correction, followed by directly smoothing the values of the polynomial coefficients as functions of the C-arm orientation parameters. When this technique was applied to a series of test images at arbitrary alpha, the root-mean-square (RMS) residual error was 0.22 pixels. The new method was extended to three degrees of freedom of the C-arm motion: the primary angle, alpha; the secondary angle, beta; and the source-to-intensifier distance, lambda. Only 75 images were used to characterize the distortion for the following ranges: alpha, +/- 45 degrees (Delta alpha=22.5 degrees); beta, +/- 36 degrees (Delta beta=18 degrees); lambda, 98-118 cm (Delta lambda=10 cm). When evaluated on a series of test images acquired at arbitrary (alpha,beta,lambda), the RMS residual error was 0.33 pixels. This method is targeted at applications such as guidance of catheter-based interventions and treatment planning for brachytherapy, which require distortion-corrected images over a large range of C-arm orientations. C1 Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. [Gutierrez, Luis F.; Lederman, Robert J.] NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. [Ozturk, Cengizhan; Lederman, Robert J.] NIH, NHLBI, Cardiovasc Branch, Div Intramural Res, Bethesda, MD 20892 USA. [Ozturk, Cengizhan] Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey. RP Gutierrez, LF (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. EM luis.gutierrez@philips.com RI Ozturk, Cengizhan/A-6177-2016; OI Ozturk, Cengizhan/0000-0002-6966-0774; lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z01 HL005062-05] NR 25 TC 13 Z9 17 U1 2 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2008 VL 35 IS 3 BP 997 EP 1007 DI 10.1118/1.2839099 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 267XL UT WOS:000253542400018 PM 18404935 ER PT J AU Bingham, A Mamyrova, G Rother, KI Oral, E Cochran, E Premkumar, A Kleiner, D James-Newton, L Targoff, IN Pandey, JP Carrick, DM Sebring, N O'Hanlon, TP Ruiz-Hidalgo, M Turner, M Gordon, LB Laborda, J Bauer, SR Blackshear, PJ Imundo, L Miller, FW Rider, LG AF Bingham, April Mamyrova, Gulnara Rother, Kristina I. Oral, Efif Cochran, Elaine Premkumar, Ahalya Kleiner, David James-Newton, Laura Targoff, Ira N. Pandey, Janardan P. Carrick, Danielle Mercatante Sebring, Nancy O'Hanlon, Terrance P. Ruiz-Hidalgo, Maria Turner, Maria Gordon, Leslie B. Laborda, Jorge Bauer, Steven R. Blackshear, Perry J. Imundo, Lisa Miller, Frederick W. Rider, Lisa G. CA Childhood Myositis Heterogeneity S TI Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity SO MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FAMILIAL PARTIAL LIPODYSTROPHY; IDIOPATHIC INFLAMMATORY MYOPATHIES; BODY-FAT DISTRIBUTION; NECROSIS-FACTOR-ALPHA; OF-THE-LITERATURE; METABOLIC DERANGEMENTS; LEPTIN CONCENTRATIONS; OMENTAL ADIPOCYTES; CLINICAL-FEATURES AB We describe the clinical features of 28 patients with juvenile dermatomyositis (JDM) and 1 patient with adult-onset dermatomyositis (DM), all of whom developed lipodystrophy (LD) that could be categorized into I of 3 phenotypes, generalized, partial, or focal, based on the pattern of fat loss distribution. LD onset was often delayed, beginning a median of 4.6 years after diagnosis of DM. Calcinosis, muscle atrophy, joint contractures, and facial rash were DM disease features found to be associated with LD. Panniculitis was associated with focal lipoatrophy while the anti-p155 autoantibody, a newly described myositis-associated autoantibody, was more associated with generalized LD. Specific LD features such as acanthosis nigricans, hirsutism, fat redistribution, and steatosis/nonalcoholic steatoliepatitis were frequent in patients with LD, in a gradient of frequency and severity among the 3 sub-phenotypes. Metabolic studies frequently revealed insulin resistance and hypertriglyceridemia in patients with generalized and partial LD. Regional fat loss from the thighs, with relative sparing of fat loss from the medial thighs, was more frequent in generalized than in partial LD and absent from DM patients without LD. Cytokine polymorphisms, the C3 nephritic factor, insulin receptor antibodies, and lamin mutations did not appear to play a pathogenic role in the development of LD in our patients. LD is an under-recognized sequela of JDM, and certain DM patients with a severe, prolonged clinical course and a high frequency of calcinosis appear to be at greater risk for the development of this complication. High-risk JDM patients should be screened for metabolic abnormalities, which are common in generalized and partial LD and result in much of the LD-associated morbidity. Further study is warranted to investigate the pathogenesis of acquired LD in patients with DM. C1 [Bingham, April; Mamyrova, Gulnara; James-Newton, Laura; Carrick, Danielle Mercatante; O'Hanlon, Terrance P.; Blackshear, Perry J.; Miller, Frederick W.; Rider, Lisa G.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Off Clin Res, Bethesda, MD 20892 USA. [Rother, Kristina I.; Oral, Efif; Cochran, Elaine] NIDDK, Bethesda, MD 20892 USA. [Kleiner, David; Turner, Maria] NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. [Bingham, April] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Oral, Efif] Univ Michigan, Ann Arbor, MI 48109 USA. [Targoff, Ira N.] Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. [Targoff, Ira N.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Pandey, Janardan P.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ruiz-Hidalgo, Maria; Laborda, Jorge; Bauer, Steven R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Gordon, Leslie B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Imundo, Lisa] Columbia Univ, New York, NY USA. [Ruiz-Hidalgo, Maria; Laborda, Jorge] Univ Castilla La Mancha, Fac Med, CRIB, Albacete, Spain. RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Off Clin Res, CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; OI Laborda, Jorge/0000-0002-9210-838X; Bauer, Steven/0000-0003-2831-846X; Oral, Elif/0000-0002-9171-1144; Kleiner, David/0000-0003-3442-4453; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [Z01 ES101074-06, Z99 DK999999]; NIAMS NIH HHS [P30 AR053483] NR 63 TC 42 Z9 44 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 2008 VL 87 IS 2 BP 70 EP 86 DI 10.1097/MD.0b013e31816bc604 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 275WW UT WOS:000254103900003 PM 18344805 ER PT J AU Danis, M Farrar, A Grady, C Taylor, C O'Donnell, P Soeken, K Ulrich, C AF Danis, Marion Farrar, Adrienne Grady, Christine Taylor, Carol O'Donnell, Patricia Soeken, Karen Ulrich, Connie TI Does fear of retaliation deter requests for ethics consultation? SO MEDICINE HEALTH CARE AND PHILOSOPHY LA English DT Article DE clinical ethics; ethics consultation; nurses; organizational ethics; retaliation; social workers ID WHISTLE; NURSES; BLOW AB Background Reports suggest that some health care personnel fear retaliation from seeking ethics consultation. We therefore examined the prevalence and determinants of fear of retaliation and determined whether this fear is associated with diminished likelihood of consulting an ethics committee. Methods We surveyed registered nurses (RNs) and social workers (SWs) in four US states to identify ethical problems they encounter. We developed a retaliation index (1-7 point range) with higher scores indicating a higher perceived likelihood of retaliation. Linear regression analysis was performed to identify socio-demographic and job characteristics associated with fear of retaliation. Logistic regression analysis was performed to determine whether fear of retaliation was associated with less likelihood of seeking consultation. Results Our sample (N = 1215) was primarily female (85%) and Caucasian (83%) with a mean age of 46 years and 17 years of practice. Among the sample, 293 (48.7%) RNs and 309 (51.3%) SWs reported access to an ethics consultation service. Amongst those with access, 2.8% (n = 17) personally experienced retaliation, 9.1% (n = 55) observed colleagues experience retaliation, 30.2% (n = 182) reported no experience with retaliation but considered it a realistic fear, and 50.8% (n = 305) did not perceive retaliation to be a problem. In logistic regression modeling, fear of retaliation was not associated with the likelihood (OR = 0.64; 95% CI = 0.22-1.89) or frequency of requesting ethics consultation (OR = 0.81; 95% CI = 0.27-2.38). Conclusion Fear of retaliation from seeking ethics consultation is common among nurses and social workers, nonetheless this fear is not associated with reduced requests for ethics consultation. C1 [Danis, Marion; Farrar, Adrienne; Grady, Christine] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. [Taylor, Carol] Georgetown Univ, Washington, DC USA. [O'Donnell, Patricia] Inova Hlth Syst, Falls Church, VA USA. [Soeken, Karen] Univ Maryland, College Pk, MD 20742 USA. [Ulrich, Connie] Univ Penn, Philadelphia, PA 19104 USA. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM mdanis@nih.gov NR 12 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1386-7423 J9 MED HEALTH CARE PHIL JI Med. Health Care Philos. PD MAR PY 2008 VL 11 IS 1 BP 27 EP 34 DI 10.1007/s11019-007-9105-z PG 8 WC Ethics; History & Philosophy Of Science SC Social Sciences - Other Topics; History & Philosophy of Science GA 524PL UT WOS:000272155100005 PM 17939060 ER PT J AU Kim, IW Booth-Genthe, C Ambudkar, SV AF Kim, In-Wha Booth-Genthe, Catherine Ambudkar, Suresh V. TI Relationship between drugs and functional activity of various mammalian P-glycoproteins (ABCB1) SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review DE ABC transporter; ATP hydrolysis; chemoprevention; multidrug resistance; pharmacokinetics; species differences; structure-activity relationship ID MULTIDRUG-RESISTANCE GENE; BLOOD-BRAIN-BARRIER; PROPAFENONE-TYPE MODULATORS; MONOCLONAL-ANTIBODIES; SPECIES-DIFFERENCES; ATPASE ACTIVITY; CELL-LINES; HUMAN MDR1; IN-VIVO; IVERMECTIN SENSITIVITY AB P-glycoprotein (Pgp, ABCB1) is an efflux transporter for a variety of amphipathic agents that can affect the pharmacokinetics of drugs. In order to extrapolate transport and pharmacokinetic data of the drug candidates obtained from in vitro and animal models to those in humans, it is important to understand the functional differences of Pgps from various mammalian species including human, monkey, dog, rat, and mouse. Here, we review differences/ similarities in the properties of Pgp from numerous mammalian species commonly used in preclinical studies and discuss their relevance to the pharmacokinetics of potential drug molecules. C1 [Kim, In-Wha; Booth-Genthe, Catherine; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI Ambudkar, Suresh/B-5964-2008 FU Intramural NIH HHS NR 100 TC 31 Z9 36 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PD MAR PY 2008 VL 8 IS 3 BP 193 EP 200 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 276FF UT WOS:000254126000001 PM 18336339 ER PT J AU Iriko, H Kaneko, O Otsuki, H Tsuboi, T Su, XZ Tanabe, K Torii, M AF Iriko, Hideyuki Kaneko, Osamu Otsuki, Hitoshi Tsuboi, Takafumi Su, Xin-zhuan Tanabe, Kazuyuki Torii, Motomi TI Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE gene conversion; malaria; polymorphism; rhoptry; selection ID RED-BLOOD-CELLS; RHOPTRY PROTEIN; MALARIA PARASITES; INFECTED ERYTHROCYTES; MEROZOITE INVASION; SEQUENCE ALIGNMENT; ALLELIC DIVERSITY; GENE CONVERSION; MAURERS CLEFTS; AOTUS MONKEYS AB complex of high-molecular-mass proteins (PfRhopH) of the human malaria parasite Plasmodium falciparum induces host protective immunity and therefore is a candidate for vaccine development. Understanding the level of polymorphism and the evolutionary processes is important for advancements in both vaccine design and knowledge of the evolution of cell invasion in this parasite. In the present study, we sequenced the entire open reading frames of seven genes encoding the proteins of the PfRhopH complex (rhoph2, rhoph3, and five rhoph1/clag gene paralogs). We found that four rhoph1/clag genes (clag2, 3.1, 3.2, and 8) were highly polymorphic. Amino acid substitutions and indels are predominantly clustered around amino acid positions 1000-1200 of these four rhoph1/clag genes. An excess of nonsynonymous substitutions over synonymous substitutions was detected for clag8 and 9, indicating positive selection. The McDonald-Kreitman test with a Plasmodium reichenowi orthologous sequence also supports positive selection on clag8. Based on the ratio of interspecific genetic distance to intraspecific distance, the time to the most recent common ancestor of the clag2 and 8 polymorphisms was estimated to be 1.89 and 0.87 million years ago, respectively, assuming divergence of P. falciparum and P. reichenowi 6 million years ago. In addition to a copy number polymorphism, gene conversion events were detected for the rhoph1/clag genes on chromosome 3, which likely play a role in increasing the diversity of each locus. Our results indicate that a high diversity of the PfRhopH1/Clag multigene family is maintained by diversifying selection forces over a considerably long period. (c) 2007 Elsevier B.V. All rights reserved. C1 [Iriko, Hideyuki; Kaneko, Osamu; Otsuki, Hitoshi; Torii, Motomi] Ehime Univ, Grad Sch Med, Dept Mol Parasitol, Toon, Ehime 7910295, Japan. [Iriko, Hideyuki; Tsuboi, Takafumi] Ehime Univ, Venture Business Lab, Matsuyama, Ehime 7908577, Japan. [Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 7908577, Japan. [Su, Xin-zhuan] NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Tanabe, Kazuyuki] Osaka Univ, Res Inst Microbial Dis, Int Res Ctr Infect Dis, Lab Malariol, Osaka 5650871, Japan. RP Kaneko, O (reprint author), Nagasaki Univ, Inst Trop Med, Dept Protozool, 1-12-4 Sakamoto, Nagasaki 8528523, Japan. OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS [Z01 AI000892-07, Z99 AI999999] NR 55 TC 24 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAR PY 2008 VL 158 IS 1 BP 11 EP 21 DI 10.1016/j.molbiopara.2007.11.004 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 277QY UT WOS:000254231000002 PM 18155305 ER PT J AU Xu, M Yu, Q Subrahmanyam, R Difilippantonio, MJ Ried, T Sen, JM AF Xu, Mai Yu, Qing Subrahmanyam, Ramesh Difilippantonio, Michael J. Ried, Thomas Sen, Jyoti Misra TI beta-catenin expression results in p53-independent DNA damage and oncogene-induced senescence in prelymphomagenic thymocytes in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; T-CELL DEVELOPMENT; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELL; V(D)J RECOMBINATION; PRE-TCR; MALIGNANT-TRANSFORMATION; LYMPHOCYTE DEVELOPMENT; INTESTINAL EPITHELIUM; GENE AMPLIFICATION AB The expression of beta-catenin, a potent oncogene, is causally linked to tumorigenesis. Therefore, it was surprising that the transgenic expression of oncogenic beta-catenin in thymocytes resulted in thymic involution instead of lymphomagenesis. In this report, we demonstrate that this is because the expression of oncogenic beta-catenin induces DNA damage, growth arrest, oncogene-induced senescence (OIS), and apoptosis of immature thymocytes. In p53-deficient mice, the expression of oncogenic beta-catenin still results in DNA damage and OIS, but the thymocytes survive and eventually progress to thymic lymphoma. beta-Catenin-induced thymic lymphomas are distinct from lymphomas that arise in p53(-/-) mice. They are CD4(-) CD8(-), while p53-dependent lymphomas are largely CD4(+) CD8(+), and they develop at an earlier age and in the absence of c-Myc expression or Notch1 signaling. Thus, we report that oncogenic beta-catenin-induced, p53-independent growth arrest and OIS and p53-dependent apoptosis protect developing thymocytes from transformation by oncogenic beta-catenin. C1 [Xu, Mai; Yu, Qing; Sen, Jyoti Misra] NIA, Immunol Lab, Lymphocyte Dev Unit, Baltimore, MD 21224 USA. [Subrahmanyam, Ramesh] NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. [Difilippantonio, Michael J.; Ried, Thomas] NCI, NIH, Genet Branch, Sect Canc Genom, Bethesda, MD 20892 USA. RP Sen, JM (reprint author), NIA, Immunol Lab, Lymphocyte Dev Unit, 5600 Nathan Shock Dr,Room 4B08 GRC, Baltimore, MD 21224 USA. EM Jyoti-Sen@nih.gov RI Subrahmanyam, Ramesh/K-5503-2012 FU Intramural NIH HHS [Z99 CA999999] NR 68 TC 44 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2008 VL 28 IS 5 BP 1713 EP 1723 DI 10.1128/MCB.01360-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 268TS UT WOS:000253603100025 PM 18160717 ER PT J AU Suino-Powell, K Xu, Y Zhang, C Tao, YG Tolbert, WD Simons, SS Xu, HE AF Suino-Powell, Kelly Xu, Yong Zhang, Chenghai Tao, Yong-guang Tolbert, W. David Simons, S. Stoney, Jr. Xu, H. Eric TI Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; STEROID-HORMONE RECEPTORS; MINERALOCORTICOID RECEPTOR; X-RECEPTOR; COACTIVATOR; MECHANISMS; DOMAIN; SPECIFICITY; ACTIVATION; CORTIVAZOL AB A common feature of nuclear receptor ligand binding domains (LBD) is a helical sandwich fold that nests a ligand binding pocket within the bottom half of the domain. Here we report that the ligand pocket of glucocorticoid receptor (GR) can be continuously extended into the top half of the LBD by binding to deacyleortivazol (DAC), an extremely potent glucocorticoid. It has been puzzling for decades why DAC, which contains a phenylpyrazole replacement at the conserved 3-ketone of steroid hormones that are normally required for activation of their cognate receptors, is a potent GR activator. The crystal structure of the GR LBD bound to DAC and the fourth LXXLL motif of steroid receptor coactivator I reveals that the GR ligand binding pocket is expanded to a size of 1,070 angstrom(3), effectively doubling the size of the GR dexamethasone-binding pocket of 540 angstrom(3) and yet leaving the structure of the coactivator binding site intact. DAC occupies only similar to 50% of the space of the pocket but makes intricate interactions with the receptor around the phenylpyrazole group that accounts for the high-affinity binding of DAC. The dramatic expansion of the DAC-binding pocket thus highlights the conformational adaptability of GR to ligand binding. The new structure also allows docking of various nonsteroidal ligands that cannot be fitted into the previous structures, thus providing a new rational template for drug discovery of steroidal and nonsteroidal glucocorticoids that can be specifically designed to reach the unoccupied space of the expanded pocket. C1 [Suino-Powell, Kelly; Xu, Yong; Zhang, Chenghai; Tolbert, W. David; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA. [Tao, Yong-guang; Simons, S. Stoney, Jr.] NIDDK, Steroid Hormones Sect, CEB, NIH, Bethesda, MD 20892 USA. RP Xu, HE (reprint author), Van Andel Res Inst, Lab Struct Sci, 333 Bostwick Ave, Grand Rapids, MI 49503 USA. EM eric.xu@vai.org FU NIDDK NIH HHS [R01 DK071662, DK066202, DK071662, R01 DK066202] NR 39 TC 63 Z9 64 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2008 VL 28 IS 6 BP 1915 EP 1923 DI 10.1128/MCB.01541-07 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270TC UT WOS:000253742100005 PM 18160712 ER PT J AU Liang, MH Wendland, JR Chuang, DM AF Liang, Min-Huel Wendland, Jens R. Chuang, De-Maw TI Lithium inhibits Smad3/4 transactivation via increased CREB activity induced by enhanced PKA and AKT signaling SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Smad; TGF-beta; bipolar disorder; lithium; CBP; p300; AKT; PKA; GSK-3beta ID TISSUE-PLASMINOGEN ACTIVATOR; GLYCOGEN-SYNTHASE KINASE-3; GROWTH-FACTOR-BETA; TPA-DEFICIENT MICE; TRANSCRIPTIONAL ACTIVATION; NEUROPROTECTIVE ACTIVITY; NEURONAL MIGRATION; COACTIVATORS P300; MOUSE HIPPOCAMPUS; INDUCED APOPTOSIS AB Smad proteins are intracellular transducers for transforming growth factor-beta (TGF-beta) signaling and play a critical role in differentiation, tissue repair and apoptosis of the central nervous system. Both TGX-beta and its regulated gene, plasminogen activator inhibitor type-1 (PAI-1), have been implicated in the etiology and progression of neurodegenerative diseases and mood disorders. We previously reported that GSK-3 beta protein depletion suppresses Smad3/4-dependent gene transcription and causes a reduction in PAI-1 expression. Here, we provide evidence that lithium, the drug for the treatment and prophylaxis of bipolar disorder, inhibits Smad-dependent signaling by regulating cAMP-protein kinase A (PKA), AKT-glycogen synthase kinase-3 beta (GSK-3 beta), and CRE-dependent signaling pathways in neuron-enriched cerebral cortical cultures of rats. We demonstrate that lithium-induced activation of these pathways inhibits Smad3/4-dependent gene transcription through an increase in pCREB(Ser133) protein levels, an enhanced interaction between pCREB(ser133) and p300/CBP, which causes Smad3/4-p300/CBP complex disruption and transcriptional suppression of Smad3/4-dependent genes. Therapeutic implications of our findings are discussed. Published by Elsevier Inc. C1 [Liang, Min-Huel; Chuang, De-Maw] Natl Inst Hlth, NIMH, Mol Neurobiol Sect, Bethesda, MD 20892 USA. [Wendland, Jens R.] Natl Inst Hlth, NIMH, Clin Sci Lab, Bethesda, MD USA. RP Chuang, DM (reprint author), Natl Inst Hlth, NIMH, Mol Neurobiol Sect, 10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov RI Wendland, Jens/A-1809-2012 FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [Z01 MH002468] NR 83 TC 48 Z9 49 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAR PY 2008 VL 37 IS 3 BP 440 EP 453 DI 10.1016/j.mcn.2007.10.017 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 273KH UT WOS:000253928500003 PM 18077182 ER PT J AU Porat-Shliom, N Kloog, Y Donaldson, JG AF Porat-Shliom, Natalie Kloog, Yoel Donaldson, Julie G. TI A unique platform for H-Ras signaling involving clathrin-independent endocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PROTEIN-KINASE CASCADE; PHOSPHOINOSITIDE 3-KINASE; K-RAS; CONSTITUTIVE MACROPINOCYTOSIS; CELL INVASION; ARF6; ACTIVATION; PATHWAY; RAB5; TRANSDUCTION AB Trafficking of H-Ras was examined to determine whether it can enter cells through clathrin-independent endocytosis (CIE). H-Ras colocalized with the CIE cargo protein, class I major histocompatibility complex, and it was sequestered in vacuoles that formed upon expression of an active mutant of Arf6, Q67L. Activation of Ras, either through epidermal growth factor stimulation or the expression of an active mutant of Ras, G12V, induced plasma membrane ruffling and macropinocytosis, a stimulated form of CIE. Live imaging of cells expressing H-RasG12V and fluorescent protein chimeras with pleckstrin homology domains that recognize specific phosphoinositides showed that incoming macropinosomes contained phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatiylinositol 3,4,5-trisphosphate (PIP3). PIP2 loss from the macropinosome was followed by the recruitment of Rab5, a downstream target of Ras, and then PIP3 loss. Our studies support a model whereby Ras can signal on macropinosomes that pass through three distinct stages: PIP2/PIP3, PIP3/Rab5, and Rab5. Vacuoles that form in cells expressing Arf6Q67L trap Ras signaling in the first stage, recruiting the active form of the Ras effectors extracellular signal-regulated kinase and protein kinase B (Akt) but not Rab5. Arf6 stimulation of macropinocytosis also involves passage through the distinct lipid phases, but recruitment of Akt is not observed. C1 [Porat-Shliom, Natalie; Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Porat-Shliom, Natalie; Kloog, Yoel] Tel Aviv Univ, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov FU National Heart, Lung, and Blood Institute; National Institutes of Health FX We thank Morris Birnbaum and Mike Frohman for Akt1 and PLD2 constructs; Tamas Balla and Carole Parent for discussions; and Lee Ann Cohen, Ed Korn, and Kirsten Remmert for comments on the manuscript. This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 54 TC 64 Z9 64 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 2008 VL 19 IS 3 BP 765 EP 775 DI 10.1091/mbc.E07-08-0841 PG 11 WC Cell Biology SC Cell Biology GA 344TY UT WOS:000258951400001 PM 18094044 ER PT J AU Ptaszynska, MM Pendrak, ML Bandle, RW Stracke, ML Roberts, DD AF Ptaszynska, Malgorzata M. Pendrak, Michael L. Bandle, Russell W. Stracke, Mary L. Roberts, David D. TI Positive feedback between vascular endothelial growth factor-A and autotaxin in ovarian cancer cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID LYSOPHOSPHATIDIC ACID PRODUCTION; LYSOPHOSPHOLIPASE-D ACTIVITY; FACTOR VEGF; PERMEABILITY FACTOR; FACTOR EXPRESSION; TUMOR; RECEPTOR; MOTILITY; IDENTIFICATION; ACTIVATION AB Tumor cell migration, invasion, and angiogenesis are important determinants of tumor aggressiveness, and these traits have been associated with the motility stimulating protein autotaxin (ATX). This protein is a member of the ectonucleotide pyrophosphatase and phosphodiesterase family of enzymes, but unlike other members of this group, ATX possesses lysophospholipase D activity. This enzymatic activity hydrolyzes lysophosphatidylcholine to generate the potent tumor growth factor and motogen lysophosphatidic acid (LPA). In the current study, we show a link between ATX expression, LPA, and vascular endothelial growth factor (VEGF) signaling in ovarian cancer cell lines. Exogenous addition of VEGF-A to cultured cells induces ATX expression and secretion, resulting in increased extracellular LPA production. This elevated LPA, acting through LPA(4), modulates VEGF responsiveness by inducing VEGF receptor (VEGFR)-2 expression. Down-regulation of ATX secretion in SKOV3 cells using antisense morpholino oligomers significantly attenuates cell motility responses to VEGF, ATX, LIDA, and lysophosphatidylcholine. These effects are accompanied by decreased LPA(4) and VEGFR2 expression as well as by increased release of soluble VEGFR1. Because LPA was previously shown to increase VEGF expression in ovarian cancer, our data suggest a positive feedback loop involving VEGF, ATX, and its product LPA that could affect tumor progression in ovarian cancer cells. C1 [Ptaszynska, Malgorzata M.; Pendrak, Michael L.; Bandle, Russell W.; Stracke, Mary L.; Roberts, David D.] NCI, Ctr Canc Res, NIH, Pathol Lab, Bethesda, MD 20892 USA. RP Stracke, ML (reprint author), NCI, Ctr Canc Res, NIH, Pathol Lab, Bethesda, MD 20892 USA. EM stracke@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS [Z01 BC010673-03] NR 45 TC 48 Z9 51 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2008 VL 6 IS 3 BP 352 EP 363 DI 10.1158/1541-7786.MCR-07-0143 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 278BS UT WOS:000254259100002 PM 18337445 ER PT J AU Robinson, VL Shalhav, O Tto, K Kawai, T Gorospe, M Rinker-Schaeffer, CW AF Robinson, Victoria L. Shalhav, Ore Otto, Kristen Kawai, Tomoko Gorospe, Myriam Rinker-Schaeffer, Carrie W. TI Mitogen-activated protein kinase kinase 4/c-Jun NH2-terminal kinase kinase 1 protein expression is subject to translational regulation in prostate cancer cell lines SO MOLECULAR CANCER RESEARCH LA English DT Article ID METASTASIS-SUPPRESSOR GENE; CANDIDATE TUMOR-SUPPRESSOR; MESSENGER-RNA; SIGNAL-TRANSDUCTION; CARCINOMA CELLS; MKK4; STRESS; IDENTIFICATION; DEGRADATION; CONNECTION AB Mitogen-activated protein kinase kinase 4/c-Jun NH2-terminal kinase kinase 1 (MKK4/JNKK1; hereafter referred to as MKK4) is a dual-specificity kinase with a critical role in regulating the activity of c-Jun NH2-terminal kinase and p38 kinases. We identified a novel biological function for MKK4 in the regulation of growth of ovarian and prostate cancer metastases. Clinical correlative studies showed that MKK4 protein levels were reduced in high-grade prostate cancer and prostate and ovarian cancer metastases compared with normal tissue, which prompted investigation into the mechanism(s) responsible for down-regulation of MKK4 in a panel of cancer cell lines. Initial studies found that low levels of MKK4 protein did not correlate with either exon deletion or decreased levels of MKK4 mRNA, suggesting that MKK4 protein levels were regulated posttranscriptionally by either reduced translation or reduced protein stability. Endogenous MKK4 was highly stable and not subject to altered proteolysis. Instead, MKK4, biosynthesis seemed to be regulated by altered translation. In support of this assertion, we found that cytosolic MKK4 mRNA was shifted toward active polysomes in cells with higher levels of MKK4 protein, suggesting that MKK4 mRNA was translated more efficiently in these cells. This study supports a novel mechanism for the regulation of MKK4 protein levels. Further, these findings have potential therapeutic implications for modulating the expression of a signaling kinase involved in the regulation of metastatic growth. C1 [Robinson, Victoria L.; Shalhav, Ore; Otto, Kristen; Rinker-Schaeffer, Carrie W.] Univ Chicago, Urol Sect, Dept Surg, Chicago, IL 60637 USA. [Robinson, Victoria L.; Shalhav, Ore; Otto, Kristen; Rinker-Schaeffer, Carrie W.] Univ Chicago, Committee Canc Biol, Chicago, IL 60637 USA. [Kawai, Tomoko; Gorospe, Myriam] NIA, Intramural Res Program, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Rinker-Schaeffer, CW (reprint author), Univ Chicago, Urol Sect, Dept Surg, MC 6038,5841 S Maryland Ave, Chicago, IL 60637 USA. EM crinkers@uchicago.edu FU Intramural NIH HHS [Z01 AG000511-10]; NCI NIH HHS [R01 CA-89569, R01 CA089569] NR 42 TC 11 Z9 13 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2008 VL 6 IS 3 BP 501 EP 508 DI 10.1158/1541-7786.MCR-07-2075 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 278BS UT WOS:000254259100016 PM 18337456 ER PT J AU Shukla, A Ho, Y Liu, X Ryscavage, A Glick, AB AF Shukla, Anjali Ho, Yan Liu, Xin Ryscavage, Andrew Glick, Adam B. TI Cripto-1 alters keratinocyte differentiation via blockade of transforming growth factor-beta 1 signaling: Role in skin carcinogenesis SO MOLECULAR CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; MAMMARY EPITHELIAL-CELLS; TGF-BETA; EPIDERMAL-KERATINOCYTES; VERTEBRATE DEVELOPMENT; MALIGNANT CONVERSION; MOUSE KERATINOCYTES; EXPRESSION; INDUCTION; ONCOGENE AB Cripto-1 is an epidermal growth factor-Cripto/FRL1/Cryptic family member that plays a role in early embryogenesis as a coreceptor for Nodal and is overexpressed in human tumors. Here we report that in the two-stage mouse skin carcinogenesis model, Cripto-1 is highly up-regulated in tumor promoter-treated normal skin and in benign papillomas. Treatment of primary mouse keratinocytes with Cripto-1 stimulated proliferation and induced expression of keratin 8 but blocked induction of tie normal epidermal differentiation marker keratin 1, changes that are hallmarks of tumor progression in squamous cancer. Chemical or genetic blockade of the transforming growth factor (TGF)-beta 1 signaling pathway using the ALK5 kinase inhibitor SB431542 and dominant negative TGF-beta type II receptor, respectively, had similar effects on keratinocyte differentiation. Our results show that Cripto-1 could block TGF-beta 1 receptor binding, phosphorylation of Smad2 and Smad3, TGF-beta-responsive luciferase reporter activity, and TGF-beta 1-mediated senescence of keratinocytes. We suggest that inhibition of TGF-beta 1 by Cripto-1 may play an important role in altering the differentiation state of keratinocytes and promoting outgrowth of squamous tumors in the mouse epidermis. C1 [Glick, Adam B.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Shukla, Anjali; Ho, Yan; Liu, Xin; Ryscavage, Andrew] Natl Canc Inst, Lab Canc Biol & Genet, Bethesda, MD USA. RP Glick, AB (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. EM abg11@psu.edu RI Shukla, Anjali/G-4046-2014 FU Intramural NIH HHS; NCI NIH HHS [CA122109] NR 36 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2008 VL 6 IS 3 BP 509 EP 516 DI 10.1158/1541-7786.MCR-07-0396 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 278BS UT WOS:000254259100017 PM 18337457 ER PT J AU Alyacloub, FS Liu, Y Tao, LH Steele, VE Lubet, RA Pereira, MA AF Alyacloub, Fadel S. Liu, Yue Tao, Lianhui Steele, Vernon E. Lubet, Ronald A. Pereira, Michael A. TI Modulation by bexarotene of mRNA expression of genes in mouse lung tumors SO MOLECULAR CARCINOGENESIS LA English DT Article DE chemoprevention; therapy; real time RT-PCR; retinoid X receptor ID RETINOID-X-RECEPTOR; PHASE-II TRIAL; APOLIPOPROTEIN-D; SIGNALING PATHWAY; TRANSGENIC MICE; CANCER CELLS; EPIREGULIN; LGD1069; GROWTH; TUMORIGENESIS AB Bexarotene has demonstrated chemopreventive and therapeutic efficacy towards mouse lung tumors. Using specimens from our published study that demonstrated the efficacy of bexarotene, we report herein its ability to modulate mRNA expression of genes in both lung and lung tumors. Strain A/J mice were administered vinyl carbamate to induce lung tumors. This was followed by 200 mg/kg body weight of bexarotene administered by oral gavage during Wks 4-25 or 23-25. The mice were sacrificed at Wk 25. The expression of 26 genes was decreased in lung tumors, whereas only two genes, Apolipoprotein D and CYP26b, had their mRNA expression increased by bexarotene. Genes with increased mRNA expression in untreated lung tumors include: epiregulin and kininogen-1 (increased by more than 40-fold) and Caspase-3, Cyclin D1, DNA methyltransferase 3a (Dnmt-3a), E-prostanoid 3 receptor (EP3), c-myc, surfactant protein-C, and survivin (increased by 1.7- to 3.6-fold). Bexarotene decreased the mRNA expression of Caspase-3, Dnmt-3a, EP3, and survivin, as well as the expression of the Cyclin El, estrogen receptor-alpha, and iNOS genes. Bexarotene had a greater effect in decreasing the expression of Caspase-3, Cyclin El, Dnmt-3a, EP3, NOS, and survivin, when administered to mice with established tumors than when administered to mice while tumors were emerging. In summary, bexarotene modulated mRNA expression of genes in mouse lung tumors, being more effective in established tumors than in emerging tumors, suggesting that modulation of expression could be useful as a biomarker for the therapeutic and chemopreventive activity of the drug, especially in established tumors. (C) 2007 Wiley-Liss, Inc. C1 [Liu, Yue; Tao, Lianhui; Pereira, Michael A.] Ohio State Univ, Coll Med, Div Hematol & Oncol, Columbus, OH 43210 USA. [Alyacloub, Fadel S.; Pereira, Michael A.] Med Univ Ohio, Dept Biochem & Canc Biol, Toledo, OH USA. [Steele, Vernon E.; Lubet, Ronald A.] NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Pereira, MA (reprint author), Ohio State Univ, Dept Internal Med, Coll Med & Publ Hlth, 300 W 10th Ave,1148 CHRI, Columbus, OH 43210 USA. FU NCI NIH HHS [N01-CN-25106, N01-CN-25126, R01-CA096129] NR 31 TC 9 Z9 9 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 2008 VL 47 IS 3 BP 165 EP 171 DI 10.1002/mc.20383 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 278CE UT WOS:000254260300001 PM 17849452 ER PT J AU Vincent, LM Blake, T Hess, R Gahl, WA Huizing, M AF Vincent, L. M. Blake, T. Hess, R. Gahl, W. A. Huizing, M. TI Rescuing a common mutation in Hermansky-Pudlak syndrome Type 1 using exon skipping. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2008) CY MAR 02-05, 2008 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders C1 [Vincent, L. M.; Hess, R.; Gahl, W. A.; Huizing, M.] NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. [Blake, T.] NIH, NHGRI, Genet & Mol Biol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2008 VL 93 IS 3 MA 11 BP 236 EP 236 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 268TU UT WOS:000253603300021 ER PT J AU Adams, D Morgan, CP Brooks, B Yang, S Tifft, CJ AF Adams, D. Morgan, C. P. Brooks, B. Yang, S. Tifft, C. J. TI Juvenile Q(M1) gangliosidosis: Clinical summary of a cohort of seven affected patients. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2008) CY MAR 02-05, 2008 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders C1 [Adams, D.; Tifft, C. J.] Natl Inst Hlth, NHGRI, Bethesda, MD USA. [Morgan, C. P.; Tifft, C. J.] Natl Inst Hlth, NIDDK, Bethesda, MD USA. [Brooks, B.] Natl Inst Hlth, NEI, Bethesda, MD USA. [Yang, S.; Tifft, C. J.] Childrens Natl Med Ctr, Dept Genet & Metab, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2008 VL 93 IS 3 MA 3 BP 240 EP 240 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 268TU UT WOS:000253603300023 ER PT J AU James, PM Ryan, C Engle, EC Tang, JR Kaler, SG Berry, GT AF James, P. M. Ryan, C. Engle, E. C. Tang, J. R. Kaler, S. G. Berry, G. T. TI Menke disease phenocopy in a female with normal ATP7A coding sequence. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2008) CY MAR 02-05, 2008 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders C1 [James, P. M.; Berry, G. T.] Childrens Hosp, Dept Pediat, Div Genet, Boston, MA USA. [Ryan, C.; Engle, E. C.] Childrens Hosp, Dept Pediat, Div Neurol, Boston, MA USA. [Tang, J. R.; Kaler, S. G.] NIH, Lab Clin Genom, Unit Pediat Genet, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2008 VL 93 IS 3 MA 9 BP 241 EP 242 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 268TU UT WOS:000253603300029 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, Randy J. Venditti, Charles P. TI Genetic therapy rescues a neonatal lethal murine model of mut(0) methylmalonic acidemia. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2008) CY MAR 02-05, 2008 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders C1 [Chandler, Randy J.; Venditti, Charles P.] Natl Inst Hlth, Natl Human Genome Res Branch, Genet Dis Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2008 VL 93 IS 3 MA 20 BP 244 EP 245 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 268TU UT WOS:000253603300040 ER PT J AU Huizing, M Pei, W Dorward, H Ly, L Klootwijk, E Wassif, CA Porter, FD Gahl, WA Feldman, B Anikster, Y AF Huizing, M. Pei, W. Dorward, H. Ly, L. Klootwijk, E. Wassif, C. A. Porter, F. D. Gahl, W. A. Feldman, B. Anikster, Y. TI 3-Methylglutaconic aciduria type III: Insights into the OPA3 protein. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2008) CY MAR 02-05, 2008 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders C1 [Huizing, M.; Dorward, H.; Ly, L.; Klootwijk, E.; Gahl, W. A.] NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Pei, W.; Feldman, B.] NIH, NHGRI, Med Genet Branch, Vertebrate Embryol Sect, Bethesda, MD 20892 USA. [Wassif, C. A.; Porter, F. D.] NIH, NICHD, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2008 VL 93 IS 3 MA 44 BP 251 EP 252 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 268TU UT WOS:000253603300064 ER PT J AU Introne, WJ Kayser, MA Tsilou, ET O'Brien, KE Bryant, J Bernardini, I Gahl, WA AF Introne, W. J. Kayser, M. A. Tsilou, E. T. O'Brien, K. E. Bryant, J. Bernardini, I. Gahl, W. A. TI Tolerance of elevated tyrosine levels in patients with alkaptonuria receiving nitisinone. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2008) CY MAR 02-05, 2008 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders C1 [Introne, W. J.; O'Brien, K. E.; Bryant, J.; Gahl, W. A.] NIH, NHGRI, OCD, Bethesda, MD 20892 USA. [Kayser, M. A.] Ctr Genet Testing St Francis, Warren Clin Ctr Genet, Tulsa, OK USA. [Tsilou, E. T.] NIH, NEI, Bethesda, MD 20892 USA. [Bernardini, I.; Gahl, W. A.] NIH, NHGRI, MGB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2008 VL 93 IS 3 MA 45 BP 252 EP 252 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 268TU UT WOS:000253603300065 ER PT J AU James, PM Ryan, C Engle, EC Tang, JR Kaler, SG Berry, GT AF James, P. M. Ryan, C. Engle, E. C. Tang, J. R. Kaler, S. G. Berry, G. T. TI Menke disease phenocopy in a female with normal ATP7A coding sequence. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2008) CY MAR 02-05, 2008 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders C1 [James, P. M.; Berry, G. T.] Childrens Hosp, Dept Pediat, Div Genet, Boston, MA USA. [Ryan, C.; Engle, E. C.] Childrens Hosp, Dept Pediat, Div Neurol, Boston, MA USA. [Tang, J. R.; Kaler, S. G.] NIH, Lab Clin Genom, Unit Pediat Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2008 VL 93 IS 3 MA 46 BP 252 EP 252 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 268TU UT WOS:000253603300066 ER PT J AU Helternes-Harris, LM Gearhart, PJ Ghosh, P Longo, DL AF Helternes-Harris, Lynn M. Gearhart, Patricia J. Ghosh, Paritosh Longo, Dan L. TI Activation-induced deaminase-mediated class switch recombination is blocked by anti-IgM signaling in a phosphatidylinositol 3-kinase-dependent fashion SO MOLECULAR IMMUNOLOGY LA English DT Article DE B cells; antibodies; activation-induced deaminase; cell activation ID INDUCED-CYTIDINE-DEAMINASE; SINGLE-STRANDED-DNA; MURINE-B-CELLS; NF-KAPPA-B; SOMATIC HYPERMUTATION; GENE CONVERSION; DIVERSIFICATION ENZYME; CD40 LIGAND; AID GENE; EXPRESSION AB Activation-induced deaminase (AID) is expressed inactivated B lymphocytes and initiates somatic hypermutation and class switch recombination. To determine if different stimuli affect the expression and function of AID, we monitored AID activity in murine B cells stimulated ex vivo with various ligands. AID was rapidly expressed at both the RNA and protein levels following stimulation with LPS, LPS plus IL-4, and anti-CD40 plus IL-4, but was delayed after stimulation with anti-IgM plus IL-4. By day 4, AID was expressed in all groups; however, cells stimulated with anti-IgM plus IL-4 did not undergo switch recombination. These cells expressed normal levels of gamma 1 germline transcripts, implying that the gamma 1 switch region was accessible. Furthermore, switching was suppressed by the addition of anti-IgM to cells stimulated with LPS plus IL-4 or anti-CD40 plus IL-4, even though AID was expressed. The lack of class switch recombination could be reversed by inhibition of phosphatidylinositol 3-kinase (PI3K). This suggests that activation through the B cell receptor induces PI3K, which interferes with the function of AID. Published by Elsevier Ltd. C1 [Gearhart, Patricia J.] NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Helternes-Harris, Lynn M.; Ghosh, Paritosh; Longo, Dan L.] NIA, NIH, Immunol Lab, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000164-06, Z01 AG000732-12] NR 43 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAR PY 2008 VL 45 IS 6 BP 1799 EP 1806 DI 10.1016/j.molimm.2007.09.020 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 276ZI UT WOS:000254181800027 PM 17983655 ER PT J AU Chouker, A Thiel, M Lukashev, D Ward, JM Kaufmann, I Apasov, S Sitkovsky, MV Ohta, A AF Chouker, Alexander Thiel, Manfred Lukashev, Dmitriy Ward, Jerrold M. Kaufmann, Ines Apasov, Sergey Sitkovsky, Michail V. Ohta, Akio TI Critical role of hypoxia and A2A adenosine receptors in liver tissue-protecting physiological anti-inflammatory pathway SO MOLECULAR MEDICINE LA English DT Article ID FULMINANT HEPATIC-FAILURE; TUMOR-NECROSIS-FACTOR; CONCANAVALIN-A; CELL ACTIVATION; INTERFERON-GAMMA; IMMUNE-RESPONSE; T-CELLS; B-VIRUS; IN-VIVO; INJURY AB Whole body exposure of wild type control littermates and A2A adenosine receptor (A2AR) gene deleted mice to low oxygen containing inspired gas mixture allowed the investigation of the mechanism that controls inflammatory liver damage and protects the liver using a mouse model of T cell-mediated viral and autoimmune hepatitis. We tested the hypothesis that the inflammatory tissue damage-associated hypoxia and extracellular adenosine 4 A2AR signaling plays an important role in the physiological anti-inflammatory mechanism that limits liver damage during fulminant hepatitis. After induction of T cell-mediated hepatitis, mice were kept in modular chambers either under normoxic (21% oxygen) or hypoxic (10% oxygen) conditions for 8 h. It was shown that the whole body exposure to hypoxic atmosphere caused tissue hypoxia in healthy animals as evidenced by a decrease in the arterial blood oxygen tension and increase of the plasma adenosine concentration (P < 0.05). This "hypoxic" treatment resulted in significantly reduced hepatocellular damage and attenuated levels of serum cytokines in mice with acute liver inflammation. The anti-inflammatory effects of hypoxia were not observed in the absence of A2AR in studies of A2AR gene-deficient mice or when A2AR have been pharmacologically antagonized with synthetic antagonist. The presented data demonstrate that total body hypoxia-triggered pathway provides protection in acute hepatitis and that hypoxia (upstream) and A2AR (downstream) function in the same immunosuppressive and liver tissue-protecting pathway. C1 [Lukashev, Dmitriy; Sitkovsky, Michail V.; Ohta, Akio] Northeastern Univ, New England Informat & Tissue Protect Inst, Boston, MA 02115 USA. [Chouker, Alexander; Thiel, Manfred; Kaufmann, Ines] Univ Munich, Dept Anesthesiol, Klinikum Grosshadern, Munich, Germany. [Chouker, Alexander; Lukashev, Dmitriy; Ward, Jerrold M.; Apasov, Sergey; Sitkovsky, Michail V.; Ohta, Akio] NIAID, NIH, Bethesda, MD 20892 USA. RP Ohta, A (reprint author), Northeastern Univ, New England Informat & Tissue Protect Inst, 360 Huntington Ave,113 Mugar Hlth Sci Bldg, Boston, MA 02115 USA. EM o.ohto@neu.edu RI Lukashev, Dmitriy/F-8133-2010 NR 43 TC 25 Z9 27 U1 0 U2 0 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR-APR PY 2008 VL 14 IS 3-4 BP 116 EP 123 DI 10.2119/2007-00075.Chouker PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 273NV UT WOS:000253938700004 PM 18163162 ER PT J AU Seiple, LA Cardellina, JH Akee, R Stivers, JT AF Seiple, Lauren A. Cardellina, John H. Akee, Rhone, II Stivers, James T. TI Potent inhibition of human apurinic/apyrimidinic endonuclease 1 by arylstibonic acids SO MOLECULAR PHARMACOLOGY LA English DT Article ID BASE-EXCISION-REPAIR; DNA-DAMAGING AGENTS; HUMAN ABASIC ENDONUCLEASE; SMALL-MOLECULE INHIBITOR; MAJOR HUMAN; PROGNOSTIC-SIGNIFICANCE; NUCLEAR EXPRESSION; ALTERED EXPRESSION; ALKYLATING-AGENTS; BINDING ACTIVITY AB Human apurinic/apyrimidinic endonuclease (Ape1) plays an important role by processing the > 10,000 highly toxic abasic sites generated in the genome of each cell every day. Ape1 has recently emerged as a target for inhibition, in that its overexpression in tumors has been linked with poor response to both radiation and chemotherapy and lower overall patient survival. Inhibition of Ape1 using siRNA or the expression of a dominant-negative form of the protein has been shown to sensitize cells to DNA-damaging agents, including various chemotherapeutic agents. However, potent small-molecule inhibitors of Ape1 remain to be found. To this end, we screened Ape1 against the NCI Diversity Set of small molecules and discovered aromatic nitroso, carboxylate, sulfonamide, and arylstibonic acid compounds with micromolar affinities for the protein. A further screen of a 37-compound arylstibonic acid sublibrary identified ligands with IC50 values in the range of 4 to 300 nM. The negatively charged stibonic acids act by a partial-mixed mode and probably serve as DNA phosphate mimics. These compounds provide a useful scaffold for development of chemotherapeutic agents against Ape1. C1 [Seiple, Lauren A.; Stivers, James T.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Cardellina, John H.] Frederick Canc Res & Dev Ctr, Natl Canc Inst, Screening Technol Branch, Frederick, MD USA. [Akee, Rhone, II] SAIC Inc, Frederick Canc Res & Dev Ctr, Nat Prod Support Grp, Frederick, MD USA. RP Stivers, JT (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, 75 N Wolfe St, Baltimore, MD 21205 USA. EM jstivers@jhmi.edu FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIGMS NIH HHS [R01 GM056834, GM56834, R01 GM056834-12] NR 40 TC 43 Z9 44 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2008 VL 73 IS 3 BP 669 EP 677 DI 10.1124/mol.107.042622 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266OE UT WOS:000253444900008 PM 18042731 ER PT J AU Loland, CJ Desai, RI Zou, MF Cao, J Grundt, P Gerstbrein, K Sitte, HH Newman, AH Katz, JL Gether, U AF Loland, Claus J. Desai, Rajeev I. Zou, Mu-Fa Cao, Jianjing Grundt, Peter Gerstbrein, Klaus Sitte, Harald H. Newman, Amy Hauck Katz, Jonathan L. Gether, Ulrik TI Relationship between conformational changes in the dopamine transporter and cocaine-like subjective effects of uptake inhibitors SO MOLECULAR PHARMACOLOGY LA English DT Article ID 3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; SEROTONIN TRANSPORTER; BENZTROPINE ANALOGS; RHESUS-MONKEYS; IN-VITRO; BINDING; LIGANDS; IDENTIFICATION; RIMCAZOLE; RESIDUES AB Cocaine exerts its stimulatory effect by inhibiting the dopamine transporter (DAT). However, novel benztropine- and rimcazole-based inhibitors show reduced stimulant effects compared with cocaine, despite higher affinity and selectivity for DAT. To investigate possible mechanisms, we compared the subjective effects of different inhibitors with their molecular mode of interaction at the DAT. We determined how different inhibitors affected accessibility of the sulfhydryl-reactive reagent [2-(trimethylammonium) ethyl]-methanethiosulfonate to an inserted cysteine (I159C), which is accessible when the extracellular transporter gate is open but inaccessible when it is closed. The data indicated that cocaine analogs bind an open conformation, whereas benztropine and rimcazole analogs bind a closed conformation. Next, we investigated the changes in inhibition potency of [H-3] dopamine uptake of the compounds at a mutant DAT (Y335A) characterized by a global change in the conformational equilibrium. We observed a close relationship between the decrease in potencies of inhibitors at this mutant and cocaine-like responding in rats trained to discriminate cocaine from saline injections. Our data suggest that chemically different DAT inhibitors stabilize distinct transporter conformations and that this in turn affects the cocaine-like subjective effects of these compounds in vivo. C1 [Loland, Claus J.; Gether, Ulrik] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, Mol Neuropharmacol Grp, DK-2200 Copenhagen, Denmark. [Zou, Mu-Fa; Cao, Jianjing; Grundt, Peter; Newman, Amy Hauck] Natl Inst Hlth, Natl Inst Drug Abuse, Dept Hlth & Human Serv, Med Discovery Res Branch,Intramural Res Program,, Baltimore, MD USA. [Gerstbrein, Klaus; Sitte, Harald H.] Med Univ Vienna, Ctr Biomol Med & Pharmacol, Inst Pharmacol, Vienna, Austria. RP Loland, CJ (reprint author), Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, Mol Neuropharmacol Grp, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM claus@neuropharm.ku.dk RI Sitte, Harald/N-2681-2013; Loland, Claus/E-5975-2014; OI Sitte, Harald/0000-0002-1339-7444; Loland, Claus/0000-0002-1773-1446; Gether, Ulrik/0000-0002-0020-3807; Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [P01 DA-12408] NR 39 TC 72 Z9 73 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2008 VL 73 IS 3 BP 813 EP 823 DI 10.1124/mol.107.039800 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266OE UT WOS:000253444900022 PM 17978168 ER PT J AU Wada, T Kang, HS Angers, M Gong, H Bhatia, S Khadem, S Ren, S Ellis, E Strom, SC Jetten, AM Xie, W AF Wada, Taira Kang, Hong Soon Angers, Martin Gong, Haibiao Bhatia, Shikha Khadem, Shaheen Ren, Songrong Ellis, Ewa Strom, Stephen C. Jetten, Anton M. Xie, Wen TI Identification of oxysterol 7 alpha-hydroxylase (Cyp7b1) as a novel retinoid-related orphan receptor alpha ( ROR alpha) (NR1F1) target gene and a functional cross-talk between ROR alpha and liver X receptor (NR1H3) SO MOLECULAR PHARMACOLOGY LA English DT Article ID ELEMENT-BINDING PROTEIN; NUCLEAR RECEPTOR; LXR-ALPHA; TRANSCRIPTIONAL REGULATION; ALZHEIMERS-DISEASE; RESPONSE ELEMENT; STAGGERER MOUSE; MICE; ACTIVATION; BETA AB The retinoid-related orphan receptors (RORs) and liver X receptors (LXRs) were postulated to have distinct functions. RORs play a role in tissue development and circadian rhythm, whereas LXRs are sterol sensors that affect lipid homeostasis. In this study, we revealed a novel function of ROR alpha (NR1F1) in regulating the oxysterol 7 alpha-hydroxylase (Cyp7b1), an enzyme critical for the homeostasis of cholesterol, bile acids, and oxysterols. The expression of Cyp7b1 gene was suppressed in the ROR alpha null (ROR alpha(sg/sg)) mice, suggesting ROR alpha as a positive regulator of Cyp7b1. Promoter analysis established Cyp7b1 as a transcriptional target of ROR alpha, and transfection of ROR alpha induced the expression of endogenous Cyp7b1 in the liver. Interestingly, Cyp7b1 regulation seemed to be ROR alpha-specific, because ROR gamma had little effect. Reporter gene analysis showed that the activation of Cyp7b1 gene promoter by ROR alpha was suppressed by LXR alpha (NR1H3), whereas ROR alpha inhibited both the constitutive and ligand-dependent activities of LXR alpha. The mutual suppression between ROR alpha and LXR was supported by the in vivo observation that loss of ROR alpha increased the expression of selected LXR target genes, leading to hepatic triglyceride accumulation. Likewise, mice deficient of LXR alpha and beta isoforms showed activation of selected ROR alpha target genes. Our results have revealed a novel role for ROR alpha and a functional interplay between ROR alpha and LXR in regulating endo-and xenobiotic genes, which may have broad implications in metabolic homeostasis. C1 [Jetten, Anton M.] NIEHS, Cell Biol Sect, Res Triangle Pk, NC 27709 USA. [Wada, Taira; Gong, Haibiao; Bhatia, Shikha; Khadem, Shaheen; Ren, Songrong; Xie, Wen] Univ Pittsburgh, Ctr Pharmacogenet, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. [Kang, Hong Soon; Angers, Martin; Jetten, Anton M.] NIEHS, NIH, Div Intramural Res, Cell Biol Sect, Res Triangle Pk, NC USA. [Ellis, Ewa; Strom, Stephen C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. RP Xie, W (reprint author), Univ Pittsburgh, Ctr Pharmacogenet, 633 Salk Hall, Pittsburgh, PA 15213 USA. EM jetten@niehs.nih.gov; wex6@pitt.edu RI Ellis, Ewa/D-5370-2014; Xie, Wen/M-1768-2016; OI Ellis, Ewa/0000-0002-3057-5337; Strom, Stephen/0000-0002-2889-3387; Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS; NCI NIH HHS [CA107011]; NIDDK NIH HHS [N01-DK70004]; NIEHS NIH HHS [ES014626]; PHS HHS [HHSN267200700004C] NR 55 TC 53 Z9 57 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2008 VL 73 IS 3 BP 891 EP 899 DI 10.1124/mol.107.040741 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266OE UT WOS:000253444900029 PM 18055760 ER PT J AU van Waterschoot, RAB van Herwaarden, AE Lagas, JS Sparidans, RW Wagenaar, E van der Kruijssen, CMM Goldstein, JA Zeldin, DC Beijnen, JH Schinkel, AH AF van Waterschoot, Robert A. B. van Herwaarden, Antonius E. Lagas, Jurjen S. Sparidans, Rolf W. Wagenaar, Els van der Kruijssen, Cornelia M. M. Goldstein, Joyce A. Zeldin, Darryl C. Beijnen, Jos H. Schinkel, Alfred H. TI Midazolam metabolism in cytochrome P450 3A knockout mice can be attributed to up-regulated CYP2C enzymes SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN LIVER-MICROSOMES; IN-VITRO METABOLISM; ARACHIDONIC-ACID; PHENYTOIN INDUCTION; TRANSGENIC MICE; MOUSE MODELS; HUMAN CYP3A4; EXPRESSION; GENE; INHIBITION AB The cytochrome P450 3A (CYP3A) enzymes represent one of the most important drug-metabolizing systems in humans. Recently, our group has generated cytochrome P450 3A knockout mice to study this drug-handling system in vivo. In the present study, we have characterized the Cyp3a knockout mice by studying the metabolism of midazolam, one of the most widely used probes to assess CYP3A activity. We expected that the midazolam metabolism would be severely reduced in the absence of CYP3A enzymes. We used hepatic and intestinal microsomal preparations from Cyp3a knockout and wild-type mice to assess the midazolam metabolism in vitro. In addition, in vivo metabolite formation was determined after intravenous administration of midazolam. We were surprised to find that our results demonstrated that there is still marked midazolam metabolism in hepatic (but not intestinal) microsomes from Cyp3a knockout mice. Accordingly, we found comparable amounts of midazolam as well as its major metabolites in plasma after intravenous administration in Cyp3a knockout mice compared with wild-type mice. These data suggested that other hepatic cytochrome P450 enzymes could take over the midazolam metabolism in Cyp3a knockout mice. We provide evidence that CYP2C enzymes, which were found to be up-regulated in Cyp3a knockout mice, are primarily responsible for this metabolism and that several but not all murine CYP2C enzymes are capable of metabolizing midazolam to its 1'-OH and/or 4-OH derivatives. These data illustrate interesting compensatory changes that may occur in Cyp3a knockout mice. Such flexible compensatory interplay between functionally related detoxifying systems is probably essential to their biological role in xenobiotic protection. C1 [van Waterschoot, Robert A. B.; van Herwaarden, Antonius E.; Lagas, Jurjen S.; Wagenaar, Els; van der Kruijssen, Cornelia M. M.; Schinkel, Alfred H.] Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands. [Sparidans, Rolf W.] Univ Utrecht, Dept Pharmaceut Sci, NL-3508 TC Utrecht, Netherlands. [Beijnen, Jos H.] Slotervaart Hosp, Dept Pharmacol & Pharm, Amsterdam, Netherlands. [Goldstein, Joyce A.] NIH, NIEHS, Chem Pharmacol Lab, Res Triangle Pk, NC USA. [Zeldin, Darryl C.] NIH, NIEHS, Lab Respirat Biol, Res Triangle Pk, NC USA. RP Schinkel, AH (reprint author), Netherlands Canc Inst, Div Expt Therapy, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM a.schinkel@nki.nl RI Goldstein, Joyce/A-6681-2012; Herwaarden, A.E./L-4369-2015 FU Intramural NIH HHS [Z01 ES025034-13] NR 28 TC 58 Z9 58 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2008 VL 73 IS 3 BP 1029 EP 1036 DI 10.1124/mol.107.043869 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266OE UT WOS:000253444900044 PM 18156313 ER PT J AU Tan, HY Callicott, JH Weinberger, DR AF Tan, H-Y Callicott, J. H. Weinberger, D. R. TI Intermediate phenotypes in schizophrenia genetics redux: is it a no brainer? SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID CATECHOL-O-METHYLTRANSFERASE; GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; WORKING-MEMORY; TWINS DISCORDANT; ENDOPHENOTYPE CONCEPT; PSYCHIATRIC GENETICS; PREFRONTAL CORTEX; MONOZYGOTIC TWINS; RISK C1 [Tan, H-Y; Callicott, J. H.; Weinberger, D. R.] Natl Inst Hlth, NIMH, Cognit & Psychosis Program, Intramural Res Program,Clin Brain Disorders, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), Natl Inst Hlth, NIMH, Cognit & Psychosis Program, Intramural Res Program,Clin Brain Disorders, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 NR 58 TC 74 Z9 76 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2008 VL 13 IS 3 BP 233 EP 238 DI 10.1038/sj.mp.4002145 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 263TE UT WOS:000253238600001 PM 18285755 ER PT J AU Buckholtz, JW Callicott, JH Kolachana, B Hariri, AR Goldberg, TE Genderson, M Egan, MF Mattay, VS Weinberger, DR Meyer-Lindenberg, A AF Buckholtz, J. W. Callicott, J. H. Kolachana, B. Hariri, A. R. Goldberg, T. E. Genderson, M. Egan, M. F. Mattay, V. S. Weinberger, D. R. Meyer-Lindenberg, A. TI Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality SO MOLECULAR PSYCHIATRY LA English DT Article DE fMRI; antisocial; functional connectivity; effective connectivity; amygdala; cingulate; emotion regulation ID MONOAMINE-OXIDASE-A; DECISION-MAKING; BRAIN ACTIVITY; FUNCTIONAL POLYMORPHISM; NEURAL MECHANISMS; MACAQUE MONKEYS; NEGATIVE AFFECT; WORKING-MEMORY; RHESUS-MONKEY; CORTEX AB Little is known about neural mechanisms underlying human personality and temperament, despite their considerable importance as highly heritable risk mediators for somatic and psychiatric disorders. To identify these circuits, we used a combined genetic and imaging approach focused on Monoamine Oxidase A (MAOA), encoding a key enzyme for monoamine metabolism previously associated with temperament and antisocial behavior. Male carriers of a low-expressing genetic variant exhibited dysregulated amygdala activation and increased functional coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted increased harm avoidance and decreased reward dependence scores, suggesting that this circuitry mediates a part of the association of MAOA with these traits. We utilized path analysis to parse the effective connectivity within this system, and provide evidence that vmPFC regulates amygdala indirectly by influencing rostral cingulate cortex function. Our data implicate a neural circuit for variation in human personality under genetic control, provide an anatomically consistent mechanism for vmPFC-amygdala interactions underlying this variation, and suggest a role for vmPFC as a superordinate regulatory area for emotional arousal and social behavior. C1 [Buckholtz, J. W.; Callicott, J. H.; Kolachana, B.; Hariri, A. R.; Goldberg, T. E.; Genderson, M.; Mattay, V. S.; Weinberger, D. R.; Meyer-Lindenberg, A.] NIH, NIMH, DHHS, Clin Brain Disorders Branch Genes Cognit & Psycho, Bethesda, MD 20892 USA. [Buckholtz, J. W.; Callicott, J. H.; Mattay, V. S.; Meyer-Lindenberg, A.] NIH, NIMH, DHHS, Neuroimaging Core Facil, Bethesda, MD USA. [Meyer-Lindenberg, A.] NIH, NIMH, DHHS, Unit Syst Neurosci Psychiat, Bethesda, MD USA. RP Meyer-Lindenberg, A (reprint author), NIH, NIMH, DHHS, Clin Brain Disorders Branch Genes Cognit & Psycho, 10-3C103, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov RI Hariri, Ahmad/D-5761-2011; Buckholtz, Joshua /E-7299-2010; Callicott, Joseph/C-9102-2009; OI Buckholtz, Joshua /0000-0002-9418-8686; Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 69 TC 127 Z9 130 U1 6 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2008 VL 13 IS 3 BP 313 EP 324 DI 10.1038/sj.mp.4002020 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 263TE UT WOS:000253238600012 PM 17519928 ER PT J AU Ducci, F Enoch, MA Hodgkinson, C Xu, K Catena, M Robin, RW Goldman, D AF Ducci, F. Enoch, M-A Hodgkinson, C. Xu, K. Catena, M. Robin, R. W. Goldman, D. TI Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women SO MOLECULAR PSYCHIATRY LA English DT Article DE alcoholism; antisocial personality disorder; MAOA; MAOA-LPR; MAOB; childhood; sexual abuse; gene by environment interaction ID MONOAMINE-OXIDASE-A; POSTTRAUMATIC-STRESS-DISORDER; AMERICAN-INDIAN TRIBE; HUMAN-BRAIN; GENE PROMOTER; MENTAL-HEALTH; CAGE QUESTIONNAIRE; GENOTYPE; LOCALIZATION; ASSOCIATION AB Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder ( ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior. Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone. Participants included 168 alcoholics (39 with ASPD (antisocial alcoholics) and 123 controls (no alcoholics, no ASPD). Antisocial behavior was also modeled as a continuous trait: ASPD symptoms count. The MAOA-LPR low activity allele was associated with alcoholism (P = 0.005), particularly antisocial alcoholism (P = 0.00009), only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women. The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P = 0.008) and antisocial alcoholics (P = 0.001). Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism (P = 0.006), and to a lesser extent with antisocial alcoholism (P = 0.03). In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone. A MAOB haplotype was associated with alcoholism independently from ASPD. C1 [Ducci, F.; Enoch, M-A; Hodgkinson, C.; Xu, K.; Goldman, D.] NIAAA, NIH, Neurogenet Lab, Rockville, MD 20852 USA. [Catena, M.] Univ Pisa, Dept Psychiat, Pisa, Italy. [Robin, R. W.] Ctr Prevent & Resolut Violence, Tucson, AZ USA. RP Ducci, F (reprint author), NIAAA, NIH, Neurogenet Lab, 5625 Fishers Lane, Rm 3S32, MSC 9412, Rockville, MD 20852 USA. EM duccif@mail.nih.gov RI Hodgkinson, Colin/F-9899-2010; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS NR 59 TC 120 Z9 131 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2008 VL 13 IS 3 BP 334 EP 347 DI 10.1038/sj.mp.4002034 PG 14 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 263TE UT WOS:000253238600014 PM 17592478 ER PT J AU Metais, JY Dunbar, CE AF Metais, Jean-Yves Dunbar, Cynthia E. TI The MDS1-EVI1 gene complex as a retrovirus integration site: Impact on behavior of hematopoietic cells and implications for gene therapy SO MOLECULAR THERAPY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; GROWTH-FACTOR-BETA; JUVENILE MYELOMONOCYTIC LEUKEMIA; ECOTROPIC VIRAL INTEGRATION; TRANSCRIPTION FACTOR GATA-1; CHRONIC MYELOCYTIC-LEUKEMIA; ZINC-FINGER PROTEIN; STEM-CELLS; EVI-1 GENE; PR DOMAIN AB Gene therapy trials have been performed with virus- based vectors that have the ability to integrate permanently into genomic DNA and thus allow prolonged expression of corrective genes after transduction of hematopoietic stem and progenitor cells. Adverse events observed during the X-linked severe combined immunodeficiency gene therapy trial revealed a significant risk of genotoxicity related to retrovirus vector integration and activation of adjacent proto- oncogenes, with several cases of T-cell leukemia linked to vector activation of the LMO2 gene. In patients with chronic granulomatous disease (CGD), rhesus macaques, and mice receiving hematopoietic stem and progenitor cells transduced with retrovirus vectors, a highly nonrandom pattern of vector integration has been reported. The most striking finding has been overrepresentation of integrations in one specific genomic locus, a complex containing the MDS1 and the EVI1 genes. Most evidence suggests that this overrepresentation is primarily due to a modification of primitive myeloid cell behavior by overexpression of EVI1 or MDS1 - EVI1, as opposed to a specific predilection for integration at this site. Three different proteins can be produced from this complex locus: MDS1, MDS1 - EVI1, and EVI1. This review will summarize current knowledge regarding this locus and its gene products, with specific focus on issues with relevance to gene therapy, leukemogenesis, and hematopoiesis. Insights into the mechanisms that result in altered hematopoiesis and leukemogenesis when this locus is dysregulated could improve the safety of gene therapy in the future. C1 [Metais, Jean-Yves; Dunbar, Cynthia E.] NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NIH, NHLBI, Hematol Branch, 10 Ctr Dr,Bldg 10-CRC,4E-5132, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 109 TC 39 Z9 39 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2008 VL 16 IS 3 BP 439 EP 449 DI 10.1038/sj.mt.6300372 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 267ZQ UT WOS:000253548100003 PM 18227842 ER PT J AU Mossoba, ME Walia, JS Rasaiah, VI Buxhoeveden, N Head, R Ying, C Foley, JE Bramson, JL Fowler, DH Medin, JA AF Mossoba, Miriam E. Walia, Jagdeep S. Rasaiah, Vanessa I. Buxhoeveden, Nicole Head, Renee Ying, Chuyan Foley, Jason E. Bramson, Jonathan L. Fowler, Daniel H. Medin, Jeffrey A. TI Tumor protection following vaccination with low doses of lentivirally transduced DCs expressing the self-antigen erbB2 SO MOLECULAR THERAPY LA English DT Article ID T-CELL RESPONSES; PLASMACYTOID DENDRITIC CELLS; COLORECTAL-CANCER PATIENTS; GENE-TRANSFER; IN-VIVO; ANTITUMOR IMMUNITY; EFFICIENT TRANSFER; PROSTATE-CANCER; FLOW-CYTOMETRY; BREAST-CANCER AB Gene therapy strategies may accelerate the development of prophylactic immunotherapy against cancer. We synthesized a lentiviral (LV) vector encoding a kinase-deficient form of erbB2 ( erbB2tr) to transduce murine dendritic cells (DCs) efficiently. Murine erbB2 models a clinically relevant tumor-associated self-antigen; its human homolog ( HER-2/neu) is overexpressed in breast cancer and in 80% of metastatic prostate cancers. Following one infection, similar to 47% of DCs overexpressed erbB2tr. To determine whether low doses of transduced DCs could protect mice from prostate cancer cells, we performed prime/boost vaccinations with 2 x 10(3) or 2 x 10(5) erbB2tr-transduced DCs. Six weeks after vaccination, mice were simultaneously bilaterally challenged with the aggressive RM-1 prostate cancer cell line and an erbB2tr-expressing variant (RM-1-erbB2tr). Whereas control mice developed both tumors, all recipients of 2 x 10(5) erbB2tr- transduced DCs developed only wild-type RM-1 tumors. One- third of mice vaccinated with just 2 x 10(3) erbB2tr-transduced DCs also demonstrated erbB2tr-specific tumor protection. Protection against RM-1-erbB2tr tumors was associated with sustained levels of anti-erbB2tr antibody production and also correlated with erbB2tr-specific Th1 cytokine secretion. Depletion of CD4(+), CD8(+), or natural killer (NK) cells prior to tumor challenge underscored their role in mediating tumor protection. We conclude that administration of DCs expressing a self- antigen through efficient LV- based gene transfer activates cellular and humoral immunity, protecting host animals against specific tumor challenge. C1 [Walia, Jagdeep S.; Rasaiah, Vanessa I.; Head, Renee; Medin, Jeffrey A.] Univ Hlth Network, Ontario Canc Inst, Div Stem Cell & Dev Biol, Toronto, ON M5G 2M1, Canada. [Mossoba, Miriam E.; Medin, Jeffrey A.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Buxhoeveden, Nicole; Foley, Jason E.; Fowler, Daniel H.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res Expt Transplantat, Rockville, MD USA. [Buxhoeveden, Nicole; Foley, Jason E.; Fowler, Daniel H.] Natl Inst Hlth, Natl Canc Inst, Immunol Branch, Rockville, MD USA. [Ying, Chuyan; Bramson, Jonathan L.] McMaster Univ, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Medin, Jeffrey A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. RP Medin, JA (reprint author), Univ Hlth Network, Ontario Canc Inst, Div Stem Cell & Dev Biol, 67 Coll St,Room 406, Toronto, ON M5G 2M1, Canada. EM jmedin@uhnres.utoronto.ca NR 50 TC 18 Z9 18 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2008 VL 16 IS 3 BP 607 EP 617 DI 10.1038/sj.mt.6300390 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 267ZQ UT WOS:000253548100024 PM 18180774 ER PT J AU Strober, W AF Strober, W. TI Vitamin A rewrites the ABCs of oral tolerance SO MUCOSAL IMMUNOLOGY LA English DT Editorial Material ID REGULATORY T-CELLS; DENDRITIC CELLS; RETINOIC-ACID; TGF-BETA; DIFFERENTIATION; GUT; EXPRESSION; INTERLEUKIN-10; COLITIS; INDUCE AB One of the chief requirements of an immune system, the mucosal immune system, that lies juxtaposed to a mass of potentially immunogenic commensal organisms is a well-developed mechanism to limit or negatively regulate nascent immune responses to those organisms. This mechanism, long subsumed under the name oral tolerance, is now understood to consist of a complex of factors, not the least of which is the ready ability to induce immunosuppressive regulatory T cells or Tregs. The emphasis here is on the "ability to induce" because the real individuality of the mucosal regulatory response lies not in the Tregs themselves, which after all can be induced anywhere and are mere tools of regulatory response. Now, as shown initially by the fact that oral tolerance is dependent on the size and mobility of its dendritic cell (DC) population, the individuality of the mucosal immune system is inherent in its inducing cells, i.e., the antigen-presenting DCs (or macrophages) of the mucosal immune system. 1,2 Recently, new data have emerged that provide much more specific information on how mucosal DCs (or macrophages) are different in this respect and thus why they have a special tendency to facilitate the development of Tregs that then mediate oral tolerance. This is the subject of this brief review. The unresponsiveness of mucosal immune system to mucosal antigens is due to a process known as oral tolerance. Recent studies addressing the mechanism of such tolerance show that mucosal tissues are replete with a unique subset of dendritic cells that secrete factors such as, TGF-beta 1 and retinoic acid, that induce foxp3+ regulatory T cells. Thus, we arrive at the somewhat surprising realization that mucosal unresponsiveness is, appropriately enough, related to the availability of a factor in the food stream. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 21 TC 32 Z9 35 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAR PY 2008 VL 1 IS 2 BP 92 EP 95 DI 10.1038/mi.2007.22 PG 4 WC Immunology SC Immunology GA 366HF UT WOS:000260470600003 PM 19079166 ER PT J AU Richardson, SP Bliem, B Lomarev, M Shamim, E Dang, N Hallett, M AF Richardson, Sarah Pirio Bliem, Barbara Lomarev, Mikhail Shamim, Ejaz Dang, Nguyet Hallett, Mark TI Changes in short afferent inhibition during phasic movement in focal dystonia SO MUSCLE & NERVE LA English DT Article DE focal hand dystonia; F-wave; short afferent inhibition; surround inhibition; transcranial magnetic stimulation ID HUMAN MOTOR CORTEX; INTRACORTICAL INHIBITION; WRITERS CRAMP; HAND DYSTONIA; SURROUND INHIBITION; LEWY BODIES; EXCITABILITY; STIMULATION; DEMENTIA; CIRCUITS AB Impaired surround inhibition could account for the abnormal motor control seen in patients with focal hand dystonia, but the neural mechanisms underlying surround inhibition in the motor system are not known. We sought to determine whether an abnormality of the influence of sensory input at short latency could contribute to the deficit of surround inhibition in patients with focal hand dystonia (FHD). To measure digital short afferent inhibition (dSAI), subjects received electrical stimulation at the digit followed after 23 ms by transcranial magnetic stimulation (TMS). Motor evoked potentials (MEPs) were recorded over abductor digiti minimi (ADM) during rest and during voluntary phasic flexion of the second digit. F-waves were also recorded. We studied 13 FHD patients and 17 healthy volunteers. FHD patients had increased homotopic dSAI in ADM during flexion of the second digit, suggesting that this process acts to diminish overflow during movement; this might be a compensatory mechanism. No group differences were observed in first dorsal interosseous. Further, no differences were seen in the F-waves between groups, suggesting that the changes in dSAI are mediated at the cortical level rather than at the spinal cord. Understanding the role of these inhibitory circuits in dystonia may lead to development of therapeutic agents aimed at restoring inhibition. C1 [Richardson, Sarah Pirio; Lomarev, Mikhail; Shamim, Ejaz; Dang, Nguyet; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Bliem, Barbara] Ruhr Univ Bochum, Int Grad Sch Neurosci, Bochum, Germany. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, 10 Ctr Dr,MSC 1428,Bldg 10,Room 5N226, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS NR 21 TC 18 Z9 18 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAR PY 2008 VL 37 IS 3 BP 358 EP 363 DI 10.1002/mus.20943 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 266AS UT WOS:000253403900010 PM 18061936 ER PT J AU Olivero, OA AF Olivero, Ofelia A. TI Relevance of experimental models for investigation of genotoxicity induced by antiretroviral therapy during human pregnancy SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article; Proceedings Paper CT 11th Alexander Hollaender Course in Genetic Toxicology CY OCT, 2006 CL Univ Bio Bio, Concepcion, CHILE HO Univ Bio Bio ID REVERSE-TRANSCRIPTASE INHIBITORS; IMMUNODEFICIENCY-VIRUS TYPE-1; EXPOSED IN-UTERO; 3-AZIDO-2,3-DIDEOXYTHYMIDINE AZT; PREFERENTIAL INCORPORATION; ZIDOVUDINE TREATMENT; NUCLEOSIDE ANALOGS; DNA INCORPORATION; THYMIDINE KINASE; HUMAN-CELLS AB The current incidence of human immunodeficiency virus (HIV-1)/AIDS affects around 7000 pregnant women in the United States. When given during pregnancy, the nucleoside analog 3'-azido-3'-deoxythymidine (AZT) significantly reduces maternal-fetal transmission. It has been previously shown that AZT is incorporated into DNA, where it causes mutations in the HPRT and TK genes. It also changes cell cycle gene expression, and induces S-phase arrest, micronuclei, chromosomal aberrations, sister chromatid exchanges, telomeric attrition, and other genotoxic effects in cultured cells. A predicted consequence of these events is genomic instability that together, with clastogenicity may contribute to the carcinogenic potency of AZT. Various aspects of genotoxicity are explored in this contribution seeking to understand the multiple effects of this antiretroviral agent in animal models and humans. This mini-review describes some of the experimental models used to elucidate the genotoxicity induced by antiretroviral therapy during human pregnancy. The use of diverse methods to detect biomarkers of exposure, such as an AZT-specific radioimmunoassay, micronuclei bearing intact chromosomes, and telomeric DNA attrition highlight the role of in vitro models to elucidate exposure and risk. The relevance of the in vitro models is followed by the introduction of the role of the nucleoside analogs in transplacental carcinogenesis along with the description of a transplacental perfusion model and a transplacental carcinogenesis rodent model. In a more direct clinical application the use of AZT-DNA incorporation as a biomarker of exposure, in experiments conducted in vivo in Erythrocebus patas monkeys and in humans, addresses the possibility of elucidation of potential cancer risk in those infants exposed in utero. Two relevant aspects of this contribution are the potential application of some of the models described in this mini-review, as diagnostic tools in antiretroviral-exposed populations, and the use of these models to understand the nature of the genotoxicities and minimize the undesirable side effects of the antiretroviral therapy. Published by Elsevier B.V. C1 NCI, Lab Canc Biol & Genet, Carcinogen DNA Interact Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Olivero, OA (reprint author), NCI, Lab Canc Biol & Genet, Carcinogen DNA Interact Sect, Ctr Canc Res,NIH, 37 Convent Dr,MSC 4255,Bldg 37,Room 4032B, Bethesda, MD 20892 USA. EM oliveroo@exchange.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 31 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD MAR-APR PY 2008 VL 658 IS 3 SI SI BP 184 EP 190 DI 10.1016/j.mrrev.2007.12.001 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 317MO UT WOS:000257024500005 PM 18295533 ER PT J AU Simitsopoulou, M Roilides, E Maloukou, A Gil-Lamaignere, C Walsh, TJ AF Simitsopoulou, Maria Roilides, Emmanuel Maloukou, Avgi Gil-Lamaignere, Cristina Walsh, Thomas J. TI Interaction of amphotericin B lipid formulations and triazoles with human polymorphonuclear leucocytes for antifungal activity against Zygomycetes SO MYCOSES LA English DT Article DE Zygomycetes; lipid formulations of amphotericin B; triazoles; polymorphonuclear leucocytes ID COLONY-STIMULATING FACTOR; INVASIVE FUNGAL-INFECTIONS; RHIZOPUS-ORYZAE HYPHAE; IN-VITRO; ASPERGILLUS-FUMIGATUS; DISSEMINATED ZYGOMYCOSIS; TRANSPLANT RECIPIENTS; ABSIDIA-CORYMBIFERA; FILAMENTOUS FUNGI; VORICONAZOLE AB The frequency of zygomycosis has increased considerably over recent years mainly in immunocompromised and diabetic patients. Little is known about the effects of host innate immunity against different Zygomycetes especially under the influence of antifungal agents. The antifungal activity of human polymorphonuclear leucocytes (PMN) in combination with liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), voriconazole (VRC) and posaconazole (PSC) against Rhizopus oryzae and Rhizopus microsporus, frequently isolated Zygomycetes, were studied and compared with Absidia corymbifera, a less pathogenic Zygomycete. Antifungal activity was evaluated as per cent of hyphal damage using the XTT metabolic assay. While A. corymbifera was more susceptible to PMN than the other two Zygomycetes, R. microsporus appeared to be the most susceptible to combined effects of amphotericin B formulations and VRC with PMN. LAMB exhibited synergistic activity with PMN in inducing hyphal damage to R. microsporus but not to the other fungi. In contrast, ABLC exhibited synergistic or additive activity with PMN against all three fungi. Among triazoles, only VRC exhibited additive effect with PMN against R. microsporus. Lipid formulations of amphotericin B and particularly ABLC interact with PMN predominantly in inducing augmented hyphal damage to three different species of Zygomycetes. C1 [Roilides, Emmanuel; Walsh, Thomas J.] NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. [Simitsopoulou, Maria; Roilides, Emmanuel; Maloukou, Avgi; Gil-Lamaignere, Cristina] Aristotle Univ Thessaloniki, Hippokration Hosp, Dept Pediat 3, Infect Dis Lab, Thessaloniki, Greece. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,CRC 1-5750, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov RI Gil-Lamaignere, Cristina/A-3866-2013 NR 46 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0933-7407 J9 MYCOSES JI Mycoses PD MAR PY 2008 VL 51 IS 2 BP 147 EP 154 DI 10.1111/j.1439-0507.2007.01457.x PG 8 WC Dermatology; Mycology SC Dermatology; Mycology GA 257QJ UT WOS:000252813300010 PM 18254752 ER PT J AU Mattson, MP van Praag, H AF Mattson, Mark P. van Praag, Henriette TI TAGing APP constrains neurogenesis SO NATURE CELL BIOLOGY LA English DT Editorial Material ID AMYLOID-PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; NOTCH; DIFFERENTIATION; GROWTH; DOMAIN; BRAIN C1 [Mattson, Mark P.; van Praag, Henriette] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; van Praag, Henriette/F-3939-2015 OI van Praag, Henriette/0000-0002-5727-434X NR 17 TC 6 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2008 VL 10 IS 3 BP 249 EP 250 DI 10.1038/ncb0308-249 PG 2 WC Cell Biology SC Cell Biology GA 271HA UT WOS:000253778300003 PM 18311177 ER PT J AU Xu, D Moon, AF Song, D Pedersen, LC Liu, J AF Xu, Ding Moon, Andrea F. Song, Danyin Pedersen, Lars C. Liu, Jian TI Engineering sulfotransferases to modify heparan sulfate SO NATURE CHEMICAL BIOLOGY LA English DT Article ID CRYSTAL-STRUCTURE; BIOSYNTHESIS AB The biosynthesis of heparan sulfate (HS) involves an array of specialized sulfotransferases. Here, we present a study aimed at engineering the substrate specificity of different HS 3-O-sulfotransferase isoforms. Based on the crystal structures, we identified a pair of amino acid residues responsible for selecting the substrates. Mutations of these residues altered the substrate specificities. Our results demonstrate the feasibility of tailoring the specificity of sulfotransferases to modify HS with desired functions. C1 [Xu, Ding; Song, Danyin; Liu, Jian] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. [Moon, Andrea F.; Pedersen, Lars C.] Natl Inst Environm Hlth Sci, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Liu, J (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. EM jian-liu@unc.edu RI Xu, Ding/B-2493-2009 OI Xu, Ding/0000-0001-9380-2712 FU Intramural NIH HHS [Z99 ES999999]; NIAID NIH HHS [AI50050, R01 AI050050, R01 AI050050-07] NR 12 TC 37 Z9 40 U1 4 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAR PY 2008 VL 4 IS 3 BP 200 EP 202 DI 10.1038/nchembio.66 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266EN UT WOS:000253417400016 PM 18223645 ER PT J AU Robbins, J Schneider, AB AF Robbins, Jacob Schneider, Arthur B. TI Chernobyl and the KI controversy in the United States SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 [Robbins, Jacob] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Schneider, Arthur B.] Univ Illinois, Coll Med, Sect Endocrinol & Metab, Chicago, IL USA. RP Robbins, J (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD MAR PY 2008 VL 4 IS 3 BP 117 EP 117 DI 10.1038/ncpendmet0779 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 264VE UT WOS:000253317700001 PM 18288124 ER PT J AU Thomas, G Jacobs, KB Yeager, M Kraft, P Wacholder, S Orr, N Yu, K Chatterjee, N Welch, R Hutchinson, A Crenshaw, A Cancel-Tassin, G Staats, BJ Wang, Z Gonzalez-Bosquet, J Fang, J Deng, X Berndt, SI Calle, EE Feigelson, HS Thun, MJ Rodriguez, C Albanes, D Virtamo, J Weinstein, S Schumacher, FR Giovannucci, E Willett, WC Cussenot, O Valeri, A Andriole, GL Crawford, ED Tucker, M Gerhard, DS Fraumeni, JF Hoover, R Hayes, RB Hunter, DJ Chanock, SJ AF Thomas, Gilles Jacobs, Kevin B. Yeager, Meredith Kraft, Peter Wacholder, Sholom Orr, Nick Yu, Kai Chatterjee, Nilanjan Welch, Robert Hutchinson, Amy Crenshaw, Andrew Cancel-Tassin, Geraldine Staats, Brian J. Wang, Zhaoming Gonzalez-Bosquet, Jesus Fang, Jun Deng, Xiang Berndt, Sonja I. Calle, Eugenia E. Feigelson, Heather Spencer Thun, Michael J. Rodriguez, Carmen Albanes, Demetrius Virtamo, Jarmo Weinstein, Stephanie Schumacher, Fredrick R. Giovannucci, Edward Willett, Walter C. Cussenot, Olivier Valeri, Antoine Andriole, Gerald L. Crawford, E. David Tucker, Margaret Gerhard, Daniela S. Fraumeni, Joseph F., Jr. Hoover, Robert Hayes, Richard B. Hunter, David J. Chanock, Stephen J. TI Multiple loci identified in a genome-wide association study of prostate cancer SO NATURE GENETICS LA English DT Article ID 94 AMINO-ACIDS; SECRETORY PROTEIN; BINDING-PROTEIN; GENE; SUSCEPTIBILITY; VARIANTS; RISK; EXPRESSION; 8Q24 AB We followed our initial genome-wide association study (GWAS) of 527,869 SNPs on 1,172 individuals with prostate cancer and 1,157 controls of European origin-nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial prospective study-by testing 26,958 SNPs in four independent studies (total of 3,941 cases and 3,964 controls). In the combined joint analysis, we confirmed three previously reported loci (two independent SNPs at 8q24 and one in HNF1B (formerly known as TCF2 on 17q); P < 10(-10)). In addition, loci on chromosomes 7, 10 (two loci) and 11 were highly significant (between P < 7.31 x 10(-13) and P < 2.14 x 10(-6)). Loci on chromosome 10 include MSMB, which encodes beta-microseminoprotein, a primary constituent of semen and a proposed prostate cancer biomarker, and CTBP2, a gene with antiapoptotic activity; the locus on chromosome 7 is at JAZF1, a transcriptional repressor that is fused by chromosome translocation to SUZ12 in endometrial cancer. Of the nine loci that showed highly suggestive associations (P < 2.5 x 10(-5)), four best fit a recessive model and included candidate susceptibility genes: CPNE3, IL16 and CDH13. Our findings point to multiple loci with moderate effects associated with susceptibility to prostate cancer that, taken together, in the future may predict high risk in select individuals. C1 [Thomas, Gilles; Yeager, Meredith; Wacholder, Sholom; Orr, Nick; Yu, Kai; Chatterjee, Nilanjan; Welch, Robert; Hutchinson, Amy; Crenshaw, Andrew; Staats, Brian J.; Wang, Zhaoming; Gonzalez-Bosquet, Jesus; Fang, Jun; Deng, Xiang; Berndt, Sonja I.; Albanes, Demetrius; Weinstein, Stephanie; Tucker, Margaret; Fraumeni, Joseph F., Jr.; Hoover, Robert; Hayes, Richard B.; Hunter, David J.; Chanock, Stephen J.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. [Yeager, Meredith; Welch, Robert; Hutchinson, Amy; Crenshaw, Andrew; Staats, Brian J.; Wang, Zhaoming; Deng, Xiang] NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Core Genotyping Facil, Frederick, MD 21702 USA. [Kraft, Peter; Schumacher, Fredrick R.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Calle, Eugenia E.; Feigelson, Heather Spencer; Thun, Michael J.; Rodriguez, Carmen] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FIN-0030 Helsinki, Finland. [Thomas, Gilles; Giovannucci, Edward; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63108 USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80014 USA. [Gerhard, Daniela S.] NCI, NIH, Dept Hlth & Human Serv, Ctr Canc Res,Off Canc Genom, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, NIH, Dept Hlth & Human Serv, Ctr Canc Res,Pediat Oncol Branch, Bethesda, MD 20892 USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] CeRePP Hop Tenon, AP HP, F-75970 Paris, France. RP Chanock, SJ (reprint author), NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov RI Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015; OI Hayes, Richard/0000-0002-0918-661X; Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [T32 CA 09001, CA55075, N01-CN-45165, N01-CO-12400, U01 CA098710, U01CA098233] NR 30 TC 618 Z9 651 U1 4 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2008 VL 40 IS 3 BP 310 EP 315 DI 10.1038/ng.91 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 267ZT UT WOS:000253548400021 PM 18264096 ER PT J AU Min, B Paul, WE AF Min, Booki Paul, William E. TI Basophils: in the spotlight at last SO NATURE IMMUNOLOGY LA English DT Editorial Material ID DENDRITIC CELLS; INTERLEUKIN-4; MATURATION; IL-4 AB Basophils have long been suspected to be potent inducers of T helper type 2 differentiation. Sokol and colleagues now demonstrate that basophils are required for adoption of the T helper type 2 fate in vivo in response to allergens with protease activity. C1 [Min, Booki] Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. [Paul, William E.] NIAID, NIH, Bethesda, MD 20892 USA. RP Min, B (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM wpaul@niaid.nih.gov NR 12 TC 16 Z9 16 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2008 VL 9 IS 3 BP 223 EP 225 DI 10.1038/ni0308-223 PG 3 WC Immunology SC Immunology GA 266BQ UT WOS:000253406700003 PM 18285768 ER PT J AU Shembade, N Harhaj, NS Parvatiyar, K Copeland, NG Jenkins, NA Matesic, LE Harhaj, EW AF Shembade, Noula Harhaj, Nicole S. Parvatiyar, Kislay Copeland, Neal G. Jenkins, Nancy A. Matesic, Lydia E. Harhaj, Edward W. TI The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20 SO NATURE IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; T-CELL LEUKEMIA; VIRUS TYPE-I; ZINC-FINGER PROTEIN; TAX TRANSFORMING PROTEIN; TUMOR-SUPPRESSOR CYLD; NECROSIS-FACTOR-ALPHA; HTLV-I; ACTIVATION; KINASE AB The ubiquitin-editing enzyme A20 is a critical negative regulator of inflammation and cytokine-mediated activation of the transcription factor NF-kappa B; however, little is known about the mechanisms of A20-mediated inactivation of signaling intermediates such as RIP1. Here we demonstrate that the regulatory molecule TAX1BP1 recruited the E3 ligase Itch to A20 via two 'PPXY' motifs. Itch was essential for the termination of tumor necrosis factor receptor signaling by controlling A20-mediated recruitment and inactivation of RIP1. Furthermore, the Tax oncoprotein of human T cell leukemia virus type I targeted this complex for inactivation by disrupting the interaction among TAX1BP1, A20 and Itch. Thus, our studies show a previously unappreciated complexity of A20 substrate recognition and inactivation whereby TAX1BP1 and Itch function as essential subunits of an A20 ubiquitin-editing complex. C1 [Shembade, Noula; Harhaj, Nicole S.; Parvatiyar, Kislay; Harhaj, Edward W.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Copeland, Neal G.; Jenkins, Nancy A.; Matesic, Lydia E.] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. [Matesic, Lydia E.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. RP Harhaj, EW (reprint author), Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Microbiol & Immunol, Miami, FL 33136 USA. EM eharhaj@med.miami.edu NR 50 TC 161 Z9 164 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2008 VL 9 IS 3 BP 254 EP 262 DI 10.1038/ni1563 PG 9 WC Immunology SC Immunology GA 266BQ UT WOS:000253406700011 PM 18246070 ER PT J AU Arthos, J Cicala, C Martinelli, E Macleod, K Van Ryk, D Wei, D Xiao, Z Veenstra, TD Conrad, TP Lempicki, RA McLaughlin, S Pascuccio, M Gopaul, R McNally, J Cruz, CC Censoplano, N Chung, E Reitano, KN Kottilil, S Goode, DJ Fauci, AS AF Arthos, James Cicala, Claudia Martinelli, Elena Macleod, Katilyn Van Ryk, Donald Wei, Danlan Xiao, Zhen Veenstra, Timothy D. Conrad, Thomas P. Lempicki, Richard A. McLaughlin, Sherry Pascuccio, Massimiliano Gopaul, Ravindra McNally, Jonathan Cruz, Catherine C. Censoplano, Nina Chung, Eva Reitano, Kristin N. Kottilil, Shyam Goode, Diana J. Fauci, Anthony S. TI HIV-1 envelope protein binds to and signals through integrin alpha(4)beta(7), the gut mucosal homing receptor for peripheral T cells SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MACROPHAGE-TROPIC HIV; GASTROINTESTINAL-TRACT; CHEMOKINE RECEPTOR; ALPHA-4 INTEGRIN; LYMPHOID-TISSUE; SIV INFECTION; DEPLETION; LFA-1; REPLICATION AB Infection with human immunodeficiency virus 1 (HIV-1) results in the dissemination of virus to gut-associated lymphoid tissue. Subsequently, HIV-1 mediates massive depletion of gut CD4(+) T cells, which contributes to HIV-1-induced immune dysfunction. The migration of lymphocytes to gut-associated lymphoid tissue is mediated by integrin alpha(4)beta(7). We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of alpha(4)beta(7). This interaction was mediated by a tripeptide in the V2 loop of gp120, a peptide motif that mimics structures presented by the natural ligands of alpha(4)beta(7). On CD4(+) T cells, engagement of alpha(4)beta(7) by gp120 resulted in rapid activation of LFA-1, the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1. C1 [Arthos, James; Cicala, Claudia; Macleod, Katilyn; Van Ryk, Donald; Wei, Danlan; Pascuccio, Massimiliano; Gopaul, Ravindra; McNally, Jonathan; Cruz, Catherine C.; Censoplano, Nina; Chung, Eva; Reitano, Kristin N.; Kottilil, Shyam; Goode, Diana J.; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Martinelli, Elena] Univ Genoa, Ctr Excellence Biomed Res, Genoa, Italy. [Xiao, Zhen; Veenstra, Timothy D.; Conrad, Thomas P.] Sci Applicat Int Corp, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. [Lempicki, Richard A.] Sci Applicat Int Corp, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. [McLaughlin, Sherry] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. RP Arthos, J (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM jarthos@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU Intramural NIH HHS; NIAID NIH HHS [AI047734, AI058894] NR 40 TC 299 Z9 312 U1 5 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2008 VL 9 IS 3 BP 301 EP 309 DI 10.1038/ni1566 PG 9 WC Immunology SC Immunology GA 266BQ UT WOS:000253406700016 PM 18264102 ER PT J AU Laurence, A O'Shea, JJ Watford, WT AF Laurence, Arian O'Shea, John J. Watford, Wendy T. TI Interleukin-22: a sheep in wolf's clothing SO NATURE MEDICINE LA English DT Editorial Material ID CELL-MEDIATED PATHOLOGY; MOUSE MODEL; INFLAMMATION; CYTOKINES; COLITIS; GROWTH; IL-17; IL-22; BETA AB Interleukin-22, a component of the immune system most studied for its role in autoimmunity, has a more beneficial side. Two studies show how this cytokine fights off microbes in the mucosa of the lung and gut ( pages 275-281 and 282-289). C1 [Laurence, Arian; O'Shea, John J.; Watford, Wendy T.] NIAMSD, Mol Immunol & Inflammat Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Laurence, A (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, US Natl Inst Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Laurence, Arian/A-8770-2009 OI Laurence, Arian/0000-0003-0942-8292 NR 12 TC 23 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2008 VL 14 IS 3 BP 247 EP 249 DI 10.1038/nm0308-247 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 271VB UT WOS:000253815700019 PM 18323844 ER PT J AU Niranjan, T Bielesz, B Gruenwald, A Ponda, MP Kopp, JB Thomas, DB Susztak, K AF Niranjan, Thiruvur Bielesz, Bernhard Gruenwald, Antje Ponda, Manish P. Kopp, Jeffrey B. Thomas, David B. Susztak, Katalin TI The Notch pathway in podocytes plays a role in the development of glomerular disease SO NATURE MEDICINE LA English DT Article ID DIABETIC-NEPHROPATHY; TGF-BETA; GROWTH ARREST; TRANSGENIC MICE; RENAL-DISEASE; RBP-J; EXPRESSION; APOPTOSIS; INHIBITION; PROTEIN AB Albuminuria associated with sclerosis of the glomerulus leads to a progressive decline in renal function affecting millions of people. Here we report that activation of the Notch pathway, which is critical in glomerular patterning, contributes to the development of glomerular disease. Expression of the intracellular domain of Notch1 (ICN1) was increased in glomerular epithelial cells in diabetic nephropathy and in focal segmental glomerulosclerosis. Conditional re-expression of ICN1 in vivo exclusively in podocytes caused proteinuria and glomerulosclerosis. In vitro and in vivo studies showed that ICN1 induced apoptosis of podocytes through the activation of p53. Genetic deletion of a Notch transcriptional partner (Rbpj) specifically in podocytes or pharmacological inhibition of the Notch pathway (with a gamma-secretase inhibitor) protected rats with proteinuric kidney diseases. Collectively, our observations suggest that Notch activation in mature podocytes is a new mechanism in the pathogenesis of glomerular disease and thus could represent a new therapeutic target. C1 [Niranjan, Thiruvur; Bielesz, Bernhard; Gruenwald, Antje; Ponda, Manish P.; Susztak, Katalin] Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10461 USA. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Thomas, David B.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. RP Susztak, K (reprint author), Albert Einstein Coll Med, Dept Med, Div Nephrol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM ksusztak@aecom.yu.edu OI Bielesz, Bernhard/0000-0002-4491-0562; Kopp, Jeffrey/0000-0001-9052-186X FU NIDDK NIH HHS [R01 DK076077, R01 DK076077-01A1, R01 DK076077-02, 1R01DK076077] NR 46 TC 194 Z9 212 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2008 VL 14 IS 3 BP 290 EP 298 DI 10.1038/nm1731 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 271VB UT WOS:000253815700035 PM 18311147 ER PT J AU Atarashi, R Wilham, JM Christensen, L Hughson, AG Moore, RA Johnson, LM Onwubiko, HA Priola, SA Caughey, B AF Atarashi, Ryuichiro Wilham, Jason M. Christensen, Leah Hughson, Andrew G. Moore, Roger A. Johnson, Lisa M. Onwubiko, Henry A. Priola, Suzette A. Caughey, Byron TI Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking SO NATURE METHODS LA English DT Letter ID CYCLIC AMPLIFICATION; IN-VITRO; PROTEIN C1 [Atarashi, Ryuichiro; Wilham, Jason M.; Christensen, Leah; Hughson, Andrew G.; Moore, Roger A.; Johnson, Lisa M.; Onwubiko, Henry A.; Priola, Suzette A.; Caughey, Byron] NIAID, Rocky Mt Labs, NIH, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. [Atarashi, Ryuichiro] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Microbiol & Immunol, Nagasaki 8528523, Japan. RP Atarashi, R (reprint author), NIAID, Rocky Mt Labs, NIH, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM bcaughey@nih.gov NR 6 TC 124 Z9 131 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD MAR PY 2008 VL 5 IS 3 BP 211 EP 212 DI 10.1038/nmeth0308-211 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 271GW UT WOS:000253777900002 PM 18309304 ER PT J AU Stranahan, AM Arumugam, TV Cutler, RG Lee, K Egan, JM Mattson, MP AF Stranahan, Alexis M. Arumugam, Thiruma V. Cutler, Roy G. Lee, Kim Egan, Josephine M. Mattson, Mark P. TI Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons SO NATURE NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; STRESS-INDUCED IMPAIRMENTS; HEALTHY ELDERLY-MEN; RAT DENTATE GYRUS; SYNAPTIC PLASTICITY; ADULT NEUROGENESIS; SPATIAL MEMORY; GRANULE CELLS; CORTISOL-LEVELS; BRAIN AB Many organ systems are adversely affected by diabetes, including the brain, which undergoes changes that may increase the risk of cognitive decline. Although diabetes influences the hypothalamic-pituitary-adrenal axis, the role of this neuroendocrine system in diabetes-induced cognitive dysfunction remains unexplored. Here we demonstrate that, in both insulin-deficient rats and insulin-resistant mice, diabetes impairs hippocampus-dependent memory, perforant path synaptic plasticity and adult neurogenesis, and the adrenal steroid corticosterone contributes to these adverse effects. Rats treated with streptozocin have reduced insulin and show hyperglycemia, increased corticosterone, and impairments in hippocampal neurogenesis, synaptic plasticity and learning. Similar deficits are observed in db/db mice, which are characterized by insulin resistance, elevated corticosterone and obesity. Changes in hippocampal plasticity and function in both models are reversed when normal physiological levels of corticosterone are maintained, suggesting that cognitive impairment in diabetes may result from glucocorticoid-mediated deficits in neurogenesis and synaptic plasticity. C1 [Stranahan, Alexis M.; Arumugam, Thiruma V.; Cutler, Roy G.; Lee, Kim; Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Cellular & Mol Neurosci Sect, Baltimore, MD 21224 USA. [Egan, Josephine M.] NIA, Intramural Res Program, Diabet Sect, Lab Child Invest, Baltimore, MD 21224 USA. [Stranahan, Alexis M.] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, Cellular & Mol Neurosci Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; OI Lee, Kim/0000-0002-5675-1896 FU Intramural NIH HHS [Z01 AG000312-07, Z01 AG000313-07, Z01 AG000314-07]; NIA NIH HHS [F31 AG024690-02, F31 AG024690, F31 AG024690-01, F31 AG024690-03, F31 AG024690-04, F31AG024690-03] NR 48 TC 305 Z9 318 U1 8 U2 38 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAR PY 2008 VL 11 IS 3 BP 309 EP 317 DI 10.1038/nn2055 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 267ZS UT WOS:000253548300014 PM 18278039 ER PT J AU Bellahcene, A Castronovo, V Ogbureke, KUE Fisher, LW Fedarko, NS AF Bellahcene, Akeila Castronovo, Vincent Ogbureke, Kalu U. E. Fisher, Larry W. Fedarko, Neal S. TI Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer SO NATURE REVIEWS CANCER LA English DT Review ID HUMAN BREAST-CANCER; DENTIN MATRIX PROTEIN-1; HUMAN PROSTATE-CANCER; SERUM BONE SIALOPROTEIN; CELL LUNG-CANCER; SIALOPHOSPHOPROTEIN GENE-EXPRESSION; ELEVATED PLASMA OSTEOPONTIN; COMPLEMENT-MEDIATED ATTACK; ENDOTHELIAL GROWTH-FACTOR; MAMMARY EPITHELIAL-CELLS AB Numerous components and pathways are involved in the complex interplay between cancer cells and their environment. The family of glycophosphoproteins comprising osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein-small integrin-binding ligand N-linked glycoproteins (SIBLINGs)-are emerging as important players in many stages of cancer progression. From their detection in various human cancers to the demonstration of their key functional roles during malignant transformation, invasion and metastasis, the SIBLINGs are proteins with potential as diagnostic and prognostic tools, as well as new therapeutic targets. C1 [Fedarko, Neal S.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. [Bellahcene, Akeila; Castronovo, Vincent] Univ Liege, Metsastat Res Lab, B-4000 Cointe Ougree, Belgium. [Ogbureke, Kalu U. E.] Med Coll Georgia, Sch Dent, Dept Oral Biol, Augusta, GA 30912 USA. [Fisher, Larry W.] NIH, Natl Inst Dent & Cranofacial Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fisher, LW (reprint author), Johns Hopkins Univ, Dept Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM lfisher@dir.nidcr.nih.gov OI Fedarko, Neal/0000-0001-6055-6279 FU Intramural NIH HHS; NCI NIH HHS [R01 CA113865, R01 CA113865-01A2, R01 CA113865-02, R01 CA113865-03, R21 CA087311, R21 CA087311-01, R21 CA087311-02, R21CA87311, Z01 BC010478]; PHS HHS [K23 017791-01A1] NR 204 TC 226 Z9 239 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAR PY 2008 VL 8 IS 3 BP 212 EP 226 DI 10.1038/nrc2345 PG 15 WC Oncology SC Oncology GA 266CB UT WOS:000253407800016 PM 18292776 ER PT J AU Schones, DE Zhao, K AF Schones, Dustin E. Zhao, Keji TI Genome-wide approaches to studying chromatin modifications SO NATURE REVIEWS GENETICS LA English DT Review ID EMBRYONIC STEM-CELLS; DNASE HYPERSENSITIVE SITES; ENHANCER-BLOCKING ACTIVITY; VARIANT HISTONE H2A.Z; RNA-POLYMERASE-II; CHIP-SEQ DATA; CPG-ISLANDS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME CONFORMATION; METHYLATION PATTERNS AB Over two metres of DNA is packaged into each nucleus in the human body in a manner that still allows for gene regulation. This remarkable feat is accomplished by the wrapping of DNA around histone proteins in repeating units of nucleosomes to form a structure known as chromatin. This chromatin structure is subject to various modifications that have profound influences on gene expression. Recently developed techniques to study chromatin modifications at a genome-wide scale are now allowing researchers to probe the complex components that make up epigenomes. Here we review genome-wide approaches to studying epigenomic structure and the exciting findings that have been obtained using these technologies. C1 [Schones, Dustin E.; Zhao, Keji] NIH, NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Schones, DE (reprint author), NIH, NHLBI, Lab Mol Immunol, Bldg 10, Bethesda, MD 20892 USA. EM schonesde@nhlbi.nih.gov; zhaok@nhlbi.nih.gov FU Intramural NIH HHS NR 141 TC 230 Z9 236 U1 3 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD MAR PY 2008 VL 9 IS 3 BP 179 EP 191 DI 10.1038/nrg2270 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 263TN UT WOS:000253239500011 PM 18250624 ER PT J AU Venturi, V Price, DA Douek, DC Davenport, MP AF Venturi, Vanessa Price, David A. Douek, Daniel C. Davenport, Miles P. TI The molecular basis for public T-cell responses? SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID COMPLEX CLASS-I; HUMAN CYTOMEGALOVIRUS; REPERTOIRE DIVERSITY; RECEPTOR RECOGNITION; PRECURSOR FREQUENCY; ANTIGEN RECEPTOR; PERSISTENT VIRUSES; STRUCTURAL BASIS; TCR REPERTOIRE; VIRAL PEPTIDE AB Public T-cell responses, in which T cells bearing identical T-cell receptors (TCRs) are observed to dominate the response to the same antigenic epitope in multiple individuals, have long been a focus of immune T-cell repertoire studies. However, the mechanism that enables the survival of a specific TCR from the diverse repertoire produced in the thymus through to its involvement in a public immune response remains unclear. In this Opinion article, we propose that the frequency of production of T cells bearing different TCRs during recombination has an important role in the sharing of TCRs in an immune response, with variable levels of 'convergent recombination' driving production frequencies. C1 [Price, David A.; Douek, Daniel C.] NIAID, NIH, Vaccine Res Ctr, Human Immunol Sect, Bethesda, MD 20892 USA. [Price, David A.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff CF14 4XN, Wales. [Venturi, Vanessa; Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Sydney, NSW 2052, Australia. RP Douek, DC (reprint author), NIAID, NIH, Vaccine Res Ctr, Human Immunol Sect, Bethesda, MD 20892 USA. EM ddouek@nih.gov; m.davenport@unsw.edu.au RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G0501963] NR 79 TC 130 Z9 132 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD MAR PY 2008 VL 8 IS 3 BP 231 EP U14 DI 10.1038/nri2260 PG 8 WC Immunology SC Immunology GA 267ZV UT WOS:000253548600017 PM 18301425 ER PT J AU Breakefield, XO Blood, AJ Li, YQ Hallett, M Hanson, PI Standaert, DG AF Breakefield, Xandra O. Blood, Anne J. Li, Yuqing Hallett, Mark Hanson, Phyllis I. Standaert, David G. TI The pathophysiological basis of dystonias SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID DEEP-BRAIN-STIMULATION; FOCAL HAND DYSTONIA; TYROSINE-HYDROXYLASE GENE; STRIATAL CHOLINERGIC INTERNEURONS; HEREDITARY PROGRESSIVE DYSTONIA; MARKED DIURNAL FLUCTUATION; EPSILON-SARCOGLYCAN GENE; DOPA-RESPONSIVE DYSTONIA; TRANSGENIC MOUSE MODEL; GTP CYCLOHYDROLASE-I AB Dystonias comprise a group of movement disorders that are characterized by involuntary movements and postures. Insight into the nature of neuronal dysfunction has been provided by the identification of genes responsible for primary dystonias, the characterization of animal models and functional evaluations and in vivo brain imaging of patients with dystonia. The data suggest that alterations in neuronal development and communication within the brain create a susceptible substratum for dystonia. Although there is no overt neurodegeneration in most forms of dystonia, there are functional and microstructural brain alterations. Dystonia offers a window into the mechanisms whereby subtle changes in neuronal function, particularly in sensorimotor circuits that are associated with motor learning and memory, can corrupt normal coordination and lead to a disabling motor disorder. C1 [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA. [Breakefield, Xandra O.; Blood, Anne J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Li, Yuqing; Standaert, David G.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Li, Yuqing; Standaert, David G.] Univ Alabama Birmingham, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. [Hanson, Phyllis I.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Blood, Anne J.] Massachusetts Gen Hosp, Dept Psychiat & Neurol & Athinoula, A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Neurol & Radiol, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu RI Li, Yuqing/G-1596-2011; Hanson, Phyllis/E-9420-2012; OI Li, Yuqing/0000-0003-1211-5529; Standaert, David/0000-0003-2921-8348 FU Intramural NIH HHS; NINDS NIH HHS [NS047692, NS050717, NS37409, P50 NS037409, R01 NS050717, R01 NS052368, R21 NS046348, R21 NS047692] NR 129 TC 245 Z9 247 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAR PY 2008 VL 9 IS 3 BP 222 EP 234 DI 10.1038/nrn2337 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 266CD UT WOS:000253408000015 PM 18285800 ER PT J AU Klement, K Novakovic, A Schurmann, A Piekorz, R Birnbaumer, L Joost, HG Haussinger, D Gohla, A Nurnberg, B AF Klement, K. Novakovic, A. Schuermann, A. Piekorz, R. Birnbaumer, L. Joost, H. -G. Haeussinger, D. Gohla, A. Nuernberg, B. TI An obligatory requirement of the heterotrimeric G protein G alpha i3 in the anti-autophagic action of insulin in the liver SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 11-13, 2008 CL Mainz, GERMANY SP German Soc Expt & Clin Pharmacol & Toxicol C1 [Klement, K.; Novakovic, A.; Piekorz, R.; Gohla, A.; Nuernberg, B.] Univ Dusseldorf, Inst Biochem & Mol Biol 2, Dusseldorf, Germany. [Schuermann, A.; Joost, H. -G.] German Inst Human Nutr Potsdam Rehbrucke, Dept Pharmacol, Nuthetal, Germany. [Birnbaumer, L.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Haeussinger, D.] Univ Dusseldorf, Clin Gastroenterol Hepatol & Infect Dis, D-4000 Dusseldorf, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2008 VL 377 SU 1 MA 84 BP 25 EP 25 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277IC UT WOS:000254204900091 ER PT J AU Nolte, MW Loscher, W Herden, C Freed, WJ Gernert, M AF Nolte, M. W. Loescher, W. Herden, C. Freed, W. J. Gernert, M. TI Benefits and risks of intranigral microtransplantation of immortalized GABA-producing cell lines in the kindling model of temporal lobe epilepsy SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 11-13, 2008 CL Mainz, GERMANY SP German Soc Expt & Clin Pharmacol & Toxicol C1 [Loescher, W.; Gernert, M.] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Hannover, Germany. [Loescher, W.; Gernert, M.] Univ Vet Med, Ctr Syst Neurosci, Hannover, Germany. [Herden, C.] Univ Vet Med, Inst Pathol, Hannover, Germany. [Freed, W. J.] NIDA IRP, NIH, DHHS, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2008 VL 377 SU 1 MA 235 BP 51 EP 51 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277IC UT WOS:000254204900241 ER PT J AU Fahrer, J Bohr, V Burkle, A AF Fahrer, J. Bohr, V. Buerkle, A. TI Poly(ADP-ribose) interacts non-covalently with Werner syndrome protein and inhibits its helicase activity SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 11-13, 2008 CL Mainz, GERMANY SP German Soc Expt & Clin Pharmacol & Toxicol C1 [Fahrer, J.; Buerkle, A.] Univ Konstanz, Dept Biol, Mol Toxicol Grp, Constance, Germany. [Fahrer, J.] Univ Ulm, Inst Pharmacol & Toxicol, Med Ctr, Ulm, Germany. [Bohr, V.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2008 VL 377 SU 1 MA 410 BP 81 EP 81 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277IC UT WOS:000254204900415 ER PT J AU Tomicic, MT Christmann, M Gestrich, C Bohr, VA Kaina, B AF Tomicic, M. T. Christmann, M. Gestrich, C. Bohr, V. A. Kaina, B. TI Werner protein protects against topoisomerase I. but not topoisomerase II inhibitors, by preventing DNA double-strand break formation SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 11-13, 2008 CL Mainz, GERMANY SP German Soc Expt & Clin Pharmacol & Toxicol C1 [Tomicic, M. T.; Christmann, M.; Gestrich, C.; Kaina, B.] Johannes Gutenberg Univ Mainz, Dept Toxicol, Mainz, Germany. [Bohr, V. A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2008 VL 377 SU 1 MA 411 BP 81 EP 82 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277IC UT WOS:000254204900416 ER PT J AU Schonfelder, G Menendez, D Inga, A Snipe, J Krysiak, O Resnick, MA AF Schoenfelder, G. Menendez, D. Inga, A. Snipe, J. Krysiak, O. Resnick, M. A. TI A polymorphism in the vascular endothelial growth factor receptor-1 (Flt-1) promoter provides synergy between p53 and estrogen receptor under environmental stress SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 11-13, 2008 CL Mainz, GERMANY SP German Soc Expt & Clin Pharmacol & Toxicol C1 [Schoenfelder, G.] Univ Wurzburg, Inst Pharmacol & Toxicol, Dept Toxicol, Wurzburg, Germany. [Menendez, D.; Snipe, J.; Resnick, M. A.] Natl Inst Environm Hlth Sci, Chromosome Stabil Sect, Mol Genet Lab, Res Triangle Pk, NC USA. [Inga, A.] Natl Inst Canc Res, IST ABC, Lab Expt Oncol B, Genoa, Italy. [Krysiak, O.] Charite Univ Med Berlin, Inst Clin Pharmacol & Toxicol, D-13353 Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2008 VL 377 SU 1 MA 418 BP 83 EP 83 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277IC UT WOS:000254204900423 ER PT J AU Gallas, BD Brown, DG AF Gallas, Brandon D. Brown, David G. TI Reader studies for validation of CAD systems SO NEURAL NETWORKS LA English DT Article; Proceedings Paper CT International Joint Conference on Neural Networks CY AUG 12-17, 2007 CL Orlando, FL SP IEEE DE ROC; reader studies; study design; multi-reader multi-case (MRMC) variance analysis ID OPERATING CHARACTERISTIC ANALYSIS; CORRELATED ROC ANALYSIS; NONPARAMETRIC APPROACH; CHARACTERISTIC CURVES; MRMC METHOD; MULTIREADER; REGRESSION; MODEL; AREA; VARIANCE AB Evaluation of computational intelligence (Cl) systems designed to improve the performance of it human operator is complicated by the need to include the effect of human variability. In this paper we consider human (reader) variability in the context of medical imaging computer-assisted diagnosis (CAD) systems, and we outline how to compare the detection performance of readers with and without the CAD. An effective and statistically powerful comparison call be accomplished with a receiver operating characteristic (ROC) experiment, summarized by the reader-averaged area under the ROC Curve (AUC). The comparison requires sophisticated yet well-developed methods for multi-reader multi-case (MRMC) variance analysis. MRMC variance analysis accounts for random readers, random cases, and correlations in the experiment. In this paper, we extend the methods available for estimating this variability. Specifically, we present a method that can treat arbitrary study designs. Most methods treat only the fully-crossed study design, where every reader reads every case in two experimental conditions. We demonstrate our method with a computer simulation, and we assess the statistical power of a variety of study designs. Published by Elsevier Ltd. C1 [Gallas, Brandon D.; Brown, David G.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Gallas, BD (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. EM brandon.galias@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 48 TC 8 Z9 8 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD MAR-APR PY 2008 VL 21 IS 2-3 BP 387 EP 397 DI 10.1016/j.neunet.2007.12.013 PG 11 WC Computer Science, Artificial Intelligence SC Computer Science GA 292AM UT WOS:000255238800030 PM 18215501 ER PT J AU Wang, L Shim, H Xie, C Cai, H AF Wang, Lizhen Shim, Hoon Xie, Chengsong Cai, Huaibin TI Activation of protein kinase C modulates BACE1-mediated beta-secretase activity SO NEUROBIOLOGY OF AGING LA English DT Article DE BACE1; APP; PKC; protein degradation; protein translocation; amyloid beta; beta-secretase; fibroblast; neuron ID AMYLOID PRECURSOR PROTEIN; UBIQUITIN-PROTEASOME PATHWAY; ALZHEIMERS-DISEASE; A-BETA; BACE1; NEURONS; CALPAIN; BRAIN; DEGENERATION; TRAFFICKING AB beta-Site APP cleavage enzyme 1 (BACE 1) is the beta-secretase responsible for generating amyloid-beta (A beta) peptides in Alzheimer's disease (AD). Previous studies suggest that activation of protein kinase C (PKC) modulates the beta-secretase-mediated cleavage of APP and reduces the production of A beta. The mechanism of PKC-mediated modulation of beta-secretase activity, however, remains elusive. We report here that activation of PKC modulated beta-secretase activity through either suppressing the accumulation or promoting the translocation of BACE1 protein in a cell type-dependent manner. We found that activation of PKC suppressed the accumulation of BACE1 protein in fibroblasts through an enhancement of intracellular protease activities. In neurons, activation of PKC did not alter the expression level of BACE1, but led to more BACE1 translocated to the cell surface, resulting in a decreased cleavage of APP at the beta 1 site. Together, Our findings provide novel mechanisms of PKC-mediated modulation of beta-secretase activity, suggesting that alteration of the intracellular trafficking of BACE1 may serve as a useful therapeutic strategy to lower the production of A beta in AD. Published by Elsevier Inc. C1 [Wang, Lizhen; Shim, Hoon; Xie, Chengsong; Cai, Huaibin] NIH, NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cai, H (reprint author), NIH, NIA, Neurogenet Lab, Bldg 35,Rm 1A116,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Intramural NIH HHS [Z01 AG000959-04, Z99 AG999999] NR 31 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2008 VL 29 IS 3 BP 357 EP 367 DI 10.1016/j.neurobiolaging.2006.11.001 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 266LJ UT WOS:000253436400005 PM 17157415 ER PT J AU Chandran, JS Lin, X Zapata, A Hoeke, A Shimoji, M Moore, SO Galloway, MP Laird, FM Wong, PC Price, DL Bailey, KR Crawley, JN Shippenberg, T Cai, HB AF Chandran, Jayanth S. Lin, Xian Zapata, Agustin Hoeke, Ahmet Shimoji, Mika Moore, Shonagh O'Leary Galloway, Matthew P. Laird, Fiona M. Wong, Philip C. Price, Donald L. Bailey, Kathleen R. Crawley, Jacqueline N. Shippenberg, Toni Cai, Huaibin TI Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function SO NEUROBIOLOGY OF DISEASE LA English DT Article DE DJ-1; knockout mouse; Parkinson's disease; dopamine; striatum; spinal cord; muscle; motor behavior ID HUMAN ALPHA-SYNUCLEIN; UBIQUITIN-PROTEASOME SYSTEM; DROSOPHILA DJ-1 MUTANTS; KNOCK-OUT MICE; PARKINSONS-DISEASE; OXIDATIVE STRESS; DOPAMINERGIC DYSFUNCTION; PREPULSE INHIBITION; TRANSGENIC MICE; MOTOR DEFICITS AB Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson's disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1(-/-)) mice. Younger (<1 year) DJ-1(-/-) mice were hypoactive and had mild gait abnormalities. Older DJ-1(-/-), however, showed decreased body weight and grip strength and more severe gait irregularities compared to wild-type littermates. The basal level of extracellular dopamine, evoked dopamine release and dopamine receptor D2 sensitivity appeared normal in the striatum of DJ-1(-/-) mice, which was consistent with similar results between DJ-1(-/-) and controls in behavioral paradigms specific for the dopaminergic system. An examination of spinal cord, nerve and muscle tissues failed to identify any pathological changes that were consistent with the noted motor deficits. Taken together, our findings suggest that loss of DJ-1 leads to progressive behavioral changes without significant alterations in nigrostriatal dopaminergic and spinal motor systems. (c) 2007 Elsevier Inc. All rights reserved. C1 [Chandran, Jayanth S.; Lin, Xian; Shimoji, Mika; Cai, Huaibin] NIH, Natl Inst Aging, Lab Neurogenet, Unit Transgenesis, Bethesda, MD 20892 USA. RP Cai, H (reprint author), NIH, Natl Inst Aging, Lab Neurogenet, Unit Transgenesis, Bldg 35,Rm 1A116,MSC 3707,35 Covent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013; OI Cai, Huaibin/0000-0002-8596-6108; Galloway, Matthew/0000-0002-7856-9606; Hoke, Ahmet/0000-0003-1215-3373 FU Intramural NIH HHS [Z01 AG000959-04, Z99 AG999999] NR 45 TC 50 Z9 50 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2008 VL 29 IS 3 BP 505 EP 514 DI 10.1016/j.nbd.2007.11.011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 270CG UT WOS:000253696900012 PM 18187333 ER PT J AU Lu, Y Christian, K Lu, B AF Lu, Yuan Christian, Kimberly Lu, Bai TI BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory? SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Review DE synaptic plasticity; TrkB; presynaptic; postsynaptic; local translation; dendritic; tetanic stimulation; synaptic tagging; encoding; consolidation; extinction ID NEUROTROPHIC FACTOR BDNF; FACTOR MESSENGER-RNA; HIPPOCAMPAL SYNAPTIC PLASTICITY; HIGH-FREQUENCY STIMULATION; FACTOR MUTANT MICE; LATE-PHASE; ADULT HIPPOCAMPUS; RAT HIPPOCAMPUS; DENTATE GYRUS; CA1 REGION AB It is generally believed that late-phase long-term potentiation (L-LTP) and long-term memory (LTM) require new protein synthesis. Although the full complement of proteins mediating the long-lasting changes in synaptic efficacy have yet to be identified, several lines of evidence point to a crucial role for activity-induced brain-derived neurotrophic factor (BDNF) expression in generating sustained structural and functional changes at hippocampal synapses thought to underlie some forms of LTM. In particular, BDNF is sufficient to induce the transformation of early to late-phase LTP in the presence of protein synthesis inhibitors, and inhibition of BDNF signaling impairs LTM. Despite solid evidence for a critical role of BDNF in L-LTP and LTM, many issues are not resolved. Given that BDNF needs to be processed in Golgi outposts localized at the branch point of one or few dendrites, a conceptually challenging problem is how locally synthesized BDNF in dendrites could ensure synapse-specific modulation of L-LTP. An interesting alternative is that BDNF-TrkB signaling is involved in synaptic tagging, a prominent hypothesis that explains how soma-derived protein could selectively modulate the tetanized (tagged) synapse. Finally, specific roles of BDNF in the acquisition, retention or extinction of LTM remain to be established. Published by Elsevier Inc. C1 [Lu, Yuan; Lu, Bai] NIMH, GCAP, NIH, Bethesda, MD 20892 USA. [Lu, Bai] NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. [Christian, Kimberly] NIMH, MAP, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), Bldg 35,Rm 1C1004,35 Convent Dr,MSC 3714, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI yu, yan/C-2322-2012 FU Intramural NIH HHS [, NIH0011553913]; PHS HHS [NIH0011553913] NR 123 TC 323 Z9 337 U1 3 U2 33 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD MAR PY 2008 VL 89 IS 3 BP 312 EP 323 DI 10.1016/j.nlm.2007.08.018 PG 12 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 285JE UT WOS:000254772300012 PM 17942328 ER PT J AU Kalueff, AV LaPorte, JL Murphy, DL AF Kalueff, Allan V. LaPorte, Justin L. Murphy, Dennis L. TI Perspectives on genetic animal models of serotonin toxicity SO NEUROCHEMISTRY INTERNATIONAL LA English DT Review DE serotonin syndrome (toxicity); genetic animal models; mutant and transgenic mice; serotonin transporter ID NEUROLEPTIC MALIGNANT SYNDROME; TRANSPORTER KNOCKOUT MICE; MONOAMINE-OXIDASE INHIBITORS; MULTIPLE ENDOCRINE NEOPLASIA; ANXIETY-LIKE BEHAVIOR; 5-HT1A RECEPTOR; CARCINOID-SYNDROME; MUTANT MICE; PROMOTER POLYMORPHISM; REUPTAKE INHIBITOR AB Serotonin syndrome, or serotonin toxicity, is a serious disorder attributable to exaggerated serotonergic function in the brain, most commonly after antidepressant overdose or after combining several psychotropic medications. Similar condition (serotonin syndrome-like behavior) can be evoked in animals experimentally, following administration of serotonergic drugs. In addition to pharmacological stimulation, some genetic and other factors may contribute to serotonin toxicity, prompting the need for new experimental genetic models relevant to this disorder. Here we discuss current problems and perspectives regarding genetic animal models of serotonin-related syndromes, and outline the potential utility of these models in experimental neurochemistry and clinical research. Published by Elsevier Ltd. C1 [Kalueff, Allan V.; LaPorte, Justin L.; Murphy, Dennis L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Bldg 10,Room 3D41,10 Ctr Dr MSC 1264, Bethesda, MD 20892 USA. EM avkalueff@inbox.ru FU Intramural NIH HHS NR 179 TC 21 Z9 21 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAR-APR PY 2008 VL 52 IS 4-5 BP 649 EP 658 DI 10.1016/j.neuint.2007.08.015 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 288EF UT WOS:000254968300015 PM 17935833 ER PT J AU Fujita, M Imaizumi, M Zoghbia, SS Fujimura, Y Farris, AG Suhara, T Hong, J Pike, VW Nnisa, RB AF Fujita, Masahiro Imaizumi, Masao Zoghbia, Sami S. Fujimura, Yota Farris, Amanda G. Suhara, Tetsuya Hong, Jinsoo Pike, Victor W. Nnisa, Robert B. TI Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation SO NEUROIMAGE LA English DT Article DE compartmental analysis; microglia; distribution volume; Monte Carlo simulation; aryloxyanilide ID HUMAN-BRAIN; BINDING-SITES; PET; DAA1106; MODEL; RAT; MICROGLIA; LIGANDS AB The peripheral benzodiazepine receptor (PBR) is upregulated on activated microglia and macrophages and thereby is a useful biomarker of inflammation. We developed a novel PET radioligand, [C-11]PBR28, that was able to image and quantify PBRs in healthy monkeys and in a rat model of stroke. The objective of this study was to evaluate the ability of [C-11]PBR28 to quantify PBRs in brain of healthy human subjects. Twelve subjects had PET scans of 120 to 180 min duration as well as serial sampling of arterial plasma to measure the concentration of unchanged parent radioligand. One- and two-tissue compartmental analyses were performed. To obtain stable estimates of distribution volume, which is a summation of B-max/K-D and nondisplaceable activity, 90 min of brain imaging was required. Distribution volumes in human were only similar to 5% of those in monkey. This comparatively low amount of receptor binding required a two-rather than a one-compartment model, suggesting that nonspecific binding was a sizeable percentage compared to specific binding. The time-activity curves in two of the twelve subjects appeared as if they had no PBR binding-i.e., rapid peak of uptake and fast washout from brain. The cause(s) of these unusual findings are unknown, but both subjects were also found to lack binding to PBRs in peripheral organs such as lung and kidney. In conclusion, with the exception of those subjects who appeared to have no PBR binding, [C-11] PBR28 is a promising ligand to quantify PBRs and localize inflammation associated with increased densities of PBRs. (c) 2007 Elsevier Inc. All rights reserved. C1 [Fujita, Masahiro; Imaizumi, Masao; Zoghbia, Sami S.; Fujimura, Yota; Farris, Amanda G.; Hong, Jinsoo; Pike, Victor W.; Nnisa, Robert B.] Natl Inst Mental Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. [Suhara, Tetsuya] Natl Inst Radiol Sci, Mol Imaging Ctr, Mol Neuroimaging Grp, Chiba 260, Japan. RP Fujita, M (reprint author), Natl Inst Mental Hlth, Mol Imaging Branch, Bldg 31,Rm B2B37, Bethesda, MD 20892 USA. EM FujitaM@intra.nimh.nih.gov FU Intramural NIH HHS [Z01 MH002852-03]; NIMH NIH HHS [Z01 MH002795] NR 32 TC 105 Z9 106 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR 1 PY 2008 VL 40 IS 1 BP 43 EP 52 DI 10.1016/j.neuroimage.2007.11.011 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 265MC UT WOS:000253362100006 PM 18093844 ER PT J AU Graciotti, L Minelli, A Minclacchi, D Procopio, A Fulgenzi, G AF Graciotti, Laura Minelli, Andrea Minclacchi, Diego Procopio, Antonio Fulgenzi, Gianluca TI GABAergic miniature spontaneous activity is increased in the CA1 hippocampal region of dystrophic mdx mice SO NEUROMUSCULAR DISORDERS LA English DT Article DE Duchenne muscular dystrophy; dystrophin; GABAaR; CA1; IPSC; interneuron; electrophysiology; mdx mouse ID DUCHENNE MUSCULAR-DYSTROPHY; CENTRAL-NERVOUS-SYSTEM; INHIBITORY SYNAPSES; GABA(A) RECEPTORS; PURKINJE-CELLS; DEFICIENT MICE; MOUSE MODEL; BRAIN; NEURONS; RAT AB Duchenne muscular dystrophy (DMD), a genetic disease due to dystrophin gene mutation and characterised by skeletal muscle failure, is associated with non-progressive cognitive deficits. In human and mouse brain, full-length dystrophin is localised postsynaptically in neocortical, hippocampal and cerebellar neurons. Evidence obtained in the CNS of dystrophic mice (mdx) suggested alterations of the GABAergic system. However, a direct functional evaluation of GABAergic synaptic transmission in mdx mice has not been conducted in the hippocampus, which is involved in cognitive processes and is rich in full-length dystrophin. Here, we investigated evoked and miniature inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal neurons of mdx mice with patch clamp recording techniques. Results showed an increased frequency of miniature spontaneous IPSCs in mdx mice compared with controls, whereas evoked IPSCs did not show significant variations. Paired-pulse facilitation (PPF) analysis showed lack of facilitation at short intervals in mdx mice compared with that in wild-type mice. Analysis of density of synapses that innervate CA1 pyramidal cell bodies did not indicate significant differences between mdx mice and controls. Therefore, we suggest that increased miniature spontaneous IPSC frequency is due to altered presynaptic release probability. The present findings are discussed in the light of the accrued evidence for alterations of inhibitory synaptic transmission in the brain of dystrophic mice. (C) 2007 Elsevier B.V. All rights reserved. C1 [Graciotti, Laura; Procopio, Antonio; Fulgenzi, Gianluca] Univ Politecn Marche, Dipartimento Patol Mol & Terapie Innovat, I-60020 Ancona, Italy. [Graciotti, Laura; Procopio, Antonio] IRCCS, INRCA, Div Cytol, Ancona, Italy. [Minelli, Andrea] Univ Urbino Carlo Bo, Inst Physiol Sci, Urbino, Italy. [Fulgenzi, Gianluca] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Minclacchi, Diego] Univ Florence, Dept Anat Histol & Forensci Med, Florence, Italy. RP Fulgenzi, G (reprint author), Univ Politecn Marche, Dipartimento Patol Mol & Terapie Innovat, Polo Murri,Via Tronto 10, I-60020 Ancona, Italy. EM g.fulgenzi@univpm.it OI Fulgenzi, Gianluca/0000-0003-2646-7728 NR 38 TC 20 Z9 22 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD MAR PY 2008 VL 18 IS 3 BP 220 EP 226 DI 10.1016/j.nmd.2007.11.009 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 300EX UT WOS:000255808200006 PM 18207404 ER PT J AU Li, X Gardner, EL Xi, ZX AF Li, Xia Gardner, Eliot L. Xi, Zheng-Xiong TI The metabotropic glutamate receptor 7 (mGluR(7)) allosteric agonist AMN082 modulates nucleus accumbens GABA and glutamate, but not dopamine, in rats SO NEUROPHARMACOLOGY LA English DT Article DE mGluR(7); AMN082; dopamine; GABA; glutamate; nucleus accumbens ID PRESYNAPTIC ACTIVE ZONES; METHYL-D-ASPARTATE; GROUP-III MGLURS; RECEPTOR SUBTYPES; NEUROTRANSMITTER RELEASE; SYNAPTIC-TRANSMISSION; NONVESICULAR RELEASE; GABAERGIC TERMINALS; TRANSMITTER RELEASE; MESSENGER-RNA AB The group III metabotropic glutamate receptor 7 (mGluR7) has been implicated in many neurological and psychiatric diseases, including drug addiction. However, it is unclear whether and how mGluR7 modulates nucleus accumbens (NAc) dopamine (DA), L-glutamate or gamma-aminobutyric acid (GABA), important neurotransmitters believed to be involved in such neuropsychiatric diseases. In the present study, we found that systemic or intra-NAc administration of the mGluR(7) allosteric agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082) dose-dependently lowered NAc extracellular GABA and increased extracellular glutamate, but had no effect on extracellular DA levels. Such effects were blocked by (R,S)-alpha-methylserine-O-phosphate (MSOP), a group III mGluR antagonist. Intra-NAc perfusion of tetrodotoxin (TTX) blocked the AMN082-induced increases in glutamate, but failed to block the AMN082-induced reduction in GABA, suggesting vesicular glutamate and non-vesicular GABA origins for these effects. In addition, blockade of NAc GABA(B) receptors by 2-hydroxy-saclofen itself elevated NAc extracellular glutamate. Intra-NAc perfusion of 2-hydroxy-saclofen not only abolished the enhanced extracellular glutamate normally produced by AMN082, but also decreased extracellular glutamate in a TTX-resistant manner. We interpret these findings to suggest that the increase in glutamate is secondary to the decrease in GABA, which overcomes mGluR7 activation-induced inhibition of non-vesicular glutamate release. In contrast to its modulatory effect on GABA and glutamate, the mGluR7 receptor does not appear to modulate NAc DA release. Published by Elsevier Ltd. C1 [Li, Xia; Gardner, Eliot L.; Xi, Zheng-Xiong] Natl Inst Drug Abuse, Intramural Res Program, NIH, DHHS, Baltimore, MD 21224 USA. RP Xi, ZX (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, DHHS, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 56 TC 36 Z9 36 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAR PY 2008 VL 54 IS 3 BP 542 EP 551 DI 10.1016/j.neuropharm.2007.11.005 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 276OF UT WOS:000254151200007 PM 18155073 ER PT J AU Gould, TD O'Donnell, KC Dow, ER Du, J Chen, G Manji, HK AF Gould, Todd D. O'Donnell, Kelley C. Dow, Eliot R. Du, Jing Chen, Guang Manji, Husseini K. TI Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test SO NEUROPHARMACOLOGY LA English DT Article DE alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA); mood stabilizer; antidepressant; lithium; forced swim test (EST); tail suspension test (TST); glutamate; bipolar disorder; depression ID METHYL-D-ASPARTATE; CEREBRAL-CORTEX SLICES; RAT HIPPOCAMPUS; GLUTAMATE RELEASE; BIPOLAR DISORDER; REFRACTORY DEPRESSION; SYNAPTIC EXPRESSION; UNIPOLAR DEPRESSION; TREATMENT INCREASES; SURFACE EXPRESSION AB In addition to its clinical antimanic effects, lithium also has efficacy in the treatment of depression. However, the mechanism by which lithium exerts its antidepressant effects is unclear. Our objective was to further characterize the effects of peripheral and central administration of lithium in mouse models of antidepressant efficacy as well as to investigate the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in these behaviors. We utilized the mouse forced swim test (FST) and tail suspension test (TST), intracerebroventricular (ICV) lithium administration, AMPA receptor inhibitors, and BS3 crosslinking followed by Western blot. Both short- and long-term administration of lithium resulted in robust antidepressant-like effects in the mouse FST and TST. Using ICV administration of lithium, we show that these effects are due to actions of lithium on the brain, rather than to peripheral effects of the drug. Both ICV and rodent chow (0.4% LiCl) administration paradigms resulted in brain lithium concentrations within the human therapeutic range. The antidepressant-like effects of lithium in the FST and TST were blocked by administration of AMPA receptor inhibitors. Additionally, administration of lithium increased the cell surface expression of GluR1 and GluR2 in the mouse hippocampus. Collectively, these data show that lithium exerts centrally mediated antidepressant-like effects in the mouse FST and TST that require AMPA receptor activation. Lithium may exert its antidepressant effects in humans through AMPA receptors, thus further supporting a role of targeting AMPA receptors as a therapeutic approach for the treatment of depression. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Gould, Todd D.; O'Donnell, Kelley C.; Dow, Eliot R.; Du, Jing; Chen, Guang; Manji, Husseini K.] NIMH, Lab Mol Pathophysiol & Expt Therapeut, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gould, TD (reprint author), Univ Maryland, Sch Med, Mood & Anxiety Disorders Program, Dept Psychiat, 701 W Pratt St,Suite 388, Baltimore, MD 21201 USA. EM tgould@psych.umaryland.edu RI Du, Jing/A-9023-2012; Chen, Guang/A-2570-2017 FU Intramural NIH HHS [Z01 MH002841-04, NIH0010875152] NR 78 TC 68 Z9 69 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAR PY 2008 VL 54 IS 3 BP 577 EP 587 DI 10.1016/j.neuropharm.2007.11.002 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 276OF UT WOS:000254151200011 PM 18096191 ER PT J AU Furey, ML Pietrini, P Haxby, JV Drevets, WC AF Furey, Maura L. Pietrini, Pietro Haxby, James V. Drevets, Wayne C. TI Selective effects of cholinergic modulation on task performance during selective attention SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE physostigmine; scopolamine; acetylcholine; human; cognition ID HUMAN EXTRASTRIATE CORTEX; CAT VISUAL-CORTEX; COGNITIVE NEUROSCIENCE; BIASED COMPETITION; TIME-COURSE; BOTTOM-UP; TOP-DOWN; ESTROGEN; BRAIN; FACES AB The cholinergic neurotransmitter system is critically linked to cognitive functions including attention. The current studies were designed to evaluate the effect of a cholinergic agonist and an antagonist on performance during a selective visual attention task where the inherent salience of attended/unattended stimuli was modulated. Two randomized, placebo-controlled, crossover studies were performed, one (n = 9) with the anticholinesterase physostigmine (1.0 mg/h), and the other (n = 30) with the anticholinergic scopolamine (0.4 mc/kg). During the task, two double-exposure pictures of faces and houses were presented side by side. Subjects were cued to attend to either the face or the house component of the stimuli, and were instructed to perform a matching task with the two exemplars from the attended category. The cue changed every 4-7 trials to instruct subjects to shift attention from one stimulus component to the other. During placebo in both studies, reaction time (RT) associated with the first trial following a cued shift in attention was longer than RT associated with later trials (p<0.05); RT also was significantly longer when attending to houses than to faces (p<0.05). Physostigmine decreased RT relative to placebo preferentially during trials greater than one (p<0.05), with no change during trial one; and decreased RT preferentially during the attention to houses condition (p<0.05) vs attention to faces. Scopolamine increased RT relative to placebo selectively during trials greater than one (p<0.05), and preferentially increased RT during the attention to faces condition (p<0.05). The results suggest that enhancement or impairment of cholinergic activity preferentially influences the maintenance of selective attention (ie trials greater than 1). Moreover, effects of cholinergic manipulation depend on the selective attention condition (ie faces vs houses), which may suggest that cholinergic activity interacts with stimulus salience. The findings are discussed within the context of the role of acetylcholine both in stimulus processing and stimulus salience, and in establishing attention biases through top-down and bottom-up mechanisms of attention. C1 NIMH, Natl Inst Hlth, Mood Anxiety Disorders Prgm, Bethesda, MD 20892 USA. Univ Pisa, Lab Clin Biochem Mol Biol, Pisa, Italy. Princeton Univ, Dept Psychol, Princeton, NJ USA. RP Furey, ML (reprint author), NIMH, Natl Inst Hlth, Mood Anxiety Disorders Prgm, 15K North Dr,Rm 115B, Bethesda, MD 20892 USA. EM mfurey@mail.nih.gov RI Furey, Maura/H-5273-2013 FU Intramural NIH HHS [ZIA MH002813-08] NR 53 TC 55 Z9 56 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2008 VL 33 IS 4 BP 913 EP 923 DI 10.1038/sj.npp.1301461 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 261OW UT WOS:000253090900020 PM 17534379 ER PT J AU Barr, TL Alexander, SA Kerr, ME Crago, E Horowitz, M Yonas, H AF Barr, Taura L. Alexander, Sheila A. Kerr, Mary E. Crago, Elizabeth Horowitz, Michael Yonas, Howard TI The impact of endovascular coiling versus surgical clipping on functional outcome after intracranial aneurysm rupture SO NEUROSURGERY QUARTERLY LA English DT Article DE ruptured intracranial aneurysm; subarachnoid hemorrhage; endovascular coiling; surgical clipping; functional outcome ID DETACHABLE COILS; TRIAL ISAT; MANAGEMENT AB Objective: The purpose of this study was to compare functional outcomes at 6 months post-subarachnoid hemorrhage (SAH) secondary to cerebral aneurysm rupture in subjects who were either surgically clipped or endovascularly coiled while controlling for aneurysm site. Method: A retrospective chart review of 228 subjects was performed. The sample included subjects (ages 18 to 75) with the diagnosis of SAH from a ruptured cerebral aneurysm verified by angiography or computed tomographic angiography with a Hunt and Hess score > 2 and/or a Fisher grade > 1. Aneurysm site was determined by the neurosurgeon then categorized into posterior or anterior circulation. The sample was stratified into 2 groups by treatment. Functional outcome was evaluated at 6 months post-SAH using the Glasgow Outcome Scale and Modified Rankin Scale. Results: There were no significant differences in age, race, sex, or Fisher grade between treatment groups. There were significant differences in Hunt and Hess scores (P = 0.02). One hundred thirty (57%) subjects received surgical clipping and 98 (43%) received endovascular coiling. There was a significant difference in aneurysm site between the 2 treatment groups (P = 0.00), with the anterior aneurysms more likely to be clipped. However, there were no significant differences in outcome based on treatment group (Glasgow Outcome Scale, P = 0.95, Modified Rankin Scale, P = 0.95) after controlling for aneurysm site. Conclusions: The results of the current study are similar to the work of others, suggesting that the decision regarding treatment option needs to be individualized based on the presentation of the patient. C1 [Barr, Taura L.; Kerr, Mary E.] NINR, NIH, Suburban Hosp, NIH Stroke Program, Bethesda, MD 20814 USA. [Barr, Taura L.; Alexander, Sheila A.; Crago, Elizabeth] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Horowitz, Michael] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Yonas, Howard] Univ New Mexico, Albuquerque, NM 87131 USA. RP Barr, TL (reprint author), NINR, NIH, Suburban Hosp, NIH Stroke Program, 4th Florr,8600 Old Georgetown Rd, Bethesda, MD 20814 USA. EM barrt@mail.nih.gov NR 22 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1050-6438 J9 NEUROSURG QUART JI Neurosurg. Q. PD MAR PY 2008 VL 18 IS 1 BP 16 EP 21 PG 6 WC Neurosciences; Surgery SC Neurosciences & Neurology; Surgery GA 273MW UT WOS:000253936000004 ER PT J AU Astradsson, A Cooper, O Vinuela, A Isacson, O AF Astradsson, Arnar Cooper, Oliver Vinuela, Angel Isacson, Ole TI Recent advances in cell-based therapy for Parkinson disease SO NEUROSURGICAL FOCUS LA English DT Article DE dopamine; Parkinson disease; stem cell; transplantation; ventral mesencephalon ID EMBRYONIC STEM-CELLS; DEEP BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; FETAL NIGRAL TRANSPLANTATION; LEVODOPA-INDUCED DYSKINESIAS; D-3 RECEPTOR STIMULATION; DOPAMINERGIC-NEURONS; SUBSTANTIA-NIGRA; RAT MODEL; MESENCEPHALIC TISSUE AB In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression as reasons for variable outcome and for some of the side effects observed in these clinical trials. To address ethical, practical, and technical issues related to the use of fetal cell sources, alternative sources of therapeutic dopaminergic neurons are being developed. The authors describe the progress in enrichment and purification strategies of stem cell-derived dopaminergic midbrain neurons. They conclude that recent advances in cell therapy for PD will create a viable long-term treatment option for synaptic repair for this debilitating disease. C1 [Isacson, Ole] Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, NINDS, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, MRC 130,115 Mill St, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu OI Cooper, Oliver/0000-0001-6567-7491 NR 87 TC 21 Z9 23 U1 3 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD MAR PY 2008 VL 24 IS 3-4 AR E5 DI 10.3171/FOC/2008/24/3-4/E5 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 308FQ UT WOS:000256374100005 PM 18341409 ER PT J AU Isacson, O AF Isacson, Ole TI Cell-based therapy for Parkinson disease - Response SO NEUROSURGICAL FOCUS LA English DT Editorial Material ID TRANSPLANTS C1 [Isacson, Ole] Harvard Univ, Belmont, MA USA. [Isacson, Ole] McLean Hosp, NINDS, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. RP Isacson, O (reprint author), Harvard Univ, Belmont, MA USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD MAR PY 2008 VL 24 IS 3-4 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 308FQ UT WOS:000256374100007 ER PT J AU Jandial, R Aryan, HE Park, J Taylor, WT Snyder, EY AF Jandial, Rahul Aryan, Henry E. Park, John Taylor, William T. Snyder, Evan Y. TI Stem cell-mediated regeneration of the intervertebral disc: cellular and molecular challenges SO NEUROSURGICAL FOCUS LA English DT Article DE intervertebral disc; regeneration; stem cell ID BONE-MARROW; ADIPOSE-TISSUE; NUCLEUS PULPOSUS; PROGENITOR CELLS; AGGRECAN GENE; IN-VIVO; THERAPY; EXPRESSION; DEGENERATION; POLYMORPHISM AB Regenerative medicine and stem cells hold great promise for intervertebral disc (IVD) disease. The therapeutic implications of utilizing stem cells to repair degenerated discs and treat back pain are highly anticipated by both the clinical and scientific communities. Although the avascular environment of the IVD poses a challenge for stem cell-mediated regeneration, neuroprogenitor cells have been discovered within degenerated discs, allowing scientists to revisit the hostile environment of the IVD as a target for stem cell therapy. Issues now under investigation include the timing of cell delivery and manipulation of stem cells to make them more efficient and adaptive in the IVD niche. This review covers the mechanisms underlying disc degeneration as well as the molecular and cellular challenges involved in directing stem cells to the desired cell type for intradiscal transplantation. C1 [Jandial, Rahul; Snyder, Evan Y.] Burnham Inst Med Res, Ctr Neurosci Aging & Stem Cell Res, La Jolla, CA 92037 USA. [Jandial, Rahul; Aryan, Henry E.; Taylor, William T.] Univ Calif San Diego, Div Neurosurg, San Diego, CA 92103 USA. [Park, John] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Porter Neurosci Res Ctr, NIH, Bethesda, MD USA. RP Snyder, EY (reprint author), Burnham Inst Med Res, Ctr Neurosci Aging & Stem Cell Res, 10901 N Torrey Pines Rd,Bldg 7, La Jolla, CA 92037 USA. EM esnyder@burnham.org NR 29 TC 2 Z9 2 U1 1 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD MAR PY 2008 VL 24 IS 3-4 AR E20 DI 10.3171/FOC/2008/24/3-4/E20 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 308FQ UT WOS:000256374100021 ER PT J AU Braunschweig, D Ashwood, P Krakowiak, P Hertz-Picciotto, I Hansen, R Croen, LA Pessah, IN Van de Water, J AF Braunschweig, Daniel Ashwood, Paul Krakowiak, Paula Hertz-Picciotto, Irva Hansen, Robin Croen, Lisa A. Pessah, Isaac N. Van de Water, Judy TI Autism: Maternally derived antibodies specific for fetal brain proteins SO NEUROTOXICOLOGY LA English DT Article DE autism; maternal antibodies; regression; autoantibodies ID IMMUNOGLOBULIN-G; SPECTRUM DISORDER; RISK-FACTORS; CHILDREN; AUTOANTIBODIES; PROTECTION; PHENOTYPE; VARICELLA; MEASLES AB Autism is a profound disorder of neurodevelopment with poorly understood biological origins. A potential role for maternal autoantibodies in the etiology of some cases of autism has been proposed in previous studies. To investigate this hypothesis, maternal plasma antibodies against human fetal and adult brain proteins were analyzed by western blot in 61 mothers of children with autistic disorder and 102 controls matched for maternal age and birth year (62 mothers of typically developing children (TD) and 40 mothers of children with non-ASD developmental delays (DD)). We observed reactivity to two protein bands at approximately 73 and 37 kDa in plasma from 7 of 61 (11.5%) mothers of children with autism (AU) against fetal but not adult brain, which was not noted in either control group (TD; 0/62 p = 0.0061 and DD; 0/40 p = 0.0401). Further, the presence of reactivity to these two bands was associated with parent report of behavioral regression in AU children when compared to the TD (p = 0.0019) and DD (0.0089) groups. Individual reactivity to the 37 kDa band was observed significantly more often in the AU population compared with TD (p = 0.0086) and DD (p = 0.002) mothers, yielding a 5.69-fold odds ratio (95% confidence interval 2.09-15.51) associated with this band. The presence of these antibodies in the plasma of some mothers of children with autism, as well as the differential findings between mothers of children with early onset and regressive autism may suggest an association between the transfer of IgG autoantibodies during early neurodevelopment and the risk of developing of autism in some children. (C) 2007 Elsevier Inc. All rights reserved. C1 [Braunschweig, Daniel; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Krakowiak, Paula; Hertz-Picciotto, Irva] Univ Calif Davis, Div Epidemiol, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Hansen, Robin] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. [Croen, Lisa A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Pessah, Isaac N.] Univ Calif Davis, Dept Vet Mol Biosci, Davis, CA 95616 USA. [Braunschweig, Daniel; Ashwood, Paul; Krakowiak, Paula; Hertz-Picciotto, Irva; Hansen, Robin; Pessah, Isaac N.; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Braunschweig, Daniel; Ashwood, Paul; Krakowiak, Paula; Hertz-Picciotto, Irva; Hansen, Robin; Pessah, Isaac N.; Van de Water, Judy] Univ Calif Davis, NIEHS, Ctr Childrens Environm Hlth, Davis, CA 95616 USA. RP Van de Water, J (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA. EM javandewater@ucdavis.edu FU NIEHS NIH HHS [P01 ES011269, P01 ES011269-070004, P01 ES11269-01, R01 ES015359] NR 31 TC 125 Z9 129 U1 3 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2008 VL 29 IS 2 BP 226 EP 231 DI 10.1016/j.neuro.2007.10.010 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 297KF UT WOS:000255614900003 PM 18078998 ER PT J AU Eddins, D Petr, A Pollard, N Freedman, JH Levin, ED AF Eddins, Donnie Petro, Ann Pollard, Ninitia Freedman, Jonathan H. Levin, Edward D. TI Mercury-induced cognitive impairment in metallothionein-1/2 null mice SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE metallothionein; mercury; learning; radial-arm maze; dopamine; serotonin ID PREFRONTAL CORTEX; WORKING-MEMORY; IN-VIVO; INDUCED AUTOIMMUNITY; DOSE-RESPONSE; NEUROBEHAVIORAL CHANGES; SYSTEMIC AUTOIMMUNITY; SEROTONIN RELEASE; DOPAMINE RELEASE; SUSCEPTIBLE MICE AB Metallothioneins are central for the metabolism and detoxification of transition metals. Exposure to mercury during early neurodevelopment is associated with neurocognitive impairment. Given the importance of metal lothioneins in mercury detoxification, metallothioneins may be a protective factor against mercury-induced neurocognitive impairment. Deletion of the murine metallothionein-1 and metallothionein-2 genes causes choice accuracy impairments in the 8-arm radial maze. We hypothesize that deletions of metal lothioneins genes will make metallothionein-null mice more vulnerable to mercury-induced cognitive impairment. We tested this hypothesis by exposing MTI/MT2-null and wild-type mice to developmental mercury (HgC12) and evaluated the resultant effects on cognitive performance on the 8-arm radial maze. During the early phase of leaming metallothionein-null mice were more susceptible to mercury-induced impairment compared to wildtype mice. Neurochemical analysis of the frontal cortex revealed that serotonin levels were higher in metallothionein-null mice compared to wild-type mice. This effect was independent of mercury exposure. However, dopamine levels in mercury-exposed metallothionein-null mice were lower compared to mercury-exposed wildtype mice. This work shows that deleting metallothioneins increase the vulnerability to developmental mercury-induced neurocognitive impairment. Metallothionein effects on monoamine transmitters may be related to this cognitive effect. (c) 2008 Elsevier Inc. All rights reserved. C1 [Freedman, Jonathan H.] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Eddins, Donnie; Petro, Ann; Pollard, Ninitia; Levin, Edward D.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. [Freedman, Jonathan H.; Levin, Edward D.] Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC 27706 USA. RP Freedman, JH (reprint author), Natl Inst Environm Hlth Sci, Mol Toxicol Lab, NIH, Box 12233,E1-05 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM freedma1@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [P42 ES010356-070002, P42 ES010356, P42 ES010356-080002] NR 49 TC 16 Z9 16 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2008 VL 30 IS 2 BP 88 EP 95 DI 10.1016/j.ntt.2007.12.005 PG 8 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 278VP UT WOS:000254314700003 PM 18226494 ER EF