FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ryan, MH Bristol, JA McDuffie, E Abrams, SI AF Ryan, MH Bristol, JA McDuffie, E Abrams, SI TI Regression of extensive pulmonary metastases in mice by adoptive transfer of antigen-specific CD8(+) CTL reactive against tumor cells expressing a naturally occurring rejection epitope SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; ANTITUMOR-ACTIVITY; IMMUNOTHERAPY; RECOMBINANT; LYMPHOCYTES; THERAPY; INTERLEUKIN-2; ACTIVATION; RESPONSES; VACCINE AB In this study, we developed a mouse model of adoptive immunotherapy reflecting immune recognition of syngeneic tumor cells naturally expressing an endogenous rejection Ag. Specifically, in a pulmonary metastases model, we examined the potency and maintenance of an antitumor CD8(+) CTL response in vivo, as well as its effectiveness against an "extensive" tumor burden. The approach taken was to first generate tumor-specific CTL from mice challenged with the CMS4 sarcoma coadministered with anti-CTLA4 mAb, which has been shown to facilitate the induction of Ag-specific T cell responses in vivo. An H-2L(d)-restrieted nonamer peptide, derived from an endogenous murine leukemia provirus was Identified as a CMS4-reactive CTL epitope based upon the following: CTL cross-recognition of another syngeneic tumor cell line (CT26 colon carcinoma) previously characterized to express that gene product; sensitization of Ag-negative lymphoblasts or P815 targets with the peptide; and by cold target inhibition assays. In vivo, the adoptive transfer of CMS4-reactive CTL (greater than or equal to1 X 10(6)) resulted in nearly the complete regression of 3-day established lung metastases. Furthermore, mice that rejected CMS4 following a single adoptive transfer of CTL displayed antitumor activity to a rechallenge 45 days later, not only in the lung, but also at a s.c. distal site. Lastly, the adoptive transfer of CTL to mice harboring extensive pulmonary metastases (> 150 nodules) led to a substantial reduction in tumor burden. Overall, these data suggest that the adoptive transfer of tumor-specific CTL may have therapeutic potential for malignancies that proliferate in or metastasize to the lung. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. NR 22 TC 38 Z9 38 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 OCT 15 PY 2001 VL 167 IS 8 BP 4286 EP 4292 PG 7 WC Immunology SC Immunology GA 487DL UT WOS:000171858300020 PM 11591751 ER PT J AU Gubina, E Luo, X Kwon, E Sakamoto, K Shi, YF Mufson, RA AF Gubina, E Luo, X Kwon, E Sakamoto, K Shi, YF Mufson, RA TI beta c cytokine receptor-induced stimulation of cAMP response element binding protein phosphorylation requires protein kinase C in myeloid cells: A novel cytokine signal transduction cascade SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR CREB; BCL-2 EXPRESSION; PHOSPHOLIPASE-C; B-LYMPHOCYTES; ACTIVATION; INTERLEUKIN-3; PATHWAY; GROWTH; EGR-1; SERINE-133 AB We have recently shown that IL-3R occupancy activates a phosphatidylcholine-specific phospholipase C, and the sustained diacylglycerol accumulation subsequently activates protein kinase C (PKC). In human IL-3-dependent myeloid cells (TF-1), the novel PKG epsilon isoform regulates bcl-2 expression and cell survival. The report of a PKC activatable cAMP response element (CRE) in the bcl-2 promoter and a role for PKC in bel-2 expression in B cells led us to the hypothesis that PKC phosphorylation activates transcription factor CREB after IL-3R engagement. We found that IL-3 and GM-CSF induced phosphorylation of CREB on Ser(133) in TF-1 cells, and this phosphorylation was blocked by two structurally unrelated classes of PKC inhibitors. An inhibitor of cyclic nucleotide-dependent kinases did not block this phosphorylation. IL-4, which is biologically active in these cells but does not use the beta common subunit, did not phosphorylate CREB on Ser(133). Inhibition of mitogen-activated protein kinase kinase activity also inhibited IL3-induced CREB phosphorylation. The PKC inhibitors, but not a cyclic nucleotide-dependent kinase inhibitor, blocked IL-3 activation of CRE-dependent transcription from an egr-1 promoter/chloramphenicol acetyltransferase (CAT) reporter construction transiently transfected into TF-1 cells. Finally, TF-1 cells stably overexpressing PKC epsilon, but not the delta isoform of PKC, enhanced CRE-dependent CAT expression from the promoter/reporter construction. Therefore, it is likely that a PKG epsilon kinase cascade resulting in CREB phosphoryIation represents a novel signal transduction cascade for regulating cellular gene expression through the beta common cytokine receptor. C1 Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. Amer Red Cross, Holland Lab, Dept Immunol, Rockville, MD 20855 USA. RP Mufson, RA (reprint author), NCI, Div Immunol, Hematol Branch, 6130 Execut Blvd,Execut Plaza N,Room 513, Rockville, MD 20852 USA. FU NCI NIH HHS [R01 CA53609-06] NR 33 TC 21 Z9 22 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2001 VL 167 IS 8 BP 4303 EP 4310 PG 8 WC Immunology SC Immunology GA 487DL UT WOS:000171858300022 PM 11591753 ER PT J AU Lapointe, R Royal, RE Reeves, ME Altomare, I Robbins, PF Hwu, P AF Lapointe, R Royal, RE Reeves, ME Altomare, I Robbins, PF Hwu, P TI Retrovirally transduced human dendritic cells can generate T cells recognizing multiple MHC class I and class II epitopes from the melanoma antigen glycoprotein 100 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CANCER-IMMUNOTHERAPY; LYMPHOCYTE RESPONSES; METASTATIC MELANOMA; MEMBRANE-PROTEINS; TUMOR-ANTIGEN; GP100; IDENTIFICATION; PEPTIDES; IMMUNIZATION; VACCINE AB Involvement of tumor-Ag specific CD4(+) and CD8(+) T cells could be critical in the generation of an effective immunotherapy for cancer. In an attempt to optimize the T cell response against defined tumor Ags, we previously developed a method allowing transgene expression in human dendritic cells (DCs) using retroviral vectors. One advantage of using gene-modified DCs is the potential ability to generate CD8(+) T cells against multiple class I-restricted epitopes within the Ag, thereby eliciting a broad antitumor immune response. To test this, we generated tumor-reactive CD8(+) T cells with DCs transduced with the melanoma Ag gp100, for which a number of HLA-A2-restricted epitopes have been described. Using gp100-transduced DCs, we were indeed able to raise T cells recognizing three distinct HLA-A2 epitopes within the Ag, gp100(154-162), gp100(209-217), and gp100(280-288). We next tested the ability of transduced DCs to raise class II-restricted CD4(+) T cells. Interestingly, stimulation with gp100-transduced DCs resulted in the generation of CD4(+) T cells specific for a novel HLA-DR beta1*0701-restricted epitope of gp100. The minimal determinant of this epitope was defined as gp100(174-190) (TGRAMLGTHTMEVTVYH). These observations suggest that retrovirally transduced DCs have the capacity to present multiple MHC class I- and class II-restricted peptides derived from a tumor Ag, thereby eliciting a robust immune response against that Ag. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Hwu, P (reprint author), NCI, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. NR 42 TC 41 Z9 42 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 OCT 15 PY 2001 VL 167 IS 8 BP 4758 EP 4764 PG 7 WC Immunology SC Immunology GA 487DL UT WOS:000171858300076 PM 11591807 ER PT J AU Lin, FYC Philips, JB Azimi, PH Weisman, LE Clark, P Rhoads, GG Regan, J Concepcion, NF Frasch, CE Troendle, J Brenner, RA Gray, BM Bhushan, R Fitzgerald, G Moyer, P Clemens, JD AF Lin, FYC Philips, JB Azimi, PH Weisman, LE Clark, P Rhoads, GG Regan, J Concepcion, NF Frasch, CE Troendle, J Brenner, RA Gray, BM Bhushan, R Fitzgerald, G Moyer, P Clemens, JD TI Level of maternal antibody required to protect neonates against early-onset disease caused by group B streptococcus type Ia: A multicenter, seroepidemiology study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CONJUGATE VACCINES; III POLYSACCHARIDE; MOUSE PROTECTION; IGG ANTIBODY; INFECTION; SUSCEPTIBILITY; IMMUNIZATION; SERUM; IMMUNOGENICITY; PREVENTION AB Because of the difficulty of conducting efficacy trials of vaccines against group B streptococcus (GBS), the licensure of these vaccines may have to rely on studies that measure vaccine-induced antibody levels that correlate with protection. This study estimates the level of maternal antibody required to protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates colonized by GBS Ia but without EOD) born at greater than or equal to 34 weeks gestation were compared. The probability of developing EOD declined with increasing maternal levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG GBS Ia antibody greater than or equal to5 mug/mL had an 88% lower risk (95% confidence interval, 7%-98%) of developing type-specific EOD, compared with those whose mothers had levels <0.5 g/mL. A vaccine that induces IgG GBS Ia antibody levels greater than or equal to5 mug/mL in mothers can be predicted to confer a high degree of type-specific immunity to EOD to their infants. C1 NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Westat Corp, Rockville, MD USA. Childrens Hosp Med Ctr No Calif, Oakland, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Florida, Dept Obstet & Gynecol, Gainesville, FL 32611 USA. Univ Med & Dent New Jersey, Dept Environm & Community Med, Piscataway, NJ 08854 USA. Columbia Univ Hlth Sci, New York, NY USA. RP Lin, FYC (reprint author), 6100 Execut Blvd,Rm 7b03,MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD-43217, HD-43220, HD-43219, HD-43215, HD-53233, HD-43214, HD-43218] NR 42 TC 51 Z9 52 U1 0 U2 2 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 OCT 15 PY 2001 VL 184 IS 8 BP 1022 EP 1028 DI 10.1086/323350 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476NG UT WOS:000171233200010 PM 11574917 ER PT J AU Wiener, MC Oram, MW Liu, Z Richmond, BJ AF Wiener, MC Oram, MW Liu, Z Richmond, BJ TI Consistency of encoding in monkey visual cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE coding; visual; cortex; V1; TE; inferior temporal cortex; monkey; natural images; mean-variance relation ID INFERIOR TEMPORAL CORTEX; LATERAL GENICULATE-NUCLEUS; MOTION-SENSITIVE NEURONS; TWO-DIMENSIONAL PATTERNS; SINGLE NEURONS; NATURAL SCENES; SIMPLE CELLS; INFORMATION-TRANSMISSION; RESPONSE VARIABILITY; CODING STRATEGIES AB Are different kinds of stimuli (for example, different classes of geometric images or naturalistic images) encoded differently by visual cortex, or are the principles of encoding the same for all stimuli? We examine two response properties: (1) the range of spike counts that can be elicited from a neuron in epochs representative of short periods of fixation (up to 400 msec), and (2) the relation between mean and variance of spike counts elicited by different stimuli, that together characterize the information processing capabilities of a neuron using the spike count code. In monkey primary visual cortex (V1) complex cells, we examine responses elicited by static stimuli of four kinds (photographic images, bars, gratings, and Walsh patterns); in area TE of inferior temporal cortex, we examine responses elicited by static stimuli in the sample, nonmatch, and match phases of a delayed match-to-sample task. In each area, the ranges of mean spike counts and the relation between mean and variance of spike counts elicited are sufficiently similar across experimental conditions that information transmission is unaffected by the differences across stimulus set or behavioral conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically significant but small differences, the median difference in transmitted information for these neurons was 0.9%]. Encoding therefore appears to be consistent across experimental conditions for neurons in both V1 and TE, and downstream neurons could decode all incoming signals using a single set of rules. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B-80, Bethesda, MD 20892 USA. RI Oram, Michael/A-2558-2010 NR 56 TC 28 Z9 29 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 2001 VL 21 IS 20 BP 8210 EP 8221 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 480BU UT WOS:000171442000041 PM 11588193 ER PT J AU Wilting, J Papoutsi, M Othman-Hassan, K Rodrigttez-Niedenfuhr, M Prols, F Tomarev, SI Eichmann, A AF Wilting, J Papoutsi, M Othman-Hassan, K Rodrigttez-Niedenfuhr, M Prols, F Tomarev, SI Eichmann, A TI Development of the avian lymphatic system SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE avian embryo; chorioallantoic membrane; lymphangiogenesis; lymphangioblast; endothelium; VEGF-C; VEGFR-3; Prox1; quail-chick chimera ID ENDOTHELIAL GROWTH-FACTOR; VEGF-C; CHORIOALLANTOIC MEMBRANE; EMBRYONIC-DEVELOPMENT; MONOCLONAL-ANTIBODY; CELLS; RECEPTOR; EXPRESSION; DIFFERENTIATION; QUAIL AB Recently, highly specific markers of the lymphatic endothelium have been found enabling us to reinvestigate the embryonic origin of the lymphatics. Here we present a review of our studies on the development of the lymphatic system in chick and quail embryos. We show that the lymphatic endothelium is derived from two sources: the embryonic lymph sacs and mesenchymal lymphangioblasts. Proliferation studies reveal a BrdU-labeling index of 11.5% of lymph sac endothelial cells by day 6.25, which drops to 3.5% by day 7. Lymphangioblasts are able to integrate into the lining of lymph sacs. Lymphatic endothelial cells express the vascular endothelial growth factor (VEGF) receptors-2 and -3. Their ligand, VEGF-C, is expressed almost ubiquitously in embryonic and fetal tissues. Elevated expression levels are found in the tunica media of large blood vessels, which usually serve as major routes for growing lymphatics. The homeobox gene, Prox1, is expressed in lymphatic but not in blood vascular endothelial cells throughout all stages examined, namely, in developing lymph sacs of day 6 embryos and in lymphatics at day 16. Experimental studies show the existence of lymphangioblasts in the mesoderm, a considerable time before the development of the lymph sacs. Lymphangioblasts migrate from the somites into the somatopleure and contribute to the lymphatics of the limbs. Our studies indicate that these lymphangioblasts already express Prox1. (C) 2001 Wiley-Liss, Inc. C1 Univ Freiburg, Inst Anat, D-79104 Freiburg, Germany. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. CNRS, Inst Embryol Cellulaire & Mol, Coll France, F-94736 Nogent Sur Marne, France. RP Wilting, J (reprint author), Univ Freiburg, Inst Anat, Albertstr 17, D-79104 Freiburg, Germany. EM wilting@uni-freiburg.de FU NICHD NIH HHS [N01-HD-6-2915] NR 60 TC 34 Z9 34 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD OCT 15 PY 2001 VL 55 IS 2 BP 81 EP 91 DI 10.1002/jemt.1159 PG 11 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 484TH UT WOS:000171705300004 PM 11596153 ER PT J AU Dietz, W Rolls, BJ Stice, E Yanovski, JA AF Dietz, W Rolls, BJ Stice, E Yanovski, JA TI Treating the obese teenager SO PATIENT CARE LA English DT Article ID BODY-MASS INDEX; ADOLESCENTS; CHILDREN; WEIGHT; ONSET AB Encouraging gradual behavior change and ruling out possible physiologic causes of extreme overweight can improve teenagers chances of long-term weight loss and better health. C1 Ctr Dis Control & Prevent, Div Nutr & Phys Act, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Penn State Univ, Coll Hlth & Human Dev, Dept Nutr, University Pk, PA 16802 USA. Univ Texas, Dept Psychol, Austin, TX 78712 USA. NICHHD, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA. RP Dietz, W (reprint author), Ctr Dis Control & Prevent, Div Nutr & Phys Act, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU MEDICAL ECONOMICS PI MONTVALE PA FIVE PARAGON DRIVE, MONTVALE, NJ 07645-1742 USA SN 0031-305X J9 PATIENT CARE JI Patient Care PD OCT 15 PY 2001 VL 35 IS 19 BP 57 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 482VX UT WOS:000171598900010 ER PT J AU Saavedra, JM Armando, I Terron, JA Falcon-Neri, A Johren, O Hauser, W Inagami, T AF Saavedra, JM Armando, I Terron, JA Falcon-Neri, A Johren, O Hauser, W Inagami, T TI Increased AT(1) receptors in adrenal gland of AT(2) receptor gene-disrupted mice SO REGULATORY PEPTIDES LA English DT Article DE renin-angiotensin system; adrenal gland zona glomerulosa; angiotensin II receptor types; gene-disrupted models ID ANGIOTENSIN-II RECEPTOR; TYPE-1 RECEPTOR; AT(2) RECEPTOR; QUANTITATIVE AUTORADIOGRAPHY; AT(1) RECEPTOR; MESSENGER-RNA; BRAIN PASTE; EXPRESSION; SUBTYPES; MOUSE AB Angiotensin II (Ang II) AT(2) receptor-gene disrupted mice have increased systemic blood pressure and response to exogenous Angiotensin II. To clarify the mechanism of these changes, we studied adrenal AT(1) receptor expression and mRNA by receptor autoradiography and in situ hybridization in female AT(1) receptor-gene disrupted mice (agtr 2-/-) and wild-type controls (agtr 2+/+). We found high expression of AT(1) receptor binding and mRNA in adrenal zona glomerulosa of female wild-type mice. AT(2) receptors and mRNA were highly expressed in adrenal medulla of wild-type mice, but were not detected in zona glomerulosa. There was no AT(2) receptor binding or mRNA in adrenal glands of AT(2) receptor-gene disrupted mice. In these animals, AT(1) receptor binding and mRNA were increased in adrenal zona glomerulosa and AT(1) receptor mRNA was increased in the adrenal medulla when compared with wild-type animals. The present data support the hypothesis of an interaction or cross talk between AT(2) and AT(1) receptors in adrenal gland. The significant increase in AT(1) receptor expression in the absence of AT(2) receptor transcription may be partially responsible for the increased blood pressure and for the enhanced response to exogenously administered Angiotensin II in this model. Published by Elsevier Science B.V. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, 10 Ctr Dr MSC 1514,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM Saavedrj@irp.nimh.nih.gov RI Johren, Olaf/G-6967-2011 NR 38 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD OCT 15 PY 2001 VL 102 IS 1 BP 41 EP 47 DI 10.1016/S0167-0115(01)00303-2 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 487YN UT WOS:000171907200006 PM 11600209 ER PT J AU Willems, BAT Melnick, RL Kohn, MC Portier, CJ AF Willems, BAT Melnick, RL Kohn, MC Portier, CJ TI A physiologically based pharmacokinetic model for inhalation and intravenous administration of naphthalene in rats and mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE PBPK; mathematical modeling; naphthalene; carcinogenicity; glutathione ID CLARA CELL CYTOTOXICITY; ETHYLENE-OXIDE; DISPOSITION; METABOLISM; PULMONARY; HAMSTERS; MOUSE AB A diffusion limited physiologically based pharmacokinetic model for rats and mice was developed to characterize the absorption, distribution, metabolism, and elimination of naphthalene after inhalation exposure. This model includes compartments for arterial and venous blood, lung, liver, kidney, fat, and other organs. Primary sites for naphthalene metabolism to naphthalene oxide are the lung and the liver. The data used to create this model were generated from National Toxicology Program inhalation and iv studies on naphthalene and consisted of blood time-course data of the parent compound in both rats and mice. To examine the basis for possible interspecies differences in response to naphthalene, the model was extended to describe the distribution and metabolism of naphthalene oxide and the depletion and resynthesis of glutathione. After testing several alternative models, the one presented in this paper shows the best fit to the data wi the fewest assumptions possible. The model indicates that tissue dosimetry of the parent compound alone does not explain why this chemical was carcinogenic to the female mouse lung but not to the rat lung. The species difference may be due to a combination of higher levels of naphthalene oxide in the mouse lung and a greater susceptibility of the mouse lung to epoxide-induced carcinogenesis. However, conclusions regarding which metabolite(s) may be responsible for the lung toxicity could not be reached. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Willems, BAT (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 38 TC 19 Z9 25 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 15 PY 2001 VL 176 IS 2 BP 81 EP 91 DI 10.1006/taap.2001.9269 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 487CM UT WOS:000171856100002 PM 11601884 ER PT J AU Simonsen, L Morens, DM Elixhauser, A Gerber, M Van Raden, M Blackwelder, WC AF Simonsen, L Morens, DM Elixhauser, A Gerber, M Van Raden, M Blackwelder, WC TI Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception SO LANCET LA English DT Article ID DEVELOPING-COUNTRIES; UNITED-STATES; IMMUNIZATION; INFECTION; CHILDREN; FUTURE AB Background Studies have reported a temporal association between a first dose of rotavirus vaccine (Rotashield) and infant intussusception. We investigated the effect of Rotashield vaccination use on intussusception admissions in ten US states. Methods We analysed electronic databases containing 100% hospital discharge records for 1993-99 from ten US states, where an estimated 28% of the birth cohort had received Rotashield (based on manufacturer's net sales data). We examined records of infants admitted to hospital (<365 days old) with any mention of intussusception (international Classification of Diseases, ninth revision. clinical modification code 560.0). Excess admissions for intussusception during the period of Rotashield availability (October 1998 to June 1999) were estimated by direct comparison with the corresponding period of October 1997 to June 1998 (before Rotashield was available) and with adjustment for secular trends during 1993-98 by Poisson regression. Findings Hospital admission for intussusception among infants younger than 365 days of age during the Rotashield period compared with previously was 4% lower (10 cases) by direct comparison and 10% lower (27 cases) by trend comparison, corresponding to a negative population attributable risk. Among infants aged 45-210 days (target age range for a first Rotashield dose), we estimated an increase in intussusception admissions of 1% (one excess admission) by direct comparison and 4% (4.6 excess admissions) by trend comparison, corresponding to a population attributable risk range of one excess admission in 66 000-302 000. Interpretation We found no evidence of increased infant intussusception admissions during the period of Rotashield availability. The total intussusception admission risk attributable to Rotashield was substantially lower than previous estimates based on studies focusing on the immediate postvaccination weeks. C1 NIAID, NIH, Bethesda, MD 20892 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. RP Simonsen, L (reprint author), 6700-B Rockledge Dr,Room 3153, Bethesda, MD 20892 USA. OI Simonsen, Lone/0000-0003-1535-8526 NR 20 TC 76 Z9 78 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 13 PY 2001 VL 358 IS 9289 BP 1224 EP 1229 DI 10.1016/S0140-6736(01)06346-2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 481NX UT WOS:000171527000012 PM 11675060 ER PT J AU Myslobodsky, MS AF Myslobodsky, MS TI Genetic risk factors in mothers and offspring SO LANCET LA English DT Letter C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Myslobodsky, MS (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 13 PY 2001 VL 358 IS 9289 BP 1268 EP 1269 DI 10.1016/S0140-6736(01)06358-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 481NX UT WOS:000171527000036 PM 11675085 ER PT J AU Tanaka, H Wakisaka, A Ogasa, H Kawai, S Liang, CT AF Tanaka, H Wakisaka, A Ogasa, H Kawai, S Liang, CT TI Local and systemic expression of insulin-like growth factor-I (IGF-I) mRNAs in rat after bone marrow ablation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE insulin-like growth factor-I; bone marrow ablation; gene expression ID MESSENGER-RNA; GENE-EXPRESSION; OVARIECTOMIZED RATS; REGENERATING BONE; RIBONUCLEIC-ACIDS; SOMATOMEDIN-C; OLD RATS; LIVER; CARTILAGE; FRACTURE AB Local and systemic expression of insulin-like growth factor-I (IGF-I) during bone formation was studied using the rat bone marrow ablation model. The temporal expression pattern of IGF-I mRNA in rat femurs was examined. The IGF-I mRNA level was enhanced rapidly after ablation reaching a level threefold greater than basal by day 3 (P < 0.01) and declined to basal or below basal level by day 5. Histological analysis showed that IGF-I immunoreactivity was predominantly associated with the mesenchymal cells at the bone/connective tissue interface and osteoblastic cells at active sites of bone formation. Serum level of IGF-I increased 50 and 130%, respectively (P < 0.005), over the basal level at days 3 and 6. We also investigated the systemic expression of IGF-I in liver and kidney. In contrast, hepatic IGF-I gene expression decreased 37 and 48%, respectively, at days 3 and 6 after marrow ablation (P < 0.001). Kidney IGF-I mRNA levels also fell 13 and 27%, respectively, at days 3 and 6 (P < 0.005). The present findings suggest that locally produced IGF-I during bone formation may not only serve as an autocrine/paracrine factor but also influence systemic expression of IGF-I in other organs. (C) 2001 Academic Press. C1 Yamaguchi Univ, Sch Med, Dept Orthoped Surg, Ube, Yamaguchi 7558505, Japan. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Natl Hlth Res Inst, Taipei 115, Taiwan. RP Tanaka, H (reprint author), Yamaguchi Univ, Sch Med, Dept Orthoped Surg, 1-1-1 Minamikogushi, Ube, Yamaguchi 7558505, Japan. NR 35 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 12 PY 2001 VL 287 IS 5 BP 1157 EP 1162 DI 10.1006/bbrc.2001.5711 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 482AG UT WOS:000171552200020 PM 11587544 ER PT J AU Schaaf, MJM Workel, JO Lesscher, HM Vreugdenhil, E Oitzl, MS de Kloet, ER AF Schaaf, MJM Workel, JO Lesscher, HM Vreugdenhil, E Oitzl, MS de Kloet, ER TI Correlation between hippocampal BDNF mRNA expression and memory performance in senescent rats SO BRAIN RESEARCH LA English DT Article DE aging; hippocampus; learning neurotrophic factor; neurotrophin; water maze ID LONG-TERM POTENTIATION; FACTOR MESSENGER-RNA; FREELY-MOVING RAT; NEUROTROPHIC FACTOR; INDIVIDUAL-DIFFERENCES; SYNAPTIC TRANSMISSION; MATERNAL-DEPRIVATION; MUTANT MICE; BRAIN; NEURONS AB Brain-derived neurotrophic factor (BDNF) has been suggested to be involved in memory processes. In the present study, the association between memory impairment at senescence and BDNF expression in the hippocampus was studied in 30-32-month-old Brown Norway rats, which had been maternally deprived early in life. These animals display a bimodal distribution in their spatial learning ability: rats are either non-impaired or impaired. BDNF mRNA expression in the hippocampus was compared between non-impaired and impaired rats. We measured BDNF mRNA expression in the hippocampus 3 h after training in the Morris water maze ('post-training') and at I month after training ('basal'). Non-impaired performers displayed a higher post-training BDNF mRNA level in the CAI region than impaired rats. In addition, only in the non-impaired performers post-training BDNF mRNA levels in CAI and dentate gyrus were increased as compared to basal levels. Thus, we have demonstrated that in senescent rats, hippocampal BDNF expression in response to water maze training is associated with memory performance. (C) 2001 Elsevier Science BY All rights reserved. C1 Leiden Amsterdam Ctr Drug Res, Sylvius Labs, Div Med Pharmacol, NL-2300 RA Leiden, Netherlands. RP Schaaf, MJM (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 41 TC 75 Z9 78 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 12 PY 2001 VL 915 IS 2 BP 227 EP 233 DI 10.1016/S0006-8993(01)02855-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 486JC UT WOS:000171813800012 PM 11595212 ER PT J AU Zubareva, OE Krasnova, IN Abdurasulova, IN Bluthe, RM Dantzer, R Klimenko, VM AF Zubareva, OE Krasnova, IN Abdurasulova, IN Bluthe, RM Dantzer, R Klimenko, VM TI Effects of serotonin synthesis blockade on interleukin-1 beta action in the brain of rats SO BRAIN RESEARCH LA English DT Article DE serotonin; interleukin-1 beta; body temperature; food intake; body weight; social behavior ID HYPOTHALAMIC SEROTONIN; METABOLISM; NUCLEUS; MICRODIALYSIS; RELEASE; WEIGHT AB The ability of the brain serotonergic system to mediate the effects of interleukin-1 beta (lL-1 beta) was investigated. Intracerebroventricular administration of IL-1 beta induced a significant pyrogenic reaction, depression in social behaviour, loss of body weight and reduced food intake in rats. Pre-treatment with p-chlorphenylalanine, an inhibitor of serotonin synthesis, blocked the IL-1 beta -induced decrease in food intake and loss of body weight, but failed to alter the temperature increase and the decrease in communicative activity. (C) 2001 Elsevier Science BY All rights reserved. C1 Russian Acad Sci, Inst Expt Med, St Petersburg 196140, Russia. Russian Acad Sci, Inst Human Brain, St Petersburg 196140, Russia. INRA, INSERM U394, Bordeaux, France. RP Krasnova, IN (reprint author), NIDA, Intramural Res Program, Mol Neuropsychiat Sect, NIH, POB 5180, Baltimore, MD 21224 USA. NR 22 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 12 PY 2001 VL 915 IS 2 BP 244 EP 247 DI 10.1016/S0006-8993(01)02910-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 486JC UT WOS:000171813800015 PM 11595215 ER PT J AU Matsuka, Y Neubert, JK Maidment, NT Spigelman, I AF Matsuka, Y Neubert, JK Maidment, NT Spigelman, I TI Concurrent release of ATP and substance P within guinea pig trigeminal ganglia in vivo SO BRAIN RESEARCH LA English DT Article DE neuropeptide; microdialysis; pain; trigeminal ganglia; substance P; ATP ID DORSAL-ROOT-GANGLIA; CROSS-EXCITATION; SENSORY NEURONS; IMMUNOCYTOCHEMICAL LOCALIZATION; ECTO-NUCLEOTIDASES; BINDING-SITES; SPINAL-CORD; RAT; RECEPTORS; P2X(3) AB Neurons within sensory ganglia have been proposed to communicate via non-synaptic release of a diffusible chemical messenger, but the identity of the chemical mediator(s) remains unknown [J. Neurosci. 16 (1996) 4733-474]. The present study addressed the possibility of co-released ATP and substance P (SP) within sensory ganglia to further advance the hypothesis of non-synaptic communication between sensory neurons. Microdialysis probes inserted into trigeminal ganglia (TRGs) of anesthetized guinea pigs were perfused with artificial cerebrospinal fluid and the collected perfusate analyzed for ATP and SP content using the firefly luciferin-luciferase (L/L) assay and radioimmunoassay, respectively. Significant reversible increases in ATP and SP levels were observed after infusion of 100 mM KCI or I mM capsaicin. Ca2+-free ACSF produced an eightfold increase in ATP levels, interpreted as a decrease in activity of Ca2+-dependent ecto-nucleotidases that degrade ATR In contrast, KCI-induced release of ATP in the presence of normal Ca2+ was blocked by Cd2+, a voltage-gated Ca2+ channel blocker, illustrating Ca2+-dependence of evoked AT? release. Since ganglionic release of ATP could arise from several neuronal and non-neuronal sources we directly tested acutely dissociated TRG neuron somata for ATP release. Neuron-enriched dissociated TRG cells were plated onto glass tubes and tested for ATP release using the L/L assay. Robust ATP release was evoked with 5 muM capsaicin. These data suggest that ATP is released concurrently with SP from the somata of neurons within sensory ganglia. (C) 2001 Elsevier Science BY. All rights reserved. C1 Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA. NIH, Pain & Neurosensory Mechanisms Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dent Res Inst, Los Angeles, CA 90024 USA. RP Spigelman, I (reprint author), Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. OI Matsuka, Yoshizo/0000-0003-1069-2605 FU NIDCR NIH HHS [DE00408, DE07212] NR 42 TC 69 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 12 PY 2001 VL 915 IS 2 BP 248 EP 255 DI 10.1016/S0006-8993(01)02888-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 486JC UT WOS:000171813800016 PM 11595216 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI How carcinogens (or telomere dysfunction) induce genetic instability: associated-selection model SO FEBS LETTERS LA English DT Article DE carcinogen; cancer; selection; genetic instability; telomerase ID GENOMIC INSTABILITY; ULCERATIVE-COLITIS; CANCER; TUMORS AB Carcinogens induce carcinogen-specific genetic instability (defects in DNA repair). According to the 'direct-selection' model, defects in DNA repair per se provide an immediate growth advantage. According to the 'associated-selection' model, carcinogens merely select for cells with adaptive mutations. Like any mutations, adaptive mutations occur predominantly in genetically unstable cells. The 'associated-selection' model predicts that carcinogen-driven selection minimizes cytotoxic but maximizes mutagenic effects of carcinogens. A purely mutagenic (neither cytotoxic, nor cytostatic) environment will favor effective DNA repair, whereas any growth-limiting conditions (telomerase deficiency, anticancer drugs) will select for genetically unstable cells. Genetic instability is a postmark of selective pressure rather than a hallmark of cancer per se. Once selected, genetic instability facilitates the development of resistance to any other growth-limiting conditions. As an example, a putative link between prior exposure to carcinogens and the ability to develop a telomerase-independent growth is discussed. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,R 12 N 226, Bethesda, MD 20892 USA. NR 27 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 12 PY 2001 VL 506 IS 3 BP 169 EP 172 DI 10.1016/S0014-5793(01)02894-0 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 484KF UT WOS:000171688200001 PM 11602239 ER PT J AU Olivares-Reyes, JA Smith, RD Hunyady, L Shah, BH Catt, KJ AF Olivares-Reyes, JA Smith, RD Hunyady, L Shah, BH Catt, KJ TI Agonist-induced signaling, desensitization, and internalization of a phosphorylation-deficient AT(1A) angiotensin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; 3RD INTRACELLULAR LOOP; ACIDIC AMINO-ACIDS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; KINASE-MEDIATED PHOSPHORYLATION; DYNAMIN-DEPENDENT ENDOCYTOSIS; DOMINANT-NEGATIVE MUTANT; MU-OPIOID RECEPTOR; ADRENERGIC-RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR AB An analysis of the functional role of a diacidic motif (Asp(236)-Asp(237)) in the third intracellular loop of the AT(1A) angiotensin II (Ang II) receptor (AT(1)-R) revealed that substitution of both amino acids with alanine (DD-AA) or asparagine (DD-NN) residues diminished Ang II-induced receptor phosphorylation in COS-7 cells. However, Ang II-stimulated inositol phosphate production, mitogen-activated protein kinase, and AT(1) receptor desensitization and internalization were not significantly impaired. Overexpression of dominant negative G protein-coupled receptor kinase 2 (GRK2)K-220M decreased agonist-induced receptor phosphorylation by similar to 40%, but did not further reduce the impaired phosphorylation of DD-AA and DD-NN receptors. Inhibition of protein kinase C by bisin-dolylmaleimide reduced the phosphorylation of both the wild-type and the DD mutant receptors by similar to 30%. The inhibitory effects of GRK2(K220M) expression and protein kinase C inhibition by bisindolylmaleimide on agonist-induced phosphorylation were additive for the wild-type AT(1)-R, but not for the DD mutant receptor. Agonist-induced internalization of the wild-type and DD mutant receptors was similar and was unaltered by coexpression of GRK2(K220M). These findings demonstrate that an acidic motif at position 236/237 in the third intracellular loop of the AT(1)-R is required for optimal Ang II-induced phosphorylation of its carboxyl-terminal tail by GRKs. Furthermore, the properties of the DD mutant receptor suggest that not only Ang II-induced signaling, but also receptor desensitization and internalization, are independent of agonist-induced GRK-mediated phosphorylation of the AT(1) receptor. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1088 Budapest, Hungary. RP NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A-36,9000 Rockville Pike, Bethesda, MD 20892 USA. EM catt@helix.nih.gov NR 54 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 12 PY 2001 VL 276 IS 41 BP 37761 EP 37768 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481NU UT WOS:000171526500007 PM 11495923 ER PT J AU Schiffer, SG Foley, S Kaffashan, A Hronowski, X Zichittella, AE Yeo, CY Miatkowski, K Adkins, HB Damon, B Whitman, M Salomon, D Sanicola, M Williams, KP AF Schiffer, SG Foley, S Kaffashan, A Hronowski, X Zichittella, AE Yeo, CY Miatkowski, K Adkins, HB Damon, B Whitman, M Salomon, D Sanicola, M Williams, KP TI Fucosylation of Cripto is required for its ability to facilitate nodal signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ONE-EYED PINHEAD; MAMMARY EPITHELIAL-CELLS; HUMAN COLON-CARCINOMA; LEFT-RIGHT ASYMMETRY; O-LINKED FUCOSE; GROWTH-FACTOR; IMMUNOHISTOCHEMICAL DETECTION; VERTEBRATE DEVELOPMENT; XENOPUS DEVELOPMENT; OVERLAP EXTENSION AB O-Linked fucose modification is rare and has been shown to occur almost exclusively within epidermal growth factor (EGF)-like modules. We have found that the EGF-CFC family member human Cripto-1 (CR) is modified with fucose and through a combination of peptide mapping, mass spectrometry, and sequence analysis localized the site of attachment to Thr-88. The identification of a fucose modification on human CR within its EGF-like domain and the presence of a consensus fucosylation site within all EGF-CFC family members suggest that this is a biologically important modification in CR, which functionally distinguishes it from the EGF ligands that bind the type 1 erbB growth factor receptors. A single CR point mutation, Thr-88 --> Ala results in a form of the protein that is not fucosylated and has substantially weaker activity in cell-based CR/Nodal signaling assays, indicating that fucosylation is functionally important for CR to facilitate Nodal signaling. C1 Biogen Inc, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, PhD Program Biol & Biomed Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NCI, Tumor Immunol & Biol Lab, Tumor Growth Factor Sect, NIH, Bethesda, MD 20892 USA. RP Williams, KP (reprint author), Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA. OI Yeo, Chang-Yeol/0000-0002-4440-1215 NR 59 TC 65 Z9 66 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 12 PY 2001 VL 276 IS 41 BP 37769 EP 37778 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481NU UT WOS:000171526500008 PM 11500501 ER PT J AU Harada, K Suzuki, M Kato, A Fujii, K Oka, H Ito, Y AF Harada, K Suzuki, M Kato, A Fujii, K Oka, H Ito, Y TI Separation of WAP-8294A components, a novel anti-methicillin-resistant Staphylococcus aureus antibiotic, using high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE antibiotics; WAP-8294A; anti-methicillin-resistant Staphylococcus aureus agent ID 2-PHASE SOLVENT SYSTEMS AB The WAP-8294A complex was isolated from the fermentation broth of Lysobacter sp. WAP-8294, whose major component, WAP-8294A2, showed a strong activity against Grain-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci in vitro, and also exhibited a potent activity against MRSA in vivo, The previous separation procedure using the conventional chromatographic methods was laborious and time-consuming, and the recovery of the desired compound was often unsatisfactory. In the present study, high-speed counter-current chromatography (HSCCC) was applied to the separation of the main components of the WAP-8294A complex. Due to the high polarity of the target compounds, we selected a hydrophilic two-phase solvent system composed of n-butanol-ethyl acetate-aqueous 0.005 M trifluoroacetic acid (1.25:3.75:5, v/v/v) which provided a suitable range of partition coefficient values for these compounds, Although the settling time of this solvent system was much longer than the optimum range, suggesting a low retention of the stationary phase under the standard experimental conditions, the separation was successfully performed at the low flow-rate of 0.5 ml/min. A sample size of 25 mg yielded pure fractions of three components (1-6 mg). The identification of each component was carried out by HPLC and fast atom bombardment mass spectrometry. The method will contribute to the clinical development of WAP-8294A2 as an anti-MRSA agent. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Meijo Univ, Fac Pharm, Tempaku Ku, Nagoya, Aichi 4688503, Japan. Wakamoto Pharmaceut Co Ltd, Kanagawa 2580018, Japan. Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Harada, K (reprint author), Meijo Univ, Fac Pharm, Tempaku Ku, Nagoya, Aichi 4688503, Japan. NR 18 TC 21 Z9 27 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD OCT 12 PY 2001 VL 932 IS 1-2 BP 75 EP 81 DI 10.1016/S0021-9673(01)01235-3 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 482KK UT WOS:000171575200008 PM 11695870 ER PT J AU Shultzaberger, RK Bucheimer, RE Rudd, KE Schneider, TD AF Shultzaberger, RK Bucheimer, RE Rudd, KE Schneider, TD TI Anatomy of Escherichia coli ribosome binding sites SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ribosome; Shine-Dalgarno; information theory; sequence logo; sequence walker ID TRANSLATIONAL INITIATION SITES; SHINE-DALGARNO SEQUENCE; DIRECTED CROSS-LINKING; MESSENGER-RNA; INFORMATION ANALYSIS; MOLECULAR MACHINES; QUANTITATIVE-ANALYSIS; ANGSTROM RESOLUTION; SECONDARY STRUCTURE; CHANNEL CAPACITY AB During translational initiation in prokaryotes, the 3' end of the 16S rRNA binds to a region just upstream of the initiation codon. The relationship between this Shine-Dalgarno (SD) region and the binding of ribosomes to translation start-points has been well studied, but a unified mathematical connection between the SD, the initiation codon and the spacing between them has been lacking. Using information theory, we constructed a model that treats these three components uniformly by assigning to the SD and the initiation region (IR) conservations in bits of information, and by assigning to the spacing an uncertainty, also in bits. To build the model, we first aligned the SD region by maximizing the information content there. The ease of this process confirmed the existence of the SD pattern within a set of 4122 reviewed and revised Escherichia coli gene starts. This large data set allowed us to show graphically, by sequence logos, that the spacing between the SD and the initiation region affects both the SD site conservation and its pattern. We used the aligned SD, the spacing, and the initiation region to model ribosome binding and to identify gene starts that do not conform to the ribosome binding site model. A total of 569 experimentally proven starts are more conserved (have higher information content) than the full set of revised starts, which probably reflects an experimental bias against the detection of gene products that have inefficient ribosome binding sites. Models were refined cyclically by removing non-conforming weak sites. After this procedure, models derived from either the original or the revised gene start annotation were similar. Therefore, this information theory-based technique provides a method for easily constructing biologically sensible ribosome binding site models. Such models should be useful for refining gene-start predictions of any sequenced bacterial genome. (C) 2001 Academic Press. C1 NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33101 USA. RP Schneider, TD (reprint author), NCI, Lab Expt & Computat Biol, POB B, Frederick, MD 21702 USA. OI Schneider, Thomas/0000-0002-9841-1531 FU NIGMS NIH HHS [GM58560] NR 59 TC 82 Z9 82 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 12 PY 2001 VL 313 IS 1 BP 215 EP 228 DI 10.1006/jmbi.2001.5040 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486KK UT WOS:000171816800016 PM 11601857 ER PT J AU Seibel, BA Walsh, PJ AF Seibel, BA Walsh, PJ TI Carbon cycle - Potential, impacts of CO2 injection on deep-sea biota SO SCIENCE LA English DT Editorial Material ID ANIMALS; METABOLISM; DEPTH; ADAPTATIONS; HABITAT; FISHES; LIFE C1 Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS,Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP Seibel, BA (reprint author), Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA. NR 28 TC 120 Z9 128 U1 1 U2 35 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 12 PY 2001 VL 294 IS 5541 BP 319 EP 320 DI 10.1126/science.1065301 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482WZ UT WOS:000171601400030 PM 11598290 ER PT J AU Wang, CY Yang, F He, XP Chow, A Du, J Russell, JT Lu, B AF Wang, CY Yang, F He, XP Chow, A Du, J Russell, JT Lu, B TI Ca2+ binding protein frequenin mediates GDNF-induced potentiation of Ca2+ channels and transmitter release SO NEURON LA English DT Article ID DEVELOPING NEUROMUSCULAR SYNAPSES; LONG-TERM POTENTIATION; BDNF KNOCKOUT MICE; NEUROTROPHIC FACTOR; NEUROTRANSMITTER RELEASE; SYNAPTIC TRANSMISSION; CALCIUM CHANNELS; DOPAMINERGIC-NEURONS; MOTOR-NEURONS; HIPPOCAMPUS AB Molecular mechanisms underlying long-term neurotrophic regulation of synaptic transmission and plasticity are unknown. We report here that long-term treatment of neuromuscular synapses with glial cell line-derived neurotrophic factor (GDNF) potentiates spontaneous and evoked transmitter release, in ways very similar to presynaptic expression of the Ca2+ binding protein frequenin. GDNF enhances the expression of frequenin in motoneurons, and inhibition of frequenin expression or activity prevents the synaptic action of GDNF. GDNF also facilitates Ca2+ influx into the nerve terminals during evoked transmission by enhancing Ca2+ currents. The effect of GDNF on Ca2+ currents is blocked by inhibition of frequenin expression, occluded by overexpression of frequenin, and is selective to N-type Ca2+ channels. These results identify an important molecular target that mediates the long-term, synaptic action of a neurotrophic factor. C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. RP Lu, B (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012; Du, Jing/A-9023-2012 NR 58 TC 83 Z9 87 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 11 PY 2001 VL 32 IS 1 BP 99 EP 112 DI 10.1016/S0896-6273(01)00434-2 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 481NF UT WOS:000171525200012 PM 11604142 ER PT J AU Fishman, A Fessler, H Martinez, F McKenna, RJ Naunheim, K Piantadosi, S Weinmann, G Wise, R AF Fishman, A Fessler, H Martinez, F McKenna, RJ Naunheim, K Piantadosi, S Weinmann, G Wise, R CA National Emphysema Treatment Trial TI Patients at high risk of death after lung-volume-reduction surgery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; SEVERE EMPHYSEMA; DIFFUSING-CAPACITY; PREDICTORS; MORBIDITY; MORTALITY; VALUES; REHABILITATION; PNEUMONOPLASTY; PNEUMOPLASTY AB Background: Lung-volume-reduction surgery is a proposed treatment for emphysema, but optimal selection criteria have not been defined. The National Emphysema Treatment Trial is a randomized, multicenter clinical trial comparing lung-volume-reduction surgery with medical treatment. Methods: After evaluation and pulmonary rehabilitation, we randomly assigned patients to undergo lung-volume-reduction surgery or receive medical treatment. Outcomes were monitored by an independent data and safety monitoring board. Results: A total of 1033 patients had been randomized by June 2001. For 69 patients who had a forced expiratory volume in one second (FEV(sub 1)) that was no more than 20 percent of their predicted value and either a homogeneous distribution of emphysema on computed tomography or a carbon monoxide diffusing capacity that was no more than 20 percent of their predicted value, the 30-day mortality rate after surgery was 16 percent (95 percent confidence interval, 8.2 to 26.7 percent), as compared with a rate of 0 percent among 70 medically treated patients (P<0.001). Among these high-risk patients, the overall mortality rate was higher in surgical patients than medical patients (0.43 deaths per person-year vs. 0.11 deaths per person-year; relative risk, 3.9; 95 percent confidence interval, 1.9 to 9.0). As compared with medically treated patients, survivors of surgery had small improvements at six months in the maximal workload (P=0.06), the distance walked in six minutes (P=0.03), and FEV(sub 1) (P<0.001), but a similar health-related quality of life. The results of the analysis of functional outcomes for all patients, which accounted for deaths and missing data, did not favor either treatment. Conclusions: Caution is warranted in the use of lung-volume-reduction surgery in patients with emphysema who have a low FEV(sub 1) and either homogeneous emphysema or a very low carbon monoxide diffusing capacity. These patients are at high risk for death after surgery and also are unlikely to benefit from the surgery. (N Engl J Med 2001;345:1075-83.) Copyright (C) 2001 Massachusetts Medical Society. C1 Baylor Coll Med, Houston, TX 77030 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Columbia Univ, New York, NY USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Duke Univ, Med Ctr, Durham, NC USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Ohio State Univ, Columbus, OH 43210 USA. St Louis Univ, St Louis, MO 63103 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Maryland, College Pk, MD 20742 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Washington, Seattle, WA 98195 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Johns Hopkins Univ, Coordinating Ctr, Baltimore, MD USA. Fred Hutchinson Canc Res Ctr, Cost Effectivness Data Ctr, Seattle, WA 98104 USA. Univ Iowa, CT Scan Image Storage & Anal Ctr, Iowa City, IA USA. Ctr Medicare & Medicaid Serv, Baltimore, MD USA. Temple Univ, Mkt Ctr, Philadelphia, PA 19122 USA. Univ Penn, Off Chair Steering Comm, Philadelphia, PA 19104 USA. NHLBI, Project Off, Bethesda, MD 20892 USA. RP Piantadosi, S (reprint author), NETT, Coordinating Ctr, 615 N Wolfe St,Rm 5010, Baltimore, MD 21205 USA. OI Wise, Robert/0000-0002-8353-2349 NR 50 TC 296 Z9 301 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 11 PY 2001 VL 345 IS 15 BP 1075 EP 1083 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 480QH UT WOS:000171473100001 ER PT J AU Mousses, S Wagner, U Chen, YD Kim, JW Bubendorf, L Bittner, M Pretlow, T Elkahloun, AG Trepel, JB Kallioniemi, OP AF Mousses, S Wagner, U Chen, YD Kim, JW Bubendorf, L Bittner, M Pretlow, T Elkahloun, AG Trepel, JB Kallioniemi, OP TI Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling SO ONCOGENE LA English DT Article DE microarray; prostate cancer; hormone-refractory; androgen-independent; CWR22 ID MAMMALIAN TARGET; GROWTH-FACTOR; RECEPTOR; CELLS; XENOGRAFT; EXPRESSION; KINASE; MODEL; CWR22; RHABDOMYOSARCOMA AB Androgen deprivation therapy for advanced prostate cancer is often effective, but not curative. Molecular pathways mediating the therapeutic response and those contributing to the subsequent hormone-refractory cell growth remain poorly understood. Here, cDNA microarray analysis of human CWR22 prostate cancer xenografts during the course of androgen deprivation therapy revealed distinct global gene expression profiles in primary, regressing and recurrent tumors. Elucidation of the genes involved in the transition between these states implicated specific molecular mechanisms in therapy failure and tumor progression. First, we identified a set of androgen-responsive genes whose expression decreased during the therapy response, but was then systematically restored in the recurrent tumors. In addition, altered expression of genes that encode known targets of rapamycin or that converge on the PI3K/AKT/FRAP pathway was observed in the recurrent tumors. Further suggestion for the involvement of these genes in hormone-refractory prostate cancer came from the observation that cells established from the recurrent xenografts were strongly inhibited in vitro by rapamycin. The results of this functional genomic analysis suggest that the combined effect of re-expression of androgen-responsive genes as well as the activation of rapamycin-sensitive signaling may drive prostate cancer progression, and contribute to the failure of androgen-deprivation therapy. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. NCI, Med Branch, NIH, Bethesda, MD 20850 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. RP Kallioniemi, OP (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 49,Rm 4A24, Bethesda, MD 20892 USA. EM okalli@nhgri.nih.gov RI Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NCI NIH HHS [CA 57179] NR 22 TC 98 Z9 101 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 11 PY 2001 VL 20 IS 46 BP 6718 EP 6723 DI 10.1038/sj.onc.1204889 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 482AA UT WOS:000171551600008 PM 11709706 ER PT J AU Bleesing, JJH Morrow, MR Uzel, G Fleisher, TA AF Bleesing, JJH Morrow, MR Uzel, G Fleisher, TA TI Human T cell activation induces the expression of a novel CD45 isoform that is analogous to murine B220 and is associated with altered O-glycan synthesis and onset of apoptosis SO CELLULAR IMMUNOLOGY LA English DT Article DE CD45; B220; apoptosis; glycoproteins; sialic acid; O-glycan; neuraminidase; N-acetylglucosaminyltransferase; lymphocyte transformation; superantigens ID SIALIC ACIDS; FAS LIGAND; IN-VIVO; LYMPHOCYTE; DEATH; BIOSYNTHESIS; SIALYLATION; GALECTIN-1; MECHANISM; RECEPTOR AB Activated T cells undergo changes during their transition to T cell blasts and, subsequently, via a phase of anergy, to apoptosis. For example, activated murine T cell blasts express the B-cell-specific CD45R isoform, B220, a marker also present on T cells in mice and humans with defective Fas-mediated apoptosis in vivo, suggesting a role for B220 up-regulation in the transition of activation to apoptosis. Human T cells, activated in vitro with superantigens and mitogens, also express B220 as they undergo blastogenesis and cell cycle progression. B220 expression peaks on T cells undergoing apoptosis. CD43-hexasaccharide glycoform expression and lectin binding profiles indicate that B220 expression is reflective of altered O-linked glycan biosynthesis found in specific T cell subsets transitioning through the phases of proliferation, anergy, and apoptosis. Potential implications of these alterations include changes in lymphocyte adhesion and trafficking and homeostasis through altered sensitivity to Fas-dependent and independent pathways of apoptosis. C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Bleesing, JJH (reprint author), Arkansas Childrens Hosp, Res Inst, 1120 Marshall St,Slot 512-13, Little Rock, AR 72202 USA. NR 40 TC 17 Z9 17 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 10 PY 2001 VL 213 IS 1 BP 72 EP 81 DI 10.1006/cimm.2001.1865 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 510NK UT WOS:000173214000009 PM 11747358 ER PT J AU Wilcox, AJ Baird, DD Dunson, D McChesney, R Weinberg, CR AF Wilcox, AJ Baird, DD Dunson, D McChesney, R Weinberg, CR TI Natural limits of pregnancy testing in relation to the expected menstrual period SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; URINE; SERUM; CYCLE AB Context Pregnancy test kits routinely recommend testing "as early as the first day of the missed period." However, a pregnancy cannot be detected before the blastocyst implants. Due to natural variability in the timing of ovulation, implantation does not necessarily occur before the expected onset of next menses. Objective To estimate the maximum screening sensitivity of pregnancy tests when used on the first day of the expected period, taking into account the natural variability of ovulation and implantation. Design and Setting Community-based prospective cohort study conducted in North Carolina between 1982 and 1986. Participants Two hundred twenty-one healthy women 21 to 42 years of age who were planning to conceive. Main Outcome Measures Day of implantation, defined by the serial assay of first morning urine samples using an extremely sensitive immunoradiometric assay for human chorionic gonadotropin (hCG), relative to the first day of the missed period, defined as the day on which women expected their next menses to begin, based on self-reported usual cycle length. Results Data were available for 136 clinical pregnancies conceived during the study, 14 (10%) of which had not yet implanted by the first day of the missed period. The highest possible screening sensitivity for an hCG-based pregnancy test therefore is estimated to be 90% (95% confidence interval [CI], 84%-94%) on the first day of the missed period. By 1 week after the first day of the missed period, the highest possible screening sensitivity is estimated to be 97% (95% Cl, 94%-99%). Conclusions In this study, using an extremely sensitive assay for hCG, 10% of clinical pregnancies were undetectable on the first day of missed menses. fn practice, an even larger percentage of clinical pregnancies may be undetected by current test kits on this day, given their reported assay properties and other practical limitations. C1 NIEHS, Epidemiol Branch, Durham, NC USA. NIEHS, Biostat Branch, Durham, NC USA. Columbia Univ Barnard Coll, Dept Biol Sci, New York, NY USA. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, MD A3-05, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 14 TC 47 Z9 47 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 10 PY 2001 VL 286 IS 14 BP 1759 EP 1761 DI 10.1001/jama.286.14.1759 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 480NC UT WOS:000171466800027 PM 11594902 ER PT J AU George, DT Umhau, JC Phillips, MJ Emmela, D Ragan, PW Shoaf, SE Rawlings, RR AF George, DT Umhau, JC Phillips, MJ Emmela, D Ragan, PW Shoaf, SE Rawlings, RR TI Serotonin, testosterone and alcohol in the etiology of domestic violence SO PSYCHIATRY RESEARCH LA English DT Article DE aggression; alcoholism; rage; cerebral spinal fluid (CSF); fear conditioning ID CEREBROSPINAL-FLUID MONOAMINE; DEFENSIVE RAGE BEHAVIOR; IMPULSIVE FIRE SETTERS; AGGRESSIVE-BEHAVIOR; CONDITIONED FEAR; PERIAQUEDUCTAL GRAY; CSF 5-HIAA; 5-HYDROXYINDOLEACETIC ACID; PERSONALITY DIMENSIONS; TRYPTOPHAN DEPLETION AB In a previous study we administered the panicogenic agent sodium lactate to a select group of perpetrators of domestic violence and comparison groups. Results of that study showed that perpetrators exhibited exaggerated lactate-induced fear, panic and rage. In this current study, we compared the cerebral spinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and testosterone obtained from perpetrators of domestic violence and a group of healthy comparison subjects, All subjects were assessed for DSM-III-R diagnoses. Perpetrators with alcohol dependence (DV-ALC) (n = 13), perpetrators without alcohol dependence (DV-NALC) (n = 10) and healthy comparison subjects (HCS) (n = 20) were clinically assessed using the Spielberger Trait Anxiety, Brown-Goodwin Aggression Scale, Buss Durkee Hostility Inventory and Straus Conflict Tactics. Following an overnight fast and bed rest, subjects received a lumbar puncture to obtain CSF concentrations of 5-HIAA and testosterone. Perpetrators scored significantly higher on measures of aggression than HCS. DV-NALC had significantly lower concentrations of CSF 5-HIAA and higher Straus Conflict Tactics (CT) physical violence scores than DV-ALC and HCS. DV-ALC had significantly higher concentrations of CSF testosterone than DV-NALC. DV-ALC also had significantly higher Straus CT physical violence scores than HCS. DV-NALC and DV-ALC differed on 5-HIAA concentrations, testosterone concentrations, Straus CT physical violence scores and alcohol dependence. These results suggest that DV-NA-LC and DV-ALC groups could have different biological mechanisms mediating domestic violence. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NIAAA, DICBR, Clin Studies Lab, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN 37232 USA. RP George, DT (reprint author), NIAAA, DICBR, Clin Studies Lab, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 82 TC 33 Z9 35 U1 2 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT 10 PY 2001 VL 104 IS 1 BP 27 EP 37 DI 10.1016/S0165-1781(01)00292-X PG 11 WC Psychiatry SC Psychiatry GA 487QB UT WOS:000171885800004 PM 11600187 ER PT J AU Fausti, S Weiler, S Cuniberto, C Hwang, KJ No, KT Gruschus, JM Perico, A Nirenberg, M Ferretti, JA AF Fausti, S Weiler, S Cuniberto, C Hwang, KJ No, KT Gruschus, JM Perico, A Nirenberg, M Ferretti, JA TI Backbone dynamics for the wild type and a double H52R/T56W mutant of the vnd/NK-2 homeodomain from Drosophila melanogaster SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; DNA COMPLEX; NMR-SPECTROSCOPY; NK-2 HOMEODOMAIN; HOMEOBOX GENES; RELAXATION; RESOLUTION; BINDING; DOMAIN; N-15 AB The N-15 relaxation behavior and heteronuclear Overhauser effect data for the wild type and an H52R/T56W double mutant protein that encompasses the vnd/NK-2 homeodomain from Drosophila melanogaster were used to characterize and describe the protein backbone dynamics. This investigation. which includes a description of a model structure for the H52R/T56W double mutant vnd/NK-2 homeodomain. was carried out for the two proteins in both the free and DNA-bound states. The double residue replacement at positions 52 and 56 within the DNA recognition helix of vnd/NK-2 has been shown to lead to a significant secondary structural modification resulting in an increase in the length of the recognition helix for the unbound protein. These structural changes are accompanied by corresponding changes in the T, and Tip relaxation times as well as in the heteronuclear Overhauser effect (XNOE) values that show that the structural stability of the protein is enhanced by the two residue replacements. The values of the rotational anisotropy, D-parallel to/D-perpendicular to, derived from analysis of the N-15 T-1 and T-1 rho relaxation values are small (1.189 for the unbound homeodomain and 1.110 for the bound homeodomain; both analyzed as prolate ellipsoids of revolution). A comparison of the T, values of the wild type and double mutant homeodomain reveals the presence of a low-frequency exchange contribution for the wild type analogue. These relaxation studies show that the motional behavior of the protein primarily reflects the tertiary structure and stability of the homeodomain backbone as well as the respective changes induced upon site-directed residue replacement or DNA binding. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. CNR, Ist Studi Chim Fis Macromol Sintet & Nat, IMAG, I-16149 Genoa, Italy. Univ Genoa, Dipartimento Chim & Chim Ind, I-16146 Genoa, Italy. Soong Sil Univ, Comp Aided Mol Design Res Ctr, Dongjak Ku, Seoul 156743, South Korea. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Ferretti, JA (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 32 TC 8 Z9 8 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 9 PY 2001 VL 40 IS 40 BP 12004 EP 12012 DI 10.1021/bi010398r PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481CV UT WOS:000171503100005 PM 11580276 ER PT J AU Gallagher, SC Gao, ZH Li, SP Dyer, B Trewhella, J Klee, CB AF Gallagher, SC Gao, ZH Li, SP Dyer, B Trewhella, J Klee, CB TI There is communication between all four Ca2+-bindings sites of calcineurin B SO BIOCHEMISTRY LA English DT Article ID TRANSFORM INFRARED-SPECTROSCOPY; SECONDARY STRUCTURE; CA2+ BINDING; MULTIDIMENSIONAL NMR; TROPONIN-C; AMINO-ACID; CALMODULIN; PEPTIDE; CALCIUM; TARGET AB We have used site-directed mutagenesis, flow dialysis, and Fourier transform infrared (FTIR) spectroscopy to study Ca2+-binding to the regulatory component of calcineurin. Single Glu-Gln(E --> Q) mutations were used to inactivate each of the four Ca2+-binding sites of CnB in turn, generating mutants Q1, Q2, Q3, and Q4, with the number indicating which Ca2+ site is inactivated. The binding data derived from flow dialysis reveal two pairs of sites in the wild-type protein, one pair with very high affinity and the other with lower affinity Ca2+-binding sites. Also, only three sites are titratable in the wild-type protein because one site cannot be decalcified. Mutation of site 2 leaves the protein with only two titratable sites, while mutation of sites 1, 3, or 4 leave three titratable sites that are mostly filled with 3 Ca2+ equiv added. The binding data further show that each of the single-site mutations Q2, Q3, and Q4 affects the affinities of at least one of the remaining sites. Mutation in either of sites 3 or 4 results in a protein with no high-affinity sites, indicating communication between the two high-affinity sites, most likely sites 3 and 4. Mutation in site 2 decreases the affinity of all three remaining sites, though still leaving two relatively high-affinity sites. The FTIR data support the conclusions from the binding data with respect to the number of titratable sites as well as the impact of each mutation on the affinities of the remaining sites. We conclude therefore that there is communication between all four Ca2+-binding sites. In addition, the Ca2+ induced changes in the FTIR spectra for the wild-type and Q4 mutant are most similar, suggesting that the same three Ca2+-binding sites are being titrated, i.e., site 4 is the very high-affinity site under the conditions of the FTIR experiments. C1 Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. Natl Canc Ctr Inst, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Trewhella, J (reprint author), Los Alamos Natl Lab, Biosci Div, POB 1663, Los Alamos, NM 87545 USA. OI Trewhella, Jill/0000-0002-8555-6766 FU NIGMS NIH HHS [GM40528] NR 38 TC 15 Z9 15 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 9 PY 2001 VL 40 IS 40 BP 12094 EP 12102 DI 10.1021/bi0025060 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481CV UT WOS:000171503100013 PM 11580284 ER PT J AU Ha-Duong, NT Dijols, S Macherey, AC Goldstein, JA Dansette, PM Mansuy, D AF Ha-Duong, NT Dijols, S Macherey, AC Goldstein, JA Dansette, PM Mansuy, D TI Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P4502C19 SO BIOCHEMISTRY LA English DT Article ID HUMAN LIVER CYTOCHROME-P450; ENGINEERED YEAST-CELLS; SUBSTRATE-BINDING SITE; THIOPHENE-S-OXIDE; TIENILIC ACID; IN-VITRO; (S)-MEPHENYTOIN 4'-HYDROXYLASE; ELECTROPHILIC METABOLITES; HETEROLOGOUS EXPRESSION; OXIDATIVE CYCLOADDITION AB Experiments using recombinant yeast-expressed human liver cytochromes P450 confirmed previous literature data indicating that ticlopidine is an inhibitor of CYP 2C19. The present studies demonstrated that ticlopidine is selective for CYP 2C19 within the CYP 2C subfamily. UV-visible studies on the interaction of a series of ticlopidine derivatives with CYP 2C19 showed that ticlopidine binds to the CYP 2C19 active site with a K-s value of 2.8 +/- 1 muM. Derivatives that do not involve either the o-chlorophenyl substituent, the free tertiary amine function, or the thiophene ring of ticlopidine did not lead to such spectral interactions and failed to inhibit CYP 2C19. Ticlopidine is oxidized by CYP 2C19 with formation of two major metabolites, the keto tautomer of 2-hydroxyticlopidine (1) and the dimers of ticlopidine S-oxide (TSOD) (V-max = 13 +/- 2 and 0.4 +/- 0.1 min(-1)). During this oxidation, CYP 2C19 was inactivated; the rate of its inactivation was time and ticlopidine concentration dependent. This process meets the chemical and kinetic criteria generally accepted for mechanism-based enzyme inactivation. It occurs in parralel with CYP 2C19-catalyzed oxidation of ticlopidine, is inhibited by an alternative well-known substrate of CYP 2C19, omeprazole, and correlates with the covalent binding of ticlopidine metabolite(s) to proteins. Moreover, CYP 2C19 inactivation is not inhibited by the presence of 5 mM glutathione, suggesting that it is due to an alkylation occurring inside the CYP 2C19 active site. The effects of ticlopidine on CYP 2C19 are very analogous with those previously described for the inactivation of CYP 2C9 by tienilic acid. This suggests that a similar electrophilic intermediate, possibly a thiophene S-oxide, is involved in the inactivation of CYP 2C19 and CYP 2C9 by ticlopidine and tienilic acid, respectively. The kinetic parameters calculated for ticlopidine-dependent inactivation of CYP 2C19, i.e., t(1/2max) = 3.4 min, k(inact) = 3.2 10(-3) s(-1), K-1 = 87 muM, k(inact)/K-1 = 37 L . mol(-1).s(-1), and r (partition ratio) = 26 (in relation with formation of 1 + TSOD), classify ticlopidine as an efficient mechanism-based inhibitor although somewhat less efficient than tienilic acid for CYP 2C9. Importantly, ticlopidine is the first selective mechanism-based inhibitor of human liver CYP 2C19 and should be a new interesting tool for studying the topology of the active site of CYP 2C19. C1 Univ Paris 05, CNRS, UMR 8601, Chim & Biochim Pharmacol & Toxicol Lab, F-75270 Paris 06, France. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Mansuy, D (reprint author), Univ Paris 05, CNRS, UMR 8601, Chim & Biochim Pharmacol & Toxicol Lab, 45 Rue St Peres, F-75270 Paris 06, France. RI Goldstein, Joyce/A-6681-2012; DANSETTE, Patrick/B-8384-2014 NR 68 TC 117 Z9 122 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 9 PY 2001 VL 40 IS 40 BP 12112 EP 12122 DI 10.1021/bi010254c PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481CV UT WOS:000171503100015 PM 11580286 ER PT J AU Bernick, C Kuller, L Dulberg, C Longstreth, WT Manolio, T Beauchamp, N Price, T AF Bernick, C Kuller, L Dulberg, C Longstreth, WT Manolio, T Beauchamp, N Price, T CA Cardiovasc Hlth Study Collaborativ TI Silent MRI infarcts and the risk of future stroke - The cardiovascular health study SO NEUROLOGY LA English DT Article ID LONG-TERM PROGNOSIS; CEREBRAL INFARCTION; LACUNAR INFARCTS; ELDERLY PEOPLE; WHITE-MATTER; OLDER ADULTS; RECURRENCE; BRAIN; PREDICTORS; PREVALENCE AB Background: Silent infarcts are commonly discovered on cranial MRI in the elderly. Objective: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors. Methods: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts. Results: Approximately 28% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes). Conclusion: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow-up in older individuals without a clinical history of stroke. C1 Univ Nevada, Sch Med, Div Neurol, Las Vegas, NV 89102 USA. Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. CHS Coordinating Ctr, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. Univ Maryland, Dept Epidemiol, Baltimore, MD 21201 USA. RP Bernick, C (reprint author), Univ Nevada, Sch Med, Div Neurol, 1707 W Charleston Blvd,220, Las Vegas, NV 89102 USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85086, N01-HC15103, N01-HC35129] NR 25 TC 177 Z9 186 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 9 PY 2001 VL 57 IS 7 BP 1222 EP 1229 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 479QQ UT WOS:000171415400013 PM 11591840 ER PT J AU Schifitto, G Yiannoutsos, C Simpson, DM Adornato, BT Singer, EJ Hollander, H Marra, CM Rubin, M Cohen, BA Tucker, T Koralnik, IJ Katzenstein, D Haidich, B Smith, ME Shriver, S Millar, L Clifford, DB McArthur, JC AF Schifitto, G Yiannoutsos, C Simpson, DM Adornato, BT Singer, EJ Hollander, H Marra, CM Rubin, M Cohen, BA Tucker, T Koralnik, IJ Katzenstein, D Haidich, B Smith, ME Shriver, S Millar, L Clifford, DB McArthur, JC CA AIDS Clinical Trials Grp Team 291 TI Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy SO NEUROLOGY LA English DT Article ID PERIPHERAL NEUROPATHY; INFECTION; COMPLEX AB HIV-associated distal sensory polyneuropathy (DSP) is a common complication of AIDS. No effective treatment is available. The authors investigated the long-term effect (48 weeks) of the neurotrophin nerve growth factor (NGF) in an open-label study of 200 subjects with HIV-associated DSP. Similar to their previously reported double-blind study, the authors showed that NGF was safe and well tolerated and significantly improved pain symptoms. However, there was no improvement of neuropathy severity as assessed by neurologic examination, quantitative sensory testing, and epidermal nerve fiber density. C1 Univ Rochester, Dept Neurol, Rochester, NY 14642 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Cornell Univ, Dept Neurol, New York, NY 10021 USA. Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21218 USA. NIAID, Bethesda, MD 20892 USA. AIDS Clin Trials Grp Operat, Rockville, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Washington Univ, Dept Neurol, St Louis, MO USA. RP Schifitto, G (reprint author), Univ Rochester, Dept Neurol, 601 Elmwood Ave,Box 673, Rochester, NY 14642 USA. FU NCRR NIH HHS [RR00722]; NIAID NIH HHS [AI34668]; NINDS NIH HHS [NS32228] NR 10 TC 61 Z9 67 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 9 PY 2001 VL 57 IS 7 BP 1313 EP 1316 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 479QQ UT WOS:000171415400029 PM 11591856 ER PT J AU Strausberg, RL Riggins, GJ AF Strausberg, RL Riggins, GJ TI Navigating the human transcriptome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID GENE-EXPRESSION; SEQUENCE TAGS; DATABASE; COLLECTION; RESOURCES; PROJECT; CANCER; GENOME; INDEX C1 NCI, Canc Genom Off, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. RP Strausberg, RL (reprint author), NCI, Canc Genom Off, 31 Ctr Dr,Room 11A03, Bethesda, MD 20892 USA. EM rls@nih.gov NR 20 TC 7 Z9 9 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 11837 EP 11838 DI 10.1073/pnas.221463598 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900001 PM 11592992 ER PT J AU Interthal, H Pouliott, JJ Champoux, JJ AF Interthal, H Pouliott, JJ Champoux, JJ TI The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TOPOISOMERASE-I; CRYSTAL-STRUCTURE; MUTAGENESIS; PHOSPHORUS; SYNTHASES; FAMILY; YEAST AB The phospholipase D (PLD) superfamily is a diverse group of proteins that includes enzymes involved in phospholipid metabolism, a bacterial toxin, poxvirus envelope proteins, and bacterial nucleases. Based on sequence comparisons, we show here that the tyrosyl-DNA phosphodiesterase (Tdp1) that has been implicated in the repair of topoisomerases I covalent complexes with DNA contains two unusual HKD signature motifs that place the enzyme in a distinct class within the PLD superfamily. Mutagenesis studies with the human enzyme in which the invariant histidines and lysines of the HKD motifs are changed confirm that these highly conserved residues are essential for Tdp1 activity. Furthermore, we show that, like other members of the family for which it has been examined, the reaction involves the formation of an intermediate in which the cleaved substrate is covalently linked to the enzyme. These results reveal that the hydrolytic reaction catalyzed by Tdp1 occurs by the phosphoryl transfer chemistry that is common to all members of the PLD superfamily. C1 Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Champoux, JJ (reprint author), Univ Washington, Sch Med, Dept Microbiol, Box 357242, Seattle, WA 98195 USA. FU NIGMS NIH HHS [R01 GM049156, GM49156] NR 22 TC 152 Z9 157 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12009 EP 12014 DI 10.1073/pnas.211429198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900035 PM 11572945 ER PT J AU Deming, PB Cistulli, CA Zhao, H Graves, PR Piwnica-Worms, H Paules, RS Downes, CS Kaufmann, WK AF Deming, PB Cistulli, CA Zhao, H Graves, PR Piwnica-Worms, H Paules, RS Downes, CS Kaufmann, WK TI The human decatenation checkpoint SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-DAMAGE CHECKPOINT; CELL-CYCLE CHECKPOINTS; ATAXIA-TELANGIECTASIA; TOPOISOMERASE-II; G(2) CHECKPOINT; NUCLEAR EXPORT; HUMAN FIBROBLASTS; CHROMOSOME CONDENSATION; RADIOSENSITIZING AGENT; KINASE-ACTIVITIES AB Chromatid catenation is actively monitored in human cells, with progression from G(2) to mitosis being inhibited when chromatids are insufficiently decatenated. Mitotic delay was quantified in normal and checkpoint-deficient human cells during treatment with ICRF-193, a topoisomerase II catalytic inhibitor that prevents chromatid decatenation without producing topoisomerase-associated DNA strand breaks. Ataxia telangiectasia (A-T) cells, defective in DNA damage checkpoints, showed normal mitotic delay when treated with ICRF-193. The mitotic delay in response to ICRF-193 was ablated in human fibroblasts expressing an ataxia telangiectasia mutated- and rad3-related (ATR) kinase-inactive ATR allele (ATR(ki)). BRCA1-mutant HCC1937 cells also displayed a defect in ICRF-193-induced mitotic delay, which was corrected by expression of wild-type BRCA1. Phosphorylations of hCds1 or Chk1 and inhibition of Cdk1 kinase activity, which are elements of checkpoints associated with DNA damage or replication, did not occur during ICRF-193-induced mitotic delay. Over-expression of cyclin B1 containing a dominant nuclear localization signal, and inhibition of Crm1-mediated nuclear export, reversed ICRF-193-induced mitotic delay. In combination, these results imply that ATR and BRCA1 enforce the decatenation G(2) checkpoint, which may act to exclude cyclin B1/Cdk1 complexes from the nucleus. Moreover, induction of ATR(ki) produced a 10-fold increase in chromosomal aberrations, further emphasizing the vital role for ATR in genetic stability. C1 Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63310 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63310 USA. NIEHS, Growth Control & Canc Grp, Res Triangle Pk, NC 27709 USA. Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. RP Kaufmann, WK (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RI Piwnica-Worms, Helen/C-5214-2012 FU NCI NIH HHS [R01 CA081343] NR 53 TC 135 Z9 139 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12044 EP 12049 DI 10.1073/pnas.221430898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900041 PM 11593014 ER PT J AU Kondrashov, FA Kondrashov, AS AF Kondrashov, FA Kondrashov, AS TI Multidimensional epistasis and the disadvantage of sex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HOLEY ADAPTIVE LANDSCAPES; SELECTION; SPECIATION; RECOMBINATION; DOBZHANSKY; ADVANTAGE; HYPERCUBE; EVOLUTION; MUTATION; GENETICS AB Sex is thought to facilitate accumulation of initially rare beneficial mutations by allowing simultaneous allele replacements at many loci. However, this advantage of sex depends on a restrictive assumption that the fitness of a genotype is determined by fitness potential, a single intermediate variable to which all loci contribute additively, so that new alleles can accumulate in any order. Individual-based simulations of sexual and asexual populations reveal that under generic selection, sex often retards adaptive evolution. When new alleles are beneficial only if they accumulate in a prescribed order, a sexual population may evolve two or more times slower than an asexual population because only asexual reproduction allows some overlap of successive allele replacements. Many other fitness surfaces lead to an even greater disadvantage of sex. Thus, either sex exists in spite of its impact on the rate of adaptive allele replacements, or natural fitness surfaces have rather specific properties, at least at the scale of intrapopulation genetic variability. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Kondrashov, FA (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 38A, Bethesda, MD 20892 USA. RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 28 TC 72 Z9 73 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12089 EP 12092 DI 10.1073/pnas.211214298 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900049 PM 11593020 ER PT J AU Visintin, A Mazzoni, A Spitzer, JA Segal, DM AF Visintin, A Mazzoni, A Spitzer, JA Segal, DM TI Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DROSOPHILA TOLL; ACTIVATION; FAMILY; TLR4; MICE; EXPRESSION; ANTIGENS; IMMUNITY; MOLECULE; SIGNAL AB Toll-like receptor 4 (TLR4), the principal signaling receptor for lipopolysaccharide (LPS) in mammals, requires the binding of MD-2 to its extracellular domain for maximal responsiveness. MD-2 contains a leader sequence but lacks a transmembrane domain, and we asked whether it is secreted into the medium as an active protein. As a source of secreted MD-2 (sMD-2), we used culture supernatants from cells stably transduced with epitope-tagged human MD-2. We show that sMD-2 exists as a heterogeneous collection of large disulfide-linked oligomers formed from stable dimeric subunits and that concentrations of sMD-2 as low as 50 pM enhance the responsiveness of TLR4 reporter cells to LPS. An MD-2-like activity is also released by monocyte-derived dendritic cells from normal donors. When coexpressed, TLR4 indiscriminately associates in the endoplasmic reticulum/cis Golgi with different-sized oligomers of MD-2, and excess MD-2 is secreted into the medium. We conclude that normal and transfected cells secrete a soluble form of MD-2 that binds with high affinity to TLR4 and that could play a role in regulating responses to LPS and other pathogen-derived substances in vivo. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Segal, DM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 160 Z9 171 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12156 EP 12161 DI 10.1073/pnas.211445098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900061 PM 11593030 ER PT J AU Hwang, CK Svarovskaia, ES Pathak, VK AF Hwang, CK Svarovskaia, ES Pathak, VK TI Dynamic copy choice: Steady state between murine leukemia virus polymerase and polymerase-dependent RNase H activity determines frequency of in vivo template switching SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL REVERSE-TRANSCRIPTASE; GENETIC-VARIATION; DNA-POLYMERASE; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS SEQUENCES; MUTATIONAL ANALYSIS; ESCHERICHIA-COLI; REPEAT DELETION; SINGLE-CYCLE AB We recently proposed a dynamic copy-choice model for retroviral recombination in which a steady state between the rates of polymerization and RNA degradation determines the frequency of reverse transcriptase (RT) template switching. The relative contributions of polymerase-dependent and polymerase-independent RNase H activities during reverse transcription and template switching in vivo have not been determined. We developed an in vivo trans-complementation assay in which direct repeat deletion through template switching reconstitutes a functional green fluorescent protein gene in a retroviral vector. Complementation in trans between murine leukemia virus Gag-Pol proteins lacking polymerase and RNase H activities restored viral replication. Because only polymerase-independent RNase H activity is present in this cell line, the relative roles of polymerase-dependent and -independent RNase H activities in template switching could be determined. We also analyzed double mutants possessing polymerase and RNase H mutations that increased and decreased template switching, respectively. The double mutants exhibited low template switching frequency, indicating that the RNase H mutations were dominant. Trans-complementation of the double mutants with polymerase-independent RNase H did not restore the high template switching frequency, indicating that polymerase-dependent RNase H activity was essential for the increased frequency of template switching. Additionally, trans-complementation of RNase H mutants in the presence and absence of hydroxyurea, which slows the rate of reverse transcription, showed that hydroxyurea increased template switching only when polymerase-dependent RNase H activity was present. This is, to our knowledge, the first demonstration of polymerase-dependent RNase H activity in vivo. These results provide strong evidence for a dynamic association between the rates of DNA polymerization and polymerase-dependent RNase H activity, which determines the frequency of in vivo template switching. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. W Virginia Univ, Dept Microbiol & Immunol, Morgantown, WV 26506 USA. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 334, Frederick, MD 21702 USA. NR 53 TC 58 Z9 59 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12209 EP 12214 DI 10.1073/pnas.221289898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900070 PM 11593039 ER PT J AU Liao, P Georgakopoulos, D Kovacs, A Zheng, MZ Lerner, D Pu, HY Saffitz, J Chien, K Xiao, RP Kass, DA Wang, YB AF Liao, P Georgakopoulos, D Kovacs, A Zheng, MZ Lerner, D Pu, HY Saffitz, J Chien, K Xiao, RP Kass, DA Wang, YB TI The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heart failure; conditional transgenesis ID ACTIVATED PROTEIN-KINASE; N-TERMINAL KINASES; HEART-FAILURE; TRANSGENIC MICE; SELECTIVE ACTIVATION; CONTRACTILE FAILURE; SIGNALING PATHWAY; HYPERTROPHY; EXPRESSION; STRESS AB Stress-induced mitogen-activated protein kinase (MAP) p38 is activated in various forms of heart failure, yet its effects on the intact heart remain to be established. Targeted activation of p38 MAP kinase in ventricular myocytes was achieved in vivo by using a gene-switch transgenic strategy with activated mutants of upstream kinases MKK3bE and MKK6bE. Transgene expression resulted in significant induction of p38 kinase activity and premature death at 7-9 weeks. Both groups of transgenic hearts exhibited marked interstitial fibrosis and expression of fetal marker genes characteristic of cardiac failure, but no significant hypertrophy at the organ level. Echocardiographic and pressure-volume analyses revealed a similar extent of systolic contractile depression and restrictive diastolic abnormalities related to markedly increased passive chamber stiffness. However, MKK3bE-expressing hearts had increased end-systolic chamber volumes and a thinned ventricular wall, associated with heterogeneous myocyte atrophy, whereas MKK6bE hearts had reduced end-diastolic ventricular cavity size, a modest increase in myocyte size, and no significant myocyte atrophy. These data provide in vivo evidence for a negative inotropic and restrictive diastolic e ect from p38 MAP kinase activation in ventricular myocytes and reveal specific roles of p38 pathway in the development of ventricular end-systolic remodeling. C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Univ Calif San Diego, Salk Program Mol Med, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Salk Program Mol Med, Ctr Genet Mol, La Jolla, CA 92093 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Wang, YB (reprint author), Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. OI Wang, Yibin/0000-0003-0852-0767 FU NHLBI NIH HHS [HL59408, R01 HL062311, P01 HL059408, HL61505-01, HL62311-01] NR 38 TC 210 Z9 215 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 9 PY 2001 VL 98 IS 21 BP 12283 EP 12288 DI 10.1073/pnas.211086598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 482DE UT WOS:000171558900083 PM 11593045 ER PT J AU Nurnberger, JI Meyer, ET Flury, L Hu, K Foroud, T AF Nurnberger, JI Meyer, ET Flury, L Hu, K Foroud, T TI Alcoholism and mania: Is there a genetic relationship? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Inst Psychiat Res, Indianapolis, IN 46202 USA. NIMH, Genet Initiat Bipolar Grp, Bethesda, MD 20892 USA. RI Meyer, Eric/C-1029-2011 OI Meyer, Eric/0000-0002-1998-7162 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2001 VL 105 IS 7 MA O20 BP 567 EP 567 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 478QZ UT WOS:000171358000022 ER PT J AU Ferraren, DO Toyota, T Badner, JA Yoshikawa, T Detera-Wadleigh, SD AF Ferraren, DO Toyota, T Badner, JA Yoshikawa, T Detera-Wadleigh, SD TI An association study on the COMT missense mutation in mood disorders and schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2001 VL 105 IS 7 MA O30 BP 570 EP 570 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 478QZ UT WOS:000171358000032 ER PT J AU Meerabux, JMA Iwayama, X Detera-Wadleigh, S DeLisi, L Yoshikawa, T AF Meerabux, JMA Iwayama, X Detera-Wadleigh, S DeLisi, L Yoshikawa, T TI Molecular cloning of a t(18;21)(p11.1; p1.1) translocation associated with psychosis in one family SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 RIKEN, BSI, Lab Mol Psychiat, Saitama, Japan. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. NYU, Dept Psychiat, New York, NY 10011 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2001 VL 105 IS 7 MA P28 BP 604 EP 604 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 478QZ UT WOS:000171358000137 ER PT J AU Takeshita, S Takeshita, F Haddad, DE Janabi, N Klinman, DM AF Takeshita, S Takeshita, F Haddad, DE Janabi, N Klinman, DM TI Activation of microglia and astrocytes by CpG oligodeoxynucleotides SO NEUROREPORT LA English DT Article DE astrocyte; CpG oligodeoxynucleotides; cytokines; microglia ID TUMOR NECROSIS FACTOR; MOTIFS; CELLS; DNA; INTERLEUKIN-6; CYTOKINES; INDUCTION AB Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate cells of the immune system to secrete a variety of cytokines and chemokines. This function can be carried out by microglia and astrocytes in the CNS. To evaluate the effect of CpG ODIN on microglia and astrocytes, purified cells were isolated and cultured in vitro. CpG ODN rapidly up-regulated their production of IL-1 beta, IL-6, IL-12, TNF alpha, MIP-I alpha and/or MIP-1 beta. In vivo, systemically administered CpG ODIN up-regulated the expression of mRNA encoding cytokines and chemokines in normal mouse brain. These findings suggest that CpG ODN can directly activate immune cells of the CNS. NeuroReport 12:3029-3032 (C) 2001 Lippincott Williams & Wilkins. C1 US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. USN, Malaria Program, Med Res Inst, Bethesda, MD 20084 USA. NINCDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3 D 10, Bethesda, MD 20892 USA. NR 20 TC 55 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 8 PY 2001 VL 12 IS 14 BP 3029 EP 3032 DI 10.1097/00001756-200110080-00010 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 476ND UT WOS:000171232800009 PM 11568631 ER PT J AU Wong, TY Klein, R Couper, DJ Cooper, LS Shahar, E Hubbard, LD Wofford, MR Sharrett, AR AF Wong, TY Klein, R Couper, DJ Cooper, LS Shahar, E Hubbard, LD Wofford, MR Sharrett, AR TI Retinal microvascular abnormalities and incident stroke: the atherosclerosis risk in communities study SO LANCET LA English DT Article ID JAPANESE PROVINCIAL CITY; BLOOD-PRESSURE; FOLLOW-UP; HYPERTENSION; RETINOPATHY; POPULATION; DISEASE; SHIBATA; COHORT AB Background Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. Methods A cohort of 10 358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. Findings Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p = 0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. Interpretation Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations. C1 Univ Wisconsin, Dept Ophthalmol, Madison, WI 53705 USA. Natl Univ Singapore, Singapore Natl Eye Ctr, Singapore 117548, Singapore. Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Mississippi, Med Ctr, Div Hypertens, Jackson, MS 39216 USA. RP Wong, TY (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 610 N Walnut St,460 WARF, Madison, WI 53705 USA. EM wong@epi.ophth.wisc.edu FU NHLBI NIH HHS [N01-HC-35126, N01-HC-35125, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55020, N01-HC-55021, N01-HC-55022]; PHS HHS [N01-C-55019] NR 28 TC 432 Z9 450 U1 1 U2 18 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 OCT 6 PY 2001 VL 358 IS 9288 BP 1134 EP 1140 DI 10.1016/S0140-6736(01)06253-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 479HM UT WOS:000171399000010 PM 11597667 ER PT J AU Ling, H Boudsocq, F Woodgate, R Yang, W AF Ling, H Boudsocq, F Woodgate, R Yang, W TI Crystal structure of a Y-family DNA polymerase in action: A mechanism for error-prone and lesion-bypass replication SO CELL LA English DT Article ID REPAIR PROTEIN MUTS; ESCHERICHIA-COLI; MISMATCH REPAIR; GENE ENCODES; LARGE FRAGMENT; THYMINE DIMER; FIDELITY; COMPLEX; IOTA; ETA AB Sulfolobus solfataricus P2 DNA polymerase IV [Dpo4) is a DinB homolog that belongs to the recently described Y-family of DNA polymerases, which are best characterized by their low-fidelity synthesis on undamaged DNA templates and propensity to traverse normally replication-blocking lesions. Crystal structures of Dpo4 in ternary complexes with DNA and an incoming nucleotide, either correct or incorrect, have been solved at 1.7 Angstrom and 2.1 Angstrom resolution, respectively. Despite a conserved active site and a hand-like configuration similar to all known polymerases, Dpo4 makes limited and nonspecific contacts with the replicating base pair, thus relaxing base selection. Dpo4 is also captured in the crystal translocating two template bases to the active site at once, suggesting a possible mechanism for bypassing thymine dimers. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ling, Hong/E-3729-2010; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 56 TC 459 Z9 462 U1 4 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 5 PY 2001 VL 107 IS 1 BP 91 EP 102 DI 10.1016/S0092-8674(01)00515-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 480GF UT WOS:000171453100012 PM 11595188 ER PT J AU Hall, JM Couse, JF Korach, KS AF Hall, JM Couse, JF Korach, KS TI The multifaceted mechanisms of estradiol and estrogen receptor signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID EPIDERMAL GROWTH-FACTOR; BETA ER-BETA; NUCLEAR RECEPTOR; BREAST-CANCER; TRANSCRIPTIONAL ACTIVATION; TISSUE DISTRIBUTION; ALPHA; MOUSE; KINASE; PROTEIN C1 NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Hall, JM (reprint author), NIEHS, Reprod & Dev Toxicol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 55 TC 754 Z9 781 U1 10 U2 73 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 36869 EP 36872 DI 10.1074/jbc.R100029200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700003 PM 11459850 ER PT J AU Schmidt, MO Brosh, RM Oliver, DB AF Schmidt, MO Brosh, RM Oliver, DB TI Escherichia coli SecA helicase activity is not required in vivo for efficient protein translocation or autogenous regulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL RECOGNITION PARTICLE; DISTINCT ATP-BINDING; BOX RNA HELICASE; DNA HELICASE; PREPROTEIN TRANSLOCATION; CRYSTAL-STRUCTURE; INNER MEMBRANE; PLASMA-MEMBRANE; MOTIF-III; IN-VIVO AB SecA is an essential ATP-driven motor protein that binds to preproteins and the translocon to promote protein translocation across the eubacterial plasma membrane. Escherichia coli SecA contains seven conserved motifs characteristic of superfamily II of DNA and RNA helicases, and it has been shown previously to possess RNA helicase activity. SecA has also been shown to be an autogenous repressor that binds to its translation initiation region on secM-secA mRNA, thereby blocking, and dissociating 30 S ribosomal subunits. Here we show that SecA is an ATP-dependent helicase that unwinds a mimic of the repressor helix of secM-secA mRNA. Mutational analysis of the seven conserved helicase motifs in SecA allowed us to identify mutants that uncouple SecA-dependent protein translocation activity from its helicase activity. Helicase-defective secA mutants displayed normal protein translocation activity and autogenous repression of secA in vivo. Our studies indicate that SecA helicase activity is nonessential and does not appear to be necessary for efficient protein secretion and secA autoregulation. C1 Wesleyan Univ, Dept Mol Biol & Biochem, Middletown, CT 06459 USA. NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Oliver, DB (reprint author), Wesleyan Univ, Dept Mol Biol & Biochem, Middletown, CT 06459 USA. FU NIGMS NIH HHS [GM 42033] NR 67 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37076 EP 37085 DI 10.1074/jbc.M104584200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700030 PM 11477104 ER PT J AU Petranka, J Wright, G Forbes, RA Murphy, E AF Petranka, J Wright, G Forbes, RA Murphy, E TI Elevated calcium in preneoplastic cells activates NF-kappa B and confers resistance to apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; NEOPLASTIC PROGRESSION; ALPHA DEGRADATION; B/REL ACTIVATION; EXPRESSION; GENE; CA2+; TRANSFORMATION; ACCUMULATION; MECHANISMS AB Early preneoplastic cells (sup+) exhibit increased susceptibility to apoptosis, which is lost in late stage pre. neoplastic cells (sup-). Sup+ cells, which undergo apoptosis when cultured in low serum, show little or no DNA binding activity to nuclear factor (NF)-kappaB either in 10% or 0.2% serum. In contrast sup- cells, which are resistant to apoptosis in low serum, show a sustained constitutive activation of NF-kappaB. The constitutive activation of NF-kappaB observed in sup - cells is not due to loss of I kappaB alpha. We considered that the activation of NF-kappaB in sup- cells might be secondary to an increase in cytosolic Ca2+ since sup - cells have a cytosolic Ca2+ level that is double that in sup+ cells. In support of a role for Ca2+, lowering cytosolic Ca2+ in sup - cells by addition of the cell-permeable Ca2+ chelator 1,2 bis(O-aminophenoxy)ethane-N, N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) reduced cytosolic Ca2+ by similar to 31% relative to untreated sup- cells, concomitant with a 65% reduction in NF-kappaB DNA binding activity and a reduction in I kappaB kinase (IKK) activity. In sup- cells in low serum, addition of BAPTA-AM also resulted in a significant (similar to 50%) increase in caspase-3 activity. Raising extracellular Ca2+ in sup+ cells resulted in a slight activation of I kappaB kinase and in enhanced NF-kappaB DNA binding activity. Using proteasome and calpain inhibitors, we determined that the basal activity of NF-kappaB in sup- cells is largely proteasome-independent, but sensitive to calpain inhibitors. Taken together these data suggest that the elevated Ca2+ in sup- cells causes a modest activation of IKK, which likely contributes to the enhanced basal activation of NF-kappaB in sup- cells; however, the predominant effect of Ca2+ appears to be mediated by Ca2+-enhanced degradation by calpain. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Murphy, E (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 34 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37102 EP 37108 DI 10.1074/jbc.M008448200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700033 PM 11479282 ER PT J AU Skiba, NP Martemyanov, KA Elfenbein, A Hopp, JA Bohm, A Simonds, WF Arshavsky, VY AF Skiba, NP Martemyanov, KA Elfenbein, A Hopp, JA Bohm, A Simonds, WF Arshavsky, VY TI RGS9-G beta 5 substrate selectivity in photoreceptors - Opposing effects of constituent domains yield high affinity of RGS interaction with the G protein-effector complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROD OUTER SEGMENTS; TRANSDUCIN GTPASE ACTIVITY; CGMP PHOSPHODIESTERASE; SUBUNIT G-BETA(5); BETA-SUBUNIT; REGULATORS; PURIFICATION; MEMBRANES; DISTINCT; BINDING AB RGS proteins regulate the duration of G protein signaling by increasing the rate of GTP hydrolysis on G protein a subunits. The complex of RGS9 with type 5 G protein beta subunit (G beta5) is abundant in photoreceptors, where it stimulates the GTPase activity of transducin. An important functional feature of RGS9-G beta5 is its ability to activate transducin GTPase much more efficiently after transducin binds to its effector, cGMP phosphodiesterase. Here we show that different domains of RGS9-G beta5 make opposite contributions toward this selectivity. G beta5 bound to the G protein gamma subunit-like domain of RGS9 acts to reduce RGS9 affinity for transducin, whereas other structures restore this affinity specifically for the transducin-phosphodiesterase complex. We suggest that this mechanism may serve as a general principle conferring specificity of RGS protein action. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Howe Labs MEEI, Boston, MA 02114 USA. Boston Biomed Res Inst, Watertown, MA 02472 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Howe Labs MEEI, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY-12859] NR 41 TC 53 Z9 54 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37365 EP 37372 DI 10.1074/jbc.M106431200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700068 PM 11495924 ER PT J AU Thompson, J Pobrish, SA Immel, S Lichtenthaler, FW Hall, BG Pikis, A AF Thompson, J Pobrish, SA Immel, S Lichtenthaler, FW Hall, BG Pikis, A TI Metabolism of sucrose and its five linkage-isomeric alpha-D-glucosyl-D-fructoses by Klebsiella pneumoniae - Participation and properties of sucrose-6-phosprate hydrolase and phospho-alpha-glucosidase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACID-SEQUENCE SIMILARITIES; PHOSPHOTRANSFERASE SYSTEM; CRYSTAL-STRUCTURE; MOLECULAR-STRUCTURE; BACILLUS-SUBTILIS; FAMILY 4; MALTITOL 4-O-ALPHA-D-GLUCOPYRANOSYL-D-GLUCITOL; FUSOBACTERIUM-MORTIFERUM; MALTOSE MONOHYDRATE; NUCLEIC-ACIDS AB Klebsiella pneumoniae is presently unique among bacterial species in its ability to metabolize not only sucrose but also its five linkage-isomeric alpha -D-glucosyl-D-fructoses: trehalulose, turanose, maltulose, leucrose, and palatinose. Growth on the isomeric compounds induced a protein of molecular mass similar to 50 kDa that was not present in sucrose-grown cells and which we have identified as an NAD(+) and metal ion-dependent 6-phospho-alpha -glucosidase (AglB). The aglB gene has been cloned and sequenced, and AglB (M-r = 49,256) has been purified from a high expression system using the chromogenic p-nitrophenyl alpha -glucopyranoside 6-phosphate as substrate. Phospho-alpha -glucosidase catalyzed the hydrolysis of a wide variety of 6-phospho-alpha -glucosides including maltose-6'-phosphate, maltitol-6-phosphate, isomaltose-6'-phosphate, and all five 6'-phosphorylated isomers of sucrose (K-m similar to 1-5 mM) yet did not hydrolyze sucrose-6-phosphate. By contrast, purified sucrose-6-phosphate hydrolase (M-r similar to 53,000) hydrolyzed only sucrose-6-phosphate (K-m similar to 80 muM). Differences in molecular shape and lipophilicity potential between sucrose and its isomers may be important determinants for substrate discrimination by the two phosphoglucosyl hydrolases. Phospho-alpha -glucosidase and sucrose-6-phosphate hydrolase exhibit no significant homology, and by sequence-based alignment, the two enzymes are assigned to Families 4 and 32, respectively, of the glycosyl hydrolase superfamily. The phospho-alpha -glucosidase gene (aglB) lies adjacent to a second gene (aglA), which encodes an EII(CB) component of the phosphoenolpyruvate-dependent sugar: phosphotransferase system. We suggest that the products of the two genes facilitate the phosphorylative translocation and subsequent hydrolysis of the five alpha -D-glucosyl-D-fructoses by K. pneumoniae. C1 NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Tech Univ Darmstadt, Inst Organ Chem, D-64287 Darmstadt, Germany. Univ Rochester, Dept Biol, Rochester, NY 14627 USA. NIDCR, Vaccine & Therapeut Dev Sect, Oral & Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Infect Dis, Washington, DC 20010 USA. RP Thompson, J (reprint author), NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 528,Convent Dr MSC-4350, Bethesda, MD 20892 USA. NR 61 TC 36 Z9 39 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37415 EP 37425 DI 10.1074/jbc.M106504200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700074 PM 11473129 ER PT J AU Tartaglia, N Du, J Tyler, WJ Neale, E Pozzo-Miller, L Lu, B AF Tartaglia, N Du, J Tyler, WJ Neale, E Pozzo-Miller, L Lu, B TI Protein synthesis-dependent and -independent regulation of hippocampal synapses by brain-derived neurotrophic factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNAPTIC VESICLE DOCKING; LONG-TERM POTENTIATION; DEVELOPING NEUROMUSCULAR SYNAPSES; BDNF KNOCKOUT MICE; CORTICAL-NEURONS; NEUROTRANSMITTER RELEASE; SYNAPTOTAGMIN MUTANTS; TRANSMITTER RELEASE; CA1 REGION; CYCLIC-AMP AB A fundamental difference between short-term and long-term forms of synaptic plasticity is the dependence on transcription and translation of new genes. Using organotypic cultures of hippocampal slices, we have investigated whether the modulation of synapses by brain-derived neurotrophic factor (BDNF) also requires protein synthesis. Long-term treatment of hippocampal slice cultures with BDNF increased the number of docked vesicles, but not that of reserve pool vesicles, at CAI excitatory synapses. BDNF also increased the levels of the vesicle proteins synaptophysin, synaptobrevin, and synaptotagmin, without affecting the presynaptic membrane proteins syntaxin and SNA-P-25, or the vesicle-binding protein synapsin-1. The increase in synaptophysin and synaptobrevin expression was moderate (2-fold) and occurred within 6 h after BDNF application. In contrast, synaptotagmin expression took 24 h to reach maximum levels (5-fold). The delayed increase in synaptotagmin was blocked by protein synthesis inhibitors, while the early increase in synaptophysin and synaptobrevin was not. Moreover, the BDNF-induced increase of synaptotagmin was blocked by inhibiting the cAMP/ protein kinase A (PKA) pathway. However, BDNF did not activate PKA, and application of a PKA activator did not mimic the BDNF effect. Taken together, these results suggest a novel, protein synthesis-dependent form of BDNF modulation that requires cAMP gating. C1 NICHHD, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Cell Biol, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. Howard Hughes Med Inst Natl Inst Hlth Res Scholar, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHHD, Unit Synapse Dev & Plast, NIH, Bldg 49,Rm 6A-80,49 Convent Dr,MSC4480, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012; Du, Jing/A-9023-2012; Tyler, William/J-1818-2012 FU NICHD NIH HHS [P01-HD38760-01]; NINDS NIH HHS [R01-NS40593-01] NR 59 TC 113 Z9 119 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37585 EP 37593 DI 10.1074/jbc.M101683200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700095 PM 11483592 ER PT J AU Vu, CCQ Bortner, CD Cidlowski, JA AF Vu, CCQ Bortner, CD Cidlowski, JA TI Differential involvement of initiator caspases in apoptotic volume decrease and potassium efflux during Fas- and UV-induced cell death SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAS/FAS LIGAND INTERACTIONS; CYTOCHROME-C; ULTRAVIOLET-LIGHT; LYMPHOCYTE APOPTOSIS; GROWTH-FACTOR; K+ CHANNELS; ACTIVATION; INHIBITORS; SHRINKAGE; CASCADE AB Caspase activation and apoptotic volume decrease are fundamental features of programmed cell death; however, the relationship between these components is not well understood. Here we provide biochemical and genetic evidence for the differential involvement of initiator caspases in the apoptotic volume decrease during both intrinsic and extrinsic activation of apoptosis. Apoptosis induction in Jurkat T lymphocytes by Fas receptor engagement (intrinsic) or ultraviolet (UV)-C radiation (extrinsic) triggered the loss of cell volume, which was restricted to cells with diminished intracellular K+ ions. These characteristics kinetically coincided with the proteolytic processing and activation of both initiator and effector caspases. Although the polycaspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone completely inhibited the Fas-mediated apoptotic volume decrease and K+ efflux, it was much less effective in preventing these processes during UV-induced cell death under conditions whereby caspase activities and DNA degradation were blocked. To define the roles of specific initiator caspases, we utilized Jurkat cells genetically deficient in caspase-8 or stably transfected with a dominant-negative mutant of caspase-9. The results show that the activation of caspase-8, but not caspase-9, is necessary for Fas-induced apoptosis. Conversely, caspase-9, but not caspase-8, is important for UV-mediated shrunken morphology and apoptosis progression. Together, these findings indicate that cell shrinkage and K+ efflux during apoptosis are tightly coupled, but are differentially regulated by either caspase-8 or caspase-9 depending on specific pathways of cell death. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 59 TC 72 Z9 76 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37602 EP 37611 DI 10.1074/jbc.M104810200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700097 PM 11431480 ER PT J AU Ye, DM Wei, M McGuire, M Huang, K Kapadia, G Herzberg, O Martin, BM Dunaway-Mariano, D AF Ye, DM Wei, M McGuire, M Huang, K Kapadia, G Herzberg, O Martin, BM Dunaway-Mariano, D TI Investigation of the catalytic site within the ATP-grasp domain of Clostridium symbiosum pyruvate phosphate dikinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID D-ALANINE LIGASE; ESCHERICHIA-COLI; DIRECTED MUTAGENESIS; BINDING SITE; PHOSPHOENOLPYRUVATE FORMATION; GLUTATHIONE SYNTHETASE; NUCLEOTIDE-BINDING; UTILIZING ENZYMES; B-DOMAIN; LOCATION AB Pyruvate phosphate dikinase (PPDK) catalyzes the interconversion of ATP, P-i, and pyruvate with AMP, PPi, and phosphoenolpyruvate (PEP) in three partial reactions as follows: 1) E-His + ATP --> E-His-PP-AMP; 2) E-His-PP.AMP + P-i --> E-His-P.AMP.PPi; and 3) E-His-P + pyruvate --> E.PEP using His-455 as the carrier of the transferred phosphoryl groups. The crystal structure of the Clostridium symbiosum PPDK (in the unbound state) reveals a three-domain structure consisting of consecutive N-terminal, central His-455, and C-terminal domains. The N-terminal and central His-455 domains catalyze partial reactions 1 and 2, whereas the C-terminal and central His-455 domains catalyze partial reaction 3. Attempts to obtain a crystal structure of the enzyme with substrate ligands bound at the nucleotide binding domain have been unsuccessful. The object of the present study is to demonstrate Mg(ll) activation of catalysis at the ATP/P-i active site, to identify the residues at the ATP/P-i active site that contribute to catalysis, and to identify roles for these residues based on their positions within the active site scaffold. First, Mg(II) activation studies of catalysis of E + ATP + P-i --> E-P + AMP + PPi partial reaction were carried out using a truncation mutant (Tem533) in which the C-terminal domain is absent. The kinetics show that a minimum of 2 Mg(II) per active site is required for the reaction. The active site residues used for substrate/cofactor binding/activation were identified by site-directed mutagenesis. Lys-22, Arg-92, Asp-321, Glu-323, and Gln-335 mutants were found to be inactive; Arg-337, Glu-279, Asp-280, and Arg-135 mutants were partially active; and Thr-253 and Gln-240 mutants were almost fully active. The participation of the nucleotide ribose 2'-OH and alpha -P in enzyme binding is indicated by the loss of productive binding seen with substrate analogs modified at these positions. The ATP, P-i, and Mg(II) ions were docked into the PPDK N-terminal domain crevice, in an orientation consistent with substrate/cofactor binding modes observed for other members of the ATP-Grasp fold enzyme superfamily and consistent with the structure-function data. On the basis of this docking model, the ATP polyphosphate moiety is oriented/activated for pyrophosphoryl transfer through interaction with Lys-22 (gamma -P), Arg-92 (alpha -P), and the Gly-101 to Met-103 loop (gamma -P) as well as with the Mg(II) cofactors. The P-i is oriented/activated for partial reaction 2 through interaction with Arg-337 and a Mg(II) cofactor. The Mg(II) ions are bound through interaction with Asp-321, Glu-323, and Gln-335 and substrate. Residues Glu-279, Asp-280, and Arg-135 are suggested to function in the closure of an active site loop, over the nucleotide ribose-binding site. C1 Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIH, Bethesda, MD 20892 USA. RP Dunaway-Mariano, D (reprint author), Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. FU NIGMS NIH HHS [GM 36260] NR 29 TC 15 Z9 17 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37630 EP 37639 DI 10.1074/jbc.M105631200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700100 PM 11468288 ER PT J AU Ramakrishnan, B Shah, PS Qasba, PK AF Ramakrishnan, B Shah, PS Qasba, PK TI alpha-Lactalbumin (LA) stimulates milk beta-1,4-galactosyltransferase I (beta 4Gal-T1) to transfer glucose from UDP-glucose to N-acetylglucosamine - Crystal structure of beta 4Gal-T1-LA complex with UDP-Glc SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-4-GALACTOSYLTRANSFERASE GENE FAMILY; GALACTOSYL TRANSFERASE; ESCHERICHIA-COLI; CLONING; EXPRESSION; CDNA; GALACTOSYLTRANSFERASE; PROTEIN; MEMBER; SITE AB beta -1,4-Galactosyltransferase 1 (Gal-T1) transfers galactose (Gal) from UDP-Gal to N-acetylglucosamine (Glc-NAc), which constitutes its normal galactosyltransferase (Gal-T) activity. In the presence of alpha -lactalbumin (IA), it transfers Gal to Glc, which is its lactose synthase (LS) activity. It also transfers glucose (Glc) from UDP-Glc to GlcNAc, constituting the glucosyltransferase (Glc-T) activity, albeit at an efficiency of only 0.3-0.4% of Gal-T activity. In the present study, we show that LA increases this activity almost 30-fold. It also enhances the Glc-T activity toward various N-acyl substituted glucosamine acceptors. Steady state kinetic studies of Glc-T reaction show that the K-m for the donor and acceptor substrates are high in the absence of LA. In the presence of LA, the K-m for the acceptor substrate is reduced 30-fold, whereas for UDP-Glc it is reduced only 5-fold. In order to understand this property, we have determined the crystal structures of the Gal-TI-IA complex with UDP-Glc.Mn2+ and with N-butanoyl-glucosamine (N-butanoyl-GlcN), a preferred sugar acceptor in the Glc-T activity. The crystal structures reveal that although the binding of UDP-Glc is quite similar to UDP-Gal, there are few significant differences observed in the hydrogen bonding interactions between UDP-Glc and Gal-T1. Based on the present kinetic and crystal structural studies, a possible explanation for the role of LA in the Glc-T activity has been proposed. C1 NCI, Struct Glycobiol Sect, LECB, CCR,NIH, Ft Detrick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC, Lab Expt & Computat Biol,Ctr Canc Res,NIH, Ft Detrick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, LECB, CCR,NIH, Bldg 469,Rm 221, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 68 Z9 71 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2001 VL 276 IS 40 BP 37665 EP 37671 DI 10.1074/jbc.M102458200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 478YD UT WOS:000171375700104 PM 11485999 ER PT J AU Hargittai, MRS Mangla, AT Gorelick, RJ Musier-Forsyth, K AF Hargittai, MRS Mangla, AT Gorelick, RJ Musier-Forsyth, K TI HIV-1 nucleocapsid protein zinc finger structures induce tRNA(Lys,3) structural changes but are not critical for primer/template annealing SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE nucleocapsid protein; RNA chaperone; terbium cleavage; tRNA structure; zinc fingers ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSFER-RNA-SYNTHETASE; YEAST TRANSFER-RNAPHE; PLUS-STRAND TRANSFER; PRIMER BINDING-SITE; REVERSE-TRANSCRIPTION; CRYSTAL-STRUCTURE; IN-VITRO; SECONDARY STRUCTURE; MAGNETIC-RESONANCE AB Retroviral reverse transcriptases use host cellular tRNAs as primers to initiate reverse transcription. In the case of human immunodeficiency virus type 1 (HIV-1), the 3' 18 nucleotides of human tRNA(Lys,3) are annealed to a complementary sequence on the RNA genome known as the primer binding site (PBS). The HIV-1 nucleocapsid protein (NC) facilitates this annealing. To understand the structural changes that are, induced upon NC binding to the tRNA alone, we employed a chemical probing method using the lanthanide metal terbium. At low concentrations of NC, the strong terbium cleavage observed in the core region of the tRNA is significantly attenuated. Thus, NC binding first results in disruption of the tRNA's metal binding pockets, including those that stabilize the D-T PC tertiary interaction. When NC concentrations approach the amount needed for complete primer/template annealing, NC further destabilizes the tRNA acceptor-T psiC stem minihelix, as evidenced by increased terbium cleavage in this domain. A mutant form of NC (SSHS NC), which lacks the zinc finger structures, is able to anneal tRNA(Lys,3) efficiently to the PBS, and to destabilize the tRNA tertiary core, albeit less effectively than wild-type NC. This mutant form of NC does not affect cleavage significantly in the helical regions, even when bound at high concentrations. These results, as well as experiments conducted in the presence of polyLys, suggest that in the absence of the zinc finger structures, NC acts as a polycation, neutralizing the highly negative phosphodiester backbone. The presence of an effective multivalent cationic peptide is sufficient for efficient tRNA primer annealing to the PBS. (C) 2001 Academic Press. C1 Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. RP Musier-Forsyth, K (reprint author), Univ Minnesota, Dept Chem, 207 Pleasant St SE, Minneapolis, MN 55455 USA. FU NCI NIH HHS [N01-CO56000]; NIAID NIH HHS [AI32231]; NIGMS NIH HHS [T32 GM08277] NR 73 TC 65 Z9 67 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 5 PY 2001 VL 312 IS 5 BP 985 EP 997 DI 10.1006/jmbi.2001.5021 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481WK UT WOS:000171543300010 PM 11580244 ER PT J AU Mack, DR Chiu, TK Dickerson, RE AF Mack, DR Chiu, TK Dickerson, RE TI Intrinsic bending and deformability at the T-A step of CCTTTAAAGG: A comparative analysis of T-A and A-T steps within A-tracts SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE A-tract bending; T-A versus A-T steps; structural deformability; sequence-structure relationships; DNA conformation ID B-DNA DODECAMER; CRYSTAL-STRUCTURE; C-G; DINUCLEOTIDE STEPS; MOLECULAR-STRUCTURE; ADENINE TRACT; MINOR-GROOVE; BASE-PAIRS; X-RAY; HELIX AB Introduction of a T-A or pyrimidine-purine step into a straight and rigid A-tract can cause a positive roll deformation that kinks the DNA helix at that step. In CCTTTAAAGG, the central T-A step has an 8.6 degrees bend toward the major groove. We report the structural analysis of CCTTTAAAGG and a comparison with 25 other representative crystal structures from the NDB containing at least four consecutive A or T bases. On average, more local bending occurs at the disruptive T-A step ') than at an A-T step (5.71). In addition, A-tracts containing an A(8.2l T step are more bent than are pure A-tracts, and hence A-A and A-T steps are not equivalent. All T-A steps examined exhibit positive roll, bending towards the major groove, while A-T steps display negative roll and bend slightly towards the minor groove. This illustrates how inherent negative and positive roll are, respectively, at A-T and T-A steps within A-tracts. T-A steps are more deformable, showing larger and more variable deformations of minor groove width, rise, cup, twist, and buckle. Standard deviations of twist, rise, and cup for T-A steps are 6.66 degrees, 0.55 Angstrom, and 15.90 degrees, versus 2.28 degrees, 0.21 Angstrom, and 2.99 degrees for A-T steps. Packing constraints determine which local values of these helical parameters an individual T-A step will adopt. For instance, with CCTTTAAAGG and three isomorphous structures, CGATTAATCG, CGATATATCG, and CGATCGATCG, crystal packing forces lead to a series of correlated changes: widened minor groove, large slide, low twist, and large rise. The difference in helical parameters between A-T steps lying within A-tracts, versus A-T steps within alternating AT sequences, demonstrates the importance of neighboring steps on the conformation of a given dinucleotide step. (C) 2001 Academic Press. C1 Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dickerson, RE (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. FU NIGMS NIH HHS [GM-31299] NR 56 TC 58 Z9 60 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 5 PY 2001 VL 312 IS 5 BP 1037 EP 1049 DI 10.1006/jmbi.2001.4994 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 481WK UT WOS:000171543300014 PM 11580248 ER PT J AU McDermott, MM Greenland, P Liu, K Guralnik, JM Criqui, MH Dolan, NC Chan, CL Celic, L Pearce, WH Schneider, JR Sharma, L Clark, E Gibson, D Martin, GJ AF McDermott, MM Greenland, P Liu, K Guralnik, JM Criqui, MH Dolan, NC Chan, CL Celic, L Pearce, WH Schneider, JR Sharma, L Clark, E Gibson, D Martin, GJ TI Leg symptoms in peripheral arterial disease - Associated clinical characteristics and functional impairment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LOWER-EXTREMITY FUNCTION; INTERMITTENT CLAUDICATION; CARDIOVASCULAR HEALTH; PHYSICAL-DISABILITY; WOMENS HEALTH; 6-MINUTE WALK; ACCELEROMETER; PREDICTOR; MORTALITY; CRITERIA AB Context Persons with lower-extremity peripheral arterial disease (PAD) are often asymptomatic or have leg symptoms other than intermittent claudication (IC). Objective To identify clinical characteristics and functional limitations associated with a broad range of leg symptoms identified among patients with PAD. Design, Setting, and Participants Cross-sectional study of 460 men and women with PAD and 130 without PAD, who were identified consecutively, conducted between October 1998 and January 2000 at 3 Chicago-area medical centers. Main Outcome Measures Ankle-brachial index score of less than 0.90; scores from 6-minute walk, accelerometer-measured physical activity over 7 days, repeated chair raises, standing balance (full tandem stand), 4-m walking velocity, San Diego claudication questionnaire, Geriatric Depression Score Short-Form, and the Walking Impairment Questionnaire. Results All groups with PAD had poorer functioning than participants without PAD. The following values are for patients without IC vs those with IC. Participants in the group with leg pain on exertion and rest (n=88) had a higher (poorer) score for neuropathy (5.6 vs 3.5; P<.001), prevalence of diabetes mellitus (48.9% vs 26.7%; P<.001), and spinal stenosis (20.8% vs 7.2%; P=.002). The atypical exertional leg pain/carry on group (exertional leg pain other than IC associated with walking through leg pain [n=41]) and the atypical exertional leg pain/stop group (exertional leg pain other than IC that causes one to stop walking [n=90]) had better functioning than the IC group. The group without exertional leg pain/inactive (no exertional leg pain in individual who walks less than or equal to6 blocks per week [n=28]) and the leg pain on exertion and rest group had poorer functioning than those with IC. Adjusting for age, sex, race, and comorbidities and compared with IC, participants with atypical exertional leg pain/carry on achieved a greater distance on the 6-minute walk (404.3 vs 328.5 m; P<.001) and were less likely to stop during the 6-minute walk (6.8% vs 36%; P=.002). The group with pain on exertion and rest had a slower time for completing 5 chair raises (13.5 vs 11.9 seconds; P=.009), completed the tandem stand less frequently (37.5% vs 60.0%; P=.004), and had a slower 4-m walking velocity (0.80 vs 0.90 m/s; P<.001). Conclusions There is a wide range of leg symptoms in persons with PAD beyond that of classic IC. Comorbid disease may contribute to these symptoms in PAD. Functional impairments are found in every PAD symptom group, and the degree of functional limitation varies depending on the type of leg symptom. C1 Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Surg, Chicago, IL 60611 USA. Evanston Northwestern Hosp, Dept Surg, Div Vasc Surg, Evanston, IL USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Catholic Hlth Partners, Dept Surg, Div Vasc Surg, Chicago, IL USA. RP McDermott, MM (reprint author), 675 N St Clair,Suite 18-200, Chicago, IL 60611 USA. FU NCRR NIH HHS [RR-00048]; PHS HHS [R01-58099] NR 37 TC 355 Z9 363 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 3 PY 2001 VL 286 IS 13 BP 1599 EP 1606 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 478HH UT WOS:000171340600027 PM 11585483 ER PT J AU Fojo, T AF Fojo, T TI Cancer, DNA repair mechanisms, and resistance to chemotherapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID STRAND BREAK REPAIR; EMBRYONIC LETHALITY; LIGASE-IV; HOMOLOGOUS RECOMBINATION; ACQUIRED-RESISTANCE; TARGETED DISRUPTION; GENOMIC STABILITY; MYELOID-LEUKEMIA; VERTEBRATE CELLS; PROTEIN-KINASE C1 Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. RP Fojo, T (reprint author), NIH, Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. NR 37 TC 36 Z9 38 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 3 PY 2001 VL 93 IS 19 BP 1434 EP 1436 DI 10.1093/jnci/93.19.1434 PG 3 WC Oncology SC Oncology GA 477DA UT WOS:000171266800001 PM 11584051 ER PT J AU Mills, GB Bast, RC Srivastava, S AF Mills, GB Bast, RC Srivastava, S TI Future for ovarian cancer screening: Novel markers from emerging technologies of transcriptional profiling and proteomics SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENE-EXPRESSION; CARCINOMA; LOCALIZATION; PROSTASIN C1 Univ Texas, MD Anderson Canc Res Ctr, Houston, TX USA. NCI, Div Canc Prevent, Canc Biomarkers Res Grp, Bethesda, MD 20892 USA. RP Srivastava, S (reprint author), NIH, 6130 Execut Blvd,Suite 3142, Rockville, MD 20851 USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 24 TC 41 Z9 46 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 3 PY 2001 VL 93 IS 19 BP 1437 EP 1439 DI 10.1093/jnci/93.19.1437 PG 3 WC Oncology SC Oncology GA 477DA UT WOS:000171266800002 PM 11584052 ER PT J AU Wendler, D Prasad, K AF Wendler, D Prasad, K TI Core safeguards for clinical research with adults who are unable to consent SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SUBSTITUTED JUDGMENT; DECISION-MAKING AB safeguards for clinical research with adults who are unable to consent. Three other major U.S. groups have also proposed additional safeguards for this population, and existing Canadian and European guidelines already include such safeguards. While these six guidelines agree on some safeguards, they disagree on others. To allow Important research to proceed while protecting adults who are unable to consent, it will be crucial to resolve these differences. This paper uses a side-by-side comparison of these six guidelines to highlight their major points of consensus, analyze their significant differences, and distill six core safeguards. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Room 1C118,Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 50 Z9 50 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 2 PY 2001 VL 135 IS 7 BP 514 EP 523 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 477EF UT WOS:000171269600006 PM 11578155 ER PT J AU Hortin, GL AF Hortin, GL TI Inflation of precision in medical reports SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 2 PY 2001 VL 135 IS 7 BP 549 EP 549 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 477EF UT WOS:000171269600013 PM 11578162 ER PT J AU Piro, MC Militello, V Leone, M Gryczynski, Z Smith, SV Brinigar, WS Cupane, A Friedman, FK Fronticelli, C AF Piro, MC Militello, V Leone, M Gryczynski, Z Smith, SV Brinigar, WS Cupane, A Friedman, FK Fronticelli, C TI Heme pocket disorder in myoglobin: Reversal by acid-induced soft refolding SO BIOCHEMISTRY LA English DT Article ID SPERM WHALE MYOGLOBIN; CO FLASH-PHOTOLYSIS; POLYCYCLIC AROMATIC-HYDROCARBONS; TIME-RESOLVED FLUORESCENCE; SITE-DIRECTED MUTAGENESIS; STRUCTURAL CHARACTERIZATION; BINDING-KINETICS; ESCHERICHIA-COLI; LIGAND-BINDING; ORIENTATIONAL DISORDER AB The protein folding process of heme proteins entails generation of not only a correct global polypeptide structure, but also a correct, functionally competent heme environment. We employed a variety of spectroscopic approaches to probe the structure and dynamics of the heme pocket of a recombinant sperm whale myoglobin. The conformational characteristics were examined by circular dichroism, time-resolved fluorescence spectroscopy, FTIR spectroscopy, and optical absorption spectroscopy in the temperature range 300-20 K. Each of these spectroscopic probes detected modifications confined exclusively to the heme pocket of the expressed myoglobin relative to the native protein. The functional properties were examined by measuring the kinetics of CO binding after flash-photolysis. The kinetics of the expressed myoglobin were more heterogeneous than those of the native protein. Mild acid exposure of the ferric derivative of the recombinant protein resulted in a protein with "nativelike" spectroscopic properties and homogeneous CO binding kinetics. The heme pocket modifications observed in this recombinant myoglobin do not derive from inverted heme. In contrast, when native apomyoglobin is reconstituted with the heme in vitro, the heme pocket disorder could be attributed exclusively to 180 degrees rotation of the bound heme [La Mar, G. N., Toi, H., and Krishnamoorthi, R. (1984) J. Am. Chem. Soc. 106, 6395-6401; Light, W. R., Rohlfs, R. J., Palmer, G., and Olson, J. S. (1987) J. Biol. Chem. 262, 46-52]. We conclude that exposure to low pH decreases the affinity of globin for the heme and allows an extended conformational sampling or "soft refolding" to a nativelike conformation. C1 Univ Palermo, Ist Nazl Struttura Mat, I-90123 Palermo, Italy. Univ Palermo, Dipartimento Sci Fis & Astron, I-90123 Palermo, Italy. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. Univ Palermo, Ist Fisiol Umana, I-90123 Palermo, Italy. Univ Maryland, Sch Med, Ctr Fluorescence Spect, Baltimore, MD 21201 USA. NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. Temple Univ, Dept Chem, Philadelphia, PA 19122 USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD 21287 USA. RP Cupane, A (reprint author), Univ Palermo, Ist Nazl Struttura Mat, Via Archirafi 36, I-90123 Palermo, Italy. RI MILITELLO, VALERIA/F-2664-2011; Leone, Maurizio/F-2353-2010; Friedman, Fred/D-4208-2016 OI Leone, Maurizio/0000-0002-0292-7657; FU NCRR NIH HHS [RR-0811]; NHLBI NIH HHS [P01 HL48517] NR 68 TC 5 Z9 5 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 2 PY 2001 VL 40 IS 39 BP 11841 EP 11850 DI 10.1021/bi010652f PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 479HZ UT WOS:000171400100020 PM 11570884 ER PT J AU Chen, H Nystrom, FH Dong, LQ Li, YH Song, SB Liu, F Quon, MJ AF Chen, H Nystrom, FH Dong, LQ Li, YH Song, SB Liu, F Quon, MJ TI Insulin stimulates increased catalytic activity of phosphoinositide-dependent kinase-1 by a phosphorylation-dependent mechanism SO BIOCHEMISTRY LA English DT Article ID 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1; RAT ADIPOSE-CELLS; EPITOPE-TAGGED GLUT4; C-ZETA; GLUCOSE-TRANSPORTER-4 TRANSLOCATION; GLUCOSE-TRANSPORT; ACTIVATION; PDK1; ADIPOCYTES; AKT AB Phosphoinositide-dependent kinase-1 (PDK-1) is a serine-threonine kinase downstream from PI 3-kinase that phosphorylates and activates other important kinases such as Akt that are essential for cell survival and metabolism. Previous reports have suggested that PDK-1 has constitutive catalytic activity that is not regulated by stimulation of cells with growth factors. We now show that insulin stimulation of NIH-3T3(IR) cells or rat adipose cells may significantly increase the intrinsic catalytic activity of PDK-1. Insulin treatment of NIH-3T3(IR) fibroblasts overexpressing PDK-1 increased both phosphorylation of recombinant PDK-1 in intact cells and PDK-1 kinase activity in an immune-complex kinase assay. Insulin stimulation of rat adipose cells also increased catalytic activity of endogenous PDK-1 immunoprecipitated from the cells. Both insulin-stimulated phosphorylation and activity of PDK-1 were inhibited by wortmannin and reversed by treatment with the phosphatase PP-2A. A mutant PDK-1 with a disrupted PH domain (W538L) did not undergo phosphorylation or demonstrate increased kinase activity in response to insulin stimulation. Similarly, a PDK-1 phosphorylation site point mutant (S244A) had no increase in kinase activity in response to insulin stimulation. Thus, the insulin-stimulated increase in PDK-1 catalytic activity may involve PI 3-kinase- and phosphorylation-dependent mechanisms. We conclude that the basal constitutive catalytic activity of PDK-1 in NIH-3T3(IR) cells and rat adipose cells can be significantly increased upon insulin stimulation. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. RP Quon, MJ (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 8C-218, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Nystrom, Fredrik/0000-0002-1680-1000; Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 43 TC 21 Z9 22 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 2 PY 2001 VL 40 IS 39 BP 11851 EP 11859 DI 10.1021/bi010743c PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 479HZ UT WOS:000171400100021 PM 11570885 ER PT J AU Heishman, SJ AF Heishman, SJ TI Tobacco - the once and future addiction SO ADDICTION LA English DT Editorial Material C1 NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Heishman, SJ (reprint author), NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD OCT PY 2001 VL 96 IS 10 BP 1389 EP 1390 DI 10.1046/j.1360-0443.2001.961013891.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 474LZ UT WOS:000171109900001 PM 11571056 ER PT J AU Fang, GW Burger, H Chappey, C Rowland-Jones, S Visosky, A Chen, CH Moran, T Townsend, L Murray, M Weiser, B AF Fang, GW Burger, H Chappey, C Rowland-Jones, S Visosky, A Chen, CH Moran, T Townsend, L Murray, M Weiser, B TI Analysis of transition from long-term nonprogressive to progressive infection identifies sequences that may attenuate HIV type 1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS; ESCAPE; AIDS; RECOMBINATION; LYMPHOCYTES; EVOLUTION; VARIANTS; RNA; PATHOGENICITY; ACTIVATION AB Long-term nonprogressive human immunodeficiency virus type 1 (HIV-1) infection and its transition to progressive infection presents an opportunity to identify the molecular determinants of HIV-1 attenuation and pathogenesis. We studied an individual who underwent a transition from long-term nonprogressive to rapidly progressive infection. Because HIV-1 RNA genomes in plasma represent replicating virus, we developed a technique to clone full-length HIV-1 RNA genomes from plasma and used this technique to obtain clones from this individual before and during the transition. Most clones assayed were infectious, demonstrating that the RNA genomes encoded viable virus. Analysis of 20 complete HIV-1 RNA genomic sequences revealed one major difference between sequences found during the two phases of infection. During the nonprogressive phase, the predominant sequences had a large deletion in an Sp1-binding site and adjacent promoter in the U3 part of the long terminal repeat (LTR); when the infection became progressive, all viruses had intact Sp1 and promoter sequences and were derived from a minor species present earlier. Analysis of 184 clones of the LTR region obtained at five time points spanning a 7-year period confirmed this switch. In an in vitro assay, the deletion downregulated LTR-driven transcription of a reporter gene. In addition, analysis of cytotoxic T lymphocyte (CTL) epitopes predicted from the complete viral RNA genomes revealed multiple potential escape mutants that accumulated by the time of progression. These studies suggest that during the nonprogressive phase, the Sp1 enhancer-promoter deletion is likely to have played a role in decreasing replication, thereby attenuating HIV-1. The accumulation of CTL escape mutants suggests that a breakdown in immunologic surveillance may have allowed proliferation of intact virus, thus leading to rapid disease progression. These data reveal the viral and immune interactions characterizing a transition from long-term nonprogressive to rapidly progressive infection. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. Albany Med Coll, Albany, NY 12208 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Oxford, Inst Mol Med, Oxford OX3 9DS, England. Univ Manitoba, Winnipeg, MB R3E 0W3, Canada. RP Weiser, B (reprint author), Wadsworth Ctr, 120 New Scotland Ave, Albany, NY 12208 USA. FU NIAID NIH HHS [R01 AI33334, R01 AI42555, U01 AI35004] NR 45 TC 15 Z9 16 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2001 VL 17 IS 15 BP 1395 EP 1404 DI 10.1089/088922201753197060 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 487CX UT WOS:000171857000004 PM 11679152 ER PT J AU Corleto, VD Annibale, B Gibril, F Angeletti, S Serrano, J Venzon, DJ Delle Fave, G Jensen, RT AF Corleto, VD Annibale, B Gibril, F Angeletti, S Serrano, J Venzon, DJ Delle Fave, G Jensen, RT TI Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome? SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID LONG-TERM TREATMENT; OMEPRAZOLE; GASTRINOMA; MANAGEMENT; EFFICACY; LANSOPRAZOLE; SURVIVAL; SURGERY; SAFETY; CURE AB Background: Proton pump inhibitors are potent acid suppressants which, at normal doses, can result in hypergastrinaemia in patients with idiopathic oesophageal reflux disease and in the control of symptoms in most patients with gastrinomas. Therefore, their use could delay or mask the diagnosis of gastrinoma. Aim: To investigate whether the widespread use of proton pump inhibitors masks or complicates the diagnosis of gastrinoma. Subjects and methods: Data from two centres with different referral criteria for suspected gastrinomas were analysed (Gastroenterology Unit, Rome, Italy and National Institutes of Health, Bethesda, AM, USA). The number of referrals and the number of new patients with gastrinoma diagnosed in the years prior to the widespread use of proton pump inhibitors (1986-1992) were compared with the numbers since proton pump inhibitors became widely available (1993-1998). Results: The decrease in referral rate (P=0.0009) and the decrease in the annual rate of gastrinoma diagnosis (P=0.0020) at both centres correlated with the increased use of proton pump inhibitors. At the Italian centre, there was a 62% decrease in annual referrals (P<0.0001) in the post-proton pump inhibitor period, relative to the pre-proton pump inhibitor period, whereas there was an increase in the rate of referral of other gastrointestinal endocrine tumours. The number of new cases of gastrinoma diagnosed decreased by 40%. At the US centre, the referral rate decreased by 28% (P=0.024) in the post-proton pump inhibitor period. There was also a 43% decrease in the number of new cases diagnosed annually in the post-proton pump inhibitor period (P=0.0012). There was a 2.6-fold increase in the post-proton pump inhibitor period in the percentage of referrals with a false diagnosis of gastrinoma as the cause of hypergastrinaemia (P=0.0040). Conclusions: In both referral centres, less patients have been referred with a possible diagnosis of gastrinoma and fewer new patients with gastrinoma have been diagnosed since proton pump inhibitors became widely available. These data support the conclusion that, since proton pump inhibitors have been released, the diagnosis of gastrinoma has been masked and will probably be delayed, with the result that patients with gastrinoma will be diagnosed at more advanced stages in their disease course. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dept Cellular Biotechnol, Gastroenterol Unit, Rome, Italy. Univ Roma La Sapienza, Dept Haematol, Rome, Italy. Natl Canc Inst, NIH, Biostatist & Data Management Sect, Bethesda, MD USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr MSC1804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 34 TC 41 Z9 44 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD OCT PY 2001 VL 15 IS 10 BP 1555 EP 1561 DI 10.1046/j.1365-2036.2001.01085.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 482PT UT WOS:000171585000005 PM 11563994 ER PT J AU Black, S AF Black, S TI Why we have life SO AMERICAN BIOLOGY TEACHER LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Black, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NATL ASSOC BIOLOGY TEACHERS INC PI RESTON PA 12030 SUNRISE VALLEY DR, #110, RESTON, VA 20191 USA SN 0002-7685 J9 AM BIOL TEACH JI Am. Biol. Teach. PD OCT PY 2001 VL 63 IS 8 BP 547 EP 547 PG 1 WC Biology; Education, Scientific Disciplines SC Life Sciences & Biomedicine - Other Topics; Education & Educational Research GA 545RY UT WOS:000175232400001 ER PT J AU Miele, PS Kogulan, PK Levy, CS Goldstein, S Marcus, KA Smith, MA Rosenthal, J Croxton, M Gill, VJ Lucey, DR AF Miele, PS Kogulan, PK Levy, CS Goldstein, S Marcus, KA Smith, MA Rosenthal, J Croxton, M Gill, VJ Lucey, DR TI Seven cases of surgical native valve endocarditis caused by coagulase-negative staphylococci: An underappreciated disease SO AMERICAN HEART JOURNAL LA English DT Article ID EPIDERMIDIS; LUGDUNENSIS; THERAPY AB Background Native valve endocarditis caused by coagulase-negative staphylococci is uncommon and the diagnosis is infrequently considered. The disease, however, appears to be increasing in frequency and can pursue an aggressive clinical course. We report the clinical features of 7 cases of coagulase-negative staphylococcal native valve endocarditis (CNS-NVE) seen at 1 institution with a large cardiovascular referral base over a 10-month period. All cases required valve replacement surgery. Methods Clinical history, echocardiograms, and microbiologic and histopathologic data were reviewed for 7 patients with surgical CNS-NVE. Results Four patients had intravenous central catheters, and 1 had recent surgery, whereas the remaining 2 had no identifiable risk factors. Presentations ranged from subacute (4 cases) to acute with complications (3 cases). Complications included congestive heart failure, stroke, and heart block. Echocardiography demonstrated valvular lesions in all 7 cases. Valve pathologic study demonstrated gram-positive cocci in all 7 cases; blood cultures grew coagulase-negative staphylococci in 6 cases and valve cultures grew Staphylococcus epidermidis in 5 cases. Conclusions Coagulase-negative staphylococci, including S epidermidis, can cause severe native valve endocarditis requiring valve replacement. The increasing use of intravascular access devices in the community may herald an increase in the incidence of CNS-NVE. A high index of diagnostic suspicion in the appropriate clinical setting Is critical for optimal management. C1 Washington Hosp Ctr, Dept Infect Dis, Washington, DC 20010 USA. Kaiser Permanente, Med Grp, Washington, DC USA. Natl Inst Hlth, Bethesda, MD USA. RP Lucey, DR (reprint author), Washington Hosp Ctr, Dept Infect Dis, Room 2A-56,110 Irving St NW, Washington, DC 20010 USA. NR 18 TC 20 Z9 20 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2001 VL 142 IS 4 BP 571 EP 576 DI 10.1067/mhj.2001.118119 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 478JK UT WOS:000171343100002 PM 11579344 ER PT J AU Comanor, L Anderson, F Ghany, M Perrillo, R Heathcote, EJ Sherlock, C Zitron, I Hendricks, D Gordon, SC AF Comanor, L Anderson, F Ghany, M Perrillo, R Heathcote, EJ Sherlock, C Zitron, I Hendricks, D Gordon, SC TI Transcription-mediated amplification is more sensitive than conventional PCR-based assays for detecting residual serum HCV RNA at end of treatment SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID C VIRUS-RNA AB OBJECTIVE: In patients chronically infected with hepatitis C virus (HCV) undergoing antiviral therapy, sustained virologic response is suggested by viral clearance by end of treatment (EOT). Viral clearance is defined by nondetection of serum HCV RNA, usually by qualitative PCR-based assays with limits of detection ranging from 100 to 1000 copies/ml. However, some individuals relapse after achieving apparent viral clearance by EOT. These individuals may have low levels of viremia not detected by current PCR methods. The aim of this retrospective study was to determine whether the Bayer HCV RNA Qualitative Assay, which employs Transcription Mediated Amplification (TMA) and detects 50 HCV RNA copies/ml, could detect residual serum HCV RNA in patients who achieved apparent viral clearance by EOT and subsequently relapsed. METHODS: Samples were obtained at EOT (wk 24 or 48) and follow-up (wk 24-26 posttreatment) from 97 patients treated for HCV (78 relapsing patients, 19 sustained responders). All samples in which HCV RNA was not detected by PCR were tested in a blinded manner for HCV RNA by the TMA-based assay. RESULTS: HCV RNA was detected by the TMA-based assay in 27 (34.6%) EOT and 76 (97.4%) follow-up samples from relapsing patients, but not in any of the EOT or follow-up samples from sustained responders. CONCLUSION: Residual serum HCV RNA was detected by the TMA-based assay in EOT samples from 34.6% of patients that had achieved apparent viral clearance by PCR. The detection of HCV RNA by the TMA-based assay could help redefine EOT response and assist in the antiviral management of HCV infection. (Am J Gastroenterol 2001;96:2968-2972. (C) 2001 by Am. Coll. of Gastroenterology). C1 Vancouver Gen Hosp, Vancouver, BC, Canada. NIH, Bethesda, MD 20892 USA. Ochsner Clin & Alton Ochsner Med Fdn, New Orleans, LA USA. Univ Toronto, Toronto, ON, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. William Beaumont Hosp, Royal Oak, MI 48072 USA. Bayer Diagnost, Emeryville, CA USA. RP Comanor, L (reprint author), 1801 Waverley St, Palo Alto, CA 94301 USA. NR 9 TC 48 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2001 VL 96 IS 10 BP 2968 EP 2972 DI 10.1016/S0002-9270(01)03231-2 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 480DC UT WOS:000171445900029 PM 11693334 ER PT J AU Morris, RW Kaplan, NL AF Morris, RW Kaplan, NL TI When is haplotype analysis advantageous for linkage-disequilibrium mapping? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 30 BP 181 EP 181 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900032 ER PT J AU Pugh, EW Witmer, PD Wanyee, JW Fan, YT Ibay, GP Voltz, A Luong, E Goldstein, JL Nussbaum, RL Korczak, JF Kelley, MJ Doheny, KD AF Pugh, EW Witmer, PD Wanyee, JW Fan, YT Ibay, GP Voltz, A Luong, E Goldstein, JL Nussbaum, RL Korczak, JF Kelley, MJ Doheny, KD TI A comparison of single nucleotide polymorphism(SNP) and microsatellite genome scans for May-Hegglin anomaly(MHA). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, CIDR, Baltimore, MD USA. NIH, NHGRI, IDRB, Bethesda, MD 20892 USA. Karmanos Canc Inst, Detroit, MI USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 32 BP 181 EP 181 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900033 ER PT J AU Modi, WS Winkler, C Goedert, JJ Vlahov, D Buchbinder, S Phair, J Donfield, S O'Brien, SJ AF Modi, WS Winkler, C Goedert, JJ Vlahov, D Buchbinder, S Phair, J Donfield, S O'Brien, SJ TI Contrasting genetic influence of alleles in the MCP-1-MCP-3-EOTAXIN chemokine cluster on HIV-1 transmission and AIDS progression. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, AIDS Link Intravenous Experience, Baltimore, MD 21205 USA. San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Rho Inc, Hemophilia Growth & Dev Study, Chapel Hill, NC 27514 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 36 BP 182 EP 182 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900037 ER PT J AU Dennis, KE Fan, T Gelman, T Yan, Q Muegge, K AF Dennis, KE Fan, T Gelman, T Yan, Q Muegge, K TI Targeted deletion of lymphocyte specific helicase (LSH) results in global hypomethylation of the mouse genome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, LMI, Frederick, MD 21701 USA. NCI, LMI, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 48 BP 185 EP 185 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900051 ER PT J AU Lindsay, RS Kobes, S Knowler, WC Hanson, RL AF Lindsay, RS Kobes, S Knowler, WC Hanson, RL TI Genome wide linkage analysis assessing parent-of-origin effects in the inheritance of birth weight. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDDK, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 50 BP 185 EP 185 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900052 ER PT J AU Lieberman, AP Harmison, G Strand, A Olson, J Fischbeck, KH AF Lieberman, AP Harmison, G Strand, A Olson, J Fischbeck, KH TI Altered androgen receptor function caused by polyglutamine expansion. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 63 BP 188 EP 188 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900064 ER PT J AU Krakowiak, PA Wassif, CA Kratz, L Vied, DA Kelley, RI Porter, FD AF Krakowiak, PA Wassif, CA Kratz, L Vied, DA Kelley, RI Porter, FD TI Lathosterol oxidase disruption: A new inborn error of cholesterol biosynthesis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHHD, Heritable Disorders Branch, Unit Mol Dysmorphology, Bethesda, MD 20892 USA. Kennedy Krieger Inst, Baltimore, MD USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 76 BP 190 EP 190 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900077 ER PT J AU Limprasert, P Taylor, JP Leverenz, J Tsuang, D Bonner, L Tanaka, F Biro, TD Sopher, BL La Spada, AR AF Limprasert, P Taylor, JP Leverenz, J Tsuang, D Bonner, L Tanaka, F Biro, TD Sopher, BL La Spada, AR TI Beta-synuclein gene alteration in dementia with Lewy bodies (DLB). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. NIH, NINDS, Bethesda, MD 20892 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Puget Sound VA, Ment Illn Res Ctr, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 106 BP 196 EP 196 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900107 ER PT J AU Suchy, SF Nussbaum, RL AF Suchy, SF Nussbaum, RL TI The deficiency of the ocrl1 PIP2 5-phosphatase in Lowe syndrome affects actin polymerization. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 130 BP 201 EP 201 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900132 ER PT J AU Huusko, P Gillanders, E Vahteristo, P Sarantaus, L Juo, S Kainu, T Rapakko, K Jones, M Markey, C Eerola, H Allinen, M Vehmanen, P Leisti, J Blanco, G Blomqvist, C Trent, J Bailey-Wilson, J Winqvist, R Nevanlinna, H Kallioniemi, O AF Huusko, P Gillanders, E Vahteristo, P Sarantaus, L Juo, S Kainu, T Rapakko, K Jones, M Markey, C Eerola, H Allinen, M Vehmanen, P Leisti, J Blanco, G Blomqvist, C Trent, J Bailey-Wilson, J Winqvist, R Nevanlinna, H Kallioniemi, O TI Genome-wide scanning for linkage in Finnish breast cancer families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. NIH, NHGRI, Inherited Dis Res Branch, Bethesda, MD 20892 USA. Columbia Genome Ctr, New York, NY USA. Oulu Univ Hosp, Dept Clin Genet, Oulu, Finland. Oulu Univ Hosp, Dept Oncol, Oulu, Finland. Univ Oulu, Oulu, Finland. Univ Helsinki, Cent Hosp, Dept Obstet Gynecol, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 149 BP 205 EP 205 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900149 ER PT J AU Tsai, YY McGlynn, KA Cassidy, AB Hu, Y Arnold, J Engstrom, PF Buetow, KH AF Tsai, YY McGlynn, KA Cassidy, AB Hu, Y Arnold, J Engstrom, PF Buetow, KH TI Dietary patterns and genetic susceptibility to lung cancer risk. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. DCEG, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 155 BP 206 EP 206 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900155 ER PT J AU Jackson, L Bianchi, D Simpson, J Elias, S Holzgreve, W Evans, M Dukes, K Sullivan, L Klinger, K Bischoff, F Hahn, S Johnson, K Lewis, D Wapner, R Dela Cruz, F AF Jackson, L Bianchi, D Simpson, J Elias, S Holzgreve, W Evans, M Dukes, K Sullivan, L Klinger, K Bischoff, F Hahn, S Johnson, K Lewis, D Wapner, R Dela Cruz, F CA NICHD Fetal Cell Isolat Study TI Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY 1 data. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Illinois, Chicago, IL USA. Univ Basel, CH-4003 Basel, Switzerland. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. DM Stat, Medford, MA USA. Genzyme, Boston, MA USA. NICHHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 161 BP 207 EP 207 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900160 ER PT J AU Hull, SC Gooding, H Warshauer-Baker, E Metosky, S Hurley, E Gutter, E Wilfond, B AF Hull, SC Gooding, H Warshauer-Baker, E Metosky, S Hurley, E Gutter, E Wilfond, B TI Variations in informed consent practices for genetic research. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Med Genet Branch, Bioeth Res Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 168 BP 209 EP 209 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900171 ER PT J AU Baig, MN Shukaliak, J Yao, K Ludwin, S Muraro, P Martin, R McFarland, H Ito, K AF Baig, MN Shukaliak, J Yao, K Ludwin, S Muraro, P Martin, R McFarland, H Ito, K TI Selection and encephalitogenic potential of T-cells specific for myelin basic protein peptide [amino acids 111-129] using transgenic mouse with HLA-DRB1*0401-IE and chimeric human T cell receptor. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Howard Univ, Dept Genet, Washington, DC 20059 USA. NINCDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Queens Univ, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 182 BP 211 EP 211 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900183 ER PT J AU Arikawa-Hirasawa, E Le, AH Nishino, I Nonaka, I Ho, NC Francomano, CA Govindra, P Hassell, J Devaney, JM Spranger, J Stevenson, RE Iannaccone, S Dalakas, MC Yamada, Y AF Arikawa-Hirasawa, E Le, AH Nishino, I Nonaka, I Ho, NC Francomano, CA Govindra, P Hassell, J Devaney, JM Spranger, J Stevenson, RE Iannaccone, S Dalakas, MC Yamada, Y TI Mutations in the perlecan gene of Schwartz-Jampel syndrome: critical role of perlecan in neuromuscular junction functions. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. Natl Inst Neurosci, Kodaira, Tokyo, Japan. NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Bayview Med Ctr, Baltimore, MD USA. Shriners Hosp Children, Tampa, FL USA. Med Genet Res Ctr, Washington, DC USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. NINCDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 186 BP 212 EP 212 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900187 ER PT J AU Scott, LJ Watanabe, RM Silander, K Mohlke, KL Stringham, HM Li, C Doheny, K Pugh, E Valle, TT Bergman, RN Tuomilehto, J Collins, F Boehnke, M AF Scott, LJ Watanabe, RM Silander, K Mohlke, KL Stringham, HM Li, C Doheny, K Pugh, E Valle, TT Bergman, RN Tuomilehto, J Collins, F Boehnke, M TI Quantitative trait loci (QTL) genome scan in two independent sets of Finnish affected sibling pair families with type 2 diabetes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. NIH, NHGRI, Bethesda, MD USA. Johns Hopkins Univ, CIDR, Bethesda, MD USA. Natl Publ Hlth Inst, Dept Epidemiol Hlth Promot, Helsinki, Finland. Univ So Calif, Keck Sch Med, Dept Physiol Biophys, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 196 BP 214 EP 214 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900197 ER PT J AU Huizing, M Anikster, Y White, J Shevchenko, Y Fitzpatrick, D Touchman, J Compton, J Bale, S Swank, R Toro, J Gahl, W AF Huizing, M Anikster, Y White, J Shevchenko, Y Fitzpatrick, D Touchman, J Compton, J Bale, S Swank, R Toro, J Gahl, W TI Mutations in a novel gene, SUTAL, cause a unique form of Hermansky-Pudlak syndrome HPS-3. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. ISC, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 211 BP 217 EP 217 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900210 ER PT J AU Srivastava, A Durmowicz, M Hurtung, A Hudson, J Ouztsi, L Donovan, D Cui, C Schlessinger, D AF Srivastava, A Durmowicz, M Hurtung, A Hudson, J Ouztsi, L Donovan, D Cui, C Schlessinger, D TI Ectodysplasin-A1 is sufficient to rescue both hair growth and sweat glands in Tabby mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Greenwood Genet Ctr, J C Self Res Inst Human Genet, Greenwood, SC 29646 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 213 BP 218 EP 218 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900214 ER PT J AU Maglott, DR Agarwala, R Chen, HC Chetvernin, S Church, D Ermolaeva, O Jang, W Kitts, P Kans, J Lipman, D Ostell, J Pruitt, K Resenchuk, S Schuler, G Sherry, S Tatusova, T Wheelan, S AF Maglott, DR Agarwala, R Chen, HC Chetvernin, S Church, D Ermolaeva, O Jang, W Kitts, P Kans, J Lipman, D Ostell, J Pruitt, K Resenchuk, S Schuler, G Sherry, S Tatusova, T Wheelan, S TI NCBI's genome annotation projects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 220 BP 219 EP 219 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900222 ER PT J AU Slavotinek, AM Al-Gazali, L Hennekam, R Schrander-Stumpel, C Orcana-Losa, M Cantani, A Capellini, Q Neri, G Zackai, E Biesecker, LG AF Slavotinek, AM Al-Gazali, L Hennekam, R Schrander-Stumpel, C Orcana-Losa, M Cantani, A Capellini, Q Neri, G Zackai, E Biesecker, LG TI Genetic heterogeneity of McKusick-Kaufman syndrome (MKS) and Bardet-Biedl syndrome (BBS) phenotypes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. United Arab Emirates Univ, Al Ain, U Arab Emirates. Univ Amsterdam Hosp, Amsterdam, Netherlands. Univ Maastricht, Maastricht, Netherlands. Univ Reina Sofia, Cordoba, Spain. Univ Roma La Sapienza, Rome, Italy. Osped Ninetto Melli, Brindisi, Italy. Univ Cattolica Sacro Cuore, Rome, Italy. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 229 BP 221 EP 221 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900229 ER PT J AU Turner, JT Cohen, MM Blesecker, LG AF Turner, JT Cohen, MM Blesecker, LG TI Natural history and complications in Proteus syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD 20892 USA. Dalhousie Univ, Halifax, NS B3H 3J5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 227 BP 221 EP 221 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900228 ER PT J AU Schiffmann, R Kopp, JB Moore, DF Weibel, T Charria, G Brady, RO AF Schiffmann, R Kopp, JB Moore, DF Weibel, T Charria, G Brady, RO TI Efficacy and safety of prolonged enzyme replacement therapy for Fabry disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINCDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 234 BP 222 EP 222 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900236 ER PT J AU Biesecker, BB Peters, KF Kong, F AF Biesecker, BB Peters, KF Kong, F TI Adults with Marfan syndrome: Sexual functioning and reproduction. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. Westat Res Inc, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 240 BP 223 EP 223 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900242 ER PT J AU Chretien, J Coresh, J Fink, NE Klag, MJ Marcovina, SM Smith, MW AF Chretien, J Coresh, J Fink, NE Klag, MJ Marcovina, SM Smith, MW TI A theoretical framework for Mapping by Admixture Linkage Disequilibrium (MALD) with application to Lipoprotein(a) [Lp(a)] in African-Americans (AAs). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. NCI, Frederick, MD 21701 USA. RI Smith, Michael/B-5341-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 260 BP 227 EP 227 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900262 ER PT J AU Brown, TC Yonescu, R Reppert, T Knutsen, T Ried, T Kirsch, IR AF Brown, TC Yonescu, R Reppert, T Knutsen, T Ried, T Kirsch, IR TI The Cancer Chromosome Aberration Project (CCAP): An update. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 288 BP 233 EP 233 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900291 ER PT J AU Knutsen, T Augustus, M Gobu, V Padilla-Nash, H Schrock, E Shenmen, C Plotkin, J Greenhut, S Kriebel, J Sirotkin, K Ried, T AF Knutsen, T Augustus, M Gobu, V Padilla-Nash, H Schrock, E Shenmen, C Plotkin, J Greenhut, S Kriebel, J Sirotkin, K Ried, T TI The NCI and NCBISKY/CGH interactive online database. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NCI, Genet Branch, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 299 BP 235 EP 235 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900300 ER PT J AU Matyakhina, LD Pack, SD Pak, E Jaikumar, J Mannan, P Kirschner, LS Stratakis, CA AF Matyakhina, LD Pack, SD Pak, E Jaikumar, J Mannan, P Kirschner, LS Stratakis, CA TI Carney complex: Cytogenetic analysis of tumors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, DEB, Bethesda, MD USA. NINCDS, SNB, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 329 BP 240 EP 240 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900330 ER PT J AU Goldstein, AM Liu, L Shennan, MG Hogg, D Tucker, MA Struewing, JP AF Goldstein, AM Liu, L Shennan, MG Hogg, D Tucker, MA Struewing, JP TI A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Toronto Sunnybrook Reg Canc Ctr, Dept Med Oncol, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 363 BP 246 EP 246 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900366 ER PT J AU Kingman, A Hemminki, K Dong, C Shugart, Y AF Kingman, A Hemminki, K Dong, C Shugart, Y TI Is there an association between Hodgkin's disease and increased risk of general cancer? - Results from a Swedish population based case-control study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDR, Bethesda, MD 20892 USA. Karolinska Inst, Novum, Dept Biosci, Huddinge, Sweden. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 396 BP 251 EP 251 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900395 ER PT J AU Stratakis, CA Carney, JA AF Stratakis, CA Carney, JA TI A new syndrome associated with autosomal dominant inheritance of familial paraganglioma and gastric stromal sarcoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, UGEN, Bethesda, MD 20892 USA. NIH, NICHD, DEB, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 413 BP 254 EP 254 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900415 ER PT J AU Vahteristo, P Bartek, J Bartkova, J Ojala, S Eerola, H Kononen, J Heikkila, P Kallioniemi, O Nevanlinna, H AF Vahteristo, P Bartek, J Bartkova, J Ojala, S Eerola, H Kononen, J Heikkila, P Kallioniemi, O Nevanlinna, H TI CHK2 in familial breast cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Helsinki, Cent Hosp, Helsinki, Finland. Danish Canc Soc, Inst Canc Biol, Copenhagen, Denmark. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA. Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011; Bartek, Jiri/G-5870-2014 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 427 BP 256 EP 256 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900428 ER PT J AU Shanmugarajah, D Lipkin, SM Hacia, JG Hunt, N Fodor, SPA Collins, FS AF Shanmugarajah, D Lipkin, SM Hacia, JG Hunt, N Fodor, SPA Collins, FS TI A novel high-density oligonucleoticle array for hereditary non-polyposis colon cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Univ So Calif, Los Angeles, CA USA. Affymetrix Corp, Santa Clara, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 431 BP 257 EP 257 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900433 ER PT J AU Crabtree, JS Ward, JM Garrett-Beal, L Scacheri, PC Hagar, J Inoue, M Hanahan, D Edlund, H Chandrasekharappa, SC Marx, SJ Spiegel, AM Collins, FS AF Crabtree, JS Ward, JM Garrett-Beal, L Scacheri, PC Hagar, J Inoue, M Hanahan, D Edlund, H Chandrasekharappa, SC Marx, SJ Spiegel, AM Collins, FS TI A conditional mouse knockout model of MEN1 develops pancreatic tumors when crossed with transgenic lines expressing Cre from the insulin promoter. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Frederick, MD 21701 USA. Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA. Umea Univ, Dept Microbiol, S-90187 Umea, Sweden. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 448 BP 260 EP 260 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900447 ER PT J AU Sandrini, F Kirschner, LS Carney, AJ Stratakis, CA AF Sandrini, F Kirschner, LS Carney, AJ Stratakis, CA TI Assessment of Protein Kinase A subunits expression in normal adrenal cortex and primary pigmented adrenocortical disease from patients with and without Carney Complex and PRKAR1A mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, UGEN, DEB, NIH, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 449 BP 260 EP 260 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900450 ER PT J AU Juo, SH AF Juo, SH CA Nordic NHGRI Breast Canc Consortiu TI Linkage of hereditary breast cancer families to a novel focus at 13q21-q22: subgroup analyses and further exclusion of BRCA2 involvement. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Columbia Univ, Genome Ctr, New York, NY USA. NIH, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. Univ Tampere, Helsinki, Finland. Univ Lund Hosp, S-22185 Lund, Sweden. Univ Hosp Iceland, Reykjavik, Iceland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 453 BP 261 EP 261 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900455 ER PT J AU Baser, ME Parry, DM Friedman, JM Wallace, A Gillespie, J Evans, DGR AF Baser, ME Parry, DM Friedman, JM Wallace, A Gillespie, J Evans, DGR TI Spinal tumor genotype-phenotype correlation in neurofibromatosis 2. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. St Marys Hosp, Dept Med Genet, Manchester M13 0JH, Lancs, England. Manchester Royal Infirm, Dept Radiol, Manchester M13 9WL, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 468 BP 263 EP 263 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900466 ER PT J AU Tseng, TL Chen, YM Shin, YP Buetow, KH AF Tseng, TL Chen, YM Shin, YP Buetow, KH TI Genotypic and phenotypic characterization of a putative tumor suppressor gene GNMT in liver cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Inst Publ Hlth, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 471 BP 264 EP 264 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900473 ER PT J AU Chang, BL Zheng, SL Hawkins, GA Isaacs, SD Wiley, KE Turner, A Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, J AF Chang, BL Zheng, SL Hawkins, GA Isaacs, SD Wiley, KE Turner, A Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, J TI Association between CYP3AP1 gene polymorphisms and the risk for hereditary prostate cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 479 BP 265 EP 265 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900480 ER PT J AU Hawkins, GA Zheng, SL Cramer, S Isaacs, SD Wiley, KE Chang, BL Mychaleckyj, J Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, J AF Hawkins, GA Zheng, SL Cramer, S Isaacs, SD Wiley, KE Chang, BL Mychaleckyj, J Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, J TI Mutation screen and association test of 1-a-hydroxylase gene in prostate cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 480 BP 265 EP 265 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900478 ER PT J AU Zheng, S Hawkins, GA Mychaleckyj, J Isaacs, SD Wiley, KE Turner, AR Chang, BL Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, J AF Zheng, S Hawkins, GA Mychaleckyj, J Isaacs, SD Wiley, KE Turner, AR Chang, BL Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB Xu, J TI Mutation screen and association test of DLC1 gene in hereditary and sporadic prostate cancer patients SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 481 BP 265 EP 265 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900481 ER PT J AU King, MC Wieand, HS Hale, K Walsh, T Owens, KM Lee, MK Costantino, JP Fisher, B AF King, MC Wieand, HS Hale, K Walsh, T Owens, KM Lee, MK Costantino, JP Fisher, B CA NSABP Investigators TI Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: A genomic resequencing study in the NSABP-P1 Breast Cancer Prevention Trial (BCPT). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Genom Sci, Seattle, WA USA. Univ Pittsburgh, NSABP, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 518 BP 272 EP 272 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900518 ER PT J AU Brown, KM MacDonald, TJ LaFleur, B Peterson, K Lawlor, C Chen, Y Packer, RJ Cogen, P Stephan, DA AF Brown, KM MacDonald, TJ LaFleur, B Peterson, K Lawlor, C Chen, Y Packer, RJ Cogen, P Stephan, DA TI Expression profiling of medulloblastoma: identification of therapeutic targets for metastatic disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC USA. Vanderbilt Univ, Dept Prevent Med, Div Biostat, Nashville, TN USA. NIH, NHGRI, Bethesda, MD USA. RI MacDonald, Tobey/D-4554-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 528 BP 273 EP 273 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900526 ER PT J AU Protopopov, A Li, J Kashuba, V Dreijerink, K Braga, E Kuzmin, I Lerman, M Zabarovsky, E AF Protopopov, A Li, J Kashuba, V Dreijerink, K Braga, E Kuzmin, I Lerman, M Zabarovsky, E TI Tetracycline-regulated expression of the candidate tumor suppressor gene, RASSF1A, from a frequently affected chromosomal region 3p21.3. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. NCI, SAIC, Lab Immunobiol & Intramural Res Support Program, Frederick, MD USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow, Russia. RI Zabarovsky, Eugene/A-6645-2010; Braga, Eleonora/P-5574-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 526 BP 273 EP 273 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900525 ER PT J AU Moslehi, R Modugno, F Ness, R Narod, S AF Moslehi, R Modugno, F Ness, R Narod, S TI Reproductive factors and ovarian cancer risk in Jewish BRCA1 and BRCA2 mutation carriers. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 534 BP 274 EP 274 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900532 ER PT J AU Lacbawan, FL Davis, RL Collins, GH Kent, P Holohan, PD Shrimpton, AE Muenke, M Krasnewich, D AF Lacbawan, FL Davis, RL Collins, GH Kent, P Holohan, PD Shrimpton, AE Muenke, M Krasnewich, D TI Familial encephalopathy with neuroserpin inclusion bodies (FENIB): Initial clinical characterization of the PI12(Syracuse) (S49P) mutation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. SUNY Syracuse, Dept Pathol, Syracuse, NY USA. SUNY Syracuse, Dept Pharmacol, Syracuse, NY USA. SUNY Syracuse, Dept Neurol, Syracuse, NY USA. NIH, Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 570 BP 281 EP 281 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900572 ER PT J AU Berg, J Porteous, M Reinhardt, D Holloway, S Gallione, C Lux, A McKinnon, W Guttmacher, A Marchuk, D AF Berg, J Porteous, M Reinhardt, D Holloway, S Gallione, C Lux, A McKinnon, W Guttmacher, A Marchuk, D TI Hereditary Haemorrhagic Telangiectasia - delineation of the different phenotypes caused by endoglin and ALK1 mutation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 GKT, Sch Med, Div Med & Mol Genet, London, England. Western Gen Hosp, SE Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. Duke Univ, Sch Med, Dept Genet, Durham, NC 27706 USA. Inst Mol Biol Zelikulturtech, Mannheim, Germany. Vermont Reg Genet Ctr, Burlington, VT USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 584 BP 283 EP 283 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900585 ER PT J AU Hay, BN Davis, J Darnell, D Karp, B Martin, JE Solomon, BI Turner, ML Puck, JM Holland, SM AF Hay, BN Davis, J Darnell, D Karp, B Martin, JE Solomon, BI Turner, ML Puck, JM Holland, SM TI A novel syndrome of elevated serum IgE, recurrent infections, vasculitis, and neurocognitive impairment with myoclonus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Genet & Mol Biol Branch, Bethesda, MD USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIH, NINDS, Bethesda, MD USA. Johns Hopkins Bayview Med Ctr, Dept Internal Med, Baltimore, MD USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIH, NCI, Bethesda, MD USA. NIH, NIAID, Host Def Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 712 BP 304 EP 304 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900712 ER PT J AU Ng, D Hadley, D Tifft, C Biesecker, L AF Ng, D Hadley, D Tifft, C Biesecker, L TI Genetic heterogeneity of X-linked recessive microphthalmia-anophthalmia with mental retardation: is Lenz syndrome a single disorder? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NIH, NIDDKD, Genet Dev & Dis Branch, Bethesda, MD USA. NIH, NHGRI, Genet Dis Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 745 BP 310 EP 310 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900744 ER PT J AU Jang, W Chen, HC Yonescu, R Cheung, V Nowak, N Trask, BJ Kirsch, I Ried, T Schuler, GD AF Jang, W Chen, HC Yonescu, R Cheung, V Nowak, N Trask, BJ Kirsch, I Ried, T Schuler, GD TI Integrating the cytogenetic map with the draft human genome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD USA. NIH, Natl Canc Inst, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 746 BP 311 EP 311 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900746 ER PT J AU Cosentino, L Marchetti, F Mabery, S Bishop, J Wyrobek, AJ AF Cosentino, L Marchetti, F Mabery, S Bishop, J Wyrobek, AJ TI Paternal exposure to cyclophosphamide induces chromosomal damage and differential DNA repair gene expression in mouse zygotes and 2-cell embryos. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. NIEHS, Expt Carcinogenesis & Mutagenesis Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 787 BP 317 EP 317 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900787 ER PT J AU Lipkin, SM Wang, V Shanmugarajah, D Cheng, J Pam, E Thomas, J Green, E Touchman, J Collins, F Cohen, P AF Lipkin, SM Wang, V Shanmugarajah, D Cheng, J Pam, E Thomas, J Green, E Touchman, J Collins, F Cohen, P TI A targeted ablation of the Mlh3 locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 804 BP 320 EP 320 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900802 ER PT J AU Wattendorf, C Krasnewich, D Smith, A Meck, J Trent, J Dennis, T AF Wattendorf, C Krasnewich, D Smith, A Meck, J Trent, J Dennis, T TI Partial 9p monosomy in a child with a der(9)t(9;11)(p24;p15.4) identified by chromosome microdissection. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 873 BP 332 EP 332 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900875 ER PT J AU dela Cruz, JM Roessler, E Bamford, RN Burdine, RD Donnai, D Schier, AF Muenke, M AF dela Cruz, JM Roessler, E Bamford, RN Burdine, RD Donnai, D Schier, AF Muenke, M TI Loss-of-function mutation in the CFC domain of TDGF-1 is associated with human forebrain defects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NYU, Skirball Inst Biomol Med, New York, NY USA. St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 937 BP 343 EP 343 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900938 ER PT J AU Galaviz-Hernandez, C Tanaka, T Ko, M Uda, K Schlessinger, D Nagaraja, R AF Galaviz-Hernandez, C Tanaka, T Ko, M Uda, K Schlessinger, D Nagaraja, R TI In search of placenta-specific genes and promoter elements. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, Genet Lab, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 941 BP 344 EP 344 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900943 ER PT J AU Herrera, LM Ko, MSH Schlessinger, D AF Herrera, LM Ko, MSH Schlessinger, D TI Differential gene expression in nascent and mature mouse ovary assessed by 15k cDNA microarray. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 946 BP 345 EP 345 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900946 ER PT J AU Jaradat, SA Yokota, T Ko, MSH AF Jaradat, SA Yokota, T Ko, MSH TI Refinement of LIF-STAT-3 pathway using microarray analysis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 948 BP 345 EP 345 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900947 ER PT J AU Schimmenti, LA Karkera, JD dela Cruz, J Tran, H Manligas, GS Roessler, E Muenke, M AF Schimmenti, LA Karkera, JD dela Cruz, J Tran, H Manligas, GS Roessler, E Muenke, M TI Developmental candidates for ocular colobomas: VAX1, VAX2 and SHH. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. NIH, Med Genet Branch, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 962 BP 347 EP 347 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900960 ER PT J AU Pshezhetsky, A Lukong, KE Landry, K Trudel, S Seyrantepe, V Ahmed, A Gahl, WA Lefrancois, S Morales, CR AF Pshezhetsky, A Lukong, KE Landry, K Trudel, S Seyrantepe, V Ahmed, A Gahl, WA Lefrancois, S Morales, CR TI Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Hop St Justine, Dept Med Genet, Montreal, PQ, Canada. McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada. NIH, NICHD, Heritable Disorders Branch, Bethesda, MD USA. RI Morales, Carlos/H-1055-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 970 BP 349 EP 349 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900970 ER PT J AU Prasad, NB Novotny, EA Crabtree, JS Elkahloun, AG Marx, SJ Spiegel, AM Collins, FS Chandrasekharappa, SC AF Prasad, NB Novotny, EA Crabtree, JS Elkahloun, AG Marx, SJ Spiegel, AM Collins, FS Chandrasekharappa, SC TI Microarray based expression analysis of mouse cells that lack or overexpress menin. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 986 BP 351 EP 351 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900984 ER PT J AU Wheelan, SJ Church, DM Ostell, JM AF Wheelan, SJ Church, DM Ostell, JM TI Spidey: An mRNA-to-genomic alignment program. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 998 BP 353 EP 353 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648900996 ER PT J AU Lu, K Lee, MH Hazard, S Brooks-Wilson, A Salen, G Dean, M Srivastava, A Patel, SB AF Lu, K Lee, MH Hazard, S Brooks-Wilson, A Salen, G Dean, M Srivastava, A Patel, SB TI Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2 encoded by ABCG5 and ABCG8 respectively. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, BioMol Comp Resource, Charleston, SC 29425 USA. Xenon Genet Inc, Vancouver, BC V6T 1Z3, Canada. Univ Med & Dent New Jersey, Div Gastroenterol, Newark, NJ 07018 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Greenwood Genet Ctr, J C Self Res Inst Human Genet, Greenwood, SC 29646 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1030 BP 359 EP 359 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901030 ER PT J AU Aerbajinai, W Miller, JL AF Aerbajinai, W Miller, JL TI Cloning and characterization of a novel apoptosis-associated gene expressed during erythroid cell differentiation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDDK, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1039 BP 360 EP 360 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901040 ER PT J AU Chae, JJ Komarow, H Wood, G Liu, PP Kastner, DL AF Chae, JJ Komarow, H Wood, G Liu, PP Kastner, DL TI The mouse homolog of pyrin, the FMF protein, regulates cytokine production and apoptosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Genet & Mol Biol Branch, Oncogenesis & Dev Sect, Bethesda, MD 20892 USA. NIH, NIAMS, Rheumat Dis Genet & Genom Branch, Inflammatory Biol Sect, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1041 BP 360 EP 360 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901041 ER PT J AU Hsu, AP Anderson, SM Buckley, R Candotti, F Uzel, G Puck, JM AF Hsu, AP Anderson, SM Buckley, R Candotti, F Uzel, G Puck, JM TI Genotypic diagnosis of T-B+ SCID by functional assay. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NIH, NHGRI, GMBB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1042 BP 361 EP 361 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901042 ER PT J AU Torosyan, Y Wood, G Raben, N Mansfield, E Kastner, DL AF Torosyan, Y Wood, G Raben, N Mansfield, E Kastner, DL TI Transfection of MEFV, the gene causing Familial Mediterranean Fever, induces alterations in arachidonate lipoxygenation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1059 BP 363 EP 363 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901059 ER PT J AU Yan, B Raben, N Plotz, P AF Yan, B Raben, N Plotz, P TI Hes-1, a known transcriptional repressor, functions as a transcriptional activator for the human acid a-glucosidase gene in human fibroblast cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIAMS, Arthritis Rheumat Br, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1076 BP 366 EP 366 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901074 ER PT J AU Wen, J Noguchi, T Shigematsu, K AF Wen, J Noguchi, T Shigematsu, K TI Tal1 binding to centromeric satellite DNA: A new role for Tal1 in transcription repression. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDDK, LCB, Bethesda, MD USA. Lawrence Berkeley Natl Lab, Dept Cell & Mol Biol, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1078 BP 367 EP 367 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901078 ER PT J AU Shoham, NG Mansfield, E Wood, G Centola, M Kastner, DL AF Shoham, NG Mansfield, E Wood, G Centola, M Kastner, DL TI The FMF protein, pyrin, specifically interacts with the SH3 domain of the cytoskeletal protein PSTPIP1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMSD, Inflammatory Biol Sect, Rheumat Dis Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1100 BP 370 EP 370 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901098 ER PT J AU Hott, AM Huether, CA McInerney, J Bender, H Christianson, C Jenkins, J Wysocki, A Markle, G Karp, R Fowler, R AF Hott, AM Huether, CA McInerney, J Bender, H Christianson, C Jenkins, J Wysocki, A Markle, G Karp, R Fowler, R TI Theory and practice in teaching human genetics to undergraduate, non-science majors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Cincinnati, Cincinnati, OH 45221 USA. Natl Col Hlth Prof Ed Gen, Baltimore, MD USA. Univ Notre Dame, Notre Dame, IN 46556 USA. Swarthmore Coll, Swarthmore, PA 19081 USA. NINR, Bethesda, MD 20892 USA. San Jose State Univ, San Jose, CA 95192 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1151 BP 379 EP 379 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901152 ER PT J AU Gooding, HC Wilfond, B Boehm, K Biesecker, BB AF Gooding, HC Wilfond, B Boehm, K Biesecker, BB TI Unintended messages: The ethics of teaching genetic "dilemmas". SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NIDCR, Off Commun & Educ, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1155 BP 380 EP 380 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901157 ER PT J AU Justice, CM Miller, NH Marosy, B Zhang, J Pugh, EW Wilson, AF AF Justice, CM Miller, NH Marosy, B Zhang, J Pugh, EW Wilson, AF TI Genetic heterogeneity comprising both X-linked and autosomal dominant forms of inheritance in families with familial idoiopathic scoliosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Genometr Sect, Baltimore, MD USA. Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Genet, Baltimore, MD USA. Johns Hopkins Univ, CIDR, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1179 BP 384 EP 384 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901177 ER PT J AU Peila, R Rodriguez, BL Launer, LJ AF Peila, R Rodriguez, BL Launer, LJ TI Type 2 diabetes, APOE gene and the risk for dementia and dementia related pathologies. The Honolulu-Asia Aging Study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Hawaii Manoa, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1186 BP 385 EP 385 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901186 ER PT J AU Struewing, JP Rutter, JL Davila, MR Smith, AM Greene, MH Tucker, MA AF Struewing, JP Rutter, JL Davila, MR Smith, AM Greene, MH Tucker, MA TI Mutation analysis of the BRCA1-interacting genes ZBRK1 and BRIP1 among BRCA1/2-negative probands from breast/ovarian cancer families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1230 BP 393 EP 393 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901232 ER PT J AU de Andrade, M Slusser, J Amos, CI Bailey-Wilson, J Fain, P Anderson, MW Petersen, G AF de Andrade, M Slusser, J Amos, CI Bailey-Wilson, J Fain, P Anderson, MW Petersen, G TI Linkage simulation enhances decision making strategies for study of lung cancer (LC) pedigrees. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NGHRI, Bethesda, MD USA. Univ Colorado, Boulder, CO 80309 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1251 BP 396 EP 396 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901249 ER PT J AU Gill, SP Leyne, M Mull, J Cuajungco, MP Robbins, CM Makalowska, I Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA AF Gill, SP Leyne, M Mull, J Cuajungco, MP Robbins, CM Makalowska, I Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA TI Survey of Ashkenazi Jewish SNPs in a 471 kb region of chromosome 9q31 as compared to the public SNP database (dbSNP). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Inst Human Genet, Boston, MA USA. NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RI Brownstein, Michael/B-8609-2009; Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1264 BP 398 EP 398 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901264 ER PT J AU Clark, VJ Peterson, RJ Dean, M AF Clark, VJ Peterson, RJ Dean, M TI Haplotype analysis of chemokine and chemokine receptor polymorphisms. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Genom Divers, Frederick, MD 21701 USA. Penn State Univ, InterColl Grad Program Genet, University Pk, PA 16802 USA. Celadon Labs Inc, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1265 BP 399 EP 399 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901265 ER PT J AU Xu, K Mangal, W Nagarajan, S Ferro, E Liu, XH Goldman, D AF Xu, K Mangal, W Nagarajan, S Ferro, E Liu, XH Goldman, D TI COMT haplotype relative risk for substance dependence in four populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Inst Alcoholism, Neurogenet Lab, Rockville, MD 20852 USA. W China Univ Med Sci, Dept Psychiat, Sichuan 610041, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1290 BP 403 EP 403 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901292 ER PT J AU Papanicolaou, GJ Siffert, W Platte, P Stunkard, AJ Francomano, C Wilson, AF AF Papanicolaou, GJ Siffert, W Platte, P Stunkard, AJ Francomano, C Wilson, AF TI An association of the G protein beta 3 subunit C825T polymorphism and systolic blood pressure in the Old-Order Amish using a regression of offspring on one parent (ROOP) method. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Genom Sect, Baltimore, MD USA. NHGRI, Baltimore, MD USA. IDRB, Baltimore, MD USA. Univ Essen Gesamthsch Klinikum, Dept Pharmacol, D-4300 Essen, Germany. Univ Trier, Ctr Psychobiol & Psychosomat Res, D-54286 Trier, Germany. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NIH, NIA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1296 BP 404 EP 404 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901298 ER PT J AU Arcos-Burgos, M Castellanos, FX Lopera, F Pineda, D Palacio, LG Berg, K Bailey-Wilson, J Muenke, M AF Arcos-Burgos, M Castellanos, FX Lopera, F Pineda, D Palacio, LG Berg, K Bailey-Wilson, J Muenke, M TI Attention-Deficit/Hyperactivity Disorder (ADHD): Power simulations to detect linkage in extended pedigrees in the Paisa community of Colombia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Antioquia, Medellin, Colombia. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1341 BP 411 EP 411 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901339 ER PT J AU Yao, Y Sorant, A Wilson, A AF Yao, Y Sorant, A Wilson, A TI A comparison of the power of the variance components method and revised Haseman-Elston method in the presence and absence of non-random ascertainment. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NHGRI, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1347 BP 412 EP 412 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901345 ER PT J AU Rutter, JL Chatterjee, N Wacholder, S Struewing, J AF Rutter, JL Chatterjee, N Wacholder, S Struewing, J TI Effect of the Her2 V655I polymorphism on breast cancer risk in BRCA1/2 mutation positive and negative families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1402 BP 421 EP 421 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901402 ER PT J AU Pollin, TI Agarwala, R Schaffer, AA Lodge, AL King, TM Shuldiner, AR Mitchell, BD AF Pollin, TI Agarwala, R Schaffer, AA Lodge, AL King, TM Shuldiner, AR Mitchell, BD TI Fecundity is a familial trait in the Old Order Amish. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Maryland, Baltimore, MD 21201 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Univ Texas, Houston, TX USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1405 BP 422 EP 422 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901404 ER PT J AU O'Neill, SM Vogel, VG Feingold, E Ferrell, RE Peters, JA Rubinstein, WS AF O'Neill, SM Vogel, VG Feingold, E Ferrell, RE Peters, JA Rubinstein, WS TI Risk-based referral to a clinical cancer genetics program: a study paralleling the real world of non-research covered service. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UPCI, Magee Womens Hosp, Comprehens Breast Program, Pittsburgh, PA USA. UPCI, Magee Womens Hosp, Canc Genet Program, Pittsburgh, PA USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. NCI, Clin Genet Branch, Rockville, MD USA. Northwestern Univ, Sch Med, Evanston NW Healthcare, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1442 BP 429 EP 429 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901441 ER PT J AU Terry, SF Cody, J Lewis, J Terry, PF Nelson, LM Davidson, ME AF Terry, SF Cody, J Lewis, J Terry, PF Nelson, LM Davidson, ME TI Catalyst for advancing research: Collaborations among industry, academia and consumer organizations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 PXE Int Inc, Sharon, MA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Genet Alliance, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1477 BP 435 EP 435 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901479 ER PT J AU Teslovich, TM McKeane, DP Pearson, KE Francomano, A Hotchkiss, R Stephan, DA AF Teslovich, TM McKeane, DP Pearson, KE Francomano, A Hotchkiss, R Stephan, DA TI The skeletal genome anatomy project (SGAP). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. NIH, NIA, Bethesda, MD 20892 USA. OrthoGene Inc, New York, NY 10021 USA. Hosp Special Surg, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1585 BP 453 EP 453 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901587 ER PT J AU Xiang, C Chen, M Brownstein, M AF Xiang, C Chen, M Brownstein, M TI New labeling method for microarray hybridization detection. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. RI Brownstein, Michael/B-8609-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1619 BP 458 EP 458 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901619 ER PT J AU Xu, Z Jia, L Eng, K Xia, C Jablons, D AF Xu, Z Jia, L Eng, K Xia, C Jablons, D TI Full-length cDNA cloning of tissue specific expressed sequence tags. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1653 BP 464 EP 464 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901654 ER PT J AU Zhu, G Lipsky, RH Xu, K Akhtar, LA Jenkins, GL Goldman, D AF Zhu, G Lipsky, RH Xu, K Akhtar, LA Jenkins, GL Goldman, D TI Transcribed single nucleotide polymorphisms as markers for screening genomic imprinting. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIAAA, Neurogenet Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1666 BP 466 EP 466 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901664 ER PT J AU Goker-Alpan, O Park, JK Schiffmann, R Orvisky, E Stubblefield, BK Tayebi, N Sidransky, E AF Goker-Alpan, O Park, JK Schiffmann, R Orvisky, E Stubblefield, BK Tayebi, N Sidransky, E TI Are type 2 and type 3 Gaucher disease a continuum? An intermediate phenotype. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, NSB, NIH, Bethesda, MD 20892 USA. NINCDS, DMMP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1727 BP 477 EP 477 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901729 ER PT J AU Fitzpatrick, DL Huizing, M Anikster, Y Hurvitz, H Klar, A Gross-Kieselstein, E Gahl, WA AF Fitzpatrick, DL Huizing, M Anikster, Y Hurvitz, H Klar, A Gross-Kieselstein, E Gahl, WA TI Evidence that rab27a mutations are associated with neurological involvement, not simply the hemophagocytic syndrome, in patients with Griscelli syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, HDB, Bethesda, MD 20892 USA. Bikur Cholim Hosp, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1735 BP 478 EP 478 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901736 ER PT J AU Sidransky, E Schiffmann, R Tayebi, N Krasnewich, D Stubblefield, BK Vortmeyer, AO Wong, K AF Sidransky, E Schiffmann, R Tayebi, N Krasnewich, D Stubblefield, BK Vortmeyer, AO Wong, K TI Gaucher disease and parkinsonism: clinical, molecular and neuropathological findings. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIMH, NSB, Bethesda, MD 20892 USA. NIH, NINDS, DMMB, Bethesda, MD 20892 USA. NIH, NINDS, SNB, Bethesda, MD 20892 USA. AFIP, Washington, DC USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1739 BP 479 EP 479 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901741 ER PT J AU Orvisky, E Tayebi, N Andrews, D Park, J McReynolds, J Sidransky, E Krasnewich, D AF Orvisky, E Tayebi, N Andrews, D Park, J McReynolds, J Sidransky, E Krasnewich, D TI A deletion-insertion mutation in the phosphomannomutase 2 gene in 2 African American siblings with Congenital Disorders of Glycosylation Type-1a(CDG-1a). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIMH, Bethesda, MD 20892 USA. NIH, NHGRI, Bethesda, MD 20892 USA. Nemours Childrens Clin, Orlando, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1748 BP 480 EP 480 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901746 ER PT J AU Kleta, R Huizing, M Strovel, E Anikster, Y Orvisky, E Aughton, DJ Krasnewich, D Gahl, WA AF Kleta, R Huizing, M Strovel, E Anikster, Y Orvisky, E Aughton, DJ Krasnewich, D Gahl, WA TI Biochemical and molecular analysis of infantile free sialic acid storage disease (ISSD) in a North American child. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, HDB, NIH, Bethesda, MD USA. NIMH, NSB, NIH, Bethesda, MD 20892 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. NHGRI, MGB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1765 BP 483 EP 483 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901766 ER PT J AU LaMarca, ME Park, JK Stone, D MacKenzie, JJ Tayebi, N Sidransky, E AF LaMarca, ME Park, JK Stone, D MacKenzie, JJ Tayebi, N Sidransky, E TI The E326K mutation and Gaucher disease: Mutation or polymorphism? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIMH, NSB, Bethesda, MD USA. Queens Univ, Kingston, ON K7L 3N6, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1766 BP 483 EP 483 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901764 ER PT J AU Park, JK Schiffmann, R Tayebi, N Orvisky, E Kaneski, C LaMarca, ME Sidransky, E AF Park, JK Schiffmann, R Tayebi, N Orvisky, E Kaneski, C LaMarca, ME Sidransky, E TI Patients with Gaucher disease and myoclonic epilepsy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, NSB, Bethesda, MD 20892 USA. NINCDS, DMNB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1775 BP 485 EP 485 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901777 ER PT J AU Tayebi, N Stubblefield, BK LaMarca, ME Park, JK Martin, BM Sidransky, E AF Tayebi, N Stubblefield, BK LaMarca, ME Park, JK Martin, BM Sidransky, E TI Cholelithiasis in patients with Gaucher disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Rambam Med Ctr, Dept Hematol, Haifa, Israel. Rappaport Fac Med, Haifa, Israel. NIMH, NSB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1776 BP 485 EP 485 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901778 ER PT J AU Tayebi, N Stubblefield, BK LaMarca, ME Park, JK Martin, BM Sidransky, E AF Tayebi, N Stubblefield, BK LaMarca, ME Park, JK Martin, BM Sidransky, E TI Gene conversion events in patients with Gaucher disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, NSB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1776 BP 485 EP 485 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901775 ER PT J AU Bernardini, I Introne, W Kleta, R Fitzpatrick, DL Gahl, WA AF Bernardini, I Introne, W Kleta, R Fitzpatrick, DL Gahl, WA TI Detection of Hartnup's disorder in an alkaptonuria sibship. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, HDB, NIH, Bethesda, MD USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1784 BP 486 EP 486 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901782 ER PT J AU Konecki, DS Lichter-Konecki, U AF Konecki, DS Lichter-Konecki, U TI Determination of the complete DNA sequence of the human phenylalanine hydroxylase gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1791 BP 487 EP 487 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901791 ER PT J AU Anderson, P Fitzpatrick, DL Huizing, M Anikster, Y Gahl, WA AF Anderson, P Fitzpatrick, DL Huizing, M Anikster, Y Gahl, WA TI SUTAL gene mutations causing Hermansky-Pudlak syndrome type-3 in a non-Puerto Rican family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, Sect Human Biochem Genet, HDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1812 BP 491 EP 491 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901811 ER PT J AU Phornphutkul, C Anikster, Y Huizing, M Chou, J Gahl, W AF Phornphutkul, C Anikster, Y Huizing, M Chou, J Gahl, W TI The CTNS promter and its mutations causing cystinosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, HDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1816 BP 492 EP 492 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901816 ER PT J AU Fingerlin, TE Erdos, MR Watanabe, RM Valle, TT Tuomilehto, J Bergman, RN Boehnke, M Collins, FS AF Fingerlin, TE Erdos, MR Watanabe, RM Valle, TT Tuomilehto, J Bergman, RN Boehnke, M Collins, FS CA FUSION Study Grp TI Variation in three SNPs in the calpain-10 gene not implicated in conferring susceptibility to type 2 diabetes in a large Finnish cohort. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Natl Publ Hlth Inst, Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1831 BP 495 EP 495 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901831 ER PT J AU Yang, Q Tofler, GH Cupples, LA Larson, MG Levy, D D'Agostino, RB O'Donnell, CJ AF Yang, Q Tofler, GH Cupples, LA Larson, MG Levy, D D'Agostino, RB O'Donnell, CJ TI A genome-wide scan for circulating levels of fibrinogen in the Framingham Heart Study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Boston Univ, Sch Publ Hlth, Boston, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RI Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1877 BP 502 EP 502 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901875 ER PT J AU Wu, X Cooper, R Zhu, X Weder, A Borecki, I Bray, M Hanis, C Lewis, B Risch, N Savage, P AF Wu, X Cooper, R Zhu, X Weder, A Borecki, I Bray, M Hanis, C Lewis, B Risch, N Savage, P TI Preliminary meta-analysis for BMI in NHLBI FBPP study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Loyola Univ, Ctr Med, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. Univ Michigan, Div Hypertens & Hyperlipidemia, Ann Arbor, MI 48109 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Univ Texas, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1938 BP 512 EP 512 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901938 ER PT J AU Yang, X Kelley, MJ Korczak, JF Sheridan, E Goldstein, AM Parry, DM AF Yang, X Kelley, MJ Korczak, JF Sheridan, E Goldstein, AM Parry, DM TI A familial chordoma locus maps to chromosome 7q33. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, DCEG, Bethesda, MD 20892 USA. Duke Univ, Dept Med, Durham, NC USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA. Karmanos Canc Inst, Epidemiol Sect, Detroit, MI USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1934 BP 512 EP 512 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901936 ER PT J AU Kelberman, D Tyson, J Chandler, DC McInerney, A Slee, J Calvert, M Goldblatt, J Haan, EA Laing, NG Malcolm, S Singer, SL Winter, RM Bitner-Glindzicz, M AF Kelberman, D Tyson, J Chandler, DC McInerney, A Slee, J Calvert, M Goldblatt, J Haan, EA Laing, NG Malcolm, S Singer, SL Winter, RM Bitner-Glindzicz, M TI Genetic heterogeneity in hemifacial microsomia: evidence for three loci at 14q32, 2q35 and 11q12-q13. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Inst Child Hlth, Clin & Mol Gen Unit, London, England. Australian Neuromuscular Res Inst, Nedlands, WA, Australia. NIH, NHGRI, Bethesda, MD USA. King Edward Mem Hosp, Genet Serv, Perth, WA, Australia. Great Ormond St Hosp Children NHS Trust, Dept Maxillofacial & Dent, London, England. Adelaide Childrens Hosp Inc, Adelaide, SA, Australia. Princess Margaret Hosp, Dept Maxillofacial Surg, Perth, WA, Australia. RI Kelberman, Daniel/K-3411-2013 OI Kelberman, Daniel/0000-0003-0583-5237 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1949 BP 514 EP 514 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901947 ER PT J AU Rotimi, C Kittles, R Parish-Gause, D Chen, G Vosganian, G Furbert-Harris, P Amoah, A Acheampong, J Oli, J Osotimehin, B Johnson, T Dunston, G Collins, F AF Rotimi, C Kittles, R Parish-Gause, D Chen, G Vosganian, G Furbert-Harris, P Amoah, A Acheampong, J Oli, J Osotimehin, B Johnson, T Dunston, G Collins, F CA AADM Study Invest Grp TI Fine mapping on chromosome 20 shows evidence of linkage for BMI and fat mass in type 2 diabetes affected sib-pairs from West Africa. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Howard Univ, Natl Human Genome Ctr, Washington, DC USA. Univ Ghana, Legon, Ghana. Univ Sci & Technol, Kumasi, Ghana. Univ Nigeria, Teaching Hosp, Nsukka, Nigeria. Univ Coll Hosp, Ibadan, Nigeria. Univ Lagos, Lagos, Nigeria. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1954 BP 515 EP 515 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901955 ER PT J AU Hanson, RL Kobes, S Lindsay, RS Knowler, WC AF Hanson, RL Kobes, S Lindsay, RS Knowler, WC TI Comparison of Haseman-Elston methods for assessing parent-of-origin effects in linkage analysis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDDK, DAES, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1981 BP 520 EP 520 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901981 ER PT J AU Hirschhorn, JN Altshuler, D Daly, MJ Lindgren, CM Burtt, NP Loomer, M Villapakkam, A Bolk, S O'Donnell, CJ Crews, JD Groop, LC Lander, ES AF Hirschhorn, JN Altshuler, D Daly, MJ Lindgren, CM Burtt, NP Loomer, M Villapakkam, A Bolk, S O'Donnell, CJ Crews, JD Groop, LC Lander, ES TI Linkage disequilibrium at PPARG and other genes assessed with dense sets of SNPs.. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Lund Univ, Div Endocrinol, Malmo, Sweden. NHLBI, Framingham Heart Study, Framingham, MA USA. MIT, Dept Biol, Cambridge, MA USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 1997 BP 522 EP 522 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648901995 ER PT J AU Wolford, JK Kobes, S Hanson, RL Bogardus, C Prochazka, M AF Wolford, JK Kobes, S Hanson, RL Bogardus, C Prochazka, M TI Linkage disequilibrium mapping of a putative type 2 diabetes locus (1q21-q23) using pooled DNA. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDDK, Phoenix, AZ USA. NIH, PECRB, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2000 BP 523 EP 523 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902002 ER PT J AU Ayyagari, R Kakuk, LE Atkins, S Sieving, PA AF Ayyagari, R Kakuk, LE Atkins, S Sieving, PA TI Linkage analysis of a family with Late Onset Atrophic Macular Degeneration and exclusion of candidate loci. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. NIH, NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2009 BP 524 EP 524 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902007 ER PT J AU Puls, I Bidus, K Drayna, D Floeter, MK Mann, E Taylor, JP Wagner, KR Fischbeck, KH Ludlow, C AF Puls, I Bidus, K Drayna, D Floeter, MK Mann, E Taylor, JP Wagner, KR Fischbeck, KH Ludlow, C TI Studies on Charcot-Marie-Tooth disease with vocal fold paralysis (CMT2C) reveal further evidence for genetic heterogeneity. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINCDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NINCDS, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. NINCDS, Electromyog Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. NIDCD, Sect Transcript Factors Sensory Receptors & Chann, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2029 BP 528 EP 528 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902029 ER PT J AU Toro, JR Gahl, WA Bale, S AF Toro, JR Gahl, WA Bale, S TI Linkage mapping to chromosome 3q24 and evidence for a founder effect for Hermansky-Pudlak Syndrome in central Puerto Rico. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2031 BP 528 EP 528 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902030 ER PT J AU Lin, JP Sholinsky, P Coon, HH Hunt, SC Myers, RH Amett, DK Hong, Y AF Lin, JP Sholinsky, P Coon, HH Hunt, SC Myers, RH Amett, DK Hong, Y TI Linkage between cholesterol 7 alpha-hydroxylase (CYP7) gene and low-density lipoprotein cholesterol (LDL-C) in increased CHD risk Caucasian families - the NHLBI Family Heart Study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84112 USA. Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2055 BP 532 EP 532 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902054 ER PT J AU Wilson, AF Roy-Gagnon, MH Justice, CM Papanicolaou, GJ Sorant, AJM Kingman, A Pugh, EW AF Wilson, AF Roy-Gagnon, MH Justice, CM Papanicolaou, GJ Sorant, AJM Kingman, A Pugh, EW TI Test of association and estimation of heritability attributable to SNP effects for quantitative traits with ROMP. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Genometr Sect, Baltimore, MD USA. NIH, NIDCR, Bethesda, MD 20892 USA. Johns Hopkins Univ, SOM, CIDR, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2074 BP 535 EP 535 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902075 ER PT J AU Ghebranious, NR Che, J David, D Rusch, T Chudyk, J Fieweger, K Dickinson, B Fan, Y Zhao, C Yu, A Marth, G Doktycz, M Weber, JL AF Ghebranious, NR Che, J David, D Rusch, T Chudyk, J Fieweger, K Dickinson, B Fan, Y Zhao, C Yu, A Marth, G Doktycz, M Weber, JL TI Genotyping diallelic insertion/deletion polymorphisms. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Marshfield Med Res Fdn, Ctr Med Genet, Marshfield, WI 54449 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2104 BP 540 EP 540 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902105 ER PT J AU Baysal, BE Willett-Brozik, JE Badner, JA Ferrell, RE Nimgaonkar, VA Detera-Wadleigh, S AF Baysal, BE Willett-Brozik, JE Badner, JA Ferrell, RE Nimgaonkar, VA Detera-Wadleigh, S TI DIBD1, a novel gene homologous to Saccaromyces cerevisiae ALG9, is disrupted in a family with bipolar affective disorder by a translocation breakpoint at 11q23. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2133 BP 545 EP 545 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902132 ER PT J AU Rudolph, JG Lipsky, RH Peoples, R AF Rudolph, JG Lipsky, RH Peoples, R TI Identification of a functional variant in the NMDAR1 receptor subunit resulting in altered effects of ethanol. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Transgenom Inc, Appl Genom & Mol, Gaithersburg, MD USA. NIH, NIAAA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2169 BP 551 EP 551 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902168 ER PT J AU Meerabux, JMA Iwayama, Y Detera-Wadleigh, S DeLisind, L Yoshikawa, T AF Meerabux, JMA Iwayama, Y Detera-Wadleigh, S DeLisind, L Yoshikawa, T TI Molecular cloning of a t(18;21)(p11.1;p1.1) translocation associated with psychosis in one family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 RIKEN, Brain Sci Inst, Wako, Saitama 35101, Japan. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2198 BP 556 EP 556 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902200 ER PT J AU Goldman, D Malhotra, A Egan, M Kolachana, B Warden, D Lipsky, RH Salazar, AM Xu, K Goldberg, T Weinberger, D AF Goldman, D Malhotra, A Egan, M Kolachana, B Warden, D Lipsky, RH Salazar, AM Xu, K Goldberg, T Weinberger, D TI COMT Val158Met and cognitive executive function. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, Rockville, MD USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Hillside Hosp, Long Isl City, NY USA. Walter Reed Army Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2237 BP 562 EP 562 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902235 ER PT J AU Silander, K Steppan, CM Mohlke, KL Lazaridis, KN Valle, TT Buchanan, TA Watanabe, RM Boehnke, M Tuomilehto, J Bergman, RN Lazar, MA Collins, FS AF Silander, K Steppan, CM Mohlke, KL Lazaridis, KN Valle, TT Buchanan, TA Watanabe, RM Boehnke, M Tuomilehto, J Bergman, RN Lazar, MA Collins, FS TI Evaluating resistin as a susceptibility gene for type 2 diabetes in the Finnish population. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Univ Penn, Sch Med, Dept Med & Genet, Philadelphia, PA USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2274 BP 568 EP 568 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902274 ER PT J AU Uhl, GR Liu, QR Walther, D AF Uhl, GR Liu, QR Walther, D TI Polysubstance abuse association genome scanning provides evidence for polygenic inheritance of common alleles at loci including BDNF and ADH. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIDA, IRP, Mol Neurol Branch, Baltimore, MD USA. JHU, Sch Med, Dept Neurol, Baltimore, MD USA. JHU, Sch Med, Dept Neurosci, Baltimore, MD USA. RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2269 BP 568 EP 568 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902269 ER PT J AU Radel, M Vallejo, R Aragon, R Long, JC Virkkunen, M Goldman, D AF Radel, M Vallejo, R Aragon, R Long, JC Virkkunen, M Goldman, D TI Analysis of GABAA receptor subunit genes in Alcohol Dependence and Obsessive-Compulsive Disorder. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIAAA, Neurogenet Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2321 BP 576 EP 576 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902319 ER PT J AU Orloff, SM Iyengar, SK Briggs, W Dart, R Kobert, S Mokryzcki, M Vlahov, D Kimmel, P Ahuja, T Berns, J Simon, E Smith, M Trachtman, H Michel, M Winkler, C Schelling, JR Sedor, JR Kopp, JB AF Orloff, SM Iyengar, SK Briggs, W Dart, R Kobert, S Mokryzcki, M Vlahov, D Kimmel, P Ahuja, T Berns, J Simon, E Smith, M Trachtman, H Michel, M Winkler, C Schelling, JR Sedor, JR Kopp, JB TI The arginine to tryptophan mutation in codon 394 of the Wilms' tumor gene (R394W), a mutation hotspot for Denys-Drash (DDS) and Frasier syndromes (FS), is uncommon in primary sporadic focal segmental glomerulosclerosis (FSGS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NIH, NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2347 BP 581 EP 581 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902347 ER PT J AU Chen, YA Lee, CM Shih, YP Tseng, TL Buetow, KH AF Chen, YA Lee, CM Shih, YP Tseng, TL Buetow, KH TI Delineation of the mechanism of glycine N-methyltransferase gene control in liver cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Yang Ming Univ, Inst Publ Hlth, Taipei, Taiwan. NCI, Div Canc Epidemiol & Genet, Lab Populat Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2368 BP 584 EP 584 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902369 ER PT J AU Kremer, H Van Hauwe, P Hoefsloot, LH de Brouwer, A Pennings, R Deutman, A Astuto, LM Kimberling, WJ Bork, JM Cremers, CWRJ Cremers, FPM AF Kremer, H Van Hauwe, P Hoefsloot, LH de Brouwer, A Pennings, R Deutman, A Astuto, LM Kimberling, WJ Bork, JM Cremers, CWRJ Cremers, FPM TI Mutations in the Cx26 and CDH23 gene cause indistinguishable profound congenital hearing loss in a large Dutch family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UMC Nijmegen, Dept Otorhinolaryngol, Nijmegen, Netherlands. UMC Nijmegen, Dept Human Genet, Nijmegen, Netherlands. UMC Nijmegen, Dept Ophthalmol, Nijmegen, Netherlands. Boys Town Natl Res Hosp, Gene Marker Lab, Omaha, NE USA. NIH, Lab Mol Genet, Rockville, MD USA. RI Kremer, Hannie/F-5126-2010; Cremers, Frans/A-5625-2014; Cremers, C.W.R.J./L-4254-2015; de Brouwer, Arjan/P-5949-2015 OI Kremer, Hannie/0000-0002-0841-8693; NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2394 BP 589 EP 589 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902393 ER PT J AU Jain, PK Chandrashekharappa, S Makalowska, I Francomano, CA AF Jain, PK Chandrashekharappa, S Makalowska, I Francomano, CA TI Physical mapping of CHH region and mutation analyses in RMRP gene amon Amish and non Amish patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, Genet Lab, Baltimore, MD USA. NIH, NHGRI, GMBB, Bethesda, MD USA. NIH, NHGRI, GTB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2424 BP 594 EP 594 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902423 ER PT J AU Marcelino, J Gong, Y Baker, M Warman, M Carpten, J AF Marcelino, J Gong, Y Baker, M Warman, M Carpten, J TI Targeted disruption of Cacp in the mouse resembles human Camptodactyly-Arthropathy-Coxa vara-Pericarditis syndrome (CACP) and provides insight into this disease's pathogenesis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. NIH, NHGRI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2422 BP 594 EP 594 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902422 ER PT J AU Kantipong, AK Karkera, JD Roessler, E Muenke, M AF Kantipong, AK Karkera, JD Roessler, E Muenke, M TI Analysis of SMAD2 as a candidate gene for holoprosencephaly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, MGB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2455 BP 599 EP 599 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902456 ER PT J AU Liu, PC Chen, YW Hoffman, EP Kaler, SG AF Liu, PC Chen, YW Hoffman, EP Kaler, SG TI Expression profiling of Menkes disease brain. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NINDS, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2460 BP 600 EP 600 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902459 ER PT J AU Kirschner, LS Sandrini, F Lenherr, SM Carney, JA Stratakis, CA AF Kirschner, LS Sandrini, F Lenherr, SM Carney, JA Stratakis, CA TI Molecular mechanism of disease in carney complex patients with mutations in PRKAR1A. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, DEB, Unit Genet & Endocrinol, Bethesda, MD USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2476 BP 603 EP 603 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902476 ER PT J AU Dagvadorj, A Park, KY Ferrans, VJ Sambuughin, N Sivakumar, K Dalakas, MC Goldfarb, LG AF Dagvadorj, A Park, KY Ferrans, VJ Sambuughin, N Sivakumar, K Dalakas, MC Goldfarb, LG TI Structural and functional defects of desmin causing cardiac and skeletal myopathy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NINDS, Bethesda, MD USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2483 BP 604 EP 604 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902485 ER PT J AU Karkera, JD Kantipong, AK Roessler, E Bamford, RN dela Cruz, J Towbin, JA Bowers, P Burdine, R Schier, A Goldmuntz, E Muenke, M AF Karkera, JD Kantipong, AK Roessler, E Bamford, RN dela Cruz, J Towbin, JA Bowers, P Burdine, R Schier, A Goldmuntz, E Muenke, M TI CFC1 as a candidate gene for congenital cardiovascular malformations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Yale Univ, New Haven, CT USA. Skirball Inst Biomol Med, New York, NY 10153 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2492 BP 605 EP 605 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902490 ER PT J AU Kaler, SG Liu, PC Wattendori, DJ Rosenbaum, KN AF Kaler, SG Liu, PC Wattendori, DJ Rosenbaum, KN TI Novel molecular mechanism for occipital horn syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NINDS, Clin Neurosci Program, Bethesda, MD 20892 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2513 BP 609 EP 609 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902515 ER PT J AU Yeowell, HN Walker, LC Willing, M Marini, JC Cabral, WA Kitamura, E Yamauchi, M AF Yeowell, HN Walker, LC Willing, M Marini, JC Cabral, WA Kitamura, E Yamauchi, M TI Characterization of a subclass of patients with Ehlers-Danlos syndrome type VI that appears unrelated to a decrease in one of the lysyl hydroxylase isoforms. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27706 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. NICHHD, Heritable Disorders Branch, Bethesda, MD USA. Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2514 BP 609 EP 609 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902513 ER PT J AU Gelvez, NY Rodriguez, M Lattig, MC Prieto, JC Friedman, T Morell, R Tamayo, ML AF Gelvez, NY Rodriguez, M Lattig, MC Prieto, JC Friedman, T Morell, R Tamayo, ML TI PAX3 and MITF mutations in Colombian patients with Waardenburg syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Javeriana, Inst Human Genet, Bogota, Colombia. NIH, NIDCD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2537 BP 613 EP 613 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902539 ER PT J AU Kan, SH Elanko, N Twigg, SRF Cornejo-Roidan, LR Muenke, M Wilkie, AOM AF Kan, SH Elanko, N Twigg, SRF Cornejo-Roidan, LR Muenke, M Wilkie, AOM TI Mutation in the IgII domain of FGFR2 causes the eponymous form of Pfeiffer syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England. NHGRI, Med Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2545 BP 614 EP 614 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902546 ER PT J AU Farmakidis, C Sandrini, F Kirschner, LS Stratakis, CA AF Farmakidis, C Sandrini, F Kirschner, LS Stratakis, CA TI AAAS mutations in patients with Allgrove Syndrome and sequence alterations of the same gene in a patient with iACTHR suggesting a new source or genetic heterogeneity for iACTHR. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, Dev Endocrinol Branch, Unit Genet & Endocrinol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2549 BP 615 EP 615 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902551 ER PT J AU Gutter, EM Smith, ACM Hecht, JT Francomano, CA AF Gutter, EM Smith, ACM Hecht, JT Francomano, CA TI Gonadal mosaicism in pseudoachondroplasia: A second family with a COMP mutation of Asp518His. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Houston, TX USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2551 BP 615 EP 615 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902552 ER PT J AU Tranebjaerg, L Teslovich, TM Barmada, MM Fagerheim, T Jones, M Dahl, A Gillanders, EM Trent, JM Stephan, DA AF Tranebjaerg, L Teslovich, TM Barmada, MM Fagerheim, T Jones, M Dahl, A Gillanders, EM Trent, JM Stephan, DA TI Homozygosity mapping in a Norwegian family of a new locus for autosomal recessive ataxia to 20q11-q13. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Bispebjerg Hosp, Dept Audiol, DK-2400 Copenhagen, Denmark. Univ Tromso Hosp, Dept Med Genet, N-9038 Tromso, Norway. Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. NIH, NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. Univ Oslo Hosp, Dept Neurol, Oslo, Norway. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2565 BP 617 EP 617 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902565 ER PT J AU Galdzicka, M Egeland, JA Hirshman, MG Patnala, S Martin, BM Kleijer, WJ Ginns, EI AF Galdzicka, M Egeland, JA Hirshman, MG Patnala, S Martin, BM Kleijer, WJ Ginns, EI TI Gene mutation and expression in Ellis van Creveld syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Massachusetts, Sch Med, Brudnick Neuropsychiat Res Inst, Dept Psychiat, Worcester, MA USA. Univ Miami, Sch Med, Dept Psychiat, Miami, FL 33152 USA. NIH, NIMH, Clin Neurosci Branch, Bethesda, MD USA. Erasmus Univ, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2582 BP 620 EP 620 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902580 ER PT J AU Johnston, JJ Olivos-Glander, IM Blancato, JK Biesecker, LG AF Johnston, JJ Olivos-Glander, IM Blancato, JK Biesecker, LG TI Breakpoint analysis of deletions in patients with Greig cephalopolysyndactyly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Georgetown Univ, Inst Mol Human Gen, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2592 BP 622 EP 622 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902591 ER PT J AU Gallagher, PG Sabatino, DE Nilson, DM Wong, C Cline, AP Garrett, LJ Bodine, DM AF Gallagher, PG Sabatino, DE Nilson, DM Wong, C Cline, AP Garrett, LJ Bodine, DM TI Erythrocyte ankyrin promoter mutations associated with recessive hereditary spherocytosis cause significant abnormalities in ankyrin expression. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. NHGRI, NIH, Hematopoiesis Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2603 BP 624 EP 624 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902605 ER PT J AU Bi, L Zheng, L Dale, JK Atkinson, TP Puck, JM Lenardo, MJ Straus, SE AF Bi, L Zheng, L Dale, JK Atkinson, TP Puck, JM Lenardo, MJ Straus, SE TI Autoimmune lymphoproliferative syndrome (ALPS) due to Fas-ligand mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NIAID, LCI & LI, Bethesda, MD USA. NIH, NHGRI, Genet Mol Biol Branch, Bethesda, MD USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2615 BP 626 EP 626 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902617 ER PT J AU Richard, G Krol, A Rouan, F Brown, N DiGiovanna, JJ Bale, SJ Uitto, J AF Richard, G Krol, A Rouan, F Brown, N DiGiovanna, JJ Bale, SJ Uitto, J TI Clinical and genetic heterogeneity in connexin disorders of the skin. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Alberta, Div Dermatol & Cutaneous Sci, Edmonton, AB T6G 2E1, Canada. Brown Univ, Dept Dermatol, Providence, RI USA. NCI, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD USA. GeneDx, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2631 BP 628 EP 628 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902631 ER PT J AU Rosenberg, MJ Makalowska, I Bouffard, G Agarawala, R Davis, J Koch, T Weber, JL Kalikin, LM Petty, EM Hilliard, MS Morton, DH Kelley, RI Schaffer, AA Biesecker, LG AF Rosenberg, MJ Makalowska, I Bouffard, G Agarawala, R Davis, J Koch, T Weber, JL Kalikin, LM Petty, EM Hilliard, MS Morton, DH Kelley, RI Schaffer, AA Biesecker, LG TI Linkage analysis, physical mapping and candidate gene analysis of the Amish microcephaly (MCPHA) focus of 17q25. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. NIH, NISC, Bethesda, MD USA. NIH, NCBI, Bethesda, MD USA. Konrad Zuse Zentrum Informationstech, Berlin, Germany. Marshfield Med Res Fdn, Marshfield, WI 54449 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Logicon ROW Sci Corp, Rockville, MD USA. Clin Special Children, Strasburg, PA USA. Kennedy Krieger Inst, Baltimore, MD USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2640 BP 630 EP 630 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902639 ER PT J AU Cabral, WA Mertts, M Leikin, S Marini, JC AF Cabral, WA Mertts, M Leikin, S Marini, JC TI Triplet Duplication in alpha 1(I) collagen chain of proband with lethal osteogenesis imperfecta shifts register of alpha chains in helix and alters incorporation of mutant trimers into fibrils and ECM. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, Sect Connect Tissue Disorders, HDB, NIH, Bethesda, MD USA. NICHHD, LPSB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2671 BP 635 EP 635 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902672 ER PT J AU Marini, JC Cabral, WA Fertala, A Green, LK Korkko, J Forlino, A AF Marini, JC Cabral, WA Fertala, A Green, LK Korkko, J Forlino, A TI Procollagen from an OI proband with alpha 1(I) exon 41 skipping has impaired binding of alpha 1(I) C-telopeptide and confirms importance of this region for fibril assembly. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD, HDB, NIH, Bethesda, MD USA. Med Coll Penn & Hahnemann Univ, Ctr Gene Therapy, Philadelphia, PA USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2674 BP 636 EP 636 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902674 ER PT J AU Hiriyanna, KT Khan, N Bingham, EL Sieving, PA AF Hiriyanna, KT Khan, N Bingham, EL Sieving, PA TI Complete-type X-linked Congenital Night Blindness (CSNB1): Novel NYX (Nyctalopin) mutations cause selective dysfunction of the ON-bipolar cell. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2715 BP 642 EP 642 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902715 ER PT J AU Shieh, JJ Terzioglu, M Pan, CJ Chen, LY Hirawa, H Chou, JY AF Shieh, JJ Terzioglu, M Pan, CJ Chen, LY Hirawa, H Chou, JY TI The molecular basis of glycogen storage disease type 1a: Structural and functional analysis of mutations in glucose-6-phosphatase. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NICHD, HDB, Bethesda, MD 20892 USA. NR 0 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 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2765 BP 651 EP 651 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902767 ER PT J AU Astuto, LM Fields, RR Askew, JW Bork, JM Morell, RJ Kremer, H van Hauwe, P Kimberling, WJ AF Astuto, LM Fields, RR Askew, JW Bork, JM Morell, RJ Kremer, H van Hauwe, P Kimberling, WJ TI CDH23 mutational and clinical analyses: a continuum of genotype/phenotype relationships in a cohort of 94 Usher Id and DFNB12 patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Boys Town Natl Res Hosp, Gene Marker Lab, Omaha, NE 68131 USA. Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD USA. Univ Nijmegen Hosp, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. RI Kremer, Hannie/F-5126-2010 OI Kremer, Hannie/0000-0002-0841-8693 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2779 BP 653 EP 653 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902780 ER PT J AU Raben, N Lee, A Lu, N Nagaraju, K Rivera, Y Yan, B McKinney, AA Ponce, E Canfield, WM Plotz, PH AF Raben, N Lee, A Lu, N Nagaraju, K Rivera, Y Yan, B McKinney, AA Ponce, E Canfield, WM Plotz, PH TI A new approach to generate mice tolerant to recombinant human proteins. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMSD, ARB, NIH, Bethesda, MD 20892 USA. Novazyme Pharmaceut Inc, Oklahoma City, OK 73104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2900 BP 675 EP 675 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902900 ER PT J AU Tsang, SH Salchow, DS Jiang, M Kong, J Redmond, M Goff, SP Gouras, P Farber, DB AF Tsang, SH Salchow, DS Jiang, M Kong, J Redmond, M Goff, SP Gouras, P Farber, DB TI Toward repair of retinal degenerations with differentiated and embryonic stem (ES) cells. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. Columbia Univ, New York, NY USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2931 BP 680 EP 680 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902933 ER PT J AU Oh, J Hughes, SH AF Oh, J Hughes, SH TI Construction and characterization of a replication competent retroviral shuttle vector. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 SU 1 MA 2939 BP 681 EP 681 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 483RD UT WOS:000171648902940 ER PT J AU Phornphutkul, C Anikster, Y Huizing, M Braun, P Brodie, C Chou, JY Gahl, WA AF Phornphutkul, C Anikster, Y Huizing, M Braun, P Brodie, C Chou, JY Gahl, WA TI The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, carkl, and causes cystinosis if mutated in a critical region SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NEPHROPATHIC CYSTINOSIS; CYSTEAMINE THERAPY; CORNEAL CRYSTALS; RENAL-FUNCTION; MUTATIONS; DISEASE; ACID; DELETION; CHILDREN; GROWTH AB Although >55 CTNS mutations occur in patients with the lysosomal storage disorder cystinosis, no regulatory mutations have been reported, because the promoter has not been defined. Using CAT reporter constructs of sequences 5' to the CTNS coding sequence, we identified the CTNS promoter as the region encompassing nucleotides -316 to +1 with respect to the transcription start site. This region contains an Sp-1 regulatory element (GGCGGCG) at positions -299 to -293, which binds authentic Sp-1, as shown by electrophoretic-mobility-shift assays. Three patients exhibited mutations in the CTNS promoter. One patient with nephropathic cystinosis carried a -295 G -->C substitution disrupting the Sp-1 motif, whereas two patients with ocular cystinosis displayed a -303 G -->T substitution in one case and a -303 T insertion in the other case. Each mutation drastically reduced CAT activity when inserted into a reporter construct. Moreover, each failed either to cause a mobility shift when exposed to nuclear extract or to compete with the normal oligonucleotide's mobility shift. The CTNS promoter region shares 41 nucleotides with the promoter region of an adjacent gene of unknown function, CARKL, whose start site is 501 bp from the CTNS start site. However, the patients' CTNS promoter mutations have no effect on CARKL promoter activity. These findings suggest that the CTNS promoter region should be examined in patients with cystinosis who have fewer than two coding-sequence mutations. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Bar Ilan Univ, Ramat Gan, Israel. RP Gahl, WA (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 28 TC 27 Z9 29 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 BP 712 EP 721 DI 10.1086/323484 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 472WP UT WOS:000171008200005 PM 11505338 ER PT J AU Atkinson, TP Schaffer, AA Grimbacher, B Schroeder, HW Woellner, C Zerbe, CS Puck, JM AF Atkinson, TP Schaffer, AA Grimbacher, B Schroeder, HW Woellner, C Zerbe, CS Puck, JM TI An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PRIMARY CONGENITAL GLAUCOMA; HYPER-IGE SYNDROME; LINKAGE ANALYSIS; GRAVES-DISEASE; SUSCEPTIBILITY LOCUS; GENETIC-LINKAGE; AMPHOTERICIN-B; LOD SCORES; HASHIMOTOS-THYROIDITIS; CYTOCHROME P4501B1 AB We describe a large family in which a combination of chronic mucocutaneous candidiasis (fungal infections of the skin, nails, and mucous membranes) and thyroid disease segregate as an autosomal dominant trait with reduced penetrance. The family includes (a) four members with both candidiasis and thyroid disease, (b) five members, including one pair of phenotype-concordant MZ twins, with candidiasis only, and (c) three members with thyroid disease only. A whole-genome scan using DNA samples from 20 members of the family identified a candidate linkage region on chromosome 2p. By sampling additional individuals and genotyping supplementary markers, we established linkage to a region of similar to 15 cM bounded by D2S367 and D2S2240 and including seven adjacent markers consistent with linkage. With a penetrance estimate of .8, which was based on pedigree and affected status, the peak two-point LOD score was 3.70 with marker D2S2328, and the peak three-point LOD score was 3.82. This is the first linkage assignment of a dominant locus for mucocutaneous candidiasis. C1 NHGRI, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol branch, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL USA. Univ Freiburg, Sch Med, Dept Rheumatol & Immunol, Freiburg, Germany. RP Puck, JM (reprint author), NHGRI, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bldg 49,Room 3A14,49 Convent Dr,MSC 4442, Bethesda, MD 20892 USA. EM jpuck@nhgri.nih.gov RI Schaffer, Alejandro/F-2902-2012 FU NHGRI NIH HHS [N01HG65403] NR 66 TC 29 Z9 30 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 BP 791 EP 803 DI 10.1086/323611 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 472WP UT WOS:000171008200012 PM 11517424 ER PT J AU Schmidt, LS Warren, MB Nickerson, ML Weirich, G Matrosova, V Toro, JR Turner, ML Duray, P Merino, M Hewitt, S Pavlovich, CP Glenn, G Greenberg, CR Linehan, WM Zbar, B AF Schmidt, LS Warren, MB Nickerson, ML Weirich, G Matrosova, V Toro, JR Turner, ML Duray, P Merino, M Hewitt, S Pavlovich, CP Glenn, G Greenberg, CR Linehan, WM Zbar, B TI Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HEREDITARY MULTIPLE FIBROFOLLICULOMAS; SMITH-MAGENIS MICRODELETION; MULTILOCUS LINKAGE ANALYSIS; HOMOLOGOUS RECOMBINATION; UNSTABLE REGION; GENE; ACROCHORDONS; PROTEIN; TRICHODISCOMAS; IDENTIFICATION AB Birt-Hogg-Dube' syndrome (BHD), an inherited autosomal genodermatosis characterized by benign tumors of the hair follicle, has been associated with renal neoplasia, lung cysts, and spontaneous pneumothorax. To identify the BHD locus, we recruited families with cutaneous lesions and associated phenotypic features of the BHD syndrome. We performed a genomewide scan in one large kindred with BHD and, by linkage analysis, localized the gene locus to the pericentromeric region of chromosome 17p, with a LOD score of 4.98 at D17S740 (recombination fraction 0). Two-point linkage analysis of eight additional families with BHD produced a maximum LOD score of 16.06 at D17S2196. Haplotype analysis identified critical recombinants and defined the minimal region of nonrecombination as being within a <4-cM distance between D17S1857 and D17S805. One additional family, which had histologically proved fibrofolliculomas, did not show evidence of linkage to chromosome 17p, suggesting genetic heterogeneity for BHD. The BHD locus lies within chromosomal band 17p11.2, a genomic region that, because of the presence of low-copy-number repeat elements, is unstable and that is associated with a number of diseases. Identification of the gene for BHD may reveal a new genetic locus responsible for renal neoplasia and for lung and hair-follicle developmental defects. C1 Natl Canc Inst, Intramural Res Support Program, IRSP, SAIC, Frederick, MD 21702 USA. Natl Canc Inst, Immunobiol Lab, Frederick, MD 21702 USA. Natl Canc Inst, Natl Inst Hlth, Dermatol Branch, Bethesda, MD USA. Natl Canc Inst, Natl Inst Hlth, Genet Epidemiol Branch, Bethesda, MD USA. Natl Canc Inst, Natl Inst Hlth, Pathol Lab, Bethesda, MD USA. Natl Canc Inst, Natl Inst Hlth, Urolog Oncol Branch, Bethesda, MD USA. Tech Univ Munich, Inst Pathol, Munich, Germany. Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB R3T 2N2, Canada. RP Schmidt, LS (reprint author), Natl Canc Inst, Intramural Res Support Program, IRSP, SAIC, Bldg 560, Room 12-69, Frederick, MD 21702 USA. OI Hewitt, Stephen/0000-0001-8283-1788 FU NCI NIH HHS [N01-CO-56000] NR 28 TC 178 Z9 183 U1 2 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2001 VL 69 IS 4 BP 876 EP 882 DI 10.1086/323744 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 472WP UT WOS:000171008200020 PM 11533913 ER PT J AU Chen, W Srinivasan, SR Elkasabany, A Ellsworth, DL Boerwinkle, E Berenson, GS AF Chen, W Srinivasan, SR Elkasabany, A Ellsworth, DL Boerwinkle, E Berenson, GS TI Combined effects of endothelial nitric oxide synthase gene polymorphism (G894T) and insulin resistance status on blood pressure and familial risk of hypertension in young adults: The Bogalusa Heart Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE endothelial nitric oxide synthase G894T; polymorphism; insulin resistance; blood pressure; parental hypertension; African American-white ID HOMEOSTASIS MODEL ASSESSMENT; RELEASE ACCOUNTS; MUSCLE; LINK; SENSITIVITY; RELAXATION; GLUCOSE; HUMANS; CELLS; FLOW AB Impaired endothelial function with decreased nitric oxide production is shared by insulin resistance and essential hypertension. Although there are limited data on the association between the endothelial nitric oxide synthase (eNOS) G894T polymorphism and hypertension, information is absent on the combined effects of eNOS G894T genotype and insulin resistance status on blood pressure (BP) levels and the familial risk of hypertension. This aspect was examined in a community-based sample of 1021 unrelated African American and white young adults aged 19 to 38 years. African Americans displayed a lower frequency of the T894 allele than whites (0.105 v 0.324, P < .001). After adjusting for sex, age, and body mass index (BMI), noncarriers versus carriers of the T894 allele had significantly higher systolic (SBP), diastolic (DBP) BP and mean arterial pressure (MAP) levels (111.7 v 109.2 mm Hg for SBP; 73.6 v 72.3 mm. Hg for DBP; 86.3 v 84.6 mm Hg for MAP), with both African Americans and whites showing similar trends. This association was modulated by insulin resistance status, measured by the homeostasis model assessment of insulin resistance (HOMA IR) using fasting insulin and glucose. Subjects with high insulin resistance (above the median HOMA IR) showed significantly greater differences in BP levels between noncarriers and carriers of the T894 allele. Furthermore, the G894T genotype and insulin resistance also showed a combined effect on the prevalence of parental hypertension, a measure of familial risk, with noncarriers versus carriers in the high insulin resistance group showing higher prevalence (70.5% v 51.3%, P = .006, adjusted for race). Thus, the allelic variation (G894T) in the eNOS gene locus in conjunction with insulin resistance may be one factor contributing to the predisposition to hypertension. Am J Hypertens 2001;14:1046-1052 (C) 2001 American Journal of Hypertension, Ltd. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Tulane Ctr Cardiovasc Hlth, New Orleans, LA 70112 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. RP Berenson, GS (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Tulane Ctr Cardiovasc Hlth, 1440 Canal St,Suite 2140, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [HL-38844]; NIA NIH HHS [AG16592] NR 35 TC 36 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 2001 VL 14 IS 10 BP 1046 EP 1052 DI 10.1016/S0895-7061(01)02192-6 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 485BV UT WOS:000171734400011 PM 11710784 ER PT J AU Lewis, J Agodoa, L Cheek, D Greene, T Middleton, J O'Connor, D Ojo, A Phillips, R Sika, M Wright, J AF Lewis, J Agodoa, L Cheek, D Greene, T Middleton, J O'Connor, D Ojo, A Phillips, R Sika, M Wright, J CA African Amer Study Hypertension Ki TI Comparison of cross-sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE glomerular filtration rate (GFR); African Americans; African-American Study of Hypertension and; Kidney Disease (AASK) ID SERUM CREATININE; KIDNEY-DISEASE; RACIAL-DIFFERENCES; PREDICTION; DIAGNOSIS; TRIAL; ESRD AB Renal function measurements were obtained in 1,703 African Americans with presumed hypertensive nephrosclerosis who were screened for entry into the African-American Study of Hypertension and Kidney Disease (AASK). We examined the effect of race on relationships involving renal variables by comparing African Americans enrolled into the AASK with non-African Americans enrolled into the Modification of Diet in Renal Disease (MDRD) study. We examined the effect of gender on renal variables by comparing African American men and women. We compared various methods for estimating glomerular filtration rate (GFR) with iodine 125-labeled (I-125)-iothalamate GFR. AASK data were also used to derive a new formula for estimating GFR in African Americans. After adjusting for age, sex, and baseline GFR, African American patients on the AASK study were heavier and had larger body surface areas and body mass indices than either MDRD African Americans or non-African Americans. African Americans had greater serum creatinine levels and urinary creatinine excretions for any given level of GFR. Mean GFR was greater in African American men than African American women (59.7 versus 51.7 mL/min/1.73 m(2)), although serum creatinine levels were also greater in men (1.91 versus 1.73 mg/dL). Seventy-eight percent of women with serum creatinine levels between 1.2 and 1.5 mg/dL had GFRs less than 65 mL/min/1.73 m(2). For African Americans in the AASK, GFR was overestimated by the 24-hour creatinine clearance and underestimated by the Cockcroft-Gault formula. A prediction formula developed in the MDRD study more accurately predicted GFR in AASK patients than these measurements. AASK data were also used to derive a new five-term formula for estimating GFR that was slightly more accurate in the African Americans in the AASK than the MDRD formula (median percentage of error, 12.4% for the MDRD formula versus 12.1% for the AASK formula). Important differences exist in renal variables between African Americans and non-African Americans and between African American men and African American women. Formulas using demographic data and readily measured serum values estimate I-125-iothalamate GFR. (C) 2001 by the National Kidney Foundation, Inc. C1 Vanderbilt Univ, Div Nephrol, Med Ctr N, Nashville, TN 37232 USA. NIDDK, Bethesda, MD USA. Med Univ S Carolina, Charleston, SC 29425 USA. SW Texas State Univ, Dallas, TX USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Mt Sinai Sch Med, New York, NY USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Lewis, J (reprint author), Vanderbilt Univ, Div Nephrol, Med Ctr N, S-3223, Nashville, TN 37232 USA. FU NCRR NIH HHS [5 M01 RR00071]; NIDDK NIH HHS [DK 45388-08] NR 18 TC 157 Z9 163 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2001 VL 38 IS 4 BP 744 EP 753 DI 10.1053/ajkd.2001.27691 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 476KQ UT WOS:000171226600004 PM 11576877 ER PT J AU Daneker, B Kimmel, PL Ranich, T Peterson, RA AF Daneker, B Kimmel, PL Ranich, T Peterson, RA TI Depression and marital dissatisfaction in patients with end-stage renal disease and in their spouses SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE depression; marriage; marital satisfaction; marital conflict; social support; functional status; Karnofsky performance status scale ID URBAN HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; SOCIAL SUPPORT; ADJUSTMENT; MORTALITY; SURVIVAL; ILLNESS; COUPLES; HEALTH; PERSPECTIVE AB Little research has been performed assessing patients with end-stage renal disease (ESRD) as parts of marital dyads or within family structures. Recent findings suggest patient interactions within such systems are associated with patient outcomes. To evaluate the relationship between level of patient depression and spouse psychosocial status, 55 couples in which one partner was undergoing chronic hemodialysis therapy for ESRD were interviewed. Two variables that alone and in interaction with one another were expected to relate to the spouse's level of depression and marital satisfaction were investigated: patient depression level and spouse's perceived social support. Depression was assessed using the Beck Depression Inventory (BDI). Spouses' levels of depressive aff ect correlated directly with patient BDI scores. A significant two-way interaction for spousal depression (patient depression and spousal support) supported viewing spouses' adjustment as a function of the interaction between spouse and patient factors. Additionally, a main effect of perceived spousal social support on spousal marital satisfaction indicated that spouses reporting high levels of social support had the least marital strain. The severity of the patient's illness did not correlate with any of the predictor variables or measures of spousal adjustment, but spouses reported significantly lower functional status for patients than did nephrologists. Spouse and patient levels of depression are related, although causal relationships cannot be determined by these studies. Moreover, spouse perception of marital satisfaction is related to depression scores. These findings suggest the patient with ESRD functions in a psychosocial dyad. Spouse psychosocial status could impact on the level of patient depression, and the spouse might be amenable to interventions that could improve patient outcome. (C) 2001 by the National Kidney Foundation, Inc. C1 George Washington Univ, Dept Psychol, Washington, DC 20052 USA. NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Kimmel, PL (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, 2150 Penn Ave NW, Washington, DC 20037 USA. NR 49 TC 43 Z9 48 U1 1 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2001 VL 38 IS 4 BP 839 EP 846 DI 10.1053/ajkd.2001.27704 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 476KQ UT WOS:000171226600015 PM 11576888 ER PT J AU Rosenthal, ET Biesecker, LG Biesecker, BB AF Rosenthal, ET Biesecker, LG Biesecker, BB TI Parental attitudes toward a diagnosis in children with unidentified multiple congenital anomaly syndromes SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE multiple congenital anomalies; birth defect; syndrome; diagnosis; genetics; genetic counseling ID NEEDS; INFORMATION; DISABILITY; ADAPTATION; SUPPORT; ILLNESS AB One of the most common and unsatisfying situations encountered in medical genetics clinics is the child with multiple congenital anomalies (MCAs) suggestive of an underlying syndrome for whom it is not possible to make a definitive diagnosis. We undertook a qualitative, descriptive study to learn more about the ways in which the lack of a diagnosis affects parental coping and adjustment to their child's special needs. Semistructured interviews were conducted with 29 parents of 16 children born with an unidentified MCA syndrome. Interviews were based on a small number of open-ended questions, with follow-up probing, asking about parents' experiences with seeking a diagnosis, obtaining treatment and special services, explaining their child's problems to others, reproductive decision making, and support group participation. Transcripts of interviews were analyzed to identify the principal themes surrounding parents' beliefs about the significance of diagnostic information. The parents in this study had been aware of their child's anomalies for 2-23 years, and all had sought multiple evaluations to find a diagnosis. A majority of parents were still interested in identifying their child's syndrome, but most felt that their interest in a diagnosis had diminished over time, and some felt that there were benefits in not having this information. We identified six areas where parents claimed a diagnosis would have impact: labels, causes, prognosis, treatment, acceptance, and social support. Significant issues included obtaining special education services, anticipating the child's future and potential medical complications, life expectancy, recurrence risks, finding sources of social support, and ensuring that the child was receiving appropriate treatment. We conclude that the significance of diagnostic information is complex and varies for different parents. Providers should explore the underlying issues associated with a parental quest for a diagnosis in order to identify and address specific concerns. Published 2001 Wiley-Liss, Inc.dagger. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Utah, Div Med Genet, Salt Lake City, UT USA. RP Rosenthal, ET (reprint author), Univ Calif San Diego, Ctr Canc, 9500 Gilman Dr,MC0987, La Jolla, CA 92093 USA. NR 33 TC 39 Z9 41 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 1 PY 2001 VL 103 IS 2 BP 106 EP 114 DI 10.1002/ajmg.1527 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 473LK UT WOS:000171045300002 PM 11568915 ER PT J AU Biesecker, LG Pelz, D AF Biesecker, LG Pelz, D TI Reply to Shaffer regarding reply to "Burning down DEFECT11" SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter C1 NHGRI, Genet Dis Res Branch, NGDR, NIH, Bethesda, MD 20892 USA. Univ Wales Hosp, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales. RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NGDR, NIH, 49 Covent Dr,Rm 4A80, Bethesda, MD 20892 USA. NR 4 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 1 PY 2001 VL 103 IS 2 BP 181 EP 181 DI 10.1002/ajmg.1522 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 473LK UT WOS:000171045300016 PM 11568929 ER PT J AU Gervasi, MT Chaiworapongsa, T Pacora, P Naccasha, N Yoon, BH Maymon, E Romero, R AF Gervasi, MT Chaiworapongsa, T Pacora, P Naccasha, N Yoon, BH Maymon, E Romero, R TI Phenotypic and metabolic characteristics of monocytes and granulocytes in preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NEVADA SP Soc Maternal Fetal Medicine DE preeclampsia; leukocyte phenotype; maternal intravascular inflammation ID WHOLE-BLOOD; NORMAL-PREGNANCY; LEUKOCYTES; EXPRESSION; ACTIVATION; WOMEN AB OBJECTIVE: The maternal syndrome of preeclampsia has recently been attributed to a systemic intravascular inflammatory response and endothelial cell activation and dysfunction. This novel hypothesis has considerable clinical and biological implications. This study was designed to determine whether women with preeclampsia have evidence of intravascular inflammation by examination of the phenotypic and metabolic activity of granulocytes and monocytes. STUDY DESIGN: A cross-sectional study was performed that included patients with preeclampsia (n = 31) and normal pregnancies (n = 58) matched for gestational age at blood draw. Intravascular inflammation was studied with use of flow cytometry. Peripheral venous blood was assayed to determine granulocyte and monocyte phenotype with the use of monoclonal antibodies for selective cluster differentiation (CD) antigens. The panel of antibodies included CD11b, CD14, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR, The quantity of basal intracellular reactive oxygen species and oxidative burst was assessed. Results were reported as mean channel brightness or intensity of detected fluorescence. Analysis was conducted with nonparametric statistics. A P value < .01 was considered to be significant. RESULTS: Preeclampsia was associated with a significant increase in mean channel brightness for CD11b on granulocytes and monocytes but lower mean channel brightness for CD62L on granulocytes than those from women with normal pregnancy (P < .01 for each). Basal intracellular reactive oxygen species were increased in monocytes but not in granulocytes. The oxidative burst was higher in both cell types. CONCLUSION: Preeclampsia is associated with phenotypic and metabolic changes in granulocytes and monocytes. C1 Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, NICHD,Dept Obstet & Gynecol, Detroit, MI 48201 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, NICHD,Dept Obstet & Gynecol, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 24 TC 103 Z9 105 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2001 VL 185 IS 4 BP 792 EP 797 DI 10.1067/mob.2001.117311 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 485BQ UT WOS:000171734000003 PM 11641653 ER PT J AU Ghidini, A Spong, CY AF Ghidini, A Spong, CY TI Severe meconium aspiration syndrome is not caused by aspiration of meconium SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE meconium aspiration syndrome; intrauterine asphyxia; infection; hypoxia; neonatal respiratory distress ID STAINED AMNIOTIC-FLUID; PERSISTENT PULMONARY-HYPERTENSION; PROPHYLACTIC AMNIOINFUSION; AIRWAY MANAGEMENT; CESAREAN DELIVERY; THICK MECONIUM; PIGLET MODEL; FETAL; NEWBORN; LABOR AB Meconium aspiration syndrome can present clinically with different degrees of severity, ranging from a mild form of respiratory compromise to severe forms that may result in perinatal death despite mechanical ventilation or extracorporeal membrane oxygenation. However, advances in our knowledge concerning meconium aspiration syndrome have revealed that most cases of severe meconium aspiration syndrome are not in fact causally related to the aspiration of meconium but rather are caused by other pathologic processes occurring in utero, primarily chronic asphyxia and infection. Proper understanding of the causative processes underlying fetal or neonatal compromise in these cases Is essential to direct future research into preventive or therapeutic treatments and for counseling of the parents of an affected child. C1 Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. NICHHD, Ctr Res Mothers & Children, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. RP Ghidini, A (reprint author), Georgetown Univ Hosp, Dept Obstet & Gynecol, 3800 Reservoir Rd,NW 3PHC, Washington, DC 20007 USA. NR 67 TC 47 Z9 49 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2001 VL 185 IS 4 BP 931 EP 938 DI 10.1067/mob.2001.116828 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 485BQ UT WOS:000171734000031 PM 11641681 ER PT J AU Ferris, DG Schiffman, M Litaker, MS AF Ferris, DG Schiffman, M Litaker, MS CA ALTS Grp TI Cervicography for triage of women with mildly abnormal cervical cytology results SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervicography; cervical neoplasia; cervical cytology ID CANCER; SMEAR AB OBJECTIVE: To estimate the sensitivity and specificity of cervicography in detecting cervical cancer precursor lesions in women participating in the National Cancer Institute's multicenter atypical squamous cells of undetermined significance and low-grade squarrous intraepithelial lesion triage study (ALTS). STUDY DESIGN: Cervigrams were obtained from 3134 women with a referral Papanicolaou smear diagnosis of atypical squamous; cells of undetermined significance or low-grade squamous intraepithelial lesion. Cervigram and cervical histology results were compared by using cervical intraepithelial neoplasia (CIN) 2 and CIN 3 disease end points. RESULTS: Of 3134 women, 444 had histologic findings of more than or equal to CIN 2 and 222 had CIN 3. Cervicography interpretation by using a threshold of greater than or equal to atypical had a sensitivity, specificity, and positive and negative predictive values of 79.3%, 61.0%, 13.4%, and 97.5%, respectively, for detecting greater than or equal to CIN 3. Cervicography was more sensitive (80.8% vs 57.1 %), but less specific (55.7% vs 81.8%), for detecting CIN 3 in women younger than 35 years compared with women 35 years or older, respectively. CONCLUSIONS: Cervicography functioned moderately well at detecting CIN 2 or CIN 3 in women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Papanicolau smear results. Cervigram sensitivity was better for younger women. C1 Med Coll Georgia, Dept Family Med, Augusta, GA 30912 USA. Med Coll Georgia, Dept Obstet & Gynecol, Augusta, GA 30912 USA. Med Coll Georgia, Off Biostat & Bioinformat, Augusta, GA 30912 USA. ALTS Grp, Bethesda, MD USA. NCI, Environm Epidemiol Branch, Bethesda, MD USA. RP Ferris, DG (reprint author), Med Coll Georgia, Dept Family Med, 1423 Harper St,HH-105, Augusta, GA 30912 USA. FU NCI NIH HHS [CN-55105, CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159] NR 19 TC 15 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2001 VL 185 IS 4 BP 939 EP 943 DI 10.1067/mob.2001.117485 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 485BQ UT WOS:000171734000032 PM 11641682 ER PT J AU Lloyd, RV Vidal, S Jin, L Zhang, SY Kovacs, K Horvath, E Scheithauer, BW Boger, ETA Fridell, RA Friedman, TB AF Lloyd, RV Vidal, S Jin, L Zhang, SY Kovacs, K Horvath, E Scheithauer, BW Boger, ETA Fridell, RA Friedman, TB TI Myosin XVA expression in the pituitary and in other neuroendocrine tissues and tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LIGHT-CHAIN KINASE; UNCONVENTIONAL MYOSIN; DEAFNESS DFNB3; CHROMOGRANIN-A; GROWTH-FACTOR; SUPERFAMILY; SHAKER-2; REGION; LOCALIZATION; ASSOCIATION AB The myosin superfamily of molecular motor proteins includes conventional myosins and several classes of unconventional myosins. Recent studies have characterized the human and mouse unconventional myosin XVA, which has a role in the formation and/or maintenance of the unique actin-rich structures of inner ear sensory hair cells. Myosin XVA is also highly expressed in human anterior pituitary cells. In this study we examined the distribution of myosin XVA protein and mRNA in normal and neoplastic human pituitaries and other neuroendocrine cells and tumors. Myosin XVA was expressed in all types of normal anterior pituitary cells and pituitary tumors and in other neuroendocrine cells and tumors including those of the adrenal medulla, parathyroid, and pancreatic islets. Most nonneuroendocrine tissues examined including liver cells were negative for myosin XVA protein and mRNA, although the distal and proximal tubules of normal kidneys showed moderate immunoreactivity for myosin XVA. Ultrastructural immunohistochemistry localized myosin XVA in association with secretory granules of human anterior pituitary cells and human pituitary tumors. These data suggest that in neuroendocrine cells myosin XVA may have a role in secretory granule movement and/or secretion. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Santiago de Compostela, Lugo, Spain. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Toronto, Toronto, ON, Canada. Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD USA. RP Lloyd, RV (reprint author), Mayo Fdn, Lab Med & Pathol, Rochester, MN 55905 USA. FU NCI NIH HHS [R01 CA090249, CA 90249]; NIDCD NIH HHS [DC00035-04, T32 DC000035] NR 35 TC 13 Z9 14 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2001 VL 159 IS 4 BP 1375 EP 1382 DI 10.1016/S0002-9440(10)62524-2 PG 8 WC Pathology SC Pathology GA 479PC UT WOS:000171411900022 PM 11583965 ER PT J AU Gabrielson, KL Hogue, BA Bohr, VA Cardounel, AJ Nakajima, W Kofler, J Zweier, JL Rodriguez, ER Martin, LJ de Souza-Pinto, NC Bressler, J AF Gabrielson, KL Hogue, BA Bohr, VA Cardounel, AJ Nakajima, W Kofler, J Zweier, JL Rodriguez, ER Martin, LJ de Souza-Pinto, NC Bressler, J TI Mitochondrial toxin 3-nitropropionic acid induces cardiac and neurotoxicity differentially in mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ADRIAMYCIN-INDUCED CARDIOMYOPATHY; HUNTINGTONS-DISEASE; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; ANIMAL-MODEL; SUCCINATE-DEHYDROGENASE; INCREASED VULNERABILITY; STRAIN DIFFERENCES; STRIATAL LESIONS; HYPOXIA-ISCHEMIA AB We investigated the effects of 3-nitropropionic acid (3NPA), a previously characterized neurotoxin, in four strains of mice to better understand the molecular basis of variable host responses to this agent. Unexpectedly, we found significant cardiac toxicity that always accompanied the neurotoxicity in all strains of mice in acute and subacute/chronic toxicity testing. Caudate putamen infarction never occurred without cardiac toxicity. All mouse strains tested are sensitive to 3NPA although the C57BL/6 and BALB/c mice require more exposure than 129SVEMS and FVB/n mice. Cardiac toxicity alone was found in 50% of symptomatic mice tested and morphologically, the cardiac toxicity is characterized by diffuse swelling of cardiomyocytes. and multifocal coagulative contraction band necrosis. In subacute to chronic exposure, atrial thrombosis, cardiac mineralization, cell loss, and fibrosis are combined with cardiomyocyte swelling and necrosis. Ultrastructurally, mitochondrial swelling occurs initially, followed by disruption of myofilaments. Biochemically, isolated heart mitochondria from the highly sensitive 129SVEMS mice have a significant reduction of succinate dehydrogenase activity, succinate oxygen consumption rates, and heart adenosine triphosphate after 3NPA treatment. The severity of morphological changes parallels the biochemical alterations caused by 3NPA, consistent with cardiac toxicity being a consequence of the effects of 3NPA on succinate dehydrogenase. These experiments show, for the first time, that 3NPA has important cardiotoxic effects as well as neurotoxic effects, and that cardiac toxicity possibly resulting from inhibition of the succinate dehydrogenase in heart mitochondria, contributes to the cause of death in 3NPA poisoning in acute and subacute/chronic studies in mice. C1 Johns Hopkins Univ, Sch Med, Div Comparat Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Kennedy Krieger Inst, Baltimore, MD 21205 USA. NIA, Mol Genet Lab, NIH, Ctr Gerontol Res, Baltimore, MD 21224 USA. Akita Univ, Sch Med, Dept Pediat, Akita 010, Japan. RP Gabrielson, KL (reprint author), Johns Hopkins Univ, Sch Med, Div Comparat Med, 720 Rutland Ave,Ross 459, Baltimore, MD 21205 USA. RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X FU NIA NIH HHS [AG16282, R01 AG016282]; NIEHS NIH HHS [R01 ESO8785, ES03819, P30 ES003819, T32 ES007141, T32 ES07141] NR 95 TC 34 Z9 34 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2001 VL 159 IS 4 BP 1507 EP 1520 DI 10.1016/S0002-9440(10)62536-9 PG 14 WC Pathology SC Pathology GA 479PC UT WOS:000171411900034 PM 11583977 ER PT J AU Ladines, CA Zeng, CY Asico, LD Sun, XG Pocchiari, F Semeraro, C Pisegna, J Wank, S Yamaguchi, I Eisner, GM Jose, PA AF Ladines, CA Zeng, CY Asico, LD Sun, XG Pocchiari, F Semeraro, C Pisegna, J Wank, S Yamaguchi, I Eisner, GM Jose, PA TI Impaired renal D-1 like and D-2-like dopamine receptor interaction in the spontaneously hypertensive rat SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE D-1-like receptors; D-2-like receptors; natriuresis; diuresis; cholecystokinin; hypertension ID BLOOD-PRESSURE; GENETIC-HYPERTENSION; CAMP PATHWAY; ACTIVATION; KIDNEY; PROTEIN; EXPRESSION; TUBULE; ATPASE; CELLS AB D-1-like (D-1, D-5) and D-2-like (D-2, D-3, D-4) dopamine receptors interact in the kidney to produce a natriuresis and a diuresis. Disruption of D-1 or D-3 receptors in mice results in hypertension that is caused, in part, by a decreased ability to excrete an acute saline load. We studied D-1-like and D-2-like receptor interaction in anesthetized spontaneously hypertensive rats (SHR) by the intrarenal infusion of Z-1046 (a novel dopamine receptor agonist with rank order potency of D(3)greater than or equal toD(4)>D-2>D-5>D-1). Z-1046 increased glomerular filtration rate (GFR), urine flow, and sodium excretion in normotensive Wistar-Kyoto rats but not in SHRs. The lack of responsiveness to Z-1046 in SHRs was not an epiphenomenon, because intrarenal cholecystokinin infusion increased GFR, urine flow, and sodium excretion to a similar extent in the two rat strains. We conclude that renal D-1-like and D-2-like receptor interaction is impaired in SHRs. The impaired D-1-like and D-2-like receptor interaction in SHRs is not caused by alterations in the coding sequence of the D-3 receptor, the D-2-like receptor expressed in rat renal tubules that has been shown to be involved in sodium transport. Because the diuretic and natriuretic effects of D-1-like receptors are, in part, caused by an interaction with D-2-like receptors, it is possible that the decreased Z-1046 action in SHRs is secondary to the renal D-1-like receptor dysfunction in this rat strain. C1 Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. Zambon Grp, I-20091 Bresso, MI, Italy. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Jose, PA (reprint author), Georgetown Univ, Med Ctr, Dept Pediat, 3800 Reservoir Rd NW, Washington, DC 20007 USA. FU NHLBI NIH HHS [HL-58536] NR 43 TC 53 Z9 57 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT PY 2001 VL 281 IS 4 BP R1071 EP R1078 PG 8 WC Physiology SC Physiology GA 473LM UT WOS:000171045500004 PM 11557612 ER PT J AU Quezado, Z Parent, C Karzai, W Depietro, M Natanson, C Hammond, W Danner, RL Cui, XZ Fitz, Y Banks, SM Gerstenberger, E Eichacker, PQ AF Quezado, Z Parent, C Karzai, W Depietro, M Natanson, C Hammond, W Danner, RL Cui, XZ Fitz, Y Banks, SM Gerstenberger, E Eichacker, PQ TI Acute G-CSF therapy is not protective during lethal E-coli sepsis SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE granulocyte colony-stimulating factor; infection ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; HUMAN SEPTIC SHOCK; ESCHERICHIA-COLI; CANINE MODEL; HUMAN NEUTROPHILS; RG-CSF; GRANULOCYTE; PNEUMONIA; RATS AB We investigated whether decreases in circulating polymorphonuclear neutrophils (PMN) during lethal Escherichia coli (E. coli) sepsis in canines are related to insufficient host granulocyte colony-stimulating factor (G-CSF). Two-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -noninfected fibrin clots surgically placed. By 10 to 12 h following clot, both infected survivors and nonsurvivors had marked increases (P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ ml +/- SE, 1,931 +/- 364 and 2,779 +/- 681, respectively) compared with noninfected controls (134 +/- 79), which decreased at 24 to 48 h. Despite increases in G-CSF, infected clot placement caused delayed (P = 0.06) increases in PMN (mean +/- SE change from baseline in cells x 10(3)/mm(3) at 24 and 48 h) in survivors (+3.9 +/- 3.9 and +13.8 +/- 3.6) compared with noninfected controls (+13.1 +/- 2.8 and +9.1 +/- 2.5). Furthermore, infected nonsurvivors had decreases in PMN (-1.4 +/- 1.0 and -1.1 +/- 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placement and continued for 96 h to produce more rapid and prolonged high levels of G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following clot in noninfected controls, it caused much smaller increases in infected survivors and decreases in infected nonsurvivors (P = 0.03 for the ordered effect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sepsis. Other factors associated with sepsis either alone or in combination with G-CSF itself may reduce increases or cause decreases in circulating PMN. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 31 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT PY 2001 VL 281 IS 4 BP R1177 EP R1185 PG 9 WC Physiology SC Physiology GA 473LM UT WOS:000171045500018 PM 11557626 ER PT J AU Bickel, CA Verbalis, JG Knepper, MA Ecelbarger, CA AF Bickel, CA Verbalis, JG Knepper, MA Ecelbarger, CA TI Increased renal Na-K-ATPase, NCC, and beta-ENaC abundance in obese Zucker rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE sodium-phosphate cotransporter type II; sodium-hydrogen exchanger type III; bumetanide-sensitive sodium-potassium-2; chloride cotransporter; insulin resistance; hypertension; sodium-chloride cotransporter; epithelial sodium channel; adenosine 5 '-triphosphatase ID EPITHELIAL SODIUM-CHANNEL; THICK ASCENDING LIMB; SPONTANEOUSLY HYPERTENSIVE RATS; OUABAIN-LIKE FACTORS; MOLECULAR-CLONING; MEDIATED REGULATION; PROXIMAL TUBULE; MECHANISMS; COTRANSPORTER; KIDNEY AB Renal sodium retention, as a result of increased abundance of sodium transporters, may play a role in the development and/or maintenance of the increased blood pressure in obesity. To address this hypothesis, we evaluated the relative abundances of renal sodium transporters in lean an obese Zucker rats at 2 and 4 mo of age by semiquantitative immunoblotting. Mean systolic blood pressure was higher in obese rats relative to lean at 3 mo, P < 0.02. Furthermore, circulating insulin levels were 6- or 13-fold higher in obese rats compared with lean at 2 or 4 mo of age, respectively. The abundances of the (1)-subunit of Na-K-ATPase, the thiazide-sensitive Na-CI cotransporter NCC or TSC), and the beta -subunit of the epithelial sodium channel (ENaC) were all significantly increased in the obese rats' kidneys. There were no differences for the sodium hydrogen exchanger (NHE3), the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2 or BSC1), the type II sodium-phosphate cotransporter (NaPi-2), or the a-subunit of ENaC. These selective increases could possibly increase sodium retention by the kidney and therefore could play a role in obesity-related hypertension. sodium-phosphate cotransporter type II; sodium-hydrogen exchanger type III; bumetanide-sensitive sodium-potassium-2 chloride cotransporter; insulin resistance; hypertension; sodium-chloride cotransporter; epithelial sodium channel; adenosine 5'-triphosphatase. C1 Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20007 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Ecelbarger, CA (reprint author), Georgetown Univ, Dept Med, Div Endocrinol & Metab, Bldg D,Rm 232,4000 Reservoir Rd NW, Washington, DC 20007 USA. EM ecelbarc@georgetown.edu FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [R01 HL073193]; NIDDK NIH HHS [K01 DK-02672, DK-38094] NR 67 TC 57 Z9 58 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2001 VL 281 IS 4 BP F639 EP F648 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 477LL UT WOS:000171285000006 PM 11553510 ER PT J AU Helfand, WH Lazarus, J Theerman, P AF Helfand, WH Lazarus, J Theerman, P TI Saudi nutrition education for pregnant women, 1988 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2001 VL 91 IS 10 BP 1591 EP 1591 DI 10.2105/AJPH.91.10.1591 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476JD UT WOS:000171221800020 PM 11574315 ER PT J AU Frank, R Liu, MC Spannhake, EW Mlynarek, S Macri, K Weinmann, GG AF Frank, R Liu, MC Spannhake, EW Mlynarek, S Macri, K Weinmann, GG TI Repetitive ozone exposure of young adults - Evidence of persistent small airway dysfunction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE adaptive response; persistent response ID HUMAN-LUNG; RESPIRATORY RESPONSES; MULTIDAY EXPOSURE; INFLAMMATION; ANTIOXIDANT; REACTIVITY; ADAPTATION; MECHANISM; MARKERS; LAVAGE AB Earlier, we found that acute ozone (O-3) exposure caused, along with inflammation, greater, more protracted changes in small airway function (isovolumetric Vmax at intermediate to low lung volumes) than in FVC or FEV1. To test if this distinction prevailed with repetitive O-3 exposure, we exposed eight healthy adults on four consecutive days alternatively to filtered air (FA) and O-3 (0.25 ppm x 2 h). Isovolumetric FEF25-75, (V) over dotmax50, and (V) over dotmax75, were grouped into a single value representing small airway function (SAW grp); respiratory frequency (f) and tidal volume (VT) were monitored during exercise. On Day 5, peripheral airway resistance (Rp) was measured followed by lavage. All daily spirometric and ventilatory changes declined in magnitude (adapted) after one or more days Of O-3 exposure. In addition, SAW(grp), f, and VT showed persistent changes beginning with Day 2, denoted either by depression of the preexposure baseline (SAWgrp) or exaggerated tachypnea during exercise. O-3-induced neutrophilia. (p = 0.04) was present in lavage fluid. The possible relationship between these persistent changes in small airway function, measured in days, and the likelihood of cumulative injury in the same region if exposure is long term, is unknown. C1 Johns Hopkins Med Inst, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. RP Frank, R (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,Room W6010, Baltimore, MD 21205 USA. FU NIEHS NIH HHS [ES03505, ES03819] NR 41 TC 27 Z9 28 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2001 VL 164 IS 7 BP 1253 EP 1260 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 489VM UT WOS:000172013200034 PM 11673219 ER PT J AU Zeldin, DC Wohlford-Lenane, C Chulada, P Bradbury, JA Scarborough, PE Roggli, V Langenbach, R Schwartz, DA AF Zeldin, DC Wohlford-Lenane, C Chulada, P Bradbury, JA Scarborough, PE Roggli, V Langenbach, R Schwartz, DA TI Airway inflammation and responsiveness in prostaglandin H synthase-deficient mice exposed to bacterial lipopolysaccharide SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ASTHMATIC-PATIENTS; ALLERGIC-ASTHMA; GENE DISRUPTION; MURINE MODEL; MOUSE; ENDOTOXIN; INHALATION; HYPERRESPONSIVENESS; HYPERREACTIVITY; DISSOCIATION AB Bacterial lipopolysaccharide (LPS) is a risk factor for exacerbation of asthma and causes airway inflammation, The aim of this study was to examine the effects of disruption of prostaglandin (PG) H synthase (PGHS)-1 and PGHS-2 genes on pulmonary responses to inhaled LPS. PGHS-1(-/-), PGHS-2(-/-), an wild-type (WT) mice were exposed to 4 to 6 mug/m(3) LPS via aerosol. Enhanced pause (PenH), a measure of bronchoconstriction, was assessed using a whole-body plethysmograph before and immediately after a 4-h LPS exposure. Bronchoalveolar lavage (BAL) was performed after LPS exposure to assess inflammatory cells, cytokines/chemokines (tumor necrosis factor-alpha, interleukin-6, and macrophage inflammatory protein-2), and PGE(2). The degree of lung inflammation was scored on hematoxylin-and-eosin-stained sections. PGHS-1 and PGHS-2 protein levels were determined by immunoblotting. All mice exhibited increased PenH and methacholine responsiveness after LPS exposure; however, these changes were much more pronounced in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). There were no significant differences in inflammation as assessed by BAL fluid (BALF) cells or lung histology between the genotypes despite reduced BALF cytokines/chemokines and PGE(2). in PGHS-1(-/-) and PGHS-2(-/-) mice relative to WT mice (P < 0.05). PGHS-2 was upregulated more in PGHS-1(-/-) mice compared with WT mice after LPS exposure. We conclude that: (1) airway inflammation and hyperresponsiveness are dissociated in PGHS-1(-/-) and PGHS-2(-/-) mice exposed to LPS; (2) the balance of PGHS-1 and PGHS-2 is important in regulating the functional respiratory responses to inhaled LPS; and (3) neither PGHS-1 nor PGHS-2 is important in regulating basal lung function or the inflammatory responses of the lung to inhaled LPS. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. RP Zeldin, DC (reprint author), NIEHS, 111 TW Alexander Dr,Bldg 101,Room D236, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES-07498] NR 38 TC 43 Z9 44 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 2001 VL 25 IS 4 BP 457 EP 465 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 491NK UT WOS:000172114600010 PM 11694451 ER PT J AU Bryan, JP Reyes, L Hakre, S Gloria, R Kishore, GM Tillett, V Engle, R Tsarev, S Cruess, D Purcell, RH AF Bryan, JP Reyes, L Hakre, S Gloria, R Kishore, GM Tillett, V Engle, R Tsarev, S Cruess, D Purcell, RH TI Epidemiology of acute hepatitis in the Stann Creek District of Belize, Central America SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID DELTA-VIRUS-INFECTION; B VIRUS; UNITED-STATES; HETEROSEXUAL TRANSMISSION; HORIZONTAL TRANSMISSION; LATIN-AMERICA; CHILDREN; VACCINATION; PREVALENCE; ANTIBODY AB Hepatitis is common in the Stann Creek District of southern Belize. To determine the etiologies, incidence, and potential risk factors for acute jaundice, we conducted active surveillance for cases. Cases of jaundice diagnosed by a physician within the previous 6 weeks were enrolled. Evaluation included a questionnaire and laboratory tests for hepatitis A, B, C, D, and E, a blood film for malaria, and a serologic test for syphilis. Etiologies of jaundice among 62 evaluable patients included acute hepatitis A, 6 (9.7%), acute hepatitis B, 49 (79.0%), hepatitis non-A-E, 2 (3.2%), and malaria, 5 (8.1%). There were no cases of acute hepatitis E. One patient each with antibody to hepatitis C and D were detected. The annualized incidence of hepatitis A was 0.26 per 1,000. All cases of hepatitis A were in children 4-16 years of age. The annualized incidence of hepatitis B, 2.17 per 1,000, was highest in adults aged 15-44, years (4.4 per 1,000) and was higher in men (36 cases; 3.09 per 1,000) than women (13 cases; 1.19 per 1,000). Four (31%) of the women with hepatitis B were pregnant. The annualized incidence was significantly higher in Mestizo (6.18 per 1000) and Maya (6.79 per 1,000) than Garifuna (0.38 per 1,000) or Creole (0.36 per I, 000). Persons with hepatitis B were significantly more likely to be born outside of Belize (82%), had been in Belize < 5 years (73%), and lived and worked in rural areas (96%) than was the general population. Of those greater than or equal to 14 years of age with hepatitis B, only 36% were married. Few persons admitted to transfusions, tattoos, IV drug use, multiple sexual partners, visiting prostitutes, or sexually transmitted diseases. Only 1 of 49 had a reactive test for syphilis. Six patients were hospitalized (including 3 with acute hepatitis B and one with hepatitis A), and none to our knowledge died. Acute hepatitis B is the most common cause of viral hepatitis in the Stann Creek District, but the modes of transmission remain obscure. Infants, women attending prenatal clinics, and new workers are potential targets for immunization with hepatitis B vaccine. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NIAID, NIH, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Minist Hlth, Dangriga, Belize. Minist Hlth, Epidemiol Res Ctr, Belize City, Belize. RP Bryan, JP (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Huang, Linlu/H-3410-2011 NR 39 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2001 VL 65 IS 4 BP 318 EP 324 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 487BF UT WOS:000171853300011 PM 11693876 ER PT J AU Fedorko, DP Nelson, NA Didier, ES Bertucci, D Delgado, RM Hruszkewycz, AM AF Fedorko, DP Nelson, NA Didier, ES Bertucci, D Delgado, RM Hruszkewycz, AM TI Speciation of human microsporidia by polymerase chain reaction single-strand conformation polymorphism SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID STOOL SPECIMENS; COLD SSCP; PCR; IDENTIFICATION; DNA; ELECTROPHORESIS; AMPLIFICATION; INFECTION AB We describe the application of single-strand conformation polymorphism (SSCP) analysis to the speciation of human microsporidia after polymerase chain reaction (PCR) amplification with the panmicrosporidian primers PMP1 and PMP2. We compared the DNA extracted and amplified from different genotypes or isolates of Enterocytozoon biencusi, Encephalitozoon cuniculi, E. hellem and E. intestinalis plus an isolate of Vittaforma corneae. The PCR-SSCP when performed at 20 degreesC, generated 2 bands in distinctive, reproducible patterns in polyacrylamide gels for each species of microsporidia tested, regardless of genotype or isolate. We found PCR-SSCP to be an easy and reproducible method for speciation of human microsporidia when the primer pair PMP I and PMP2 is used. C1 NIH, Warren G Magnuson Clin Ctr, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA. Tulane Reg Primate Res Ctr, Dept Microbiol, Covington, LA 70433 USA. NIH, Warren G Magnuson Clin Ctr, Chem Serv, Dept Lab Med, Bethesda, MD 20892 USA. RP Fedorko, DP (reprint author), NIH, Warren G Magnuson Clin Ctr, Microbiol Serv, Dept Lab Med, Bldg 10,Room 2C385,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 18 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2001 VL 65 IS 4 BP 397 EP 401 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 487BF UT WOS:000171853300026 PM 11693891 ER PT J AU Stevenson, MAM Fox, JM Wolfinbarger, JB Bloom, ME AF Stevenson, MAM Fox, JM Wolfinbarger, JB Bloom, ME TI Effect of a valine residue at codon 352 of the VP2 capsid protein on in vivo replication and pathogenesis of Aleutian disease parvovirus in mink SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID ACUTE INTERSTITIAL PNEUMONIA; FELINE PANLEUKOPENIA VIRUS; CANINE HOST-RANGE; MINUTE VIRUS; IN-VIVO; 5'-TERMINAL PALINDROME; NUCLEOTIDE-SEQUENCE; MOLECULAR CLONES; CELL-CULTURE; KITS AB Objective-To determine whether a group of 3 genetic differences in the nonstructural protein (NS1) or 1 genetic difference in the structural protein (VP2) of Aleutian disease parvovirus (ADV) is responsible for an increase in the in vivo replication and pathogenicity of G/U-8, a chimera of ADV-G (nonpathogenic) and ADV-Utah (pathogenic), compared with G/U-10. Animals-32 eight-month-old female sapphire mink (Mustela vison). Procedure-Chimeric viruses were constructed, propagated in vitro, and used to inoculate mink. Antiviral antibody responses, presence of serum viral nucleic acid, and serum gamma globulin concentrations were monitored for 120 days following inoculation. Histologic examination of the liver, kidneys, spleen, and mesenteric lymph nodes was performed after necropsy. Results-A chimera containing only the 3 amino acid substitutions in NS1 did not elicit measurable responses indicative of replication or pathogenicity in inoculated mink. Serum antiviral antibody responses, frequency of detection of viral nucleic acid in serum, gamma globulin response, and histologic changes in mink inoculated with chimeras containing a valine residue at codon 352 (352V) of VP2 capsid were increased, compared with values from mink inoculated with chimeric viruses that did not contain 352V. Conclusions and Clinical Relevance-A valine residue at codon 352 in the VP2 capsid protein of ADV affects in vivo viral replication and pathogenicity. This amino acid may be part of an incompletely defined pathogenic determinant of ADV. Further characterization of the pathogenic determinant may allow future development of focused preventive and therapeutic interventions for Aleutian disease of mink. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Bloom, ME (reprint author), Univ Georgia, Coll Vet Med, Dept Small Anim Med, Athens, GA 30602 USA. NR 27 TC 4 Z9 5 U1 0 U2 3 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD OCT PY 2001 VL 62 IS 10 BP 1658 EP 1663 DI 10.2460/ajvr.2001.62.1658 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 477ET UT WOS:000171270700025 PM 11592336 ER PT J AU Myers, CW Daly, JW AF Myers, CW Daly, JW TI An example of the uses of biodiversity knowledge SO AMERICAN NATURALIST LA English DT Article C1 Amer Museum Nat Hist, New York, NY 10024 USA. NIDDKD, Bethesda, MD 20892 USA. RP Myers, CW (reprint author), Amer Museum Nat Hist, New York, NY 10024 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0003-0147 J9 AM NAT JI Am. Nat. PD OCT PY 2001 VL 158 SU S BP 7 EP 7 PG 1 WC Ecology; Evolutionary Biology SC Environmental Sciences & Ecology; Evolutionary Biology GA 478WC UT WOS:000171370200003 ER PT J AU Abbott, KC Oglesby, RJ Hypolite, IO Kirk, AD Ko, CW Welch, PG Agodoa, LY Duncan, WE AF Abbott, KC Oglesby, RJ Hypolite, IO Kirk, AD Ko, CW Welch, PG Agodoa, LY Duncan, WE TI Hospitalizations for fractures after renal transplantation in the United States SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE fracture; osteoporosis; renal transplant; weight; dialysis duration; complication; USRDS ID KIDNEY-TRANSPLANTATION; INTERVENTION TRIAL; DIALYSIS PATIENTS; INCREASED RISK; HIP-FRACTURES; BONE-DISEASE; OSTEOPOROSIS; WOMEN; MORTALITY; COMPLICATIONS AB PURPOSE: To investigate the incidence, risk factors, and associated mortality of fractures in renal transplant recipients. METHODS: Retrospective registry study of 33,479 patients in the United States Renal Data System (USRDS) who received kidney transplants between I July 1994 and 30 June 1997. Associations with hospitalizations for a primary discharge diagnosis of fractures (all causes) were assessed. RESULTS: Renal transplant recipients had an adjusted incidence ratio for fractures of 4.59 (95% confidence interval 3.29 to 6.31). In multivariate analysis, recipients with prevalent fractures, as well as recipients who were Caucasian, women, in the lower quartiles of recipient weight (< 95.9 kg), had end stage renal disease caused by diabetes, and had prolonged pretransplant dialysis were at increased risk for hospitalization because of fractures after transplantation. Recipients hospitalized for hip fracture,, had decreased all-cause survival (hazard ratio for mortality 1.60, 95% CI 1.13 to 2.26) in Cox Regression analysis, CONCLUSIONS: In the early post,transplant course (<3 years), renal transplant recipients had a greater incidence of fractures than the general population, which were associated with decreased patient survival. Preventive efforts should focus on recipients with the risk factors identified in this analysis, most of which can be easily obtained through history and physical examination. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Rheumatol Serv, Washington, DC 20307 USA. NIDDK, Off Minor Res Hlth Coordinat, NIDDKD, NIH, Bethesda, MD USA. NIH, Organ Transplantat Serv, Bethesda, MD 20892 USA. NIDCD, Epidemiol Stat & Data Syst Branch, Natl Inst Deafness & Commun Disorders, NIH, Bethesda, MD USA. Walter Reed Army Med Ctr, Serv Endocrinol, Washington, DC 20307 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. RI Kirk, Allan/B-6905-2012; OI Abbott, Kevin/0000-0003-2111-7112 NR 45 TC 64 Z9 68 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2001 VL 11 IS 7 BP 450 EP 457 DI 10.1016/S1047-2797(01)00226-5 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 475LH UT WOS:000171165100002 PM 11557176 ER PT J AU Ruhl, CE Sonnenberg, A Everhart, JE AF Ruhl, CE Sonnenberg, A Everhart, JE TI Hospitalization with respiratory disease following hiatal hernia and reflux esophagitis in a prospective, population-based study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE gastroesophageal reflux; peptic esophagitis; hiatal hernia; respiratory tract diseases; epidemiology; cohort studies ID CHRONIC PERSISTENT COUGH; GASTROESOPHAGEAL REFLUX; POSTERIOR LARYNGITIS; PULMONARY-DISEASE; GASTRIC-ACID; PREVALENCE; ASTHMATICS; LARYNGEAL; PATHOGENESIS; ASPIRATION AB PURPOSE: Hiatal hernia and reflux esophagitis have been associated with respiratory manifestations, though the temporal sequence of this relationship is uncertain. This study examined prospectively the relationship of hiatal hernia and reflux esophagitis with respiratory outcomes in a representative sample of the United States population. METHODS: 6928 participants in the first National Health and Nutrition Examination Survey, a population-based sample initially examined in 1971-1975, who were hospitalized during follow-up through 1992-1993 composed the study population. The relationship between hiatal hernia and reflux esophagitis hospitalization and a subsequent hospitalization with respiratory outcomes was measured in persons free of respiratory disease at baseline and at first hospitalization. RESULTS: Multivariable survival analysis showed higher rates of hospitalization with any respiratory diagnosis [rate ratio (RR) = 1.4, 95% confidence interval (CI) 1.2-1.7] in persons with preceding hiatal hernia or reflux esophagitis hospitalization. Individually, rate ratios of pharyngitis (RR = 5.6, CI 2.0-15.7), tonsillitis (RR = 8.0, CI 2.5-25.8), bronchitis (RR 1.8, CI 1.2-2.7), pneumonia (RR = 1.3, CI 1.0-1.7), emphysema (RR = 2.9, CI 1.5-5.5), asthma (RR 2.1, CI 1.1-4.2), bronchiectasis (RR = 6.2, Cl 1.1-34.3), and empyema or abscess (RR = 7.4, CI 1.3-42.3) were all higher following hiatal hernia and reflux esophagitis. Rate ratios were similar when reflux esophagitis and hiatal hernia were examined separately. CONCLUSIONS: A prior hiatal hernia or reflux esophagitis hospitalization increased risk of respiratory disease hospitalization. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Social & Sci Syst Inc, Bethesda, MD 20814 USA. Dept Vet Affairs, Albuquerque, NM USA. Univ New Mexico, Albuquerque, NM 87131 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, Suite 1300,7101 Wisconsin Ave, Bethesda, MD 20814 USA. FU NIDDK NIH HHS [N01-DK-62220] NR 52 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2001 VL 11 IS 7 BP 477 EP 483 DI 10.1016/S1047-2797(01)00236-8 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 475LH UT WOS:000171165100005 PM 11557179 ER PT J AU Soldan, SS Fogdell-Hahn, A Brennan, MB Mittleman, BB Ballerini, C Massacesi, L Seya, T McFarland, HF Jacobson, S AF Soldan, SS Fogdell-Hahn, A Brennan, MB Mittleman, BB Ballerini, C Massacesi, L Seya, T McFarland, HF Jacobson, S TI Elevated serum and cerebrospinal fluid levels of soluble human herpesvirus type 6 cellular receptor, membrane cofactor protein, in patients with multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; DECAY-ACCELERATING FACTOR; COMPLEMENT CONTROL PROTEINS; MEASLES-VIRUS; NERVOUS-SYSTEM; FACTOR CD55; CD46; INFECTION; MCP; DEMYELINATION AB Membrane cofactor protein (CD46) is a member of a family of glycoproteins that are regulators of complement and prevent activation of complement on autologous cells. Recently, CD46 has been identified as the cellular receptor for human herpesvirus Type 6 (HHV-6). Elevated levels of soluble CD46 have been described in several autoimmune disorders, and may be implicated in the pathogenesis of these diseases. As several reports have supported an association of HHV-6 and multiple sclerosis, it was of interest to compare levels of soluble CD46 in the sera of multiple sclerosis patients to that of healthy controls, other neurological disease controls, and other inflammatory disease controls. Using an immunoaffinity column comprised of immobilized monoclonal antibodies to CD46, serum levels of soluble CD46 were found to be significantly elevated in multiple sclerosis patients compared with healthy and other neurological disease controls. Moreover, multiple sclerosis patients who tested positive for HHV-6 DNA in serum had significantly elevated levels of soluble CD46 in their serum compared with those who were negative for HHV-6 DNA. A significant increase in soluble CD46 was also found in the serum of other inflammatory disease controls tested compared to healthy controls. Additionally, a significant correlation was demonstrated between levels of soluble CD46 in the serum and cerebrospinal fluid of multiple sclerosis patients. Collectively, these data suggest that elevated levels of soluble CD46 may contribute to the pathogenesis of inflammatory diseases, including multiple sclerosis. C1 NINCDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Dept Genet, Washington, DC USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Florence, Dept Neurol & Psychiat, Florence, Italy. Osaka Sijinbyo Ctr, Osaka Med Ctr Canc & Cardiovasc Dis, Osaka, Japan. RP Jacobson, S (reprint author), NINCDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. RI Seya, Tsukasa/A-4336-2012; ballerini, clara/I-6460-2012; OI Massacesi, Luca/0000-0001-5083-372X; ballerini, clara/0000-0002-7812-9029 NR 51 TC 34 Z9 34 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2001 VL 50 IS 4 BP 486 EP 493 DI 10.1002/ana.1135 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 479JX UT WOS:000171402200010 PM 11603380 ER PT J AU Norton, JA Alexander, HR Fraker, DL Venzon, DJ Gibril, F Jensen, RT AF Norton, JA Alexander, HR Fraker, DL Venzon, DJ Gibril, F Jensen, RT TI Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 121st Annual Scietific Session of the American-Surgical-Association CY APR, 2001 CL COLORADO SPRINGS, COLORADO SP Amer Surg Assoc ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; DUODENAL GASTRINOMAS; PROGNOSTIC FACTORS; LONG-TERM; CLINICAL PRESENTATION; PANCREATIC TUMORS; MANAGEMENT; SURGERY; EXPERIENCE; DEATH AB Objective To determine the role of surgery in patients with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia type 1 (MEN1) with either limited or advanced pancreatic endocrine tumors (PETs). Summary Background Data The role of surgery in patients with MEN1 and ZES is controversial. There have been numerous previous studies of surgery in patients with PETs; however, there are no prospective studies on the results of surgery in patients with advanced disease. Methods Eighty-one consecutive patients with MEN 1 and ZES were assigned to one of four groups depending on the results of imaging studies. Group 1 (n = 17) (all PETs smaller than 2.5 cm) and group 3 (n = 8) (diffuse liver metastases) did not undergo surgery. All patients in group 2A (n = 17; single PET 2.5-6 cm [limited disease]) and group 2B (n = 31; two or more lesions, 2.5 cm in diameter or larger, or one lesion larger than 6 cm) underwent laparotomy. Tumors were preferably removed by simple enucleation, or if not feasible resection. Patients were reevaluated yearly. Results Pancreatic endocrine tumors were found in all patients at surgery, with groups 2A and 2B having 1.7 +/- 0.4 and 4.8 +/- 1 PETs, respectively. Further, 35% of the patients in group 2A and 88% of the patients in group 2B had multiple PETs, 53% and 84% had a pancreatic PET, 53% and 68 Ja had a duodenal gastrinoma, 65% and 71 % had lymph node metastases, and 0% and 12% had liver metastases. Of the patients in groups 2A and 2B, 24% and 58% had a distal pancreatectomy, 0% and 13% had a hepatic resection, 0% and 6% had a Whipple operation, and 53% and 68% had a duodenal resection. No patient was cured at 5 years. There were no deaths. The early complication rate, 29%, was similar for groups 2A and 2B. Mean follow-up from surgery was 6.9 +/- 0.8 years, and during follow-up liver metastases developed in 6 % of the patients in groups 2A and 2B. Groups 1, 2A, and 2B had similar 15-year survival rates (89-100%); they were significantly better than the survival rate for group 3 (52%). Conclusions Almost 40% of patients with MEN1 and ZES have advanced disease without diffuse distant metastases. Despite multiple primaries and a 70% incidence of lymph node metastases, tumor can be removed with no deaths and complication rates similar to those in patients with limited disease. Further, despite previous studies showing that patients with advanced disease have decreased survival rates, in this study the patients with advanced tumor who underwent surgical resection had the same survival as patients with limited disease and patients without identifiable tumor. This suggests that surgical resection should be performed in patients with MEN1 who have ZES and advanced localized PET. C1 Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Norton, JA (reprint author), Dept Vet Affairs, Surg Serv 112, Bldg 200,3rd Fl,Rm 3B-135,4150 Clement St, San Francisco, CA 94121 USA. RI Venzon, David/B-3078-2008 NR 62 TC 95 Z9 99 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 OCT PY 2001 VL 234 IS 4 BP 495 EP 505 DI 10.1097/00000658-200110000-00009 PG 11 WC Surgery SC Surgery GA 481CT UT WOS:000171502900016 PM 11573043 ER PT J AU Feldman, AL Alexander, HR Bartlett, DL Kranda, KC Miller, MS Costouros, NG Choyke, PL Libutti, SK AF Feldman, AL Alexander, HR Bartlett, DL Kranda, KC Miller, MS Costouros, NG Choyke, PL Libutti, SK TI A prospective analysis of plasma endostatin levels in colorectal cancer patients with liver metastases SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 54th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2001 CL WASHINGTON, D.C. SP Soc Surg Oncol DE angiogenesis; endostatin; colorectal cancer; liver metastasis; vascular endothelial growth factor ID COLLAGEN-XVIII; ANGIOGENESIS; SUPPRESSION; ANGIOSTATIN; GENERATION; INHIBITOR; CARCINOMA; HYPOXIA; GROWTH; CELLS AB Background: Circulating inhibitors of angiogenesis have been suggested to affect the growth of distant micrometastatic disease in patients with cancer. This study was designed to evaluate circulating endostatin levels in colorectal cancer patients with liver metastases. Methods: Plasma samples from 30 colorectal cancer patients with liver metastases were analyzed for endostatin and vascular endothelial growth factor (VEGF) by using competitive enzyme immunoassays. Samples were compared with plasma from age- and sex-matched healthy controls; values >2 SD above the control mean were considered elevated, Results: Plasma endostatin levels were significantly higher in the 30 cancer patients than controls (P < .0001) and correlated with preoperative VEGF levels (P = .0008). Eighteen patients underwent surgical treatment (liver resection, n = 10; or isolated hepatic perfusion with melphalan, n = 8). Seventeen treated patients were available for follow-up. Eight of 11 patients who progressed had elevated plasma endostatin levels at the time of progression. None of six patients who remained progression free had elevated endostatin levels at last follow-up (P = .02). Conclusions: Plasma endostatin levels are elevated in colorectal cancer patients with liver metastases and correlate with VEGF levels. Elevated endostatin levels during follow-up are associated with disease progression. Understanding the role of endogenous endostatin in cancer patients may lead to novel strategies to inhibit tumor angiogenesis. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 NR 19 TC 39 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2001 VL 8 IS 9 BP 741 EP 745 DI 10.1245/aso.2001.8.9.741 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 479PH UT WOS:000171412400010 PM 11597016 ER PT J AU Groll, AH Mickiene, D Petraitiene, R Petraitis, V Lyman, CA Bacher, JS Piscitelli, SC Walsh, TJ AF Groll, AH Mickiene, D Petraitiene, R Petraitis, V Lyman, CA Bacher, JS Piscitelli, SC Walsh, TJ TI Pharmacokinetic and pharmacodynamic modeling of anidulafungin (LY303366): Reappraisal of its efficacy in neutropenic animal models of opportunistic mycoses using optimal plasma sampling SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID EXPERIMENTAL DISSEMINATED CANDIDIASIS; IN-VITRO ACTIVITY; SEMISYNTHETIC ECHINOCANDIN; CRYPTOCOCCUS-NEOFORMANS; PULMONARY ASPERGILLOSIS; ANTIFUNGAL ACTIVITY; AMPHOTERICIN-B; RABBITS; CILOFUNGIN; LY-303366 AB The compartmental pharmacokinetics of anidulafungin (VER-002; formerly LY303366) in plasma were characterized with normal rabbits, and the relationships between drug concentrations and antifungal efficacy were assessed in clinically applicable infection models in persistently neutropenic animals. At intravenous dosages ranging from 0.1 to 20 mg/kg of body weight, anidulafungin demonstrated linear plasma pharmacokinetics that fitted best to a three-compartment open pharmacokinetic model. Following administration over 7 days, the mean (+/- standard error of the mean) peak plasma concentration (C-max) increased from 0.46 +/- 0.02 mug/ml at 0.1 mg/kg to 63.02 +/- 2.93 mug/ml at 20 mg/kg, and the mean area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) rose from 0.71 +/- 0.04 to 208.80 +/- 24.21 mug . h/ml. The mean apparent volume of distribution at steady state (V-ss) ranged from 0.953 +/- 0.05 to 1.636 +/- 0.22 liter/kg (nonsignificant [NS]), and clearance ranged from 0.107 +/- 0.01 to 0.149 +/- 0.00 liter/kg/h (NS). Except for a significant prolongation of the terminal half-life and a trend toward an increased V-ss at the higher end of the dosage range after multiple doses, no significant differences in pharmacokinetic parameters were noted in comparison to single-dose administration. Concentrations in tissue at trough after multiple dosing (0.1 to 10 mg/kg/day) were highest in lung and liver (0.85 +/- 0.16 to 32.64 +/- 2.03 and 0.32 +/- 0.05 to 43.76 +/- 1.62 mug/g, respectively), followed by spleen and kidney (0.24 +/- 0.65 to 21.74 +/- 1.86 and <0.20 to 16.92 +/- 0.56, respectively). Measurable concentrations in brain tissue were found at dosages of greater than or equal to0.5 mg/kg (0.24 +/- 0.02 to 3.90 +/- 0.25). Implementation of optimal plasma sampling in persistently neutropenic rabbit infection models of disseminated candidiasis and pulmonary aspergillosis based on the Bayesian approach and model parameters from normal animals as priors revealed a significantly slower clearance (P < 0.05 for all dosage groups) with a trend toward higher AUC(0-24) values, higher plasma concentrations at the end of the dosing interval, and a smaller volume of distribution (P < 0.05 to 0.193 for the various comparisons among dosage groups). Pharmacodynamic modeling using the residual fungal tissue burden in the main target sites as the primary endpoint and C-max, AUC(0-24), time during the dosing interval of 24 h with plasma drug concentration equaling or exceeding the MIC or the minimum fungicidal concentration for the isolate, and tissue concentrations as pharmacodynamic parameters showed predictable pharmacokinetic-pharmacodynamic relationships in experimental disseminated candidiasis that fitted well with an inhibitory sigmoid maximum effect pharmacodynamic model (r(2), 0.492 to 0.819). However, no concentration-effect relationships were observed in experimental pulmonary aspergillosis using the residual fungal burden in lung tissue and survival as parameters of antifungal efficacy. Implementation of optimal plasma sampling in discriminative animal models of invasive fungal infections and pharmacodynamic modeling is a novel approach that holds promise of improving and accelerating our understanding of the action of antifungal compounds in vivo. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Surg Branch, Vet Resources Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NIH, Pharmacokinet Res Lab, Dept Pharm, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 35 TC 77 Z9 79 U1 0 U2 2 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 OCT PY 2001 VL 45 IS 10 BP 2845 EP 2855 DI 10.1128/AAC.45.10.2845-2855.2001 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 475GQ UT WOS:000171154500027 PM 11557479 ER PT J AU Ruff, MR Melendez-Guerrero, LM Yang, QE Ho, WZ Mikovits, JW Pert, CB Ruscetti, FA AF Ruff, MR Melendez-Guerrero, LM Yang, QE Ho, WZ Mikovits, JW Pert, CB Ruscetti, FA TI Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5) SO ANTIVIRAL RESEARCH LA English DT Article DE peptide T; macrophage; HIV-1; entry inhibitor; therapeutic ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; CELL-LINE; AIDS DEMENTIA; TYPE-1 ENTRY; PROTEIN; REPLICATION; BRAIN; MACROPHAGES; MICROGLIA AB Peptide T, which is derived from the V2 region of HIV-1, inhibits replication of R5 and dual-tropic (R5/X4) HIV-1 strains in monocyte-derived macrophages (MDMs), microglia, and primary CD4(+) T cells. Little to no inhibition by peptide T was observed with lab adapted X4 viruses such as IIIB. MN. or NL4-3 propagated in CD4(+) T cells or in the MAGI entry assay. The more clinically relevant R5/X4 early passage patient isolates were inhibited via either the X4 or R5 chemokine receptors, although inhibition was greater with R5 compared to X4 receptors. Virus inhibition ranged from 60 to 99%, depending on the assay, receptor target, viral isolate and amount of added virus. Peak inhibitory effects were detected at concentrations from 10(-12) to 10(-9) M. Peptide T acted to block viral entry as it inhibited in the MAGI cell assay and blocked infection in the luciferase reporter assay using HIV virions pseudotyped with ADA envelope. These results using early passage virus grown in primary cells, together with two different entry reporter assays, show that peptide T selectively inhibits HIV replication using chemokine receptor CCR5 compared to CXC4, explaining past inconsistencies of in vitro antiviral effects. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. Univ Puerto Rico, Sch Med, Dept Microbiol & Med Zool, San Juan, PR 00936 USA. NCI, Lab Antiviral Drug Mechanisms, Screening Technol Branch, FCRDC, Ft Detrick, MD 21702 USA. Childrens Hosp Philadelphia, Div Immunol & Infect Dis, Philadelphia, PA 19104 USA. NCI, Leukocyte Biol Sect, Canc Res Ctr, FCRDC, Frederick, MD 21702 USA. RP Ruff, MR (reprint author), Georgetown Univ, Sch Med, Dept Physiol & Biophys, Basic Sci Bldg,Room 215,3900 Reservoir Rd NW, Washington, DC 20007 USA. FU PHS HHS [3S06M08244] NR 63 TC 20 Z9 24 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 2001 VL 52 IS 1 BP 63 EP 75 DI 10.1016/S0166-3542(01)00163-2 PG 13 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 500JP UT WOS:000172623800007 PM 11530189 ER PT J AU Wu, JM DiPietrantonio, AM Hsieh, TC AF Wu, JM DiPietrantonio, AM Hsieh, TC TI Mechanism of fenretinide (4-HPR)-induced cell death SO APOPTOSIS LA English DT Review DE fenretinide (4-HPR); induction of apoptosis; caspases ID RETINOID N-(4-HYDROXYPHENYL) RETINAMIDE; CERVICAL-CARCINOMA CELLS; BREAST-CANCER PATIENTS; NECROSIS-FACTOR-ALPHA; BCL-2 HOMOLOG BAK; NF-KAPPA-B; INDUCED APOPTOSIS; PROSTATE-CANCER; IN-VITRO; GROWTH-INHIBITION AB 4-HPR (fenretinide) is a synthetic analog of retinoic acid (RA) whose potential as a chemopreventative agent has gained support from in vitro and animal experiments and in limited clinical trials. Comparative analyses of cellular, biochemical, and molecular properties of fenretinide with RA using various tissue culture cells reveal that a key distinction between these two retinoids lies in the ability of fenretinide to induce programmed cell death, also known as apoptosis. Here we review the composite evidence for induction of apoptosis in fenretinide-treated cells. Assays used to validate apoptosis in various cell types are also summarized. Apoptosis in response to fenretinide primarily occurs by a receptor-independent mechanism, which is accompanied by increases in signaling molecules, e.g., ceramide, and cysteine-dependent aspartate-directed proteases, termed caspases, including execution caspase-3. Both caspase-3 inhibitor DEVD-CHO and ceramide synthase inhibitor fumonisin B-1 (FB1) block fenretinide-induced apoptosis. Increase in caspase-3 appears to result from fenretinide-elicited stabilization of procaspase-3 zymogen. We also review apoptotic regulatory proteins such as inhibitor of apoptosis (IAPs) and second mitochondria-derived activator of caspase (SMACs) that participate in the coordinate control of caspase activities. The existence of a large number of proteins capable of modulating apoptosis via activation or inhibition of caspases, coupled with the fact that both the initiation and execution phases of apoptosis utilize pre-existing zymogens, which, once set in motion, culminates in an irreversible apoptotic cascade, raise the possibility that the on/off switch of apoptosis is linked to an intricate intracellular regulatory network, capable of responding to external stimuli such as fenretinide. This network functions to provide checks/balances of the need for apoptosis as well as to minimize and prevent untimely errors in apoptosis. We suggest that dynamic and coordinated regulation of apoptosis by such a hypothetical network in vivo may involve co-localization of pro- and anti-apoptotic proteins and their respective activators/inhibitors in a macromolecular modular unit which we propose to be named caspasomes. Fenretinide also induces apoptosis by elevating reactive oxygen species (ROS), unrelated to changes in ceramide-caspases. Thus multiple, distinct pathways contribute to the induction of apoptosis by fenretinide. C1 New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. NIH, NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Wu, JM (reprint author), New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. NR 153 TC 83 Z9 87 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD OCT PY 2001 VL 6 IS 5 BP 377 EP 388 DI 10.1023/A:1011342220621 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 458ZF UT WOS:000170224800008 PM 11483862 ER PT J AU Hilsabeck, RC LeCompte, DC Marks, AR Grafman, J AF Hilsabeck, RC LeCompte, DC Marks, AR Grafman, J TI The Word Completion Memory Test (WCMT): a new test to detect malingered memory deficits SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE malingering; neuropsychological; analogue; coaching; WCMT ID MMPI-2 VALIDITY SCALES; HEAD-INJURY; IMPAIRMENT; FRAMEWORK AB In recent years, much research has focused on developing tests to detect malingering. A drawback of existing tests is their poor ability to detect malingerers possessing more "sophisticated" knowledge of neuropsychological deficits. The current study presents preliminary validation data on a new measure, the Word Completion Memory Test (WCMT), which is the first malingering test to utilize a sophisticated coaching methodology in its development. The WCMT was administered to control participants, memory-impaired patients, and coached simulators. The coached simulators were provided with specific information about and examples of memory deficits commonly experienced following closed head injury (CHI; e.g., anterograde vs. retrograde amnesia). They also read a detailed scenario describing the lifestyle and motivations likely experienced by CHI litigants, and then practiced their roles by taking a quiz about their deficits. Results showed that 93% of coached simulators and 100% of control and memory-impaired participants were correctly classified by the WCMT. (C) 2001 National Academy of Neuropsychology. Published by Elsevier Science Ltd. C1 Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. BMC Software, Houston, TX USA. NINDS, NIH, Bethesda, MD USA. RP Hilsabeck, RC (reprint author), Univ Calif San Diego, Med Ctr, 200 W Arbor Dr, San Diego, CA 92103 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 31 TC 13 Z9 13 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD OCT PY 2001 VL 16 IS 7 BP 669 EP 677 DI 10.1016/S0887-6177(00)00077-9 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 473RK UT WOS:000171061700004 PM 14589785 ER PT J AU Pope, HG Gruber, AJ Hudson, JI Huestis, MA Yurgelun-Todd, D AF Pope, HG Gruber, AJ Hudson, JI Huestis, MA Yurgelun-Todd, D TI Neuropsychological performance in long-term cannabis users SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; CHRONIC MARIJUANA USE; ABSTINENCE SYMPTOMS; EXECUTIVE FUNCTIONS; CONDUCT DISORDER; EEG SEQUELAE; ATTENTION; RELIABILITY; WITHDRAWAL; VALIDITY AB Background: Although cannabis is the most widely used illicit drug in the United States, its long-term cognitive effects remain inadequately studied. Methods: We recruited individuals aged 30 to 55 years in 3 groups: (1) 63 current heavy users who had smoked cannabis at least 5000 times in their lives and who were smoking daily at study entry; (2) 45 former heavy users who had also smoked at least 5000 times but fewer than 12 times in the last 3 months and (3) 72 control subjects who had smoked no more than 50 times in their lives. Subjects underwent a 28-day washout from cannabis use, monitored by observed urine samples. On days 0, 1, 7, and 28, we administered a neuropsychological test battery to assess general intellectual function, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information. Test results were analyzed by repeated- measures regression analysis, adjusting for potentially confounding variables. Results: At days 0, 1. and 7, current heavy users scored significantly below control subjects on recall of word lists, and this deficit was associated with users' urinary 11-nor-9-carboxy-Delta9-tetrahydrocannabinol concentrations at study entry. By day 28, however, there were virtually no significant differences among the groups on any of the test results, and no significant associations between cumulative lifetime cannabis use and test scores. Conclusion: Some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use. C1 Harvard Univ, McLean Hosp, Sch Med, Biol Psychiat Lab, Belmont, MA 02478 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. NIDA, Intramural Res Program, Baltimore, MD USA. RP Pope, HG (reprint author), Harvard Univ, McLean Hosp, Sch Med, Biol Psychiat Lab, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [5 R37 DA-10346] NR 41 TC 362 Z9 367 U1 8 U2 58 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2001 VL 58 IS 10 BP 909 EP 915 DI 10.1001/archpsyc.58.10.909 PG 7 WC Psychiatry SC Psychiatry GA 478YB UT WOS:000171375400003 PM 11576028 ER PT J AU Rosenthal, NE AF Rosenthal, NE TI Lithium: An orphan drug SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. RP Rosenthal, NE (reprint author), NIMH, Clin Psychobiol Branch, Bldg 10,Rm 45239, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2001 VL 58 IS 10 BP 973 EP 973 DI 10.1001/archpsyc.58.10.973 PG 1 WC Psychiatry SC Psychiatry GA 478YB UT WOS:000171375400012 PM 11576037 ER PT J AU Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanley, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Camille, J Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Dubois-Moran, J Callahan, C Evans, C Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, NJ Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY AF Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanley, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Camille, J Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Dubois-Moran, J Callahan, C Evans, C Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, NJ Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY CA AREDS Res Grp TI A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss - AREDS Report No. 8 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BLUE MOUNTAINS EYE; BEAVER DAM EYE; VISUAL IMPAIRMENT; ORAL ZINC; MACULOPATHY; ANTIOXIDANT; PREVALENCE; PIGMENT; COHORT; RISK AB Background: Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. Objective: To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. Design: The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main Outcome Measures: (1)Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline ( : 15 letters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results: Average follow-up of the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80 (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to advanced AMD. Odds reduction estimates increased when these 1063 participants were excluded (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR, 0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in this higher-risk group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54-0.99). No statistically significant serious adverse effect was associated with any of the formulations. Conclusions: Persons older than 55 years should have dilated eye examinations to determine their risk of developing advanced AMD. Those with extensive intermediate size drusen, at least 1 large druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye, and without contraindications such as smoking, should consider taking a supplement of antioxidants plus zinc such as that used in this study. C1 Eye Ctr Mem, Albany, NY USA. Emory Univ, Atlanta, GA 30322 USA. Ingalls Mem Hosp, Harvey, IL USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NEI, Ctr Clin, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Elman Retina Grp PA, Baltimore, MD USA. Univ Wisconsin, Reading Ctr, Madison, WI USA. Ctr Dis Control & Prevent, Cent Lab, Atlanta, GA USA. NEI, Project Off, Bethesda, MD 20892 USA. RP Kassoff, A (reprint author), Eye Ctr Mem, Albany, NY USA. NR 52 TC 1310 Z9 1344 U1 13 U2 113 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2001 VL 119 IS 10 BP 1417 EP 1436 PG 20 WC Ophthalmology SC Ophthalmology GA 481RD UT WOS:000171532700001 ER PT J AU Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanely, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Werner, JC Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, J Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY AF Kassoff, A Kassoff, J Buehler, J Eglow, M Kaufman, F Mehu, M Kieval, S Mairs, M Graig, B Quattrocchi, A Jones, D Locatelli, J Ruby, A Capone, A Garretson, B Hassan, T Trese, MT Williams, GA Regan, V Manatrey, P Streasick, P Szydlowski, L McIver, F Bridges, C Stanely, C Cumming, K Lewis, B Zajechowski, M Margherio, RR Cox, MS Werner, JC Falk, R Siedlak, P Neubert, C Klein, ML Stout, JT O'Malley, A Lauer, AK Robertson, JE Wilson, DJ Beardsley, C Anderson, H Wallace, P Smith, G Howard, S Dreyer, RF Ma, C Chenoweth, RG Zilis, JD Johnson, M Rice, P Daniel, H Crider, H Parker, S Sherman, K Martin, DF Aaberg, TM Sternberg, P Curtis, LT Ju, B Gilman, J Myles, B Strittman, S Gentry, C Yi, H Capone, A Lambert, M Meredith, T Aaberg, TM Saperstein, D Lim, JI Stribling, B Armiger, D Swords, R Orth, DH Flood, TP Civantos, J deBustros, S Packo, KH Merrill, PT Cohen, JA Figliulo, C Morrison, C Bryant, DA Doherty, D McVicker, M Drefcinski, T Seddon, JM Pinnolis, MK Davis, N Burton, I Taitsel, T Walsh, D Snow, KK Jones-Devonish, DA Crouse, VD Rosenberg, J Chew, EY Csaky, K Ferris, FL Shimel, KH Woods, MA Kuehl, EM Ciatto, PF Palmer, M Babilonia-Ayukawa, G Foster, GE Goodman, L Kim, YJ Kivitz, IJ Koutsandreas, D LaReau, A Mercer, RF Nashwinter, R McCarthy, SA Ayres, LM Lopez, P Randalls, A Friberg, TR Eller, AW Gorin, MB Nixon, S Mack, B Curtin, DY Ostroska, PP Fijewski, E Alexander, J Paine, MK Corbin, PS Warnicki, J Bressler, SB Bressler, NM Cassel, G Finkelstein, D Goldberg, M Haller, JA Ratner, L Schachat, AP Sherman, SH Sunness, JS Schenning, S Sackett, C Cain, D Emmert, D Herring, M McDonald, J Falk, R Wheeler, S Mcmillan, M George, T Elman, MJ Ballinger, R Betancourt, A Glasser, D Herr, M Hirsh, D Kilingsworth, D Kohlhepp, P Lammlein, J Raden, RZ Seff, R Shuman, M Starr, J Carrigan, A Sotirakos, P Cain, T Mathews, T Ringrose, C Chandra, SR Gottlieb, JL Ip, MS Klein, R Nork, TM Stevens, TS Blodi, BA Altaweel, M Klein, BEK Olson, M Soderling, B Blatz, M Perry-Raymond, JR Burke, K Knutson, G Peterson, J Krolnik, D Harrison, R Somers, G Myers, FL Wallow, I Olsen, TW Bresnik, G De Venecia, G Perkins, T Walker, W Miller, JL Neider, M Wabers, HD Weber, G Myers, HEL Davis, MD Klein, BEK Klein, R Hubbard, L Neider, M Wabers, HD Magli, YL Ansay, S Armstrong, J Lang, K Badal, D Geithman, PL Miner, KD Dohm, KL Esser, B Hurtenbach, C Craanen, S Webster, M Elledge, J Reed, S Benz, W Reimers, J Fisher, MR Gangnon, R King, W Gai, CY Baliker, J Carr, A Osterby, K Kastorff, L Robinson, N Onofrey, J Glander, KE Brickbauer, J Miller, D Sowell, A Gunter, E Bowman, B Lindblad, AS Milton, RC Clemons, TE Ederer, F Gensler, G Henning, A Entler, G McBee, W Roberts, K Stine, E Berlin, SH Tomlin, K Pallas, S Scholl, PR Mengers, SA Anand, R Ferris, FL Sperduto, RD Kurinij, N Chew, EY CA AREDS Res Grp TI A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss - AREDS Report No. 9 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPACITIES CASE-CONTROL; LENS OPACITIES; CARDIOVASCULAR-DISEASE; ANTIOXIDANT VITAMINS; NUTRIENT INTAKE; EYE DISEASE; RISK; EXTRACTION; PHYSICIANS; NUTRITION AB Background: Experimental and observational data suggest that micronutrients with antioxidant capabilities may retard the development of age-related cataract. Objective: To evaluate the effect of a high-dose antioxidant formulation on the development and progression of age-related lens opacities and visual acuity loss. Design: The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked clinical trial. Participants were randomly assigned to receive daily oral tablets containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg) or no antioxidants. Participants with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial. Baseline and annual (starting at year 2) lens photographs were graded at a reading center for the severity of lens opacities using the AREDS cataract grading scale. Main Outcome Measures: Primary outcomes were (1) an increase from baseline in nuclear, cortical, or posterior subcapsular opacity grades or cataract surgery, and (2) at least moderate visual acuity loss from baseline (greater than or equal to 15 letters). Primary analyses used repeated-measures logistic regression with a statistical significance level of P = .01. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results: Of 4757 participants enrolled, 4629 who were aged from 55 to 80 years had at least 1 natural lens present and were followed up for an average of 6.3 years. No statistically significant effect of the antioxidant formulation was seen on the development or progression of age-related lens opacities (odds ratio = 0.97, P = .55). There was also no statistically significant effect of treatment in reducing the risk of progression for any of the 3 lens opacity types or for cataract surgery. For the 1117 participants with no age-related macular degeneration at baseline, no statistically significant difference was noted between treatment groups for at least moderate visual acuity loss. No statistically significant serious adverse effect was associated with treatment. Conclusion: Use of a high-dose formulation of vitamin C, vitamin E, and beta carotene in a relatively well-nourished older adult cohort had no apparent effect on the 7-year risk of development or progression of age-related lens opacities or visual acuity loss. C1 Eye Ctr Mem, Albany, NY USA. Emory Univ, Atlanta, GA 30322 USA. Ingalls Mem Hosp, Harvey, IL USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NEI, Ctr Clin, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Elman Retina Grp PA, Baltimore, MD USA. Univ Wisconsin, Reading Ctr, Madison, WI 53706 USA. Ctr Dis Control & Prevent, Genet Lab, Atlanta, GA USA. NEI, Project Off, Bethesda, MD 20892 USA. RP Kassoff, A (reprint author), Eye Ctr Mem, Albany, NY USA. NR 49 TC 303 Z9 311 U1 4 U2 29 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2001 VL 119 IS 10 BP 1439 EP 1452 PG 14 WC Ophthalmology SC Ophthalmology GA 481RD UT WOS:000171532700002 ER PT J AU Velez, G Yuan, P Sung, C Tansey, G Reed, GF Chan, CC Nussenblatt, RB Robinson, MR AF Velez, G Yuan, P Sung, C Tansey, G Reed, GF Chan, CC Nussenblatt, RB Robinson, MR TI Pharmacokinetics and toxicity of intravitreal chemotherapy for primary intraocular lymphoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NERVOUS-SYSTEM LEUKEMIA; GLUCOCORTICOID RECEPTORS; CNS LYMPHOMA; METHOTREXATE; 5-FLUOROURACIL; FLUOROURACIL; DEXAMETHASONE; THERAPY; CANCER; VINCRISTINE AB Objective: To investigate the pharmacokinetics and toxicity of intravitreal chemotherapeutic agents in the rabbit eye for the potential treatment of primary intraocular lymphoma and other intraocular malignancies. Methods: The ocular pharmacokinetics of intravitreal methotrexate sodium (400 mug) was studied in 10 New Zealand white rabbits, and a single-compartment, first-order elimination model was used to calculate the drug half-life. With the use of these data, a treatment schedule using serial injections of intravitreal methotrexate and single injections of fluorouracil and dexamethasone sodium phosphate was developed. This schedule was studied in 4 New Zealand white rabbits to explore the combined toxicity of these agents. Results: Methotrexate vitreous levels, following a 400-mug intravitreal injection, remained therapeutic (> 0.5 muM) in the rabbit eye for 48 to 72 hours. Intravitreal methotrexate, combined with fluorouracil and dexamethasone, showed no evidence of drug toxicity as determined by electroretinography and histopathologic examination. Conclusions: A treatment schedule for primary intraocular lymphoma consisting of methotrexate intravitreal injections every 48 to 72 hours provides therapeutic drug concentrations in the vitreous and, in combination with fluorouracil and dexamethasone, appears to be safe in the rabbit eye. Clinical Relevance: Although responsive to conventional chemotherapy or radiotherapy, recurrence of ocular involvement with primary central nervous system lymphoma occurs in more than 50% of treated cases. Anecdotal reports of the use of intravitreal chemotherapy for primary intraocular lymphoma have been encouraging. However, animal data on the pharmacokinetics and toxicity of combined intravitreal agents for the treatment of this disease are lacking. C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NEI, Vet Res & Resources Sec, NIH, Bethesda, MD 20892 USA. NEI, Bioengn & Phys Sci Program, Off Director, NIH, Bethesda, MD 20892 USA. NEI, Dept Pharm, Ctr Clin, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Velez, G (reprint author), 85 Washington Pk, Newton, MA 02460 USA. NR 46 TC 54 Z9 58 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2001 VL 119 IS 10 BP 1518 EP 1524 PG 7 WC Ophthalmology SC Ophthalmology GA 481RD UT WOS:000171532700013 PM 11594954 ER PT J AU Corsi, A Riminucci, M Fisher, LW Bianco, P AF Corsi, A Riminucci, M Fisher, LW Bianco, P TI Achondrogenesis type IB - Agenesis of cartilage interterritorial matrix as the link between gene defect and pathological skeletal phenotype SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DYSPLASIA SULFATE TRANSPORTER; CHONDROCYTES; MUTATIONS; PATIENT AB Achondrogenesis type 1B is a lethal osteochondrodysplasia caused by mutations in the diastrophic dysplasia sulfate transporter gene. How these mutations lead to the skeletal phenotype is not known. Histology of plastic-embedded skeletal fetal achondrogenesis type 1B samples suggested that interterritorial epiphyseal cartilage matrix was selectively missing. Cartilage was organized in "chondrons" separated by cleft spaces; chondrocyte seriation, longitudinal septa, and, in turn, mineralized cartilaginous septa were absent. Agenesis of interterritorial matrix as the key histologic change was confirmed by immunohistology using specific markers of territorial and interterritorial matrix. Biglycan-enriched territorial matrix was preserved; decorin-enriched interterritorial areas were absent, although immunostaining was observed within chondrocytes. Thus, in achondrogenesis type 1B: (1) a complex derangement in cartilage matrix assembly lies downstream of the deficient sulfate transporter activity; (2) the severely impaired decorin deposition participates in the changes in matrix organization with lack of development of normal interterritorial matrix; and (3) this change determines the lack of the necessary structural substrate for proper endochondral bone formation and explains the severe skeletal phenotype. C1 Univ Roma La Sapienza, Policlin Umberto I, Sect Pathol, Dept Expt Med & Pathol, I-00161 Rome, Italy. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Bianco, P (reprint author), Univ Roma La Sapienza, Policlin Umberto I, Sect Pathol, Dept Expt Med & Pathol, Viale Regina Elena 324, I-00161 Rome, Italy. NR 10 TC 8 Z9 10 U1 1 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2001 VL 125 IS 10 BP 1375 EP 1378 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 482JX UT WOS:000171574000024 PM 11570921 ER PT J AU Bussey, TJ Wise, SP Murray, EA AF Bussey, TJ Wise, SP Murray, EA TI The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta) SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID INFEROTEMPORAL-FRONTAL DISCONNECTION; PERIRHINAL CORTEX; WORKING-MEMORY; ORBITOFRONTAL CORTEX; FORNIX TRANSECTION; NEURONAL-ACTIVITY; LESIONS; ABLATION; MACAQUE; SYSTEM AB Four rhesus monkeys (Macaca mulatta) were trained to learn novel sets of visuomotor associations in 50 trials or less. within single test sessions. After bilateral ablation of the orbital and ventral prefrontal cortex, the monkeys lost the ability to learn these associations within a session, although they could learn them when given several daily sessions, Thus, relatively slow, across-session visuomotor learning depends on neither the ventral nor orbital prefrontal cortex. but rapid, within-session teaming does. The ablations also eliminated at least 2 response strategies, repeat-stay and lose-shift. which might account, in part, for the deficit in rapid learning. The deficit is unlikely to result from a failure of visual discriminative ability or working memory: The monkeys could discriminate similar stimulus material within a session. and reducing the working memory load did not improve within-session learning. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Bussey, TJ (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB1 3EB, England. RI Bussey, Timothy/M-2758-2016; OI Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 50 TC 101 Z9 104 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2001 VL 115 IS 5 BP 971 EP 982 DI 10.1037//0735-7044.115.5.971 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 476PG UT WOS:000171237500001 PM 11584930 ER PT J AU Buck, DL Seager, MA Schreurs, BG AF Buck, DL Seager, MA Schreurs, BG TI Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus) nictitating membrane response: Generality and nature of the phenomenon SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID PAVLOVIAN UNCONDITIONED STIMULUS; INTERSTIMULUS-INTERVAL; CEREBELLAR LESIONS; NEURONAL-ACTIVITY; BLINK REFLEX; RED NUCLEUS; BRAIN-STEM; AMYGDALA; FACILITATION; FEAR AB Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to an unconditioned stimulus in the absence of a conditioned stimulus. This form of reflex modification suggests that learning modifies the unconditioned reflex pathway. Rabbit (Oryctolagus cuniculus) nictitating membrane responses to 5 intensities and 3 durations of airpuff (AP) or periorbital electrical stimulation (ES) were monitored before and after conditioning. AP tests detected strong CRM after conditioning with ES and modest levels of CRM after conditioning with AP. After conditioning with AP, ES tests failed to detect CRM. After conditioning with a stronger AP, CRM was again detected by AP tests. CRM is a general phenomenon but is more readily detected after training with a relatively aversive stimulus; thus, it may be a function of level of arousal. C1 W Virginia Univ, Blanchette Rockefeller Neurosci Inst, Morgantown, WV 26506 USA. NIH, Bethesda, MD 20892 USA. RP Schreurs, BG (reprint author), W Virginia Univ, Blanchette Rockefeller Neurosci Inst, POB 9300, Morgantown, WV 26506 USA. OI Schreurs, Bernard/0000-0002-5776-0807 NR 52 TC 22 Z9 22 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2001 VL 115 IS 5 BP 1039 EP 1047 DI 10.1037//0735-7044.115.5.1039 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 476PG UT WOS:000171237500007 PM 11584916 ER PT J AU Holmes, A Hollon, TR Gleason, TC Liu, Z Dreiling, J Sibley, DR Crawley, JN AF Holmes, A Hollon, TR Gleason, TC Liu, Z Dreiling, J Sibley, DR Crawley, JN TI Behavioral characterization of dopamine D-5 receptor null mutant mice SO BEHAVIORAL NEUROSCIENCE LA English DT Review ID INBRED MOUSE STRAINS; FORCED-SWIMMING TEST; TARGETED GENE DELETION; LONG-TERM POTENTIATION; PREPULSE INHIBITION; ANIMAL-MODEL; LOCOMOTOR-ACTIVITY; D1 RECEPTOR; HIPPOCAMPAL-LESIONS; RAT-BRAIN AB To study behavioral functions of the D-5 subtype, mice were generated with null mutations in the D-5 gene. This I st behavioral characterization of D-5 null mutant mice (D-5(-/-)) indicated normal general health, sensory abilities, and neurological reflexes. Under basal conditions, D-5(-/-) mice were generally nor-mat on locomotor activity, the rotarod test, acoustic startle response, prepulse inhibition, elevated plus-maze, light <----> dark exploration, Morris water maze, and cued and contextual fear conditioning. In the Porsolt forced swim test for antidepressant activity, male D-5(-/-) mice showed lower levels of immobility. D-5(-/-) mice showed some evidence of reduced responses to the hyperactivity-inducing effects of the D-1/D-5 receptor agonist SKF 81297. The ability of SKF 81297 to disrupt acoustic startle and prepulse inhibition appeared to be attenuated in D-5(-/-) mice, These results suggest that the D-5 receptor is not essential for many dopamine-mediated behaviors but may contribute to the pharmacological activation of dopaminergic pathways relevant to exploratory locomotion, startle, and prepulse inhibition. C1 NIMH, Sect Behav Genom, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Mol Neuropharmacol Sect, NIH, Bethesda, MD USA. RP Holmes, A (reprint author), NIMH, Sect Behav Genom, NIH, Bldg 10,Room 4D11, Bethesda, MD 20892 USA. NR 112 TC 115 Z9 121 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2001 VL 115 IS 5 BP 1129 EP 1144 DI 10.1037//0735-7044.115.5.1129 PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 476PG UT WOS:000171237500017 PM 11584926 ER PT J AU Roessler, E Muenke, M AF Roessler, E Muenke, M TI Midline and laterality defects: left and right meet in the middle SO BIOESSAYS LA English DT Review ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; ZEBRAFISH ORGANIZER; SONIC HEDGEHOG; VERTEBRATE DEVELOPMENT; CONVERGENT EXTENSION; PRIMITIVE ENDODERM; SIGNALING PATHWAY; PRECHORDAL PLATE; NODAL EXPRESSION AB The aim of this review is to summarize some of the recent advances in molecular embryology that help to explain the pathogenesis of holoprosencephaly (HPE), or its related malformation in model organisms, cyclopia, and laterality defects in humans, derived from detailed analysis of similar malformations in animal models. Recently, defects in several developmental pathways including those operated by the Sonic hedgehog and Nodal signaling factors have been implicated as causes of HPE or laterality defects in humans. Here we summarize the findings in animal models that indicate that both defects can be explained by mechanisms that relate to the proper development of the axial midline in vertebrates. Published 2001 John Wiley & Sons, Inc. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, Bld 10,10C103, Bethesda, MD 20892 USA. NR 67 TC 47 Z9 48 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 2001 VL 23 IS 10 BP 888 EP 900 DI 10.1002/bies.1130 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 478PH UT WOS:000171354200005 PM 11598956 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI Paradox of Bcl-2 (and p53): why may apoptosis-regulating proteins be irrelevant to cell death? SO BIOESSAYS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ETOPOSIDE-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; B-LYMPHOMA CELLS; IN-VITRO; ELEVATED EXPRESSION; CLONOGENIC SURVIVAL; CASPASE ACTIVATION; ANTICANCER AGENTS; BREAST CARCINOMAS AB Although the Bcl-2 family members and p53 are involved in the regulation of apoptosis, the status of apoptotic machinery (eg caspases) plays a major role in determining the mode and timing of cell death. If the apoptotic machinery is lost, inhibited, or intrinsically inactivated, the "death stars", Bcl-2 and p53, may become irrelevant to cell death. In this light, high levels of Bcl-2 may indicate that downstream apoptotic pathways are still functional. This explains why Bcl-2 overexpression can be a marker of chemosensitivity and favorable prognosis in certain cancers and why retention of wild-type p53 may manifest inactivation of caspases in aggressive cancers. (C) 2001 John Wiley & Sons, Inc. C1 NIH, Med Branch, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NIH, Med Branch, Bldg 10,Room 12 N 226, Bethesda, MD 20892 USA. NR 84 TC 42 Z9 45 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 2001 VL 23 IS 10 BP 947 EP 953 DI 10.1002/bies.1135 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 478PH UT WOS:000171354200010 PM 11598961 ER PT J AU Lane, MA AF Lane, MA TI Caloric restriction a fountain of youth? SO BIOFUTUR LA French DT Article ID DIETARY RESTRICTION; PRIMATES; DISEASE C1 NIA, Nutr & Mol Physiol Unit, Neurosci Lab, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Nutr & Mol Physiol Unit, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 21 TC 0 Z9 0 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD OCT PY 2001 VL 2001 SI SI BP 40 EP 42 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 490TD UT WOS:000172066400014 ER PT J AU Mattson, MP Greig, NH AF Mattson, MP Greig, NH TI Slowing down cerebral degeneration SO BIOFUTUR LA French DT Article ID DIETARY RESTRICTION; APOPTOSIS; NEURONS C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 21 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD OCT PY 2001 VL 2001 SI SI BP 51 EP 53 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 490TD UT WOS:000172066400017 ER PT J AU Rogozin, IB Kochetov, AV Kondrashov, FA Koonin, EV Milanesi, L AF Rogozin, IB Kochetov, AV Kondrashov, FA Koonin, EV Milanesi, L TI Presence of ATG triplets in 5 ' untranslated regions of eukaryotic cDNAs correlates with 'weak' context of the start codon SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Georgia-Tech-Emory International Conference on Bioinformatics in Silico Biology: Bioinformatics after the Human Genome CY NOV 15-18, 2001 CL ATLANTA, GA ID VERTEBRATE MESSENGER-RNAS; NUCLEIC-ACID SEQUENCES; SACCHAROMYCES-CEREVISIAE; TRANSLATION INITIATION; ISOCHORE ORGANIZATION; INTERNAL INITIATION; CODING SEQUENCES; COMPUTER METHODS; HUMAN GENES; AUG AB Motivation: The context of the start codon (typically, AUG) and the features of the 5 ' Untranslated Regions (5 ' UTRs) are important for understanding translation regulation in eukaryotic: mRNAs, and for accurate prediction of the coding! region in genomic and cDNA sequences. The presence of AUG triplets in 5 ' UTRs (upstream AUGs) might effect the initiation rate and, in, the context of gene prediction, could! reduce the accuracy of the identification of the authentic start. To reveal potential connections between the presence of upstream AUGs and other features of 5 ' UTRs, such as their length and the start codon context, we undertook a systematic analysis of the available eukaryotic 5 ' UTR sequences. Results: We show that a large fraction of 5 ' UTRs in the available cDNA sequences, 15-53% depending on the organism, contain upstream ATGs. A negative correlation, was observed between the information content of the translation start signal and the length of the 5 ' UTR. Similarly, a negative correlation exists between the 'strength' of the start context and the number of upstream ATGs. Typically, cDNAs containing long 5 ' UTRs with multiple upstream AT, Gs have a 'weak' start context, and in contrast, cDNAs, containing short 5 ' UTRs without ATGs have 'strong' starts. These counter-intuitive results maybe interpreted in terms, of upstream AUGs having an important role in the regulation! of translation efficiency by ensuring tow, basal translation level via double negative control and creating the potential for additional regulatory mechanisms. One of such mechanisms, supported by experimental studies of some mRNAs, includes removal of the AUG-containing portion of the 5 ' UTR by alternative splicing. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20804 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. CNR, Ist Tecnol Biomed Avanzate, I-20090 Segrate, MI, Italy. RP Rogozin, IB (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A,Rm 805, Bethesda, MD 20894 USA. EM rogozin@ncbi.nlm.nih.gov; milanesi@itba.mi.cnr.it RI Kondrashov, Fyodor Alexeevich/H-6331-2015; Kochetov, Alex/R-9689-2016; OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694; Kochetov, Alex/0000-0003-3151-5181; Milanesi, Luciano/0000-0002-1201-3939 NR 51 TC 99 Z9 107 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD OCT PY 2001 VL 17 IS 10 BP 890 EP 900 DI 10.1093/bioinformatics/17.10.890 PG 11 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 484LA UT WOS:000171690300005 PM 11673233 ER PT J AU Jordan, IK Bishop, GR Gonzalez, DS AF Jordan, IK Bishop, GR Gonzalez, DS TI Sequence and structural aspects of functional diversification in class I alpha-mannosidase evolution SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 3rd Georgia Tech-Emory International Conference on Bioinformatics-in Silico Biology: Bioinformatics after the Human Genome CY NOV 15-18, 2001 CL ATLANTA, GEORGIA ID ASPARAGINE-LINKED OLIGOSACCHARIDES; N-GLYCAN MATURATION; ENDOPLASMIC-RETICULUM; HUMAN ALPHA-1,2-MANNOSIDASE; MOLECULAR EVOLUTION; PROTEIN FAMILIES; GENE DUPLICATION; EXPRESSION; BIOSYNTHESIS; GLYCOSIDASES AB Motivation: Class I alpha -mannosidases comprise a homologous and functionally diverse family of glycoside hydrolases. Phylogenetic analysis based on an amino acid sequence alignment of the catalytic domain of class I alpha -mannosidases reveals four well-supported phylogenetic groups within this family. These groups include a number of paralogous members generated by gene duplications that occurred as far back as the initial divergence of the crown-group of eukaryotes. Three of the four phylogenetic groups consist of enzymes that have group-specific biochemical specificity and/or sites of activity. An attempt has been made to uncover the role that natural selection played in the sequence and structural divergence between the phylogenetically and functionally distinct Endoplasmic Reticulum (ER) and Golgi apparatus groups. Results: Comparison of site-specific amino acid variability profiles for the ER and Golgi groups revealed statistically significant evidence for functional diversification at the sequence level and indicated a number of residues that are most likely to have played a role in the functional divergence between the two groups. The majority of these sites appear to contain residues that have been fixed within one organelle-specific group by positive selection. Somewhat surprisingly these selected residues map to the periphery of the a-mannosidase catalytic domain tertiary structure. Changes in these peripherally located residues would not seem to have a gross effect on protein function. Thus diversifying selection between the two groups may have acted in a gradual manner consistent with the Darwinian model of natural selection. C1 Millsaps Coll, Dept Chem, Jackson, MS 39210 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. USDA, Aquat Anim Hlth Res Unit, Auburn, AL 36831 USA. RP Bishop, GR (reprint author), Millsaps Coll, Dept Chem, Jackson, MS 39210 USA. NR 55 TC 7 Z9 8 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 OCT PY 2001 VL 17 IS 10 BP 965 EP 976 DI 10.1093/bioinformatics/17.10.965 PG 12 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 484LA UT WOS:000171690300014 PM 11673242 ER PT J AU Clay, JR Shrier, A AF Clay, JR Shrier, A TI Action potentials occur spontaneously in squid giant axons with moderately alkaline intracellular pH SO BIOLOGICAL BULLETIN LA English DT Article ID SODIUM-CHANNEL; LOLIGO-OPALESCENS; INACTIVATION; CURRENTS; ESCAPE AB This report demonstrates a novel finding from the classic giant axon preparation of the squid. Namely, the axon can be made to fire autonomously (spontaneously occurring action potentials) when the intracellular PH (pH(i)) was increased to about 7.7, or higher. (Physiological pHi is 7.3.) The frequency of firing was 33 Hz (T = 5 degrees). No changes in frequency or in the voltage waveform. itself were observed when pHi was increased from 7.7 up to 8.5. In other words, the effect has a threshold at a pHi of about 7.7. A mathematical model that is sufficient to mimic these results is provided using a modified version of the Clay (1998) description of the axonal ionic currents. C1 Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada. RP Clay, JR (reprint author), Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 26 TC 8 Z9 8 U1 0 U2 2 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 J9 BIOL BULL JI Biol. Bull. PD OCT PY 2001 VL 201 IS 2 BP 186 EP 192 DI 10.2307/1543333 PG 7 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 488UB UT WOS:000171953200007 PM 11687390 ER PT J AU Clay, JR Kuzirian, AM AF Clay, JR Kuzirian, AM TI A novel, kinesin-rich preparation derived from squid giant axons SO BIOLOGICAL BULLETIN LA English DT Article; Proceedings Paper CT General Scientific Meeting of the Marine-Biological-Laboratory CY AUG 13-14, 2001 CL WOODS HOLE, MA SP Marine Biol Lab ID TRANSPORT; LOCALIZATION; LOLIGO; HSC70 C1 Marine Biol Lab, Woods Hole, MA 02543 USA. RP Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 EI 1939-8697 J9 BIOL BULL-US JI Biol. Bull. PD OCT PY 2001 VL 201 IS 2 BP 243 EP 245 DI 10.2307/1543345 PG 3 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 488UB UT WOS:000171953200019 PM 11687402 ER PT J AU van de Laar, N Henter, L Bartko, JJ Wyatt, RJ AF van de Laar, N Henter, L Bartko, JJ Wyatt, RJ TI Adverse events during a placebo phase for inpatients with chronic schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; adverse events; placebo ID MEDICATION-FREE RESEARCH; RISK; DANGEROUSNESS; ETHICS AB Background: This report builds on a previous analysis examining the long-term effects of a placebo period on a group of inpatients with chronic schizophrenia. In the present analysis, outcome was evaluated through the use of the Psychiatric Adverse Events Rating Scale. Methods: This retrospective analysis examined adverse events for 55 patients with chronic schizophrenia who were placed in a double-blind placebo study on the inpatient units of the National Institute of Mental Health Neuropsychiatric Research Hospital. The number and severity of adverse events experienced by these patients during baseline, placebo, and discharge periods were analyzed. Results: The frequency and severity of adverse events for this group of patients were modest. Most patients did not experience a statistically significant increase in adverse events during their placebo phase; however, a subgroup of patients who were hospitalized for less than 2 months after antipsychotic medications were restored did experience a statistical elevation in adverse events, and that frequency remained statistically elevated at discharge. Conclusions: The results confirm the findings from our previous analysis. Regardless of whether outcome is measured by a behavioral rating scale or by an adverse event scale, given a sufficiently lengthy recovery period, patients with chronic schizophrenia who go through a placebo phase return to baseline. Biol Psychiatry 2001-, 50:487-492 (C) 2001 Society of Biological Psychiatry. C1 NIMH, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Med Ctr, Utrecht, Netherlands. RP Wyatt, RJ (reprint author), NIMH, Neuropsychiat Branch, NIH, 5415 W Cedar Lane,Suite 106B,MSC 2610, Bethesda, MD 20892 USA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2001 VL 50 IS 7 BP 487 EP 492 DI 10.1016/S0006-3223(01)01225-2 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 482NL UT WOS:000171582200002 PM 11600101 ER PT J AU LeTiran, A Stables, JP Kohn, H AF LeTiran, A Stables, JP Kohn, H TI Functionalized amino acid anticonvulsants: Synthesis and pharmacological evaluation of conformationally restricted analogues SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID CIS AMIDE BOND; ANGIOTENSIN-CONVERTING ENZYME; CONVENIENT SYNTHESIS; DERIVATIVES; PEPTIDES; DIPEPTIDE; SURROGATE; PEPTIDOMIMETICS; SPECTROSCOPY; CONSTRAINTS AB Proven conformationally restricted analogues of anticonvulsant functionalized amino acids (FAAs) were prepared using short-range cyclizations and evaluated in pharmacological assays providing new information concerning the structural requirements for FAA function. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. Univ Houston, Dept Chem, Houston, TX 77204 USA. NINCDS, Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Kohn, H (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. EM harold_kohn@unc.edu NR 71 TC 50 Z9 51 U1 0 U2 3 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 OCT PY 2001 VL 9 IS 10 BP 2693 EP 2708 DI 10.1016/S0968-0896(01)00204-8 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 478PJ UT WOS:000171354300021 PM 11557357 ER PT J AU Solovyova, A Schuck, P Costenaro, L Ebel, C AF Solovyova, A Schuck, P Costenaro, L Ebel, C TI Non-ideality by sedimentation velocity of halophilic malate dehydrogenase in complex solvents SO BIOPHYSICAL JOURNAL LA English DT Article ID X-RAY-SCATTERING; 2ND VIRIAL-COEFFICIENTS; PROTEIN CRYSTAL-GROWTH; HALOARCULA-MARISMORTUI; LAMM EQUATION; CONCENTRATION-DEPENDENCE; INTERACTION POTENTIALS; NUMERICAL-SOLUTIONS; CRYSTALLIZATION; ARCHAEBACTERIUM AB We have investigated the potential of sedimentation velocity analytical ultracentrifugation for the measurement of the second virial coefficients of proteins, with the goal of developing a method that allows efficient screening of different solvent conditions. This may be useful for the study of protein crystallization. Macromolecular concentration distributions were modeled using the Lamm equation with the approximation of linear concentration dependencies of the diffusion constant, D = D degrees (1 + k(D)c), and the reciprocal sedimentation coefficient s = s degrees/(1 + k(s)c). We have studied model distributions for their information content with respect to the particle and its non-ideal behavior, developed a strategy for their analysis by direct boundary modeling, and applied it to data from sedimentation velocity experiments on halophilic malate dehydrogenase in complex aqueous solvents containing sodium chloride and 2-methyl-2,4-pentanediol, including conditions near phase separation. Using global modeling for three sets of data obtained at three different protein concentrations, very good estimates for k(s) and s degrees and also for D degrees and the buoyant molar mass were obtained. It was also possible to obtain good estimates for k(D) and the second virial coefficients. Modeling of sedimentation velocity profiles with the non-ideal Lamm equation appears as a good technique to investigate weak inter-particle interactions in complex solvents and also to extrapolate the ideal behavior of the particle. C1 Inst Biol Struct, Lab Mol Biophys, F-38027 Grenoble, France. Natl Acad Sci Ukraine, Inst Problems Cryobiol & Cryomed, UA-61015 Kharkov, Ukraine. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Ebel, C (reprint author), CEA, Lab Mol Biophys, Inst Biol Struct JP Ebel, UMR 5075,CNRS,UJF, 41 Rue Jules Horowitz, F-38027 Grenoble 01, France. EM christine.ebel@ibs.fr RI Costenaro, Lionel/K-8008-2014; OI Costenaro, Lionel/0000-0002-6157-6682; Schuck, Peter/0000-0002-8859-6966 NR 50 TC 49 Z9 50 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2001 VL 81 IS 4 BP 1868 EP 1880 PG 13 WC Biophysics SC Biophysics GA 476AY UT WOS:000171205100004 PM 11566761 ER PT J AU Post, RM Altshuler, LL Frye, MA Suppes, T Rush, AJ Keck, PE McElroy, SL Denicoff, KD Leverich, GS Kupka, R Nolen, WA AF Post, RM Altshuler, LL Frye, MA Suppes, T Rush, AJ Keck, PE McElroy, SL Denicoff, KD Leverich, GS Kupka, R Nolen, WA TI Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers SO BIPOLAR DISORDERS LA English DT Article DE antidepressants; biopolar; bupropion; controlled trial; depression; hypomania; mania; sertraline; switching; venlafaxine ID DEPRESSIVE SYMPTOMATOLOGY IDS; AFFECTIVE-ILLNESS; LITHIUM-CARBONATE; PROPHYLACTIC EFFICACY; AFFECTIVE-DISORDERS; NUCLEUS-ACCUMBENS; ANTI-DEPRESSANTS; CAUSE MANIA; BUPROPION; IMIPRAMINE AB Introduction: Bipolar patients with breakthrough major depressive episodes despite ongoing adequately-dosed mood stabilizer medication were randomized in a double-blind manner to one of three antidepressants with different mechanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial. Methods: Subjects included 64 bipolar patients who participated at five sites in a 10-week double-blind trial for depression and a 1-year blinded continuation maintenance phase for responders. Nonresponders were re-randomized such that there were 95 acute treatment phases. In the acute phase, doses were titrated to clinical response, side effects, or maximum dose of bupropion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Daily ratings on the National Institute of Mental Health-Life Chart Methodology (NIMH-LCM) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness (CGI-BP) and the occurrence of hypomania or mania. Results: Thirty-five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI-BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty-two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania. Results: Thirty-five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI-BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty-two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania. Conclusions: In this randomized double-blind prospective study of three second-generation antidepressants (bupropion, sertraline, and venlafaxine) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers, switches into hypomania or mania occurred in 14% of the acute phases and 33% of the continuation phases. Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Los Angeles VA Hosp, Los Angeles, CA USA. Univ Calif Los Angeles, Ambulatory Clin Res Ctr, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Utrecht, Med Ctr, Utrecht, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, 10 Ctr Dr,MSC 1272,Bldg 10,Room 3S239, Bethesda, MD 20892 USA. RI Nolen, Willem/E-9006-2014; OI Rush, Augustus/0000-0003-2004-2382 NR 50 TC 92 Z9 95 U1 2 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2001 VL 3 IS 5 BP 259 EP 265 DI 10.1034/j.1399-5618.2001.030505.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 484VH UT WOS:000171709900005 PM 11912569 ER PT J AU Ferrari, MG Rivadeneira, ED Jarrett, R Stevceva, L Takemoto, S Markham, P Franchini, G AF Ferrari, MG Rivadeneira, ED Jarrett, R Stevceva, L Takemoto, S Markham, P Franchini, G TI HVMNE, a novel lymphocryptovirus related to Epstein-Barr virus, induces lymphoma in New Zealand White rabbits SO BLOOD LA English DT Article ID T-CELL LYMPHOMA; CUTANEOUS LYMPHOPROLIFERATIVE DISORDERS; CONSTITUTIVE ACTIVATION; MYCOSIS-FUNGOIDES; STAT PROTEINS; EBV-DNA; INFECTION; HERPESVIRUS; LYMPHOCYTES; DISEASE AB HVMNE is a novel Epstein-Barr (EBV)-like virus Isolated from a Macaca nemestrina with CD8(+) T-cell mycosis fungoidescutaneous T-cell lymphoma. Here it Is demonstrated that intravenous inoculation of irradiated HVMNE-infected T cells or cell-free virus from the J94356(PBMC) cell line In New Zealand White rabbits results In seroconversion to the viral capsid antigen (VCA) of EBV; all animals that seroconverted to VCA developed malignant lymphoma within months of inoculation. In contrast, control rabbits, inoculated with heat-inactivated culture supernatants from the same cell line, failed to seroconvert to VCA and did not develop disease. Disseminated lymphoma cells of mixed origin were detected in most vital organs, including the spleen, liver, lungs, kidneys, and heart of the affected rabbits. Neoplastic infiltrates were also observed in lymph nodes, thymus, skin, and subcutaneous tissues. HVMNE DNA and EBV-like RNA expression was demonstrated in the lymphomatous organs and in 2 transformed T-cell lines, one established from the lymph node and the other from the blood of the 2 lymphomatous animals. Analysis of one of these T-cell lines demonstrated the persistence of HVMNE DNA, expression of an LMP1-like protein, and acquisition of interleukin-2 independence, and constitutive activation of the Jak/STAT pathway. Thus, HVMNE in rabbits provides a valuable animal model for human T-cell lymphoma whereby genetic determinants for T-cell transformation by this EBV-like animal virus can be studied. (C) 2001 by The American Society of Hematology. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Leukaemia Res Fund Ctr, Virus Ctr, Glasgow, Lanark, Scotland. Adv Biosci Labs, Kensington, MD USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. OI Takemoto, Shigeki/0000-0003-4130-074X NR 47 TC 8 Z9 8 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 OCT 1 PY 2001 VL 98 IS 7 BP 2193 EP 2199 DI 10.1182/blood.V98.7.2193 PG 7 WC Hematology SC Hematology GA 477UN UT WOS:000171302800033 PM 11568007 ER PT J AU Gerin, W Marion, RM Friedman, R James, GD Bovbjerg, DH Pickering, TG AF Gerin, W Marion, RM Friedman, R James, GD Bovbjerg, DH Pickering, TG TI How should we measure blood pressure in the doctor's office? SO BLOOD PRESSURE MONITORING LA English DT Article DE blood pressure measurement; ambulatory monitoring; home blood pressure monitoring; reliability; validity ID RANDOM-ZERO; HYPERTENSION; SPHYGMOMANOMETER; NURSE; PREDICTORS; RESPONSES; PHYSICIAN AB Background Blood pressure is the most ubiquitous diagnostic recording made in the doctor's office, but the measurement is subject to a number of sources of bias, which may lead to over- or underestimation. The current study examined the systematic influence of the way in which the measurements were taken - by the physician, by a nurse, or with the patient sitting alone, using an automated device. Subjects and methods Blood pressure was measured in 17 essential hypertensive and 10 white-coat hypertensive individuals. On separate clinic visits, measurements were taken by the attending physician, by a nurse and using an automated device (Arteriosonde 1216). Results A repeated-measures ANOVA revealed that, for systolic pressure, there was a significant effect of measurement modality on blood pressure. Physician systolic pressures were on average approximately 10 mmHg higher than those taken by a nurse, nurse pressures being approxiamtely 7 mmHg higher than those recorded using Arteriosonde. The effect on diastolic pressure was similar but smaller, and no nurse -Arteriosonde difference was observed. Conclusions We conclude that the routine clinical assessment of blood pressure would be more representative of daily ambulatory pressure if an automated device, without doctor or nurse present, were used. (C) 2001 Lippincott Williams Wilkins. C1 Mt Sinai Med Ctr, New York, NY 10029 USA. SUNY Binghamton, Binghamton, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. Cornell Univ, Joan & Sanford I Weill Med Coll, New York Presbyterian Hosp, New York, NY USA. RP Gerin, W (reprint author), Cornell Univ, Med Ctr, New York Hosp, Hypertens Ctr, ST405,525 E 68th St, New York, NY 10021 USA. FU NHLBI NIH HHS [HL 57540] NR 28 TC 38 Z9 38 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1359-5237 J9 BLOOD PRESS MONIT JI Blood Press. Monit. PD OCT PY 2001 VL 6 IS 5 BP 257 EP 262 DI 10.1097/00126097-200110000-00006 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 516QN UT WOS:000173568400006 PM 12055421 ER PT J AU Braun, AR Guillemin, A Hosey, L Varga, M AF Braun, AR Guillemin, A Hosey, L Varga, M TI The neural organization of discourse - An (H2O)-O-15-PET study of narrative production in English and American sign language SO BRAIN LA English DT Article DE language; speech; ASL; rCBF; discourse ID POSITRON EMISSION TOMOGRAPHY; RIGHT-HEMISPHERE DAMAGE; PRIMARY VISUAL-CORTEX; FUNCTIONAL-ANATOMY; EPISODIC MEMORY; CORTICAL AREAS; WORKING-MEMORY; BRAIN-REGIONS; SPEECH; ACTIVATION AB In order to identify brain regions that play an essential role in the production of discourse, (H2O)-O-15-PET scans were acquired during spontaneous generation of autobiographical narratives in English and in American Sign Language in hearing subjects who were native users of both. We compared languages that differ maximally in their mode of expression yet share the same core linguistic properties in order to differentiate the stages of discourse production: differences between the languages should reflect later, modality-dependent stages of phonological encoding and articulation; congruencies are more likely to reveal the anatomy of earlier modality-independent stages of conceptualization and lexical access. Common activations were detected in a widespread array of regions; left hemisphere language areas classically related to speech were also robustly activated during sign production, but the common neural architecture extended beyond the classical language areas and included extrasylvian regions in both right and left hemispheres. Furthermore, posterior perisylvian and basal temporal regions appear to play an integral role in spontaneous self-generated formulation and production of language, even in the absence of exteroceptive stimuli. Results additionally indicate that anterior and posterior areas may play distinct roles in early and late stages of language production, and suggest a novel model for lateralization of cerebral activity during the generation of discourse: progression from the early stages of lexical access to later stages of articulatory-motor encoding may constitute a progression from bilateral to left-lateralized activation. This pattern is not predicted by the standard Wernicke-Geschwind model, and may become apparent when language is produced in an ecologically valid context. C1 NIDOCD, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. RP Braun, AR (reprint author), NIDOCD, Language Sect, Voice Speech & Language Branch, NIH, Bldg 10,Room 5N118A,10 Ctr Dr MSC 1407, Bethesda, MD 20892 USA. NR 80 TC 95 Z9 98 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2001 VL 124 BP 2028 EP 2044 DI 10.1093/brain/124.10.2028 PN 10 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 481BX UT WOS:000171501000012 PM 11571220 ER PT J AU Grafman, J AF Grafman, J TI The frontal lobe has evolved to represent aspects of structured event complexes SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 NIH, NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT-NOV PY 2001 VL 47 IS 1-2 BP 16 EP 17 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 489YR UT WOS:000172021100020 ER PT J AU Koechlin, E Corrado, G Pietrini, P Grafman, J AF Koechlin, E Corrado, G Pietrini, P Grafman, J TI Dissociating the functional properties of the medial and lateral anterior prefrontal cortex SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 Univ Paris 06, INSERM, U483, Paris, France. NIH, Cognit Neurosci Sect, Bethesda, MD USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT-NOV PY 2001 VL 47 IS 1-2 BP 93 EP 97 PG 5 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 489YR UT WOS:000172021100064 ER PT J AU Lane, RD Reiman, EM Ahern, GL Thayer, JF AF Lane, RD Reiman, EM Ahern, GL Thayer, JF TI Activity in medial prefrontal cortex correlates with vagal component of heart rate variability during emotion SO BRAIN AND COGNITION LA English DT Meeting Abstract ID STIMULATION C1 Univ Arizona, Dept Psychiat, Tucson, AZ 85721 USA. Univ Arizona, Dept Neurol, Tucson, AZ 85721 USA. NIA, Bethesda, MD 20892 USA. NR 5 TC 68 Z9 70 U1 3 U2 11 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT-NOV PY 2001 VL 47 IS 1-2 BP 97 EP 100 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 489YR UT WOS:000172021100065 ER PT J AU Lamar, M Zonderman, AB Resnick, S AF Lamar, M Zonderman, AB Resnick, S TI Strategic processing in relation to success and failure on a complex task of working memory SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT-NOV PY 2001 VL 47 IS 1-2 BP 162 EP 165 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 489YR UT WOS:000172021100085 ER PT J AU Fischbeck, KH AF Fischbeck, KH TI Polyglutamine expansion neurodegenerative disease SO BRAIN RESEARCH BULLETIN LA English DT Article; Proceedings Paper CT Meeting on Triplet Repeat Diseases CY JUN 01-03, 2000 CL MILAN, ITALY SP C Besta Natl Neurol Inst, Univ Milan, Inst Endocrinol, Italian Soc Neurosci, Telethon Italia Fdn DE neurodegeneration; Kennedy's disease; Huntington's disease; spinocerebellar ataxia; CREB-binding protein; drug screens ID BULBAR MUSCULAR-ATROPHY; SCA1 TRANSGENIC MICE; CREB-BINDING PROTEIN; EXPANDED POLYGLUTAMINE; INTRANUCLEAR INCLUSIONS; TRINUCLEOTIDE REPEAT; HUNTINGTONS-DISEASE; AGGREGATION; DROSOPHILA; TOXICITY AB Kennedy's disease was the first of eight neurodegenerative disorders found to be caused by expanded polyglutamine repeats. Each of these disorders is likely caused by a toxic gain of function in the disease gene product, often associated with inclusions of mutant protein in susceptible neurons. The mechanism of toxicity may involve sequestration and depletion of a polyglutamine-containing protein that is important to neuronal survival, such as CREB-binding protein. Recent insights into the biochemistry and cellular pathology of the polyglutamine expansion neurodegenerative diseases provide the opportunity for systematic drug screens and a rational approach to effective therapy. (C) 2001 Elsevier Science Inc. C1 NINCDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Fischbeck, KH (reprint author), NINCDS, Neurogenet Branch, NIH, Bldg 10,Room 3B14,10 Ctr Dr, Bethesda, MD 20892 USA. NR 17 TC 55 Z9 57 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD OCT-NOV PY 2001 VL 56 IS 3-4 BP 161 EP 163 DI 10.1016/S0361-9230(01)00577-9 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 495RN UT WOS:000172354300002 PM 11719245 ER PT J AU Grabczyk, E Kumari, D Usdin, K AF Grabczyk, E Kumari, D Usdin, K TI Fragile X syndrome and Friedreich's ataxia: Two different paradigms for repeat induced transcript insufficiency SO BRAIN RESEARCH BULLETIN LA English DT Article; Proceedings Paper CT Meeting on Triplet Repeat Diseases CY JUN 01-03, 2000 CL MILAN, ITALY SP C Besta Natl Neurol Inst, Univ Milan, Inst Endocrinol, Italian Soc Neurosci, Telethon Italia Fdn DE trinucleotide repeat expansion; triplex; transcription; methylation ID MENTAL-RETARDATION PROTEIN; RNA-BINDING PROTEIN; TRIPLET-REPEAT; FMR1 GENE; MYOTONIC-DYSTROPHY; IN-VITRO; CGG REPEAT; TRINUCLEOTIDE REPEAT; HAIRPIN STRUCTURES; IRON ACCUMULATION AB DNA repeat expansion is the genetic basis for a growing number of neurological disorders. While the largest subset of these diseases results in an increase in the length of a polyglutamine tract in the protein encoded by the affected gene the most common form of inherited mental retardation, fragile X syndrome, and the most common inherited ataxia, Friedreich's ataxia, are both caused by expansions that are transcribed but not translated. These expansions both decrease expression of the gene in which the expanded repeat is located, but they do so by quite different mechanisms. In fragile X syndrome, CGG (.) CCG expansion in the 5' untranslated region of the FMR1 gene leads to hypermethylation of the repeats and the adjacent CpG-rich promoter. Methylation prevents the binding of the transcription factor alpha -PaI/NRF-1, and may indirectly affect the binding of other factors via the formation of transcriptionally silent chromatin. In Friedreich's ataxia, GAA (.) TTC expansion in an intron of the FRDA gene reduces expression by interfering with transcription elongation. The model that best describes the available data is transcription-driven formation of a transient purine (.) purine (.) pyrimidine DNA triplex behind an advancing RNA polymerase. This structure lassoes the RNA polymerase that caused it, trapping the enzyme on the template. (C) 2001 Elsevier Science Inc. C1 NIDDKD, Mol & Cellular Biol Lab, Sect Genom Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Mol & Cellular Biol Lab, Sect Genom Struct & Funct, NIH, Bldg 8,Room 202,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. NR 88 TC 11 Z9 11 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD OCT-NOV PY 2001 VL 56 IS 3-4 BP 367 EP 373 DI 10.1016/S0361-9230(01)00572-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA 495RN UT WOS:000172354300031 PM 11719274 ER PT J AU Hallett, M AF Hallett, M TI Plasticity of the human motor cortex and recovery from stroke SO BRAIN RESEARCH REVIEWS LA English DT Article; Proceedings Paper CT Symposium of the Swiss-National-Science-Foundation CY MAR 29-31, 2001 CL WARTH, SWITZERLAND SP Swiss Natl Sci Fdn DE plasticity; rehabilitation; transcranial magnetic stimulation; stroke; amputation; motor learning; deafferentation ID TRANSCRANIAL MAGNETIC STIMULATION; INDUCED MOVEMENT THERAPY; ADULT SQUIRREL-MONKEYS; HUMAN CEREBRAL-CORTEX; FUNCTIONAL REORGANIZATION; BRAIN-STIMULATION; ISCHEMIC STROKE; HORIZONTAL CONNECTIONS; PHYSICAL THERAPY; PROGNOSTIC VALUE AB By a variety of mechanisms, the human brain is constantly undergoing plastic changes. Plasticity can be studied with phenomena such as peripheral deafferentation and motor learning. Spontaneous recovery from stroke in the chronic stag likely comes about because of plasticity, and the best recovery seems to result from reorganization in the damaged hemisphere. Knowledge about the physiology of brain plasticity has led to the development of new techniques for rehabilitation. Published by Elsevier Science BY. C1 NINCDS, Human Motor Control Sect, NIH, Med Neurol Branch, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINCDS, Human Motor Control Sect, NIH, Med Neurol Branch, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 67 TC 185 Z9 197 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD OCT PY 2001 VL 36 IS 2-3 SI SI BP 169 EP 174 DI 10.1016/S0165-0173(01)00092-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 497WU UT WOS:000172479100009 PM 11690613 ER PT J AU Goldstein, JA AF Goldstein, JA TI Clinical relevance of genetic polymorphisms in the human CYP2C subfamily SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE CYP2C; CYP2C9; CYP2C19; mephenytoin; omeprazole; phenytoin; polymorphisms; tolbutamide; warfarin ID MEPHENYTOIN OXIDATION POLYMORPHISM; PROTON PUMP INHIBITOR; POOR METABOLIZER PHENOTYPE; S-MEPHENYTOIN; PROGUANIL METABOLISM; CHINESE SUBJECTS; IN-VITRO; 4'-HYDROXYLATION PHENOTYPE; OMEPRAZOLE METABOLISM; DOSE REQUIREMENT AB The human CYP2Cs are an important subfamily of P450 enzymes that metabolize approximately 20% of clinically used drugs. There are four members of the subfamily, CYP2C8, CYP2C9, CYP2C19, and CYP2C18. Of these CYP2C8, CYP2C9, and CYP2C19 are of clinical importance. The CYP2Cs also metabolize some endogenous compounds such as arachidonic acid. Each member of this subfamily has been found to be genetically polymorphic. The most well-known of these polymorphisms is in CYP2C19. Poor metabolizers (PMs) of CYP2C19 represent approximately 3-5% of Caucasians, a similar percentage of African-Americans and 12-100% of Asian groups. The polymorphism affects metabolism of the anticonvulsant agent mephenytoin, proton pump inhibitors such as omeprazole, the anxiolytic agent diazepam, certain antidepressants, and the antimalarial drug proguanil. Toxic effects can occur in PMs exposed to diazepam, and the efficacy of some proton pump inhibitors may be greater in PMs than EMs at low doses of these drugs. A number of mutant alleles exist that can be detected by genetic testing. CYP2C9 metabolizes a wide variety of drugs including the anticoagulant warfarin, antidiabetic agents such as tolbutamide, anticonvulsants such as phenytoin, and nonsteroidal anti-inflammatory drugs. The incidence of functional polymorphisms is much lower, estimated to be 1/250 in Caucasians and lower in Asians. However, the clinical consequences of these rarer polymorphisms can be severe. Severe and life-threatening bleeding episodes have been reported in CYP2C9 PMs exposed to warfarin. Phenytoin has been reported to cause severe toxicity in PMs. New polymorphisms have been discovered in CYP2C8, which metabolizes taxol (paclitaxel). Genetic testing is available for ill of the known CYP2C variant alleles. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. RI Goldstein, Joyce/A-6681-2012 NR 64 TC 400 Z9 434 U1 2 U2 19 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD OCT PY 2001 VL 52 IS 4 BP 349 EP 355 DI 10.1046/j.0306-5251.2001.01499.x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 477MB UT WOS:000171286400002 PM 11678778 ER PT J AU Kollia, P Stavroyianni, N Stamatopoulos, K Zoi, K Viniou, N Mantzourani, M Noguchi, CT Paterakis, G Abazis, D Pangalos, C Loukopoulos, D Yataganas, X AF Kollia, P Stavroyianni, N Stamatopoulos, K Zoi, K Viniou, N Mantzourani, M Noguchi, CT Paterakis, G Abazis, D Pangalos, C Loukopoulos, D Yataganas, X TI Molecular analysis of transferrin receptor mRNA expression in acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE transferrin receptor; mRNA; acute myeloid leukaemia ID IRON UPTAKE; CELLS; LEUKEMIA; PCR; MECHANISMS; GROWTH AB Transferrin receptor (TfR, CD71) is an integral membrane glycoprotein that mediates cellular uptake of iron. In most tissues, TfR expression is correlated positively with proliferation and regulated at the post-transcriptional level. The available data regarding the pattern of TfR gene expression in haematological malignancies are very Limited. In the present study, we evaluated TfR gene expression at the molecular level in bone marrow (BM) samples of 44 patients with de novo acute myeloid leukaemia (AXIL) at diagnosis with BM blasts > 85%. TfR mRNA levels were determined by densitometric analysis of quantitative reverse transcription polymerase chain reaction products corresponding to TfR exons 15-17. Each sample was tested in at least two independent experiments. In 13/44 patients, TfR messages were not detected (this is probably an underestimate as some positive results may be attributed to residual normal erythroid cells present in the samples). In 17/44, TfR mRNA levels were low-intermediate, and were high in the remaining patients (14/44). TfR mRNA positivity was significantly associated with older age. No statistically significant correlations were found either with specific French-American-British (FAB) subtypes or attainment of complete remission, incidence of relapse and survival (after adjusting accordingly for age and FAB subtype). The absence of TfR mRNA transcripts in a significant minority of cases suggests that alternative mechanisms of iron uptake may function in AML blast cells. C1 Univ Thessaly, Sch Med, Dept Biol, Larisa, Greece. Univ Athens, Dept Med 1, Athens, Greece. NIH, Biol Chem Lab, Bethesda, MD 20892 USA. G Gennimatas Hosp, Dept Immunol, Athens, Greece. Diagnost Genet Ctr, Athens, Greece. RP Kollia, P (reprint author), Univ Thessaly, Sch Med, Dept Biol, Nafpliou 75, Glyfada 16674, Greece. NR 30 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2001 VL 115 IS 1 BP 19 EP 24 DI 10.1046/j.1365-2141.2001.03065.x PG 6 WC Hematology SC Hematology GA 483JN UT WOS:000171632400005 PM 11722405 ER PT J AU Nakamura, R Bahceci, E Read, EJ Leitman, SF Carter, CS Childs, R Dunbar, CE Gress, R Altemus, R Young, NS Barrett, AJ AF Nakamura, R Bahceci, E Read, EJ Leitman, SF Carter, CS Childs, R Dunbar, CE Gress, R Altemus, R Young, NS Barrett, AJ TI Transplant dose of CD34(+) and CD3(+) cells predicts outcome in patients with haematological malignancies undergoing T cell-depleted peripheral blood stem cell transplants with delayed donor lymphocyte add-back SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE T cell-depleted allogeneic PBSCT; HLA-identical sibling; GVHD; delayed DLI; CD34(+) and CD3(+) cell doses ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-HOST; COLONY-STIMULATING FACTOR; HEMATOLOGIC MALIGNANCIES; HIGH-RISK; MYELOGENOUS LEUKEMIA; DISEASE; CYTOMEGALOVIRUS; SURVIVAL; RELAPSE AB We sought to optimize and standardize stem cell and lymphocyte doses of T cell-depleted peripheral blood stem cell transplants (T-PBSCT), using delayed add-back of donor T cells (DLI) to prevent relapse and enhance donor immune recovery. Fifty-one patients with haematological malignancies received a T-PBSCT from an HLA-identical sibling, followed by DLI of 1 x 10(7) and 5 x 10(7) CD3(+) cells/kg on d +45 and +100 respectively. Twenty-four patients were designated as standard risk and twenty-seven patients with more advanced leukaemia were designated as high risk. Median recipient age was 38 years (range 10-56). Median (range) of CD34(+) and CD3(+) cell transplant doses were 4.6 (2.3-10.9) x 10(6)/kg and 0.83 (0.38-2) x 10(5)/kg respectively. The cumulative probability of acute GVHD was 39%. No patient died from GVHD or its consequences. The probability of developing chronic GVHD was 54% (18% extensive). The probability of relapse was 12% for the standard-risk patients and 66% for high-risk patients. In multivariate analysis, the risk factors for lower disease-free survival and overall survival were high-risk disease, CD34(+) dose <4.6 x 10(6)/kg and CD3(+) dose <0.83 x 10(5)/kg. Predictive factors for chronic GVHD were a T-cell dose at transplant > 0.83 x 10(5) CD3(+) cells/ kg. These results further define the impact of CD34 and CD3 cell dose on transplant outcome and show that careful dosing of stem cells and lymphocytes may permit the control and optimization of transplant outcome. C1 NHLBI, Stem Cell Transplantat Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Transplantat Unit, Hematol Branch, NIH, 2000 Rockville Pike,Bldg 10,Rm 7C 103, Bethesda, MD 20892 USA. NR 38 TC 45 Z9 46 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2001 VL 115 IS 1 BP 95 EP 104 DI 10.1046/j.1365-2141.2001.02983.x PG 10 WC Hematology SC Hematology GA 483JN UT WOS:000171632400018 PM 11722418 ER PT J AU Zenan, JS Rambo, N Burroughs, CM Alpi, KM Cahn, MA Rankin, J AF Zenan, JS Rambo, N Burroughs, CM Alpi, KM Cahn, MA Rankin, J TI Public Health Outreach Forum: report SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article C1 Univ Nevada, Savitt Med Lib 306, Reno, NV 89557 USA. Ctr Dis Control & Prevent, CDC Informat Ctr, Atlanta, GA 30333 USA. Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, Bethesda, MD 20894 USA. Cornell Univ, Weill Med Coll, Samuel J Wood Lib, New York, NY 10021 USA. Univ Washington, Natl Network Lib Med, NNLM Outreach, Evaluat Resource Ctr, Seattle, WA 98195 USA. RP Zenan, JS (reprint author), Univ Nevada, Savitt Med Lib 306, 1664 N Virginia St, Reno, NV 89557 USA. OI Rambo, Neil/0000-0003-2376-5121 NR 0 TC 6 Z9 6 U1 0 U2 1 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 2001 VL 89 IS 4 BP 400 EP 403 PG 4 WC Information Science & Library Science SC Information Science & Library Science GA 530JX UT WOS:000174355500011 PM 11837264 ER PT J AU Rambo, N Zenan, JS Alpi, KM Burroughs, CM Cahn, MA Rankin, J AF Rambo, N Zenan, JS Alpi, KM Burroughs, CM Cahn, MA Rankin, J TI Public Health Outreach Forum: lessons learned SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article C1 Univ Washington, Natl Network Lib Med, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, CDC Informat Ctr, Atlanta, GA 30333 USA. Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, Bethesda, MD 20894 USA. Cornell Univ, Weill Med Coll, Samuel J Wood Lib, New York, NY 10021 USA. Univ Nevada, Savitt Med Lib 306, Reno, NV 89557 USA. RP Rambo, N (reprint author), Univ Washington, Natl Network Lib Med, Box 357155,Pacific NW Reg, Seattle, WA 98195 USA. OI Rambo, Neil/0000-0003-2376-5121 NR 0 TC 18 Z9 19 U1 0 U2 1 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 2001 VL 89 IS 4 BP 403 EP 406 PG 4 WC Information Science & Library Science SC Information Science & Library Science GA 530JX UT WOS:000174355500012 PM 11837265 ER PT J AU Hatcher, JL Baris, D Olshan, AF Inskip, PD Savitz, DA Swanson, GM Pottern, LM Greenberg, RS Schwartz, AG Schoenberg, JB Brown, LM AF Hatcher, JL Baris, D Olshan, AF Inskip, PD Savitz, DA Swanson, GM Pottern, LM Greenberg, RS Schwartz, AG Schoenberg, JB Brown, LM TI Diagnostic radiation and the risk of multiple myeloma (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; ionizing radiation; multiple myeloma; X-rays AB Objective: To evaluate the relationship between cumulative lifetime exposure to diagnostic radiation and the risk of multiple myeloma using data from a large, multi-center, population-based case-control study. Methods: Study subjects included a total of 540 cases with newly diagnosed multiple myeloma and 1998 frequency-matched population controls living in three areas of the United States (Georgia, Michigan, New Jersey). Information on exposure to diagnostic X-rays was obtained by personal interview. Results: No association was found between case-control status and the total number of reported diagnostic X-rays of any type (odds ratio (OR) for 20 or more compared to less than 5 X-rays = 0.9, 95% confidence interval (95% CI) = 0.7-1.2). There was no evidence of an excess risk of multiple myeloma among individuals who reported exposure to 10 or more diagnostic X-rays that impart a relatively high radiation dose to the bone marrow, as compared to individuals reporting no such exposures (OR 0.7, 95% CI 0.4-1.3). Conclusions: These data suggest that exposure to diagnostic X-rays has a negligible impact, if any, on risk of developing multiple myeloma. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Michigan Canc Fdn, Detroit, MI 48201 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. New Jersey State Dept Hlth, Trenton, NJ 08625 USA. Karmanos Canc Inst, Detroit, MI USA. RP Hatcher, JL (reprint author), 433 3rd St NE, Washington, DC 20002 USA. FU NCI NIH HHS [N01-CN-05227, N01-CN-31022, N01-CN-05225, N01-CP-51089, N01-CP51092, N01-CP-51090] NR 32 TC 9 Z9 9 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2001 VL 12 IS 8 BP 755 EP 761 DI 10.1023/A:1011205908596 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 460AA UT WOS:000170282600010 PM 11562116 ER PT J AU Warren, KE Patel, MC Aikin, AA Widemann, B Libucha, M Adamson, PC Neuwirth, R Benziger, D O'Toole, T Ford, K Patronas, N Packer, RJ Balis, FM AF Warren, KE Patel, MC Aikin, AA Widemann, B Libucha, M Adamson, PC Neuwirth, R Benziger, D O'Toole, T Ford, K Patronas, N Packer, RJ Balis, FM TI Phase I trial of lobradimil (RMP-7) and carboplatin in children with brain tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE pediatric; blood : brain barrier; lobradimil; carboplatin ID BRADYKININ ANALOG; INTRACAROTID INFUSION; DRUG-DELIVERY; BARRIER; GLIOMAS; PERMEABILITY AB Purpose: To determine the maximum tolerated dose (MTD), the incidence and severity of toxicities, and the pharmacokineties of lobradimil administered intravenously over 10 min in combination with carboplatin in children with refractory brain tumors. Methods: A group of 25 children with primary brain tumors received carboplatin and lobradimil on two consecutive days every 28 days. The 10-min lobradimil infusion began 5 min before the end of the carboplatin infusion. Four lobradimil dose levels (100, 300, 450 and 600 ng/kg ideal body weight, IBW) were studied in cohorts of 4 to 13 patients. Carboplatin was adaptively dosed based on the glomerular filtration rate to achieve a target plasma area under the concentration-time curve (AUC) of 7.0 mg(.)min/ml per course (5.0 mg(.)min/ml for patients who had previously received craniospinal radiation or myeloablative chemotherapy). Results: Lobradimil toxicity was immediate, tolerable and rapidly reversible. The most frequent toxicities were hypotension, flushing, headache and gastrointestinal complaints. One patient on the 600 ng/kg dose level had a seizure during the lobradimil infusion. The incidence and severity of lobradimil toxicities were not dose-related and the lobradimil dose was not escalated beyond the 600 ng/kg IBW dose level. Two patients had partial responses and ten patients had stable disease. Myelosuppression (thrombocytopenia more prominent than neutropenia) was the primary toxicity attributed to carboplatin. Lobradimil pharmacokine tics were characterized by rapid clearance from the plasma compartment and substantial interpatient variability. Conclusions: The combination of carboplatin and lobradimil is safe and tolerable. An MTD for lobradimil was not defined because toxicity was not dose-related. The recommended pediatric phase II dose of lobradimil is 600 ng/kg IBW. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Alkermes Inc, Cambridge, MA USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Warren, KE (reprint author), NCI, Neurooncol Branch, Bldg 10,Rm 12S245,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. NR 16 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2001 VL 48 IS 4 BP 275 EP 282 DI 10.1007/s002800100356 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 486EQ UT WOS:000171805800004 PM 11710627 ER PT J AU Herman, EH Zhang, J Rifai, N Lipshultz, SE Hasinoff, BB Chadwick, DP Knapton, A Chai, J Ferrans, VJ AF Herman, EH Zhang, J Rifai, N Lipshultz, SE Hasinoff, BB Chadwick, DP Knapton, A Chai, J Ferrans, VJ TI The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin and mitoxantrone-induced cardiotoxicity SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE doxorubicin; mitoxantrone; dexrazoxane; cardiotoxicity; cardiac troponin T ID SPONTANEOUSLY HYPERTENSIVE RATS; ACUTE MYOCARDIAL-INFARCTION; CARDIOPROTECTIVE AGENT; BEAGLE DOGS; DIAGNOSTIC EFFICIENCY; ANTICANCER COMPOUND; SAFETY ASSESSMENT; BREAST-CANCER; ICRF-187; TOXICITY AB Purpose: To compare the protective effect of dexrazoxane (DRZ) against cardiotoxicity induced by doxorubicin (DXR) and mitoxantrone (MTX). Methods: Adult male spontaneously hypertensive rats (SHR) were treated with 1 mg/kg DXR (i.v.) or 0.5 mg/kg MTX (i.v.), either alone or 30 min after 25 mg/kg DRZ (i.p.) weekly for up to 12 weeks. Animals treated with DXR alone either died (n = 2) or were killed (n = 3) at a cumulative dose of 10 mg/kg. The severity of cardiac lesions (cytoplasmic vacuolization and myofibrillar loss) were graded semiquantitatively by light microscopy on a scale of 0 to 3. Results: Cardiac lesions were observed in all SHR given DXR or MTX alone, and were attenuated in those given DRZ prior to either DXR (mean lesion scores 2.7 vs 1.5; P < 0.05) or MTX (mean lesion scores 2.0 vs 1.25; P <0.05). Cardioprotection was also demonstrated by monitoring serum levels of cardiac troponin T (cTnT), which were elevated in all animals receiving DXR or MTX alone. These elevations were attenuated in SHR given the combination of DXR and DRZ (mean values 0.79 ng/ml vs 0.24 ng/ml; P < 0.05) and MTX and DRZ (mean values 0.19 ng/ml vs 0.04 ng/ml; P < 0.05). Biochemical studies have shown that both DXR and MTX form potentially cardiotoxic complexes with iron. ADR-925 (the hydrolysis product of DRZ) and other chelators (EDTA., diethylenetriaminepentaacetic acid and desferrioxamine) removed Fe(III) from its complex with MTX or DXR. Conclusions: The present study showed that DRZ significantly attenuates the cardiotoxicity induced by DXR and MTX, and that this protective activity can be assessed by morphological evaluation of cardiac tissues and by monitoring the concentrations of cTnT in serum. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD910, Laurel, MD 20708 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Sch Med & Dent, Div Pediat Cardiol, Rochester, NY 14642 USA. Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD910, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 42 TC 74 Z9 76 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2001 VL 48 IS 4 BP 297 EP 304 DI 10.1007/s002800100348 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 486EQ UT WOS:000171805800007 PM 11710630 ER PT J AU Engelstad, LP Stewart, SL Nguyen, BH Bedeian, KL Rubin, MM Pasick, RJ Hiatt, RA AF Engelstad, LP Stewart, SL Nguyen, BH Bedeian, KL Rubin, MM Pasick, RJ Hiatt, RA TI Abnormal pap smear follow-up in a high-risk population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INCOME MINORITY WOMEN; PAPANICOLAOU SMEARS; COLORECTAL-CANCER; ADHERENCE; BREAST; CARE AB Low-income women are at high risk of developing cervical cancer attributable not only to the higher prevalence of risk factors in this population but also to the lack of timely follow-up of abnormal Pap smears. This study evaluates the efficacy of an aggressive follow-up strategy. Women with abnormal Pap smear results after screening in a public hospital emergency department were randomly assigned to follow-up either by a case-managed approach using computerized tracking and universal colposcopy or by traditional care. The main outcome was the proportion of women receiving follow-up in 6 months. A secondary outcome was the proportion of women receiving follow-up by 6 months and diagnostic resolution in 18 months. Of 54 women in the intervention group, 65% kept at least one follow-up appointment in 6 months compared with 41% of the 54 women in the control group (P = 0.012). Half the women in the intervention group versus 19% of women in the control group had follow-up in 6 months and diagnostic resolution in 18 months (P = 0.001). After adjusting for age, initial Pap smear result, and race/ethnicity, the odds of having follow-up in 6 months were four times greater for women in the intervention group (odds ratio = 4.0; 95% confidence interval, 1.6-9.7), and the odds of having both follow-up in 6 months and diagnostic resolution in 18 months were more than six times greater (odds ratio = 6.5; 95% confidence interval, 2.4-17.8). This study demonstrates that an aggressive follow-up strategy significantly improves the rate of both initial follow-up and diagnostic resolution of abnormal Pap smears along low-income women with atypical squamous cells of undetermined significance and atypical glandular cells of undetermined significance when compared with traditional care. C1 Alameda Cty Med Ctr, Oakland, CA 94602 USA. San Francisco State Univ, San Francisco, CA 94132 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Engelstad, LP (reprint author), Highland Hosp, Alameda Cty Med Ctr, Dept Internal Med, 1411 E 31st St, Oakland, CA 94602 USA. FU NCI NIH HHS [5 PO1 CA55112, P01 CA055112-09S3] NR 28 TC 38 Z9 38 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2001 VL 10 IS 10 BP 1015 EP 1020 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 480ZH UT WOS:000171492900001 PM 11588126 ER PT J AU Castle, PE Hillier, SL Rabe, LK Hildesheim, A Herrero, R Bratti, MC Sherman, ME Burk, RD Rodriguez, AC Alfaro, M Hutchinson, ML Morales, J Schiffman, M AF Castle, PE Hillier, SL Rabe, LK Hildesheim, A Herrero, R Bratti, MC Sherman, ME Burk, RD Rodriguez, AC Alfaro, M Hutchinson, ML Morales, J Schiffman, M TI An association of cervical inflammation with high-grade cervical neoplasia in women infected with oncogenic human papillomavirus (HPV) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK-FACTORS; BACTERIAL VAGINOSIS; CANCER; POPULATION; DIAGNOSIS AB Previous reports of genital conditions, such as nonspecific genital infection/sore or vaginal discharge associated with cervical cancer (L. A. Brinton et al., J. Natl. Cancer Inst. (Bethesda), 79: 23-30, 1987; C. J. Jones et al., Cancer Res., 50: 3657-3662, 1990), suggest a possible link between either genital tract inflammation or changes in bacteria flora consistent with bacterial vaginosis (BV) and cervical cancer. To test whether changes in vaginal bacterial flora or the degree of cervical inflammation are associated with women having a human papillomavirus (HPV) infection or with women infected with oncogenic HPV having high-grade cervical lesions (high-grade squamous intraepithelial lesions or cancer), we conducted a case-control study of women < 50 years old enrolled in the Costa Rican natural history study of HPV and cervical neoplasia. To test whether BV and inflammation were associated with HPV DNA positivity, Analysis 1 was restricted to women with no or mild (low-grade or equivocal) cytological abnormalities, and the degree of inflammation and Nugent score (a measure of BV) were compared between women infected (it = 220) and not infected (it = 130) with HPV. To test whether BV and inflammation were associated with high-grade lesions, Analysis 2 was restricted to women infected with oncogenic HPV, and the degree of inflammation and Nugent score were compared between women with (it = 95) and without (re = 158) high-grade cervical lesions. In Analysis 1, BV and cervical inflammation were not associated with HPV infection. In Analysis 2, BV was not associated with high-grade lesions. However, we found a marginally significant positive trend of increasing cervical inflammation associated with high-grade lesions in oncogenic HPV-infected Women, (P-trend = 0.05). Overt cervicitis was associated with a 1.9-fold increase in risk of high-grade lesions (95% confidence interval, 0.90-4.1). The results of this study suggest that cervical inflammation may be associated with high-grade lesions and may be a cofactor for high-grade cervical lesions in women infected with oncogenic HPV. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. Magee Womens Res Inst, Pittsburgh, PA 15213 USA. Caja Costarricense Seguro Social, San Jose 1000, Costa Rica. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. NR 25 TC 123 Z9 129 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2001 VL 10 IS 10 BP 1021 EP 1027 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 480ZH UT WOS:000171492900002 PM 11588127 ER PT J AU Mayne, ST Risch, HA Dubrow, R Chow, WH Gammon, MD Vaughan, TL Farrow, DC Schoenberg, JB Stanford, JL Ahsan, H West, AB Rotterdam, H Blot, WJ Fraumeni, JF AF Mayne, ST Risch, HA Dubrow, R Chow, WH Gammon, MD Vaughan, TL Farrow, DC Schoenberg, JB Stanford, JL Ahsan, H West, AB Rotterdam, H Blot, WJ Fraumeni, JF TI Nutrient intake and risk of subtypes of esophageal and gastric cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL REFLUX DISEASE; ASCORBIC-ACID CONCENTRATIONS; BODY-MASS; CARDIA; ADENOCARCINOMA; DIETARY; TOBACCO; ALCOHOL; STOMACH AB Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been rising rapidly. We examined nutrient intake as a risk factor for esophageal and gastric cancers in a population-based case-control study in Connecticut, New Jersey, and western Washington state. Interviews were completed for cases with histologically confirmed esophageal adenocarcinoma (it = 282), adenocarcinoma of the gastric cardia (it = 255), esophageal squamous cell carcinoma (it = 206), and noncardia gastric adenocarcinoma (it = 352), along with population controls (it = 687). Associations between nutrient intake and risk of cancer were estimated by adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of intake. The following nutrients were significantly inversely associated with risk of all four tumor types: fiber, beta -carotene, folate, and vitamins C and B6. In contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly positively associated with risk of all four tumor types. Dietary fat [OR, 2.18; 95% confidence interval (CI), 1.27-3.76] was significantly associated with risk of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16) was associated with noncardia gastric cancer only. Vitamin C supplement use was associated with a significantly lower risk for noncardia gastric cancer (OR, 0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant-based foods was associated with a reduced risk of adenocarcinomas of the esophagus and gastric cardia, whereas higher intake of nutrients found primarily in foods of animal origin was associated with an increased risk. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. New Jersey Dept Hlth & Senior Serv, Canc Epidemiol Serv, Trenton, NJ 08625 USA. Columbia Univ, Div Epidemiol, New York, NY USA. Columbia Univ, Dept Pathol, New York, NY USA. NYU Med Ctr, Dept Pathol, New York, NY 10016 USA. Int Epidemiol Inst, Rockville, MD USA. RP Mayne, ST (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. FU NCI NIH HHS [N01-CN05230, N02-CP40501, U01-CA57923, U01-CA57949, U01-CA57983] NR 37 TC 266 Z9 281 U1 1 U2 19 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2001 VL 10 IS 10 BP 1055 EP 1062 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 480ZH UT WOS:000171492900006 PM 11588131 ER PT J AU Hsing, AW Chen, C Chokkalingam, AP Gao, YT Dightman, DA Nguyen, HT Deng, J Cheng, JR Sesterhenn, IA Mostofi, FK Stanczyk, FZ Reichardt, JKV AF Hsing, AW Chen, C Chokkalingam, AP Gao, YT Dightman, DA Nguyen, HT Deng, J Cheng, JR Sesterhenn, IA Mostofi, FK Stanczyk, FZ Reichardt, JKV TI Polymorphic markers in the SRD5A2 gene and prostate cancer risk: A population-based case-control study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID STEROID 5-ALPHA-REDUCTASE-2 DEFICIENCY; MOLECULAR-GENETICS; HIRSUTE WOMEN; TYPE-2 GENE; ASSOCIATION; CYP17; SUBSTITUTION; GENOTYPE AB It has been suggested that the activity of the steroid 5 alpha -reductase type II enzyme (encoded by the SRD5A2 gene) may be associated with prostate cancer risk and that population differences in this enzyme's activity may account for part of the substantial racial/ethnic disparity in prostate cancer risk. To provide etiological clues, we evaluated the relationships of four polymorphic markers in the SRD5A2 gene, specifically, A49T (a substitution of threonine for alanine at codon 49), V89L (a substitution of leucine for valine at codon 89), R227Q (a substitution of glutamine for arginine at codon 227), and a (TA) dinucleotide repeat, with prostate cancer risk in a population-based case-control study in China, a population with the lowest reported prostate cancer incidence rate in the world. Genotypes of these four markers were determined from genomic DNA of 191 incident cases of prostate cancer and 304 healthy controls using PCR-based assays, and serum androgen levels were measured in relation to these genotypes. All study subjects had the wild-type AA genotype of the A49T marker, and 99% had the RR genotype of the R227Q marker. For the V89L marker, prevalences of the LL, VV, and VL genotypes among controls were 35%, 21%, and 45%, respectively. Compared with men with the VV genotype, those with the LL genotype had a statistically nonsignificant 12% reduced risk (odds ratio = 0.88, 95% confidence interval, 0.53-1.47). In addition, men with the LL genotype had significantly higher serum levels of testosterone and significantly lower serum levels of 5 alpha -androstane-3 alpha ,17 beta -diol glucuronide than men with other genotypes. Men heterozygous for the (TA)(0) allele of the (TA) marker had a modest, statistically nonsignificant risk reduction (odds ratio = 0.67; 95% confidence interval, 0.39-1.12) compared with men homozygous for the (TA) allele, along with significantly higher serum dihydrotestosterone levels. The observed V89L genotype prevalences and the association between V89L genotypes and serum androgen levels support the hypothesis that genotypes associated with lower levels of 5 alpha -reductase activity are more common in low-risk populations. Although we found no statistically significant associations of these SRD5A2 polymorphisms with prostate cancer risk, a small effect of these markers cannot be ruled out because of the rarity of certain marker genotypes. Larger studies are needed to further clarify the role of these markers and to elucidate whether genetic diversity of the SRD5A2 gene, alone or in combination with other susceptibility genes, can help explain the large racial/ethnic differences in prostate cancer risk. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Shanghai Canc Inst, Shanghai 200032, Peoples R China. Univ So Calif, Keck Genet Med, Inst Med Genet, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS MSC 7234,6120 Execut Blvd, Rockville, MD 20852 USA. FU NCI NIH HHS [CA68581] NR 39 TC 88 Z9 92 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2001 VL 10 IS 10 BP 1077 EP 1082 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 480ZH UT WOS:000171492900009 PM 11588134 ER PT J AU Lacey, JV Hsing, AW Fillmore, CM Hoffman, S Helzlsouer, KJ Comstock, GW AF Lacey, JV Hsing, AW Fillmore, CM Hoffman, S Helzlsouer, KJ Comstock, GW TI Null association between insulin-like growth factors, insulin-like growth factor-binding proteins, and prostate cancer in a prospective study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FACTOR-I; RISK C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. RP Lacey, JV (reprint author), Environm Epidemiol Branch, 6120 Execut Blvd,MSC 7234, Rockville, MD 20852 USA. NR 5 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2001 VL 10 IS 10 BP 1101 EP 1102 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 480ZH UT WOS:000171492900013 PM 11588138 ER PT J AU Yamanaka, R Zullo, SA Ramsey, J Onodera, M Tanaka, R Blaese, M Xanthopoulos, KG AF Yamanaka, R Zullo, SA Ramsey, J Onodera, M Tanaka, R Blaese, M Xanthopoulos, KG TI Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus SO CANCER GENE THERAPY LA English DT Article DE endostatin; Semliki Forest virus; antiangiogenic therapy; malignant brain tumor ID ADENOVIRUS-MEDIATED TRANSFER; TUMOR-GROWTH; GENE-THERAPY; SINDBIS VIRUS; ANGIOGENESIS; CANCER; ANGIOSTATIN; METASTASES; EXPRESSION; SUPPRESSION AB Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors. C1 Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 9518122, Japan. NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Yamanaka, R (reprint author), Niigata Univ, Brain Res Inst, Dept Neurosurg, Asahimachi Dori 1-757, Niigata 9518122, Japan. NR 34 TC 43 Z9 46 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD OCT PY 2001 VL 8 IS 10 BP 796 EP 802 DI 10.1038/sj.cgt.7700367 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 483MF UT WOS:000171638300012 PM 11687903 ER PT J AU Middelton, LA Peters, KF AF Middelton, LA Peters, KF TI Genes and inheritance SO CANCER NURSING LA English DT Article DE genes; chromosomes; pedigree; mutation; inheritance AB The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are be introduced and the biochemistry of genetic errors is described. C1 NCI, UOB, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. RP Middelton, LA (reprint author), NCI, UOB, NIH, 10 Ctr Dr,MSC 1873, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD OCT PY 2001 VL 24 IS 5 BP 357 EP 369 DI 10.1097/00002820-200110000-00006 PG 13 WC Oncology; Nursing SC Oncology; Nursing GA 479NK UT WOS:000171410300004 PM 11605706 ER PT J AU Stella, A Wagner, A Shito, K Lipkin, SM Watson, P Guanti, G Lynch, HT Fodde, R Liu, B AF Stella, A Wagner, A Shito, K Lipkin, SM Watson, P Guanti, G Lynch, HT Fodde, R Liu, B TI A nonsense mutation in MLH1 causes exon skipping in three unrelated HNPCC families SO CANCER RESEARCH LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; MESSENGER-RNA; COLON-CANCER; GENE; HMLH1; ASSOCIATION; KINDREDS; MSH6 AB Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 are responsible for the majority of hereditary nonpolyposis colorectal cancer (HNPCC) families. A common mutation mechanism is to disrupt MLH1 and MSH2 mRNA splicing. The disruption creates aberrant mRNAs lacking specific coding exons (exon skipping). Here, we report a novel skipping of MLH1 exon 12 caused by an AAG to TAG nonsense mutation at codon 461 in three HNPCC families of North American origins. The nonsense codon was found in a conserved haplotype in the three unrelated families and seems to represent a founder mutation. The skipping created an aberrant MLH1 mRNA transcript lacking exon 12. The effect of the codon 461 nonsense mutation on exon 12 skipping is evident even though it was placed in a minigene construct containing entirely different coding sequences. Notably, the effect of the nonsense mutation on exon skipping is incomplete. Accordingly, a second aberrant MLH1 transcript encompassing the nonsense codon is also produced. Whereas the latter transcript is unstable, presumably because of nonsense-mediated mRNA decay, neither of the aberrant transcripts seems to affect the stability of wild-type MLH1 mRNA. This study demonstrates that the germ-fine nonsense mutation at codon 461 of MLH1 disrupts normal MLH1 mRNA processing, and that exon skipping underlies pathogenesis in these HNPCC families. C1 Leiden Univ, Med Ctr, Dept Human & Clin Genet, Leiden, Netherlands. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Univ Bari, DIMIMP Policlin, Sez Genet Med, I-70124 Bari, Italy. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Creighton Univ, Sch Med, Dept Prevent Med, Omaha, NE 68178 USA. RP Fodde, R (reprint author), Leiden Univ, Med Ctr, Dept Human & Clin Genet, Leiden, Netherlands. RI Stella, Alessandro/I-8832-2012; OI Stella, Alessandro/0000-0002-9035-6267; Fodde, Riccardo/0000-0001-9839-4324 FU NCI NIH HHS [CA74684-03, CA81357-01] NR 26 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2001 VL 61 IS 19 BP 7020 EP 7024 PG 5 WC Oncology SC Oncology GA 479PB UT WOS:000171411800010 PM 11585727 ER PT J AU Hua, XQH Genini, D Gussio, R Tawatao, R Shih, H Kipps, TJ Carson, DA Leoni, LM AF Hua, XQH Genini, D Gussio, R Tawatao, R Shih, H Kipps, TJ Carson, DA Leoni, LM TI Biochemical genetic analysis of indanocine resistance in human leukemia SO CANCER RESEARCH LA English DT Article ID CANCER-CELLS; TUBULIN; AGENTS AB Indanocine is a potent tubulin-binding drug that is cytotoxic to multidrug-resistant cancer cell lines. We demonstrated that indanocine specifically induces apoptosis in malignant B cells from patients with chronic lymphocytic leukemia. To address the exact biochemical basis for indanocine toxicity, an indanocine-resistant clone was selected from mutagenized CEM human lymphoblastoid cells. The resistant cells displayed a stable indanocine-resistant phenotype for at least 9 months in drug-free culture. The cloned cells are cross-resistant to colchicine and vinblastine, but not to paclitaxel, and do not have increased expression of the multidrug-resistant p170 glycoprotein. In both parental cells and cell extracts, indanocine treatment caused tubulin depolymerization. In contrast, the tubulin in the resistant clone did not depolymerize under identical conditions. Both extract mixing and cell fusion experiments suggested that a stable structural change in microtubules, rather than a soluble factor, was responsible for indanocine resistance. Sequence analysis of parental and resistant cells revealed a single point mutation in the M40 isotype of beta -tubulin at nucleotide 1050 (G-->T, Lys(350)-->Asn) in the indanocine-resistant clone, in a region close to the putative colchicine binding site. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, La Jolla, CA 92093 USA. NCI, Target Struct Based Brug Discovery Grp, Informat Technol Branch, NIH, Frederick, MD 21702 USA. RP Leoni, LM (reprint author), Univ Calif San Diego, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NCI NIH HHS [CA81534]; NIGMS NIH HHS [GM23200] NR 14 TC 28 Z9 31 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2001 VL 61 IS 19 BP 7248 EP 7254 PG 7 WC Oncology SC Oncology GA 479PB UT WOS:000171411800045 PM 11585762 ER PT J AU Abeysinghe, RD Greene, BT Haynes, R Willingham, MC Turner, JL Planalp, RP Brechbiel, MW Torti, FM Torti, SV AF Abeysinghe, RD Greene, BT Haynes, R Willingham, MC Turner, JL Planalp, RP Brechbiel, MW Torti, FM Torti, SV TI p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron chelator SO CARCINOGENESIS LA English DT Article ID EFFECTIVE ANTIPROLIFERATIVE AGENTS; ISONICOTINOYL HYDRAZONE CLASS; TRANSFERRIN RECEPTOR; CELL-LINES; MONOCLONAL-ANTIBODIES; DNA FRAGMENTATION; METAL CHELATOR; TUMOR-GROWTH; IN-VITRO; P53 GENE AB Iron is involved in essential biochemical reactions ranging from respiration to DNA synthesis. Consequently, iron deprivation has been proposed as a strategy for inhibition of tumor cell growth. We recently described a novel iron chelator, tachypyridine [N,N ' ,N " -tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane], and demonstrated that it not only inhibited growth of cultured tumor cells, but was actively cytotoxic. Here we explore the mechanisms underlying tachpyridine cytotoxicity. Using several criteria, including time-lapse video microscopy, DNA staining and TUNEL assays, tachpyridine was shown to specifically induce apoptotic cell death. Further, unlike numerous cytotoxic chemotherapeutic drugs which induce apoptosis by activating p53-dependent pathways, tachpyridine-mediated cell death did not require p53 activation. Although immunoblotting revealed rapid accumulation of p53 following treatment with tachpyridine, p21(WAF1) was not induced. Further, neither cytotoxicity nor apoptosis required p53. p53 null human lung cancer H1299 cells transfected with an ecdysone-inducible p53 exhibited equivalent sensitivity to tachpyridine in the presence and absence of p53, demonstrating the lack of requirement for p53 in an isogenic cell system. Further, time-lapse video microscopy and TUNEL assays demonstrated that both p53 null and p53 wildtype cells underwent apoptotic cell death in response to tachpyridine. In addition, in 55 human cancer cell lines the mean GI(50) of tachpyridine in cells with mutant p53 was virtually identical to the GI(50) in cells with wild-type p53. These results demonstrate that tachpyridine initiates an apoptotic mode of cell death that does not require functional p53. Since over 50% of human tumors contain a functionally defective p53 that reduces sensitivity to commonly used chemotherapeutic agents, such as etoposide and cisplatin, the ability of tachpyridine to induce apoptosis independently of p53 may offer an advantage in antitumor therapy. C1 Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Canc Biol, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Torti, SV (reprint author), Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27109 USA. FU NIDDK NIH HHS [DK 57781] NR 54 TC 63 Z9 65 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2001 VL 22 IS 10 BP 1607 EP 1614 DI 10.1093/carcin/22.10.1607 PG 8 WC Oncology SC Oncology GA 480ZD UT WOS:000171492500004 PM 11576999 ER PT J AU Goodman, JE Lavigne, JA Wu, K Helzlsouer, KJ Strickland, PT Selhub, J Yager, JD AF Goodman, JE Lavigne, JA Wu, K Helzlsouer, KJ Strickland, PT Selhub, J Yager, JD TI COMT genotype, micronutrients in the folate metabolic pathway and breast cancer risk SO CARCINOGENESIS LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; S-ADENOSYLHOMOCYSTEINE; PLASMA HOMOCYSTEINE; GENETIC POLYMORPHISMS; VITAMIN STATUS; ADENOSYLMETHIONINE; 5-METHYLTETRAHYDROFOLATE; INTERRELATIONS; ASSOCIATION; CONSUMPTION AB Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens (CEs), using S-adenosylmethionine (SAM) as a methyl donor. Several studies have indicated that the val108met COMT polymorphism, which results in a 3-4-fold decrease in activity, is associated with increased breast cancer risk. Folate, whose intake levels have also been associated with breast cancer risk, and other micronutrients in the folate metabolic pathway influence levels of SAM and S-adenosylhomocysteine (SAH), a COMT inhibitor generated by the demethylation of SAM. Because these micronutrients have been shown to alter SAM and SAH levels, we hypothesized that they could also affect COMT-catalyzed CE methylation. Although measurements of SAM and SAH were not initially collected, a secondary analysis of data from two nested case-control studies was performed to examine whether serum levels of folate, vitamin B12 (B12), pyridoxal 5 ' -phosphate (PLP), cysteine and homocysteine, in conjunction with COMT genotype, were associated with breast cancer risk. COMTHH (high activity COMT homozygote) breast cancer cases had statistically significantly lower levels of homocysteine (P = 0.05) and cysteine (P = 0.04) and higher levels of PLP (P = 0.02) than COMTHH controls. In contrast, COMTLL (low activity COMT homozygote) cases had higher levels of homocysteine than COMTLL controls (P = 0.05). No associations were seen between B12, COMT genotype, and breast cancer risk. An increasing number of COMTL alleles was significantly associated with increased breast cancer risk in women with below median levels of folate (P-trend = 0.05) or above median levels of homocysteine (P-trend = 0.02). These findings are consistent with a role for certain folate pathway micronutrients in mediating the association between COMT genotype and breast cancer risk. C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Tufts Univ, Human Nutr Res Ctr Aging, James Mayer USDA, Dept Vitamin Bioavailabil, Boston, MA 02111 USA. RP Yager, JD (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA/ES62988, CA77550, R21 CA/ES66204]; NIEHS NIH HHS [ES07141] NR 38 TC 48 Z9 49 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 OCT PY 2001 VL 22 IS 10 BP 1661 EP 1665 DI 10.1093/carcin/22.10.1661 PG 5 WC Oncology SC Oncology GA 480ZD UT WOS:000171492500011 PM 11577006 ER PT J AU Divi, RL Dragan, YP Pitot, HC Poirier, MC AF Divi, RL Dragan, YP Pitot, HC Poirier, MC TI Immunohistochemical localization and semi-quantitation of hepatic tamoxifen-DNA adducts in rats exposed orally to tamoxifen SO CARCINOGENESIS LA English DT Article ID SURGICAL-ADJUVANT-BREAST; BOWEL-PROJECT; LIVER; EXPRESSION; CARCINOMA; CANCER; FOCI; RESISTANCE; KIDNEY; CELLS AB Administration of tamoxifen (TAM) has been shown to induce hepatocellular carcinogenesis and TAM-DNA adduct formation in rat liver. Here we present TAM-DNA adduct localization and semi-quantitation in hepatic tissue of rats by immunohistochemical staining followed by image analysis. We have also used a quantitative immunoassay to provide a validation for the immunohistochemical values. Rats were fed diets containing 0, 5, 50, 150 or 500 p.p.m. TAM for 45 weeks. Serial sections of paraffin-embedded liver were stained for TAM-DNA adducts using a polyclonal TAM-DNA antiserum. Subsequently, visualization of TAM-DNA adducts was performed by peroxidase-conjugated secondary antibody-mediated signal amplification using biotinyl tyramide followed by streptavidin-alkaline phosphatase and fast red. Semi-quantitation of nuclear color intensity was achieved with an Automated Cellular Imaging System (ACIS), with a detection limit of 1 TAM-DNA adduct per 10(7) nt for these experiments. In parenchymal cells of liver sections from TAM-exposed animals a dose-dependent increase in nuclear staining was observed by ACIS and the TAM-DNA adduct levels determined by ACIS were validated in liver DNA by quantitative chemiluminescence immunoassay (CIA). Comparison of semi-quantitative values determined by ACIS with quantitative values determined by CIA showed a strong correlation (r = 0.924) between the two methods. At 45 weeks of TAM exposure the liver cytoplasm contained placental glutathione S-transferase (GST-p)-positive foci, as indicated by new fuchsin staining. Staining of serial sections revealed a relative lack of TAM-DNA adducts within these enzyme-altered foci. In addition, some GSTp foci contained islands of cells that did not stain for GSTp but were positive for TAM-DNA adduct formation. This study validates the use of ACIS for TAM-DNA adduct formation and demonstrates that steady-state TAM-DNA adduct levels observed in livers of rats chronically fed TAM for several months increase in relation to dose. In addition, unlike the normal surrounding liver, preneoplastic GST-p-positive foci have virtually no TAM-DNA adducts. C1 NCI, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Wisconsin, Madison, WI 53706 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Bldg 37,Room 2A05,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 31 TC 23 Z9 24 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 OCT PY 2001 VL 22 IS 10 BP 1693 EP 1699 DI 10.1093/carcin/22.10.1693 PG 7 WC Oncology SC Oncology GA 480ZD UT WOS:000171492500016 PM 11577011 ER PT J AU Pile, LA Lee, FWH Wassarman, DA AF Pile, LA Lee, FWH Wassarman, DA TI The histone deacetylase inhibitor trichostatin A influences the development of Drosphila melanogaster SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE trichostatin A; RPD3; SIN3; HDAC; deacetylase; SINA; Drosophila ID TRANSCRIPTIONAL REPRESSION; DROSOPHILA-MELANOGASTER; PATHWAY; EXPRESSION; H4 AB We examined the consequences of the deacetylase inhibitor trichostatin A (TSA) on the development of Drosophila melanogaster. When fed to flies, TSA caused lethality and delayed development at concentrations as low as 5 muM, had stronger effects on males than females, and acted synergistically with mutations in the gene encoding the RPD3 deacetylase to cause notched wings, but did not appear to affect a SINA signaling pathway that is normally repressed by the SIN3 corepressor. These findings suggest that deacetylated histones play an important role in normal developmental progression and establish parameters for genetic screens to dissect the role of deacetylases in this process. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Wassarman, DA (reprint author), Univ Wisconsin, Sch Med, Dept Pharmacol, 1300 Univ Ave, Madison, WI 53706 USA. NR 22 TC 12 Z9 13 U1 1 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 OCT PY 2001 VL 58 IS 11 BP 1715 EP 1718 DI 10.1007/PL00000809 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 489UL UT WOS:000172010700015 PM 11706997 ER PT J AU Ma, XM Camacho, C Aguilera, G AF Ma, XM Camacho, C Aguilera, G TI Regulation of corticotropin-releasing hormone (CRH) transcription and CRH mRNA stability by glucocorticoids SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE corticotropin-releasing hormone; hypothalamic paraventricular nucleus; transcription; mRNA stability; glucocorticoids; adrenalectomy ID MESSENGER RIBONUCLEIC-ACID; PARAVENTRICULAR NUCLEUS; ARGININE-VASOPRESSIN; RECEPTOR EXPRESSION; GENE-EXPRESSION; TAIL LENGTH; RNA; STRESS; ADRENALECTOMY; CELLS AB 1. The increases in corticotropin-releasing hormone (CRH) mRNA following long-term adrenalectomy are associated with low levels of CRH gene transcription, suggesting that glucocorticoids regulate CRH mRNA at the posttranscriptional level. In this study we determined the time course of transcriptional activation after early adrenalectomy by intronic in situ hybridization, and evaluated the effects of glucocorticoids on CRH mRNA stability. 2. Plasma corticosterone was undetectable 3 h after adrenalectomy, but CRH hnRNA increased only by 12 h, and remained elevated for the next 72 h. CRH mRNA increased 18 h after adrenalectomy and reached a plateau lasting from 2 to 6 days, despite very low CRH hnRNA levels. 3. Assessment of CRH mRNA stability, by incubation of slide-mounted hypothalamic sections in an intracellular-like medium at 37degreesC, prior to measuring CRH mRNA levels by in situ hybridization, revealed a half-life (t(1/2)) of 11.5 min in sham-operated rats, and a slower decrease adrenalectomized rats (t(1/2)-26.3 min). Corticosterone administration for 3 days markedly decreased CRH mRNA t(1/2) in both sham-operated and adrenalectomized rats (6.5 and 5.0 min, respectively). 4. The data show that adrenalectomy causes transient increases in CRH mRNA transcription, followed by decreases in the rate of CRH mRNA degradation. This suggests that glucocorticoids regulate CRH mRNA at two sites, by inhibiting transcription and by decreasing mRNA stability. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10 Rm 10N 262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 28 TC 24 Z9 25 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD OCT PY 2001 VL 21 IS 5 BP 465 EP 475 DI 10.1023/A:1013863205647 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 523FZ UT WOS:000173944500003 PM 11860185 ER PT J AU Smith, MA Anderson, B AF Smith, MA Anderson, B TI Where to next with retinoids for cancer therapy? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ACUTE PROMYELOCYTIC LEUKEMIA; BONE-MARROW TRANSPLANTATION; CARCINOMA-CELLS; 13-CIS-RETINOIC ACID; HISTONE DEACETYLASE; PHASE-I; NEUROBLASTOMA; APOPTOSIS; FENRETINIDE; INDUCTION C1 NCI, Natl Canc Inst, Pediat Sect, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), NCI, Natl Canc Inst, Pediat Sect, Canc Therapy Evaluat Program, Room 7025,EPN,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 43 TC 13 Z9 14 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 2001 VL 7 IS 10 BP 2955 EP 2957 PG 3 WC Oncology SC Oncology GA 482KD UT WOS:000171574600002 PM 11595682 ER PT J AU Adamson, PC Widemann, BC Reaman, GH Seibel, NL Murphy, RF Gillespie, AF Balis, FM AF Adamson, PC Widemann, BC Reaman, GH Seibel, NL Murphy, RF Gillespie, AF Balis, FM TI A phase I trial and pharmacokinetic study of 9-cis-retinoic acid (ALRT1057) in pediatric patients with refractory cancer: A Joint Pediatric Oncology Branch, National Cancer Institute, and Children's Cancer Group Study SO CLINICAL CANCER RESEARCH LA English DT Article ID TRANS-RETINOIC ACID; RHABDOMYOSARCOMA CELL-LINE; HUMAN NEUROBLASTOMA-CELLS; BINDING PROTEIN-II; ACUTE PROMYELOCYTIC LEUKEMIA; INDUCED GROWTH-INHIBITION; HUMAN OSTEOSARCOMA CELLS; HUMAN NEURO-BLASTOMA; 13-CIS-RETINOIC ACID; MORPHOLOGIC DIFFERENTIATION AB Purpose: To determine the maximum tolerated dose and describe the toxicities of 9-cis-retinoic acid (9cRA, ALRT1057) administered p.o. tid in pediatric patients with refractory cancer and to stud), the pharmacokinetics of 9cRA and determine whether systemic drug exposure changes with chronic dosing. Patients and Methods: Children with refractory cancer (stratified by age, less than or equal to 12 and > 12 years) were treated with p.o. 9cRA for 28 consecutive days. The starting dose was 50 mg/m(2)/day divided into 3 doses with planned escalations to 65, 85, and 110 mg/m(2)/day. Pharmacokinetic sampling was performed on days I and 29 of the first cycle. Results: Of the 37 patients entered, 18 patients less than or equal to 12 years of age and I I patients > 12 years of age were evaluable for toxicity. In patients > 12 years of age, dose-limiting headache occurred in 2/2 patients at the 110 mg/m2/day dose level; 1/8 patients at 85 mg/m(2)/day developed dose-limiting pseudotumor cerebri. In patients less than or equal to 12 years of age, 3/5 patients at the starting dose level of 50 mg/m(2)/day developed dose-limiting pseudotumor cerebri; and 0/6 patients experienced dose-limiting toxicity at 35 mg/m(2)/day. Reversible non-dose-limiting hepatotoxicity was observed in 15 patients across all of the dose levels. There was considerable interpatient variability in 9cRA plasma concentrations. Peak plasma concentrations of 9cRA occurred at a median of 1.5 h after a p.o. dose, and the harmonic-mean terminal half-life was 43 min. By day 29 of 9cRA administration, the plasma 9cRA area under the curve declined by an average of 65% from day I values. Conclusions: The dose-limiting toxicity of 9cRA in pediatric patients was neurotoxicity, primarily pseudotumor cerebri. Younger children tolerate significantly lower doses of 9cRA than older children. Similar to all-trans-retinoic acid, the pharmacokinetics of 9cRA demonstrated a wide degree of interpatient variability and decreased over time when administered on a daily basis. The recommended Phase It dose of 9cRA in patients :less than or equal to2 and > 12 years of age is 35 and 85 mg/m(2)/day, respectively. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Canc Grp, Arcadia, CA 91066 USA. RP Adamson, PC (reprint author), Childrens Hosp Philadelphia, Abramson 907,3516 Civic Ctr Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA 02971, CA 03888, CA 10198, CA 10382, CA 13539, CA 17829, CA 26126, CA 26270, CA 28882, CA 36015] NR 50 TC 12 Z9 14 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 2001 VL 7 IS 10 BP 3034 EP 3039 PG 6 WC Oncology SC Oncology GA 482KD UT WOS:000171574600012 PM 11595692 ER PT J AU Srinivas, PR Srivastava, S Hanash, S Wright, GL AF Srinivas, PR Srivastava, S Hanash, S Wright, GL TI Proteomics in early detection of cancer SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 33rd Annual Oak Ridge Conference CY MAY 04-05, 2001 CL SEATTLE, WASHINGTON ID LASER CAPTURE MICRODISSECTION; FLIGHT-MASS-SPECTROMETRY; SQUAMOUS-CELL CARCINOMAS; HUMAN BREAST-LESIONS; POLYPEPTIDE EXPRESSION; PROSTATE-CANCER; PROTEIN BIOCHIP; TISSUE MICROARRAYS; BIOLOGICAL TISSUE; MALIGNANT-TUMORS AB Early detection is critical in cancer control and prevention. Biomarkers help in this process by providing valuable information about a the status of a cell at any given point in time. As a cell transforms from nondiseased to neoplastic, distinct changes occur that could be potentially detected through the identification of the appropriate biomarkers. Biomarker research has benefited from advances in technology such as proteomics. We discuss here ongoing research in this field, focusing on proteomic technologies. The advances in two-dimensional electrophoresis and mass spectrometry are discussed in light of their contribution to biomarker research. Chip-based techniques, such as surface-enhanced laser desorption, and ionization and emerging methods, such as tissue and antibody arrays, are also discussed. The development of bioinformatic tools that have and are being developed in parallel to proteomics is also addressed. This report brings into focus the efforts of the Early Detection Research Network at the National Cancer Institute in harnessing scientific expertise from leading institutions to identify and validate biomarkers for early detection and risk assessment. (C) 2001 American Association for Clinical Chemistry. C1 NCI, Div Canc Prevent, Canc Biomarkers Res Grp, Rockville, MD 20852 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA. Eastern Virginia Med Sch, Virginia Prostate Canc, Norfolk, VA 23501 USA. RP Srivastava, S (reprint author), NCI, Div Canc Prevent, Canc Biomarkers Res Grp, 6130 Execut Blvd,Rm EPN 330F, Rockville, MD 20852 USA. NR 83 TC 178 Z9 196 U1 1 U2 14 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 OCT PY 2001 VL 47 IS 10 BP 1901 EP 1911 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 474GU UT WOS:000171098600038 PM 11568117 ER PT J AU Peters, KF Kong, F Horne, R Francomano, CA Biesecker, BB AF Peters, KF Kong, F Horne, R Francomano, CA Biesecker, BB TI Living with Marfan syndrome I. Perceptions of the condition SO CLINICAL GENETICS LA English DT Article DE body image; depression; dissection; genetic counseling; illness perception; Marfan syndrome ID YOUNG-ADULTS; ADOLESCENTS; ADAPTATION; DISORDERS; GENE AB We present data from an exploratory study of 174 adults with Marfan syndrome regarding their cognitive perceptions of the condition as postulated by the self-regulatory model (Leventhal H, Benyamini Y, Brownlee S et al. In: Petrie KI, Weinman JA, eds. Perceptions of Health and Illness: Current Research and Applications. Amsterdam, The Netherlands: Harwood Academic, 1997: 19-45; Leventhal H, Nerenz DR, Steele DJ. In: Baum A, Taylor SE, Singer JE, eds. Handbook of Psychology and Health. Hillsdale, NJ: Lawrence Erlbaum Associates, 1984: 219-252). The vast majority of the respondents had adequate general knowledge about Marfan syndrome. Eighty-three percent of the respondents perceived Marfan syndrome as having had significant adverse consequences on their lives. Having striae, pain (sore joints), and depression were each independently correlated with this view. Fifty-eight percent of the respondents indicated that they felt they had low to moderate control over their condition, demonstrating variability. History of aortic dissection, pain (sore joints), and depressive symptoms were each negatively correlated with the view that Marfan syndrome is a curable/controllable condition. Moreover, approximately 28% view the condition as a lethal condition, whereas 67% view it as a serious condition. Forty-four percent of the cohort were found to have significant symptomatology of depression independent of beta- and Ca2+-channel blockade use. Respondents cited both advantages and disadvantages of being affected. Genetic counseling that addresses patients' perceptions of Marfan syndrome, and its associated pain, fatigue, and depressive symptoms, may enhance patient adaptation to the condition. C1 Penn State Univ, Dept Med, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. Westat Corp, Rockville, MD USA. Brighton Univ, Ctr Hlth Care Res, Brighton, E Sussex, England. NIH, Human Genet & Integrat Med Sect, Genet Lab, NIA, Baltimore, MD USA. RP Peters, KF (reprint author), Penn State Univ, Dept Med, Ctr Dev & Hlth Genet, 101 Amy Gardner House, University Pk, PA 16802 USA. NR 26 TC 30 Z9 31 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD OCT PY 2001 VL 60 IS 4 BP 273 EP 282 DI 10.1034/j.1399-0004.2001.600405.x PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 489EC UT WOS:000171978200007 PM 11683773 ER PT J AU Peters, KF Horne, R Kong, F Francomano, CA Biesecker, BB AF Peters, KF Horne, R Kong, F Francomano, CA Biesecker, BB TI Living with Marfan syndrome II. Medication adherence and physical activity modification SO CLINICAL GENETICS LA English DT Article DE beta-blocker; exercise; health beliefs; Marfan syndrome; medication ID COGNITIVE REPRESENTATION; PATIENTS BELIEFS; YOUNG-ADULTS; MEDICINES; QUESTIONNAIRE; ADOLESCENTS; ILLNESS; GENE AB We investigated the perceptions of and adherence to medication and physical activity guidelines in 174 adults with Marfan syndrome. Over 80% of those prescribed beta- and Ca2+-channel blockade reportedly adhere well to their medication regimen. The presence of cardiovascular symptoms and fatigue were positively correlated with the medication use. Medication-takers reported that they are psychologically receptive to the use of medication for prophylactic treatment of their cardiovascular problems. However, all do not view their medication as essential for their health. Duration of the medication regimen, type of medication, and perception of controllability of the condition were each independently associated with respondents' perceptions of the necessity of taking beta- or Ca2+-channel blockers. Over 80% of the respondents reported that they choose their physical activities with their diagnosis in mind. Modifying exercise activities was significantly correlated with an increased perception of Marfan syndrome as having negative consequences on the respondents' lives. Genetic counseling should address beliefs about medication use and physical activity restrictions, as perceptions of these health behaviors may have significant impact on how adults with Marfan syndrome adhere to these recommendations and cope with their condition. C1 Penn State Univ, Dept Med, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD USA. Brighton Univ, Ctr Hlth Care Res, Brighton, E Sussex, England. Westat Corp, Rockville, MD USA. NIH, NIA, Genet Lab, Human Genet & Integrat Med Sect, Baltimore, MD USA. RP Peters, KF (reprint author), Penn State Univ, Dept Med, Ctr Dev & Hlth Genet, 101 Amy Gardner House, University Pk, PA 16802 USA. NR 38 TC 34 Z9 35 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD OCT PY 2001 VL 60 IS 4 BP 283 EP 292 DI 10.1034/j.1399-0004.2001.600406.x PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 489EC UT WOS:000171978200008 PM 11683774 ER PT J AU Lazarova, Z Yee, C Lazar, J Yancey, KB AF Lazarova, Z Yee, C Lazar, J Yancey, KB TI IgG autoantibodies in patients with anti-epiligrin cicatricial pemphigoid recognize the G domain of the laminin 5 alpha-subunit SO CLINICAL IMMUNOLOGY LA English DT Article DE autoimmunity; bullous disease; basement membrane; epitope ID INDUCE SUBEPIDERMAL BLISTERS; CELL-ADHESION; NEONATAL MICE; INTEGRIN; KALININ; CHAIN; SKIN; REQUIREMENT; AUTOIMMUNE; ANTIBODIES AB Anti-epiligrin cicatricial pemphigoid (A-ECP) is a mucosal-predominant, subepithelial blistering disease characterized by IgG anti-basement membrane autoantibodies to laminin 5 (alpha3 beta3 gamma2). This and prior studies found that autoantibodies from most patients recognize the alpha -subunit of this laminin isoform. Accordingly, sera from 10 representative patients were tested against prokaryotic recombinants of this polypeptide in epitope mapping studies. cDNAs spanning the full length of the alpha -subunit were generated by PCR, directionally cloned into the pGEX-4T-3 vector, and expressed as glutathione-S-transferase fusion proteins of appropriate size and immunoreactivity. Sera from 9 of 10 AECP patients immunoblotted fusion proteins corresponding to subdomains G2, G3, G4, and G5 at the carboxyl terminus of the laminin 5 alpha -subunit. Serum from 1 patient (and that from normal volunteers) showed no reactivity to any fusion proteins; no sera bound recombinant glutathione-S-transferase alone. Immunoadsorption of patient sera with fusion proteins corresponding to the G domain substantially reduced basement membrane autoantibody titers. IgG from patients with this form of cicatricial pemphigoid recognize the portion of laminin 5 thought to play a key role in promoting keratinocyte adhesion to epidermal basement membrane. (C) 2001 Academic Press. C1 NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Res Serv, Baltimore, MD 21201 USA. RP Lazarova, Z (reprint author), NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 26 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC 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 OCT PY 2001 VL 101 IS 1 BP 100 EP 105 DI 10.1006/clim.2001.5091 PG 6 WC Immunology SC Immunology GA 481QQ UT WOS:000171531400014 PM 11580232 ER PT J AU Sterling, TR Dorman, SE Chaisson, RE Ding, L Hackman, J Moore, K Holland, SM AF Sterling, TR Dorman, SE Chaisson, RE Ding, L Hackman, J Moore, K Holland, SM TI Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-10, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; TOLL-LIKE RECEPTORS; CD4 CELL COUNTS; MYCOBACTERIUM-TUBERCULOSIS; FACTOR-ALPHA; PULMONARY TUBERCULOSIS; INFECTION; INTERLEUKIN-12; MACROPHAGES AB Extrapulmonary tuberculosis is presumably a marker of underlying immunodeficiency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from human immunodeficiency virus-seronegative adults with prior culture-confirmed extrapulmonary tuberculosis were compared with those of persons with latent Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-gamma production, interleukin (IL)-12 production, and -gamma receptor- and IL-12 receptor-mediated cytokine production did not differ between case patients and control patients. However, median resting IL-8 production was significantly lower in case patients than control patients (8051 vs. 19,290 pg/mL; P=.009). In addition, the median tumor necrosis factor (TNF)-alpha response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. Baltimore City Hlth Dept Eastern Chest Clin, Baltimore, MD USA. NIAID, NIH, Lab Host Def, Bethesda, MD USA. RP Sterling, TR (reprint author), Ctr TB Res, 424 N Bond St, Baltimore, MD 21231 USA. FU NIAID NIH HHS [AI-01637, AI-01654] NR 39 TC 28 Z9 30 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 BP 976 EP 982 DI 10.1086/322670 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900008 PM 11528568 ER PT J AU Taranger, J Trollfors, B Bergfors, E Knutsson, N Sundh, V Lagergard, T Lind-Brandberg, L Zackrisson, G White, J Cicirello, H Fusco, J Robbins, JB AF Taranger, J Trollfors, B Bergfors, E Knutsson, N Sundh, V Lagergard, T Lind-Brandberg, L Zackrisson, G White, J Cicirello, H Fusco, J Robbins, JB TI Mass vaccination of children with pertussis toxoid - Decreased incidence in both vaccinated and nonvaccinated persons SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BORDETELLA-PERTUSSIS; CONTROLLED TRIAL; HOUSEHOLD EXPOSURE; WHOOPING-COUGH; EFFICACY; IMMUNIZATION; IMMUNITY AB During 1979-1995, there was no vaccination against pertussis in Sweden. With the aim of studying the epidemiology and transmission of pertussis, mass vaccination with pertussis toxoid of children born during the 1990s was instituted in the Goteborg area (population, 778,597) in 1995. Infants were offered 3 doses of pertussis toxoid combined with diphtheria and tetanus toxoids. Children aged greater than or equal to1 year were offered 3 doses of pertussis toxoid alone. From June 1995 through February 1999, 167,810 doses of pertussis toxoid were given to 61,219 children born during the 1990s (56% received 3 doses). The number of Bordetella pertussis isolates per year declined from 1214 (1993-1995) to 64 (January 1997 through June 1999; P<.0001), and hospitalizations due to pertussis declined from 62 to 5 (P<.0001). Significant decreases in B. pertussis isolates and hospitalizations occurred in all age groups, including adults and nonvaccinated infants. Thus, mass vaccination of children with pertussis toxoid decreases spread of B. pertussis in the population. C1 Univ Gothenburg, Dept Med Microbiol & Immunol, Goteburg Primary Hlth Care, Goteborg Pertussis Vaccine Study, Gothenburg, Sweden. Univ Gothenburg, Dept Clin Bacteriol, Gothenburg, Sweden. Baxter Hlthcare, Columbia, MD USA. NICHHD, NIH, Bethesda, MD USA. RP Taranger, J (reprint author), Pediat Outpatient Clin, Topasgatan 58, S-42148 Vastra Frolunda, Sweden. NR 23 TC 58 Z9 58 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 BP 1004 EP 1009 DI 10.1086/322639 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900012 PM 11528572 ER PT J AU Miller, FG Grady, C AF Miller, FG Grady, C TI The ethical challenge of infection-inducing challenge experiments SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID VOLUNTEERS; VACCINE; EFFICACY; MALARIA AB Challenge experiments that induce infections in healthy volunteers are an important method for initial efficacy testing of candidate vaccines and for study of the pathogenesis of infectious diseases. Although these studies can be conducted safely for selected infectious diseases that are either fully treatable or self-limiting, they raise significant ethical issues. An ethical framework is offered for evaluating infection-inducing challenge experiments, which focuses on the scientific and public health rationale for conducting these studies, the risks that they pose and the ways in which these risks can be minimized, the symptoms experienced by healthy volunteers that may cause discomfort or distress, the exclusion of vulnerable research subjects, the informed consent process, the payment of volunteers, and the use of isolation of volunteers to prevent infection of others. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. NR 20 TC 39 Z9 39 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 BP 1028 EP 1033 DI 10.1086/322664 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900016 PM 11528576 ER PT J AU Marovich, MA Lira, R Shepard, M Fuchs, GH Kruetzer, R Nutman, TB Neva, FA AF Marovich, MA Lira, R Shepard, M Fuchs, GH Kruetzer, R Nutman, TB Neva, FA TI Leishmaniasis recidivans recurrence after 43 years: A clinical and immunologic report after successful treatment SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID GROWTH-FACTOR-BETA; CUTANEOUS LEISHMANIASIS; INFECTION; CELLS AB We describe a patient with very late recurring leishmaniasis recidivans from whom lesional biopsy samples were obtained during and after topical steroid treatment that demonstrated the ability of the host to contain the parasite in the absence of therapy. Combination therapy with intralesional sodium stibogluconate and oral itraconazole was successful and immunologic data suggest that both CD4(+) and CD8(+) T cell subsets had roles in this disease process. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Med, Washington, DC USA. George Washington Univ, Dept Dermatol, Washington, DC USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. RP Marovich, MA (reprint author), Combined US Mil HIV Res Program, 13 Taft Ct,Ste 200, Rockville, MD 20852 USA. NR 11 TC 20 Z9 20 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 BP 1076 EP 1079 DI 10.1086/322643 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900023 PM 11528583 ER PT J AU Bradford, RD Kimberlin, DW Lakeman, FD Cloud, G Boppana, SB Britt, WJ Sanchez, PJ Demmler, G Dankner, W Shelton, M Jacobs, RF Whitley, RJ AF Bradford, RD Kimberlin, DW Lakeman, FD Cloud, G Boppana, SB Britt, WJ Sanchez, PJ Demmler, G Dankner, W Shelton, M Jacobs, RF Whitley, RJ CA NIAID CASG TI Baseline viremia in congenital cytomegalovirus (CMV) infection correlates with clinical outcome SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Cook Childrens Med Ctr, Ft Worth, TX USA. Univ Arkansas, Little Rock, AR 72204 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 7 BP 1089 EP 1089 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900033 ER PT J AU Wood, BJ Regan, MJ Theodore, ML Hsieh, YH Green, WR Quinn, TC Stone, JH Gaydos, C AF Wood, BJ Regan, MJ Theodore, ML Hsieh, YH Green, WR Quinn, TC Stone, JH Gaydos, C TI Role of Chlamydia pneumoniae in the diagnosis of temporal arteritis SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Baltimore, MD USA. RI Gaydos, Charlotte/E-9937-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 37 BP 1095 EP 1095 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900063 ER PT J AU Farjo, RS Holland, SM Shope, TC Krasan, GP AF Farjo, RS Holland, SM Shope, TC Krasan, GP TI Recurrent Mycobacteria avium complex osteomyelitis in a patient with interferon-gamma receptor deficiency SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 172 BP 1117 EP 1117 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900198 ER PT J AU Kottilil, S Malech, HL Gill, VJ Holland, SM AF Kottilil, S Malech, HL Gill, VJ Holland, SM TI Infections with Haemophilus species in chronic granulomatous disease: Codependence of bacterial catalase and hydrogen peroxide production SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 174 BP 1118 EP 1118 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900200 ER PT J AU Fahey, BJ Gill, VJ Preuss, J Bordner, M Michelin, AV Curnow, ES Bevans, M Henderson, DK AF Fahey, BJ Gill, VJ Preuss, J Bordner, M Michelin, AV Curnow, ES Bevans, M Henderson, DK TI Preventing influenza transmission among severely immunocompromised patients SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 229 BP 1127 EP 1127 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900255 ER PT J AU Navoa, JD Laal, S Pirofski, L Robbins, JB Schneerson, R Casadevall, A Glatman-Freedman, A AF Navoa, JD Laal, S Pirofski, L Robbins, JB Schneerson, R Casadevall, A Glatman-Freedman, A TI Characterization of human antibody response to M. tuberculosis arabinomannan SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. NYU, Med Ctr, VA Med Ctr, New York, NY 10016 USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 337 BP 1146 EP 1146 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900363 ER PT J AU Baker, CJ Rench, MA McInnes, P AF Baker, CJ Rench, MA McInnes, P TI Safety and immunogenicity of group B streptococcal (GBS) type III capsular polysaccharide (CPS)-tetanus toxoid (III-TT) conjugate vaccine in pregnant woman SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. NIAID, Bethesda, MD 20892 USA. NR 0 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 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 370 BP 1151 EP 1151 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900396 ER PT J AU Wilson, LE Umemura, T Astemborski, J Ray, SC Alter, HJ Strathdee, SA Vlahov, D Thomas, DL AF Wilson, LE Umemura, T Astemborski, J Ray, SC Alter, HJ Strathdee, SA Vlahov, D Thomas, DL TI Dynamics of SEN virus infection among injection drug users SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. New York Acad Med, New York, NY USA. RI Strathdee, Steffanie/B-9042-2009; Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 406 BP 1158 EP 1158 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900432 ER PT J AU Kirk, GD Lesi, F Mendy, M Goedert, J Montesano, R AF Kirk, GD Lesi, F Mendy, M Goedert, J Montesano, R TI Age and sex differences in hepatitis C- vs, hepatitis B-related hepatocellular carcinoma from The Gambia, West Africa SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIAID, NIH, Rockville, MD USA. Gambia Hepatitis Intervent Study, Lyon, France. NCI, NIH, Bethesda, MD 20892 USA. RI Kirk, Gregory/A-8484-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 436 BP 1163 EP 1163 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900462 ER PT J AU Ju, J Marr, K Holland, SM Polhamus, C Bennett, JE AF Ju, J Marr, K Holland, SM Polhamus, C Bennett, JE TI Caspofungin and fluconazole therapy of C-glabrata infection in p47phox knockout mice SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 640 BP 1197 EP 1197 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900666 ER PT J AU Ostrosky-Zeichner, L Rex, JH Pappas, PG Hammill, RJ Larsen, RA Horowitz, HG Powderly, WG Hyslop, N Kauffman, CA Chapman, SW Mangino, JE Lee, J AF Ostrosky-Zeichner, L Rex, JH Pappas, PG Hammill, RJ Larsen, RA Horowitz, HG Powderly, WG Hyslop, N Kauffman, CA Chapman, SW Mangino, JE Lee, J TI Three year survey of regional and temporal trends in fluconazole (FLU) resistance (R) among bloodstream Candida isolates from the United States (US) SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Univ Texas, Sch Med, Houston, TX USA. Univ Alabama, Birmingham, AL USA. NIAID, MSG Candidiasis Subproject, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 643 BP 1198 EP 1198 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900669 ER PT J AU Rex, JH Ostrosky-Zeichner, L Pappas, PG Hammill, RJ Larsen, RA Horowitz, HG Powderly, WG Hyslop, N Kauffman, CA Chapman, SW Mangino, JE Lee, J AF Rex, JH Ostrosky-Zeichner, L Pappas, PG Hammill, RJ Larsen, RA Horowitz, HG Powderly, WG Hyslop, N Kauffman, CA Chapman, SW Mangino, JE Lee, J TI Antifungal susceptibility survey of 2,000 bloodstream Candida isolates from the United States (US) SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Univ Texas, Sch Med, Houston, TX USA. Univ Alabama, Birmingham, AL USA. NIAID, MSG Candidiasis Subproject, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 642 BP 1198 EP 1198 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900668 ER PT J AU Biggar, RJ Engels, E Goedert, J Whitby, D AF Biggar, RJ Engels, E Goedert, J Whitby, D TI Longitudinal patterns of HHV-8 antibody reactivity to K8.1 (lytic) glycoprotein in homosexual men SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 NCI, VEB, DCEG, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 727 BP 1212 EP 1212 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900753 ER PT J AU Augenbraun, M Feldman, J Wilson, T Hershow, R French, A Nowicki, MJ Greenblatt, R Goedert, J AF Augenbraun, M Feldman, J Wilson, T Hershow, R French, A Nowicki, MJ Greenblatt, R Goedert, J TI Incident hepatitis C virus (HCV) infection among HIV infected woman SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 SUNY Downstate Med Ctr, Brooklyn, NY USA. Univ Illinois, Chicago, IL 60680 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 752 BP 1216 EP 1216 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900778 ER PT J AU Smith, H Reporter, R Rood, M Linscott, A Mascola, L Hogrefe, W Purcell, R AF Smith, H Reporter, R Rood, M Linscott, A Mascola, L Hogrefe, W Purcell, R TI Seroprevalence study for antibody to ratborne pathogens and other agents among skid row residents - Los Angeles 2000 SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. Los Angeles Cty Dept Hlth Serv, Monterey Pk, CA USA. Focus Technol Inc, Cypress, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 909 BP 1243 EP 1243 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900935 ER PT J AU Theodore, ML Dalesio, N Wood, BJ Quinn, TC Gaydos, C AF Theodore, ML Dalesio, N Wood, BJ Quinn, TC Gaydos, C TI Comparison of three nucleic acid amplification tests for the detection of Chlamydia trachomatis in urine specimens SO CLINICAL INFECTIOUS DISEASES LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RI Gaydos, Charlotte/E-9937-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2001 VL 33 IS 7 MA 926 BP 1246 EP 1246 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 476KU UT WOS:000171226900952 ER PT J AU Rex, JH Pfaller, MA Walsh, TJ Chaturvedi, V Espinel-Ingroff, A Ghannoum, MA Gosey, LL Odds, FC Rinaldi, MG Sheehan, DJ Warnock, DW AF Rex, JH Pfaller, MA Walsh, TJ Chaturvedi, V Espinel-Ingroff, A Ghannoum, MA Gosey, LL Odds, FC Rinaldi, MG Sheehan, DJ Warnock, DW TI Antifungal susceptibility testing: Practical aspects and current challenges SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID IN-VITRO SUSCEPTIBILITY; AMPHOTERICIN-B SUSCEPTIBILITY; BROTH MICRODILUTION METHODS; FLUCONAZOLE-RESISTANT CANDIDA; LABORATORY STANDARDS METHOD; MEDIATED GROWTH-INHIBITION; VIRUS-INFECTED PATIENTS; TIME-KILL METHODS; CRYPTOCOCCUS-NEOFORMANS; ASPERGILLUS-FUMIGATUS C1 Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, Houston, TX 77030 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. NCI, Pediat Branch, Infect Dis Sect, Bethesda, MD 20892 USA. New York State Dept Hlth, Albany, NY 12201 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Case Western Reserve Univ, Dept Dermatol, Cleveland, OH 44106 USA. US FDA, Rockville, MD 20857 USA. Inst Med Sci, Aberdeen, Scotland. Vet Adm Med Ctr, San Antonio, TX 78284 USA. Pfizer Inc, Pfizer Pharmaceut Grp, New York, NY 10017 USA. Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA USA. RP Rex, JH (reprint author), 6431 Fannin,1728 JFB, Houston, TX 77030 USA. NR 218 TC 260 Z9 284 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2001 VL 14 IS 4 BP 643 EP 658 DI 10.1128/CMR.14.4.643-658.2001 PG 16 WC Microbiology SC Microbiology GA 482KP UT WOS:000171575600001 PM 11585779 ER PT J AU Leandri, M Gottlieb, A Cruccu, G AF Leandri, M Gottlieb, A Cruccu, G TI Head extensor reflex evoked by trigeminal stimulation in humans SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE reflex; trigeminal; early; head extensor; neck; oligosynaptic ID CERVICAL REFLEXES; NECK MOTONEURONS; CAT AB Objective: Excitatory and inhibitory responses have been recognized in human cervical muscles following trigeminal stimulation. However, no evidence has so far been published of a crossed, short-latency, excitatory response resembling the early head extensor reflex seen in the cat. We seek its existence in humans. Methods: The study was carried out in 14 voluntary healthy subjects. Percutaneous and surface electrical stimulation of the supraorbital and infraorbital nerves was performed with single, double and repetitive stimuli. Signals were recorded from the relaxed splenius and sternomastoid muscles bilaterally. Results: Percutaneous stimulation of infraorbital nerve with single stimuli evoked an early response in the contralateral splenius muscle, with onset latency ranging from 11 to 14 ms (HR1). This response was greatly facilitated by double or repetitive stimuli. Single stimuli also gave rise to two larger responses in all 4 muscles in the latency ranges 50-70 ms (HR2) and 100-160 ms (HR3). Surface stimulation of one nerve alone could not elicit any early activity. Single surface stimuli delivered simultaneously to the supraorbital and infraorbital nerves evoked HR1 in only 5 subjects. Conclusions: We detected a crossed early reflex of the head extensor muscles to trigeminal stimuli. Its timing is similar to the 8-ms response seen in cats. The evidence provided suggests that the reflex is mediated by an oligosynaptic circuit and that it needs a strong spatial summation at central synapses. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Genoa, Interuniv Ctr Pain Neurophysiol, I-16146 Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, I-16146 Genoa, Italy. Natl Canc Inst, Ctr Pain Relief & Palliat Care, Genoa, Italy. Univ Rome, Dept Neurol Sci, Rome, Italy. Univ Rome, Interuniv Ctr Pain Neurophysiol, Rome, Italy. RP Leandri, M (reprint author), Univ Genoa, Interuniv Ctr Pain Neurophysiol, Via Dodecaneso 35, I-16146 Genoa, Italy. NR 10 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2001 VL 112 IS 10 BP 1828 EP 1832 DI 10.1016/S1388-2457(01)00648-4 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 478KV UT WOS:000171346100007 PM 11595141 ER PT J AU Poggi, MM Patronas, N Buttman, JA Hewitt, SM Fuller, B AF Poggi, MM Patronas, N Buttman, JA Hewitt, SM Fuller, B TI Intramedullary spinal cord metastasis from renal cell carcinoma - Detection by positron emission tomography SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE oncology; positron emission tomography; renal cell carcinoma; spine AB Although positron emission tomography (PET) is an established diagnostic method in brain and lung cancer, its use is often confined to research. The authors report a case of a minimally symptomatic intramedullary spinal cord metastasis, an uncommon and often diagnostically challenging lesion, that was confirmed by PET. A 37-year-old man with a history of metastatic renal cell carcinoma treated with systemic agents, an autologous stem cell transplant, and local palliative radiotherapy with a 2-month history of vague right foot numbness and right leg dysesthesias was found to have an intramedullary lesion at the level of T12. Although the findings of magnetic resonance imaging suggested central necrosis, a PET scan revealed a metabolically active lesion and confirmed the diagnosis of intramedullary metastasis. PET can be used to detect and confirm intramedullary spinal cord metastatic carcinoma. PET imaging may have a vital role in clinical diagnosis by helping to distinguish diagnostically troublesome lesions based on metabolic activity. C1 NCI, NIH, Radiat Oncol Branch, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. NCI, Diagnost Radiol Branch, Bethesda, MD 20892 USA. NCI, Pathol Branch, Bethesda, MD 20892 USA. RP Poggi, MM (reprint author), NCI, NIH, Radiat Oncol Branch, Radiat Oncol Sci Program, B3B69 Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 5 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2001 VL 26 IS 10 BP 837 EP 839 DI 10.1097/00003072-200110000-00006 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 499BE UT WOS:000172550000006 PM 11564920 ER PT J AU Dmitrieva, NI Michea, LF Rocha, GM Burg, MB AF Dmitrieva, NI Michea, LF Rocha, GM Burg, MB TI Cell cycle delay and apoptosis in response to osmotic stress SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT European-Society-for-Comparative-Physiology-and-Biochemistry Congress CY JUL, 2000 CL LIEGE, BELGIUM SP European Soc Comparat Physiol & Biochem DE osmolality; renal cells; NaCl; urea; G2 arrest; cell growth; apoptosis; p53 ID NUCLEOTIDE EXCISION-REPAIR; HIGH UREA CONCENTRATIONS; RENAL MEDULLARY CELLS; C-TERMINAL DOMAIN; MDCK CELLS; ORGANIC OSMOLYTES; HUMAN FIBROBLASTS; EPITHELIAL-CELLS; P53 MODULATION; PROTEIN-KINASE AB As part of the urinary concentrating mechanism, renal inner medulla cells may be exposed to extremely variable NaCl and urea concentrations that can reach very high levels. A number of studies, reviewed herein, aim to understand how such osmotic stress affects the cells and what protective mechanisms might exist. The majority of these studies are done on inner medullary epithelial cells that grow continuously in tissue culture (mIMCD3). Cells grown at 300 mosmol/kg survive increase to 500 mosmol/ka by adding NaCl or urea, but only after a growth arrest of similar to 24 h. At a higher osmolality (650-700 mosmol/kg) most cells die within hours by apoptosis. The cells both in vitro and in vivo adapt to high osmolality by a number of mechanisms, including accumulation of variety of organic osmolytes and induction of heat shock proteins. The cell cycle delay results from blocks at the G1 and G2/M checkpoints and slowing during S. After adding NaCl, but not urea, the amount and transcriptional activity of p53 (the tumor suppressor protein) increases. The p53 is phosphorylated on ser-15 and is transcriptionally active at 500 mosmol/kg (associated with cell survival), but not at 700 mosmol/ka (associated with apoptosis). Reduction of p53 expression by p53 antisense oligonucleotide increases sensitivity of renal cells in culture to hyperosmotic stress caused by NaCl. The possible mechanisms of the protection action of p53 against hypertonic stress are discussed. (C) 2001 Published by Elsevier Science Inc. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, Bldg 10,Room 6N260, Bethesda, MD 20892 USA. RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 NR 48 TC 34 Z9 36 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD OCT PY 2001 VL 130 IS 3 SI SI BP 411 EP 420 DI 10.1016/S1095-6433(01)00439-1 PG 10 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 486NH UT WOS:000171823500007 PM 11913454 ER PT J AU Petraitiene, R Petraitis, V Bacher, J Das, SR Parlow, AF Walsh, TJ AF Petraitiene, R Petraitis, V Bacher, J Das, SR Parlow, AF Walsh, TJ TI Cyclosporine A-induced mammary hyperplasia and hyperprolactinemia in New Zealand White rabbits SO COMPARATIVE MEDICINE LA English DT Article ID EXPERIMENTAL CRYPTOCOCCAL MENINGITIS; RENAL-TRANSPLANT RECIPIENTS; PULMONARY ASPERGILLOSIS; INDUCED NEPHROTOXICITY; THERAPEUTIC RESPONSE; PROLACTIN RECEPTORS; OVARIAN-FUNCTION; CORNEAL EDEMA; IN-VITRO; MODEL AB Purpose: To investigate the potential activity of cyclosporin A (CsA) to induce mammary hyperplasia in New Zealand White (NZW) rabbits. Methods: Female NZW rabbits were used throughout experiments. To simulate the conditions of immunosuppression, CsA (10 mg/kg of body weight/d) was administered intravenously on a daily basis for 14 days and methylprednisolone (5 mg/kg/d) was administered on the first two days. The CsA (10 mg/kg/d) also was administered without methylprednisolone for 14 days to another cohort of rabbits. Mammary tissue of each rabbit was palpated and serially measured during this treatment period. The CsA was discontinued, and rabbits were monitored for 14 more days during the washout period. Sequential plasma concentrations of prolactin, 17 betap-estradiol, and progesterone in each blood sample were determined by use of radioimmunoassay. Results: All NZW rabbits treated with CsA and methylprednisolone for immunosuppression consistently developed striking mammary tissue hyperplasia. At the end of treatment with CsA and methylprednisolone, mammary glands had extensive changes consistent with actively lactating glands. Similar but less extensive hyperplasia developed in response to CsA alone. Plasma concentration of prolactin increased during treatment and decreased during the washout period. Plasma concentration of 17 betap-estradiol increased during treatment and continued to increase during the washout period. Plasma progesterone concentration decreased at the end of treatment. On discontinuation of CsA, mammary hyperplasia regressed. Conclusions: Cyclosporine A, with or without methylprednisolone, induces mammary hyperplasia and hyperprolactinemia in NZW rabbits. This rabbit model may be a reliable in vivo system by which to study immunosuppressant-induced structural and functional changes of mammary glands similar to those observed in humans. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Surg Serv, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. Ani Lyt Inc, Gaithersburg, MD USA. Harbor UCLA Med Ctr, Res & Educ Inst, Natl Hormone & Peptide Program, Torrance, CA 90502 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Room 13N240,Ctr Dr, Bethesda, MD 20892 USA. NR 51 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 COMPARATIVE MED JI Comparative Med. PD OCT PY 2001 VL 51 IS 5 BP 430 EP 435 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 491AB UT WOS:000172084900006 PM 11924803 ER PT J AU Gandjbakhche, AH AF Gandjbakhche, AH TI Diffuse optical imaging and spectroscopy, in vivo SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE IV PHYSIQUE ASTROPHYSIQUE LA English DT Article DE scattering; fluorescence; absorption; tomography; optical biopsy; biological tissues ID HIGHLY SCATTERING MEDIA; RESOLVED TRANSILLUMINATION EXPERIMENTS; ANISOTROPIC RANDOM-WALKS; DOMAIN PHOTON MIGRATION; IN-VIVO; FLUORESCENCE SPECTROSCOPY; SCALING RELATIONSHIPS; BIOLOGICAL MEDIA; TISSUE; RECONSTRUCTION AB Based on photon migration the new goal of diffuse optical imaging is to reveal optical contrasts in the depth of biological tissues. We discuss first the origin of contrast mechanism (absorption, fluorescence and scattering) used on diffuse optical imaging and spectroscopy. Then, various experimental approaches are described based on CW, pulsed and modulated light excitation and detection. Theoretical models which provide solutions for direct and inverse problems are presented using random walk theory. Finally two studies on breast imaging and on the use of fluorescence exogeneous markers are discussed in detail. Publie par Editions scientifiques et medicales Elsevier SAS. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Gandjbakhche, AH (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 62 TC 8 Z9 8 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1296-2147 J9 CR ACAD SCI IV-PHYS JI C. R. Acad. Sci. Ser. IV-Phys. Astrophys. PD OCT PY 2001 VL 2 IS 8 BP 1073 EP 1089 DI 10.1016/S1296-2147(01)01251-3 PG 17 WC Astronomy & Astrophysics; Physics, Multidisciplinary SC Astronomy & Astrophysics; Physics GA 499KK UT WOS:000172570200002 ER PT J AU De Gruttola, VG Clax, P DeMets, DL Downing, GJ Ellenberg, SS Friedman, L Gail, MH Prentice, R Wittes, J Zeger, SL AF De Gruttola, VG Clax, P DeMets, DL Downing, GJ Ellenberg, SS Friedman, L Gail, MH Prentice, R Wittes, J Zeger, SL TI Considerations in the evaluation of surrogate endpoints in clinical trials: Summary of a National Institutes of Health Workshop SO CONTROLLED CLINICAL TRIALS LA English DT Article DE surrogate endpoints; biomarkers; meta-analysis ID END-POINTS; TRANSMISSION; ZIDOVUDINE; DYNAMICS; MARKERS; AIDS AB We report on recommendations from a National Institutes of Health Workshop on methods for evaluating the use of surrogate endpoints in clinical trials, which was attended by experts in biostatistics and clinical trials from a broad array of disease areas. Recent advances in biosciences and technology have increased the ability to understand, measure, and model biological mechanisms; appropriate application of these advances in clinical research settings requires collaboration of quantitative and laboratory scientists. Biomarkers, new examples of which arise rapidly from new technologies, are used frequently in such areas as early detection of disease and identification of patients most likely to benefit from new therapies. There is also scientific interest in exploring whether, and under what conditions, biomarkers may substitute for clinical endpoints of phase III trials, although workshop participants agreed that these considerations apply primarily to situations where trials using clinical endpoints are not feasible. Evaluating candidate biomarkers in the exploratory phases of drug development and investigating surrogate endpoints in confirmatory trials require the establishment of a statistical and inferential. framework. As a first step, participants reviewed methods for investigating the degree to which biomarkers can explain or predict the effect of treatments on clinical endpoints measured in clinical trials. They also suggested new approaches appropriate in settings where biomarkers reflect only indirectly the important processes on the causal path to clinical disease and where biomarker measurement errors are of concern. Participants emphasized the need for further research on development of such models, whether they are empirical in nature or attempt to describe mechanisms in mathematical terms. Of special interest were meta-analytic models for combining information from multiple studies involving interventions for the same condition. Recommendations also included considerations for design and conduct of trials and for assemblage of databases needed for such research. Finally, there was a strong recommendation for increased training of quantitative scientists in biologic research as well as in statistical methods and modeling to ensure that there will be an adequate workforce to meet future research needs. Control Clin Trials 2001; 22:485-502 (C) Elsevier Science Inc. 2001. C1 Harvard Univ, Sch Publ Hlth, Adult Stat & Data Anal Ctr, Boston, MA 02115 USA. NIAID, Bethesda, MD 20892 USA. NIH, Off Director, Bethesda, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NHLBI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Stat Collaborat, Washington, DC USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Univ Wisconsin, Madison, WI USA. RP De Gruttola, VG (reprint author), Harvard Univ, Sch Publ Hlth, Adult Stat & Data Anal Ctr, Bldg 2-439,655 Huntington Ave, Boston, MA 02115 USA. NR 17 TC 211 Z9 222 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2001 VL 22 IS 5 BP 485 EP 502 DI 10.1016/S0197-2456(01)00153-2 PG 18 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 474JH UT WOS:000171103000001 PM 11578783 ER PT J AU Dixon, DO AF Dixon, DO TI Untitled SO CONTROLLED CLINICAL TRIALS LA English DT Letter C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20857 USA. RP Dixon, DO (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2001 VL 22 IS 5 BP 548 EP 550 DI 10.1016/S0197-2456(01)00151-9 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 474JH UT WOS:000171103000006 PM 11589208 ER PT J AU Proschan, M Waclawiw, M AF Proschan, M Waclawiw, M TI Untitled - Reply SO CONTROLLED CLINICAL TRIALS LA English DT Letter C1 NHLBI, Bethesda, MD 20892 USA. RP Proschan, M (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2001 VL 22 IS 5 BP 550 EP 552 DI 10.1016/S0197-2456(01)00150-7 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 474JH UT WOS:000171103000007 ER PT J AU Nutman, TB AF Nutman, TB TI Lymphatic filariasis: new insights and prospects for control SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID INFECTIVE-STAGE LARVAE; BRUGIA-MALAYI; BANCROFTIAN FILARIASIS; WOLBACHIA BACTERIA; IN-VITRO; DIETHYLCARBAMAZINE TREATMENT; LITOMOSOIDES-SIGMODONTIS; MICROFILAREMIC PATIENTS; ECONOMIC BURDEN; NORTHERN GHANA AB Although lymphatic filariasis remains among the major causes of disability among the tropical infectious diseases, dramatic advances have been made in the approach to its diagnosis, epidemiology and treatment, in our understanding of the molecular composition of the parasites that cause these infections, and in the factors underlying the pathology seen. Superimposing the tools of modern epidemiology, immunology, and molecular biology on field-based clinical trials has allowed the emergence of the concept of elimination of lymphatic filariasis. Much of the important new research emphasizes parasite development in the context of the host response, the importance of both the adult worm and other factors in the pathogenesis of lymphatic filarial disease, the role the Wolbachia endosymbiont holds as both a target for drug treatment and in inducing post-treatment reactions, and the various principles underlying the implementation of control programs. Curr Opin Infect Dis 14:539-546 (C) 2001 Lippincott Williams & Wilkins. C1 NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 126 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD OCT PY 2001 VL 14 IS 5 BP 539 EP 546 PG 8 WC Infectious Diseases SC Infectious Diseases GA 478CA UT WOS:000171324300006 PM 11964873 ER PT J AU Andersen, CL Hostetter, G Grigoryan, A Sauter, G Kallioniemi, A AF Andersen, CL Hostetter, G Grigoryan, A Sauter, G Kallioniemi, A TI Improved procedure for fluorescence in situ hybridization on tissue microarrays SO CYTOMETRY LA English DT Article DE protocol; fluorescence in situ hybridization (FISH); tissue microarray (TMA); denaturation; copy number analysis ID PARAFFIN-EMBEDDED TUMORS AB Background: The recently developed tissue microarray (TMA) technology allows the arrangement of up to a thousand tissue specimens on a single microscope slide, This technology enables researchers to perform gene copy number studies on very large series of archival formalin-fixed tissues using fluorescence in situ hybridization (FISH), However, the hybridization properties of individual archival specimens can van, considerably. Therefore a highly optimized protocol is needed to fulfill the task of producing evaluable hybridization signals simultaneously in hundreds of specimens in a TMA. Methods: The performance of two different FISH protocols, the standard protocol for paraffin embedded tissues and our new optimized protocol, was tested on TMAs using probes for the HER-2 and ZNF217 genes as well as the chromosome 17 centromere. Results: The new protocol resulted in greatly increased signal intensity and an almost 30% increase in the number of tissue samples with evaluable hybridization signals. Conclusions: Our improved protocol for FISH on TMAs provides standardized hybridization conditions leading to high-quality hybridization signals in the majority of specimens. The increases in the signal intensity and the number of evaluable samples are extremely important for the successful analyses of TMAs by FISH and will allow the utilization of the TMA technology in its full potential. Published 2001 Wiley-Liss, Inc. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Aarhus Univ Hosp, Cancercytogenet Lab, Dept Haematol, DK-8000 Aarhus, Denmark. Univ Texas, Coll Engn, San Antonio, TX 78285 USA. Univ Basel, Inst Pathol, Basel, Switzerland. RP Kallioniemi, A (reprint author), NHGRI, Canc Genet Branch, NIH, 49 Convent Dr,Rm 4B24,MSC 4465, Bethesda, MD 20892 USA. RI Andersen, Claus Lindbjerg/A-9217-2012; OI Andersen, Claus Lindbjerg/0000-0002-7406-2103; Kallioniemi, Anne/0000-0003-3552-8158 NR 6 TC 43 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 1 PY 2001 VL 45 IS 2 BP 83 EP 86 DI 10.1002/1097-0320(20011001)45:2<83::AID-CYTO1149>3.0.CO;2-P PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 480ZL UT WOS:000171493300001 PM 11590619 ER PT J AU Lawson, ND Scheer, N Pham, VN Kim, CH Chitnis, AB Campos-Ortega, JA Weinstein, BM AF Lawson, ND Scheer, N Pham, VN Kim, CH Chitnis, AB Campos-Ortega, JA Weinstein, BM TI Notch signaling is required for arterial-venous differentiation during embryonic vascular development SO DEVELOPMENT LA English DT Article DE artery; notch; vein; zebrafish ID NEUROGENIC GENE-DELTA; ZEBRAFISH EMBRYOS; CARDIOVASCULAR DEVELOPMENT; TRANSCRIPTION FACTORS; DROSOPHILA-NOTCH; EXPRESSION; HOMOLOG; XENOPUS; VERTEBRATE; VASCULOGENESIS AB Recent evidence indicates that acquisition of artery or vein identity during vascular development is governed, in part, by genetic mechanisms. The artery-specific expression of a number of Notch signaling genes in mouse and zebrafish suggests that this pathway may play a role in arterial-venous cell fate determination during vascular development. We show that loss of Notch signaling in zebrafish embryos leads to molecular defects in arterial-venous differentiation, including loss of artery-specific markers and ectopic expression of venous markers within the dorsal aorta. Conversely, we find that ectopic activation of Notch signaling leads to repression of venous cell fate. Finally, embryos lacking Notch function exhibit defects in blood vessel formation similar to those associated with improper arterial-venous specification. Our results suggest that Notch signaling is required for the proper development of arterial and venous blood vessels, and that a major role of Notch signaling in blood vessels is to repress venous differentiation within developing arteries. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Cologne, Inst Entwicklungsbiol, D-50923 Cologne, Germany. RP Weinstein, BM (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RI Scheer, Nico/G-5242-2015 OI Scheer, Nico/0000-0002-8847-0415 FU NICHD NIH HHS [ZO1 HD 01011] NR 50 TC 503 Z9 518 U1 3 U2 27 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 2001 VL 128 IS 19 BP 3675 EP 3683 PG 9 WC Developmental Biology SC Developmental Biology GA 489CK UT WOS:000171974300003 PM 11585794 ER PT J AU Badenhorst, P AF Badenhorst, P TI Tramtrack controls glial number and identity in the Drosophila embryonic CNS SO DEVELOPMENT LA English DT Article DE tramtrack; gliogenesis; Drosophila; CNS ID TRANSCRIPTIONAL REPRESSOR TRAMTRACK; CELL FATE DETERMINATION; MAMMALIAN NEURAL CREST; ZINC-FINGER PROTEINS; VENTRAL NERVE CORD; LOOP-HELIX GENE; OLIGODENDROCYTE DEVELOPMENT; NEURONAL DIFFERENTIATION; ASYMMETRIC DIVISION; RETINA AB Neurons and glia are often derived from common multipotent stem cells. In Drosophila, neural identity appears to be the default fate of these precursors. Stem cells that generate either neurons or glia transiently express neural stem cell-specific markers. Further development as glia requires the activation of glial-specific regulators. However, this must be accompanied by simultaneous repression of the alternate neural fate. I show that the Drosophila transcriptional repressor Tramtrack is a key repressor of neuronal fates. It is expressed at high levels in all mature glia of the embryonic central nervous system. Analysis of the temporal profile of Tramtrack expression in glia shows that it follows that of existing glial markers. When expressed ectopically before neural stem cell formation, Tramtrack represses the neural stem cell-specific genes asense and deadpan. Surprisingly, Tramtrack protein levels oscillate in a cell cycle-dependent manner in proliferating glia, with expression dropping before replication, but re-initiating after S phase. Overexpression of Tramtrack blocks glial development by inhibiting S-phase and repressing expression of the S-phase cyclin, cyclin E. Conversely, in tramtrack mutant embryos, glia are disrupted and undergo additional rounds of replication. I propose that Tramtrack ensures stable mature glial identity by both repressing neuroblast-specific genes and controlling glial cell proliferation. C1 MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Badenhorst, P (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Room 6066, Bethesda, MD 20892 USA. OI Badenhorst, Paul/0000-0002-2542-0250 NR 53 TC 53 Z9 53 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 2001 VL 128 IS 20 BP 4093 EP 4101 PG 9 WC Developmental Biology SC Developmental Biology GA 487RC UT WOS:000171888200019 PM 11641231 ER PT J AU Hennighausen, L Robinson, GW AF Hennighausen, L Robinson, GW TI Signaling pathways in mammary gland development SO DEVELOPMENTAL CELL LA English DT Review ID HORMONE-RELATED PROTEIN; MICE LACKING; PROGESTERONE-RECEPTOR; C/EBP-BETA; OSTEOPROTEGERIN-LIGAND; DUCTAL MORPHOGENESIS; TOOTH DEVELOPMENT; TRANSGENIC MICE; KNOCKOUT MICE; CYCLIN D1 AB Unlike most other organs, development of the mammary gland occurs predominantly after birth, under the control of steroid and peptide hormones. Once the gland is established, cycles of proliferation, functional differentiation, and death of alveolar epithelium occur repeatedly with each pregnancy. Although it is unique in this respect, the signaling pathways utilized by the gland are shared with other cell types, and have been tailored to meet the needs of this secretory tissue. Here we discuss the signaling pathways that have been adopted by the mammary gland for its own purposes, and the functions they perform. C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RI Robinson, Gertraud/I-2136-2012 NR 67 TC 243 Z9 246 U1 4 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2001 VL 1 IS 4 BP 467 EP 475 DI 10.1016/S1534-5807(01)00064-8 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 546XK UT WOS:000175301500007 PM 11703938 ER PT J AU Frank, S Gaume, B Bergmann-Leitner, ES Leitner, WW Robert, EG Catez, F Smith, CL Youle, RJ AF Frank, S Gaume, B Bergmann-Leitner, ES Leitner, WW Robert, EG Catez, F Smith, CL Youle, RJ TI The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis SO DEVELOPMENTAL CELL LA English DT Article ID CYTOCHROME-C; MAMMALIAN-CELLS; OUTER-MEMBRANE; ENDOPLASMIC-RETICULUM; BAX; GTPASE; BCL-2; RELEASE; DNM1P; DIVISION AB In healthy cells, fusion and fission events participate in regulating mitochondrial morphology. Disintegration of the mitochondrial reticulum into multiple punctiform organelles during apoptosis led us to examine the role of Drp1, a dynamin-related protein that mediates outer mitochondrial membrane fission. Upon induction of apoptosis, Drp1 translocates from the cytosol to mitochondria, where it preferentially localizes to potential sites of organelle division. Inhibition of Drp1 by overexpression of a dominant-negative mutant counteracts the conversion to a punctiform mitochondrial phenotype, prevents the loss of the mitochondrial membrane potential and the release of cytochrome c, and reveals a reproducible swelling of the organelles. Remarkably, inhibition of Drp1 blocks cell death, implicating mitochondrial fission as an important step in apoptosis. C1 NINCDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Light Imaging Facil, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINCDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922 NR 59 TC 846 Z9 867 U1 6 U2 51 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2001 VL 1 IS 4 BP 515 EP 525 DI 10.1016/S1534-5807(01)00055-7 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 546XK UT WOS:000175301500011 PM 11703942 ER PT J AU Hovey, RC Trott, JF Ginsburg, E Goldhar, A Sasaki, MM Fountain, SJ Sundararajan, K Vonderhaar, BK AF Hovey, RC Trott, JF Ginsburg, E Goldhar, A Sasaki, MM Fountain, SJ Sundararajan, K Vonderhaar, BK TI Transcriptional and spatiotemporal regulation of prolactin receptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland SO DEVELOPMENTAL DYNAMICS LA English DT Article DE prolactin; progesterone; receptors; mammary gland; ovarian steroids; epithelial-stromal; ductal branching ID GENE-EXPRESSION; EPITHELIAL-CELLS; TRANSGENIC MICE; MULTIPLE FORMS; PREGNANT MOUSE; PRL RECEPTOR; C/EBP-BETA; FAT PAD; ESTROGEN; BINDING AB Ductal branching within the mammary gland is stimulated by prolactin (PRL) and progesterone (P) acting through their receptors (PRLR and PR). Analysis of mammary gland PRLR expression revealed increasing expression of the long form (L-PRLR) and two of the three short forms (S1- and S3-PRLR) during puberty that became maximal late in pubescence and early gestation, then declined during gestation. By contrast, S2-PRLR mRNA levels remained constant. Examination of stromal PRLR revealed the consistent expression of L-PRLR mRNA. By contrast, S1-PRLR was present only in the mammary fat pad of neonates, whereas high neonatal expression of S2-PRLR became undetectable during puberty. Stromal expression of S3-PRLR decreased to low levels during puberty and was undetectable during lactation and involution. Exogenous PRL stimulated DNA synthesis in both epithelial and adjacent stromal cells in vivo. Distribution of PRLR mRNA in mammary epithelium was homogeneous before puberty, and heterogeneous during puberty, gestation, and early lactation. A mutual role for PRLR and PR was suggested wherein PR mRNA increased beyond 6 weeks to maximal levels during puberty and gestation then became undetectable during lactation. In situ hybridization revealed that PR mRNA distribution is homogeneous in the ductal epithelium before 6 weeks and heterogenous during puberty and gestation and that PRLR and PR are similarly distributed in the ductal epithelium. Neither hormone stimulated DNA synthesis in mammary glands of ovariectomized females while their effects interacted markedly. These results demonstrate differential PRLR transcription by epithelial and stromal cells and a. similar distribution of PRLR and PR that may facilitate the interaction between P and PRL during ductal branching in the Mammary gland. Published 2001 Wiley-Liss, Inc. C1 NCI, Mol & Cellular Endocrinol Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Hovey, RC (reprint author), NCI, Mol & Cellular Endocrinol Sect, Canc Res Ctr, NIH, Bldg 10,Room 5B47,10 Ctr Dr, Bethesda, MD 20892 USA. NR 57 TC 73 Z9 74 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2001 VL 222 IS 2 BP 192 EP 205 DI 10.1002/dvdy.1179 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 479AR UT WOS:000171382200006 PM 11668597 ER PT J AU Papoutsi, M Tomarev, SI Eichmann, A Prols, F Christ, B Wilting, J AF Papoutsi, M Tomarev, SI Eichmann, A Prols, F Christ, B Wilting, J TI Endogenous origin of the lymphatics in the avian chorioallantoic membrane SO DEVELOPMENTAL DYNAMICS LA English DT Article DE chorioallantoic membrane; lymphangiogenesis; lymphangioblast; endothelium; VEGF-C; VEGFR-3; Prox1; quail-chick chimera ID ENDOTHELIAL GROWTH-FACTOR; HOMEOBOX GENE PROX-1; VEGF-C; EMBRYONIC-DEVELOPMENT; RECEPTOR; CELLS; EXPRESSION; LYMPHANGIOGENESIS; PRECURSORS; ANGIOGENESIS AB The lymphatics of the intestinal organs have important functions in transporting chyle toward the jugulosubclavian junction, but the lymphangiogenic potential of the splanchnic mesoderm has not yet been tested. Therefore, we, studied the allantoic bud of chick and quail embryos. It is made up of endoderm and splanchnic mesoderm and fuses with the. chorion to form the chorioallantoic membrane (CAM) containing both blood vessels and lymphatics. In day 3 embryos (stage 18 of Hamburger and Hamilton [HH]), the allantoic mesoderm consists of mesenchymal cells that form blood islands during stage 19 (HH). The endothelial network of the allantoic bud, some intraluminal and some mesenchymal cells express the hemangiopoietic marker QH1. The QH1-positive endothelial cells, also express the vascular endothelial growth factor receptor-3 (VEGYR-3), whereas the integrating angioblasts and the round hematopoietic cells are QH1-positive/VEGER-3-negative. The ligand, VEGF-C, is expressed ubiquitously in the allantoic bud, and later predominantly in the allantoic epithelium and the wall of larger blood vessels. Allantoic buds of stage 17-18 (HH) quail embryos were grafted homotopically into chick embryos and reincubated until day 13. In the chimeric CAMs, quail endothelial cells are present in blood vessels and lymphatics, the latter being QH1 and VEGFR-3 double-positive. QH1-positive hematopoietic cells are found at many extra- and intraembryonic sites, whereas endothelial cells are confined to the grafting site. Our results show that the early allantoic bud contains hemangioblasts and lymphangioblasts. The latter can be identified with Prox1 antibodies and mRNA probes in the allantoic mesoderm of day 4 embryos (stage 21 HH). Prox1 is a specific marker of the lymphatic endothelium throughout CAM development. (C) 2001 Wiley-Liss, Inc. C1 Univ Freiburg, Inst Anat, D-79104 Freiburg, Germany. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD USA. Coll France, CNRS, Inst Embryol Cellulaire & Mol, Nogent Sur Marne, France. RP Wilting, J (reprint author), Univ Freiburg, Inst Anat, Albertstr 17, D-79104 Freiburg, Germany. FU NICHD NIH HHS [N01-HD-6-2915] NR 51 TC 50 Z9 50 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2001 VL 222 IS 2 BP 238 EP 251 DI 10.1002/dvdy.1187 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 479AR UT WOS:000171382200010 PM 11668601 ER PT J AU Takahashi, K Nuckolls, GH Takahashi, I Nonaka, K Nagata, M Ikura, T Slavkin, HC Shum, L AF Takahashi, K Nuckolls, GH Takahashi, I Nonaka, K Nagata, M Ikura, T Slavkin, HC Shum, L TI Msx2 is a repressor of chondrogenic differentiation in migratory cranial neural crest cells SO DEVELOPMENTAL DYNAMICS LA English DT Article DE cranial neural crest cell migration; cell fate determination; mandibulofacial dysostosis; mouse embryo; adenovirus gene delivery; loss-of-function; mutagenesis; Msx2; Sox9; Meckel's cartilage; alcian blue staining; type II collagen; aggrecan; explant culture; RT-PCR ID VITAL DYE ANALYSIS; MOUSE EMBRYOS; TOOTH DEVELOPMENT; GENE-EXPRESSION; TRANSGENIC MICE; COLLAGEN GENE; II COLLAGEN; DNA-BINDING; IN-VITRO; SOX9 AB During early mouse embryogenesis, cranial neural crest cells (CNCC) emigrate from the posterior midbrain and rhombomeres I and 2 of the anterior hindbrain into the first branchial arch-derived maxillary and mandibular processes and there provide cell lineages for several phenotypes, including cartilage, bone, and tooth. Here, we report that Sox9 and Msx2 were coexpressed in a subpopulation of CNCC during their migration. Because Sox9 is a transactivator of chondrogenesis, and Msx genes can act as transcriptional repressors, we hypothesized that Sox9 expression indicates the determination of CNCC-derived chondrogenic cell lineage and that Msx2. represses chondrogenic differentiation until CNCC migration is completed within the mandibular processes. To test whether Msx2 represses chondrogenesis,, we designed experiments to inhibit Msx2 function in migratory CNCC in primary cultures through the expression of loss-of-function Msx2 mutants. We showed that infection of migratory CNCC with adenovirus Msx2 mutants accelerated the rate and extent of chondrogenesis, as indicated by the expression level of type II collagen and aggrecan, and the amount of alcian blue staining. Adenovirus infections did not apparently interfere with CNCC proliferation or migration. These findings suggest that an important early event in craniofacial morphogenesis is a transient expression of both Sox9 and Msx2 during emigration into the forming mandibular processes followed by restricted expression of Sox9 within CNCC-derived chondroprogenitor cells. We conclude that Msx2 serves as a repressor of chondrogenic differentiation during CNCC migration. Published 2001 Wiley-Liss, Inc. C1 NIAMS, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. RP Shum, L (reprint author), NIAMS, Craniofacial Dev Sect, NIH, Room 324,Bldg 6,6 Ctr Dr,MSC-2745, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [Z01 AR 41114] NR 59 TC 51 Z9 52 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2001 VL 222 IS 2 BP 252 EP 262 DI 10.1002/dvdy.1185 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 479AR UT WOS:000171382200011 PM 11668602 ER PT J AU Sachs, LM Amano, T Rouse, N Shi, YB AF Sachs, LM Amano, T Rouse, N Shi, YB TI Involvement of histone deacetylase at two distinct steps in gene regulation during intestinal development in Xenopus laevis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE amphibian metamorphosis; histones deacetylase; thyroid hormone receptor ID THYROID-HORMONE RECEPTOR; TRANSCRIPTIONAL REPRESSION; TRICHOSTATIN-A; AMPHIBIAN METAMORPHOSIS; FROG METAMORPHOSIS; NUCLEAR RECEPTORS; CELL-DEATH; BETA GENE; TR-BETA; N-COR AB Amphibian metamorphosis is marked by dramatic thyroid hormone (T-3)-induced changes including de novo morphogenesis, tissue remodeling and organ resorption through programmed cell death. These changes involve cascades of gene regulation initiated by thyroid hormone and. its. receptors. Previous studies suggest that chromatin remodeling involving changes in core histone acetylation plays a fundamental role in transcriptional regulation. A basic model has been suggested where targeted histone deacetylation is involved, in transcriptional repression and histone acetylation is involved in transcriptional activation. On the other hand, the developmental roles of histone acetylation remain to be elucidated. Here we demonstrate that tadpole treatment with trichostatin A, a specific potent histone deacetylase inhibitor, blocks metamorphosis; Gene expression analyses show that trichostatin A. induces the release of T-3-response gene repression without affecting T-3-induction of direct T-3-response genes. However, the drug blocks the regulation of late T-3-response genes, which may be responsible for its inhibitory effects on metamorphosis. These data support a role of deacetylases in transcriptional repression by unliganded T-3 receptor during premetamorphosis and another role at a, downstream step of the gene regulation cascade induced by T-3 during metamorphosis. (C) 2001,Wiley-Liss, Inc. C1 NICHHD, Lab Gene Regulat & Dev, Unit Mol Morphogenesis, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Lab Gene Regulat & Dev, Unit Mol Morphogenesis, NIH, Bldg 18 T,Rm 106, Bethesda, MD 20892 USA. NR 68 TC 18 Z9 19 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2001 VL 222 IS 2 BP 280 EP 291 DI 10.1002/dvdy.1195 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 479AR UT WOS:000171382200014 PM 11668605 ER PT J AU Cai, T Xie, JP She, JX Notkins, AL AF Cai, T Xie, JP She, JX Notkins, AL TI Analysis of the coding and promoter regions of the autoantigen IA-2 in subjects with and without autoantibodies to IA-2 SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; PROTEIN-TYROSINE-PHOSPHATASE; HLA-DQ; INSULIN; GENE; IDDM; MUTATIONS; SUSCEPTIBILITY; POLYMORPHISMS; LOCATION AB Despite extensive studies on HLA polymorphism, there have been few, if any, studies on allelic forms or mutations in proteins that serve as autoantigens. The present experiments were designed to look for alterations in the coding and promoter regions of the autoantigen IA-2 in type one (insulin-dependent) diabetic patients with autoantibodies to IA-2 as compared with siblings without diabetes or autoantibodies to IA-2. Genomic DNA was used as a template and was amplified by polymerase chain reaction, with pairs of primers encompassing the promoter region and the 23 exons of the coding region of IA-2. A total of nine nucleotide changes were found in the coding region of the six type 1 diabetic patients; four were silent and five were missense changes, but all occurred in the extracellular domain of IA-2 to which autoantibodies are not directed. Few, if any, changes were found in the 5 ' upstream (-706 to +135) promoter region. The results of the experiments support the null hypothesis that differences among individuals in the nucleotide and amino acid sequences of the promoter and coding regions of IA-2, respectively, do not account for why some individuals develop autoantibodies to IA-2 and others do not. C1 NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. RP Notkins, AL (reprint author), NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 121,30 Convent Dr MSC 4322, Bethesda, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2001 VL 50 IS 10 BP 2406 EP 2409 DI 10.2337/diabetes.50.10.2406 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 477KR UT WOS:000171283200032 PM 11574427 ER PT J AU Ravi, RG Kertesy, SB Dubyak, GR Jacobson, KA AF Ravi, RG Kertesy, SB Dubyak, GR Jacobson, KA TI Potent P2X(7) receptor antagonists: Tyrosyl derivatives synthesized using a sequential parallel synthetic approach SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ion channels; nucleotides; structure activity relationships; purines; isoquinolines; KN-62 ID NUCLEOTIDE RECEPTOR; DENDRITIC CELLS; RAT MICROGLIA; CA2+ INFLUX; ATP; KN-62; ACTIVATION; INHIBITOR; SUBTYPES; RELEASE AB Novel analogs of 1-(N,O-bis[5-isoquinolinesulfonyl]-N-methyl-L-tyrosyl)-4-phenylpiperazine (KN-62, 1) were synthesized and found to be potent antagonists in a functional assay, inhibition of ATP-induced K+ efflux in HEK293 cells expressing recombinant human P2X(7) receptors. Antagonism of murine P2X7 receptors was also observed. The analogs consisted of L-tyrosine derivatives, of the general structure R-1-Tyr(OR2)-piperazinyl-R-3, in which three positions were systematically varied in structure through facile acylation reactions. Each of the three positions was optimized in sequence through parallel synthesis alternating with biological evaluation, leading to the identification and optimization of potent P2X7 antagonists. The optimal groups at R-1 were found to be large hydrophobic groups, linked to the alpha -amino position through carbamate, amide, or sulfonamide groups. The benzyloxycarbonyl (Cbz) group was preferred over most sulfonamides and other acyl groups examined, except for quinoline sulfonyl. At R-2, an arylsulfonate ester was preferred, and the order of potency was p-tolyl, p-methoxyphenyl, phenyl > alpha -naphthyl, beta -naphthyl. A benzoyl ester was of intermediate potency. Aliphatic esters and carbonate derivatives at the tyrosyl phenol were inactive, while a tyrosyl O-benzyl ether was relatively potent. The most potent P2X(7) receptor antagonists identified in this study contained Cbz at the R-1 position, an aryl sulfonate at the R-2 position, and various acyl groups at the R-3 position. At R-3, t-butyloxycarbonyl- and benzoyl groups were preferred. The opening of the piperazinyl ring to an ethylene diamine moiety abolished antagonism. In concentration-response studies, a di-isoquinolinyl, Boc derivative, 4 (MRS2306), displayed an IC50 value of 40 nM as an antagonist of P2X(7) receptor- mediated ion flux and was more potent than the reference compound 1. N-alpha-Cbz, Boc-piperazinyl derivatives, 11 (MRS2317), 22 (MRS2326), and 41 (MRS2409) were less potent than 1, with IC50 values of 200-300 nM. C1 NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031127-01, Z99 DK999999]; NIGMS NIH HHS [R01 GM036387] NR 32 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 2001 VL 54 IS 2 BP 75 EP 87 DI 10.1002/ddr.1207 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 507CN UT WOS:000173009500004 PM 27019545 ER PT J AU Issaq, HJ AF Issaq, HJ TI The role of separation science in proteomics research SO ELECTROPHORESIS LA English DT Review DE proteome; multidimensional; isotope-coded affinity tags; proteins; peptides; review ID CAPILLARY-ZONE-ELECTROPHORESIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; IONIZATION MASS-SPECTROMETRY; CARCINOMA CELL-LINE; GEL-ELECTROPHORESIS; 2-DIMENSIONAL ELECTROPHORESIS; PROTEIN EXPRESSION; COMPLEX-MIXTURES; IDENTIFICATION; PEPTIDES AB In the last few years there has been an increased effort into the separation, quantification and identification of all proteins in a cell or tissue. This is a review of the role gel electrophoresis, high performance liquid chromatography (HPLC), and capillary electrophoresis (CE) play in proteomics research. The capabilities and limitations of each separation technique have been pointed out. Instrumental strategies for the resolution of cell proteins which are based on efficient separation employing either a single high-resolution procedure or a multidimensional approach on-line or off-line, and a mass spectrometer for protein identification have been reviewed. A comparison of the advantages of multi-dimensional separations such as two-dimensional polyacrylamide gel electrophoresis, HPLC-HPLC, and HPLC-CE to the separation of cell and tissue proteins are discussed. Also, a discussion of novel approaches to protein concentration, separation, detection, and quantification is given. C1 NCI Frederick, SAIC Frederick, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI Frederick, SAIC Frederick, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 68 TC 146 Z9 161 U1 3 U2 17 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 2001 VL 22 IS 17 BP 3629 EP 3638 DI 10.1002/1522-2683(200109)22:17<3629::AID-ELPS3629>3.0.CO;2-O PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 484WT UT WOS:000171713100004 PM 11699900 ER PT J AU Guarne, A Junop, MS Yang, W AF Guarne, A Junop, MS Yang, W TI Structure and function of the N-terminal 40 kDa fragment of human PMS2: a monomeric GHL ATPase SO EMBO JOURNAL LA English DT Article DE DNA binding; GHL ATPase; HNPCC; mismatch repair; PMS2 ID DNA MISMATCH REPAIR; NONPOLYPOSIS COLORECTAL-CANCER; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; MICROSATELLITE INSTABILITY; PROTEIN MUTS; TUMOR-CELLS; BINDING; GENES AB Human MutL alpha, a heterodimer of hMLH1 and hPMS2, is essential for DNA mismatch repair. Inactivation of the hmlh1 or hpms2 genes by mutation or epigenesis causes genomic instability and a predisposition to hereditary non-polyposis cancer. We report here the X-ray crystal structures of the conserved N-terminal 40 kDa fragment of hPMS2, NhPMS2, and its complexes with ATP gammaS and ADP at 1.95, 2.7 and 2.7 Angstrom resolution, respectively. The NhPMS2 structures closely resemble the ATPase fragment of Escherichia coli MutL, which coordinates protein-protein interactions in mismatch repair by undergoing structural transformation upon binding of ATP. Unlike the E.coli MutL, whose ATPase activity requires protein dimerization, the monomeric form of NhPMS2 is active both in ATP hydrolysis and DNA binding. NhPMS2 is the first example of a GHL ATPase active as a monomer, suggesting that its activity may be modulated by hMLH1 in MutL alpha, and vice versa. The potential heterodimer interface revealed by crystallography provides a mutagenesis target for functional studies of MutL alpha. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Yang, Wei/D-4926-2011; Junop, Murray/E-4160-2015 OI Yang, Wei/0000-0002-3591-2195; Junop, Murray/0000-0001-6676-5717 NR 40 TC 74 Z9 76 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 1 PY 2001 VL 20 IS 19 BP 5521 EP 5531 DI 10.1093/emboj/20.19.5521 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 481BZ UT WOS:000171501200024 PM 11574484 ER PT J AU Weinstein, LS Yu, SH Warner, DR Liu, J AF Weinstein, LS Yu, SH Warner, DR Liu, J TI Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting SO ENDOCRINE REVIEWS LA English DT Review ID MCCUNE-ALBRIGHT-SYNDROME; GUANINE-NUCLEOTIDE-BINDING; POLYOSTOTIC FIBROUS DYSPLASIA; PSEUDOHYPOPARATHYROIDISM TYPE-IB; CYCLASE COUPLING PROTEIN; RECEPTOR-MEDIATED ACTIVATION; G(S)ALPHA GENE GNAS1; TYROSINE KINASE-ACTIVITY; CYCLIC ADENOSINE-3,5-MONOPHOSPHATE RESPONSE; NEUROENDOCRINE SECRETORY PROTEIN AB The heterotrimeric G protein G(s) couples hormone receptors (as well as other receptors) to the effector enzyme adenylyl cyclase and is therefore required for hormone-stimulated intracellular cAMP generation. Receptors activate G(s) by promoting exchange of GTP for GDP on the G(s) alpha -subunit (G(s)alpha) while an intrinsic GTPase activity of G(s)alpha that hydrolyzes bound GTP to GDP leads to deactivation. Mutations of specific G(s)alpha residues (Arg(201) or Gln(227)) that are critical for the GTPase reaction lead to constitutive activation of G(s)-coupled signaling pathways, and such somatic mutations are found in endocrine tumors, fibrous dysplasia of bone, and the McCune-Albright syndrome. Conversely, heterozygous loss-of-function mutations may lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, brachydactyly, se ossifications, and mental deficits. Similar mutations are also associated with progressive osseous heteroplasia. Interestingly, paternal transmission of GNAS1 mutations leads to the AHO phenotype alone (pseudopseudohypoparathyroidism), while maternal transmission leads to AHO plus resistance to several hormones (e.g., PTH, TSH) that activate G(s) in their target tissues (pseudohypoparathyroidism type IA). Studies in G(s)alpha knockout mice demonstrate that G(s)alpha is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in some tissues (e.g., renal proximal tubule, the major site of renal PTH action), while being biallelically expressed in most other tissues. Disrupting mutations in the maternal allele lead to loss of G(s)alpha expression in proximal tubules and therefore loss of PTH action in the kidney, while mutations in the paternal allele have little effect on G(s)alpha expression or PTH action. G(s)alpha has recently been shown to be also imprinted in human pituitary glands. The G(s)alpha gene GNAS1 (as well as its murine ortholog Gnas) has at least four alternative promoters and first exons, leading to the production of alternative gene products including G(s)alpha, XL alphas (a novel G(s)alpha isoform that is expressed only from the paternal allele), and NESP55 (a chromogranin-like protein that is expressed only from the maternal allele). A fourth alternative promoter and first exon (exon 1A) located approximately 2.5 kb upstream of the G,a promoter is normally methylated on the maternal allele and transcriptionally active on the paternal allele. In patients with isolated renal resistance to PTH (pseudohypoparathyroidisin type EB), the exon 1A promoter region has a paternal-specific imprinting pattern on both alleles (unmethylated, transcriptionally active), suggesting that this region is critical for the tissue-specific imprinting of G(s)alpha. The GNAS1 imprinting defect in pseudohypoparathyroidisin type IB is predicted to decrease G(s)alpha expression in renal proximal tubules. Studies in G(s)alpha knockout mice also demonstrate that this gene is critical in the regulation of lipid and glucose metabolism. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Louisville, Sch Dent, Dept Mol Cellular & Craniofacial Biol, Louisville, KY 40202 USA. RP NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov OI Weinstein, Lee/0000-0002-1899-5152 NR 416 TC 284 Z9 293 U1 0 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD OCT PY 2001 VL 22 IS 5 BP 675 EP 705 DI 10.1210/er.22.5.675 PG 31 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 481AT UT WOS:000171496700006 PM 11588148 ER PT J AU Doyle, ME Greig, NH Holloway, HW Betkey, JA Bernier, M Egan, JM AF Doyle, ME Greig, NH Holloway, HW Betkey, JA Bernier, M Egan, JM TI Insertion of an N-terminal 6-aminohexanoic acid after the 7 amino acid position of glucagon-like peptide-1 produces a long-acting hypoglycemic agent SO ENDOCRINOLOGY LA English DT Article ID BIOLOGICAL-ACTIVITY; IV; STABILITY; CELLS; AMIDE AB The use of glucagon-like peptide-1 (GLP-1) as a routine treatment for type 2 diabetes mellitus is undermined by its short biological half-life. A cause of degradation is its cleavage at the N-terminal HAE sequence by the enzyme dipeptidyl peptidase IV (DPP IV). To protect from DPP IV, we have studied the biological activity of a GLP-1 analog in which 6-aminohexanoic acid (Aha) is inserted between histidine and alanine at positions 7 and 8. We have compared the biological activity of this new compound, GLP-1 Aha(8), with the previously described GLP-1 8-glycine (GLP-1 Gly(8)) analog. GLP-1 Aha(8) (10 nm) was equipotent with GLP-1 (10 nm) in stimulating insulin secretion in RIN 1046-38 cells. As with GLP-1 Gly(8), the binding affinity of GLP-1 Aha8 for the GLP-1 receptor in intact Chinese hamster ovary (CHO) cells expressing the human GLP-1 receptor (CHO/GLP-1R cells) was reduced (IC50: GLP-1, 3.7 +/- 0.2 nm; GLP-1 Gly(8), 41 +/- 9 um; GLP-1 Aha(8), 22 +/- 7 um). GLP-1 Aha(8) was also shown to stimulate intracellular cAMP production 4-fold above basal at concentrations as low as 0.5 nm. However, it exhibited a higher ED50 when compared to GLP-1 and GLP-1 Gly(8) (ED50: GLP-1, 0.036 +/- 0.002 nm, GLP-1 Gly(8), 0.13 +/- 0.02 nm, GLP-1 Aha(8), 0.58 +/- 0.03 nm). A series of D-amino acid-substituted GLP-1 compounds were also examined to assess the importance of putative peptidase-sensitive cleavage sites present in the GLP-1 molecule. They had poor binding affinity for the GLP-1 receptor, and none of these compounds stimulated the production of intracellular cAMP in CHO/GLP-1R cells or insulin secretion in RIN 1046-38 cells. GLP-1 Aha(8) (24 nmol/kg) administered se to fasted Zucker (fa/fa) rats (mean blood glucose, 195 +/- 32 mg/dl) lowered blood glucose levels to a nadir of 109 +/- 3 mg/dl, and it remained significantly lower for 8 h. Matrix-assisted linear desorption ionization-time of flight mass spectrometry of GLP-1 Abe incubated with DPP IV (37 C, 2 h) did not exhibit an N-terminal degradation product. Taken together, these results show that insertion of Aba after the 7 position in GLP-1 produces an effective, long-acting GLP-1 analog, which may be useful in the treatment of type 2 diabetes mellitus. C1 NIA, Diabet Sect 23, NIH, Baltimore, MD 21224 USA. NIA, Drug Design & Dev Sect, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Diabet Sect 23, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Bernier, Michel/0000-0002-5948-368X NR 15 TC 30 Z9 32 U1 1 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2001 VL 142 IS 10 BP 4462 EP 4468 DI 10.1210/en.142.10.4462 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 476PV UT WOS:000171238700038 PM 11564711 ER PT J AU Centeno, JA Mullick, FG Gibb, H Longfellow, D Thompson, C AF Centeno, JA Mullick, FG Gibb, H Longfellow, D Thompson, C TI The International Tissue and Tumor Repository for Chronic Arseniasis at the Armed Forces Institute of Pathology SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 USAF, Inst Pathol, Washington, DC 20330 USA. US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. NCI, Bethesda, MD 20892 USA. Natl Inst Enironm Hlth Sci, Res Triangle Pk, NC USA. RP Centeno, JA (reprint author), USAF, Inst Pathol, Washington, DC 20330 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2001 VL 109 IS 10 BP A465 EP A465 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 487GF UT WOS:000171864800004 PM 11700620 ER PT J AU Melnick, R AF Melnick, R TI Peroxisome proliferators: Response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID SUSCEPTIBILITY; WY-14,643; MCF-7; LIVER; CELLS C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Melnick, R (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 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 OCT PY 2001 VL 109 IS 10 BP A463 EP A464 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 487GF UT WOS:000171864800003 ER PT J AU Tomatis, L Huff, J AF Tomatis, L Huff, J TI Evolution of cancer etiology and primary prevention SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 40 TC 13 Z9 13 U1 0 U2 0 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 OCT PY 2001 VL 109 IS 10 BP A458 EP A460 DI 10.1289/ehp.109-a458 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 487GF UT WOS:000171864800001 PM 11675275 ER PT J AU Ballestar, E Pile, LA Wassarman, DA Wolffe, AP Wade, PA AF Ballestar, E Pile, LA Wassarman, DA Wolffe, AP Wade, PA TI A Drosophila MBD family member is a transcriptional corepressor associated with specific genes SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE methyl-CpG-binding protein; histone deacetylase; Mi-2 complex; transcriptional repression; Drosophila melanogaster ID CPG-BINDING-PROTEINS; HISTONE DEACETYLASE; DNA METHYLATION; CHROMOSOMAL PROTEIN; REPRESSION; COMPLEX; MELANOGASTER; CHROMATIN; DOMAIN; LOCALIZATION AB DNA methylation in Drosophila melanogaster is restricted temporally during development and occurs at a significantly lower frequency than in mammals. Thus, the regulatory functions, if any, of this form of DNA modification in Drosophila are unclear. However, the presence of homologs of vertebrate methyl-CpG-binding proteins implies functional consequences for DNA methylation in flies. This work describes the properties of dMBD-like, a Drosophila homolog of vertebrate MBD2 and MBD3. dMBD-like and dMBD-like Delta (a splice variant) failed to bind model methylated DNA probes, inconsistent with their function as mediators of methyl CpG-directed transcriptional repression. However, the MBD-like proteins exhibit transcriptional and biochemical properties consistent with roles as components of a histone deacetylase-dependent corepressor complex similar to the vertebrate Mi-2 complex. The two proteins are differentially expressed during development, suggesting functional specialization. dMBD-like and/or dMBD-like Delta is present at the chromocenter on larval polytene chromosomes as well as at discrete bands interspersed along the euchromatic chromosome arms, many of which are coincident with known ecdysone-induced loci. This banding pattern suggests gene-specific regulatory functions for dMBD-like and the Drosophila Mi-2 complex. C1 NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Ballestar, E (reprint author), Univ Valencia, Dept Biochem & Mol Biol, C Dr Moliner 50, E-46100 Valencia, Spain. NR 39 TC 34 Z9 35 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT PY 2001 VL 268 IS 20 BP 5397 EP 5406 DI 10.1046/j.0014-2956.2001.02480.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 484LP UT WOS:000171692100020 PM 11606202 ER PT J AU Parkin, DM Bray, FI Devesa, SS AF Parkin, DM Bray, FI Devesa, SS TI Cancer burden in the year 2000. The global picture SO EUROPEAN JOURNAL OF CANCER LA English DT Review ID PRIMARY LIVER-CANCER; LARGE-BOWEL-CANCER; REPUBLIC-OF-CHINA; ORAL-CONTRACEPTIVE USE; INVASIVE CERVICAL-CANCER; HEPATITIS-B VACCINATION; SQUAMOUS-CELL CARCINOMA; MALE BRITISH DOCTORS; BREAST-CANCER; LUNG-CANCER C1 Int Agcy Res Canc, F-69372 Lyon, France. NCI, Bethesda, MD 20892 USA. RP Parkin, DM (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France. NR 317 TC 939 Z9 1014 U1 2 U2 29 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 2001 VL 37 SU 8 BP S4 EP S66 PG 63 WC Oncology SC Oncology GA 491UA UT WOS:000172126400003 PM 11602373 ER PT J AU Liu, XG Narang, PK Li, RC AF Liu, XG Narang, PK Li, RC TI Induction of hepatic and presystemic metabolism of antipyrine in the mice: Rifampicin versus rifabutin SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article DE rifampicin; rifabutin; P450; GI tract; liver; enzyme induction ID P-GLYCOPROTEIN; ORAL BIOAVAILABILITY; PHARMACOKINETICS AB The effects of hepatic and presystemic enzyme induction on the bioavailability (F) and disposition of antipyrine after repeated rifampicin (RFM) and rifabutin (RBT) exposure were studied in mice. ICR mice were divided to receive 4 daily oral dosing of either the dosing vehicle or 50 mg/kg of REM or RBT. At the completion of rifamycin dosing, the pharmacokinetics of antipyrine were assessed following either a single 50 mg/kg oral dose or a 20 mg/kg intravenous dose. Blood samples were collected (n=4/timePoint) over a 6 h period. The content of P450 in the liver and small intestine (GI) was also assessed in parallel. Systemic antipyrine clearance (CL) increased from 31.8 ml/min/kg (controls) by 64% and 42% following repeated exposure to RFM and RBT, respectively. Estimate of F for antipyrine decreased from 0.97 in controls to 0.58 and 0.82 in animals treated with RFM and RBT, respectively. The content of P450 (nmol/mg protein) in the liver increased from 0.61 (control) to 1.36 following RFM and 0.82 for RBT, while no significant changes were observed for the GI tract. The i.v. dosing data confirmed the induction of antipyrine metabolism in the liver by both rifamycins yet the induction potential was approximately 1/3 lower for RBT. This difference was consistent with the changes observed in the hepatic P450 protein content, but this alone could not account for the reduction in the F for antipyrine. Therefore, predictions for changes in F of an interacting agent should not be judged solely on the basis of the metabolic status of the liver. The relative contribution of metabolic induction and presystemic drug loss to bioavailability/absorption should also be further delineated for its relevance to poly-pharmacy in patients likely to receive long term rifamycin based treatment. C1 NIDDK, NIH, Bethesda, MD USA. Pharmacia & Upjohn Inc, Global Regulatory Affairs, Kalamazoo, MI 49001 USA. Chinese Univ Hong Kong, Fac Med, Dept Pharm, Hong Kong, Peoples R China. RP Li, RC (reprint author), RW Johnson Pharmaceut Res Inst, Pharmacokinet Pharmacodynam Clin Drug Evaluat, 920 Route 202, Raritan, NJ 08869 USA. NR 19 TC 5 Z9 5 U1 1 U2 4 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78, AVE DE LA ROSERAIE, CASE POSTALE 456,, CH-1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD OCT-DEC PY 2001 VL 26 IS 4 BP 209 EP 213 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 512GT UT WOS:000173317200001 PM 11808861 ER PT J AU Derby, MA Snyder, JT Tse, R Alexander-Miller, MA Berzofsky, JA AF Derby, MA Snyder, JT Tse, R Alexander-Miller, MA Berzofsky, JA TI An abrupt and concordant initiation of apoptosis: antigen-dependent death of CD8(+) CTL SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article; Proceedings Paper CT 7th Human Leukocyte Differentiation Antigen Workshop (HLDA7) CY 2000 CL HARROGATE, ENGLAND DE apoptosis; CTL; TNFR2; MHC; flow cytometry ID TUMOR-NECROSIS-FACTOR; CYTOTOXIC T-LYMPHOCYTES; SERIAL TCR ENGAGEMENT; KAPPA-B ACTIVATION; MEDIATED APOPTOSIS; SIGNALING EVENTS; CELL ACTIVATION; MHC MOLECULE; CLASS-I; RECEPTOR AB The ability of CD8(+) cytotoxic T lymphocytes (CTL) to clear viral infections may be limited when high avidity CTL encounter supra-optimal antigen density on antigen-presenting cells (APC) and undergo antigen-dependent apoptosis of CTL (ADAC). Previously, we have shown ADAC in CD8(+) populations to be Fas independent, TNF-alpha receptor 2 (TNFR2) mediated, caspase dependent, and accompanied by a decrease in Bcl-2. We now employ flow cytometry to follow ADAC within individual CD8(+) cells to demonstrate that the intense TCR signal induced in high avidity CTL by supra-optimal antigen density results 8-16 h later in a caspase-independent TNFR2 down-modulation that is directly related to the stimulating APC antigen density and concludes in a rapid onset of apoptosis by 18-24 h. Individual CTL undergoing apoptosis exhibit a dramatic and concurrent: (1) positive staining with Annexin V and propidium iodide; (2) transformation to a smaller cell size characteristic of apoptosis; and (3) a nearly complete loss of Bcl-2, c-IAP-1, and TRAF2. We conclude that the antigen-dependent apoptosis of CD8(+) CTL occurs when a tandem TCR/TNFR2 signal initiates an abrupt and concordant onset of multiple apoptotic events. C1 NCI, Metab Branch, NIH, Mol Immunogenet & Vaccine Res Sect, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Metab Branch, NIH, Mol Immunogenet & Vaccine Res Sect, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 42 TC 23 Z9 23 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2001 VL 31 IS 10 BP 2951 EP 2959 DI 10.1002/1521-4141(2001010)31:10<2951::AID-IMMU2951>3.0.CO;2-Q PG 9 WC Immunology SC Immunology GA 485WA UT WOS:000171785400014 PM 11592071 ER PT J AU Shibaki, A Katz, SI AF Shibaki, A Katz, SI TI Activation through CD40 ligation induces functional Fas ligand expression by Langerhans cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article; Proceedings Paper CT 7th Human Leukocyte Differentiation Antigen Workshop (HLDA7) CY 2000 CL HARROGATE, ENGLAND DE Langerhans cell; Fas ligand; apoptosis; T cell; inflammation ID RECEPTOR TRANSGENIC MICE; DENDRITIC CELLS; INDUCED APOPTOSIS; IN-VIVO; T-CELLS; TOLERANCE INDUCTION; EPIDERMAL-CELLS; SELF-ANTIGENS; CD95 FAS; BCL-X AB Langerhans cells (LC) are professional antigen-presenting cells of dendritic cell (DC) lineage and are critical for the induction of primary immune responses in skin. Following antigenic stimulation, LC migrate to regional lymph nodes and induce antigen-specific activation of T cells. After primary expansion, the majority of T cells undergo Fas/Fas ligand (FasL)mediated apoptotic cell death, thereby suppressing their excessive expansion. Although recent investigations have indicated an immunoregulatory function for DC, whether LC could be involved in Fas/FasL-mediated suppression of activated T cells is still unclear. In this study, we found that LC express FasL after activation triggered through CD40 molecules on their surface, but not by stimulation with LPS or IFN-gamma. The functional significance of FasL expression by LC was demonstrated using two different assays for apoptosis induced in Jurkat cells. The apoptosis in Jurkat cells was completely blocked by anti-FasL blocking antibody, suggesting a Fas/FasL-mediated mechanism. These results indicate a new feedback mechanism to down-regulate T cell activation by LC through the interaction of the TNF receptor/ligand superfamily, CD40/CD40L and Fas/FasL. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Rm 12N238,10 Ctr Dr,MSC1908, Bethesda, MD 20892 USA. NR 47 TC 27 Z9 27 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2001 VL 31 IS 10 BP 3006 EP 3015 DI 10.1002/1521-4141(2001010)31:10<3006::AID-IMMU3006>3.0.CO;2-L PG 10 WC Immunology SC Immunology GA 485WA UT WOS:000171785400020 PM 11592077 ER PT J AU Brambila, E Tenorio, N Garcia-Luna, E Waalkes, MP AF Brambila, E Tenorio, N Garcia-Luna, E Waalkes, MP TI Effect of abdominal surgery on the activity of acid and alkaline ribonucleases in rats SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE acid ribonuclease; alkaline ribonuclease; ribonuclease inhibitor; surgery ID PURIFICATION; INHIBITOR; RNASE AB Ribonucleases (RNases) are a group of enzymes that hydrolyze different classes of RNA. It has been suggested that RNase activity in cells can act to indirectly regulate protein synthesis by controlling RNA degradation. However, little is known about the role of RNases under conditions characterized by a sudden increase of protein synthesis, such as with surgical trauma. The aim of this study was to investigate the effect of abdominal surgery on acid and alkaline RNase activities in rat liver. Acid and alkaline RNase activities decreased significantly at 3 h after surgery, reaching the lowest level at 16 h (63% less than control) for the acid and 6 h (39% less than control) for the alkaline activities. Acid RNase activity returned to its initial values 20 h after surgery, while alkaline RNase activity remained decreased even 24 h after surgery. In order to determine whether the observed decreases in RNase activity were produced by RNase inhibitors (RIs), the enzymatic activities of both RNases were measured after the addition of zinc, to dissociate possible RI/RNase complexes. Zinc addition increased acid RNase activity by 61%, but had no significant effect on alkaline RNase activity. Administration of cycloheximide (an inhibitor of protein synthesis) 2 h before surgery prevented the decrease of acid RNase activity 12 h after surgery, while there was no effect on the decrease in alkaline RNase activity. These results show that surgery produces a decrease in hepatic acid and alkaline RNase activities. The decreased acid RNase activity could be a consequence of the de novo synthesis of RNase inhibitors as a response to surgical trauma, while the mechanism involved in the decrease of alkaline RNase activity is unclear. Under pathophysiological conditions, which induce a high rate of protein synthesis, such as surgical wounding, decreased acid and alkaline RNase activity could provide an important mechanism for enhanced protein synthesis, by prolonging RNA half-life. (C) 2001 Academic Press C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Durham, NC 27706 USA. Univ Autonoma Puebla, Fac Ciencias Quim, Puebla 72570, Mexico. RP Brambila, E (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr,Bldg 101 SC MD-FO-09,Room F095, Durham, NC 27706 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD OCT PY 2001 VL 71 IS 2 BP 125 EP 131 DI 10.1006/exmp.2001.2383 PG 7 WC Pathology SC Pathology GA 485CR UT WOS:000171736400004 PM 11599918 ER PT J AU Kasprzak, KS Nakabeppu, Y Kakuma, T Sakai, Y Tsuruya, K Sekiguchi, M Ward, JM Diwan, BA Nagashima, K Kasprzak, BH AF Kasprzak, KS Nakabeppu, Y Kakuma, T Sakai, Y Tsuruya, K Sekiguchi, M Ward, JM Diwan, BA Nagashima, K Kasprzak, BH TI Intracellular distribution of the antimutagenic enzyme MTH1 in the liver, kidney and testis of F344 rats and its modulation by cadmium SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE acrosomic body; acrosomic vesicle; cadmium toxicity; immunohistochemistry; kidney; liver; MTH1 protein; rat; testis; 8-oxo-2 '-deoxyguanosine 5 '-triphosphate pyrophosphohydrolase; 8-oxo-dGTPase ID 5'-TRIPHOSPHATE PYROPHOSPHOHYDROLASE 8-OXO-DGTPASE; HUMAN MUTT HOMOLOG; DNA-SYNTHESIS; MUTAGENIC SUBSTRATE; ESCHERICHIA-COLI; ENCODING 8-OXO-DGTPASE; HUMAN-CELLS; PROTEIN; INHIBITION; NUCLEOTIDE AB Cellular distribution of the antimutagenic MTH1 protein in the liver, kidney, and testis of Fischer rat was evaluated using the immunohistochemical staining with anti-MTH1 polyclonal antibody. The present investigation revealed a non-uniform distribution of MTH1 among cells and among the cytoplasmic, nuclear, and membranal structures of cells within a given tissue. A particularly strong expression of MTH1 was observed for the first time in the perinuclear acrosomic bodies of spermatocytes and in the acrosomic vesicles of sperm heads. Treatment of rats with a single sc dose of 20 mu mol Cd(II)/kg body wt. produced histopathologic changes in these organs accompanied by redistribution of the cellular MTH1 protein between the cytoplasm and nuclei. The acute phase of Cd ll) toxicity, that in the liver and especially in the testes (but not in kidneys) led to cell necrosis, was accompanied by a characteristic decrease in the abundance of MTH1-expressing nuclei. Chronic toxicity without necrosis, persisting in the kidney over the entire 14-day study, as well as the survival and proliferation of cells, observed in the liver and testis after the necrotizing phase, were signified by increased number of nuclei expressing MTH1. Thus, unlike previous biochemical studies, immunohistochemistry managed to reveal alterations in the patterns of inter- and intracellular distribution of MTH1, associated apparently with the conditional changes in the dynamics of synthesis of nucleic acids, assisted by this protein. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Kyushu Univ, Med Inst Bioregulat, Dept Biochem, Fukuoka 812, Japan. Kyushu Univ, Japan Sci & Technol Corp, CREST, Fukuoka 812, Japan. Kyushu Univ, Dept Med & Clin Sci, Grad Sch Med Sci, Fukuoka 812, Japan. Fukuoka Dent Coll, Dept Biol, Fukuoka, Japan. Fukuoka Dent Coll, Frontier Res Ctr, Fukuoka, Japan. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. SAIC Frederick, Electron Microscope Core Facil, Frederick, MD USA. SAIC Frederick, Pathol Histotechnol Lab, Frederick, MD USA. RP Kasprzak, KS (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205E, Frederick, MD 21702 USA. RI Nakabeppu, Yusaku/A-8902-2011 FU NCI NIH HHS [N01-CO-56000] NR 46 TC 9 Z9 10 U1 0 U2 1 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD OCT PY 2001 VL 53 IS 5 BP 325 EP 335 DI 10.1078/0940-2993-00201 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 496DG UT WOS:000172380300001 PM 11817101 ER PT J AU Gainer, H Fields, RL House, SB AF Gainer, H Fields, RL House, SB TI Vasopressin gene expression: Experimental models and strategies SO EXPERIMENTAL NEUROLOGY LA English DT Article DE hypothalamus; magnocellular neurons; vasopressin; oxytocin; transgenic mice; cell-specific gene expression; biolistics; organotypic culture ID HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; MULTIPLE SEQUENCE ALIGNMENT; CELL-SPECIFIC EXPRESSION; MAGNOCELLULAR NEURONS; OXYTOCIN GENES; QUANTITATIVE-ANALYSIS; ORGANOTYPIC CULTURES; SUPRAOPTIC NEURONS; TRANSGENIC MICE; RAT VASOPRESSIN AB The intergenic region (IGR) separating the genes for vasopressin (VP) and oxytocin (OT) has been shown to be critical for the cell-specific expression of these peptide genes in hypothalamic neurons. To date, the most relevant information about the putative cis-elements in the IGR that might determine cell-specific gene expression has come from studies in transgenic models. As a first step toward increasing the efficiency of the IGR sequence deletion studies in transgenic animals, a comparative genomics approach comparing the IGR sequence in humans versus mice was used to identify conserved sequences that might be candidate regulatory elements. The nucleotide sequence of the IGR between the human VP and OT genes was determined and compared to the mouse IGR, and 26 conserved sequences in three distinct clusters were found. These conserved sequences and motifs may be important for the cell-specific expression of the VP and OT genes. However, before further significant progress can be made, a "high-throughput" method for the analysis of deletion constructs in relevant cell types in vitro is needed. It is proposed here that organotypic culture models combined with the use of particle-mediated gene transfer methods may provide an effective, general strategy for the study of cell-specific expression in the central nervous system. C1 NINCDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINCDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 51 TC 23 Z9 23 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2001 VL 171 IS 2 BP 190 EP 199 DI 10.1006/exnr.2001.7769 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 481EC UT WOS:000171506100002 PM 11573971 ER PT J AU Ecelbarger, CA Kim, GH Wade, JB Knepper, MA AF Ecelbarger, CA Kim, GH Wade, JB Knepper, MA TI Regulation of the abundance of renal sodium transporters and channels by vasopressin SO EXPERIMENTAL NEUROLOGY LA English DT Article DE vasopressin; NaCl transport; kidney; urinary concentrating mechanism; Brattleboro rats; ENaC; Na-K-2Cl cotransporter; Na-K-ATPase; Na-Cl cotransporter ID THICK ASCENDING LIMB; CORTICAL COLLECTING TUBULES; DEPENDENT ADENYLATE-CYCLASE; AMINO-ACID-SEQUENCE; MOLECULAR-CLONING; RAT NEPHRON; HENLES LOOP; MEDIATED REGULATION; NACL COTRANSPORT; BRATTLEBORO RAT AB Vasopressin plays a role in both salt and water balance in the kidney. Classic studies, utilizing isolated perfused tubules, have revealed that vasopressin increases sodium reabsorption in the kidney thick ascending limb and the collecting duct. Furthermore, the activity of several sodium transport proteins expressed in these segments, such as the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and the epithelial sodium channel (ENaC), have been shown to be directly increased by vasopressin. Increased protein abundance might be one means through which sodium transporter and channel activity is enhanced. We have used immunoblotting and immunohistochemistry in order to investigate the regulation of abundance of the major sodium transporters and channels expressed along the renal tubule in response to vasopressin. Chronic (7-day) studies were performed in which vasopressin levels were elevated either endogenously by water restriction of Sprague-Dawley rats or exogenously through infusion of the vasopressin V2-receptor-selective agonist, dDAVP (1-deamino-8D-arginine-vasopressin), to Brattleboro rats. We found a significant increase in protein abundance for NKCC2 and the beta- and gamma -subunits of ENaC with either water restriction or dDAVP infusion. The a-subunit of Na-K-ATPase was increased by water restriction, but not by dDAVP infusion, and alpha -ENaC and the thiazide-sensitive cotransporter (NCC) were increased by dDAVP infusion but not by water restriction. Acute (60-min) in vivo exposure to dDAVP led to an increase in both beta -and gamma -ENaC abundance in kidney cortex homogenates, displaying the rapid nature of some of these changes. Overall these increases in sodium transporter and channel abundances likely contribute to both the antidiuretic and antinatriuretic actions of vasopressin. (C) 2001 Academic Press. C1 Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20007 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. RP Ecelbarger, CA (reprint author), Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20007 USA. OI Kim, Gheun-Ho/0000-0002-8445-9892 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [K01 DK002672] NR 56 TC 82 Z9 87 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2001 VL 171 IS 2 BP 227 EP 234 DI 10.1006/exnr.2001.7775 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 481EC UT WOS:000171506100006 PM 11573975 ER PT J AU Jeong, SW Castel, M Zhang, BJ Fields, RL Paras, P Arnheiter, H Chin, H Gainer, H AF Jeong, SW Castel, M Zhang, BJ Fields, RL Paras, P Arnheiter, H Chin, H Gainer, H TI Cell-specific expression and subcellular localization of neurophysin-CAT-fusion proteins expressed from oxytocin and vasopressin gene promoter-driven constructs in transgenic mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE hypothalamus; magnocellular neurons; vasopressin; oxytocin; transgenic mice; protein trafficking; gene expression ID HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; MAGNOCELLULAR NEURONS; RAT VASOPRESSIN; MONOCLONAL-ANTIBODIES; NEGATIVE REGULATION; SUPRAOPTIC NEURONS; NEUROSECRETION; TRANSCRIPTION; DIVERSITY AB The cell-specific expression of both the oxytocin (OT) and vasopressin (V-P) genes in magnocellular neurons (MCNs) of the hypothalamus has been proposed to be under the control of cis-elements in an intergenic region downstream of the V-P gene. We examined this hypothesis using transgenic mice containing mouse genomic DNA-derived constructs linked to chloramphenicol acetyltransferase (CAT) reporters. VP gene expression was studied using constructs containing 3.8 kbp of the 5 ' flanking region and all the exons and introns in the mouse V-P gene, which was fused at the end of exon 3 to a CAT reporter. The two VP-transgene constructs differed by the lengths of their VP gene 3 ' flanking regions (2.1 versus 3.6 kbp). A similar construct for the oxytocin CAT transgene was used which contained the full-length (3.6 kbp) downstream intergenic region between the mouse genes. All three transgenic constructs produced cell-specific expression of the CAT-reporter in the magnocellular neurons as determined by CAT-immunoreactivity. Oxytocin transgene expression was restricted to OT cells in two founders, and the two VP transgenes to V-P cells in five founders. Electron microscopic immunocytochemistry showed that the CAT fusion proteins produced from the OT- and VP-transgenes were efficiently trafficked through the regulated secretory pathways in their respective magnocellular neurons, packaged into large dense core vesicles, and transported to nerve terminals in the posterior pituitary. (C) 2001 Academic Press. C1 NINCDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINCDS, Mammalian Dev Sect, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Cell & Anim Biol, Jerusalem, Israel. RP Jeong, SW (reprint author), Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea. NR 50 TC 19 Z9 19 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2001 VL 171 IS 2 BP 255 EP 271 DI 10.1006/exnr.2001.7785 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 481EC UT WOS:000171506100009 PM 11573978 ER PT J AU Grinevich, V Ma, XM Verbalis, J Aguilera, G AF Grinevich, V Ma, XM Verbalis, J Aguilera, G TI Hypothalamic pituitary adrenal axis and hypothalamic-neurohypophyseal responsiveness in water-deprived rats SO EXPERIMENTAL NEUROLOGY LA English DT Article DE hypothalamus; parvocellular neurons; magnocellular neurons; immune challenge; immobilization; osmotic stimulation ID CORTICOTROPIN-RELEASING HORMONE; VASOPRESSIN GENE-EXPRESSION; MESSENGER-RNA; ADRENOCORTICOTROPIN SECRETION; ARGININE-VASOPRESSIN; MAGNOCELLULAR NEURONS; NEUROSECRETORY-SYSTEM; RECEPTOR ANTAGONIST; SUPRAOPTIC NUCLEI; STRESS AB The differential effects of osmotic stimulation on magnocellular and parvocellular hypothalamic neurons were studied by analysis of corticotropin-releasing hormone (CRH) and vasopressin (VP) expression in controls and 48-h water-deprived rats subjected to either restraint for 1 h or a single lipopolysaccharide injection (250 mug/100 g). Water deprivation reduced basal CRH mRNA levels but the increments following 4 h of restraint or 6 h lipopolysaccharide (LPS) injection were similar to those in controls. In contrast, water deprivation had no effect on basal VP heteronuclear RNA (hnRNA) and mRNA levels in parvocellular neurons, but responses to restraint or LPS injection were reduced. VP expression in magnocellular paraventricular and supraoptic nuclei, and plasma sodium and vasopressin were higher in water-deprived rats, changes which were unaffected by restraint. LPS injection reduced VP mRNA but not hnRNA levels in magnocellular neurons and increased plasma vasopressin levels only in water-deprived rats independently of changes in plasma sodium. This was accompanied by an increase in vasopressin mRNA content in the posterior pituitary. The data show that the blunted ACTH responses to acute stress during chronic osmotic stimulation are correlated with the inability of parvocellular neurons to increase VP rather than CRH expression. In addition, LPS-induced endotoxemia causes disturbances of the magnocellular vasopressinergic system with an unexpected potentiation of osmotic simulated VP secretion. The lack of increase in VP transcription after LPS and changes in VP mRNA distribution suggest that endotoxemia affect the secretory process at the levels of the neurohypophyseal axon terminal. (C) 2001 Academic Press. C1 Georgetown Univ, Dept Med, Washington, DC USA. NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Grinevich, V (reprint author), Univ Jena, Klinikum, Inst Anat 2, D-07740 Jena, Germany. NR 46 TC 13 Z9 15 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 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2001 VL 171 IS 2 BP 329 EP 341 DI 10.1006/exnr.2001.7784 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 481EC UT WOS:000171506100017 PM 11573986 ER PT J AU Rapoport, SI AF Rapoport, SI TI Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE arabinose; blood-brain barrier; bulk flow; calcium; capillary; chemotherapy; cytoskeleton endothelium; diffusion; mannitol; oedema; osmosis; permeability; rat; shrinkage; tight junctions; tumour ID POSITRON EMISSION TOMOGRAPHY; CAPILLARY ENDOTHELIAL-CELLS; RAT-BRAIN; HYPEROSMOLAR MANNITOL; INTRAARTERIAL CHEMOTHERAPY; INTRACAROTID INJECTION; CEREBRAL ENDOTHELIUM; TIGHT JUNCTIONS; CALCIUM-ION; IN-VIVO AB The blood-brain barrier (BBB) to water-soluble drugs and macromolecules can be opened in vivo by infusing a hypertonic solution of arabinose or mannitol into the carotid artery for 30 sec. Opening involves widening of tight junctions between endothelial cells of the cerebrovasculature and is mediated by endothelial cell shrinkage, vascular dilatation associated with removal of water from brain, and modulation of the contractile state of the endothelial cytoskeleton and junctional proteins by increased intracellular calcium. A 10-fold increase in BBB permeability to intravascular substances, lasting about 10 min following osmotic exposure, reflects both increased diffusion and bulk fluid flow from blood into brain. Furthermore, recent evidence indicates that the duration of peak BBB opening can be extended beyond 30 min, by pre-treatment with a Na+/Ca2+ channel blocker. In experimental animals, the osmotic method has been used to grant wide access to brain of water-soluble drugs, peptides, antibodies, boron compounds for neutron capture therapy, viral vectors for gene therapy and enzymes. Ongoing multi-centre clinical studies suggest that the method, when used with intra-arterially administered anticancer drugs, can prolong survival in patients with malignant brain tumours, with minimal morbidity. However, controlled clinical trials are critical to see if the osmotic procedure with intraarterial drugs enhances survival in brain tumour patients compared with intra-arterial drug alone. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Rm 6N 202, Bethesda, MD 20892 USA. NR 94 TC 59 Z9 63 U1 1 U2 18 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD OCT PY 2001 VL 10 IS 10 BP 1809 EP 1818 DI 10.1517/13543784.10.10.1809 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 481YW UT WOS:000171548900003 PM 11772287 ER PT J AU Hess, S AF Hess, S TI Recent advances in adenosine receptor antagonist research SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE adenosine antagonists; adenosine receptor; affinity; selectivity; structure-activity relationships; subtypes ID STRUCTURE-AFFINITY PROFILE; SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTOR; A(3) RECEPTOR; A(1)-ADENOSINE RECEPTOR; A(2A) RECEPTORS; A(1) RECEPTOR; HUMAN A(2B); BIOLOGICAL EVALUATION; FUTURE DRUGS AB Four types of adenosine receptors (ARs) have been identified and designated A(1), A(2A), A(2B) and A(3). During the past decades, potent antagonists have been developed for each of these subtypes. Adenosine antagonists have been developed as potential therapeutic agents for CNS disorders, inflammatory diseases, asthma, kidney failure and ischaemic injuries. Structurally, antagonists can be classified as xanthines and non-xanthines. Many ligands that were previously considered selective at the ARs have been found to be less selective at human ARs and therapeutic potential may need to be re-evaluated. Due to the high lipophilicity and corresponding low water-solubility of many very potent adenosine antagonists, bioavailability is often very low. To address this problem, recent approaches have led to the development of water-soluble prodrugs that release highly potent antagonists in vivo with substantially improved bioavailability. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hess, S (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 NR 144 TC 43 Z9 43 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD OCT PY 2001 VL 11 IS 10 BP 1533 EP 1561 DI 10.1517/13543776.11.10.1533 PG 29 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 479QE UT WOS:000171414400003 ER PT J AU Toyofuku, K Wada, I Valencia, JC Kushimoto, T Ferrans, VJ Hearing, VJ AF Toyofuku, K Wada, I Valencia, JC Kushimoto, T Ferrans, VJ Hearing, VJ TI Oculocutaneous albinism types 1 and 3 are ER retention diseases: mutation of tyrosinase or Tyrp1 can affect the processing of both mutant and wild-type proteins SO FASEB JOURNAL LA English DT Article DE albinism; chaperones; pigmentation; melanogenesis ID DHICA OXIDASE ACTIVITY; ENDOPLASMIC-RETICULUM; MAMMALIAN TYROSINASE; ULTRASTRUCTURAL-LOCALIZATION; BINDING-SPECIFICITY; MELANOGENIC COMPLEX; MEMBRANE-PROTEINS; MELANIN FORMATION; MOLECULAR-BASIS; B-16 MELANOMA AB Various types of oculocutaneous albinism (OCA) are associated with reduced pigmentation in the skin, hair, and eyes that results from mutations in genes involved in melanin synthesis. Immortal mouse melanocyte lines (melan-a, melan-b, and melan-c) provide opportune models with which to investigate the etiology of two different types of OCA (types I and III), which arise from mutations in Tyr and Tyrp1, respectively. We compared intracellular processing, sorting, and degradation of tyrosinase and Tyrp1, and the effects on their catalytic function and melanin synthesis, in these wild-type and mutant melanocytes. A mutation in either Tyr or Tyrp1 increased the time of association of tyrosinase and Tyrp1 with calnexin and Bip, which in turn resulted in the retention of these mutant products in the ER. A mutation in either gene selectively enhanced the duration and efficiency of chaperone interactions (even with the wild-type protein in the mutant melanocytes) and markedly slowed their transport to melanosomes. These results show that OCA1 and OCA3 are (in some cases, at least) ER retention diseases wherein a mutation in one melanogenic protein affects the maturation and stability of the other in the melanogenic pathway. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Sapporo Med Univ, Dept Biochem, Sapporo, Hokkaido, Japan. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 66 TC 93 Z9 99 U1 2 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2001 VL 15 IS 12 BP 2149 EP 2161 DI 10.1096/fj.01-0216com PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 488DM UT WOS:000171920400026 PM 11641241 ER PT J AU Kamohara, H Yamashiro, S Galligan, C Yoshimura, T AF Kamohara, H Yamashiro, S Galligan, C Yoshimura, T TI Discoidin domain receptor 1 isoform-a (DDR1a) promotes migration of leukocytes in three-dimensional collagen lattices SO FASEB JOURNAL LA English DT Article DE receptor tyrosine kinase; cell migration; adherence; extracellular matrix; inflammation ID TYROSINE KINASE; FOCAL ADHESIONS; MESSENGER-RNA; CELLS; INTEGRINS; EXPRESSION; MATRIX; NEUTROPHILS; ACTIVATION; STRATEGIES AB Although integrins are crucial for migration of leukocytes through endothelium, integrin-independent mechanisms appear to take over and mediate the migration of leukocytes through extracellular matrix (ECM) in a three-dimensional tissue microenvironment. Discoidin domain receptor (DDR) 1 is a receptor tyrosine kinase activated by collagen, the most abundant ECM protein. In the present study, we detected that peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophils were induced to express DDR1 after incubation in RPMI 1640. The expression level of DDR1 in PBMC was increased further by stimulation with tumor necrosis factor-alpha, interleukin-1 beta, granulocyte-macrophage colony-stimulating factor, lipopolysaccharide, or phytohemagglutinin, but not with interferon-gamma. In vivo, DDR1 mRNA was detectable in mononuclear leukocytes infiltrating human renal tumor tissue. Among three DDR1 isoforms, DDR1a was the major transcript in leukocytes. Functionally, overexpression of either DDR1a or DDR1b in THP-1 cells resulted in increased adherence to collagen-coated plates in a beta1-integrin independent manner. However, only DDR1a-, but not DDR1b-, overexpressing cells exhibited marked pseudopod extension and migrated successfully through three-dimensional collagen lattices. Consequently, we propose that the interaction of DDR1a with collagen of the ECM results in a requisite intracellular signaling that enables leukocytes to migrate in a tissue microenvironment and participate in host defense. C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Yoshimura, T (reprint author), NCI, Mol Immunoregulat Lab, Bldg 559,Room 9, Frederick, MD 21702 USA. EM yoshimur@mail.ncifcrf.gov NR 36 TC 74 Z9 76 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2001 VL 15 IS 12 BP 2724 EP + DI 10.1096/fj.01-0359fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 488DM UT WOS:000171920400015 PM 11606478 ER PT J AU Katsifa, H Tsaparidou, S Diza, E Gil-Lamaignere, C Walsh, TJ Roilides, E AF Katsifa, H Tsaparidou, S Diza, E Gil-Lamaignere, C Walsh, TJ Roilides, E TI Effects of interleukin-13 on antifungal activity of human monocytes against Candida albicans SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article; Proceedings Paper CT 10th Immunocompromised-Host-Society Meeting CY JUN, 1998 CL DAVOS, SWITZERLAND SP Immunocompromise Host Soc DE interleukin-13; monocyte; Candida albicans ID SYNOVIAL-FLUID MACROPHAGES; COLONY-STIMULATING FACTOR; MONONUCLEAR PHAGOCYTES; IFN-GAMMA; IL-13; CELLS; EXPRESSION; CYTOKINES; LYMPHOCYTES; MODULATION AB We investigated the effects of human interleukin-13 (IL-13) on human monocytes' (MNC) activities against Candida albicans, an important human pathogen. Increased phagocytosis of blastoconidia was observed after incubation with 50 U ml(-1) of IL-13 for 4 h or 48 h in the presence or absence of serum. The latter effect was inhibited by anti-IL-13 monoclonal antibody or mannose. Incubation of MNC with 50 U ml(-1) or IL-13 for 2 h significantly enhanced superoxide anion production in response to phorbol myristate acetate. IL-13 did not, however, alter the damage caused by MNC to hyphae, whereas it suppressed killing of blastoconidia. IL-13 has variable effects on MNC activities and may play an important immunoregulatory role against C albicans. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science BN. All rights reserved. C1 Aristotelian Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54642 Thessaloniki, Greece. Aristotelian Univ Thessaloniki, Dept Microbiol, GR-54006 Thessaloniki, Greece. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Roilides, E (reprint author), Aristotelian Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54642 Thessaloniki, Greece. RI Gil-Lamaignere, Cristina/A-3866-2013 NR 25 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD OCT PY 2001 VL 31 IS 3 BP 211 EP 217 DI 10.1016/S0928-8244(01)00263-2 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 496MG UT WOS:000172398900008 PM 11720817 ER PT J AU Raybourne, RB Roth, G Deuster, PA Sternberg, EM Singh, A AF Raybourne, RB Roth, G Deuster, PA Sternberg, EM Singh, A TI Uptake and killing of Listeria monocytogenes by normal human peripheral blood granulocytes and monocytes as measured by flow cytometry and cell sorting SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE flow cytometry; human; neutrophil; monocyte; peripheral blood; Listeria monocytogenes ID MONOCLONAL-ANTIBODY; MURINE LISTERIOSIS; PHOSPHOLIPASE-C; HOST-DEFENSE; NEUTROPHILS; INFECTION; MICE; HEMOLYSIN; GROWTH; ROLES AB Cellular components of innate immunity (NK cells, monocytes and granulocytes) play an important role in early resistance to Listeria monocytogenes in the mouse model. Minimally invasive methods of measuring the bacteriocidal capacity of these cells may be useful as a biomarker of susceptibility in humans. A technique was developed whereby the uptake and survival of L. monocytogenes could be measured in human granulocytes and monocytes using small volumes of peripheral blood. This method used flow cytometry to detect the presence of PKH-2-labeled bacteria within these cells. Survival of bacteria was determined by sorting of infected cells based on a combination of fluorescence and light scattering properties. Considerable variation in bacterial recovery was seen between normal volunteers. There was consistently greater survival of a fully virulent strain of L. monocytogenes within monocytes and granulocytes compared with an isogenic strain lacking the hemolysin, listeriolysin O, when measured at baseline. There was no evidence of longer-term bacterial survival or growth at 2 or 24 h. This technique may be useful for assessment of both host resistance and pathogen virulence. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science BN. All rights reserved. C1 US FDA, Immunobiol Branch, Laurel, MD 20708 USA. Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Raybourne, RB (reprint author), US FDA, Immunobiol Branch, MOD 1,8301 Muirkirk Rd, Laurel, MD 20708 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 24 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD OCT PY 2001 VL 31 IS 3 BP 219 EP 225 DI 10.1016/S0928-8244(01)00264-4 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 496MG UT WOS:000172398900009 PM 11720818 ER PT J AU Levi, AJ Raynault, MF Bergh, PA Drews, MR Miller, BT Scott, RT AF Levi, AJ Raynault, MF Bergh, PA Drews, MR Miller, BT Scott, RT TI Reproductive outcome in patients with diminished ovarian reserve SO FERTILITY AND STERILITY LA English DT Article DE diminished ovarian reserve; basal follicle-stimulating hormone; pregnancy loss; live birth ID FOLLICLE-STIMULATING-HORMONE; IN-VITRO FERTILIZATION; CHROMOSOME-ABNORMALITIES; MATERNAL AGE; WOMEN; DAY-3; ESTRADIOL; PREGNANCY; EMBRYOS AB Objective: To compare reproductive outcome between women with normal ovarian reserve and women with abnormal ovarian reserve. Design: Retrospective. Setting: Tertiary care center. Patient(s): Nine thousand eight hundred and two patients who had basal follicle-stimulating hormone (FSH) concentrations measured as part of an infertility evaluation. Intervention(s): Monitoring of early pregnancy. Main Outcome Measure(s): Pregnancy loss rates, live birth rates. Result(s): Of 1,034 patients with diminished ovarian reserve (DOR) (FSH greater than or equal to 14.2 IU/L), 28 (2.7%) conceived. Twenty of these pregnancies (20/28; 71.4%) were lost in the first trimester. Pregnancy loss rates in women with DOR were 57.1% in women <35 years old, 63.5% in women 35-40 years old, and 90.0% in women >40 years old. These rates of pregnancy loss were significantly higher compared to age-matched patients with normal ovarian reserve. Conclusion(s): Women with DOR have exceedingly high rates of pregnancy loss, regardless of age. Women with diminished ovarian reserve should be counseled that, in addition to a low probability of conception, live birth rates are poor. (Fertil Steril(R) 2001;76:666-9. (C) 2001 by American Society for Reproductive Medicine.). C1 Reprod Med Associates New Jersey, Morristown, NJ 07962 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. St Barnabus Med Ctr, Inst Reprod Med & Sci, Livingston, NJ USA. RP Scott, RT (reprint author), Reprod Med Associates New Jersey, 111 Madison Ave,Suite 100, Morristown, NJ 07962 USA. NR 15 TC 129 Z9 139 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2001 VL 76 IS 4 BP 666 EP 669 DI 10.1016/S0015-0282(01)02017-9 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 481GM UT WOS:000171511600004 PM 11591396 ER PT J AU Levi, AJ Drews, MR Bergh, PA Miller, BT Scott, RT AF Levi, AJ Drews, MR Bergh, PA Miller, BT Scott, RT TI Controlled ovarian hyperstimulation does not adversely affect endometrial receptivity in in vitro fertilization cycles SO FERTILITY AND STERILITY LA English DT Article DE endometrium; implantation; receptivity; controlled ovarian hyperstimulation; in vitro fertilization ID SERUM ESTRADIOL CONCENTRATIONS; HUMAN INVITRO FERTILIZATION; EMBRYO IMPLANTATION; OOCYTE DONATION; UTERINE RECEPTIVITY; PREGNANCY RATES; IVF CYCLES; FAILURE; MATURATION; INDUCTION AB Objective: To determine whether exposure of developing endometrium to supraphysiologic E-2 levels during controlled ovarian hyperstimulation (COH) in IVF cycles inhibits endometrial receptivity. Design: Retrospective analysis of lVF-ET and ovum donation data. Setting: Tertiary-care teaching hospital. Patient(s): Four hundred ten patients <33 years of age undergoing lVF-ET and 181 anonymous ovum donors (<33 years of age) and their associated ovum recipients. Main Outcome Measure(s): Implantation, pregnancy, and delivery rates. Result(s): Ovarian response to COH (duration of stimulation, peak E-2 level, area under the curve for E-2 exposure, and number of oocytes retrieved) was similar for IVF-ET patients and ovum donors. Donors were younger than lVF-ET patients (mean age, 27.5 +/- 0.2 years vs. 30.4 +/- 0.1 years). A similar number of embryos with similar number of blastomeres were transferred in lVF-ET patients and ovum recipients. The fragmentation rate at time of transfer differed slightly between groups (5.2 +/- 0.2% vs. 4.3 +/- 0.3%). Implantation, pregnancy, and delivery rates did not differ between lVF-ET patients and recipients of donor oocytes. Conclusion(s): Exposure of the developing endometrium to controlled ovarian hyperstimulation during IVF cycles does not inhibit embryo implantation or affect pregnancy and delivery rates. (Fertil Steril(R) 2001;76: 670-4. (C) 2001 by American Society for Reproductive Medicine.). C1 Reprod Med Associates New Jersey, Morristown, NJ 07962 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Scott, RT (reprint author), Reprod Med Associates New Jersey, 111 Madison Ave,Suite 100, Morristown, NJ 07962 USA. NR 28 TC 47 Z9 56 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2001 VL 76 IS 4 BP 670 EP 674 DI 10.1016/S0015-0282(01)01988-4 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 481GM UT WOS:000171511600005 PM 11591397 ER PT J AU Uzel, G Kleiner, DE Kuhns, DB Holland, SM AF Uzel, G Kleiner, DE Kuhns, DB Holland, SM TI Dysfunctional LAD-1 neutrophils and colitis SO GASTROENTEROLOGY LA English DT Article ID LEUKOCYTE ADHESION DEFICIENCY; ICAM-1 ANTISENSE OLIGONUCLEOTIDE; CROHNS-DISEASE; P150,95 GLYCOPROTEINS; BETA-SUBUNIT; MAC-1; LFA-1; MICE; INFLAMMATION; INTEGRINS AB Leukocyte adhesion deficiency 1 (LAD-1) is characterized by absent or dysfunctional beta2 integrin (CD18), leading to defective chemotaxis, adherence, phagocytosis, and bacterial killing. Colitis, except for rare intestinal necrotizing events, is not a well-recognized feature of this immunodeficiency. A case of nonspecific colitis clinically resembling Crohn's disease in a patient with the severe form of LAD-1 (0.5% < CD18) has been previously reported. We describe an adult patient with the moderate form of LAD-1 and chronic colitis characterized by extensive inflammation and ulceration of the right colon and terminal ileum, leading to adhesions and strictures. The chronic colitis described in this article associated with the dysfunctional neutrophils of LAD-1 represents a distinct pathology from the commonly encountered forms of inflammatory bowel disease (IBD). The existence of active IBD in the presence of dysfunctional CD18/CD11(a-b) intercellular adhesion molecules (ICAM-1) interaction is relevant to the proposed targeting of ICAM-1 for the treatment of Crohn's disease. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCI, Neutrophil Monitoring Lab, Clin Serv Program, SAIC, Frederick, MD 21701 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Serv Immunol, Dept Lab Med, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 36 TC 29 Z9 29 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2001 VL 121 IS 4 BP 958 EP 964 DI 10.1053/gast.2001.28022 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 479UW UT WOS:000171422800027 PM 11606509 ER PT J AU El-Omar, EM Chow, WH Rabkin, CS AF El-Omar, EM Chow, WH Rabkin, CS TI Gastric cancer and H-pylori: Host genetics open the way SO GASTROENTEROLOGY LA English DT Editorial Material ID HELICOBACTER-PYLORI C1 Univ Aberdeen, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP El-Omar, EM (reprint author), Univ Aberdeen, Dept Med & Therapeut, Polwarth Bldg, Aberdeen AB25 2ZD, Scotland. NR 12 TC 37 Z9 40 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2001 VL 121 IS 4 BP 1002 EP 1004 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 479UW UT WOS:000171422800031 PM 11606513 ER PT J AU Barsov, E Oh, J Zheng, H Ferris, AL Hughes, SH AF Barsov, E Oh, J Zheng, H Ferris, AL Hughes, SH TI RCAs vectors: New applications and old problems. SO GENE THERAPY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2001 VL 8 SU 1 BP S2 EP S2 PG 1 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 476KC UT WOS:000171224500009 ER PT J AU Stevceva, L Pavli, P Husband, A Ramsay, A Doe, WF AF Stevceva, L Pavli, P Husband, A Ramsay, A Doe, WF TI Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice SO GENES AND IMMUNITY LA English DT Article DE immunoglobulins; interferon-gamma; IL-10; knockout; 'in situ'; colitis; IBD ID INFLAMMATORY-BOWEL-DISEASE; CHRONIC ULCERATIVE-COLITIS; SULFATE SODIUM; INTERFERON-GAMMA; MURINE MODEL; T-CELLS; RECEPTOR; INTESTINE; RESPONSES; IL-4 AB The importance of IL-4 and its effects in inflammatory bowel disease (IBD) was studied using the dextran sulphate sodium-induced model of experimental colitis. The model resembles ulcerative colitis in humans. IL-4 deficient mice and IL-4+/+ littermates were used to induce colitis. Activity of disease, extent of tissue damage, immunoglobulin isotypes, IFN gamma and IL-10 production was assessed. Both disease activity index (DAI) and histological scores were consistently lower in the IL-4 deficient mice than in the IL-4+/+ littermates. Furthermore, the lower histological scores reflected the milder inflammatory lesions and decreased ulceration found in the IL-4 deficient mice. Analysis of immunoglobulin subtypes showed that IgG1 was almost absent in the sera of IL-4 deficient mice. IFN gamma contents was much higher in colonic tissues from IL-4 deficient mice. Dextran sulphate sodium-induced colitis is ameliorated in IL-4 deficient mice. IL-4 either directly or through its effects on T and B cells influences its severity. It is unclear if the higher immunoglobulin-producing cells in the colonic tissues of IL-4 deficient mice before colitis was induced could have influenced the outcome of the disease. The high IFN-gamma contents in colonic tissues of IL-4 deficient mice argue against the role of this cytokine as a crucial mediator of tissue damage during the acute phase of colitis. C1 Australian Natl Univ, John Curtin Sch Med Res, Div Mol Med, Canberra, ACT 2601, Australia. Australian Natl Univ, John Curtin Sch Med Res, Div Biochem & Mol Biol, Canberra, ACT 2601, Australia. Univ Sydney, Dept Vet Anat & Pathol, Sydney, NSW 2006, Australia. RP Stevceva, L (reprint author), NCI, Basic Biol Lab, NIH, Bldg 41-C303, Bethesda, MD 20892 USA. NR 38 TC 25 Z9 31 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2001 VL 2 IS 6 BP 309 EP 316 DI 10.1038/sj.gene.6363782 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 479FW UT WOS:000171395200003 PM 11607786 ER PT J AU Sahagun-Ruiz, A Colla, JS Juhn, J Gao, JL Murphy, PM McDermott, DH AF Sahagun-Ruiz, A Colla, JS Juhn, J Gao, JL Murphy, PM McDermott, DH TI Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R SO GENES AND IMMUNITY LA English DT Article DE polymorphism; inflammation; neutrophil; monocyte; chemotaxis; infectious disease ID FORMYL PEPTIDE RECEPTOR; SINGLE-NUCLEOTIDE POLYMORPHISMS; PROTEIN-COUPLED RECEPTOR; JUVENILE PERIODONTITIS; GENE-CLUSTER; HOST-DEFENSE; EXPRESSION; CLONING; RHODOPSIN; SEQUENCE AB N-formylpeptides are phagocyte chemoattractants that act by binding to two structurally related receptors, FPR (formylpeptide receptor) and FPRL1R (FPR-like-1 receptor), which are encoded by the human genes FPR1 and FPRL1. Single nucleotide polymorphisms (SNPs) in the FPR coding region have been reported and two have been associated with the disease juvenile periodontitis; however, their frequency and linkage relationships are unknown. Here we systematically analyzed polymorphism in the open reading frames of FPR1 and FPRL1 by direct sequencing of cloned alleles from random blood donors from North America. For FPR1 we detected five non-synonymous SNPs and two synonymous SNPs in a sample of 26 chromosomes one each from 17 Caucasian and nine black random blood donors. Although all five non-synonymous SNPs were common in Caucasians, Blacks, and Asians, notable differences in allele frequency were found for each SNP in the different racial groups, suggesting differential selective pressures. We found that the FPR1 polymorphisms are linked in 15 common haplotypes. No polymorphisms were detected in FPRL1 after sampling 44 chromosomes from 36 random blood donors from the same three racial groups. Thus FPR1 and FPRL1, though they originated from a common gene, appear to have undergone markedly different evolutionary events. C1 NIAID, Host Def Lab, Mol Signalling Sect, NIH, Bethesda, MD USA. RP McDermott, DH (reprint author), Bldg 10,Room 11N111,9000 Rockville Pike, Bethesda, MD 20892 USA. OI McDermott, David/0000-0001-6978-0867 NR 30 TC 29 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2001 VL 2 IS 6 BP 335 EP 342 DI 10.1038/sj.gene.6363787 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 479FW UT WOS:000171395200007 PM 11607790 ER PT J AU Caballero, OL Cohen, D Liu, Q Esteller, M Bonacum, J White, P Engles, J Yochem, R Herman, JG Westra, WH Lengauer, C Sidransky, D Jen, J AF Caballero, OL Cohen, D Liu, Q Esteller, M Bonacum, J White, P Engles, J Yochem, R Herman, JG Westra, WH Lengauer, C Sidransky, D Jen, J TI Loss of chromosome arms 3p and 9p and inactivation of P16 (INK4a) in normal epithelium of patients with primary lung cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID BRONCHIAL EPITHELIUM; TUMOR-CELLS; FORMER SMOKERS; EARLY-STAGE; DELETIONS; CARCINOMA; ABNORMALITIES; ABERRATIONS; P16(INK4A); LESIONS AB The accumulation of genetic alterations in the respiratory epithelium may give rise to cancer and often is accompanied by a series of histologic alterations over a period of several years. Recent studies have identified some molecular alterations in histologically normal-appearing epithelium among patients with lung cancer. To extend these observations, we investigated clonal genetic alterations by using fluorescence in situ hybridization (FISH) analysis and immunohistochemistry in 69 biopsy samples of histologically normal-appearing bronchial epithelium from 22 patients with or without lung cancer. Thirty-seven biopsy specimens from 13 patients were examined for loss of 3p14, and 48 biopsy specimens from 18 patients were examined for loss at 9p21 by FISH. P16(INK4a) expression was analyzed in 54 biopsy samples from 19 patients. In at least one biopsy specimen from five of the 13 patients with primary lung cancer, FISH or immunohistochemistry detected loss of the 3p14 or 9p21 region. In contrast, no alterations were detected for the same regions in the nine patients without primary lung cancer. Our results support the concept that the normal epithelial surface of large bronchi of patients with lung cancer has molecular changes suggestive of the outgrowth of numerous clonal foci. (C) 2001 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Canc Res, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Jen, J (reprint author), NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA. RI Esteller, Manel/L-5956-2014 OI Esteller, Manel/0000-0003-4490-6093 FU NCI NIH HHS [CA 58184] NR 33 TC 14 Z9 15 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2001 VL 32 IS 2 BP 119 EP 125 DI 10.1002/gcc.1173 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 471MW UT WOS:000170934000003 PM 11550279 ER PT J AU Elson, DA Thurston, G Huang, LE Ginzinger, DG McDonald, DM Johnson, RS Arbeit, JM AF Elson, DA Thurston, G Huang, LE Ginzinger, DG McDonald, DM Johnson, RS Arbeit, JM TI Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1 alpha SO GENES & DEVELOPMENT LA English DT Article DE hypoxia; HIF-1 alpha; angiogenesis; skin; epidermis; keratin ID ENDOTHELIAL GROWTH-FACTOR; FACTOR MESSENGER-RNA; MULTISTAGE EPIDERMAL CARCINOGENESIS; HIPPEL-LINDAU PROTEIN; VEGF GENE DELIVERY; FACTOR 1-ALPHA; UP-REGULATION; MYOCARDIAL-ISCHEMIA; FACTOR EXPRESSION; O-2 HOMEOSTASIS AB Hypoxia-inducible factor-1 alpha (HIF-1 alpha) transactivates genes required for energy metabolism and tissue perfusion and is necessary for embryonic development and tumor explant growth. MF-la is overexpressed during carcinogenesis, myocardial infarction, and wound healing; however, the biological consequences of HIF-1 alpha overexpression are unknown. Here, transgenic mice expressing constitutively active HIF-1 alpha in epidermis displayed a 66% increase in dermal capillaries, a 13-fold elevation of total vascular endothelial growth factor (VEGF) expression, and a six- to ninefold induction of each VEGF isoform. Despite marked induction of hypervascularity, HIF-1 alpha did not induce edema, inflammation, or vascular leakage, phenotypes developing in transgenic mice overexpressing VEGF cDNA in skin. Remarkably, blood vessel leakage resistance induced by HIF-1 alpha overexpression was not caused by up-regulation of angiopoietin-1 or angiopoietin-2. Hypervascularity induced by HIF-1 alpha could improve therapy of tissue ischemia. C1 Univ Calif San Francisco, Ctr Comprehens Canc, Canc Genet Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, Genome Anal Core Facil, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Regeneron Pharmaceut Inc, Tarrytown, NY USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. RP Arbeit, JM (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, Canc Genet Program, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA-71398]; NHLBI NIH HHS [HL-24136, HL-59157, P01 HL024136, R01 HL059157] NR 59 TC 218 Z9 243 U1 3 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2001 VL 15 IS 19 BP 2520 EP 2532 DI 10.1101/gad.914801 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 480UW UT WOS:000171482000005 PM 11581158 ER PT J AU Izraeli, S Lowe, LA Bertness, VL Campaner, S Hahn, H Kirsch, IR Kuehn, MR AF Izraeli, S Lowe, LA Bertness, VL Campaner, S Hahn, H Kirsch, IR Kuehn, MR TI Genetic evidence that Sil is required for the sonic hedgehog response pathway SO GENESIS LA English DT Article DE Sil; sonic hedgehog; patched; signaling; apoptosis ID CELL-DEATH; PROLIFERATION; INHIBITION; ACTIVATION; INDUCTION; SURVIVAL; TARGET AB The Sil gene encodes a cytosolic protein required for mouse embryonic midline and left/right axial development. Based on the phenotype of Sil mutant embryos, we hypothesized that Sil may be required for the activity of Sonic Hedgehog (Shh), a secreted signaling molecule also critically important for the development of the embryonic axes and found mutated in multiple types of cancer. Here we tested the genetic interaction between Sil and the Shh pathway by generating and analyzing embryos carrying mutations in both Sil and Patched (Ptch), a Shh receptor that normally inhibits the signaling pathway in the absence of ligand and when mutated leads to constitutive activation of the pathway. We find that Sil(-/-) Ptch(-/-) embryos do not activate the Shh pathway and instead have a phenotype indistinguishable from Sil(-/-) embryos, in which there is a loss of activity of Shh. These results provide genetic evidence that Sil is an essential component of the Shh response, acting downstream to Ptch. (C) 2001 Wiley-Liss, Inc. C1 NCI, Expt Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. GSF, Res Ctr Environm & Hlth, Inst Pathol, Neuherberg, Germany. Chaim Sheba Med Ctr, Dept Pediat Hematol Oncol, IL-52621 Tel Hashomer, Israel. RP Kuehn, MR (reprint author), NCI, Expt Immunol Branch, Canc Res Ctr, NIH, Bldg 10,Room 4B-36,10 Ctr Dr, Bethesda, MD 20892 USA. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 27 TC 41 Z9 43 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD OCT PY 2001 VL 31 IS 2 BP 72 EP 77 DI 10.1002/gene.10004 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 488XH UT WOS:000171961800003 PM 11668681 ER PT J AU Clark, RM Marker, PC Roessler, E Dutra, A Schimenti, JC Muenke, M Kingsley, DM AF Clark, RM Marker, PC Roessler, E Dutra, A Schimenti, JC Muenke, M Kingsley, DM TI Reciprocal mouse and human limb phenotypes caused by gain- and loss-of-function mutations affecting Lmbr1 SO GENETICS LA English DT Article ID SONIC-HEDGEHOG; TRIPHALANGEAL THUMB; CANDIDATE GENE; VARIABLE EXPRESSION; POLARIZING ACTIVITY; CHROMOSOME 7Q36; CELL-DEATH; MAPS; LINKAGE; MUTANT AB The major locus for dominant preaxial polydactyly in humans has been mapped to 7q36. In mice the dominant Hemimelic extra toes (Hx) and Hammertoe (Hm) mutations map to a homologous chromosomal region and cause similar limb defects. The Lmbr1 gene is entirely within the small critical intervals recently defined for both the mouse and human mutations and is misexpressed at the exact time that the mouse Hx phenotype becomes apparent during limb development. This result suggests that Lmbr1 may underlie preaxial polydactyly in both mice and humans. We have used deletion chromosomes to demonstrate that the dominant mouse and human limb defects arise from gain-of-function mutations and not from haploinsufficiency. Furthermore, we created a loss-of-function mutation in the mouse Lmbr1 gene that causes digit number reduction (oligodactyly) on its own and in trans to a deletion chromosome. The loss of digits that we observed in mice with reduced Lmbr1 activity is in contrast to the gain of digits observed in Hx mice and human polydactyly patients. Our results suggest that the Lmbr1 gene is required for limb formation and that reciprocal changes in levels of Lmbr1 activity can lead to either increases or decreases in the number of digits in the vertebrate limb. C1 Stanford Univ, Howard Hughes Med Inst, Beckman Ctr, Stanford, CA 94305 USA. Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NHGRI, Cytogenet & Confocal Microscopy Core, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Kingsley, DM (reprint author), Stanford Univ, Howard Hughes Med Inst, Beckman Ctr, B300,279 Campus Dr, Stanford, CA 94305 USA. NR 46 TC 24 Z9 32 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2001 VL 159 IS 2 BP 715 EP 726 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 485GJ UT WOS:000171744900024 PM 11606546 ER PT J AU Kratz, CP Emerling, BM Donovan, S Laig-Webster, M Taylor, BR Thompson, P Jensen, S Banerjee, A Bonifas, J Makalowski, W Green, ED Le Beau, MM Shannon, KM AF Kratz, CP Emerling, BM Donovan, S Laig-Webster, M Taylor, BR Thompson, P Jensen, S Banerjee, A Bonifas, J Makalowski, W Green, ED Le Beau, MM Shannon, KM TI Candidate gene isolation and comparative analysis of a commonly deleted segment of 7q22 implicated in myeloid malignancies SO GENOMICS LA English DT Article DE acute myeloid leukemia (AML); myelodysplastic sydrome (MDS); tumor suppressor genes; monosomy 7; deletion 7q ID ACUTE MYELOGENOUS LEUKEMIA; ORIGIN RECOGNITION COMPLEX; LONG-ARM DELETIONS; BONE-MARROW; MOLECULAR DELINEATION; UTERINE LEIOMYOMAS; PHYSICAL MAP; CELL-GROWTH; YAC CONTIG; WILD-TYPE AB Monosomy 7 and deletion of 7q are recurring abnormalities in malignant myeloid diseases. Here we extensively characterize an similar to 2-Mb commonly deleted segment (CDS) of 7q22 bounded by D7S1503 and D7S1841. Approximately 1.8 Mb of sequence have been generated from this interval, facilitating the construction of a transcript map that includes large numbers of genes and ESTs. The intron/exon organization of seven genes and expression patterns of three genes were determined, and leukemia samples were screened for mutations in five genes. We have used polymorphic markers from this region to examine leukemia cells for allelic loss within 7q22. Finally, we isolated mouse genomic clones orthologous to several of the characterized human genes. Fluorescence in situ hybridization studies using these clones indicate that a region of orthologous synteny lies on proximal mouse chromosome 5. These resources should greatly accelerate the pace of candidate gene discovery in this region. C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. RP Shannon, KM (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RI Makalowski, Wojciech/I-2843-2016 FU NCI NIH HHS [CA40046, CA72614]; NIDDK NIH HHS [DK07636] NR 49 TC 32 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 2001 VL 77 IS 3 BP 171 EP 180 DI 10.1006/geno.2001.6636 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 481GZ UT WOS:000171512700008 PM 11597142 ER PT J AU Mattison, JA Roth, GS Tilmont, EM Ingram, DK Lane, MA AF Mattison, JA Roth, GS Tilmont, EM Ingram, DK Lane, MA TI Hematology, morbidity, and mortality in squirrel monkeys on long-term calorie restriction SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, IRP, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 86 EP 86 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400302 ER PT J AU Roth, GS Ingram, DK Metter, EJ Lane, MA AF Roth, GS Ingram, DK Metter, EJ Lane, MA TI Caloric restriction (CR) mimetics: Possible alternative to CR for humans SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 86 EP 86 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400303 ER PT J AU Niederehe, G AF Niederehe, G TI Aging research initiatives at NIMH SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 212 EP 212 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400755 ER PT J AU Hodes, RJ AF Hodes, RJ TI NIA symposium: Research initiatives, funding and training opportunities at the National Institute on Aging. SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 247 EP 247 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360400883 ER PT J AU Guralnik, JM Leveille, SG AF Guralnik, JM Leveille, SG TI Translating epidemiology into practice and policy: Symposium of the epidemiology of aging interest group SO GERONTOLOGIST LA English DT Meeting Abstract C1 Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 314 EP 314 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360401117 ER PT J AU Simonsick, EM AF Simonsick, EM TI Cognitive and mental health of well-functioning older adults: Insights from the Health ABC study SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2001 VL 41 SI 1 BP 320 EP 320 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 478TA UT WOS:000171360401140 ER PT J AU Guo, HB Lee, I Kamar, M Akiyama, SK Pierce, M AF Guo, HB Lee, I Kamar, M Akiyama, SK Pierce, M TI Induction of GnT-V activity causes reduced alpha 5 beta 1 integrin adhesion to fibronectin and increased cell migration SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Univ Georgia, Dept Biochem & Mol Biol, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 20 BP 869 EP 869 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800027 ER PT J AU Ramakrishnan, B Boeggeman, E Ramasamy, V Qasba, PK AF Ramakrishnan, B Boeggeman, E Ramasamy, V Qasba, PK TI Structure of Lactose Synthase: Ligand binding induces a large conformational change in beta-1,4-galactosyltransferase creating binding sites for metal ion, sugar acceptor and alpha-Lactalbumin, and the latter modulates the sugar acceptor specificity of the enzyme towards glucose. SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, LECB, DBS, Struct Glycobiol Sect, Frederick, MD 21702 USA. NR 2 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 49 BP 879 EP 879 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800056 ER PT J AU Ten Hagen, KG Tran, D AF Ten Hagen, KG Tran, D TI Cloning and characterization of the gene family encoding the UDP-GalNAc : polypeptide N-acetylgalactosaminyltransferases from Drosophila melanogaster SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NIDDK, Sect Biol Chem, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 57 BP 882 EP 882 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800064 ER PT J AU Stone, AL AF Stone, AL TI Structure-Function Relations of heparin-mimetic sulfated oligoxylans in the inhibition of the invasion of hepatocytes by malaria parasites in vitro SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, LDMI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 113 BP 901 EP 902 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800120 ER PT J AU Longas, MO Stone, AL AF Longas, MO Stone, AL TI Structure-function relations of heparin-mimetic sulfated oligosaccharides: Study of alternate chair conformations by NMR spectroscopy SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Purdue Univ Calumet, Dept Chem & Phys, Hammond, IN 46323 USA. NIH, NICHD, Dev & Mol Immun Lab, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 178 BP 921 EP 922 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800185 ER PT J AU Ramakrishnan, B Qasba, P AF Ramakrishnan, B Qasba, P TI Crystal structure of human lactose synthase: Oligosaccharide acceptor specificity of beta 4Gal-T family members SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Struct Glycobiol Sect, LECB, CCR, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 183 BP 923 EP 923 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800190 ER PT J AU Ramakrishnan, B Qasba, P AF Ramakrishnan, B Qasba, P TI Polymorphic donor specificity of beta 1,4-galactosyltransferase: Rational design of a novel glycosyltransferase with dual enzyme transferase property SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Struct Glycobiol Sect, LECB, CCR, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 182 BP 923 EP 923 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800189 ER PT J AU Boeggeman, E Qasba, PK AF Boeggeman, E Qasba, PK TI Metal binding studies of the catalytic domain of bovine beta 1,4-galactosyltransferase SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI CCR, Struct Glycobiol Sect, LECB, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 185 BP 924 EP 924 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800192 ER PT J AU Sheeley, DM Barnes, C Fritz, BJ Kolf, CM Pannell, LK Manfredi, KP AF Sheeley, DM Barnes, C Fritz, BJ Kolf, CM Pannell, LK Manfredi, KP TI Detailed structural characterization of a series of glycoside resins using mass spectrometry SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ No Iowa, Dept Chem, Cedar Falls, IA 50614 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2001 VL 11 IS 10 MA 192 BP 925 EP 926 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480JG UT WOS:000171457800199 ER PT J AU Vargas, H Laskus, T Wilkinson, J Radkowski, M Adair, D Buskell, Z Seeff, L Rakela, J AF Vargas, H Laskus, T Wilkinson, J Radkowski, M Adair, D Buskell, Z Seeff, L Rakela, J TI HCV quasispecies transmission and evolution in acute hepatitis C in patients infected via blood transfusion. SO HEPATOLOGY LA English DT Meeting Abstract C1 Mayo Clin Scottsdale, Scottsdale, AZ USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 173 BP 217A EP 217A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700173 ER PT J AU Tanaka, Y Mizokami, M Shih, JW Alter, HJ AF Tanaka, Y Mizokami, M Shih, JW Alter, HJ TI Timing the ancestry of hepatitis C virus genotype 1a strains in the United States. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Nagoya City Univ, Sch Med, Nagoya, Aichi 467, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 177 BP 218A EP 218A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700177 ER PT J AU Promrat, K McDermott, DH Gonzalez, CM Lessie, MD Merrell, MN Koziol, D Ghany, M Park, Y Alter, HJ Hoofnagle, JH Murphy, PM Liang, TJ AF Promrat, K McDermott, DH Gonzalez, CM Lessie, MD Merrell, MN Koziol, D Ghany, M Park, Y Alter, HJ Hoofnagle, JH Murphy, PM Liang, TJ TI Effect of CCR5 Delta 32 on HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 225 BP 230A EP 230A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700225 ER PT J AU Brown, RS Richardson, M Lai, M Everhart, J Russo, MW Hoofnagle, JH AF Brown, RS Richardson, M Lai, M Everhart, J Russo, MW Hoofnagle, JH TI Adult living donor liver transplantation (LDLT) in the US: Results of the survey from the NIH LDLT meeting. SO HEPATOLOGY LA English DT Meeting Abstract C1 Columbia Univ, Coll Phys & Surg, New York, NY USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 245 BP 235A EP 235A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700245 ER PT J AU Schwabe, RF Hatano, E Purbeck, C Quian, T Lemasters, JJ Wada, R Hahiramoto, A Proia, R Brenner, DA AF Schwabe, RF Hatano, E Purbeck, C Quian, T Lemasters, JJ Wada, R Hahiramoto, A Proia, R Brenner, DA TI Differential effects of GD3 on Fas- and TNF alpha-mediated apoptosis in mouse liver. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 297 BP 248A EP 248A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700297 ER PT J AU Bukh, J Thimme, R Satterfield, W Forns, X Chang, KM Yanagi, M Emerson, SU Chisari, FV Purcell, RH AF Bukh, J Thimme, R Satterfield, W Forns, X Chang, KM Yanagi, M Emerson, SU Chisari, FV Purcell, RH TI Sterilizing immunity against hepatitis C virus is subtype specific, is apparently not mediated by neutralizing antibodies, but is correlated with anamnestic cellular immune responses. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Scripps Res Inst, La Jolla, CA USA. Univ Texas, MD Anderson Canc Ctr, Bastrop, TX USA. RI Chisari, Francis/A-3086-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 318 BP 253A EP 253A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700319 ER PT J AU Huh, CG Ton, P Factor, VM Schoeffner, DJ Lemmer, ER Conner, EA Liu, JT Kim, JC Thorgeirsson, UP Thorgeirsson, SS AF Huh, CG Ton, P Factor, VM Schoeffner, DJ Lemmer, ER Conner, EA Liu, JT Kim, JC Thorgeirsson, UP Thorgeirsson, SS TI Generation of a "floxed" conditional mutant mouse for the HGF receptor gene c-Met: Impact of selective inactivation in liver and mammary gland. SO HEPATOLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 363 BP 263A EP 263A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700357 ER PT J AU Shiomi, H Lee, JS Hironaka, K Thorgeirsson, SS AF Shiomi, H Lee, JS Hironaka, K Thorgeirsson, SS TI Differential gene expression during hepatocellular carcinogenesis in c-myc/TGF-alpha transgenic mice. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 374 BP 265A EP 265A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700368 ER PT J AU El-Serag, HB Everhart, JE AF El-Serag, HB Everhart, JE TI Does diabetes increase the risk of acute hepatic failure?. SO HEPATOLOGY LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 491 BP 295A EP 295A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700485 ER PT J AU Ghany, MG Gonzalez, C Kim, BI Kleiner, DE Hoofnagle, JH Liang, TJ AF Ghany, MG Gonzalez, C Kim, BI Kleiner, DE Hoofnagle, JH Liang, TJ TI Association of hepatitis B virus pre-S1 variant with ground-glass hepatocytes. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 541 BP 307A EP 307A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700534 ER PT J AU Ghany, MC Doo, E Heller, T Ong, J Promrat, K Kleiner, DE Park, Y Gauthier, J Condreay, L Liang, TJ Hoofnagle, JH AF Ghany, MC Doo, E Heller, T Ong, J Promrat, K Kleiner, DE Park, Y Gauthier, J Condreay, L Liang, TJ Hoofnagle, JH TI Changes in liver histology after four years of lamivudine therapy in chronic hepatitis B. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. GSK, Raleigh, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 606 BP 323A EP 323A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700600 ER PT J AU Thimme, R Wieland, S Steiger, C Guidotti, L Reimann, KA Purcell, RH Chisari, FV AF Thimme, R Wieland, S Steiger, C Guidotti, L Reimann, KA Purcell, RH Chisari, FV TI Absolute requirement for CD8+cells to control acute HBV infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, La Jolla, CA USA. Harvard Univ, Sch Med, Boston, MA USA. NIH, Bethesda, MD 20892 USA. RI Chisari, Francis/A-3086-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 614 BP 325A EP 325A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700608 ER PT J AU Arteel, GE Gaebele, E Wheeler, MD Uesugi, T Kadiiska, MB Connor, HD Mason, RP Thurman, RG AF Arteel, GE Gaebele, E Wheeler, MD Uesugi, T Kadiiska, MB Connor, HD Mason, RP Thurman, RG TI Inducible nitric oxide synthase is necessary for alcohol induced liver injury: Studies with knock-out mice. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 670 BP 339A EP 339A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700664 ER PT J AU Nascimbeni, M Major, M Mihalik, K Rice, CM Feinstone, SM Rehermann, B AF Nascimbeni, M Major, M Mihalik, K Rice, CM Feinstone, SM Rehermann, B TI Intrahepatic innate and adaptive immune responses in HCV infected chimpanzees. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Rockefeller Univ, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 669 BP 339A EP 339A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700662 ER PT J AU Bollineni, J Swaby, L Sinal, C Gonzalez, F Shefer, S Suchy, F Ananthanarayanan, M AF Bollineni, J Swaby, L Sinal, C Gonzalez, F Shefer, S Suchy, F Ananthanarayanan, M TI Bile acid transporter (Ntcp, Bsep) protein levels and bile acid synthetic enzyme activities in wild type and FXR-null mice fed cholic acid and chow diets: Differential regulation of mRNA and protein expression. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 725 BP 353A EP 353A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700718 ER PT J AU Thomson, M Nascimbeni, M Gonzales, S Murthy, K Rehermann, B Liang, J AF Thomson, M Nascimbeni, M Gonzales, S Murthy, K Rehermann, B Liang, J TI Analysis of the molecular evolution in chimpanzees of HCV RNA from a cloned source reveals the emergence of a distinct pattern of mutations. SO HEPATOLOGY LA English DT Meeting Abstract C1 SW Fdn Biomed Res, San Antonio, TX 78284 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 745 BP 358A EP 358A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700738 ER PT J AU Bergasa, NV Dersh, CM Rothman, RB AF Bergasa, NV Dersh, CM Rothman, RB TI A study of bile acids as opioid receptor ligands. SO HEPATOLOGY LA English DT Meeting Abstract C1 Columbia Univ, Coll Phys & Surg, New York, NY USA. NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 766 BP 363A EP 363A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224700760 ER PT J AU Baumert, TF Klumpp, B Steinmann, D Barth, H Wellnitz, S Depla, E Inchauspe, G Gerlach, JT Pape, GR Triyatni, M Liang, TJ Blum, HE AF Baumert, TF Klumpp, B Steinmann, D Barth, H Wellnitz, S Depla, E Inchauspe, G Gerlach, JT Pape, GR Triyatni, M Liang, TJ Blum, HE TI Binding of hepatitis C viruslike particles to target cells as a model for the study of virus neutralizing antibodies. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Freiburg, Dept Med 2, Freiburg, Germany. Innogenet Corp, Ghent, Belgium. INSERM 271, Lyon, France. Univ Munich, Dept Med 2, Munich, Germany. NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1064 BP 438A EP 438A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701057 ER PT J AU Thimme, R Bukh, J Steiger, C Ghrayeb, J Reimann, KA Purcell, RH Chisari, FV AF Thimme, R Bukh, J Steiger, C Ghrayeb, J Reimann, KA Purcell, RH Chisari, FV TI Control of hepatitis C during chronic infection is not mediated by CD4+T cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, La Jolla, CA USA. NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. Centocor Inc, Malvern, PA 19355 USA. RI Chisari, Francis/A-3086-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1068 BP 439A EP 439A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701061 ER PT J AU Lee, JS Thorgeirsson, SS AF Lee, JS Thorgeirsson, SS TI Functional and genomic implications of global gene expression profiles in human hepatocellular cancer. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1104 BP 448A EP 448A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701097 ER PT J AU Chan, KA Truman, A Gurwitz, J Hurley, J Martinson, B Platt, R Everhart, JE Moseley, R Terrault, N Ackerson, L AF Chan, KA Truman, A Gurwitz, J Hurley, J Martinson, B Platt, R Everhart, JE Moseley, R Terrault, N Ackerson, L TI A cohort study of the incidence of acute liver failure in diabetic patients treated with hypoglycemic agents. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Massachusetts, Fallon Hlth Care Syst, Meyers Primary Care Inst, Worcester, MA USA. Lovelace Respiratory Res Inst, Albuquerque, NM USA. Health Partners Res Fdn, Minneapolis, MN USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIDDKD, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1186 BP 468A EP 468A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701178 ER PT J AU Zhang, MD Emerson, S Shapiro, M Govindarajan, S Purcell, R AF Zhang, MD Emerson, S Shapiro, M Govindarajan, S Purcell, R TI Pre-clinical evaluation of a recombinant candidate vaccine for hepatitis E: Duration of protection. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID, NCI, Rockville, MD USA. Bioqual Inc, Rockville, MD USA. Univ So Calif, Rancho Los Amigos Med Ctr, Downey, CA 90242 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1257 BP 486A EP 486A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701247 ER PT J AU Umemura, T Alter, HJ Tanaka, E Yeo, AE Shih, JW Orii, K Matsumoto, A Yoshizawa, K Kiyosawa, K AF Umemura, T Alter, HJ Tanaka, E Yeo, AE Shih, JW Orii, K Matsumoto, A Yoshizawa, K Kiyosawa, K TI SEN virus infection in high- and non-endemic areas for hepatitis C in Japan. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Shinshu Univ, Sch Med, Matsumoto, Nagano 390, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1262 BP 487A EP 487A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701253 ER PT J AU Lemmer, ER Conner, EA Leveen, P Factor, VM Tsai, TL Huh, CG Karlsson, S Thorgeirsson, SS AF Lemmer, ER Conner, EA Leveen, P Factor, VM Tsai, TL Huh, CG Karlsson, S Thorgeirsson, SS TI Impact of selective inactivation of transforming growth factor-beta type II receptor gene (TGFBR2) during viral hepatitis. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Lund Hosp, S-22185 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1277 BP 491A EP 491A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701267 ER PT J AU Han, C Demetris, AJ Michalopoulos, GK Shelhamer, JH Wu, T AF Han, C Demetris, AJ Michalopoulos, GK Shelhamer, JH Wu, T TI 85-KDA cytosolic phospholipase A(2) plays a critical role in PPAR-mediated gene transcription in human hepatoma cells. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1294 BP 495A EP 495A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701285 ER PT J AU Terai, S Sakaida, I Shirahashi, H Uchida, K Yamamoto, N Miyamoto, K Thorgeirsson, SS Okita, K AF Terai, S Sakaida, I Shirahashi, H Uchida, K Yamamoto, N Miyamoto, K Thorgeirsson, SS Okita, K TI HHM: A new dominant inhibitory HLH protein which is associated with liver carcinogenesis. SO HEPATOLOGY LA English DT Meeting Abstract C1 Yamaguchi Univ, Sch Med, Dept Mol Sci & Appl Med, Ube, Yamaguchi 755, Japan. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1309 BP 499A EP 499A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701299 ER PT J AU Farci, P Serra, G Chessa, L Strazzera, R Scioscia, R Coiana, A Balestrieri, C Carriero, PL Sarracino, M Zahm, F Purcell, RH Balestrieri, A AF Farci, P Serra, G Chessa, L Strazzera, R Scioscia, R Coiana, A Balestrieri, C Carriero, PL Sarracino, M Zahm, F Purcell, RH Balestrieri, A TI Individualized long-term treatment of chronic hepatitis C with interferon alpha (IFN alpha)-2a. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Cagliari, I-09124 Cagliari, Italy. Roche Italy, Milan, Italy. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. NIH, Bethesda, MD 20892 USA. RI Chessa, Luchino/H-7561-2012 OI Chessa, Luchino/0000-0002-9474-0995 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1676 BP 591A EP 591A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701668 ER PT J AU Thimme, R Wieland, S Steiger, C Guidotti, L Reimann, KA Purcell, R Chisari, FV AF Thimme, R Wieland, S Steiger, C Guidotti, L Reimann, KA Purcell, R Chisari, FV TI Absolute requirement for CD8+cells to control acute HBV infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, La Jolla, CA USA. Harvard Univ, Sch Med, Boston, MA USA. NIH, Bethesda, MD 20892 USA. RI Chisari, Francis/A-3086-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1751 BP 610A EP 610A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701742 ER PT J AU Lau, DT Bartholomeusz, A Ayres, A Ma, HB Hoofnagle, JH Condreay, L Gauthier, J Maertens, G Locarnini, S AF Lau, DT Bartholomeusz, A Ayres, A Ma, HB Hoofnagle, JH Condreay, L Gauthier, J Maertens, G Locarnini, S TI Comparison of sequencing, restriction fragment length polymorphism (RFLP) and line probe assays for detection of HBV mutants associated with lamivudine therapy. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Victoria Infect Dis Reference Lab, North Melbourne, Vic, Australia. NIH, NIDDK, Bethesda, MD 20892 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1758 BP 611A EP 611A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701749 ER PT J AU Umemura, T Tanaka, Y Kiyosawa, K Alter, HJ Shih, JW AF Umemura, T Tanaka, Y Kiyosawa, K Alter, HJ Shih, JW TI The evolutionary rate of SEN virus, a newly identified single-stranded circular DNA virus, is more similar to RNA viruses than classic DNA viruses. SO HEPATOLOGY LA English DT Meeting Abstract C1 Shinshu Univ, Sch Med, Matsumoto, Nagano 390, Japan. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1857 BP 636A EP 636A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701847 ER PT J AU Kirk, GD Lesi, F Hainaut, P Mendy, M Goedert, J Montesano, R AF Kirk, GD Lesi, F Hainaut, P Mendy, M Goedert, J Montesano, R TI Hepatitis B and C infection and aflatoxin exposure in hepatocellular carcinoma: A case-control study from the Gambia, West Africa. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NIH, NIAID, Rockville, MD USA. Gambia Hepatitis Intervent Study, Banjul, Gambia. Int Agcy Res Canc, F-69372 Lyon, France. RI Kirk, Gregory/A-8484-2009; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 1978 BP 666A EP 666A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224701969 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI What explains the association of overweight with liver disease in the United States population?. SO HEPATOLOGY LA English DT Meeting Abstract C1 Social & Sci Syst, Bethesda, MD USA. NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2001 VL 34 IS 4 SU S MA 2059 BP 687A EP 687A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 476KE UT WOS:000171224702050 ER PT J AU Kudva, YC Deng, YJ Govindarajan, R Abraham, RS Marietta, EV Notkins, AL David, CS AF Kudva, YC Deng, YJ Govindarajan, R Abraham, RS Marietta, EV Notkins, AL David, CS TI HLA-DQ8 transgenic and NOD mice recognize different epitopes within the cytoplasmic region of the tyrosine phosphatase-like molecule, IA-2 SO HUMAN IMMUNOLOGY LA English DT Article DE IA-2 epitopes; DQ8; transgenic; NOD ID DEPENDENT DIABETES-MELLITUS; T-CELL RESPONSES; AUTOANTIGEN IA-2; GENETIC-ANALYSIS; IMMUNE-RESPONSE; SUSCEPTIBILITY; LOCUS; MOUSE; IDDM; AUTOANTIBODIES AB Type 1 diabetes mellitus is strongly associated with HLA-DQ8 in humans and I-A(g7) in the NOD mouse. The disease is characterized by loss of tolerance to auto-antigens such as GAD, insulin, and the protein tyrosine phosphatase-like molecule, IA-2. We identified T cell epitopes on the intracytoplasmic region of IA-2 by immunizing DQ8/NOD, DQ8/B10, and NOD mice with overlapping 18 met peptides in CFA. We identified four peptides presented both by DQ8 and NOD, five DQ8 specific peptides, and six NOD specific peptides, Both mouse lines failed to respond to ten peptides. We demonstrated MHC class II and CD4 restriction of proliferative responses using appropriate blocking antibodies. To understand the role of non-MHC genes in the generation of immune response to the islet auto-antigen, we evaluated cytokine secretion following immunization of DQ8 transgenic mice with strongly immunogenic peptides. The NOD background resulted in increased secretion of cytokines. in conclusion, we have identified IA-2 peptides that induce lymphoproliferative responses in DQ8 transgenic and NOD mice and shown that these peptides stimulate production of Th1 and Th2 cytokines. (C) American Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc. C1 Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Metab Endocrinol & Nutr, Rochester, MN 55905 USA. Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP David, CS (reprint author), Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. NR 31 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2001 VL 62 IS 10 BP 1099 EP 1105 DI 10.1016/S0198-8859(01)00308-1 PG 7 WC Immunology SC Immunology GA 484KH UT WOS:000171688400006 PM 11600216 ER PT J AU Zachary, AA Bias, WB Johnson, A Rose, SM Leffell, MS AF Zachary, AA Bias, WB Johnson, A Rose, SM Leffell, MS TI Antigen, allele, and haplotype frequencies report of the ASHI Minority Antigens Workshops: Part 1, African-Americans SO HUMAN IMMUNOLOGY LA English DT Article DE HLA antigens; alleles; haplotypes; frequencies ID UNOS REGISTRY; HLA ANTIGENS; DONORS; POPULATION; VACCINE; MARROW; CANCER AB HLA typing was performed on 977 African Americans residing throughout most of the United States. Class I and class II antigens and class II alleles were defined for all individuals and class I alleles were determined for a subset of individuals, The occurrence of 854 of the individuals in family groups permitted direct counting of allele and haplotype frequencies. The data were analyzed for antigen, allele, and haplotype frequencies; recombination frequencies; segregation distortion; distribution of haplotype frequencies; linkage disequilibria; and geographic distribution of DR antigens. Tables of the antigen, allele, the most common two and three point haplotypes, and 88 extended haplotypes that include class I and class II alleles are presented. Notable findings include a lower than expected frequency of recombination between the B and DR loci (theta = 0.0013), lower than expected frequency of inheritance (44.5% vs 54.5%) of the DRB1*1503; DQB1*0602 haplotype, lower than anticipated linkage disequilibrium values for DR; DQ haplotypes, and a skewed geographic distribution of DR antigens. (C) American Society for Histocompatibility and Irnmunogenetics, 2001. Published by Elsevier Science Inc. C1 Johns Hopkins Univ, Sch Med, Immunogenet Lab, Baltimore, MD 21205 USA. Georgetown Univ, Sch Med, Dept Pediat, Washington, DC 20057 USA. NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. RP Zachary, AA (reprint author), Johns Hopkins Univ, Sch Med, Immunogenet Lab, 2041 E Monument St, Baltimore, MD 21205 USA. NR 15 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2001 VL 62 IS 10 BP 1127 EP 1136 DI 10.1016/S0198-8859(01)00305-6 PG 10 WC Immunology SC Immunology GA 484KH UT WOS:000171688400010 PM 11600220 ER PT J AU Nwosu, V Carpten, J Trent, JM Sheridan, R AF Nwosu, V Carpten, J Trent, JM Sheridan, R TI Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease SO HUMAN MOLECULAR GENETICS LA English DT Review ID ANDROGEN RECEPTOR GENE; CAG REPEAT POLYMORPHISM; BULBAR MUSCULAR-ATROPHY; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; HIGH-RISK; CHROMOSOME 1Q42.2-43; ALLELIC IMBALANCE; FAMILY HISTORY; CLINICAL PRESENTATION AB Prostate cancer is a complex, multifactorial disease with genetic and environmental factors involved in its etiology. The search for genetic determinants involved in the disease has proven to be challenging, in part because such complex diseases are often not amenable to characterization by linkage analysis and positional cloning as is the case for diseases with simple Mendelian genetic inheritance. Prostate cancer susceptibility loci that have been reported so far include HPC1 (1q24-q25), PCAP (1q42-q43), HPCX (Xq27-q28), CAPB (1p36), HPC20 (20q13), HPC2/ELAC2 (17p11) and 16q23. Prostate cancer aggressiveness loci have also been reported (5q31-q33, 7q32 and 19q12). Further complicating the process is the existence of polymorphisms in several genes associated with prostate cancer including, AR, PSA, SRD5A2, VDR and CYP isoforms. These polymorphisms, however, are not thought to be highly penetrant alleles in families at high risk for prostate cancer. It is clear that prostate cancer etiology involves several genetic loci with no major gene accounting for a large proportion of susceptibility to the disease. C1 N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. NHGRI, NIH, Bethesda, MD 20892 USA. DNA Sci Labs, Morrisville, NC 27560 USA. RP Carpten, J (reprint author), N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. NR 78 TC 82 Z9 85 U1 1 U2 5 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 OCT 1 PY 2001 VL 10 IS 20 BP 2313 EP 2318 DI 10.1093/hmg/10.20.2313 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 486AG UT WOS:000171795300018 PM 11673416 ER PT J AU Domanski, M Norman, J Wolz, M Mitchell, G Pfeffer, M AF Domanski, M Norman, J Wolz, M Mitchell, G Pfeffer, M TI Cardiovascular risk assessment using pulse pressure in the First National Health and Nutrition Examination Survey (NHANES I) SO HYPERTENSION LA English DT Article DE pulse; arteries; cardiovascular diseases ID ISOLATED SYSTOLIC HYPERTENSION; CORONARY HEART-DISEASE; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; DEATH CERTIFICATES; AORTIC STIFFNESS; MORTALITY; ATHEROSCLEROSIS; DYSFUNCTION; PREDICTOR AB Increased stiffness of the conduit arteries has been associated with increased risk of death and cardiovascular death in a number of populations. None of these populations, however, are fully representative of the US population. The cohort examined in the First National Health and Nutrition Examination Survey (NHANES I) that was free of overt cardiovascular disease was selected to be representative of the US population. We assessed and quantified the increased risk of death associated with elevated pulse pressure in this population. A cohort of 5771 subjects from NHANES I was used to determine the value of adding pulse pressure to standard cardiovascular disease risk factors for assessment of the risk of death during a mean follow-up period of 16.5 years. Analyses were performed by use of the SUDAAN statistical package for performing Cox proportional regression, logistic regression, and other standard methods in complex, weighted samples. Pulse pressure increased with increasing age, body mass index, cholesterol level, and mean arterial pressure. With increasing pulse pressure, the percentage of cigarette smokers decreased and the percentage of diabetics increased. Despite these associations with known risk factors, pulse pressure was independently predictive of an increased risk of death from cardiovascular disease, coronary heart disease, and all-cause mortality. It provides independent prognostic information beyond that provided by known risk factors that were evaluated in this study, including the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure hypertension classification. A 10 mm Hg increase in pulse pressure in persons 25 to 45 of age was associated with a 26% increase in risk of cardiovascular death (95% confidence interval [CI], 5 to 50) and with an 10% increase (95% CI, 2 to 19) in persons 46 to 77 years of age. In a cohort designed to be representative of the US population, elevated pulse pressure has been shown to provide independent prognostic information. This variable may be a marker for the extent of vascular disease and may contribute to the occurrence of clinical events. C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. Cardiovasc Engn Inc, Boston, MA USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. RP Domanski, M (reprint author), NHLBI, Rockledge Ctr 2, 6701 Rockledge Dr,Room 8146, Bethesda, MD 20892 USA. NR 43 TC 116 Z9 125 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 OCT PY 2001 VL 38 IS 4 BP 793 EP 797 DI 10.1161/hy1001.092966 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487NN UT WOS:000171882300007 PM 11641288 ER PT J AU Eckstein, DA Penn, ML Korin, YD Scripture-Adams, DD Zack, JA Kreisberg, JF Roederer, M Sherman, MP Chin, PS Goldsmith, MA AF Eckstein, DA Penn, ML Korin, YD Scripture-Adams, DD Zack, JA Kreisberg, JF Roederer, M Sherman, MP Chin, PS Goldsmith, MA TI HIV-1 actively replicates in naive CD4(+) T cells residing within human lymphoid tissues SO IMMUNITY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTES IN-VITRO; ANTIRETROVIRAL THERAPY; CD45RO ISOFORMS; CORECEPTOR USE; AMINO-ACIDS; INFECTION; TYPE-1; CYCLE; MEMORY AB Although HIV-1 gene expression is detected in naive, resting T cells in vivo, such cells are resistant to productive infection in vitro. However, we found that the endogenous. microenvironment of human lymphoid tissues supports de novo infection and depletion of this population. Cell cycle analysis and DNA labeling experiments established that these cells were definitively quiescent and thus infected de novo. Quantitation of the "burst size" within naive cells further demonstrated that these cells were productively infected and contributed to the local viral burden. These findings demonstrate that lymphoid tissues support active HIV-1 replication in resting, naive T cells. Moreover, these cells are not solely reservoirs of latent virus but are permissive hosts for viral replication that likely targets them for elimination. C1 Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94141 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94141 USA. Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Goldsmith, MA (reprint author), Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA. RI Roederer, Mario/G-1887-2011 FU NIAID NIH HHS [R37-AI36059, R01-AI36554, R01-AI43695]; NIDCR NIH HHS [T32-DEO7296] NR 45 TC 166 Z9 167 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2001 VL 15 IS 4 BP 671 EP 682 DI 10.1016/S1074-7613(01)00217-5 PG 12 WC Immunology SC Immunology GA 485MH UT WOS:000171757800017 PM 11672548 ER PT J AU Montgomery, SP Hale, DA Hirshberg, B Harlan, DM Kirk, AD AF Montgomery, SP Hale, DA Hirshberg, B Harlan, DM Kirk, AD TI Preclinical evaluation of tolerance induction protocols and islet transplantation in non-human primates SO IMMUNOLOGICAL REVIEWS LA English DT Review ID LONG-TERM SURVIVAL; DEPENDENT DIABETES-MELLITUS; RENAL-ALLOGRAFT REJECTION; DONOR-SPECIFIC TOLERANCE; PANCREATIC-ISLETS; MONOCLONAL-ANTIBODY; NONHUMAN-PRIMATES; KIDNEY ALLOGRAFTS; MIXED CHIMERISM; RHESUS-MONKEYS AB Non-human primate studies of tolerance induction strategies in solid organ transplantation represent a critical bridge between studies in rodents and humans. Our work demonstrates that strategies involving the blockade of co-stimulatory molecules, especially the CD40-CD154 pathway, have great potential for clinical adaptation, While the combination of anti-CD15.4 antibody with blockade of the CD28 pathway reduced donor antibody production, graft survival was not significantly improved over that achieved with anti-CD154 antibody alone. Moreover, although long courses of steroids seem to interfere with this approach, it may be possible to combine blockade of the CD40-CD154 pathway with other conventional immunosuppressants without sacrificing efficacy. This is a key issue for reducing the risk associated with eventual clinical triads. Work in the non-human primate islet transplant model demonstrates that viable islets can be recovered, isolated and infused in a reliable fashion. it also confirms the efficacy of a steroid sparing approach to immunosuppression for islet transplantation. These data have been expanded to the kidney allograft model, Setting the stage for kidney islet transplantation studies. Overall, tolerance induction and islet transplant studies in non-human primates permit the preclinical screening of promising immunohistochemistry approaches developed in rodents and reduce the inherent uncertainties associated with adapting new regimens to the clinic. C1 NIDDKD, NIH, Navy Transplant & Autoimmun Branch, Bethesda, MD 20892 USA. RP Hale, DA (reprint author), NIDDKD, NIH, Navy Transplant & Autoimmun Branch, 10 Ctr Dr,Room 11S-219, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 FU NIAID NIH HHS [AI43900-01] NR 43 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2001 VL 183 BP 214 EP 222 DI 10.1034/j.1600-065x.2001.1830117.x PG 9 WC Immunology SC Immunology GA 506GM UT WOS:000172961600017 PM 11782259 ER PT J AU Peng, B Robert-Guroff, M AF Peng, B Robert-Guroff, M TI Deletion of N-terminal myristoylation site of HIV Nef abrogates both MHC-1 and CD4 down-regulation SO IMMUNOLOGY LETTERS LA English DT Article DE HIV Nef; down regulation; myristoylation ID CYTOTOXIC T-LYMPHOCYTES; VIRUS TYPE-1 NEF; VIRAL INFECTIVITY; IN-VIVO; CELLS; PROTEIN; ENHANCEMENT; REPLICATION; SUPPRESSION; TRAFFICKING AB HIV-1 Nef is a desirable vaccine component because it is expressed early and abundantly during HIV infection, and contains many CTL, T-helper cell, and B-cell epitopes. Nef, however, down-regulates MHC-1 and CD4 cell surface expression, contributing to viral escape from host immunity. To prevent Nef from down-regulating both MHC-1 and CD4 while preserving most CTL epitopes, a panel of Nef mutants was constructed and assessed. Some mutants, as expected, modulated either MHC-1 or CD4 expression, Others prevented down-regulation of both proteins but sacrificed numerous immunogenic epitopes. Deletion of 19 N-terminal amino acids including the myristoylation signal from Nef completely abrogated both MHC-1 and CD4 down-regulation while preserving most CTL, T-helper and B-cell epitopes. Our results demonstrate that the myristoylation signal in the Nef protein is critical for Nef-mediated endocytosis of both MHC-1 and CD4. Non-myristoylated Nef containing a full complement of CTL epitopes has greater potential as a vaccine component than wild-type Nef. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NCI, NIH, Basic Res Lab, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), NCI, NIH, Basic Res Lab, 41 Libary Dr,Bldg 41 Room d804, Bethesda, MD 20892 USA. NR 27 TC 34 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD OCT 1 PY 2001 VL 78 IS 3 BP 195 EP 200 DI 10.1016/S0165-2478(01)00250-4 PG 6 WC Immunology SC Immunology GA 486NY UT WOS:000171824900012 PM 11578695 ER PT J AU Koay, MA Christman, JW Segal, BH Venkatakrishnan, A Blackwell, TR Holland, SM Blackwell, TS AF Koay, MA Christman, JW Segal, BH Venkatakrishnan, A Blackwell, TR Holland, SM Blackwell, TS TI Impaired pulmonary NF-kappa B activation in response to lipopolysaccharide in NADPH oxidase-deficient mice SO INFECTION AND IMMUNITY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; DINUCLEOTIDE PHOSPHATE OXIDASE; INFLAMMATORY RESPONSE; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; MOUSE MODEL; BINDING; TARGET; LIVER AB Reactive oxygen species (ROS) are thought to be involved in intracellular signaling, including activation of the transcription factor NF-kappaB. We investigated the role of NADPH oxidase in the NF-KB activation pathway by utilizing knockout mice (p47(phox-/-)) lacking the p47(phox) component of NADPH oxidase. Wild-type (WT) controls and P47(phox-/-) mice were treated with intraperitoneal (i.p.) Escherichia coli lipopolysaccharide (LPS) (5 or 20 mug/g of body weight). LPS-induced NF-kappaB binding activity and accumulation of RelA in nuclear protein extracts of lung tissue were markedly increased in WT compared to p47(phox-/-) mice 90 min after treatment with 20 but not 5 mug of i.p. LPS per g. In another model of lung inflammation, RelA nuclear translocation was reduced in p47(phox-/-) mice compared to. WT mice following treatment with aerosolized LPS. In contrast to NF-kappaB activation in p47(phox-/-) mice, LPS-induced production of macrophage inflammatory protein 2 in the lungs and neutrophilic lung inflammation were not diminished in these mice compared to WT mice. We conclude that LPS-induced NF-KB activation is deficient in the lungs of p47(phox-/-) mice compared to WT mice, but this abnormality does not result in overt alteration in the acute inflammatory response. C1 Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Med, Nashville, TN USA. Dept Vet Affairs, Nashville, TN 37243 USA. NIH, Host Def Lab, Bethesda, MD 20892 USA. RP Christman, JW (reprint author), Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Dept Med, T-1217 MCN, Nashville, TN USA. FU NHLBI NIH HHS [HL 61419, R01 HL061419] NR 31 TC 59 Z9 62 U1 0 U2 3 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 OCT PY 2001 VL 69 IS 10 BP 5991 EP 5996 DI 10.1128/IAI.69.10.5991-5996.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 474RR UT WOS:000171121100005 PM 11553535 ER PT J AU Abdo, KM Grumbein, S Chou, BJ Herbert, R AF Abdo, KM Grumbein, S Chou, BJ Herbert, R TI Toxicity and carcinogenicity study in F344 rats following 2 years of whole-body exposure to naphthalene vapors SO INHALATION TOXICOLOGY LA English DT Article ID CLARA CELL CYTOTOXICITY; ZERO DOSE CONTROL; CYTOCHROME-P450 ACTIVITY; METABOLIC-ACTIVATION; COVALENT BINDING; MICE; GLUTATHIONE; ENZYMES; HAMSTERS; CATARACT AB The toxicologic and carcinogenic potential of naphthalene was studied by exposing groups of 49 male and 49 female F344 rats to atmospheres containing 0, 10, 30, or 60 ppm of the chemical for 6 h daily, 5 days/wk for 2 yr. Mean body weights of exposed groups of male rats were less than for the control group throughout most of the study. Mean body weights of exposed female rats were generally similar to those of controls. Survival of exposed and control rats was similar. Under the conditions of this 2-yr inhalation study, naphthalene was carcinogenic to male and female F344/N rats, causing increased incidences of respiratory epithelial adenoma ( males: control, 0%; low dose, 12%, mid dose, 17%; high dose, 31%; females: 0%; 0%; 8%; 4%) and olfactory epithelial neuroblastoma ( males: control, 0%; low dose, 0%; mid dose, 8%; high dose, 6%; females: 0; 4%; 6%; 24%) of the nose. In both sexes of rats, exposure to naphthalene also caused significant increases in the incidences of nasal lesions including hyperplasia, atrophy, chronic inflammation, and hyaline degeneration of the olfactory epithelium and hyperplasia; squamous metaplasia, hyaline degeneration, and goblet-cell hyperplasia of the respiratory epithelium; and glandular hyperplasia and squamous metaplasia. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Toxicol NW, Richland, WA USA. RP Abdo, KM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 57 TC 44 Z9 46 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD OCT PY 2001 VL 13 IS 10 BP 931 EP 950 PG 20 WC Toxicology SC Toxicology GA 474JJ UT WOS:000171103100005 PM 11696867 ER PT J AU Grillon, C AF Grillon, C TI Unpredictability and context conditioning in humans SO INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE LA English DT Meeting Abstract C1 NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TRANSACTION PERIOD CONSORTIUM PI PISCATAWAY PA RUTGERS UNIV, DEPT 8010, 35 BERRUE CIRCLE, PISCATAWAY, NJ 08854-8042 USA SN 1053-881X J9 INTEGR PHYS BEH SCI JI Integr. Physiol. Behav. Sci. PD OCT-DEC PY 2001 VL 36 IS 4 BP 316 EP 316 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 548DT UT WOS:000175373900020 ER PT J AU Siesser, W Zhao, J Cheng, SY McDonald, MP AF Siesser, W Zhao, J Cheng, SY McDonald, MP TI Reinforcement processes in a novel model of attention deficits and hyperactivity SO INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE LA English DT Meeting Abstract C1 Vanderbilt Univ, Sch Med, Program Neurosci, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TRANSACTION PERIOD CONSORTIUM PI PISCATAWAY PA RUTGERS UNIV, DEPT 8010, 35 BERRUE CIRCLE, PISCATAWAY, NJ 08854-8042 USA SN 1053-881X J9 INTEGR PHYS BEH SCI JI Integr. Physiol. Behav. Sci. PD OCT-DEC PY 2001 VL 36 IS 4 BP 326 EP 326 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 548DT UT WOS:000175373900040 ER PT J AU Kaldjian, EP Gretz, JE Anderson, AO Shi, YH Shaw, S AF Kaldjian, EP Gretz, JE Anderson, AO Shi, YH Shaw, S TI Spatial and molecular organization of lymph node T cell cortex: a labyrinthine cavity bounded by an epithelium-like monolayer of fibroblastic reticular cells anchored to basement membrane-like extracellular matrix SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE T lymphocyte migration; lymph node; microanatomy; extracellular matrix; fibroblastic reticular cell ID HIGH-ENDOTHELIAL VENULES; III PN-COLLAGEN; IV-COLLAGEN; MICROSCOPIC LOCALIZATION; MONOCLONAL-ANTIBODY; DENDRITIC CELLS; CARCINOMA-CELLS; TENASCIN; LAMININ; RAT AB Naive T cells encounter antigen-presenting cells within the cortex of lymph nodes to initiate primary immune responses. Within this T cell cortex is the reticular network (RN)-a system of collagen fibers and extracellular matrix (ECM) wrapped by fibroblastic reticular cells (FRC). We have investigated the distribution of various molecules, including ECM proteins and proteoglycans, in the T cell cortex of both human and rodent lymph node. We confirm and extend reports of matrix elements in the RN. In addition, we find that staining for the laminin-alpha3 chain and for tenascin reveals a 'hollow' reticular pattern, consistent with localization to the basement membrane-like covering of reticular fibers. In contrast, keratan sulfate is observed in a fine linear pattern within the RN, suggesting it is localized to the core of the fibers. Staining with the marker ER-TR7 indicates that FRC cover all identifiable ECM surfaces of the T cell cortex. Based on these findings and previous reports, we conclude that cortical lymphocytes migrate within a 'labyrinthine cavity' free of fibrillar ECM, distinguishing the T cell cortex from other loose connective tissues, and that the FRC lining of the cavity constitutes an epithelium-like boundary. We propose that this spatial organization facilitates ameboid leukocyte crawling along preformed paths of least resistance and that the basement membrane-like ECM of the FRC may facilitate fluid transport within the RN by limiting leakage from the fiber. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48105 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Shaw, S (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 71 TC 100 Z9 102 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 2001 VL 13 IS 10 BP 1243 EP 1253 DI 10.1093/intimm/13.10.1243 PG 11 WC Immunology SC Immunology GA 484MB UT WOS:000171693200004 PM 11581169 ER PT J AU Nocito, A Kononen, J Kallioniemi, OP Sauter, G AF Nocito, A Kononen, J Kallioniemi, OP Sauter, G TI Tissue microarrays (TMAs) for high-throughput molecular pathology research SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE tissue microarrays; high throughput; pathology; immunohistochemistry; prognostic markers ID PROSTATE-CANCER; GENE AMPLIFICATION; COMPLEMENTARY-DNA; CDNA MICROARRAY; EXPRESSION; OVEREXPRESSION AB A rapidly increasing number of genes are being suspected to play a role in cancer biology. To evaluate the clinical significance of newly detected potential cancer genes, it is usually required to examine a high number of well-characterized primary tumors. Using traditional methods of molecular pathology, this is a time consuming endeavor rapidly exhausting precious tissue resources. To allow for a high throughput tissue analysis we have developed a "tissue chip" approach (Kononen et al., Nat. Med. 1998;4:844-7). Using this tissue microarray (TMA) technology, samples from up to 1,000 different tumors are arrayed in one recipient paraffin block, sections of which can be used for all kind of in situ analyses. Sections from TMA blocks can then be utilized for the simultaneous analysis of up to 1,000 different tumors on the DNA, RNA or protein level. TMAs allow a high through-put molecular analysis of thousands of tumors within a few burs. All currently available data have suggested that minute arrayed tissue specimens are highly representative of their donor tissues. There are multiple different types of TMAs that can be utilized in cancer research including multi tumor arrays (containing different tumor types), tumor progression arrays (tumors of different stages) and prognostic arrays (tumors with clinical endpoints). The combination of multiple different TMAs allows a very quick but comprehensive characterization of biomarkers of interest. We anticipate that the use of TMAs will greatly accelerate the transition of basic research findings to clinical applications. (C) 2001 Wiley-Liss, Inc. C1 Univ Basel, Inst Pathol, Basel, Switzerland. Univ Tampere, Tampere Univ Hosp, Canc Genet Lab, FIN-33101 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sauter, G (reprint author), Univ Hosp, Inst Pathol, Schonbeinstr 40, CH-4003 Basel, Switzerland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 18 TC 153 Z9 166 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 1 PY 2001 VL 94 IS 1 BP 1 EP 5 DI 10.1002/ijc.1385 PG 5 WC Oncology SC Oncology GA 468HT UT WOS:000170752600001 PM 11668471 ER PT J AU Jimenez, N Jongsma, J Calvo, A van der Kwast, TH Treston, AM Cuttitta, F Schroder, FH Montuenga, LM van Steenbrugge, GJ AF Jimenez, N Jongsma, J Calvo, A van der Kwast, TH Treston, AM Cuttitta, F Schroder, FH Montuenga, LM van Steenbrugge, GJ TI Peptidylglycine alpha-amidating monooxygenase- and proadrenomedullin-derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE adrenomedullin; androgen blockade; neuroendocrine; prostate cancer; proadrenomedullin N-terminal 20 peptide; peptidyl-glycine alpha-amidating monooxygenase; peptidylglycine alpha-hydroxylating monooxygenase ID N-TERMINAL-20 PEPTIDE; ADRENOMEDULLIN GENE; VENTRAL PROSTATE; MESSENGER-RNA; CELLS; EXPRESSION; CARCINOMA; CANCER; LOCALIZATION; PITUITARY AB Most PCs show NE differentiation. Several studies have tried to correlate NE expression with disease status, but the reported findings have been contradictory. Prostatic NE cells synthesize peptides with a wide spectrum of potential functions. Some of these active peptides, such as PAMP, are amidated. PAM is the only carboxy-terminal peptide-amidating enzyme identified. We studied expression of PAMP and PAM in normal prostate and prostatic tumors (clinical specimens and human xenograft models) with or without prior androgen-deprivation therapy and found a wide distribution of both molecules in NE subpopulations of all kinds. Although the correlation of either marker to tumor grade, clinical progression or disease prognosis did not reach statistical significance, PAMP- or PAM-immunoreactive cells were induced after androgen-blockade therapy. In the PC-310 and PC-295 androgen-dependent models, PAMP or PAM NE differentiation was induced after castration in different ways, being higher in PC-310, which might explain its long-term survival after androgen deprivation. We show induction of expression of 2 new NE markers in clinical specimens and xenografted PC after endocrine therapy. (C) 2001 Wiley-Liss, Inc. C1 Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. Josephine Nefkens Inst, Dept Expt Urol & Pathol, Rotterdam, Netherlands. NCI, NIH, Rockville, MD USA. RP Jimenez, N (reprint author), Univ Navarra, Dept Histol & Pathol, POB 177, E-31080 Pamplona, Spain. RI Jimenez, Nuria/C-6374-2012 NR 37 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 1 PY 2001 VL 94 IS 1 BP 28 EP 34 DI 10.1002/ijc.1436 PG 7 WC Oncology SC Oncology GA 468HT UT WOS:000170752600005 PM 11668475 ER PT J AU Kogulan, PK Smith, M Seidman, J Chang, G Tsokos, M Lucey, D AF Kogulan, PK Smith, M Seidman, J Chang, G Tsokos, M Lucey, D TI Malakoplakia involving the abdominal wall, urinary bladder, vagina, and vulva: Case report and discussion of malakoplakia-associated bacteria SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article ID CUTANEOUS MALACOPLAKIA; DIAGNOSIS; AIDS AB A 29-year-old woman presented with a 3-month history of multiple purulent discharging nodules involving her lower abdomen, vulva, and left thigh. Physical examination also disclosed vaginal nodules and a left pelvic mass. Cystoscopy revealed multiple mucosal nodules and a perforation of the left vesical wall that appeared to communicate with the pelvic mass. Biopsies of the vesical and vulvar nodules revealed malakoplakia. Surgery and antibiotic therapy resulted in regression of all the lesions. C1 Washington Hosp Ctr, Infect Dis Serv, Dept Infect Dis, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Pathol, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Urol, Washington, DC 20010 USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. RP Lucey, D (reprint author), Washington Hosp Ctr, Infect Dis Serv, Dept Infect Dis, Room 2A-56,110 Irving St NW, Washington, DC 20010 USA. NR 10 TC 11 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2001 VL 20 IS 4 BP 403 EP 406 DI 10.1097/00004347-200110000-00016 PG 4 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 478CQ UT WOS:000171325700016 PM 11603228 ER PT J AU Masood, R Gordon, EM Whitley, MD Wu, BW Cannon, P Evans, L Anderson, WF Gill, P Hall, FL AF Masood, R Gordon, EM Whitley, MD Wu, BW Cannon, P Evans, L Anderson, WF Gill, P Hall, FL TI Retroviral vectors bearing IgG-binding motifs for antibody-mediated targeting of vascular endothelial growth factor receptors SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE retroviral vectors; vascular endothelial growth factor receptors ID STAPHYLOCOCCAL PROTEIN-A; ENVELOPE PROTEIN; VIRUS VECTORS; GENE-TRANSFER; THERAPY; SYSTEM; GLYCOPROTEINS; DELIVERY; FRAGMENT; COMPLEX AB Targeting retroviral vectors to tumor vasculature is an important goal of cancer gene therapy. In this study, we report a novel targeting approach wherein IgG-binding peptides were inserted into the Moloney murine leukemia virus (MuLV) envelope (env) protein. The modifications on the viral env included replacement of the entire receptor binding region of the viral env with protein A (or ZZ) domains. The truncated env incorporating IgG-binding motifs (known as 'escort' proteins) provided the targeting function, while the coexpressed wild-type (WT) env protein enabled viral fusion and cell entry. An anti-human VEGF receptor (Flk-1/KDR) antibody served as a molecular bridge, directing the retroviral vector to the endothelial cell. Hence, the IgG-targeted vectors bound to the Flk-1/KDR antibody which in turn bound to VEGF receptors on Kaposi sarcoma, KSY1, endothelial cells. The net effect was increased viral fusion and infectivity of IgG-bound retroviral vectors when compared to non-targeted vectors bearing WT env alone. These data provide the proof of concept that IgG-binding vector/VEGF receptor antibody complexes may be used to enhance retroviral gene delivery to activated endothelial cells. C1 Univ So Calif, Sch Med, Gene Therapy Labs, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Surg, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Biochem, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Mol Pharmacol Toxicol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Hall, FL (reprint author), USC, Gene Therapy Labs, 1975 Zonal Ave,KAM30, Los Angeles, CA 90089 USA. NR 31 TC 19 Z9 24 U1 1 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD OCT PY 2001 VL 8 IS 4 BP 335 EP 343 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 474YZ UT WOS:000171136000001 PM 11562769 ER PT J AU Snitker, S Tataranni, PA Ravussin, E AF Snitker, S Tataranni, PA Ravussin, E TI Spontaneous physical activity in a respiratory chamber is correlated to habitual physical activity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE energy metabolism; indirect calorimetry; doubly labeled water; stable isotopes; non-exercise activity thermogenesis ID ENERGY-EXPENDITURE; WEIGHT-GAIN; OBESITY AB OBJECTIVE: During a stay in a respiratory chamber without an exercise protocol, physical activity is limited to activities of daily living, change of posture and 'fidgeting,' collectively referred to as Spontaneous physical activity (SPA). SPA is quite variable among individuals and is a heritable trait. A low SPA during a chamber stay is a predictor of weight gain in men. However, it remains to be established whether physical activity in a respiratory chamber relates to physical activity under habitual, free-living conditions. The purpose of the present study was to determine whether physical activity in a chamber is correlated to habitual, free-living physical activity. DESIGN: Fifty healthy, non-diabetic Pima Indians (30 M/20 F, 30 +/- 6 y; 37 +/- 10% body fat; means +/- s.d.) completed a 24 h stay in the respiratory chamber followed by a 7 day measurement of habitual, free-living energy expenditure by doubly labeled water. Free-living physical activity was expressed as activity energy expenditure (AEE(FL); daily energy expenditure - (sleeping metabolic rate + thermic effect of food)), physical activity level (PAL(FL); daily energy expenditure/sleeping metabolic rate) and body-size independent activity units. Activity during the chamber stay was expressed as PAL(Ch), AEE(Ch), and based on radar sensor measurements, as percentage of time with activity (SPA(Radar)). RESULTS: AEE(FL) (averaging 930 +/- 310 kcal/day (3.89 +/- 1.30 MJ/day)) was correlated to AEE(CH) (averaging 440 +/- 160 kcal/day (1.84 +/- 0.67 MJ/day)) and higher in men than in women (r=0.53, P=0.003) and r=0.53, P=0.02, respectively). Likewise, PAL(FL) (averaging 1.75 +/- 0.21) was correlated to PAL(Ch) (averaging 1.42 +/- 0.10) and higher in men than in women (r=0.49, P=0.006 and r=0.42, P=0.02, respecitvely). Free-living activity expressed in body-size independent activity units (averaging 17.8 +/- 7.0) was correlated to SPA(Radar) (averaging 6.4 +/- 1.7) with no effect of sex (r=0.30, P=0.03). CONCLUSION: Physical activity in a respiratory chamber was correlated to habitual physical activity, whether expressed as AEE, PAL or body-size independent activity units, providing a plausible explanation for the demonstrated association between a low SPA in the chamber and weight gain. The study encourages further studies of the genetic and non-genetic determinants of SPA and non-exercise activity thermogenesis (NEAT). C1 Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Snitker, S (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Rm 498-B, Baltimore, MD 21201 USA. NR 24 TC 38 Z9 38 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD OCT PY 2001 VL 25 IS 10 BP 1481 EP 1486 DI 10.1038/sj.ijo.0801746 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 481JH UT WOS:000171515800014 PM 11673770 ER PT J AU Yunmbam, MK Li, QDQ Mimnaugh, EG Kayastha, GL Yu, JJ Jones, LN Neckers, L Reed, E AF Yunmbam, MK Li, QDQ Mimnaugh, EG Kayastha, GL Yu, JJ Jones, LN Neckers, L Reed, E TI Effect of the proteasome inhibitor ALLnL on cisplatin sensitivity in human ovarian tumor cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE proteasome inhibitor; ALLnL; cisplatin; DNA repair; ovarian cancer ID DNA ADDUCT FORMATION; REPAIR GENE RAD6; EXCISION-REPAIR; CANCER CELLS; DRUG ACCUMULATION; RNA EXPRESSION; RESISTANCE; APOPTOSIS; PLATINUM; LINES AB Small molecules suppressing proteasome function inhibit the post-translational ubiquitination of selected proteins. Ubiquitin H2A is an example of an abundant chromatin-associated protein that is known to be ubiquitinated, which is important for several proteins involved in the repair of DNA damage. We therefore studied the effect of the proteasome inhibitor, N-acetyl leucyl-leucyl norlucinal (ALLnL), on cisplatin sensitivity in three human ovarian tumor cell lines. The proteasome inhibitor ALLnL was administered for 4 h before cells were subsequently exposed to cisplatin for 1 h. Our results showed that ALLnL, at its respective IC, concentration, increased cellular sensitivity to cisplatin in an additive manner in human ovarian cancer A2780, A2780/CP70, and OVCAR3 cells. We also demonstrated that ALLnL caused a 50% increase in total cellular accumulation of cisplatin, and reduced the rate of cisplatin efflux by about 50%. In addition, DNA damage levels were increased after ALLnL treatment. By contrast, DNA repair was inhibited 2 to 3-fold in ALLnL-pretreated cells, as compared to the controls. Furthermore, our study showed that ALLnL deubiquitinated nucleosomal histone H2A in these cells in a concentration-dependent fashion, as assessed by Western blot analysis. These data suggest that sublethal levels of exposure to agents that inhibit proteasome function may alter the subcellular pharmacology of platinum in human ovarian carcinoma cells. C1 NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA. NCI, Tumor Cell Biol Sect, Cell & Canc Biol Dept, Med Branch,Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Reed, E (reprint author), W Virginia Univ, Hlth Sci Ctr, Mary Babb Randolph Canc Ctr, POB 9300, Morgantown, WV 26506 USA. NR 42 TC 23 Z9 24 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2001 VL 19 IS 4 BP 741 EP 748 PG 8 WC Oncology SC Oncology GA 474YV UT WOS:000171135600012 PM 11562749 ER PT J AU Kunert, KS Keane-Myers, AM Spurr-Michaud, S Tisdale, AS Gipson, IK AF Kunert, KS Keane-Myers, AM Spurr-Michaud, S Tisdale, AS Gipson, IK TI Alteration in goblet cell numbers and mucin gene expression in a mouse model of allergic conjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ATOPIC KERATOCONJUNCTIVITIS; VERNAL KERATOCONJUNCTIVITIS; SIALOMUCIN COMPLEX; OCULAR SURFACE; IN-VIVO; EPITHELIUM; EOSINOPHIL; AIRWAYS; RECRUITMENT; ASTHMA AB PURPOSE. To determine whether the number of filled conjunctival goblet cells and mucin gene expression are altered in a mouse model of allergic conjunctivitis. METHODS. A/J mice were sensitized intraperitoneally with cat dander or the peptide P3-1 from the protein Fel d1. Two weeks later, the mice were challenged for 7 consecutive days with eye drops containing the allergens. Conjunctival tissue was harvested at 0, 6, 24, or 48 hours after final antigen challenge. Control samples were naive animals and mice sensitized with cat dander and challenged with OVA-peptide or PBS. The mean number of filled goblet cells per square millimeter in three forniceal fields for each group was determined in wholemounts of conjunctiva prepared using rhodamine-phalloidin labeling followed by confocal microscopy. RNA was isolated from conjunctiva of the contralateral eye and taken for relative quantitation of mRNA of the goblet cell mucin Muc5AC and the epithelial membrane-spanning mucin Muc4, by real-time RT-PCR. RESULTS. The number of filled goblet cells was significantly decreased with both cat dander and P3-1, after final ocular challenge (P < 0.001). The most significant decrease over naive mice was seen at 6 hours after final challenge with both allergens. The number of filled goblet cells was still decreased but was returning toward naive levels at 24 hours (P < 0.05), and at 48 flours no significant difference was seen compared with naive, PBS-treated, and OVA-peptide-treated control samples. For both cat dander and P3-1, Muc5AC and Muc4 mRNA was found to be decreased at the time of final ocular challenge. The level of Muc5AC mRNA from goblet cells rebounded from the decrease to show an increase over control by 24 hours after final challenge, and by 48 hours, the mRNA level had returned to naive control range. In contrast, significant increases in Muc5AC mRNA were evident after final control challenge with PBS or OVA-peptide, indicating a potential irritant effect of drop application. The Muc4 mRNA level was significantly reduced at all time points except 24 hours after the last challenge. By comparison with allergen-challenged eyes, no change in Muc4 message levels was noted at any time point in OVA-peptide- or PBS-treated control eyes. CONCLUSIONS. These findings demonstrate that, in the conjunctiva of mice, repetitive application of allergens induces a reduction in the number of filled goblet cells and a decrease in Muc5AC and Muc4 mRNAs. After a period of 24 to 48 hours, the goblet cell number return to naive levels, and goblet cell mucin mRNA levels return to above or within normal range, indicating a rapid recovery in the mucus secretion system. C1 Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. NEI, NIH, Bethesda, MD 20892 USA. RP Gipson, IK (reprint author), Harvard Univ, Schepens Eye Res Inst, Sch Med, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [R37-EY03306] NR 37 TC 37 Z9 39 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2001 VL 42 IS 11 BP 2483 EP 2489 PG 7 WC Ophthalmology SC Ophthalmology GA 479ZA UT WOS:000171433300009 PM 11581187 ER PT J AU Becker, MD Garman, K Whitcup, SM Planck, SR Rosenbaum, JT AF Becker, MD Garman, K Whitcup, SM Planck, SR Rosenbaum, JT TI Inhibition of leukocyte sticking and infiltration, but not rolling, by antibodies to ICAM-1 and LFA-1 in murine endotoxin-induced uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MONOCLONAL-ANTIBODIES; ADHESION MOLECULES; P-SELECTIN; CD11A; CD54; MIGRATION; BLOCKING; DISEASE; MALA-2; MODEL AB PURPOSE. Cell-adhesion molecules are critical elements in intravascular roiling and sticking of leukocytes during acute inflammation. In this process, selectins are thought to be involved in initial adhesion and rolling, and integrin-Ig superfamily interactions are believed primarily to mediate stronger adhesion and transendothelial migration. This study clarifies the role of two adhesion molecules, intercellular adhesion molecule (ICAM)-1 and leukocyte functional antigen (LFA)-1, in endotoxin-induced uveitis (EIU). METHODS. Intravital microscopy was used to record the movement and location of leukocytes in the irises of mice with uveitis induced by intravitreal injection of 250 ng Escherichia coli endotoxin. Each mouse concurrently received an intraperitoneal injection of monoclonal neutralizing antibodies for ICAM-1, LFA-1, or both or control irrelevant antibodies. RESULTS. Mice treated with endotoxin and control antibodies had an inflammatory response that was clearly present at the 6- and 24-hour time points and was mostly resolved by 48 hours. Mice that received anti-ICAM-1 or anti-LFA-1 had significantly fewer cells infiltrating their irises at 6 and 24 hours. Detailed analysis of the 6-hour time point recordings revealed that neither anti-ICAM-1 nor anti-LFA-1 significantly reduced the number of leukocytes rolling on venule endothelial surfaces, but the treatments reduced the number of firmly adherent cells. CONCLUSIONS. These data confirm previous reports that ICAM-1 and LFA-1 are important mediators of EIU. The dynamic in vivo images clearly support the hypothesis that integrin-mediated cell adhesion is more critical for the firm adhesion of sticking cells than for leukocyte rolling. C1 Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA. NEI, Bethesda, MD 20892 USA. RP Planck, SR (reprint author), Oregon Hlth Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. RI Becker, Matthias/A-8733-2014 OI Becker, Matthias/0000-0003-4933-7010 FU NEI NIH HHS [EY06477, EY06484, EY13093] NR 19 TC 52 Z9 55 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2001 VL 42 IS 11 BP 2563 EP 2566 PG 4 WC Ophthalmology SC Ophthalmology GA 479ZA UT WOS:000171433300021 PM 11581199 ER PT J AU Knopp, MV Giesel, FL Radeleff, J von Tengg-Kobligk, H AF Knopp, MV Giesel, FL Radeleff, J von Tengg-Kobligk, H TI Bile-tagged 3D magnetic resonance colonography after exclusive intravenous administration of gadobenate dimeglumine, a contrast agent with partial hepatobiliary excretion SO INVESTIGATIVE RADIOLOGY LA English DT Article DE MR colonography; hepatobiliary excretion; virtual endoscopy; intraluminal contrast ID MRI AB RATIONALE AND OBJECTIVES. Imaging of the colon is an important diagnostic procedure. Endoscopic colonoscopy and x-ray barium enemas are currently the standard diagnostic procedures. Magnetic resonance (MR) and computed tomographic colonography have been recently introduced with true three-dimensional (3D) cross-sectional imaging. Up to now, all imaging techniques have required the use of oral and/or aboral contrast agents for luminal enhancement and commonly, a relaxation medication (glucagon or N-butylseopolamine). While performing several phase I, II, and III studies with a new partially hepatobiliary excreted gadolinium-based MR contrast agent, we noted substantial intraluminal enhancement within the colon and investigated its potential for imaging. METHODS. Three-dimensional MR angiographic techniques enable imaging of large volumes. We have used these sequences to detect contrast enhancement within the hepatobiliary and gastrointestinal systems. A 3D volume of 40 x 32 x 12 cm with 42 images was acquired under breath-hold. Six volunteers were studied according to the protocol. No bowel preparation was performed and no medication given. Subsequent follow-ups of the abdomen were performed at 1, 12, 24, 36, 48, 70, and 105 hours postinjection. Gadobenate dimeglumine at 0.1 mmol/kg body weight was given intravenously. Images were assessed quantitatively and by blinded reader analysis. RESULTS. Intense intraluminal contrast enhancement within the colon was seen within 24 hours in all subjects. The homogeneous enhancement was of sufficient intensity to enable 3D visualization and virtual endoscopy. The optimal time window for imaging was determined to be 16 to 50 hours postinjection. CONCLUSIONS. We report for the first time the feasibility of exclusively bile-tagged MR colonography with the use of only an intravenous MR contrast that exhibits partial hepatobiliary excretion. This new diagnostic procedure will enable not only morphological assessment of the colon but also functional and pathophysiological studies on the transport kinetics of bile and stool without any preparation of the patient. C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. German Canc Res Ctr, Dept Radiol, D-6900 Heidelberg, Germany. RP Knopp, MV (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bldg 10,Room 1C624,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. RI von Tengg-Kobligk, Hendrik/A-1420-2017 OI von Tengg-Kobligk, Hendrik/0000-0003-3207-3223 NR 21 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD OCT PY 2001 VL 36 IS 10 BP 619 EP 623 DI 10.1097/00004424-200110000-00008 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 482QH UT WOS:000171586400008 PM 11577273 ER PT J AU Matsumoto, Y Takano, H Kunishio, K Nagao, S Fojo, T AF Matsumoto, Y Takano, H Kunishio, K Nagao, S Fojo, T TI Incidence of mutation and deletion in topoisomerase II alpha mRNA of etoposide and mAMSA-resistant cell lines SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE topoisomerase II; mutation; drug resistance; multidrug resistance; chemotherapy ID CASEIN KINASE-II; AGENTS; CYCLE AB The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to VP-16 (etoposide) or mAMSA (m-amsacrine). Subsequently, a population of cells from each subline was exposed to three-fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. Finally, 66 sublines were picked up. The frequency and nature of mutations in the topoisomerase II gene in the drug-selected cell lines were evaluated. In order to screen a large number of cell lines, an RNAse protection assay was developed and mismatches were observed in 13.6% of resistant cell lines (12% of resistant cell lines exposed to lower drug concentrations and 18.8% of resistant cell lines exposed to higher drug concentrations). Some of these mutations are located in vital regions of topoisomerase II (phosphorylation sites in the C-terminal or N-terminal, and nuclear localizing signal of topoisomerase II). Our findings suggest that mutations of topoisomerase II gene are an important and frequent mechanism of resistance to topoisomerase II inhibitors. C1 Kagawa Med Univ, Dept Neurol Surg, Kagawa 7610793, Japan. NCI, NIH, DCS, Med Branch, Bethesda, MD 20892 USA. RP Matsumoto, Y (reprint author), Kagawa Med Univ, Dept Neurol Surg, 1750-1 Ikenobe, Kagawa 7610793, Japan. NR 15 TC 6 Z9 7 U1 0 U2 2 PU BUSINESS CENTER ACADEMIC SOCIETIES JAPAN PI TOKYO PA 5-16-9 HONKOMAGOME, BUNKYO-KU, TOKYO, 113-8633, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD OCT PY 2001 VL 92 IS 10 BP 1133 EP 1137 PG 5 WC Oncology SC Oncology GA 487BM UT WOS:000171853800016 PM 11676865 ER PT J AU Augenbraun, M Tarwater, P Greenblatt, R Cohen, M French, A Gore, ME Watts, H Preston-Martin, J Anastos, K AF Augenbraun, M Tarwater, P Greenblatt, R Cohen, M French, A Gore, ME Watts, H Preston-Martin, J Anastos, K TI Opportunistic infection prophylaxis in the Women's Interagency HIV Study (WIHS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID COMMUNITY; DISEASE C1 Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cook Cty Hosp, Chicago, IL 60612 USA. NICHHD, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. Lincoln Med Ctr, Bronx, NY USA. RP Augenbraun, M (reprint author), Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. FU NCRR NIH HHS [5-MO1-RR00083, 5-MO1-RR00079]; NIAID NIH HHS [U01-AI-31834, U01-AI-35004, U-01-AI-34993, U01-AI-34994, U01-AI-34989, U01-AI-42590]; NICHD NIH HHS [U01-HD-32632] NR 12 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD OCT 1 PY 2001 VL 28 IS 2 BP 195 EP 197 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 480NK UT WOS:000171467600014 PM 11588516 ER PT J AU Smith, ML Shimomura, ET Summers, J Paul, BD Jenkins, AJ Darwin, WD Cone, EJ AF Smith, ML Shimomura, ET Summers, J Paul, BD Jenkins, AJ Darwin, WD Cone, EJ TI Urinary excretion profiles for total morphine, free morphine, and 6-acetyl morphine following smoked and intravenous heroin SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID INTRANASAL SNORTED HEROIN; OPIATE IMMUNOASSAYS; GAS-CHROMATOGRAPHY; DETECTION TIMES; DRUG; PHARMACOKINETICS; PHARMACODYNAMICS; CODEINE; SPECIMENS; USERS C1 Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, Washington, DC 20306 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Paul, BD (reprint author), Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, Washington, DC 20306 USA. NR 25 TC 17 Z9 21 U1 1 U2 5 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2001 VL 25 IS 7 BP 504 EP 514 PG 11 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 478JY UT WOS:000171344300004 PM 11599592 ER PT J AU Spanbauer, AC Casseday, S Davoudzadeh, D Preston, KL Huestis, MA AF Spanbauer, AC Casseday, S Davoudzadeh, D Preston, KL Huestis, MA TI Detection of opiate use in a methadone maintenance treatment population with the CEDIA (R) 6-acetyl morphine and CEDIA DAU opiate assays SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID ABSTINENCE REINFORCEMENT; HEROIN; URINE; DRUG C1 NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Microgenics Corp, Fremont, CA USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 10 TC 9 Z9 10 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2001 VL 25 IS 7 BP 515 EP 519 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 478JY UT WOS:000171344300005 PM 11599593 ER PT J AU Huang, W Moody, DE Andrenyak, DM Smith, EK Foltz, RL Huestis, MA Newton, JF AF Huang, W Moody, DE Andrenyak, DM Smith, EK Foltz, RL Huestis, MA Newton, JF TI Simultaneous determination of Delta(9)-tetrahydrocannabinol and 11-nor-9-Carboxy-Delta(9)-tetrahydrocannabinol in human plasma by solid-phase extraction and gas chromatography-negative ion chemical ionization-mass spectrometry SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CANNABINOID RECEPTOR; WHOLE-BLOOD; DELTA-9-TETRAHYDROCANNABINOL THC; ANTAGONIST; STABILITY; MARIJUANA; DRIVERS; SMOKING; DRUGS; TETRAHYDROCANNABINOL C1 Univ Utah, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Sanofi Synthelabo Pharmaceut Inc, Malvern, PA 19355 USA. RP Moody, DE (reprint author), Univ Utah, Ctr Human Toxicol, 20 S 2030 E,Rm 490, Salt Lake City, UT 84112 USA. FU NIDA NIH HHS [N01DA-6-7052] NR 31 TC 36 Z9 40 U1 1 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2001 VL 25 IS 7 BP 531 EP 537 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 478JY UT WOS:000171344300008 PM 11599596 ER PT J AU Lyons, TP Okano, CK Kuhnle, JA Bruins, MR Darwin, WD Moolchan, ET Huestis, MA AF Lyons, TP Okano, CK Kuhnle, JA Bruins, MR Darwin, WD Moolchan, ET Huestis, MA TI A comparison of Roche Kinetic Interaction of Microparticles in Solution (KIMS (R)) assay for cannabinoids and GC-MS analysis for 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID EMIT-II; IMMUNOASSAY; METABOLITES; MARIJUANA; ONLINE; URINE C1 Tripler Army Med Ctr, Forens Toxicol Drug Testing Lab, Honolulu, HI 96859 USA. NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Lyons, TP (reprint author), Tripler Army Med Ctr, Forens Toxicol Drug Testing Lab, Honolulu, HI 96859 USA. NR 15 TC 5 Z9 6 U1 0 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2001 VL 25 IS 7 BP 559 EP 564 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 478JY UT WOS:000171344300012 PM 11599600 ER PT J AU Dixon, DM AF Dixon, DM TI Coccidioides immitis as a Select Agent of bioterrorism SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article; Proceedings Paper CT 2nd Conference on Dangerous Pathogens 2000 CY SEP 04-07, 2000 CL UNIV PLYMOUTH, PLYMOUTH, ENGLAND HO UNIV PLYMOUTH AB Coccidioides immitis is the most virulent of the primary fungal pathogens of humans and other animals. As such, it is the only fungal aetiological agent designated as Biosafety Level 3 in Biosafety in Microbiological and Biomedical Laboratories, 3rd edn (Department of Health and Human Services 1993; http://www.nih.gov/od/ors/ds/pubs/bmbl/index.htm). Natural infection occurs via inhalation of aerosolized conidia from a primary environmental focus, and can also occur from traumatic implantation. In both instances, analogies can be drawn to Bacillus anthracis. Similarly, C. immitis was listed amongst the 'Select Agents' in the Final rule on Additional Requirements for Facilities Transferring or Receiving Select Agents in response to the US Antiterrorism and Effective Death Penalty Act of 1996, (Department of Health and Human Services 1996). Natural infection can resolve spontaneously following a primary pulmonary, flu-like episode, or can progress to a serious and life-threatening local or disseminated disease. Natural or experimental infection, appears to confer immunity, and efforts are underway to develop a protective vaccine. Such would be a welcomed addition to the limited antifungal armamentarium. C1 NIAID, Bacteriol & Mycol Branch, Div Microbiol & Infect Dis, NIH, Bethesda, MD USA. RP Dixon, DM (reprint author), NIAID, Bacteriol & Mycol Branch, Div Microbiol & Infect Dis, NIH, Bethesda, MD USA. NR 16 TC 35 Z9 37 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD OCT PY 2001 VL 91 IS 4 BP 602 EP 605 DI 10.1046/j.1365-2672.2001.01496.x PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 477YZ UT WOS:000171315300006 PM 11576294 ER PT J AU Sternberg, KJ Lamb, ME Esplin, PW Orbach, Y Mitchell, S AF Sternberg, KJ Lamb, ME Esplin, PW Orbach, Y Mitchell, S TI Use of a structured investigative protocol enhances young children's responses to free-recall prompts in the course of forensic interviews SO JOURNAL OF APPLIED PSYCHOLOGY LA English DT Article ID ANATOMICALLY DETAILED DOLLS; SEXUAL ABUSE VICTIMS; PEDIATRIC EXAMINATION; EYEWITNESS TESTIMONY; PRESCHOOL-CHILDREN; UTTERANCE TYPES; MEMORY; WITNESSES; QUESTION; STYLE AB One hundred alleged victims of child sexual abuse (ages 4-12 years; M = 8.1 years) were interviewed by police investigators about their alleged experiences. Half of the children were interviewed using the National Institute of Child Health and Human Development's structured interview protocol, whereas the other children-matched with respect to their age, relationship with the alleged perpetrator, and seriousness of the alleged offenses-were interviewed using standard interview practices. Protocol-guided interviews elicited more information using open-ended prompts and less information using option-posing and suggestive questions than did standard interviews; there were no age differences in the amount of information provided in response to open-ended invitations. In 89% of the protocol interviews, children made their preliminary allegations in response to open-ended prompts, compared with 36% in the standard interviews. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. Salt Lake Cty Childrens Justice Ctr, Salt Lake City, UT USA. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, 6705 Rockledge Dr,Suite 8048, Bethesda, MD 20892 USA. EM michael_lamb@nih.gov NR 55 TC 124 Z9 124 U1 2 U2 18 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-9010 EI 1939-1854 J9 J APPL PSYCHOL JI J. Appl. Psychol. PD OCT PY 2001 VL 86 IS 5 BP 997 EP 1005 DI 10.1037/0021-9010.86.5.997 PG 9 WC Psychology, Applied; Management SC Psychology; Business & Economics GA 476YN UT WOS:000171256500017 PM 11596815 ER PT J AU Tilly, K Elias, AF Errett, J Fischer, E Iyer, R Schwartz, I Bono, JL Rosa, P AF Tilly, K Elias, AF Errett, J Fischer, E Iyer, R Schwartz, I Bono, JL Rosa, P TI Genetics and regulation of chitobiose utilization in Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; CIRCULAR PLASMID; PERITROPHIC MEMBRANE; ESCHERICHIA-COLI; IXODES-DAMMINI; TICKS; CULTIVATION; EXPRESSION; CLONING; VECTORS AB Borrelia burgdorferi spends a significant proportion of its life cycle within an ixodid tick, which has a cuticle containing chitin, a polymer of N-acetylglucosamine (GlcNAc). The B. burgdorferi celA, celB, and celC genes encode products homologous to transporters for cellobiose and chitobiose (the dimer subunit of chitin) in other bacteria, which could be useful for bacterial nutrient acquisition during growth within ticks. We found that chitobiose efficiently substituted for GlcNAc during bacterial growth in culture medium. We inactivated the celB gene, which encodes the putative membrane-spanning component of the transporter, and compared growth of the mutant in various media to that of its isogenic parent. The mutant was no longer able to utilize chitobiose, while neither the mutant nor the wild type can utilize cellobiose. We propose renaming the three genes chbA, chbB, and chbC, since they probably encode a chitobiose transporter. We also found that the chbC gene was regulated in response to growth temperature and during growth in medium lacking GlcNAc. C1 NIAID, NIH, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. NIAID, NIH, Rocky Mt Labs, Microscopy Branch, Hamilton, MT 59840 USA. RP Tilly, K (reprint author), 903 S,4th St, Hamilton, MT 59840 USA. FU NIAID NIH HHS [R01 AI045801, R01 AI045801-04, AI45801]; NIAMS NIH HHS [R01 AR041511, AR41511] NR 33 TC 43 Z9 44 U1 0 U2 3 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 OCT PY 2001 VL 183 IS 19 BP 5544 EP 5553 DI 10.1128/JB.183.19.5544-5553.2001 PG 10 WC Microbiology SC Microbiology GA 471ZQ UT WOS:000170958900011 PM 11544216 ER PT J AU Cabrera, JE Jin, DJ AF Cabrera, JE Jin, DJ TI Growth phase and growth rate regulation of the rapA gene, encoding the RNA polymerase-associated protein RapA in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TRANSCRIPT CLEAVAGE FACTORS; RATE-DEPENDENT REGULATION; STRINGENT CONTROL; BACTERIAL HOMOLOG; BINDING-SITES; SIGMA-FACTOR; FIS PROTEIN; PROMOTER; INITIATION; EXPRESSION AB The Escherichia coli rapA gene encodes the RNA polymerase (RNAP)-associated protein RapA, which is a bacterial member of the SWI/SNF helicase-like protein family. We have studied the rapA promoter and its regulation in vivo and determined the interaction between RNAP and the promoter in vitro. We have found that the expression of rapA is growth phase dependent, peaking at the early log phase. The growth phase control of rapA is determined at least by one particular feature of the promoter: it uses CTP as the transcription-initiating nucleotide instead of a purine, which is used for most E. coli promoters. We also found that the rapA promoter is subject to growth rate regulation in vivo and that it forms intrinsic unstable initiation complexes with RNAP in vitro. Furthermore, we have shown that a GC-rich or discriminator sequence between the -10 and +1 positions of the rapA promoter is responsible for its growth rate control and the instability of its initiation complexes with RNAP. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Jin, DJ (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 2B16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 20 Z9 21 U1 1 U2 3 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 OCT PY 2001 VL 183 IS 20 BP 6126 EP 6134 DI 10.1128/JB.183.20.6126-6134.2001 PG 9 WC Microbiology SC Microbiology GA 477DD UT WOS:000171267100038 PM 11567013 ER PT J AU Chernomordik, V Gandjbakhche, A Lepore, M Esposito, R Delfino, I AF Chernomordik, V Gandjbakhche, A Lepore, M Esposito, R Delfino, I TI Depth dependence of the analytical expression for the width of the point spread function (spatial resolution) in time-resolved transillumination SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical imaging; photon migration; point spread functions; spatial resolution; time of flight; breast imaging ID OPTICAL IMAGING-SYSTEM; DIFFUSION EQUATION; CONTRAST FUNCTIONS; SCATTERING MEDIA; PERFORMANCE; MEDICINE AB Simple analytical expressions for the point spread function (PSF) at different depths can save computation time and improve the performance of inverse algorithms for optical imaging. In particular, application of such formulas simplifies quantification of the optical characteristics of tissue abnormalities inside highly scattering media. Earlier it was shown within the random walk theory framework that the PSF for time-resolved transillumination imaging through a highly scattering slab is well represented by a Gaussian. We have experimentally validated a simple formula of the random walk model for the effective width of this Gaussian, as a function of time delay, at different depths of the target. Presented analysis of published experimental data, concerning effective width of the PSF, for a slab of considerably smaller thickness also demonstrates good agreement between the data and predictions of our model. This PSF width determines spatial resolution of the time-resolved imaging and is widely discussed in the literature. (C) 2001 Society of Photo-Optical Instrumentation Engineers. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Ist Nazl Fis Mat, Unita Napoli, Dipartimento Sci Fis, I-80126 Naples, Italy. RP Chernomordik, V (reprint author), NICHHD, NIH, Bldg 12A,Rm 2041,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Esposito, Rosario/G-7472-2012; OI Esposito, Rosario/0000-0002-3834-6045; LEPORE, Maria/0000-0003-2743-5904 NR 14 TC 22 Z9 22 U1 0 U2 1 PU SPIE-INT SOCIETY OPTICAL ENGINEERING 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 OCT PY 2001 VL 6 IS 4 BP 441 EP 445 DI 10.1117/1.1412225 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 505DF UT WOS:000172895700008 PM 11728203 ER PT J AU Collins, MT Riminucci, M Corsi, A Murphey, MD Wientroub, S Bianco, P Robey, PG AF Collins, MT Riminucci, M Corsi, A Murphey, MD Wientroub, S Bianco, P Robey, PG TI Angiomatosis of bone with localized mineralization defect SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Aquila, Dept Expt Med, Div Pathol, I-67100 Laquila, Italy. Univ La Sapienza, Dept Expt Med, Div Pathol, Rome, Italy. Armed Forces Inst Pathol, Dept Radiol Pathol, Washington, DC 20306 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. Univ Maryland, Med Ctr, Dept Diagnost Radiol, Baltimore, MD 21201 USA. Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, Dept Pediat Orthoped Surg, IL-64239 Tel Aviv, Israel. RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 8 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 2001 VL 16 IS 10 BP 1750 EP 1753 DI 10.1359/jbmr.2001.16.10.1750 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 475BP UT WOS:000171142000003 PM 11585337 ER PT J AU Abad, V Chrousos, GP Reynolds, JC Nieman, LK Hill, SC Weinstein, RS Leong, GM AF Abad, V Chrousos, GP Reynolds, JC Nieman, LK Hill, SC Weinstein, RS Leong, GM TI Glucocorticoid excess during adolescence leads to a major persistent deficit in bone mass and an increase in central body fat SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoporosis; Cushing's syndrome; peak bone mass; body composition; glucocorticoids ID GROWTH-HORMONE DEFICIENCY; CUSHINGS-DISEASE; MINERAL DENSITY; INDUCED OSTEOPOROSIS; PHYSICAL-ACTIVITY; SURGICAL CURE; CHILDREN; ADULTS; PUBERTY; WOMEN AB Endogenous Cushing's syndrome (CS) in children causes growth retardation, decreased bone mass, and increased total body fat. No prospective controlled studies have been performed in children to determine the long-term sequelae of CS on peak bone mass and body composition. A 15-year-old girl with Cushing disease (CD), and her healthy identical co-twin, were followed for 6 years after the CD was cured. At the 6-year follow-up both twins had areal bone mineral density (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA) and three-dimensional quantitative computed tomography (3DQCT). Z scores for height, weight, and body mass index (BMI) were -2.3, -0.8 and 0.2, and 1.2, 0.2, and -0.6, in the twin with CD and her co-twin, respectively. In the twin with CD, areal BMD and bone mineral apparent density (BMAD) at different sites varied from 0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was -0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was 42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin, respectively. The relationship between total body fat and L2-L4 BMAD was inverse in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and direct (p < 0.001). In the twin with CD, despite cure, there was a persistent deficit in bone mass and increase in total and visceral body fat. These observations suggest that hypercortisolism (exogenous or endogenous) during adolescence may have persistent adverse effects on bone and fat mass. C1 Garvan Inst Med Res, Pituitary Res Unit, Sydney, NSW 2010, Australia. Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW 2010, Australia. Natl Inst Child Hlth & Human Dev, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD USA. Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD USA. Univ Arkansas Med Sci, Ctr Osteoporosis & Metabol Bone Dis, Div Endocrinol & Metabol, Dept Internal Med, Little Rock, AR USA. RP Garvan Inst Med Res, Pituitary Res Unit, 384 Victoria St, Sydney, NSW 2010, Australia. NR 40 TC 33 Z9 33 U1 1 U2 2 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2001 VL 16 IS 10 BP 1879 EP 1885 DI 10.1359/jbmr.2001.16.10.1879 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 475BP UT WOS:000171142000019 PM 11585353 ER PT J AU Neelapu, SS Baskar, S Kwak, LW AF Neelapu, SS Baskar, S Kwak, LW TI Detection of keyhole limpet hemocyanin (KLH)-specific immune responses by intracellular cytokine assay in patients vaccinated with idiotype-KLH vaccine SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 24th Congress of the German-Cancer-Society CY MAR 20-23, 2000 CL BERLIN, GERMANY SP German Cancer Soc ID T-CELL ACTIVATION; FLOW-CYTOMETRY; INDUCTION; LYMPHOMA; ANTIBODY; SURFACE AB Keyhole limpet hemocyanin (KLH) has been used as an immune potentiator to enhance antigen-specific responses against haptens and weak antigens including self-antigens. In the present study, we describe the optimization of the intracellular cytokine response to KLH in peripheral blood mononuclear cells (PBMC) of lymphoma and myeloma patients that were vaccinated with tumor-specific immunoglobulin (ld) conjugated to KLH. Addition of anti-CD28 antibody significantly enhanced cytokine-producing CD4(+) T cells. While fresh PBMC showed maximal cytokine response 14 h after antigen stimulation, the frozen PBMC showed maximal cytokine responses by 24 h. Supplementation or the culture medium with fetal bovine serum gave a better signal-to-noise ratio than human AB serum in the intracellular detection of cytokines. The intracellular cytokine responses correlated with the cytokine measurements by enzyme-linked immunosorbent assay (ELISA). Together these results indicate that the intracellular cytokine assay is very helpful to measure antigen-specific immune responses, and in subsequent studies, we have utilized this sensitive technique to detect immune responses against tumor antigens such as idiotype. C1 NCI, Expt Transplantat & Immunol Branch, Frederick, MD 21702 USA. NCI, ETI Branch, Frederick, MD 21702 USA. SAIC, Frederick, MD USA. RP Kwak, LW (reprint author), NCI, Expt Transplantat & Immunol Branch, Bldg 567,Room 205, Frederick, MD 21702 USA. NR 15 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD OCT PY 2001 VL 127 SU 2 BP R14 EP R19 DI 10.1007/BF01470994 PG 6 WC Oncology SC Oncology GA 506KD UT WOS:000172968800004 PM 11768619 ER PT J AU Danen, EHJ Yamada, KM AF Danen, EHJ Yamada, KM TI Fibronectin, integrins, and growth control SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID FOCAL ADHESION KINASE; CELL-CYCLE PROGRESSION; RECEPTOR TYROSINE KINASES; ACTIVATED PROTEIN-KINASE; JUN NH2-TERMINAL KINASE; BREAST-CANCER CELLS; SRC FAMILY KINASES; MAP KINASE; SIGNAL-TRANSDUCTION; ADAPTER PROTEIN AB Cell proliferation is controlled not only by soluble mitogens but also by components of the extracellular matrix (ECM) such as fibronectin, to which cells adhere via the integrin family of transmembrane receptors. Input from both growth factor receptors and integrins is required to stimulate progression through the G1 phase of the cell cycle, via induction of G1 cyclins and suppression of inhibitors of the G1 cyclin-dependent kinases. Extensive crosstalk takes place between integrin and growth factor receptor signaling pathways, and mitogenic signaling is weak and transient in the absence of integrin-mediated cell adhesion. In normal untransformed cells, all of the important mitogenic signal transduction cascades, namely those downstream of the Ras and Rho family small GTPases and the phosphoinositicle 3-OH kinase-PKB/Akt pathway, are regulated by integrin-mediated cell adhesion. As a result, these cells are anchorage-dependent for growth. In contrast, constitutive activity of each of these pathways has been reported in cancer cells, which not only reduces their mitogen dependence but also allows these cells to grow in an anchorage-independent fashion. J. Cell. Physiol. 189: 1-13, 2001. (C) 2001 Wiley-Liss, Inc. C1 Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Danen, EHJ (reprint author), Netherlands Canc Inst, Div Cell Biol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. NR 169 TC 322 Z9 330 U1 4 U2 20 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2001 VL 189 IS 1 BP 1 EP 13 DI 10.1002/jcp.1137 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 470ND UT WOS:000170877300001 PM 11573199 ER PT J AU Gronthos, S Franklin, DM Leddy, HA Robey, PG Storms, RW Gimble, JM AF Gronthos, S Franklin, DM Leddy, HA Robey, PG Storms, RW Gimble, JM TI Surface protein characterization of human adipose tissue-derived stromal cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN BONE-MARROW; MESENCHYMAL PROGENITOR CELLS; SMOOTH-MUSCLE DIFFERENTIATION; ADULT HUMAN BONE; MONOCLONAL-ANTIBODY; STEM-CELLS; ADHESION MOLECULE; PRECURSOR CELLS; ALKALINE-PHOSPHATASE; LYMPHO-HEMATOPOIESIS AB Human bone marrow stromal cells are a multipotent population of cells capable of differentiating into a number of mesodermal lineages as well as supporting hematopoeisis. Their distinct protein and gene expression phenotype is well characterized in the literature. Human adipose tissue presents an alternative source of multipotent stromal cells. In this study, we have defined the phenotype of the human adipose tissue-derived stromal cells in both the differentiated and undifferentiated states. Flow cytometry and immunohistochemistry show that human adipose tissue-derived stromal cells have a protein expression phenotype that is similar to that of human bone marrow stromal cells. Expressed proteins include CD9, CD10, CD13, CD29, CD34, CD44, CD 49(d), CD 49(e), CD54, CD55, CD59, CD105, CD106, CD146, and CD166. Expression of some of these proteins was further confirmed by PCR and immunoblot detection. Unlike human bone marrow-derived stromal cells, we did not detect the STRO-1 antigen on human adipose tissue-derived stromal cells. Cells cultured under adipogenic conditions uniquely expressed C/EBP alpha and PPAR delta, two transcriptional regulators of adipogenesis. Celts cultured under osteogenic conditions were more likely to be in the proliferative phases of the cell cycle based on flow cytometric analysis of PCNA and Ki67. The similarities between the phenotypes of human adipose tissue-derived and human bone marrow-derived stromal cells could have broad implications for human tissue engineering. J. Cell. Physiol. 189: 54-63, 2001. (C) 2001 Wiley-Liss, Inc. C1 Artecel Sci Inc, Durham, NC 27703 USA. NIDCR, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. Zen Bio Inc, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Dept Biomed Engn, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Gimble, JM (reprint author), Artecel Sci Inc, 801 Capitola Dr,Suite F, Durham, NC 27703 USA. RI Suzu, Shinya/F-5786-2013; Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 53 TC 607 Z9 706 U1 4 U2 40 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2001 VL 189 IS 1 BP 54 EP 63 DI 10.1002/jcp.1138 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 470ND UT WOS:000170877300006 PM 11573204 ER PT J AU Lam, K Zhang, LF Yamada, KM Lafrenie, RM AF Lam, K Zhang, LF Yamada, KM Lafrenie, RM TI Adhesion of epithelial cells to fibronectin or collagen I induces alterations in gene expression via a protein kinase C-dependent mechanism SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RAT EMBRYO FIBROBLASTS; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; ANCHORAGE DEPENDENCE; DISTINCT MECHANISMS; CYCLE PROGRESSION; ENDOTHELIAL-CELLS; PLASMA-MEMBRANE; SALIVARY-GLAND AB Adhesion of human salivary gland (HSG) epithelial cells to fibronectin- or collagen I gel-coated substrates, mediated by beta1 integrins, has been shown to upregulate the expression of more than 30 genes within 3-6 h. Adhesion of HSG cells to fibronectin or collagen I for 6 h also enhanced total protein kinase C (PKC) activity by 1.8-2.3-fold. HSG cells expressed PKC-alpha, gamma, delta, epsilon, mu, and zeta. Adhesion of HSG cells to fibronectin or collagen I specifically activated PKC-gamma and PKC-delta. Cytoplasmic PKC-gamma and PKC-delta became membrane-associated, and immunoprecipitated PKC-gamma and PKC-delta kinase activities were enhanced 2.5-4.0-fold in HSG cells adherent to fibronectin or collagen I. In addition, adhesion of fibronectin-coated beads to HSG monolayers co-aggregated beta1 integrin and PKC-gamma and PKC-delta but not other PKC isoforms. Thus, integrin-dependent adhesion of HSG cells to fibronectin or collagen I activated PKC-gamma and PKC-delta. The role of this PKC upregulation on adhesion-responsive gene expression was then tested. HSG cells were treated with the specific PKC inhibitor bisindolylmaleimide I, cultured on non-precoated, fibronectin- or collagen I-coated substrates, and analyzed for changes in adhesion-responsive gene expression. Bisindolylmaleimide I strongly inhibited the expression of seven adhesion-responsive genes including calnexin, decorin, S-adenosylmethionine decarboxylase, steroid sulfatase, and 3 mitochondrial genes. However, the expression of two adhesion-responsive genes was not affected by bisindolylmaleimide I. Treatment with bisindolylmaleimide I did not affect cell spreading and did not significantly affect the actin cytoskeleton. These data suggest that adhesion of HSG cells to fibronectin or collagen I induces PKC activity and that this induction contributes to the upregulation of a variety of adhesion-responsive genes. J. Cell. Physiol. 189: 79-90, 2001. C 2001 Wiley-Liss, Inc. C1 NE Ontario Reg Canc Ctr, Sudbury, ON P3E 5J1, Canada. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Lafrenie, RM (reprint author), NE Ontario Reg Canc Ctr, 41 Ramsey Lake Rd, Sudbury, ON P3E 5J1, Canada. NR 74 TC 13 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 2001 VL 189 IS 1 BP 79 EP 90 DI 10.1002/jcp.1142 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 470ND UT WOS:000170877300009 PM 11573207 ER PT J AU Chan, JCC Eckert, H AF Chan, JCC Eckert, H TI C-rotational echo double resonance: Heteronuclear dipolar recoupling with homonuclear dipolar decoupling SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; MULTIPLE-SPIN SYSTEMS; H-1/AL-27 TRAPDOR NMR; DISTANCE DETERMINATIONS; PULSE SEQUENCE; ALUMINOBORATE GLASSES; SODIUM ALUMINOBORATE; CATION DISTRIBUTIONS; SITE CONNECTIVITIES AB We propose a series of heteronuclear dipolar recoupling schemes which are insensitive to the presence of homonuclear dipolar interaction. The schemes are based on the pulse symmetry CNnnu. The optimum choices for N, n, and nu were determined with the help of Average Hamiltonian Theory (AHT). The lowest-order AHT shows that the pulse symmetries with n=N and nu =1 are suitable for the recoupling of heteronuclear dipolar interactions. Together with the parabolic approximation of the dephasing curve, we develop a powerful experimental strategy to characterize the van Vleck's second moments for multiple-spin systems under conditions of very fast magic-angle spinning. These new pulse symmetries are superior to the rotational echo double resonance (REDOR) method and other recoupling schemes as far as the interference of the homonuclear dipolar interaction is concerned. Preliminary experimental results on crystalline model compounds are given to illustrate the utility of our approach. (C) 2001 American Institute of Physics. C1 Univ Munster, Inst Phys Chem, D-48149 Munster, Germany. RP Chan, JCC (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Chan, Jerry/F-8075-2010 OI Chan, Jerry/0000-0002-5108-4166 NR 57 TC 36 Z9 37 U1 2 U2 7 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 1 PY 2001 VL 115 IS 13 BP 6095 EP 6105 DI 10.1063/1.1394217 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 472ZP UT WOS:000171015100044 ER PT J AU Liu, XG Li, RC AF Liu, XG Li, RC TI Effects of repeated rifabutin administration on the pharmacokinetics of intravenous and oral ciprofloxacin in mice SO JOURNAL OF CHEMOTHERAPY LA English DT Article DE pharmacokinetics; rifabutin; ciprofloxacin; drug interaction; bioavailability; mice ID DRUG-METABOLISM; REDISTRIBUTION; ELIMINATION; RIFAMPICIN; RAT AB The combination of rifabutin and ciprofloxacin is potentially useful for the treatment of disseminated Mycobacterium avium-intracellulare (MAC) diseases in HIV-infected patients. Rifabutin is a metabolic enzyme inducer structurally similar to its predecessor, rifampin. Using a mouse model, the effects of repeated exposure of rifabutin on the pharmacokinetics of ciprofloxacin after intravenous (i.v.) and oral (p.o.) dosing were investigated in the present study. Results showed that repeated exposure of rifabutin, relative to control, caused a 16% increase in the plasma clearance (CL) of ciprofloxacin after i.v. dosing (4.19 vs. 4.87 L/h/kg). Estimates of elimination half-life (T1/2) were not affected by rifabutin (control: 0.81 vs. rifabutin pretreated: 1.18 h). The data obtained after oral dosing showed that repeated rifabutin dosing caused a significant reduction in the maximal plasma concentration (Cmax: 1.34 vs. 0.91 mug/mL) and a longer time to Cmax (Tmax: 0.17 vs. 0.33 h). These changes might be in part attributable to the increase in oral clearance (CL/F) by 18%. With or without rifabutin pretreatment, the T1/2 estimates of ciprofloxacin for p.o. dosing were similar (2.37-2.58 h) and were approximately twice as long as those obtained after i.v. dosing. Since the changes in systemic exposure as a result of rifabutin pretreatment were similar after i.v. and p.o. dosing, the oral bioavailability (F) of ciprofloxacin remained unaffected by rifabutin at approximately 38%. The effects of rifabutin on the pharmacokinetics of ciprofloxacin appear to be moderate in the mouse model which might be attributable to the absorption and distribution behavior of the quinolone antibiotic. The therapeutic implications of this interaction, if any, remain to be defined. C1 NIDDK, NIH, Bethesda, MD USA. RP Li, RC (reprint author), RW Johnson Pharmaceut Res Inst, 920 Route 202,POB 300, Raritan, NJ 08869 USA. NR 22 TC 3 Z9 3 U1 0 U2 2 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD OCT PY 2001 VL 13 IS 5 BP 563 EP 568 PG 6 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 486JZ UT WOS:000171815800013 PM 11760222 ER PT J AU Quon, MJ AF Quon, MJ TI Editorial: Limitations of the fasting glucose to insulin ratio as an index of insulin sensitivity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID MINIMAL MODEL; PREMATURE ADRENARCHE; HOMEOSTASIS MODEL; CLAMP; RESISTANCE; TOLERANCE; AMERICAN; OBESITY; GIRLS C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 8C-218,10 Ctr Dr MSC 1755, Bethesda, MD 20892 USA. EM quoran@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 33 TC 86 Z9 90 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 OCT PY 2001 VL 86 IS 10 BP 4615 EP 4617 DI 10.1210/jc.86.10.4615 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 485LG UT WOS:000171755400008 PM 11600512 ER PT J AU Weinstein, LS AF Weinstein, LS TI Editorial: The stimulatory G protein alpha-subunit gene: Mutations and imprinting lead to complex phenotypes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID HUMAN GNAS1 GENE; ALBRIGHT HEREDITARY OSTEODYSTROPHY; PSEUDOHYPOPARATHYROIDISM TYPE IB; ADENYLYL CYCLASE; ENDOCRINE; KINDREDS C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov OI Weinstein, Lee/0000-0002-1899-5152 NR 27 TC 28 Z9 31 U1 0 U2 0 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 OCT PY 2001 VL 86 IS 10 BP 4622 EP 4626 DI 10.1210/jc.86.10.4622 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 485LG UT WOS:000171755400010 PM 11600514 ER PT J AU Charmandari, E Matthews, DR Johnston, A Brook, CGD Hindmarsh, PC AF Charmandari, E Matthews, DR Johnston, A Brook, CGD Hindmarsh, PC TI Serum cortisol and 17-hydroxyprogesgterone interrelation in classic 21-hydroxylase deficiency: Is current replacement therapy satisfactory? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; 17 HYDROXYPROGESTERONE LEVELS; DEXAMETHASONE TREATMENT; PUBERTAL CHANGES; FILTER-PAPER; PLASMA; HYDROCORTISONE; SALIVARY; CHILDREN; PATTERN AB One of the main aims in the management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency is to achieve adequate suppression of the adrenal cortex with the smallest possible dose of glucocorticoid substitution. To evaluate the administration schedule of current replacement therapy regimens, we investigated the cortisol-17-hydroxyprogesterone interrelation in 36 patients (13 males and 23 females; median age, 12.3 yr; range, 6.1-18.8 yr) with salt-wasting congenital adrenal hyperplasia. As sufficient variation in 17-hydroxyprogesterone concentrations was required to allow analysis of the cortisol-17-hydroxyprogesterone interrelation, patients were divided into 2 groups depending on the adequacy of hypothalamic-pituitary-adrenal axis suppression. The first group consisted of 17 patients with suppressed 17-hydroxyprogesterone concentrations (group 1), and the second group consisted of 19 patients with nonsuppressed. 17-hydroxyprogesterone concentrations (group 2). We determined serum cortisol and 17-hydroxyprogesterone concentrations at 20-min intervals for a total of 24 h while patients were receiving their usual replacement treatment with hydrocortisone and 9 alpha -fludrocortisone. We also determined the lowest dose of dexamethasone required to suppress the 0800 h serum ACTH concentrations when ad-ministered as a single dose (0.3 or 0.5 mg/m(2)) the night before. Mean 24-h cortisol and 17-hydroxyprogesterone concentrations were 3.9 mug/dl (SD = 2.1) and 66.2 ng/dl (SD = 92.7), respectively, in group 1 and 4.1 mug/dl (SD = 2.5) and 4865.7 ng/dl (SD = 6951) in group 2. The 24-h 17-hydroxyprogesterone concentrations demonstrated circadian variation, with peak values observed between 0400-0900 h. In group 2,17-hydroxyprogesterone concentrations decreased gradually in response to the rise in cortisol concentrations during the day, but remained low during the night despite the almost undetectable cortisol concentrations between 1600-2000 h. Mean 0800 h androstenedione concentrations correlated strongly with integrated 17-hydroxyprogesterone concentrations (r = 0.81; P < 0.0001), but not with integrated cortisol concentrations. There was a significant negative correlation between cortisol and 17-hydroxyprogesterone at lag time 0 min (r = -0.187; P < 0.0001), peaking at lag time 60 min (r = -0.302; P < 0.0001), with cortisol leading 17-hydroxyprogesterone by these time intervals. Finally, 0800 h serum ACTH concentrations were sufficiently suppressed after a dexamethasone dose of 0.3 mg/m(2) in all but three patients. These findings indicate that in classic 21-hydroxylase deficiency, hydrocortisone should be administered during the period of increased hypothalamic-pituitary-adrenal axis activity, between 0400-1600 h, with the biggest dose given in the morning. Blood investigations performed as part of monitoring of congenital adrenal hyperplasia patients should include androstenedione and 17-hydroxyprogesterone concentrations determined in the morning before the administration of hydrocortisone. It should also be emphasized that blood investigations are only complementary to the overall assessment of these patients, which is primarily based on the evaluation of growth and pubertal progress. C1 UCL, London Ctr Pediat Endocrinol, London W1T 3AA, England. Radcliffe Infirm, Diabet Res Labs, Oxford OX2 6HE, England. St Bartholomews & Royal London Sch Med & Dent, Dept Clin Pharmacol, London EC1M 6BQ, England. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Hindmarsh, Peter/C-4964-2008; Charmandari, Evangelia/B-6701-2011 NR 35 TC 27 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2001 VL 86 IS 10 BP 4679 EP 4685 DI 10.1210/jc.86.10.4679 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 485LG UT WOS:000171755400021 PM 11600525 ER PT J AU Klein, KO Barnes, KM Jones, JV Feuillan, PP Cutler, GB AF Klein, KO Barnes, KM Jones, JV Feuillan, PP Cutler, GB TI Increased final height in precocious puberty after long-term treatment with LHRH agonists: The National Institutes of Health Experience SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; BONE-MINERAL DENSITY; ITALIAN STUDY-GROUP; GNRH ANALOG; BAYLEY-PINNEAU; SLOW-RELEASE; ADULT HEIGHT; GIRLS; THERAPY; BOYS AB We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3 +/- 2.1 yr old at the start of treatment and were treated with either deslorelin (4 mug/kg.d sc) or histrelin (4-10 mug/kg.d) for an average of 6.1 +/- 2.5 yr. Final height averaged 159.8 +/- 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 +/- 9.6 cm) but still significantly less than midparental height (MPH) (163.7 +/- 5.6). Final height averaged 171.1 +/- 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 +/- 14.2 cm) but still significantly less than MPH (178.3 +/- 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height SD score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Klein, KO (reprint author), 6633 Maycrest Lane, San Diego, CA 92121 USA. EM koklein@juno.com NR 40 TC 81 Z9 93 U1 0 U2 0 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 OCT PY 2001 VL 86 IS 10 BP 4711 EP 4716 DI 10.1210/jc.86.10.4711 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 485LG UT WOS:000171755400026 PM 11600530 ER PT J AU Elenkov, IJ Wilder, RL Bakalov, VK Link, AA Dimitrov, MA Fisher, S Crane, M Kanik, KS Chrousos, GP AF Elenkov, IJ Wilder, RL Bakalov, VK Link, AA Dimitrov, MA Fisher, S Crane, M Kanik, KS Chrousos, GP TI IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: Implications for autoimmune disease activity during these times SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MULTIPLE-SCLEROSIS; 1,25-DIHYDROXYVITAMIN D-3; RHEUMATOID-ARTHRITIS; CYTOKINE PRODUCTION; HUMAN PLACENTA; MESSENGER-RNA; CELL CLONES; INTERLEUKIN-12; INHIBITION; EXPRESSION AB Clinical observations indicate that some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, frequently remit during pregnancy but exacerbate, or have their onset, in the postpartum period. The immune basis for these phenomena is poorly understood. Recently, excessive production of IL-12 and TNF-alpha was causally linked to rheumatoid arthritis and multiple sclerosis. We studied 18 women with normal pregnancies in their third trimester and during the early postpartum period. We report that during the third trimester pregnancy, ex vivo monocytic IL-12 production was about 3-fold and TNF-alpha production was approximately 40% lower than postpartum values. At the same time, urinary cortisol and norepinephrine excretion and serum levels of 1,25-dihydroxyvitamin were 2- to 3-fold higher than postpartum values. As shown previously, these hormones can directly suppress IL-12 and TNF-alpha production by monocytes/macrophages in vitro. We suggest that a cortisol-, norepinephrine-, and 1,25-dihydroxyvitamin-induced inhibition and subsequent rebound of IL-12 and TNF-alpha production may represent a major mechanism by which pregnancy and postpartum alter the course of or susceptibility to various autoimmune disorders. C1 NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), Georgetown Univ, Med Ctr, Div Rheumatol Allergy & Immunol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM ije@gunet.georgetown.edu NR 33 TC 159 Z9 166 U1 0 U2 5 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 OCT PY 2001 VL 86 IS 10 BP 4933 EP 4938 DI 10.1210/jc.86.10.4933 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 485LG UT WOS:000171755400061 PM 11600565 ER PT J AU Namkung, Y Skrypnyk, N Jeong, MJ Lee, T Lee, MS Kim, HL Chin, H Suh, PG Kim, SS Shin, HS AF Namkung, Y Skrypnyk, N Jeong, MJ Lee, T Lee, MS Kim, HL Chin, H Suh, PG Kim, SS Shin, HS TI Requirement for the L-type Ca2+ channel alpha(1D) subunit in postnatal pancreatic beta cell generation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INCREASED INSULIN SENSITIVITY; DEPENDENT CALCIUM-CHANNEL; ACTIVIN RECEPTOR; FUNCTIONAL EXPRESSION; DIABETES-MELLITUS; TRANSGENIC MICE; B-CELLS; SECRETION; GROWTH; ISLETS AB Pancreatic 5 cells are the source of insulin, which directly lowers blood glucose levels in the body. Our analyses Of alpha (1D) gene-knockout (alpha (1D-/-)) mice show that the L-type calcium channel, alpha (1D), is required for proper beta cell generation in the postnatal pancreas. Knockout mice were characteristically slightly smaller than their littermates and exhibited hypoinsulinemia and glucose intolerance. However, isolated a(1D)(-/-) islets persisted in glucose sensing and insulin secretion, with compensatory overexpression of another L-type channel gene, alpha (1C). Histologically, newborn a(1D)(-/-) mice had an equivalent number of islets to wild-type mice. in contrast, adult alpha (-/-)(1D) mice showed a decrease in the number and size of islets, compared with littermate wild-type mice due to a decrease in beta cell generation. TUNEL staining showed that there was no increase in cell. death in alpha (-/-)(1D) islets, and a 5-bromo-2 ' deoxyuridine-labeling (BrdU-labeling) assay illustrated significant reduction in the proliferation rate of beta cells in alpha (-/-)(1D) islets. C1 Pohang Univ Sci & Technol, Natl Creat Res Initiat Ctr Calcium & Learning, Pohang, South Korea. Pohang Univ Sci & Technol, Dept Life Sci, Div Mol & Life Sci, Pohang, South Korea. Sungkyunkwan Univ, Coll Med, Samsung Med Ctr, Dept Med,Div Endocrinol, Seoul, South Korea. Ewha Womans Univ, Coll Med, Dept Biochem, Seoul 120750, South Korea. NIH, Genet Res Branch, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. Ulsan Univ Hosp, Dept Pathol, Ulsan, South Korea. RP Shin, HS (reprint author), Korea Inst Sci & Technol, Natl CRI Ctr Calcium & Learning, POB 131, Seoul 130650, South Korea. EM shin@kist.re.kr RI Suh, Pann-Ghill/F-3610-2010; Lee, Myung Shik/C-9606-2011 NR 48 TC 85 Z9 88 U1 0 U2 6 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 OCT PY 2001 VL 108 IS 7 BP 1015 EP 1022 DI 10.1172/JCI13310 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 478HR UT WOS:000171341400010 PM 11581302 ER PT J AU Markovic-Plese, S Cortese, I Wandinger, KP McFarland, HF Martin, R AF Markovic-Plese, S Cortese, I Wandinger, KP McFarland, HF Martin, R TI CD4(+)CD28(-) costimulation-independent T cells in multiple sclerosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MYELIN BASIC-PROTEIN; AUTOIMMUNE-DISEASE; RHEUMATOID-ARTHRITIS; CEREBROSPINAL-FLUID; PERIPHERAL-BLOOD; CTLA-4 BLOCKADE; EXPRESSION; ACTIVATION; RECEPTOR; MEMORY AB Multiple lines of evidence suggest that CD4(+) lymphocytes initiate autoimmune responses against myelin antigens in multiple sclerosis (MS). The increased frequency of activated myelin-specific cells in MS patients indicates that the activation of autoreactive cells represents a central event in the pathogenesis of the disease. We identified a CD4(+) subpopulation that is characterized phenotypically by the persistent absence of surface CD28 expression and functionally by CD28-independent activation and Th 1 cytokine secretion. Owing to their costimulation-independent activation and their expression of a full agonist signaling activation pattern, CD4(+)CD28(-) cells have the potential to initiate autoimmune responses in the central nervous system, a compartment devoid of professional antigen presenting cells. Long-term memory CD4(+)CD28(-) cells produce high amounts of IFN-gamma and maximally upregulate IFN-gamma and IL-12R beta2 chain expression in the absence of costimulation. They exhibit prominent growth characteristics and increased survival after activation, likely related to their persistent lack of CTLA-4 surface expression. The CD4(+)CD28(-) population is expanded in a subgroup of MS patients. Myelin basic protein-specific cells detected in this cell subset may play an important role in the inflammatory response within the central nervous system. C1 NINCDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Martin, R (reprint author), NINCDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr, Bethesda, MD 20892 USA. NR 42 TC 161 Z9 173 U1 1 U2 7 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 OCT PY 2001 VL 108 IS 8 BP 1185 EP 1194 DI 10.1172/JCI12516 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 483BU UT WOS:000171614500013 PM 11602626 ER PT J AU Nataraj, C Thomas, DW Tilley, SL Nguyen, M Mannon, R Koller, BH Coffman, TM AF Nataraj, C Thomas, DW Tilley, SL Nguyen, M Mannon, R Koller, BH Coffman, TM TI Receptors for prostaglandin E-2 that regulate cellular immune responses in the mouse SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LIVER-TRANSPLANTATION; ALLOGRAFT RECIPIENTS; PROSTANOID RECEPTORS; T-CELLS; MICE; CYCLOSPORINE; EXPRESSION; PROLONGATION; SUPPRESSION; ACTIVATION AB Production of prostaglandin E-2 (PGE(2)) is enhanced during inflammation, and this Lipid mediator can dramatically modulate immune responses. There are four receptors for PGE(2) (EP1-EP4) with unique patterns of expression and different coupling to intracellular signaling pathways. To identify the EP receptors that regulate cellular immune responses, we used mouse lines in which the genes encoding each of the four EP receptors were disrupted by gene targeting. Using the mixed lymphocyte response (MLR) as a model cellular immune response, we confirmed that PGE(2) has potent antiproliferative effects on wild-type responder cells. The absence of either the EP1 or EP3 receptors did not alter the inhibitory response to PGE(2) in the MLR. In contrast, when responder cells lacked the EP2 receptor, PGE(2) had little effect on proliferation. Modest resistance to PGE(2) was also observed in EP4(-/-) responder cells. Reconstitution experiments suggest that EP2 receptors primarily inhibit the MLR through direct actions on T cells. Furthermore, PGE(2) modulates macrophage function by activating the EN receptor and thereby inhibiting cytokine release. Thus, PGE(2) regulates cellular immune responses through distinct EP receptors on different immune cell populations: EP2 receptors directly inhibit T cell proliferation while EP2 and EP4 receptors regulate antigen presenting cells functions. C1 Vet Affairs Med Ctr, Durham, NC 27705 USA. Duke Univ, Div Nephrol, Durham, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. NIDDKD, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Coffman, TM (reprint author), Vet Affairs Med Ctr, Bldg 6 Nephrol,508 Fulton St, Durham, NC 27705 USA. FU NIAID NIH HHS [AI-001389]; NIDDK NIH HHS [DK-38103] NR 35 TC 221 Z9 223 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 OCT PY 2001 VL 108 IS 8 BP 1229 EP 1235 DI 10.1172/JCI13640 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 483BU UT WOS:000171614500018 PM 11602631 ER PT J AU Cheson, BD AF Cheson, BD TI Some like it hot! SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MONOCLONAL-ANTIBODY THERAPY; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; PHASE I/II TRIAL; LOW-GRADE; I-131 TOSITUMOMAB; FOLLOW-UP; ANTI-CD20; RADIOIMMUNOTHERAPY; CHEMOTHERAPY C1 NCI, Bethesda, MD 20892 USA. RP Cheson, BD (reprint author), NCI, Bethesda, MD 20892 USA. NR 29 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2001 VL 19 IS 19 BP 3908 EP 3911 PG 4 WC Oncology SC Oncology GA 476UB UT WOS:000171246200002 PM 11579110 ER PT J AU Scott, AM Lee, FT Hopkins, W Cebon, JS Wheatley, JM Liu, ZQ Smyth, FE Murone, C Sturrock, S MacGregor, D Hanai, N Inoue, K Yamasaki, M Brechbiel, MW Davis, ID Murphy, R Hannah, A Lim-Joon, M Chan, T Chong, G Ritter, G Hoffman, EW Burgess, AW Old, LJ AF Scott, AM Lee, FT Hopkins, W Cebon, JS Wheatley, JM Liu, ZQ Smyth, FE Murone, C Sturrock, S MacGregor, D Hanai, N Inoue, K Yamasaki, M Brechbiel, MW Davis, ID Murphy, R Hannah, A Lim-Joon, M Chan, T Chong, G Ritter, G Hoffman, EW Burgess, AW Old, LJ TI Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma: Results of a phase I trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MALIGNANT-MELANOMA; ANTIGENIC SYSTEMS; GD3 GANGLIOSIDE; SURFACE; CELLS; R24; CISPLATIN; BINDING; BREAST AB Purpose: KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma. Patients and Methods: Seventeen patients were entered onto one of five dose levels (1, 5, 10, 20, and 40 mg/m(2)). Patients received three infusions of KM871 at 2-week intervals, with the first infusion of KM871 trace-labeled with indium-111 (In-111) to enable assessment of biodistribution in vivo. Biopsies of metastatic melanoma sites were performed on days 7 to 10. Results: Fifteen of 17 patients completed a cycle of three infusions of KM871. No dose-limiting toxicity was observed during the trial; the maximum-tolerated dose was therefore not reached. Three patients (at the 1-, 5-, and 40-mg/m(2) dose levels) developed pain and/or erythema at tumor sites consistent with an inflammatory response. No normal tissue uptake of In-111-KM871 was observed, and tumor uptake of In-111-KM871 was observed in all lesions greater than 1.5 cm (tumor biopsy (111)KM871 uptake results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to normal tissue was 15:1. Pharmacokinetic analysis revealed a In-111-KM871 terminal half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that lasted 11 months. There was no serologic evidence of human antichimeric antibody in any patient, including one patient who received 16 infusions over a 12-month period. Conclusion: This study is the first to demonstrate the biodistribution and specific targeting of an anti-GD3 antibody to metastatic melanoma in patients. The long half-life and lack of immunogenicity of KM871 makes this antibody an attractive potential therapy for patients with metastatic melanoma. (C) 2001 by American Society of Clinical Oncology. C1 Austin & Repatriat Med Ctr, Ludwig Inst Canc Res, Melbourne Tumor Biol Branch, Melbourne, Vic, Australia. Austin & Repatriat Med Ctr, Dept Nucl Med, Melbourne, Vic, Australia. Austin & Repatriat Med Ctr, Ctr Positron Emiss Tomog, Melbourne, Vic, Australia. Austin & Repatriat Med Ctr, Dept Surg, Melbourne, Vic, Australia. Austin & Repatriat Med Ctr, Dept Anat Pathol, Melbourne, Vic, Australia. Kyowa Hakko Kogyo Co Ltd, Tokyo, Japan. NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, New York, NY USA. RP Scott, AM (reprint author), Austin & Repatriat Med Ctr, Ludwig Inst Canc Res, Tumour Targeting Program, Level 1,Harold Stokes Bldg,Studley Rd, Heidelberg, Vic 3084, Australia. RI Davis, Ian/A-1430-2012 OI Davis, Ian/0000-0002-9066-8244 NR 31 TC 45 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2001 VL 19 IS 19 BP 3976 EP 3987 PG 12 WC Oncology SC Oncology GA 476UB UT WOS:000171246200011 PM 11579119 ER PT J AU Roby, CA Dryer, DA Burstein, AH AF Roby, CA Dryer, DA Burstein, AH TI St. John's wort: Effect on CYP2D6 activity using dextromethorphan-dextrorphan ratios SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter C1 St Agnes Hosp, Dept Pharm, Baltimore, MD 21229 USA. Univ Maryland, Student & Employee Hlth Serv, Baltimore, MD 21201 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. RP Roby, CA (reprint author), St Agnes Hosp, Dept Pharm, Baltimore, MD 21229 USA. NR 15 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2001 VL 21 IS 5 BP 530 EP 532 DI 10.1097/00004714-200110000-00013 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 478HT UT WOS:000171341500013 PM 11593081 ER PT J AU Turville, SG Cameron, PU Arthos, J MacDonald, K Clark, G Hart, D Cunningham, AL AF Turville, SG Cameron, PU Arthos, J MacDonald, K Clark, G Hart, D Cunningham, AL TI Bitter-sweet symphony: defining the role of dendritic cell gp120 receptors in HIV infection SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article; Proceedings Paper CT 12th Annual Medical and Scientific Conference on the AUstralasian Society for HIV Medicine (ASHM) CY OCT 12-DEC 14, 2000 CL MELBOURNE, AUSTRALIA DE HIVgp120; dendritic cell; C Type Lectin; mannose receptor; CD4; DC-SIGN ID EPIDERMAL LANGERHANS CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; C-TYPE LECTIN; CD4+ T-CELLS; ENVELOPE GLYCOPROTEIN GP120; LYMPHOCYTE SUBSETS; INTRAVAGINAL INOCULATION; PRODUCTIVE INFECTION; SURFACE-RECEPTOR; IMMUNE-RESPONSE AB Background: Dendritic cells (DC) are believed to be one of the first cell types infected during HIV transmission. Recently a single C-type lectin receptor (CLR), DC-SIGN, has been reported to be the predominant receptor on monocyte derived DC (MDDC) rather than CD4. The role of other CLRs in HIV binding and HIV binding by CLRs on other types of DC in vivo is largely unknown. Objectives and study design: Review HIV binding to DC populations, both in vitro and in vivo, in light of the immense interest of a recently re-identified CLR called DC-SIGN. Results and conclusions: From recent work, it is clear that immature MDDC have a complex pattern of HIV gp120 binding. In contrast to other cell types gp120 has the potential to bind to several receptors on DC including CD4 and several types of C type lectin receptor, not just exclusively DC-SIGN. Given the diverse types of DC in vivo future work will need to focus on defining the receptors for HIV binding to these different cell types. Mucosal transmission of HIV in vivo targets immature sessile DCs, including Langerhans cells which lack DC-SIGN. The role of CLRs and DC-SIGN in such transmission remains to be defined. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Westmead Millennium Inst, Ctr Virus Res, Sydney, NSW 2145, Australia. Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. NIAID, NIH, Bethesda, MD 20892 USA. Mater Med Res Inst, Brisbane, Qld 4101, Australia. RP Cunningham, AL (reprint author), Westmead Millennium Inst, Ctr Virus Res, POB 412 Darcy Rd, Sydney, NSW 2145, Australia. RI Cunningham, Tony/B-7011-2013; MacDonald, Kelli/O-2722-2016; OI MacDonald, Kelli/0000-0003-3451-4221; Cameron , Paul Urquhart/0000-0002-1906-6945; Cunningham, Anthony/0000-0002-6744-5667 NR 70 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD OCT PY 2001 VL 22 IS 3 SI SI BP 229 EP 239 DI 10.1016/S1386-6532(01)00194-9 PG 11 WC Virology SC Virology GA 480DX UT WOS:000171447700003 PM 11564587 ER PT J AU Crits-Christoph, P Siqueland, L McCalmont, E Weiss, RD Gastfriend, DR Frank, A Moras, K Barber, JP Blaine, J Thase, ME AF Crits-Christoph, P Siqueland, L McCalmont, E Weiss, RD Gastfriend, DR Frank, A Moras, K Barber, JP Blaine, J Thase, ME TI Impact of psychosocial treatments on associated problems of cocaine-dependent patients SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID PSYCHOMETRIC PROPERTIES; NATIONAL-INSTITUTE; PSYCHOTHERAPY; INVENTORY; PHARMACOTHERAPY; ABUSERS AB A previous report from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (P. Crits-Christoph et al., 1999) found relatively superior cocaine and drug use outcomes for individual drug counseling plus group drug counseling compared with other treatments. Using data from that study, the authors examined the relative efficacy of 4 treatments for cocaine dependence on psychosocial and other addiction-associated problems. The 487 patients were randomly assigned to 6 months of treatment with cognitive therapy, supportive-expressive therapy, or individual drug counseling (each with additional group drug counseling), or to group drug counseling alone. Assessments were made at baseline and monthly for 6 months during the acute treatment phase, with follow-up visits at 9 and 12 months. No significant differences between treatments were found on measures of psychiatric symptoms, employment, medical, legal, family-social, interpersonal, or alcohol use problems. The authors concluded that the superiority of individual drug counseling in modifying cocaine use does not extend broadly to other addiction-associated problems. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. Brookside Hosp, Nashua, NH USA. NIDA, Treatment Res Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Crits-Christoph, P (reprint author), 3535 Market St,Room 650, Philadelphia, PA 19104 USA. OI barber, jacques/0000-0002-8762-2595 FU NIDA NIH HHS [U01-DA07673, K05-DA00168, U01-DA07693, U18 DA007090, K02-DA 00326, R01 DA012249, U01-DA07085, U01-DA07090, U01-DA07663]; NIMH NIH HHS [P30-MH-45178] NR 24 TC 42 Z9 42 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2001 VL 69 IS 5 BP 825 EP 830 DI 10.1037/0022-006X.69.5.825 PG 6 WC Psychology, Clinical SC Psychology GA 482JE UT WOS:000171572400009 PM 11680559 ER PT J AU Nguyen-Vu, PA Fackler, I Rust, A DeClue, JE Sander, CA Volkenandt, M Flaig, M Yeung, RS Wienecke, R AF Nguyen-Vu, PA Fackler, I Rust, A DeClue, JE Sander, CA Volkenandt, M Flaig, M Yeung, RS Wienecke, R TI Loss of tuberin, the tuberous-sclerosis-complex-2 gene product is associated with angiogenesis SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TARGET RAP1; SCLEROSIS; EXPRESSION; HAMARTOMAS; CARCINOMA; INTERACTS AB Background: Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder associated with an alteration of the TSC2 tumor suppressor gene which encodes for the protein product tuberin. The disease is characterized by the development of hamartomas, e.g. cutaneous angiofibromas which consist of vascular cells, interstitial cells, and normal components of the skin. The Eker rat model, an animal model of inherited cancer, has been shown to carry a mutation of TSC2. Methods: Immunohistochemical analyses of human angiofibromas were performed using antibodies directed against tuberin and angiogenic growth factors. Proliferation of human dermal microvascular endothelial cells (HDMEC) was determined after incubation with the supernatants of TSC2 (+/+) and TSC2 (-/-) rat embryonic fibroblasts (REF) that were derived from the Eker strain. Results: Loss of the expression of tuberin was observed in the interstitial cells of 13 of 39 angiofibromas. The expression of tuberin was retained in the vascular cells. In all analyzed angiofibromas, the angiogenic factors bFGF, PD-ECGF, VEGF and angiogenin were detected in the interstitial cells and/or vascular cells. Expression of PDGF-B and TGF-beta1 was weak. Tissue culture supernatants from TSC2 (-/-) REF stimulated the growth of HDMEC significantly more than supernatants from TSC2 (+/+) REF. Conclusion: A functional loss of tuberin may stimulate vascular growth. C1 Univ Munich, Dept Dermatol, D-80337 Munich, Germany. Mayo Clin & Mayo Fdn, Dept Dermatol, Rochester, MN 55905 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Div Med Genet, Seattle, WA 98195 USA. RP Wienecke, R (reprint author), Univ Munich, Dept Dermatol, Frauenlobstr 9-11, D-80337 Munich, Germany. NR 29 TC 25 Z9 27 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD OCT PY 2001 VL 28 IS 9 BP 470 EP 475 DI 10.1034/j.1600-0560.2001.028009470.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA 475MJ UT WOS:000171167800005 PM 11553313 ER PT J AU Ratliff-Schaub, K Hunt, CE Crowell, D Golub, H Smok-Pearsall, S Palmer, P Schafer, S Bak, S Cantey-Kiser, J O'Bell, R AF Ratliff-Schaub, K Hunt, CE Crowell, D Golub, H Smok-Pearsall, S Palmer, P Schafer, S Bak, S Cantey-Kiser, J O'Bell, R CA CHIME Study Grp TI Relationship between infant sleep position and motor development in preterm infants SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Developmental-and-Behavioral-Pediatrics CY SEP 24-28, 1998 CL CLEVELAND, OHIO SP Soc Dev & Behav Pediat DE infant development; sleep position; preterm infants; Bayley Scales of Infant Development; 2nd Edition (BSID-II); sudden infant death syndrome ID DEATH-SYNDROME; SIDS; RISK AB To determine whether motor development in premature infants varies according to sleep position, we evaluated 213 infants < 1750 g birth weight enrolled in the Collaborative Home Infant Monitoring Evaluation (CHIME). At 56 weeks postconceptional age (PCA), sleep position was determined by maternal report, and the Bayley Scales of Infant Development 2nd Edition (BSID-II) were performed. Infants who slept supine were less likely than infants who slept prone to receive credit for maintaining the head elevated to 45 degrees (p = .021), and infants who slept nonprone were less likely than prone sleepers to receive credit for maintaining the head elevated to 90 degrees and lowering with control (p = .001). The Psychomotor and Mental Development Indices at 56 and 92 weeks PCA were not altered by usual sleep position at 56 weeks PCA. In summary, infants sleeping supine are less able to lift the head and lower with control at 56 weeks PCA, but global developmental status was unaffected. Supine sleeping has been associated with decreased risk for sudden infant death syndrome, but compensatory strategies while awake may be needed to avoid delayed acquisition of head control. C1 NHLBI, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. RP Hunt, CE (reprint author), NHLBI, Natl Ctr Sleep Disorders Res, 2 Rockledge Ctr,Room 10038,6701 Rockledge Dr,MSC, Bethesda, MD 20892 USA. FU PHS HHS [34625, 28971, 29056, 29060, 29067, 29071, 29073] NR 28 TC 19 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2001 VL 22 IS 5 BP 293 EP 299 PG 7 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 487YE UT WOS:000171906200003 PM 11718232 ER PT J AU Long, LR Thoma, GR AF Long, LR Thoma, GR TI Landmarking and feature localization in spine x-rays SO JOURNAL OF ELECTRONIC IMAGING LA English DT Article ID VERTEBRAL MORPHOMETRY; HAND RADIOGRAPHS; DIGITAL IMAGES; SEGMENTATION; NOISE; FRACTURES; DATABASES AB The general problem of developing algorithms for the automated or computer-assisted indexing of images by structural contents is a significant research challenge. This is particularly so in the case of biomedical images, where the structures of interest are commonly irregular, overlapping, and partially occluded. Examples are the images created by digitizing film x-rays of the human cervical and lumbar spines. We have begun work toward the indexing of 17 000 such spine images for features of interest in the osteoarthritis and vertebral morphometry research communities. This work requires the segmentation of the images into vertebral structures with sufficient accuracy to distinguish pathology on the basis of shape, labeling of the segmented structures by proper anatomical name, and classification of the segmented, labeled structures into groups corresponding to high level semantic features of interest, using training data provided by biomedical experts. In this paper we provide a technical characterization of the cervical spine images and the biomedical features of interest, describe the evolving technical approach for the segmentation and indexing problem, and provide results of algorithms to acquire basic landmark data and localization of spine regions in the images. (C) 2001 SPIE and IS&T. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Natl Lib Med, 86 Rockville Pike, Bethesda, MD 20894 USA. EM long@nlm.nih.gov NR 36 TC 12 Z9 12 U1 0 U2 0 PU IS&T & SPIE PI BELLINGHAM PA 1000 20TH ST, BELLINGHAM, WA 98225 USA SN 1017-9909 EI 1560-229X J9 J ELECTRON IMAGING JI J. Electron. Imaging PD OCT PY 2001 VL 10 IS 4 BP 939 EP 956 DI 10.1117/1.1406503 PG 18 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA 495RY UT WOS:000172355200010 ER PT J AU Koch, CA Sarlis, NJ AF Koch, CA Sarlis, NJ TI The spectrum of thyroid diseases in childhood and its evolution during transition to adulthood: Natural history, diagnosis, differential diagnosis and management SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Review DE adolescence; childhood; congenital; goiter; hyperthyroidism; hypothyroidism; infancy; iodine deficiency; levothyroxine; radioactive iodine; thyroid cancer; thyroid gland; thyroid hormone; thyroid nodule; thyrotoxicosis; thyrotropin ID ACUTE SUPPURATIVE THYROIDITIS; THYROTROPIN-RECEPTOR GENE; INSTITUTES-OF-HEALTH; L-THYROXINE THERAPY; TERM FOLLOW-UP; CONGENITAL HYPOTHYROIDISM; GRAVES-DISEASE; TSH-RECEPTOR; NEONATAL HYPERTHYROIDISM; AUTOIMMUNE-THYROIDITIS AB In this contribution, we review current knowledge on the pathogenesis, diagnosis and differential diagnosis of thyroid disorders in childhood and adolescence, as well as present an update on therapy methods and management guidelines for these disorders. This overview is conceptually divided into two parts, one focusing on thyroid functional disorders, i.e. conditions leading to hyper- and hypothyroidism, and another one pertinent to structural abnormalities of the thyroid gland, i.e. nodular disorders and thyroid cancer. Currently, congenital hypothyroidism is diagnosed in a much more timely fashion rather than in the past, rendering hypothyroidism-related mental retardation and developmental deficits very rare in newborns and children and, hence, diminishing significantly its public health impact. At the same time, considerable advances have occurred in our understanding of the molecular basis of several genetic conditions affecting the thyroid gland in childhood, such as familial non-autoimmune hyperthyroidism, as well as of the pathways leading to thyroid neoplasia. (C) 2001, Editrice Kurtis. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,Rm 8D12, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 122 TC 21 Z9 24 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD OCT PY 2001 VL 24 IS 9 BP 659 EP 675 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 484WN UT WOS:000171712700004 PM 11716153 ER PT J AU Feuillan, PP Jones, JV Barnes, K Klein, KO Cutler, GB AF Feuillan, PP Jones, JV Barnes, K Klein, KO Cutler, GB TI Follow-up of children and young adults after GnRH-agonist therapy for central precocious puberty SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Editorial Material DE precocious puberty; GnRH-agonist; gonadotropin; hamartoma; deslorelin; histrelin ID GIRLS C1 NICHHD, DEB, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Feuillan, PP (reprint author), NICHHD, DEB, NIH, Bdg 10,Room 10N 262,10 Ctr Dr, Bethesda, MD 20892 USA. NR 7 TC 4 Z9 7 U1 2 U2 3 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD OCT PY 2001 VL 24 IS 9 BP 734 EP 736 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 484WN UT WOS:000171712700011 PM 11716160 ER PT J AU Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS AF Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS CA Chronic Prostatitis Collaborative TI Quality of life is impaired in men with chronic prostatitis - The chronic prostatitis collaborative research network SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the American-Urological-Association CY APR 29-MAY 04, 2000 CL ATLANTA, GEORGIA SP Amer Urol Assoc DE prostatitis; health-related quality of life ID CHRONIC NONBACTERIAL PROSTATITIS; CHRONIC ABACTERIAL PROSTATITIS; PELVIC PAIN SYNDROME; HEALTH-STATUS; OF-LIFE; SICKNESS IMPACT; SYMPTOMS; VALIDATION; DIAGNOSIS AB OBJECTIVE: Health-related quality of life (HRQOL) Impairment may be a central component of chronic prostatitis for men afflicted with this condition. Our objective was to examine HRQOL, and factors associated with HRQOL, using both general and condition-specific instruments. DESIGN: Chronic Prostatitis Cohort (CPC) study. SETTING: Six clinical research centers across the United States and Canada. PARTICIPANTS: Two hundred seventy-eight men with chronic prostatitis. MEASUREMENTS AND MAIN RESULTS: The Short Form 12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS), and the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) were measures used. CPC subjects' MCS scores (44.0 +/- 9.8) were lower than those observed in the most severe subgroups of patients with congestive heart failure and diabetes mellitus, and PCS scores (46.4 +/- 9.5) were worse than those among the general U.S. male population. Decreasing scores were seen in both domains with worsening symptom severity (P <.01). History of psychiatric disease and younger age were strongly associated with worse MCS scores, whereas history of rheumatologic disease was associated with worse PCS scores. Predictors of more severe NIH-CPSI scores included lower educational level and lower income; history of rheumatic disease was associated with higher scores. CONCLUSIONS: Men with chronic prostatitis experience impairment in the mental and physical domains of general HRQOL, as well as condition-specific HRQOL. To optimize the care of men with this condition, clinicians should consider administering HRQOL Instruments to their patients to better understand the impact of the condition on patients' lives. C1 Massachusetts Gen Hosp, Gen Med Unit, Med Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Urol Surg, Dept Surg, Boston, MA 02115 USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. Univ Penn, Med Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Northwestern Univ, Sch Med, Inst Hlth Serv & Hlth Policy Studies, Chicago, IL USA. NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Med Serv, 50 Staniford St,9th Floor, Boston, MA 02114 USA. RI Landis, J. Richard/A-9330-2010 NR 35 TC 86 Z9 88 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2001 VL 16 IS 10 BP 656 EP 662 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 485RV UT WOS:000171773400002 ER PT J AU Balk, EM Zucker, DR Engels, EA Wong, JB Williams, JW Lau, J AF Balk, EM Zucker, DR Engels, EA Wong, JB Williams, JW Lau, J TI Strategies for diagnosing and treating suspected acute bacterial sinusitis - A cost-effectiveness analysis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 1998 SMDM Conference CY SEP, 1998 CL BOSTON, MASSACHUSETTS SP SMDS DE acute bacterial sinusitis; decision analysis; cost-effectiveness analysis; Markov model ID RECOMMENDATIONS; METAANALYSIS; AMOXICILLIN; ANTIBIOTICS; MEDICINE; ADULTS; HEALTH AB OBJECTIVE: Symptoms suggestive of acute bacterial sinusitis are common. Available diagnostic and treatment options generate substantial costs with uncertain benefits. We assessed the cost-effectiveness of alternative management strategies to identify the optimal approach. DESIGN. For such patients, we created a Markov model to examine four strategies: 1) no antibiotic treatment; 2) empirical antibiotic treatment; 3) clinical criteria-guided treatment; and 4) radiography-guided treatment. The model simulated a 14-day course of illness, included sinusitis prevalence, antibiotic side effects, sinusitis complications, direct and indirect costs, and symptom severity. Strategies costing less than $50,000 per quality-adjusted life year gained were considered "cost-effective." MEASUREMENTS AND MAIN RESULTS: For mild or moderate disease, basing antibiotic treatment on clinical criteria was cost-effective in clinical settings where sinusitis prevalence is within the range of 15% to 93% or 3% to 63%, respectively. For severe disease, or to prevent sinusitis or antibiotic side effect symptoms, use of clinical criteria was cost-effective in settings with lower prevalence (below 51% or 44%, respectively); empirical antibiotics was cost-effective with higher prevalence. Sinus radiography-guided treatment was never cost-effective for initial treatment. CONCLUSIONS: Use of a simple set of clinical criteria to guide treatment Is a cost-effective strategy in most clinical settings. Empirical antibiotics are cost-effective in certain settings; however, their use results in many unnecessary prescriptions. If this resulted in increased antibiotic resistance, costs would substantially rise and efficacy would fall. Newer, expensive antibiotics are of limited value. Additional testing is not cost-effective. Further studies are needed to find an accurate, low-cost diagnostic test for acute bacterial sinusitis. C1 Tufts Univ, Sch Med, New England Med Ctr, Div Clin Care Res,Evidenced Based Practice Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, New England Med Ctr, Div Clin Decis Making Informat & Telemed, Boston, MA 02111 USA. NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. Durham VAMC, Vet Affairs HSR&D Ctr Excellence, Durham, NC USA. Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC USA. RP Lau, J (reprint author), Tufts Univ, Sch Med, New England Med Ctr, Div Clin Care Res,Evidenced Based Practice Ctr, 63,750 Washington St, Boston, MA 02111 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 FU AHRQ HHS [R25 HS009796, R25 HS09796, T32 HS000060, T32 HS00060] NR 35 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2001 VL 16 IS 10 BP 701 EP 711 DI 10.1111/j.1525-1497.2001.00429.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 485RV UT WOS:000171773400009 PM 11679039 ER PT J AU Saif, MW Allegra, CJ Greenberg, B AF Saif, MW Allegra, CJ Greenberg, B TI Bleeding diathesis in multiple myeloma SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Article ID DISORDER; INHIBITOR; PATIENT; ANTICOAGULANT; AMYLOIDOSIS; DEFICIENCY; THROMBIN AB Patients with multiple myeloma having a higher titer of serum paraproteins can manifest hemostatic abnormalities. Most of these abnormalities predispose the patient to hemorrhage. Less commonly, thrombotic complications may occur in association with paraprotein disorders. We investigated a 56-year-old female diagnosed with multiple myeloma (type IgG kappa, 59 g/L) whose coagulation profile showed an increase in thrombin time and prothrombin time. To investigate the etiology of the abnormal coagulopathy, further diagnostic studies including coagulation factor assays, platelet aggregation studies, replitase time, mixing studies using pooled normal plasma, and protamine were performed. Mixing studies demonstrated correction of the prothrombin time. Thrombin time was near-corrected but the replitase-time was not corrected by these mixing studies. After chemotherapy, the paraprotein concentration decreased (12g/L) and the coagulation results returned to normal. Patients with multiple myeloma may develop bleeding diathesis secondary to a variety of mechanisms. One such mechanism is direct inhibition of fibrin monomer aggregation due to the paraprotein, resulting in prolongation of the thrombin time and the replitase time. The failure to correct the former by the addition of protamine further augments the direct role of FAB portion of the paraprotein molecule on inhibition of fibrin monomers. C1 Wallace Tumor Inst, UAB Div Hematol Oncol, Birmingham, AL 35294 USA. NCI, NIH, Bethesda, MD 20889 USA. Chester Cty Hematol Oncol Serv, W Chester, PA 19380 USA. RP Saif, MW (reprint author), Wallace Tumor Inst, UAB Div Hematol Oncol, Room 262-A,1824 6th Ave S, Birmingham, AL 35294 USA. NR 18 TC 14 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD OCT PY 2001 VL 10 IS 5 BP 657 EP 660 DI 10.1089/152581601753193869 PG 4 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 483RC UT WOS:000171648800010 PM 11672511 ER PT J AU Cerino, A Meola, A Segagni, L Furione, M Marciano, S Triyatni, M Liang, TJ Nicosia, A Mondelli, MU AF Cerino, A Meola, A Segagni, L Furione, M Marciano, S Triyatni, M Liang, TJ Nicosia, A Mondelli, MU TI Monoclonal antibodies with broad specificity for hepatitis C virus hypervariable region 1 variants can recognize viral particles SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL EPITOPE; IMMUNE-RESPONSE; INSECT CELLS; IN-VITRO; INFECTION; CHIMPANZEES; SEQUENCE; BINDING; CD81; E2 AB The hypervariable region 1 (HVR1) of the E2 protein of hepatitis C virus (HCV) is a highly heterogeneous sequence that is promiscuously recognized by human sera via binding to amino acid residues with conserved physicochemical properties. We generated a panel of mAbs from mice immunized with HVR1 surrogate peptides (mimotopes) affinity-selected with sera from HCV-infected patients from a phage display library. A high number of specific clones was obtained after immunization with a pool of nine mimotopes, and the resulting mAbs were shown to recognize several 16- and 27-mer peptides derived from natural HVR1 sequences isolated from patients with acute and chronic HCV infection, suggesting that HVR1 mimotopes were efficient antigenic and immunogenic mimics of naturally occurring HCV variants. Moreover, most mAbs were shown to bind HVR1 in the context of a complete soluble form of the E2 glycoprotein, indicating recognition of correctly folded HVR1. In addition, a highly promiscuous mAb was able to specifically capture bona fide viral particles (circulating HCV RNA) as well as rHCV-like particles assembled in insect cells expressing structural viral polypeptides derived from an HCV la isolate. These findings demonstrate that it is possible to induce a broadly cross-reactive clonal Ab response to multiple HCV variants. In consideration of the potentially important role of HVR1 in virus binding to cellular receptor(s), such a mechanism could be exploited for induction of neutralizing Abs specific for a large repertoire of viral variants. C1 IRCCS Policlin San Mateo, Lab Riv Area Infettivol, I-27100 Pavia, Italy. IRCCS Policlin San Mateo, Dipartimento Malattie Infett, I-27100 Pavia, Italy. IRCCS Policlin San Mateo, Serv Virol, I-27100 Pavia, Italy. Univ Pavia, I-27100 Pavia, Italy. Ist Ric Biol Mol P Angeletti, I-00040 Pomezia, Italy. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Mondelli, MU (reprint author), IRCCS Policlin San Mateo, Lab Riv Area Infettivol, Via Taramelli 5, I-27100 Pavia, Italy. OI Milena, Furione/0000-0001-7328-1454 NR 38 TC 28 Z9 29 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2001 VL 167 IS 7 BP 3878 EP 3886 PG 9 WC Immunology SC Immunology GA 496JH UT WOS:000172392100043 PM 11564805 ER EF