FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Palmer, S Vuitton, D Gonzales, MJ Bassignot, A Shafer, RW AF Palmer, S Vuitton, D Gonzales, MJ Bassignot, A Shafer, RW TI Reverse transcriptase and protease sequence evolution in two HIV-1-infected couples SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; antiretroviral resistance; HIV transmission history; AF487122; AF487139 ID ACID MUTATION PATTERNS; VIRUS TYPE-1 PROTEASE; TRANSMISSION HISTORY; HIV-1; RESISTANCE; SUBTYPES; INDIVIDUALS; GAG AB We analyzed the reverse transcriptase (RT) and protease sequences of HIV-1 isolates obtained over 7 years from two couples with known transmission histories. Phylogenetic trees constructed from the sequence data reflected the known transmission histories, despite the fact that the drug resistance mutations were most consistent with the drug treatment histories. However, the RT sequences from one couple diverged by 2.9% even before therapy was begun, and three (0.9%) of 339 unrelated individuals had viruses that shared a common ancestor with sequences from the recipient member of the couple but not with sequences from the transmitter. The divergence between the first two isolates from this couple is consistent with a pre-transmission interval during which the transmitter developed a heterogeneous virus population. The closeness between the three controls and the recipient's first RT sequence may indicate slower evolution on the branches of the control sequences. Although the RT and protease genes contain phylogenetic information, they are suboptimal for reconstructing transmission history because the genetic distance between RT and protease isolates from unrelated individuals may occasionally approximate the distance between RT and protease isolates from related individuals. C1 NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. Univ Franche Comte, Ctr Hosp Univ, F-25030 Besancon, France. Stanford Univ, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. RP Palmer, S (reprint author), NCI, HIV Drug Resistance Program, NIH, 1050 Boyles St,Bldg 535,Room 109, Frederick, MD 21702 USA. FU NIAID NIH HHS [R01 AI046148-08, R01 AI046148] NR 18 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD NOV 1 PY 2002 VL 31 IS 3 BP 285 EP 290 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 612NR UT WOS:000179082800003 PM 12439203 ER PT J AU Blair, RJR Mitchell, DGV Richell, RA Kelly, S Leonard, A Newman, C Scott, SK AF Blair, RJR Mitchell, DGV Richell, RA Kelly, S Leonard, A Newman, C Scott, SK TI Turning a deaf ear to fear: Impaired recognition of vocal affect in psychopathic individuals SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID NEURAL RESPONSES; PERSONALITY; EMOTION; EXPRESSIONS; AMYGDALA; CHILDREN AB The processing of emotional expressions is fundamental for normal socialization and interaction. Reduced responsiveness to the expressions of sadness and fear has been implicated in the development of psychopathy (R. J. R. Blair, 1995). The current study investigates the ability of adult psychopathic individuals to process vocal affect. Psychopathic and nonpsychopathic adults, defined by the Hare Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991), were presented with neutral words spoken with intonations conveying happiness, disgust, anger, sadness, and fear and were asked to identify the emotion of the speaker on the basis of prosody. The results indicated that psychopathic inmates were particularly impaired in the recognition of fearful vocal affect. These results are interpreted with reference to the low-fear and violence inhibition mechanism models of psychopathy. C1 NIMH, Mood & Anxiety Disorders Program, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA. UCL, Inst Cognit Neurosci, London, England. UCL, Dept Psychol, London, England. Keele Univ, Dept Psychol, Keele, Staffs, England. HMP Wormwood Scrubs, Dept Psychol, London, England. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Disorders Program, Unit Affect Cognit Neurosci, 15K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov RI Scott, Sophie/A-1843-2010 OI Scott, Sophie/0000-0001-7510-6297 FU Wellcome Trust [090961] NR 23 TC 96 Z9 98 U1 1 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2002 VL 111 IS 4 BP 682 EP 686 DI 10.1037//0021-843X.111.4.682 PG 5 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 610BV UT WOS:000178941600017 PM 12428783 ER PT J AU Angst, J Gamma, A Sellaro, R Zhang, HP Merikangas, K AF Angst, J Gamma, A Sellaro, R Zhang, HP Merikangas, K TI Toward validation of atypical depression in the community: results of the Zurich cohort study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE atypical depression; prevalence; comorbidity; validity; gender ID CHRONIC FATIGUE SYNDROME; BIPOLAR II DISORDER; LATENT CLASS ANALYSIS; MAJOR DEPRESSION; DSM-IV; NEUROVEGETATIVE SYMPTOMS; OXIDASE-INHIBITORS; SOMATIC SYMPTOMS; ANXIETY STATES; CLINICAL-TRIAL AB Aims: This paper (1) examines the validity of the atypical subtype of depression in a community-based longitudinal cohort study, (2) presents estimates of the prevalence and sex differences of DSM-IV atypical depression and a newly more broadly defined atypical syndrome in the community and (3) compares the clinical correlates and treatment patterns of those with atypical depression with other depressives. Methods: The Zurich cohort study is comprised of 591 subjects selected from a population-based cohort of young adults representative of the canton of Zurich in Switzerland, who were screened in 1978 with the Symptom Checklist 90-R [L.R. Derogatis (1977)] and followed prospectively with five interviews between 1979 and 1993. Atypical depression was defined on a spectrum ranging from atypical major to minor to atypical depressive symptoms alone. Results: The rate of DSM-lV atypical major depressive episodes in this community is 4.8% and for major atypical depression syndrome is 7.3%. Whereas there was no marked sex difference for nonatypical features, there was a significant female preponderance for DSM-lV and broadly defined atypical depressive subtypes. Systematic investigation of the diagnostic criteria for atypical depression revealed that a nonhierarchical definition of atypical depression with respect to mood reactivity yielded as valid a syndromic definition as the current hierarchy based on mood reactivity as an essential feature. Very high comorbidity (odd ratios > 2.0) was found with seasonality, bipolar 11, social phobia, binge eating, neurasthenia and sociopathy. Limitations: Atypical depression was not defined A priori, its criteria were derived from two sections of the Zurich interview. Conclusions: Atypical depression has high population prevalence and substantial significance in terms of clinical severity, impairment, and service use. The intriguing finding that the sex difference in depression may be attributed to atypical features of depression will need further investigation. Overall, our data indicate that the atypical subtype of depression is a valid entity based on evidence from such traditional indicators of validity as inclusion criteria and indicators of course. However, there are some problems with discriminatory validity from other disorders. Although comorbidity with these disorders may in part reflect an operational artifact of symptom overlap, further work needs to be done in distinguishing atypical depression from bipolar II. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Zurich, Hosp Psychiat, CH-8029 Zurich, Switzerland. NIMH, Depress & Anxiety Program, Bethesda, MD 20892 USA. RP Angst, J (reprint author), Univ Zurich, Hosp Psychiat, Lenggstr 31,POB 68, CH-8029 Zurich, Switzerland. EM jangst@bli.unizh.ch; kathleen.merikangas@nih.gov FU NIMH NIH HHS [K02-MH00499] NR 81 TC 139 Z9 143 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 2002 VL 72 IS 2 BP 125 EP 138 AR PII S0165-0327(02)00169-6 DI 10.1016/S0165-0327(02)00169-6 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 597ZH UT WOS:000178250300002 PM 12200203 ER PT J AU McHugh, RS Shevach, EM AF McHugh, RS Shevach, EM TI The role of suppressor T cells in regulation of immune responses SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE CD4(+) CD25(+) T cells; immunoregulation; tolerance; autoimmunity; tumor immunity; chronic infection; allergy; immunotherapy ID GROWTH-FACTOR-BETA; IN-VIVO; AUTOIMMUNE-DISEASE; SELF-TOLERANCE; TRANSPLANTATION TOLERANCE; INTESTINAL INFLAMMATION; IMMUNOREGULATORY CELLS; ANTITUMOR IMMUNITY; EFFECTOR FUNCTION; TUMOR REJECTION AB Suppressor T cells play important roles in the regulation of immune responses and the mediation of dominant immunologic tolerance. Studies of suppressor T-cell function have been hampered until their recent identification as a minor fraction (approximately 10%) of CD4(+) T cells that coexpress CD25. CD4(+)CD25(+) T cells have been shown to play a critical role in the prevention of organ-specific autoimmunity and allograft rejection. Because tumor antigens are self-antigens, it is not surprising that CD4(+)CD25(+) T cells also inhibit the induction of tumor immunity. The spectrum of activity of CD4(+)CD25(+) cells extends to non-self-antigens, including infectious agents. Indeed, T cell-mediated suppression might be responsible for the low level of chronic infection seen with many pathogens. Interestingly, however, this persistent level of infection might be beneficial to the host and needed for maintenance of immunologic memory. Although CD4(+)CD25(+) T cells are capable of inhibiting T(H)2 responses, their role in the suppression of allergic responses has not been firmly established. Depending on the desired immune response, enhancement or restraint of suppressor T-cell function might be required. Therefore immunologic or pharmacologic manipulation of regulatory T-cell populations represents an important future approach to immunotherapy of a wide range of immune responses. C1 NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, NIH, 9000 Rockville Pike,Bldg 10,Rm 11N311, Bethesda, MD 20892 USA. NR 78 TC 121 Z9 131 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2002 VL 110 IS 5 BP 693 EP 702 DI 10.1067/mai.2002.129339 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 612NN UT WOS:000179082500002 PM 12417876 ER PT J AU Busse, WW Lenfant, C Lemanske, RF AF Busse, WW Lenfant, C Lemanske, RF TI Asthma guidelines: A changing paradigm to improve asthma care SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID LONG-TERM TREATMENT; INHALED BUDESONIDE; DOUBLE-BLIND; CHILDREN; MONTELUKAST; ANTIBIOTICS C1 Univ Wisconsin Hosp, Ctr Clin Sci, Allergy Sect, Madison, WI 53792 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Busse, WW (reprint author), Univ Wisconsin Hosp, Ctr Clin Sci, Allergy Sect, K4-912,600 Highland Ave, Madison, WI 53792 USA. NR 19 TC 10 Z9 10 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2002 VL 110 IS 5 BP 703 EP 705 DI 10.1067/mai.2002.129368 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 612NN UT WOS:000179082500003 PM 12417877 ER PT J AU Faden, VB Baskin, ML AF Faden, VB Baskin, ML TI An evaluation of college online alcohol-policy information SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE college alcohol policy; Web site ID HARVARD-SCHOOL; BINGE DRINKING; STUDENTS; PREVENTION; TRENDS AB Excessive and underage drinking by US college and university students continues to be a significant problem. Curtailing the misuse of alcohol on college campuses is an important goal of college and university administrators because of the many negative consequences resulting from alcohol misuse. As part of their prevention programs, US colleges and universities are required by law to make information about their alcohol policies available to students. Often the source of this information is the school's Web site. The authors evaluated the alcohol-policy information that is available on the Web sites of the 52 top national universities listed in the 2002 rankings of US News and World Report. In general, they found that the information was difficult to find, was located in many areas of the Web site, and did not provide complete information about the school's alcohol policy. C1 NIAAA, DBE, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Faden, VB (reprint author), NIAAA, DBE, Epidemiol Branch, NIH, 6000 Execut Blvd,Suite 514, Bethesda, MD 20892 USA. NR 19 TC 6 Z9 7 U1 0 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD NOV PY 2002 VL 51 IS 3 BP 101 EP 107 PG 7 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 651WW UT WOS:000181346000001 PM 12638991 ER PT J AU Fahlman, A Lin, WC Whitman, WB Kayar, SR AF Fahlman, A Lin, WC Whitman, WB Kayar, SR TI Modulation of decompression sickness risk in pigs with caffeine during H-2 biochemical decompression SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE cardiac output; hydrogen diving; hyperbaria; intestine; perfusion ID OXYGEN-CONSUMPTION; EXERCISE; METABOLISM AB In H-2 biochemical decompression, H-2-metabolizing intestinal microbes remove gas stored in tissues of animals breathing hyperbaric H-2, thereby reducing decompression sickness (DCS) risk. We hypothesized that increasing intestinal perfusion in pigs would increase the activity of intestinal Methanobrevibacter smithii, lowering DCS incidence further. Pigs (Sus scrofa, 17-23 kg, n = 20) that ingested caffeine (5 mg/kg) increased O-2 consumption rate in 1 atm air by similar to20% for at least 3 h. Pigs were given caffeine alone or caffeine plus injections of M. smithii. Animals were compressed to 24 atm (20.5-23.1 atm H-2, 0.3-0.5 atm O-2) for 3 h, then decompressed and observed for signs of DCS. In previous studies, DCS incidence in animals without caffeine treatment was significantly (P < 0.05) lower with M. smithii injections (7/16) than in controls (9/10). However, contrary to our hypothesis, DCS incidence was marginally higher (P = 0.057) in animals that received caffeine and M. smithii (9/10) than in animals that received caffeine but no M. smithii (4/10). More information on gas kinetics is needed before extending H-2 biochemical decompression to humans. C1 Naval Med Res Ctr, Environm Physiol Dept, Silver Spring, MD 20910 USA. Univ Georgia, Dept Microbiol, Athens, GA 30602 USA. RP Kayar, SR (reprint author), Natl Ctr Res Resources, NIH, 6705 Rockledge Dr,Suite 6030, Bethesda, MD 20892 USA. RI Fahlman, Andreas/A-2901-2011 OI Fahlman, Andreas/0000-0002-8675-6479 NR 18 TC 0 Z9 0 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2002 VL 93 IS 5 BP 1583 EP 1589 DI 10.1152/japplphysiol.00349.2002 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 606QJ UT WOS:000178744400002 PM 12381741 ER PT J AU Andreatta, RD Mann, EA Poletto, CJ Ludlow, CL AF Andreatta, RD Mann, EA Poletto, CJ Ludlow, CL TI Mucosal afferents mediate laryngeal adductor responses in the cat SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sensorimotor; electromyogram; servomotor displacement; thyroarytenoid ID LONG-LATENCY RESPONSES; SENSORY NERVE-FIBERS; SUPERIOR LARYNGEAL; CRICOARYTENOID JOINT; NODOSE GANGLION; MUSCLE-ACTIVITY; AWAKE HUMANS; RECEPTORS; LARYNGOSPASM; VOCALIZATION AB Laryngeal adductor responses (LAR) close the airway in response to stimulation of peripheral afferents in the superior laryngeal nerve. Although both mucosal afferents and proprioceptive receptors are present in the larynx, their relative contribution for reflex elicitation is unknown. Our purpose was to determine which receptor types are of importance in eliciting the LAR. A servomotor with displacement feedback was used to deliver punctate displacements to the body of the arytenoid cartilage and overlying mucosa on each side of the larynx in eight anesthetized cats. The same displacements were delivered both before and after surgical excision of the overlying mucosa. With the mucosa intact, early short-latency component R1 LAR responses recorded from the thyroarytenoid muscles were frequent (ipsilateral > 92%, contralateral > 95%). After the mucosa was removed, the LAR became infrequent (<3%) and was reduced in amplitude in both the ipsilateral and contralateral thyroarytenoid muscle recording sites (P < 0.0005). These findings demonstrate that mucosal mechanoreceptors and not proprioceptive afferents contribute to the elicitation of LAR responses in the cat. C1 Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. RP Andreatta, RD (reprint author), Univ Georgia, Dept Commun Sci & Disorders, 514 Aderhold Hall, Athens, GA 30602 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 54 TC 21 Z9 22 U1 3 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2002 VL 93 IS 5 BP 1622 EP 1629 DI 10.1152/japplphysiol.00417.2002 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 606QJ UT WOS:000178744400007 PM 12381746 ER PT J AU Guo, TL Zhang, XL Leffel, EK Peachee, VL Karrow, NA Germolec, DR White, KL AF Guo, TL Zhang, XL Leffel, EK Peachee, VL Karrow, NA Germolec, DR White, KL TI Differential stimulation of IgE production, STAT activation and cytokine and CD86 expression by 2,4-dinitrochlorobenzene and trimellitic anhydride SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE 2,4-dinitrochlorobenzene; trimellitic anhydride; IL-4; STAT6; CD86 (B7.2); IgE ID HYPERSENSITIVITY RESPONSES; CHEMICAL ALLERGENS; CONTACT ALLERGENS; MICE; IL-4; B7-2; HYPERREACTIVITY; IDENTIFICATION; MODULATION; INDUCTION AB It has been reported that dermal exposure to trimellitic anhydride (TMA, 50%), a respiratory allergen, induced greater production of serum IgE and expression of Th2 cytokines than 2,4-dinitrochlorobenzene (DNCB, 1%), a potent contact sensitizer, in female BALB/C mice. To determine if there is any strain difference, four strains (B6C3F1, C57BL/6, BDF1 and BALB/C) of female mice were employed in this study to compare the differential effects of these chemicals on the hypersensitivity responses. Serum IgE levels were increased in TMA-treated B6C3F1, C57BL/6 and BDF1 mice when compared with the DNCB treatment and vehicle controls; in contrast, no difference was observed between TMA- and DNCB-treated BALB/C mice, although both chemicals induced greater IgE production than vehicle controls. In vitro expression of interleukin 4 (IL-4) and IL-13 mRNA by overnight concanavalin A (ConA)-stimulated draining lymph node cells was enhanced following in vivo treatment with TMA but not with DNCB in the B6C3F1, C57BL/6 and BDF1 mice. In contrast, TMA and DNCB induced similar levels of IL-4 and IL-13 mRNA in the BALB/C mice. The IL-4 protein levels in the supernatants of overnight ConA-treated draining lymph node cells were also increased in TMA-treated B6C3F1 and C57BL/6 mice when compared with the DNCB treatment and vehicle controls. Further mechanistic evaluation in the B6C3F1 mice indicated that the activation of STAT6 but not STAT4 by ConA plus IL-2-treated draining lymph node cells was increased in TMA- but not DNCB-treated mice when compared with the vehicle controls. Furthermore, surface expression of B7.2 (CD86) by B cells was increased in both TMA- and DNCB-treated B6C3F1 mice when compared with the vehicles; however, greater B7.2 expression was observed in TMA-treated compared with DNCB-treated. Overall, these results demonstrate that a similar pattern of IgE and cytokine production was observed in these strains of mice except for BALB/C. Furthermore, differential activation of STAT6 and expression of CD86 following exposure to TMA and DNCB may contribute to the differential production of IgE and cytokines. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. FU NIEHS NIH HHS [ES 05454] NR 31 TC 10 Z9 10 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV-DEC PY 2002 VL 22 IS 6 BP 397 EP 403 DI 10.1002/jat.876 PG 7 WC Toxicology SC Toxicology GA 617UY UT WOS:000179380300005 PM 12424743 ER PT J AU Sobel, DO Han, J Williams, J Yoon, JW Jun, HS Ahvazi, B AF Sobel, DO Han, J Williams, J Yoon, JW Jun, HS Ahvazi, B TI Gamma interferon paradoxically inhibits the development of diabetes in the NOD mouse SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE diabetes; gamma interferon; NOD mouse ID INTERCELLULAR-ADHESION MOLECULE-1; TUMOR NECROSIS FACTOR; T-CELLS; IFN-GAMMA; BB RAT; FREUND ADJUVANT; MICE; EXPRESSION; PREVENTION; INSULITIS AB Gamma interferon (IFN-gamma) has been thought to play an important role in the pathogenesis of diabetes. This report determines if rIFN-gamma administration to NOD mice paradoxically inhibits the development of diabetes. Injections of recombinant rIFN-gamma of 5 X 10(3), 20 x 10(3), and 100 X 10(3) units, dose dependently inhibited the development of diabetes. The maximal rIFN-y dose decreased the incidence of diabetes from 74% in control animals to 42%. 100 x 10(3) unit rIFN-y dose significantly decreased insulitis score, and increased islet number. The development of diabetes in irradiated NOD mice was slower in animals injected with spleen cells from rIFN-gamma treated than from saline treated NOD mice suggesting that rIFN-gamma decreases anti-islet effector cell activity. The susceptibility to apoptosis was increased in splenic cells of rIFN-gamma treated mice. The expressions of the co-stimulatory molecules B7-2 and ICAM-1 were significantly increased in spleen cells of rIFN-gamma treated mice while the expression of MHC class I was decreased. In vitro studies demonstrated that NOD mouse mononuclear spleen cells preincubated with rIFN-gamma and subsequently cocultured with responder cells, potently inhibited responder T-cell proliferative responses. rIFN-gamma administration decreased IL-12 and IL-2 mRNA expression in spleen cells while increasing IL-1 expression. In conclusion, rIFN-gamma inhibits the diabetic process in NOD mice by decreasing anti-islet effector activity and in turn decreasing insulitis and islet destruction. The suppression of Th1 cell related cytokines and/or augmentation of the macrophage cytokine IL-1 may play a role in the diabetes sparing effect of rIFN-y. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Georgetown Univ, Med Ctr, Div Pediat Endocrinol & Metab, Washington, DC 20007 USA. Univ Calgary, McFarlane Diabet Res Ctr, Calgary, AB T2N 1N4, Canada. NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Sobel, DO (reprint author), Georgetown Univ Hosp, Dept Pediat, 3800 Reservoir Rd NW,2 PHC, Washington, DC 20007 USA. NR 57 TC 32 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV PY 2002 VL 19 IS 3 BP 129 EP 137 DI 10.1006/jaut.2002.0604 PG 9 WC Immunology SC Immunology GA 618LE UT WOS:000179418900005 PM 12419283 ER PT J AU Reid, SD Green, NM Sylva, GL Voyich, JM Stenseth, ET DeLeo, FR Palzkill, T Low, DE Hill, RH Musser, JM AF Reid, SD Green, NM Sylva, GL Voyich, JM Stenseth, ET DeLeo, FR Palzkill, T Low, DE Hill, RH Musser, JM TI Postgenomic analysis of four novel antigens of group A Streptococcus: Growth phase-dependent gene transcription and human serologic response SO JOURNAL OF BACTERIOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Streptococcal, Lactococcal, and Enterococcal Genetics CY APR 14-17, 2002 CL ASHEVILLE, NORTH CAROLINA ID GROUP-A STREPTOCOCCUS; FIBRONECTIN-BINDING PROTEIN; GRAM-POSITIVE BACTERIA; CELL-WALL; POPULATION-GENETICS; VACCINE CANDIDATES; SURFACE-PROTEINS; PYOGENES; IDENTIFICATION; SEQUENCE AB Analysis of three group A Streptococcus genomes (serotypes M1, M3, and M18) recently identified four previously undescribed genes that encode extracellular proteins. Each of these genes encode proteins with an LPXTG amino acid motif that covalently links many virulence factors produced by gram-positive bacteria to the cell surface. Western immunoblot analysis of serum samples obtained from 80 patients with invasive infections, noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated that these four proteins are expressed in vivo. However, the level of gene transcript and the time of maximal gene transcription varied in representative serotype M1, M3, and M18 strains. Surface expression of two proteins was confirmed by How cytometry. Studies using a mouse infection model suggest that antibodies specific for one of the proteins (Spy0843) may contribute to a protective host immune response against a serotype M1 infection. These results are additional evidence that postgenomic strategies provide new ways to identity and investigate novel bacterial proteins that may participate in host-pathogen interactions or serve as targets for therapeutics research. C1 NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX USA. Mt Sinai Hosp, Dept Microbiol, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jmusser@niaid.nih.gov RI Low, Donald/B-1726-2012; OI DeLeo, Frank/0000-0003-3150-2516 NR 43 TC 34 Z9 34 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 NOV PY 2002 VL 184 IS 22 BP 6316 EP 6324 DI 10.1128/JB.184.22.6316-6324.2002 PG 9 WC Microbiology SC Microbiology GA 609QU UT WOS:000178916700025 PM 12399501 ER PT J AU Minkovsky, N Zarimani, A Chary, VK Johnstone, BH Powell, BS Torrance, PD Court, DL Simons, RW Piggot, PJ AF Minkovsky, N Zarimani, A Chary, VK Johnstone, BH Powell, BS Torrance, PD Court, DL Simons, RW Piggot, PJ TI Bex, the Bacillus subtilis homolog of the essential Escherichia coli GTPase era, is required for normal cell division and spore formation SO JOURNAL OF BACTERIOLOGY LA English DT Article ID 16S RIBOSOMAL-RNA; BINDING PROTEIN; GENE-EXPRESSION; RECO OPERON; GROWTH-RATE; SPORULATION; CHROMOSOME; NUCLEOIDS; BACTERIA; SEQUENCE AB The Bacillus subtilis bex gene complemented the defect in an Escherichia coli era mutant. The Bex protein showed 39% identity and 67% similarity to the E. coli Era GTPase. In contrast to era, bex was not essential in all strains. bex mutant cells were elongated and filled with diffuse nucleoid material. They grew slowly and exhibited severely impaired spore formation. C1 Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. NCI, Div Basic Sci, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Piggot, PJ (reprint author), Temple Univ, Sch Med, Dept Microbiol & Immunol, 3400 N Broad St, Philadelphia, PA 19140 USA. EM piggotp@temple.edu OI Minkovsky, Natalie/0000-0002-2707-0506 FU NIAID NIH HHS [T32 AI007101, T32 AI07101]; NIGMS NIH HHS [GM43577, GM50831, R01 GM043577] NR 42 TC 16 Z9 17 U1 0 U2 1 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 NOV PY 2002 VL 184 IS 22 BP 6389 EP 6394 DI 10.1128/JB.184.22.6389-6394.2002 PG 6 WC Microbiology SC Microbiology GA 609QU UT WOS:000178916700035 PM 12399511 ER PT J AU Boulanger, L Sabatino, DE Wong, EY Cline, AP Garrett, LJ Garbarz, M Dhermy, D Bodine, DM Gallagher, PG AF Boulanger, L Sabatino, DE Wong, EY Cline, AP Garrett, LJ Garbarz, M Dhermy, D Bodine, DM Gallagher, PG TI Erythroid expression of the human alpha-spectrin gene promoter is mediated by GATA-1-and NF-E2-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; PORPHOBILINOGEN DEAMINASE GENE; MEMBRANE SKELETAL PROTEINS; DIMER-DIMER ASSOCIATION; LEUCINE ZIPPER PROTEIN; HUMAN ANKYRIN-1 GENE; LOCUS-CONTROL REGION; KRUPPEL-LIKE FACTOR; BETA-SPECTRIN; FACTOR NF-E2 AB alpha-Spectrin is a highly expressed membrane protein critical for the flexibility and stability of the erythrocyte. Qualitative and quantitative defects of alpha-spectrin are present in the erythrocytes of many patients with abnormalities of red blood cell shape including hereditary spherocytosis and elliptocytosis. We wished to determine the regulatory elements that determine the erythroid-specific expression of the alpha-spectrin gene. We mapped the 5' end of the alpha-spectrin erythroid cDNA and cloned the 5' flanking genomic DNA containing the putative alpha-spectrin gene promoter. Using transfection of promoter/reporter plasmids in human tissue culture cell lines, in vitro DNase I footprinting analyses, and gel mobility shift assays, an alpha-spectrin gene erythroid promoter with binding sites for GATA-1- and NF-E2-related proteins was identified. Both binding sites were required for full promoter activity. In transgenic mice, a reporter gene directed by the alpha-spectrin promoter was expressed in yolk sac, fetal liver, and erythroid cells of bone marrow but not adult reticulocytes. No expression of the reporter gene was detected in nonerythroid tissues. We conclude that this alpha-spectrin gene promoter contains the sequences necessary for low level expression in erythroid progenitor cells. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Univ Paris 07, Assoc Claude Bernard, INSERM, U409, F-75870 Paris 18, France. NHGRI, Genet & Mol Biol Branch, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. RP Gallagher, PG (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. FU NHLBI NIH HHS [HL65448] NR 72 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 2002 VL 277 IS 44 BP 41563 EP 41570 DI 10.1074/jbc.M208184200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 610WR UT WOS:000178985300035 PM 12196550 ER PT J AU Huang, LE Pete, EA Schau, M Milligan, J Gu, J AF Huang, LE Pete, EA Schau, M Milligan, J Gu, J TI Leu-574 of HIF-1 alpha is essential for the von Hippel-Lindau (VHL)-mediated degradation pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; INDUCIBLE FACTOR 1-ALPHA; UBIQUITIN-PROTEASOME PATHWAY; ARNT TRANSCRIPTION FACTOR; PROLYL HYDROXYLATION; PROLINE HYDROXYLATION; SIGNAL-TRANSDUCTION; BINDING-PROTEIN; ALPHA-SUBUNIT; HIF-ALPHA AB Oxygen homeostasis is crucial for a myriad of developmental, physiological, and pathophysiological processes. Hypoxia-inducible factor 1alpha (HIF-1alpha) plays a pivotal role in response to hypoxia by transcriptionally activating target genes involving oxygen uptake, transport, delivery, and consumption. HIF-1alpha activity is regulated primarily through the ubiquitin-proteasome degradation pathway, which targets the oxygen-dependent degradation domain (ODD) of HIF-1alpha. In particular, the von Hippel-Lindau (VHL) protein complex, an E3 ubiquitin ligase, binds to the ODD upon hydroxylation of HIF-1alpha Pro-564. Here, we show that in vivo VHL interacts with the N-terminal as well as the C-terminal ODD independently, supporting the notion of functional redundancy within the ODD. Moreover, we demonstrate that Leu-574 of HIF-1alpha is essential for VHL binding to the C-terminal ODD. Despite the presence of Pro-564, deletion or mutation of Leu-574 resulted in a loss of VHL binding and a gain of protein stability. Furthermore, the identification of Leu-574 redefines the N-terminal activation domain of HIF-1alpha to be constitutively active. Taken together, this study provides new insight into the mechanisms underlying VHL-mediated HIF-1alpha degradation and transcriptional activation, and a molecular basis for drug targeting. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. RP Huang, LE (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK41234] NR 53 TC 26 Z9 32 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 2002 VL 277 IS 44 BP 41750 EP 41755 DI 10.1074/jbc.M207280200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 610WR UT WOS:000178985300058 PM 12205091 ER PT J AU Cecconi, I Scaloni, A Rastelli, G Moroni, M Vilardo, PG Costantino, L Cappiello, M Garland, D Carper, D Petrash, JM Del Corso, A Mura, U AF Cecconi, I Scaloni, A Rastelli, G Moroni, M Vilardo, PG Costantino, L Cappiello, M Garland, D Carper, D Petrash, JM Del Corso, A Mura, U TI Oxidative modification of aldose reductase induced by copper ion - Definition of the metal-protein interaction mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; BOVINE LENS; CATALYZED OXIDATION; WILSONS-DISEASE; MUTANT ENZYME; DNA; COMPLEXES; RADICALS; BINDING; DAMAGE AB Aldose reductase (ALR2) is susceptible to oxidative inactivation by copper ion. The mechanism underlying the reversible modification of ALR2 was studied by mass spectrometry, circular dichroism, and molecular modeling approaches on the enzyme purified from bovine lens and on wild type and mutant recombinant forms of the human placental and rat lens ALR2. Two equivalents of copper ion were required to inactivate ALR2: one remained weakly bound to the oxidized protein whereas the other was strongly retained by the inactive enzyme. Cys(303) appeared to be the essential residue for enzyme inactivation, because the human C303S mutant was the only enzyme form tested that was not inactivated by copper treatment. The final products of human and bovine ALR2 oxidation contained the intramolecular disulfide bond Cys(298)-Cys(303). However, a Cys(80)-Cys(303) disulfide could also be formed. Evidence for an intramolecular rearrangement of the Cys(80)-Cys(303) disulfide to the more stable product Cys(111)-Cys(303) is provided. Molecular modeling of the holoenzyme supports the observed copper sequestration as well as the generation of the Cys(80)-Sys(303) disulfide. However, no evidence of conditions favoring the formation of the Cys(298)-Cys(303) disulfide was observed. Our proposal is that the generation of the Cys(298)Cys(303) disulfide, either directly or by rearrangement of the Cys(80)-Cys(303) disulfide, may be induced by the release of the cofactor from ALR2 undergoing oxidation. The occurrence of a less interactive site for the cofactor would also provide the rationale for the lack of activity of the disulfide enzyme forms. C1 Univ Pisa, Dept Fisiol & Biochim, I-56100 Pisa, Italy. CNR, IABBAM, Proteom & Mass Spectrometry, I-80147 Naples, Italy. Univ Modean & Reggio Emilia, Dipartimento Sci Farmaceut, I-41100 Modena, Italy. NEI, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Visual Sci, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Mura, U (reprint author), Univ Pisa, Dept Fisiol & Biochim, Via S Maria 55, I-56100 Pisa, Italy. RI Rastelli, Giulio/D-2224-2015; Costantino, Luca/D-7608-2015 OI Rastelli, Giulio/0000-0002-2474-0607; Costantino, Luca/0000-0001-5334-8084 NR 56 TC 33 Z9 34 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 2002 VL 277 IS 44 BP 42017 EP 42027 DI 10.1074/jbc.M206945200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 610WR UT WOS:000178985300091 PM 12183464 ER PT J AU Jang, SI Steinert, PM AF Jang, SI Steinert, PM TI Loricrin expression in cultured human keratinocytes is controlled by a complex interplay between transcription factors of the Sp1, CREB, AP1, and AP2 families SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CORNIFIED CELL ENVELOPES; PROLINE-RICH PROTEINS; NERVE GROWTH-FACTOR; MOUSE KERATINOCYTES; PROXIMAL PROMOTER; GENE-EXPRESSION; C-FOS; EPIDERMAL-KERATINOCYTES; TRANSGENIC MICE; NUCLEAR-PROTEIN AB The major protein component of the cornified cell envelope barrier structure of the epidermis is loricrin, and it is expressed late during terminal differentiation in epidermal keratinocytes. We have previously shown that an AP1 site located in the proximal promoter region (position -55) is essential for human loricrin promoter activity (Rossi, A., Jang, S-I., Ceci, R., Steinert, P. M., and Markova, N. G. (1998) J. Invest. Dermatol 110, 34-40). In this study we show that its regulation requires complex cooperative and competitive interactions between multiple transcription factors in keratinocytes located in different compartments of the epidermis. We show that as few as 154 base pairs of 5'-upstream sequences from the cap site can direct the keratinocyte-specific expression in cultured keratinocytes. Mutation and DNA-protein analyses show that Sp1, c-Jun, an unidentified regulator, and the co-activator p300/CREB-binding protein up-regulate whereas Sp3, CREB-1/CREMalpha/ATF-1, Jun B, and an AP2-like protein (termed the keratinocyte-specific repressor-1 (KSR-1)) suppress loricrin promoter activity. We show that CREB protein can compete with c-Jun for the AP1 site and repress loricrin promoter activity. We show here that the protein kinase A pathway can activate loricrin expression by manipulation of the Sp1, Sp3, and KSR-1 levels in the nucleus. Thus, in undifferentiated cells, loricrin expression is suppressed by Jun B, Sp3, and KSR-1 proteins. But in advanced differentiated cells, levels of Sp3, KSR-1, and CREB proteins are lower; the unidentified regulator protein can bind; Sp1 and c-Jun are increased; and then p300/CBP is recruited. Together, these events allow loricrin transcription to proceed. Indeed, the synergistic effects of the Sp1, c-Jun, and p300 factors indicate that p300/CBP might act as bridge to form an active transcription complex. C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Jang, SI (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 50,Rm 1529, Bethesda, MD 20892 USA. NR 69 TC 69 Z9 74 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 2002 VL 277 IS 44 BP 42268 EP 42279 DI 10.1074/jbc.M205593200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 610WR UT WOS:000178985300122 PM 12200429 ER PT J AU Cornilescu, G Lee, BR Cornilescu, CC Wang, GS Peterkofsky, A Clore, GM AF Cornilescu, G Lee, BR Cornilescu, CC Wang, GS Peterkofsky, A Clore, GM TI Solution structure of the phosphoryl transfer complex between the cytoplasmic A domain of the mannitol transporter IIMannitol and HPr of the Escherichia coli phoshotransferase system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PHOSPHOTRANSFERASE SYSTEM; PHOSPHOCARRIER PROTEIN HPR; HISTIDINE-CONTAINING PROTEIN; RESIDUAL DIPOLAR COUPLINGS; C-TERMINAL DOMAIN; ACTIVE-SITE; ENZYME-II; NMR-SPECTROSCOPY; BACTERIAL PHOSPHOENOLPYRUVATE; STAPHYLOCOCCUS-CARNOSUS AB The solution structure of the complex between the cytoplasmic A domain (IIA(Mtl)) of the mannitol transporter IIMannitol and the histidine-containing phosphocarrier protein (HPr) of the Escherichia coli phosphotransferase system has been solved by NMR, including the use of conjoined rigid body/torsion angle dynamics, and residual dipolar couplings, coupled with cross-validation, to permit accurate orientation of the two proteins. A convex surface on HPr, formed by helices 1 and 2, interacts with a complementary concave depression on the surface of IIA(Mtl) formed by helix 3, portions of helices 2 and 4, and beta-strands 2 and 3. The majority of intermolecular contacts are hydrophobic, with a small number of electrostatic interactions at the periphery of the interface. The active site histidines, His-15 of HPr and His-65 of IIA(Mtl), are in close spatial proximity, and a pentacoordinate phosphoryl transition state can be readily accommodated with no change in protein-protein orientation and only minimal perturbations of the backbone immediately adjacent to the histidines. Comparison with two previously solved structures of complexes of HPr with partner proteins of the phosphotransferase system, the N-terminal domain of enzyme I (EIN) and enzyme IIA(Glucose) (IIA(Glc)), reveals a number of common features despite the fact that EIN, IIA(Glc), and IIA(Mtl) bear no structural resemblance to one another. Thus, entirely different underlying structural elements can form binding surfaces for HPr that are similar in terms of both shape and residue composition. These structural comparisons illustrate the roles of surface and residue complementarity, redundancy, incremental build-up of specificity and conformational side chain plasticity in the formation of transient specific protein-protein complexes in signal transduction pathways. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm B1-30I, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008; Cornilescu, Claudia/H-1959-2012; Cornilescu, Claudia/K-1981-2015; Cornilescu, Gabriel/H-3113-2011 OI Clore, G. Marius/0000-0003-3809-1027; Cornilescu, Claudia/0000-0002-2401-7806; Cornilescu, Gabriel/0000-0002-1204-8904 NR 78 TC 56 Z9 56 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 1 PY 2002 VL 277 IS 44 BP 42289 EP 42298 DI 10.1074/jbc.M207314200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 610WR UT WOS:000178985300124 PM 12202490 ER PT J AU Bradford, M Schroeder, AJ Morse, HC Vogel, SN Cowdery, JS AF Bradford, M Schroeder, AJ Morse, HC Vogel, SN Cowdery, JS TI CpG DNA induced IL-12 p40 gene activation is independent of STAT1 activation or production of interferon consensus sequence binding protein SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE CpG DNA; interleukin-12; interferon-gamma; interferon consensus sequence binding protein ID TOLL-LIKE RECEPTOR-2; BACTERIAL-DNA; IFN-GAMMA; NUCLEAR FACTOR; IN-VIVO; KAPPA-B; MURINE MACROPHAGES; CELL ACTIVATION; MONOCYTIC CELLS; INTERLEUKIN-12 AB The host immune system responds to CpG motifs in bacterial DNA by rapidly producing proinflammatory cytokines. The host response to CpG DNA resembles, in many ways, the response to bacterial lipopolysaccharide (LPS). While both agents can induce a powerful inflammatory response, CpG DNA promotes Th1 and suppresses Th2 immunity. The regulation of macrophage IL-12 p40 secretion in response to stimulation with LPS and interferon-gamma (IFN-gamma) is dependent on the action of a nuclear transacting factor, interferon consensus sequence binding protein (ICSBP), a STAT1-dependent gene product. We found that CpG DNA induced IL-12 p40 secretion by macrophages from mice with either disrupted STAT1 or ICSBP genes. Additionally, CpG DNA did not induce translocation of transcription factors that bind to the gamma-activated sequence in the ICSBP gene nor did CpG DNA induce ICSBP transcription. CpG DNA, which activates macrophages by the TLR9 pathway, is a strong inducer of IL-12 p40, yet does so independently of IFN-gamma, STAT1 or ICSBP. Thus, CpG DNA-induced IL-12 p40 secretion is mediated by one or more signaling elements distinct from those induced by either LPS or IFN-gamma. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel. C1 Univ Iowa, Coll Med, VA Med Ctr, Dept Internal Med, Iowa City, IA 52246 USA. Univ Iowa, Coll Med, Interdisciplinary Immunol Program, Iowa City, IA 52246 USA. NIAID, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Cowdery, JS (reprint author), Univ Iowa, Coll Med, VA Med Ctr, Dept Internal Med, 6W34,601 Highway 6 W, Iowa City, IA 52246 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [AI18797] NR 47 TC 8 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD NOV-DEC PY 2002 VL 9 IS 6 BP 688 EP 696 DI 10.1159/000067280 PN 2 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 618FU UT WOS:000179408700014 PM 12432235 ER PT J AU Traicoff, JL Willson, JKV Markowitz, SD AF Traicoff, JL Willson, JKV Markowitz, SD TI Early loss of deleted in colorectal carcinoma gene transcript detected in a group of benign colon adenomas SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE colon adenoma; tumor progression; deleted in colorectal carcinoma gene ID DCC PROTEIN; EXPRESSION; CANCERS AB We examined the expression of the putative tumor suppressor gene deleted in colorectal carcinoma (DCC) in human colon adenoma tissues and cell lines. One allele of DCC is deleted in 70% of human colon carcinomas, and DCC expression is undetectable in 90% of colon carcinoma cell lines. One DCC allele is also deleted in 50% of human colon adenomas, but results from protein expression studies have differed as to whether complete loss of DCC expression could occur in colon adenomas, or instead correlates with progression of colon adenoma to carcinoma. To further examine the timing of DCC expression loss in colon adenomas, we assayed DCC transcript levels in adenoma cell lines and tissues. We measured DCC expression by a sensitive assay using Southern blot detection of the RT-PCR-amplified DCC transcript. DCC expression was negligible or greatly reduced in 4 of 14 colon adenomas, including 2 of 2 adenoma cell lines and 2 of 12 adenoma tissue samples. These data are the first evidence that expression of DCC transcript can be silenced in colon adenoma cell lines and tissues. These data indicate that loss of DCC expression occurs in some colon adenomas, but is insufficient to drive the adenoma to carcinoma progression. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel. C1 Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. Howard Hughes Med Inst, Cleveland, OH USA. RP Traicoff, JL (reprint author), NIH, 6701 Rockledge Dr,Room 6188,MSC 7804, Bethesda, MD 20892 USA. FU NCI NIH HHS [P01 CA51183, P30 CA43703, CA67409, CA72160] NR 7 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD NOV-DEC PY 2002 VL 9 IS 6 BP 716 EP 720 DI 10.1159/000067291 PN 2 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 618FU UT WOS:000179408700017 PM 12432238 ER PT J AU Rich, EA Orenstein, JM Jeang, KT AF Rich, EA Orenstein, JM Jeang, KT TI A macrophage-tropic HIV-1 that expresses green fluorescent protein and infects alveolar and blood monocyte-derived macrophages SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV-1; alveolar macrophages; blood monocytes; enhanced green fluorescent protein; AIDS; cigarette smoking ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VIVO; T-CELLS; MONONUCLEAR PHAGOCYTES; PRODUCTIVE INFECTION; CIGARETTE-SMOKING; VIRAL ENTRY; TAT; REPLICATION; KINASE AB We describe the construction of a macrophage-tropic HIV-1 molecular clone, pNLAD8-EGFP, which expresses enhanced green fluorescent protein. We show that NLAD8-EGFP can infect monocyte-derived macrophages as well as alveolar macrophages. NLAD8-EGFP-infected macrophages can be easily and sensitively detected based on the visualization of intracellular green fluorescent protein. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel. C1 Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. George Washington Univ, Dept Pathol, Washington, DC USA. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 39 TC 10 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD NOV-DEC PY 2002 VL 9 IS 6 BP 721 EP 726 DI 10.1159/000067293 PN 2 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 618FU UT WOS:000179408700018 PM 12432239 ER PT J AU Jacob, J Louis, JM Nesheiwat, I Torchia, DA AF Jacob, J Louis, JM Nesheiwat, I Torchia, DA TI Biosynthetically directed fractional C-13 labeling facilitates identification of Phe and Tyr aromatic signals in proteins SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE amino acid; aromatic; NMR; non-random C-13 labeling; proteins ID AMINO-ACIDS; ASSIGNMENTS; RELAXATION; LEUCINE; VALINE AB Analysis of 2D [C-13,H-1]-HSQC spectra of biosynthetic fractionally C-13 labeled proteins is a reliable, straightforward means to obtain stereospecific assignments of Val and Leu methyl sites in proteins. Herein we show that the same fractionally labeled protein sample facilitates observation and identification of Phe and Tyr aromatic signals. This is the case, in part, because the fractional C-13 labeling yields aromatic rings in which some of the C-13-C-13 J-couplings, present in uniformly labeled samples, are absent. Also, the number of homonuclear J-coupling partners differs for the delta-, epsilon- and zeta-carbons. This enabled us to vary their signal intensities in distinctly different ways by appropriately setting the C-13 constant-time period in 2D [C-13,H-1]-HSQC spectra. We illustrate the application of this approach to an 18 kDa protein, c-VIAF, a modulator of apoptosis. In addition, we show that cancellation of the aromatic C-13 CSA and C-13-H-1 dipolar interactions can be fruitfully utilized in the case of the fractionally labeled sample to obtain high resolution C-13 constant-time spectra with good sensitivity. C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Torchia, DA (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NR 12 TC 6 Z9 6 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 2002 VL 24 IS 3 BP 231 EP 235 DI 10.1023/A:1021662423490 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 625GY UT WOS:000179809800005 PM 12522310 ER PT J AU Alexander, HR Chen, CC Shawker, T Choyke, P Chan, TJ Chang, R Marx, SJ AF Alexander, HR Chen, CC Shawker, T Choyke, P Chan, TJ Chang, R Marx, SJ TI Role of preoperative localization and intraoperative localization maneuvers including intraoperative PTH assay determination for patients with persistent or recurrent hyperparathyroidism SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Asymptomatic Primary Hyperparathyroidism CY APR 08-09, 2002 CL NIH, BETHESDA, MARYLAND HO NIH ID INVASIVE RADIOGUIDED PARATHYROIDECTOMY; GAMMA-PROBE LOCALIZATION; REOPERATIVE NECK; HORMONE ASSAY; 99M SESTAMIBI; ADENOMAS; ULTRASOUND; MANAGEMENT; GLANDS; MRI C1 NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, Bethesda, MD USA. NIH, Dept Imaging Sci, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), Surg Metab Sect, 10 Ctr Dr,Bldg 10-2B07, Bethesda, MD 20892 USA. NR 34 TC 21 Z9 21 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 NOV PY 2002 VL 17 SU 2 BP N133 EP N140 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609BV UT WOS:000178883500021 PM 12412790 ER PT J AU Marx, SJ Simonds, WF Agarwal, SK Burns, AL Weinstein, LS Cochran, C Skarulis, MC Spiegel, AM Libutti, SK Alexander, HR Chen, CC Chang, R Chandrasekharappa, SC Collins, FS AF Marx, SJ Simonds, WF Agarwal, SK Burns, AL Weinstein, LS Cochran, C Skarulis, MC Spiegel, AM Libutti, SK Alexander, HR Chen, CC Chang, R Chandrasekharappa, SC Collins, FS TI Hyperparathyroidism in hereditary syndromes: Special expressions and special managements SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Asymptomatic Primary Hyperparathyroidism CY APR 08-09, 2002 CL NIH, BETHESDA, MARYLAND HO NIH DE MEN1; MEN2; RET; HRPT2; calcium-sensing receptor; FHH; oncogene ID FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; COMPARATIVE GENOMIC HYBRIDIZATION; CALCIUM-SENSING RECEPTOR; NEOPLASIA TYPE-I; PARATHYROID ADENOMAS; MUTATIONS; GENE; TUMORS; CELLS; LOCALIZATION AB Hyperparathyroidism (HPT) in its hereditary variants assumes special forms, has special associations, and requires special managements. Familial hypocalciuric hypercalcemia (FHH or FBHH) and neonatal severe primary hyperparathyroidism (NSHPT) reflect heterozygous or homozygous mutations, respectively, in the calcium-sensing receptor. FHH and NSHPT represent the mildest and severest variants of HPT. Both cause hypercalcemia from birth and atypical HPT that always and uniquely persists after subtotal parathyroidectomy. Their HPT is likely polyclonal and nonneoplastic. In contrast, mono- or oligo-clonal parathyroid neoplasia underlays most other HPT variants: multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and hyperparathyroidism-jaw tumor syndrome (HPT-JT). Familial-isolated HPT combines several diagnoses, including occult forms of the above syndromes. Each neoplastic variant has tumors in multiple parathyroids and a delayed, but still early age of onset for HPT (average age, 25-35 years). Each justifies special and similar approaches to parathyroidectomy: typically, identification of four glands, subtotal parathyroidectomy, rapid intraoperative parathyroid hormone (PTH) assays, and parathyroid cryopreservation. Outcomes of parathyroidectomy remain suboptimal in each. Each syndrome of parathyroid neoplasia associates with characteristic cancer(s): enteropancreatic neuroendocrine or foregut carcinoid tissues (MEN1), thyroidal C cells (MEN2A), or parathyroid (HPT-JT). HPT has promoted gene discovery more through its rare hereditary variants than through common adenoma; the main genes causing four of six hereditary variants are known. The RET mutation test became essential in management of MEN2A. The MEN1 test is less urgent, because it rarely guides a major patient benefit. The CASR test, perhaps least urgent, has largely been unavailable. Further progress in molecular genetics will enhance understandings, diagnosis, and therapy of HPT. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Off Director, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Ctr Clin, Dept Diagnost Radiol & Nucl Med, Bethesda, MD USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 9C-101, Bethesda, MD 20892 USA. RI Weinstein, Lee/I-5575-2015; Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 31 TC 83 Z9 84 U1 0 U2 1 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 NOV PY 2002 VL 17 SU 2 BP N37 EP N43 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609BV UT WOS:000178883500007 PM 12412776 ER PT J AU Nielsen, JA Hudson, LD Armstrong, RC AF Nielsen, JA Hudson, LD Armstrong, RC TI Nuclear organization in differentiating oligodendrocytes SO JOURNAL OF CELL SCIENCE LA English DT Article DE gene expression; nuclear organization; oligodendrocyte; proteolipid protein; splicing factors ID DNA-BINDING PROTEIN; RNA-POLYMERASE-II; MESSENGER-RNA; IN-VIVO; EMBRYONIC-DEVELOPMENT; TRANSCRIPTION FACTORS; GENE-EXPRESSION; NERVOUS-SYSTEM; CELL-NUCLEUS; SITES AB Many studies have suggested that the 3D organization of chromatin and proteins within the nucleus contributes to the regulation of gene expression. We tested multiple aspects of this nuclear organization model within a primary cell culture system. Oligodendrocyte lineage cells were examined to facilitate analysis of nuclear organization relative to a highly expressed tissue-specific gene, proteolipid protein (PLP), which exhibits transcriptional upregulation during differentiation from the immature progenitor stage to the mature oligodendrocyte stage. Oligodendrocyte lineage cells were isolated from brains of neonatal male rodents, and differentiation from oligodendrocyte progenitors to mature oligodendrocytes was controlled with culture conditions. Genomic in situ hybridization was used to detect the single copy of the X-linked PLP gene within each interphase nucleus. The PLP gene was not randomly distributed within the nucleus, but was consistently associated with the nuclear periphery in both progenitors and differentiated oligodendrocytes. PLP and a second simultaneously upregulated gene, the myelin basic protein (MBP) gene, were spatially separated in both progenitors and differentiated oligodendrocytes. Increased transcriptional activity of the PLP gene in differentiated oligodendrocytes corresponded with local accumulation of SC35 splicing factors. Differentiation did not alter the frequency of association of the PLP gene with domains of myelin transcription factor 1 (Myt1), which binds the PLP promoter. In addition to our specific findings related to the PLP gene, these data obtained from primary oligodendrocyte lineage cells support a nuclear organization model in which (1) nuclear proteins and genes can exhibit specific patterns of distribution within nuclei, and (2) activation of tissue-specific genes is associated with changes in local protein distribution rather than spatial clustering of coordinately regulated genes. This nuclear organization may be critical for complex nucleic-acid-protein interactions controlling normal cell development, and may be an important factor in aberrant regulation of cell differentiation and gene expression in transformed cells. C1 Uniformed Serv Univ Hlth Sci, Program Mol & Cell Biol, Bethesda, MD 20814 USA. NINDS, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Neurosci Program, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Armstrong, RC (reprint author), Uniformed Serv Univ Hlth Sci, Program Mol & Cell Biol, Bethesda, MD 20814 USA. NR 48 TC 38 Z9 41 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2002 VL 115 IS 21 BP 4071 EP 4079 DI 10.1242/jcs.00103 PG 9 WC Cell Biology SC Cell Biology GA 615PA UT WOS:000179254000010 PM 12356912 ER PT J AU Steinbach, PJ AF Steinbach, PJ TI Inferring lifetime distributions from kinetics by maximizing entropy using a bootstrapped model SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article AB A bootstrapped model is used to improve the lifetime distribution recovered using the maximum entropy method from kinetics that involves overlapping exponential and distributed phases. The model defaulted to in the limit of low signal-to-noise is iteratively derived from the data to counter the tendency of regularization methods to over-smooth sharp features while under-smoothing broad ones, Upon each revision, some of the lifetime distribution is focused and the rest is blurred. This differential blurring can produce distributions that are virtually free of artifacts. The change in the result obtained upon a reasonable change in the default model provides a useful measure of the uncertainty in the lifetime distribution. In particular. the widths of peaks may not be well determined. C1 NIH, Ctr Informat Technol, Ctr Mol Modelling, Bethesda, MD 20892 USA. RP Steinbach, PJ (reprint author), NIH, Ctr Informat Technol, Ctr Mol Modelling, Bldg 12A Room 2051,12 South Dr, Bethesda, MD 20892 USA. EM steinbac@helix.nih.gov NR 6 TC 57 Z9 58 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD NOV-DEC PY 2002 VL 42 IS 6 BP 1476 EP 1478 DI 10.1021/ci025551i PG 3 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 620HH UT WOS:000179527600025 PM 12444746 ER PT J AU Moffat, SD Zonderman, AB Metter, EJ Blackman, MR Harman, SM Resnick, SM AF Moffat, SD Zonderman, AB Metter, EJ Blackman, MR Harman, SM Resnick, SM TI Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; ESTROGEN REPLACEMENT THERAPY; SEX-DIFFERENCES; ALZHEIMERS-DISEASE; OLDER MEN; HORMONE-REPLACEMENT; SPATIAL COGNITION; VERBAL MEMORY; VISUAL MEMORY; RAT-BRAIN AB Circulating testosterone (T) levels have behavioral and neurologicaI effects in both human and nonhuman species. Both T concentrations and neuropsychological function decrease substantially with age in men. The purpose of this prospective, longitudinal study was to investigate the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance. Participants were volunteers from the Baltimore Longitudinal Study of Aging, aged 50-91 yr at baseline T assessment. Four hundred seven men were followed for an average of 10 yr, with assessments of multiple cognitive domains and contemporaneous determination of serum total T, SHBG, and a free T index (FTI). We administered neuropsychological tests of verbal and visual memory, mental status, visuomotor scanning and attention, verbal knowledge/language, visuospatial ability, and depressive symptomatology. Higher FTI was associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning and a reduced rate of longitudinal decline in visual memory. Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory. No relations between total T or the FTI and measures of verbal knowledge, mental status, or depressive symptoms were observed. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. NIH, Natl Ctr Complementary & Alternat Med, Clin Invest Lab, Bethesda, MD 20892 USA. RP Resnick, SM (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM resnick@lpc.grc.nia.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Zonderman, Alan B/0000-0002-6523-4778 FU NIA NIH HHS [AG 05146, AG 08325] NR 50 TC 234 Z9 242 U1 1 U2 8 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 NOV PY 2002 VL 87 IS 11 BP 5001 EP 5007 DI 10.1210/jc.2002-020419 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 613FL UT WOS:000179121800026 PM 12414864 ER PT J AU Weise, M Eisenhofer, G Merke, DP AF Weise, M Eisenhofer, G Merke, DP TI Pubertal and gender-related changes in the sympathoadrenal system in healthy children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN ADRENOCORTICAL-CELLS; CATECHOLAMINE SECRETION; CHROMAFFIN CELLS; ADRENOMEDULLARY FUNCTION; STEROIDOGENIC ENZYME; MENTAL STRESS; ADRENAL-GLAND; HUMAN OBESITY; EPINEPHRINE; PLASMA AB A critical amount of body fat is necessary for the initiation of puberty, and leptin, an adipocyte-derived hormone, is necessary for pubertal development. The sympathoadrenal system modulates body fat stores and leptin secretion and interacts with adrenocortical androgen production, suggesting a possible role in sexual maturation. We studied sympathetic nerve and adrenomedullary activity at rest in 80 healthy children (ages, 5-17 yr; 37 boys and 43 girls) in relation to age, pubertal stage, gender, physical activity, body mass index, and serum levels of sex steroids, dehydroepiandrosterone sulfate, corti. sol, leptin, and insulin. Plasma concentrations of the adrenomedullary hormone, epinephrine (E), and its metabolite metanephrine (MN), decreased significantly with advancing puberty and were higher in boys than in girls. E and MN correlated significantly and inversely with dehydroepi and rosterone sulfate, estradiol, testosterone, leptin, and insulin. Plasma norepinephrine, which is primarily derived from sympathetic nerve endings, increased significantly with advancing puberty and increasing testosterone levels in boys. Stepwise multiple regression analysis revealed that E was best predicted by pubertal stage and leptin, and MN by estradiol and leptin. Our data suggest that sympathoadrenal hormones may play a role in the complex process of sexual maturation. Further studies are needed to investigate a possible modulatory role of the adrenal medulla in the body weight-related timing of adrenarche and/or gonadarche. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 13S260,10 Ctr Dr,MSC 1932, Bethesda, MD 20892 USA. EM dmerke@nih.gov NR 53 TC 55 Z9 58 U1 0 U2 3 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 NOV PY 2002 VL 87 IS 11 BP 5038 EP 5043 DI 10.1210/jc.2002-020590 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 613FL UT WOS:000179121800031 PM 12414869 ER PT J AU Akintoye, SO Chebli, C Booher, S Feuillan, P Kushner, H Leroith, D Cherman, N Bianco, P Wientroub, S Robey, PG Collins, MT AF Akintoye, SO Chebli, C Booher, S Feuillan, P Kushner, H Leroith, D Cherman, N Bianco, P Wientroub, S Robey, PG Collins, MT TI Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATORY G-PROTEIN; SECRETING PITUITARY-ADENOMA; FIBROUS DYSPLASIA; MOLECULAR-BASIS; CLINICAL IMPLICATIONS; SOMATOTROPH ADENOMAS; ACTIVATING MUTATIONS; ACROMEGALIC PATIENTS; ADENYLYL CYCLASE; GENETIC-DEFECTS AB McCune-Albright syndrome (MAS) is a disorder characterized by the triad of cafe-au-lait skin pigmentation, polyostotic fibrous dysplasia of bone, and hyperfunctioning endocrinopathies, including GH excess. The molecular etiology of the disease is postzygotic activating mutations of the GNAS1 gene product, G(S)alpha. The term gsp oncogene has been assigned to these mutations due to their association with certain neoplasms. The aim of this study was to estimate the prevalence of GH excess in MAS, characterize the clinical and endocrine manifestations, and describe the response to treatment. Fifty-eight patients with MAS were screened, and 22 with stigmata of acromegaly and/or elevated GH or IGF-I underwent oral glucose tolerance testing. Twelve patients (21%) had GH excess, based on failure to suppress serum GH on oral glucose tolerance test, and underwent a TRH test, serial GH sampling from 2000-0800 h, and magnetic resonance imaging of the sella. We found that vision and hearing deficits were more common in patients with GH excess (4 of 12, 3350 than those without (2 of 56, 4%). Of interest, patients with a history of precocious puberty and GH excess who had reached skeletal maturity achieved normal adult height despite a history of early epiphyseal fusion. All 9 patients tested had an increase in serum GH after TRH, 11 of 12 (92%) had hyperprolactinemia, and all 8 tested had detectable or elevated nighttime GH levels. Pituitary adenoma was detected in 4 of 12 (33%) patients. All patients with elevated IGF-I levels were treated with cabergoline (7 patients), long-acting octreotide (LAO; 8 patients), or a combination of cabergoline and LAO (4 patients). In six of the seven patients (86%,) treated with cabergoline, serum IGF-I decreased, but not to the normal range. In the eight patients treated with LAO alone, IGF-I decreased, and, in four, returned to the normal range. The remaining 4 patients were treated with a combination of cabergoline and 1AO. For them, symptoms of GH excess diminished, and IGF-I decreased further, but did not enter the normal range. GH excess is common in MAS and results in a distinct clinical phenotype characterized by inappropriately normal stature, TRH responsiveness, prolactin cosecretion, small or absent pituitary tumors, a consistent but inadequate response to treatment with cabergoline, and an intermediate response to LAO. C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Dana Childrens Hosp, Tel Aviv Med Ctr, Dept Orthoped Surg, IL-64139 Tel Aviv, Israel. Univ Roma La Sapienza, Dept Expt Med, I-100161 Rome, Italy. Biomed Comp Res Inst, Philadelphia, PA 19115 USA. Univ Maryland, Dept Orthoped Surg, Baltimore, MD 21201 USA. NIDDK, Mol Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dept Nursing, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. EM mcollins@dir.nidcr.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 44 TC 81 Z9 85 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 NOV PY 2002 VL 87 IS 11 BP 5104 EP 5112 DI 10.1210/jc.2001-012022 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 613FL UT WOS:000179121800041 PM 12414879 ER PT J AU Arraztoa, JA Monget, P Bondy, C Zhou, J AF Arraztoa, JA Monget, P Bondy, C Zhou, J TI Expression patterns of insulin-like growth factor-binding proteins 1, 2, 3, 5, and 6 in the mid-cycle monkey ovary SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; I IGF-I; FACTOR SYSTEM COMPONENTS; GENE-EXPRESSION; FOLLICULAR-FLUID; CORPUS-LUTEUM; ENDOTHELIAL-CELLS; ANTRAL FOLLICLES; GRANULOSA-CELLS; ESTROUS-CYCLE AB IGFs and IGF-binding proteins (IGFBPs) are thought to play important roles in ovarian follicular growth and selection. To elucidate the role of IGFBPs in primate ovarian function, we analyzed IGFBP mRNA expression patterns in ovaries from mid-cycle rhesus monkeys using in situ hybridization. IGFBP-1 mRNA was concentrated in theca-interstitial cells and was present at low levels in granulosa cells of atretic follicles. IGFBP-2 mRNA was expressed in the ovarian surface epithelium and granulosa cells of all antral follicles, including obviously atretic as well as dominant follicles. IGFBP-3 mRNA was localized in oocytes and in the ovarian vascular endothelium.; this mRNA was also concentrated in the superficial cortical stroma in which it was distinctly more abundant in the nondominant ovary. Granulosa cells of mature dominant and ovulatory follicles selectively expressed IGFBP-5 mRNA. IGFBP-5 mRNA was also widely expressed in the ovarian stroma, in which, in contrast to IGFBP-3, it was distinctly more abundant in dominant, compared with nondominant, ovary. IGFBP-6 mRNA was present at low levels in the ovary interstitium. and theca externa and was more abundant in the ovary surface epithelium. These novel data reveal distinctive cellular expression patterns for IGFBPs 1, 2, 3, 5, and 6 in the nonhuman primate ovary, suggesting distinct roles for each binding protein in ovarian function. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. INRA, URA CNRS 1291, F-37380 Nouzilly, France. RP Arraztoa, JA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM arrazj@mail.nih.gov NR 37 TC 21 Z9 21 U1 0 U2 4 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 NOV PY 2002 VL 87 IS 11 BP 5220 EP 5228 DI 10.1210/jc.2002-020407 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 613FL UT WOS:000179121800056 PM 12414895 ER PT J AU Armoni, M Quon, MJ Maor, G Avigad, S Shapiro, DN Harel, C Esposito, D Goshen, Y Yaniv, I Karnieli, E AF Armoni, M Quon, MJ Maor, G Avigad, S Shapiro, DN Harel, C Esposito, D Goshen, Y Yaniv, I Karnieli, E TI PAX3/Forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TRANSCRIPTION FACTOR FKHR; PAX3-FKHR FUSION PROTEIN; HUMAN BREAST-CANCER; ALVEOLAR RHABDOMYOSARCOMA; CHILDHOOD RHABDOMYOSARCOMA; INSULIN RESISTANCE; FORKHEAD FAMILY; PAIRED DOMAIN; BINDING-SITE; DNA-BINDING AB Increased levels of glucose uptake and increased expression of the glucose transporter (GLUT) genes are characteristic features of tumors. In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. In muscle tissues, glucose transport is primarily mediated by GLUT4. However, the mechanisms that regulate GLUT4 gene expression in tumor tissues are largely unknown. Therefore, we evaluated the role of PAX3/FEMR in the regulation of GLUT4 gene expression in muscle tumorigenesis. GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. Progressive 5'-deletion analysis of GLUT4-P further identified a specific region of the promoter, -66/+163 bp, which retained about 65% of the full transactivation effect. EMSA studies established that the PAX3/FKHR protein directly and specifically hinds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/ +36-bp region within the GLUT4 promoter. Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. C1 Technion Israel Inst Technol, Rambam Med Ctr, Inst Endocrinol Diabet & Metab, Unit Endocrinol Mol, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Morphol, IL-31096 Haifa, Israel. NIH, Natl Ctr Alternat & Complementary Med, Bethesda, MD 20892 USA. Sackler Fac Med, Schneider Childrens Med Ctr, Pediat Hematol Oncol Dept, IL-49100 Petah Tiqwa, Israel. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Armoni, M (reprint author), Technion Israel Inst Technol, Rambam Med Ctr, Inst Endocrinol Diabet & Metab, Unit Endocrinol Mol, IL-31096 Haifa, Israel. EM amichal@tx.technion.ac.il RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 56 TC 22 Z9 23 U1 0 U2 4 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 NOV PY 2002 VL 87 IS 11 BP 5312 EP 5324 DI 10.1210/jc.2002-020318 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 613FL UT WOS:000179121800068 PM 12414908 ER PT J AU Fellner, S Bauer, B Miller, DS Schaffrik, M Fankhanel, M Spruss, T Bernhardt, G Graeff, C Farber, L Gschaidmeier, H Buschauer, A Fricker, G AF Fellner, S Bauer, B Miller, DS Schaffrik, M Fankhanel, M Spruss, T Bernhardt, G Graeff, C Farber, L Gschaidmeier, H Buschauer, A Fricker, G TI Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESISTANCE-ASSOCIATED PROTEIN; P-GLYCOPROTEIN; ENDOTHELIAL-CELLS; ORAL BIOAVAILABILITY; SOLID TUMORS; LUNG-CANCER; STAGE-III; PSC 833; EXPRESSION; MICE AB Paclitaxel concentrations in the brain are very low after intravenous injection. Since paclitaxel is excluded from some tumors by p-glycoprotein (p-gp), the same mechanism may prevent entry into the brain. in vitro, paclitaxel transport was examined in capillaries from rat brains by confocal microscopy using BODIPY Fl-paclitaxel. Western blots and immunostaining demonstrated apical expression of p-gp in isolated endothelial cells, vessels, and tissue. Secretion of BODIPY Fl-paclitaxel into capillary lumens was specific and energy-dependent. Steady state luminal fluorescence significantly exceeded cellular fluorescence and was reduced by NaCN, paclitaxel, and SDZ PSC-833 (valspodar), a p-gp blocker. Leukotriene C-4 (LTC4), an Mrp2-substrate, had no effect. Luminal accumulation of NBDL-cyclosporin, a p-gp substrate, was inhibited by paclitaxel. In vivo, paclitaxel levels in the brain, liver, kidney, and plasma of nude mice were determined after intravenous injection. Co-administration of valspodar led to increased paclitaxel levels in brains compared to monotherapy. Therapeutic relevance was proven for nude mice with implanted intracerebral human U-118 MG glioblastoma. Whereas paclitaxel did not affect tumor volume, co-administration of paclitaxel (intravenous) and PSC833 (peroral) reduced tumor volume by 90%. Thus, p-gp is an important obstacle preventing paclitaxel entry into the brain, and inhibition of this transporter allows the drug to reach sensitive tumors within the CNS. C1 Univ Regensburg, Inst Pharm, D-8400 Regensburg, Germany. Univ Heidelberg, Inst Pharmaceut & Biopharm, Heidelberg, Germany. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Novartis Pharma GmbH, Nurnberg, Germany. RP Fricker, G (reprint author), Inst Pharmazeut Technol & Biopharm, Neuenheimer Feld 366, D-69120 Heidelberg, Germany. EM jw3@ix.urz.uni-heidelberg.de RI Buschauer, Armin/D-2861-2009 NR 53 TC 213 Z9 219 U1 7 U2 28 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 NOV PY 2002 VL 110 IS 9 BP 1309 EP 1318 DI 10.1172/JCI200215451 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 612HW UT WOS:000179069500014 PM 12417570 ER PT J AU Hong, F Jaruga, B Kim, WH Radaeva, S El-Assal, ON Tian, ZG Nguyen, VA Gao, B AF Hong, F Jaruga, B Kim, WH Radaeva, S El-Assal, ON Tian, ZG Nguyen, VA Gao, B TI Opposing roles of STAT1 and STAT3 in T cell-mediated hepatitis: regulation by SOCS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID A-INDUCED HEPATITIS; ALCOHOLIC LIVER-DISEASE; C VIRUS-INFECTION; CONCANAVALIN-A; IFN-GAMMA; INTERFERON-GAMMA; INTERLEUKIN-6-DEFICIENT MICE; TRANSCRIPTIONAL ACTIVATION; AUTOIMMUNE HEPATITIS; TARGETED DISRUPTION AB T cell-mediated fulminant hepatitis is a life-threatening event for which the underlying mechanism is not fully understood. Injection of concanavalin A (Con A) into mice recapitulates the histological and pathological sequelae of T cell-mediated hepatitis. In this model, both signal transducer and activator of transcription factor 1 (STAT1) and STAT3 are activated in the liver. Disruption of the STAT1 gene by way of genetic knockout attenuates liver injury, suppresses CD4(+) and NK T cell activation, and downregulates expression of proapoptotic interferon regulatory factor-1 protein and suppressor of cytokine signaling-1 (SOCS1), but enhances STAT3 activation and STAT3-controlled antiapoptotic signals. Studies from IFN-gamma-deficient mice indicate that IFN-gamma not only is the major cytokine responsible for STAT1 activation but also partially accounts for STAT3 activation. Moreover, downregulation of STAT3 activation in IL-6-deficient mice is associated with decreased STAT3-controlled antiapoptotic signals and expression of SOCS3, but upregulation of STAT1 activation and STAT1-induced proapoptotic signals and exacerbation of liver injury. Taken together, these findings suggest that STAT1 plays a harmful role in Con A-mediated hepatitis by activation of CD4(+) and NK T cells and directly inducing hepatocyte death, whereas STAT3 protects against liver injury by suppression of IFN-gamma signaling and induction of antiapoptotic protein Bcl-X-L. STAT1 and STAT3 in hepatocytes also negatively regulate one another through the induction of SOCS. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Pk Bldg,Room 120,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. RI Tian, Zhigang/J-3512-2013 NR 59 TC 193 Z9 204 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 NOV PY 2002 VL 110 IS 10 BP 1503 EP 1513 DI 10.1172/JC1200215841 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 617TM UT WOS:000179377000017 PM 12438448 ER PT J AU Diemert, DJ Libman, MD Lebel, P AF Diemert, DJ Libman, MD Lebel, P TI Confirmation by 16S rRNA PCR of the COBAS AMPLICOR CT/NG test for diagnosis of Neisseria gonorrhoeae infection in a low-prevalence population SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS; MULTICENTER EVALUATION; DISCREPANT ANALYSIS; TEST SENSITIVITY; ABBOTT LCX; SPECIMENS; ASSAY; SPECIFICITY; URINE AB The COBAS AAIPLICOR CT/NG test is widely used for the diagnosis of Neisseria gonorrhoeae infection using genital swabs or urine samples. Although highly specific, cross-reactivity occurs with sonic nonpathogenic strains of Neisseria and Lactobacillus species. In low-prevalence populations, even highly specific assays may require confirmatory testing of positive results. We assessed the positive predictive value (PPV) of this test in a low-prevalence (0.5%) setting. Genital and urine specimens testing positive using the COBAS AMPLICOR NG test were retested using an investigational 16S rRNA PCR assay. Additionally, 737 specimens were tested in parallel by both culture and the above PCR protocol. Of 9,772 specimens tested in-house, 168 were positive by the AMPLICOR test; in addition, 62 AMPLICOR-positive specimens were referred to our laboratory for confirmatory testing, yielding 230 positive specimens. Of these, 72 were confirmed positive by 16S rRNA PCR, yielding a specificity of 98.7% and a PPV of 31.3%. Specificity was similar for all specimen types, whereas PPV varied with prevalence: specimens from males, females, urine specimens, and genital swabs had PPV's of 70.8, 13.3, 51.9, and 20.1%, respectively. The PPV was higher when the initial AMPLICOR optical density (OD) was greater than or equal to3.5 versus initial and repeat OD readings in an equivocal zone of greater than or equal to0.2 to <3.5 (65.1 versus 10.1%; P < 0.001). On repeat testing of specimens with ODs in the equivocal zone, 54 gave ODs of greater than or equal to0.2 and <2.0, 35 gave ODs of greater than or equal to2.0 and <3.5, and 12 gave ODs of; greater than or equal to3.5, with 3.7, 20, and 33.3% confirmed positive, respectively (P = 0.004). Comparing PCR to culture as the "gold standard," specificity increased from 96.8 to 99.9% when 16S rRNA PCR was performed on specimens positive by the COBAS AMPLICOR NG test. Confirmatory testing with a more specific method such as 16S rRNA PCR should be considered in low-prevalence populations, especially for specimens with an OD in the equivocal zone. C1 McGill Univ, Montreal Gen Hosp, Ctr Hlth, Dept Microbiol, Montreal, PQ H3G 1A4, Canada. RP Diemert, DJ (reprint author), NIAID, Malaria Vaccine Dev Unit, Twinbrook 1,Room 1123,5640 Fishers Ln, Rockville, MD 20852 USA. OI Diemert, David/0000-0002-2789-0512 NR 24 TC 35 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2002 VL 40 IS 11 BP 4056 EP 4059 DI 10.1128/JCM.40.11.4056-4059.2002 PG 4 WC Microbiology SC Microbiology GA 612BH UT WOS:000179053200028 PM 12409374 ER PT J AU Khalsa, JH Genser, S Francis, H Martin, B AF Khalsa, JH Genser, S Francis, H Martin, B TI Clinical consequences of marijuana SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article AB As documented in national surveys, for the post several years, marijuana has been the most commonly abused drug in the United States, with approximately 6% of the population 12 years and older having used the drug in the month prior to interview. The use of marijuana is not without significant health hazards. Marijuana is associated with effects on almost every organ system in the body, ranging from the central nervous system to the cardiovascular, endocrine, respiratory/pulmonary, and immune systems. Research presented in this special supplement will show that in addition to marijuana abuse/dependence, marijuana use is associated in some studies with impairment of cognitive function in the young and old, fetal and developmental consequences, cardiovascular effects (heart rate and blood pressure changes), respiratory/pulmonary complications such as chronic cough and emphysema, impaired immune function leading to vulnerability to and increased infections, and the risk of developing head, neck, and/or lung cancer. In general, acute effects are better studied than those of chronic use, and more studies are needed that focus on disentangling effects of marijuana from those of other drugs and adverse environmental conditions. C1 Natl Inst Drug Abuse, Ctr Aids & Other Med Consequences Drug Abuse, Natl Inst Hlth, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA. RP Khalsa, JH (reprint author), Natl Inst Drug Abuse, Ctr Aids & Other Med Consequences Drug Abuse, Natl Inst Hlth, 6001 Executive Blvd,Room 5198, Bethesda, MD 20892 USA. NR 3 TC 19 Z9 21 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD NOV PY 2002 VL 42 IS 11 SU S BP 7S EP 10S DI 10.1177/0091270002238788 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 623HW UT WOS:000179698400001 PM 12412830 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 Cognitive measures in long-term cannabis users SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; MARIJUANA USE; ABSTINENCE SYMPTOMS; EXECUTIVE FUNCTIONS; CONDUCT DISORDER; ATTENTION; ADHD AB The cognitive effects of long-term cannabis use are insufficiently understood. Most studies concur that cognitive deficits persist at least several days after stopping heavy cannabis use. But studies differ on whether such deficits persist long term,or whether they are correlated with increasing duration of lifetime cannabis use. The authors administered neuropsychological tests to 77 current heavy cannabis users who had smoked cannabis at least 5000 times in their lives, and to 87 control subjects who hod smoked no more than 50 times in their lives. The heavy smokers showed deficits on memory of word lists on Days 0, 1, and 7 of a supervised abstinence period. By Day 28, however, few significant differences were found between users and controls on the test measures, and there were few significant associations between total lifetime cannabis consumption and test performance. Although these findings may be affected by residual confounding, as in all retrospective studies, they suggest that cannabis-associated cognitive deficits are reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use. Journal of Clinical Pharmacology, 2002. C1 Harvard Univ, McLean Hosp, Sch Med, Biol Psychiat Lab, 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 44 TC 57 Z9 59 U1 3 U2 18 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD NOV PY 2002 VL 42 IS 11 SU S BP 41S EP 47S DI 10.1177/10091270002238793 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 623HW UT WOS:000179698400006 PM 12412835 ER PT J AU Chuang, DM Ren, M Senatorov, V Hashimoto, R Leeds, P AF Chuang, DM Ren, M Senatorov, V Hashimoto, R Leeds, P TI The therapeutic potential of lithium for excitotoxicity-related neurodegenerative diseases SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the International College-of-Geriatric-Psychoneuropharmacology CY OCT 10-12, 2002 CL BARCELONA, SPAIN SP Coll Geriatr Psychoneuropharmacol C1 NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RI Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 NR 0 TC 1 Z9 1 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2002 VL 63 IS 11 BP 1059 EP 1060 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 619JB UT WOS:000179471900048 ER PT J AU Lu, Z Tomchik, SM AF Lu, Z Tomchik, SM TI Effects of a red-tide toxin on fish hearing SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE audiogram; auditory brainstem response; brevetoxin; goldfish; neurotoxin ID SENSITIVE SODIUM-CHANNELS; DINOFLAGELLATE TOXINS; PTYCHODISCUS-BREVIS; RAT-BRAIN; BREVETOXINS; DERIVATIVES AB Red tides are formed from blooms of marine algae. Among them, the dinoflagellate (Karenia brevis) that is responsible for Florida red tides can release many types of natural toxins, which cause massive kills of marine animals, including endangered species, and threaten human health. This study was to investigate whether or not a neurotoxin, brevetoxin-3, purified from Florida red tides affects hearing sensitivity of a teleost fish, the goldfish (Carassius auratus). LD50 of the goldfish that were intraperitoneally injected with brevetoxin-3 was 0.068 mug g(-1). Evoked auditory brainstem responses were recorded, and hearing threshold was determined using a correlation method. By comparing thresholds of fish before and after a sublethal-dose injection (0.064 mug g(-1)) of the toxin, we found that brevetoxin-3 signiticantly reduces auditory sensitivity up to 9 dB at low frequencies (100 Hz and 500 Hz), but not at a high frequency (2,000 Hz). Reduction of hearing sensitivity was recovered within 24 h. To our knowledge, this is the first study showing a natural red-tide toxin causes minor hearing loss in vertebrates. Results of the study indicate that brevetoxin-3 could affect hearing capabilities of marine animals that survived exposure to red tides. Mechanisms of the toxin-induced reduction of hearing sensitivity are discussed. C1 Univ Miami, Dept Biol, Coral Gables, FL 33146 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Univ Miami, Neurosci Program, Miami, FL 33101 USA. RP Lu, Z (reprint author), Univ Miami, Dept Biol, 1301 Mem Dr, Coral Gables, FL 33146 USA. FU NIDCD NIH HHS [R29DC03275]; NIEHS NIH HHS [P30ES05705] NR 29 TC 19 Z9 20 U1 1 U2 9 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD NOV PY 2002 VL 188 IS 10 BP 807 EP 813 DI 10.1007/s00359-002-0369-8 PG 7 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 628AE UT WOS:000179968700007 PM 12466956 ER PT J AU Ling, SH Summers, RM Loew, MH McCollough, CH Johnson, CD AF Ling, SH Summers, RM Loew, MH McCollough, CH Johnson, CD TI Computer-aided detection of polyps in a colon phantom: Effect of scan orientation, polyp size, collimation, and dose SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CT colonography; computer-assisted diagnosis; phantom; colon cancer ID CT COLONOGRAPHY; VIRTUAL COLONOSCOPY; SPIRAL CT; FEASIBILITY; ACQUISITION; CHALLENGES; ARTIFACTS; LESIONS AB Purpose: To determine the importance of polyp size, orientation to the scan plane, collimation, scanner type (single or multislice helical), and radiation dose on computed tomography (CT) colonography computer-aided detection. Materials and Methods: Eight tissue-equivalent simulated polyps were placed into the interior of an air-filled acrylic tube placed within a water-filled box. Their sizes, expressed by diameter and height in millimeters, were 10 x 10, 10 x 7, 10 x 5, 10 x 3, 7 x 7, 7 x 5, 7 x 3, and 5 x 5. Detection of the polyps was performed by applying our prototype automated polyp detector software to 48 CT colonography data sets of the phantom acquired with different CT scanner settings. Results: We detected at least six of the eight polyps in 47 of 48 experiments. The two most frequently undetected polyps (7 x 7 and 5 x 5) had extreme eccentricity (their height was twice the radius of the base) and were most commonly missed for 90degrees tube orientation, 5-mm collimation, and high table speed. False-positive detections occurred in only 5 of 48 experiments. Conclusion: Clinically significant 10-mm polyps can be detected with 100%, sensitivity in all orientations, doses, collimations, and modes that we examined. C1 Mayo Clin, Dept Radiol, Rochester, MN USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. George Washington Univ, Dept Elect & Comp Engn, Inst Med Imaging & Image Anal, Washington, DC USA. RP Summers, RM (reprint author), NIH, Dept Radiol, Bldg 10,Room 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov NR 18 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2002 VL 26 IS 6 BP 1013 EP 1018 DI 10.1097/00004728-200211000-00027 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 629LT UT WOS:000180051700027 PM 12488752 ER PT J AU Sims, GP Aitken, R Rogerson, A AF Sims, GP Aitken, R Rogerson, A TI Identification and phylogenetic analysis of morphologically similar naked amoebae using small subunit ribosomal RNA SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE amoeba; cell surface structure; glycocalyx; gymnamoebae; molecular phylogeny; Platyamoeba; protozoa; ssrRNA; taxonomy; Vannella ID CLYDE-SEA AREA; GENUS ACANTHAMOEBA; BENTHIC SEDIMENTS; N-SP; AMEBAS; ABUNDANCE; SOIL; GYMNAMOEBAE; DIVERSITY; SCOTLAND AB Fan-shaped, naked amoebae are commonly encountered in samples from freshwater and marine habitats suggesting that they are an important component of the microbial food web. However, there are considerable problems in both detecting these amoebae and identifying them, given their morphological similarity. In this study we used restriction analysis and partial sequence analysis of the small-subunit 18S ribosomal RNA gene to examine the phylogenetic relationships between nine "fan-shaped" Vannella and Platyamoeba species. The molecular phylogeny showed that the marine Vannella and Platyamoeba isolates are closely related, whereas the freshwater isolates are disparate. Thus, the current reliance on the fine structure of the cell coat (glycocalyx) used to separate these genera is not justified. The study also highlights sequence elements that might be targeted by fluorescent probes for the direct detection of these amoebae in field samples. The molecular data were also used to aid the identification of three unknown fan-shaped isolates. All three unknowns resembled Vannella or Platyamoeba. However, one of the strains (a small < 10 mum, benthic, fan-shaped amoeba) probably represents a new genus. C1 Univ Marine Biol Stn, Millport KA28 0EG, Isle Cumbrae, Scotland. Univ Glasgow, Inst Biomed & Life Sci, Div Infect & Immun, Glasgow G12 8QQ, Lanark, Scotland. RP Sims, GP (reprint author), NIH, Bldg 10,Room 6N44,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 22 Z9 23 U1 0 U2 7 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD NOV-DEC PY 2002 VL 49 IS 6 BP 478 EP 484 DI 10.1111/j.1550-7408.2002.tb00232.x PG 7 WC Microbiology SC Microbiology GA 626GK UT WOS:000179863300009 PM 12503684 ER PT J AU Thompson, ED Mayer, GD Walsh, PJ Hogstrand, C AF Thompson, ED Mayer, GD Walsh, PJ Hogstrand, C TI Sexual maturation and reproductive zinc physiology in the female squirrelfish SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE zinc; metallothionein; vitellogenin; estradiol; sexual maturity; reproductive physiology; female; squirrelfish ID RAINBOW-TROUT; SALMO-GAIRDNERI; METALLOTHIONEIN; VITELLOGENIN; PROTEIN; BINDING; TRANSPORTERS; FAMILY; LIVER AB Female squirrelfish (Holocentridae) accumulate higher concentrations of hepatic zinc than any other known organism. In the liver cells, up to 70% of zinc is bound to metallothionein (NIT), which is expressed at extremely high levels. These attributes are related to reproduction in ways that have not been fully characterized. In the present study, we have demonstrated that female-specific zinc and NIT accumulation and distribution are strongly correlated to the onset of sexual maturity in Holocentrus adsenscionis. Sexual maturation not only resulted in increased concentrations of zinc in the liver and plasma, but also increased levels of hepatic NIT mRNA. Furthermore, mature female squirrelfish exhibited greater proportions of NIT protein in the nuclear liver cell fractions. To characterize the physiology further, we have examined the influence of the female sex hormone 17 beta-estradiol (E-2). E-2 was not sufficient to elicit an increase in hepatic zinc concentrations or NIT mRNA levels. E-2 administration did, however, result in increased levels of NIT in the nuclear fraction as well as overall hepatic NIT protein. E-2 also increased concentrations of zinc in the plasma. The changes in zinc concentration in the bloodstream followed the same time course as vitellogenin (VTG) transport from the liver. However, the high ratio of molar concentrations of zinc to VTG in the bloodstream suggest that VTG may not be the primary vehicle for hepato-ovarian zinc transport in squirrelfish. C1 Univ Kentucky, TH Morgan Sch Biol Sci, Lexington, KY 40506 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, Miami, FL 33149 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Kings Coll London, Sch Hlth & Life Sci, London SE1 9NN, England. RP Univ Kentucky, TH Morgan Sch Biol Sci, 101 Morgan Bldg, Lexington, KY 40506 USA. EM christer.hogstrand@kcl.ac.uk RI Mayer, Gregory/K-4496-2012; Hogstrand, Christer/C-9041-2013; Mayer, Gregory/A-8459-2017 OI Mayer, Gregory/0000-0002-2652-9856; Mayer, Gregory/0000-0002-2652-9856 FU NIEHS NIH HHS [P30 ES057705] NR 30 TC 23 Z9 24 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 EI 1477-9145 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 2002 VL 205 IS 21 BP 3367 EP 3376 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 618JR UT WOS:000179415400010 PM 12324546 ER PT J AU Akhmedkhanov, A Revich, B Adibi, JJ Zeilert, V Masten, SA Patterson, DG Needham, LL Toniolo, P AF Akhmedkhanov, A Revich, B Adibi, JJ Zeilert, V Masten, SA Patterson, DG Needham, LL Toniolo, P TI Characterization of dioxin exposure in residents of Chapaevsk, Russia SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE blood level; dibenzofuran; dioxin; nonoccupational exposure; PCB; Russia ID TOXIC EQUIVALENCY FACTORS; POLYCHLORINATED-BIPHENYLS; SEX-RATIO; INFANTS; SERUM; CHILDREN; HEALTH; PCBS; DIBENZOFURANS; MORTALITY AB Since 1967, a chemical plant in the town of Chapaevsk (Samara province, Russia) has produced large amounts of chlorinated compounds and is suspected to be a major source of local environmental dioxin contamination. Dioxins have been detected in the local air, soil, drinking water, vegetables, and cow's milk. Human exposure to dioxins is suspected as a factor in the deteriorating local public health. In an effort to characterize nonoccupational dioxin exposure among local residents, during the summer of 1998, 24 volunteers were recruited to donate blood and to provide information about their residence, employment, demographics, medical history, and dietary habits. Selected polychlorinated dibenzodioxins, dibenzofurans, and coplanar biphenyls were measured in blood serum samples. The mean concentration of total dioxin World Health Organization toxic equivalents (WHO - TEQ(98)) based on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) was 61.2 (range 16.4-168.1) pg/g lipid. Subjects living in close proximity to the plant (less than 5 km) had significantly higher dioxin levels (mean WHO - TEQ(98), 75.7 pg/g lipid), as compared to subjects living more than 5 km from the plant (mean WHO - TEQ(98), 44.1 pg/g lipid) (P<0.04). Comparisons of the study results with available published data indicate that average blood dioxin levels were substantially higher in Chapaevsk residents than in nonoccupationally exposed populations of other parts of Russia, Europe, and North America. Chronic exposures of such magnitude may have appreciable adverse effects on public health. C1 NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA. Russian Acad Sci, Ctr Demog & Human Ecol, Inst Forcasting, Moscow 117418, Russia. Columbia Univ, Sch Publ Hlth, New York, NY 10032 USA. Chapaevsk Cent City Hosp, Chapaevsk 446100, Samara Oblast, Russia. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. RP Akhmedkhanov, A (reprint author), NYU, Sch Med, Dept Obstet & Gynecol, 550 1St Ave,NBV-9E2, New York, NY 10016 USA. RI Needham, Larry/E-4930-2011; Adibi, Jennifer/I-8077-2016; masten, scott/R-1403-2016 OI Adibi, Jennifer/0000-0001-6562-8315; masten, scott/0000-0002-7847-181X FU NCI NIH HHS [CA16087]; NIEHS NIH HHS [ES00260, Y1-ES-8062-02] NR 37 TC 7 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD NOV PY 2002 VL 12 IS 6 BP 409 EP 417 DI 10.1038/sj.jea.7500243 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 630ZL UT WOS:000180141700003 PM 12415489 ER PT J AU Coble, J Hoppin, JA Engel, L Elci, OC Dosemeci, M Lynch, CF Alavanja, M AF Coble, J Hoppin, JA Engel, L Elci, OC Dosemeci, M Lynch, CF Alavanja, M TI Prevalence of exposure to solvents, metals, grain dust, and other hazards among farmers in the Agricultural Health Study SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE confounding; exposure; farmers; pesticides ID CANCER AB Exposures to multiple chemical, physical, and biological agents in agricultural work environments can result in confounding that may obscure or distort risks observed in epidemiologic studies. The Agricultural Health Study (AHS) is a large epidemiology study being conducted to investigate health risks among pesticide applicators and their families. During enrollment in the AHS, questionnaires were administered to over 52,000 licensed pesticide applicators from North Carolina and Iowa, who were mostly farmers. Questions about the frequency of various farming tasks were used to estimate the prevalence of exposure to solvents (25%), metals (68%), grain dusts (65%), diesel exhaust fumes (93%), and other hazards, including exposure to pesticides. Most of the farmers in the AHS reported performing routine maintenance tasks at least once a month, such as painting (63%), welding (64%), and repair of pesticide equipment (58%). The majority of farmers (74% in North Carolina; 59% in Iowa) reported holding nonfarm jobs, of which the most frequent were construction and transportation. The majority of the farmers enrolled in the AHS (55%) also reported that they mixed or applied pesticides on 10 or more days per year. The associations between the use of pesticides and the frequency with which the farmers in the AHS reported performing various types of specific farming activities were assessed to evaluate potential confounding. Confounding risk ratios calculated for these activities suggest that the magnitude of bias due to confounding is likely to be minimal. C1 NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Rockville, MD 20892 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. RP Coble, J (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, 6120 Execut Blvd,EPS8110, Rockville, MD 20892 USA. OI Engel, Lawrence/0000-0001-9268-4830 NR 14 TC 28 Z9 28 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD NOV PY 2002 VL 12 IS 6 BP 418 EP 426 DI 10.1038/sj.jea.7500248 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 630ZL UT WOS:000180141700004 PM 12415490 ER PT J AU Morales, LS Lara, M Kington, RS Valdez, RO Escarce, JJ AF Morales, LS Lara, M Kington, RS Valdez, RO Escarce, JJ TI Socioeconomic, cultural, and behavioral factors affecting Hispanic health outcomes SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Review DE Hispanic Americans; Hispanic health paradox; socioeconomic status; health status; review ID MEXICAN-AMERICANS; UNITED-STATES; RISK-FACTORS; GENERATIONAL-DIFFERENCES; EPIDEMIOLOGIC PARADOX; EDUCATIONAL-LEVEL; LIFE EXPECTANCY; MORTALITY-RATES; ADULT HISPANICS; HHANES 1982-84 AB Evidence suggests that social and. economic factors are important determinants of health. Yet, despite higher poverty rates, less education, and worse access to health care, health outcomes of many Hispanics living in the United States today are equal to, or better than, those of non-Hispanic whites. This paradox is described in the literature as the epidemiological paradox or Hispanic health paradox. In this paper, the authors selectively review data and research supporting the existence of the epidemiological paradox. They find substantial support for the existence of the epidemiological paradox, particularly among Mexican Americans. Census undercounts of Hispanics, misclassification of Hispanic deaths, and emigration of Hispanics do not fully account for the epidemiological paradox. Identifying protective factors underlying the epidemiological paradox, while improving access to care and the economic conditions among Hispanics, are important research and policy implications of this review. C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. NIH, Bethesda, MD 20892 USA. Med Coll Penn & Hahnemann Univ, Sch Publ Hlth, Philadelphia, PA 19129 USA. RP Morales, LS (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. FU AHRQ HHS [U18 HS009204, U18HS09204]; NIA NIH HHS [P30 AG021684]; NIMHD NIH HHS [P20 MD000148] NR 103 TC 166 Z9 167 U1 4 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2002 VL 13 IS 4 BP 477 EP 503 DI 10.1177/104920802237532 PG 27 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 604ME UT WOS:000178624600005 PM 12407964 ER PT J AU Forns, X Bukh, J Purcell, RH AF Forns, X Bukh, J Purcell, RH TI The challenge of developing a vaccine against hepatitis C virus SO JOURNAL OF HEPATOLOGY LA English DT Review ID CELLULAR IMMUNE-RESPONSES; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; INFECTIOUS MOLECULAR CLONE; STIMULATING FACTOR GENE; DNA-BASED IMMUNIZATION; HYPERVARIABLE REGION-1; PLASMID DNA; E2 PROTEIN; NONSTRUCTURAL PROTEINS; STRUCTURAL PROTEINS C1 Hosp Clin Barcelona, Inst Malalties Digest, Liver Unit, E-08036 Barcelona, Spain. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Forns, X (reprint author), Hosp Clin Barcelona, Inst Malalties Digest, Liver Unit, Villaroel 170, E-08036 Barcelona, Spain. NR 114 TC 44 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2002 VL 37 IS 5 BP 684 EP 695 AR PII S0168-8278(02)00308-2 DI 10.1016/S0168-8278(02)00308-2 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 615JQ UT WOS:000179242400022 PM 12399239 ER PT J AU Rose, KM Holme, I Light, KC Sharrett, AR Tyroler, HA Heiss, G AF Rose, KM Holme, I Light, KC Sharrett, AR Tyroler, HA Heiss, G TI Association between the blood pressure response to a change in posture and the 6-year incidence of hypertension: prospective findings from the ARIC study SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE postural blood pressure change; isolated systolic hypertension; orthostatic hypotension ID ORTHOSTATIC HYPOTENSION; CARDIOVASCULAR REACTIVITY; STRESS; PREVALENCE; PREDICTOR AB The association between the blood pressure response to a change from the supine to the standing position and the 6-year incidence of hypertension was studied in a biethnic, middle-aged cohort of 6951 normotensive men and women free of coronary heart disease at baseline. Postural change in systolic blood pressure (SBP) was categorized into deciles, and the middle four deciles served as the referent (no change) group. In unadjusted analyses, the incidence of hypertension was higher among both those with SBP increases and decreases relative to those in the referent group. Associations were modestly attenuated after controlling for age, ethnicity, and gender and cardiovascular disease risk factors. However, after adjustment for baseline, seated SBP, a modest association with incident hypertension persisted only for SBP decreases. Orthostatic hypotension (upon standing) was associated with incident hypertension and isolated systolic hypertension and, unexpectedly, this increased risk was highest among those with the lowest levels of baseline, resting SBP. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Bank Amer Ctr, Chapel Hill, NC 27514 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27514 USA. Ulleval Hosp, Inst Med Stat, Life Insurance Co, Oslo, Norway. RP Rose, KM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Bank Amer Ctr, Suite 306,137 E Franklin St, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [N01-HC55015, 5T32HL07055, N01-HC-55016, N01-HC-55019, N01-HC-55020, N01-HC-55022, N01-HC55021] NR 32 TC 27 Z9 28 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD NOV PY 2002 VL 16 IS 11 BP 771 EP 777 DI 10.1038/sj.jhh.1001482 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 633MA UT WOS:000180286000004 PM 12444538 ER PT J AU Hel, Z Nacsa, J Tryniszewska, E Tsai, WP Parks, RW Montefiori, DC Felber, BK Tartaglia, J Pavlakis, GN Franchini, G AF Hel, Z Nacsa, J Tryniszewska, E Tsai, WP Parks, RW Montefiori, DC Felber, BK Tartaglia, J Pavlakis, GN Franchini, G TI Containment of simian immunodeficiency virus infection in vaccinated macaques: Correlation with the magnitude of virus-specific pre- and postchallenge CD4(+) and CD8(+) T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RHESUS-MONKEYS; VIRAL LOAD; IN-VIVO; HELPER RESPONSES; DENDRITIC CELLS; IMMUNE EVASION; VIREMIA; SIV; AIDS; TYPE-1 AB Macaques infected with the SIV strain SIVmac251 develop a disease closely resembling human AIDS characterized by high viremia, progressive loss of CD4(+) T cells, occurrence of opportunistic infection, cachexia, and lymphomas. We report in this study that vaccination with the genetically attenuated poxvirus vector expressing the structural Ags of SIVmac (NYVAC-SIV-gag, pol, env) in combination with priming with DNA-SIV-gag, env resulted in significant suppression of viremia within 2 mo after mucosal exposure to the highly pathogenic SIVmac251 in the majority of vaccinated macaques. The control of viremia in these macaques was long lasting and inversely correlated to the level of both pre- and postchallenge Gag-specific lymphoproliferative responses, as well as to the level of total SIV-specific CD4(+) T lymphocyte responses at the peak of acute viremia as detected by intracellular cytokine-staining assay. Viremia containment also correlated with the frequency of the immunodominant Gag(181-189)CM9 epitope-specific CD8(+) T cells present before the challenge or expanded during acute infection. These data indicate, for the first time, the importance of vaccine-induced CD4(+) Th cell responses as an immune correlate of viremia containment. The results presented in this work also further demonstrate the potential of a DNA-prime/attenuated poxvirus-boost vaccine regimen in an animal model that well mirrors human AIDS. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Med Acad Bialystok, Dept Pediat, Bialystok, Poland. Duke Univ, Med Ctr, Durham, NC 27710 USA. Aventis Pasteur, Toronto, ON, Canada. RP Franchini, G (reprint author), 41-D804, Bethesda, MD 20892 USA. OI Hel, Zdenek/0000-0002-4923-4794 FU NIAID NIH HHS [AI85343] NR 54 TC 113 Z9 116 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 NOV 1 PY 2002 VL 169 IS 9 BP 4778 EP 4787 PG 10 WC Immunology SC Immunology GA 607DY UT WOS:000178777400013 PM 12391187 ER PT J AU Medvedev, AE Lentschat, A Wahl, LM Golenbock, DT Vogel, SN AF Medvedev, AE Lentschat, A Wahl, LM Golenbock, DT Vogel, SN TI Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; DENDRITIC CELLS; CUTTING EDGE; BACTERIAL LIPOPOLYSACCHARIDE; DIFFERENTIAL EXPRESSION; MURINE MACROPHAGES; ENDOTHELIAL-CELLS; LIPOTEICHOIC ACID AB Prior exposure to LPS induces a transient state of cell refractoriness to subsequent LPS restimulation, known as endotoxin tolerance. Induction of LPS tolerance has been reported to correlate with decreased cell surface expression of the LPS receptor complex, Toll-like receptor 4 (TLR4)/MD-2. However, other results have underscored the existence of mechanisms of LPS tolerance that operate downstream of TLR4/MD-2. In the present study we sought to delineate further the molecular basis of LPS tolerance by examining the TLR4 signaling pathway in endotoxin-tolerant cells. Pretreatment of human monocytes with LPS decreased LPS-mediated NF-kappaB activation, p38 mitogen-activated protein kinase phosphorylation, and TNF-alpha gene expression, documenting the induction of endotoxin tolerance. FACS and Western blot analyses of LPS-tolerant monocytes showed increased TLR2 expression, whereas TLR4 expression levels were not affected. Comparable levels of mRNA and protein for myeloid differentiation factor 88 (MyD88), IL-1R-associated kinase I (IRAK-1), and TNFR-associated factor-6 were found in normal and LPS-tolerant monocytes, while MD-2 mRNA expression was slightly increased in LPS-tolerant cells. LPS induced the association of MyD88 with TLR4 and increased IRAK-1 activity in medium-pretreated cells. In LPS-tolerant monocytes, however, MyD88 failed to be recruited to TLR4, and IRAK-I was not activated in response to LPS stimulation. Moreover, endotoxin-tolerant CHO cells that overexpress human TLR4 and MD-2 also showed decreased IRAK-1 kinase activity in response to LPS despite the failure of LPS to inhibit cell surface expression of transfected TLR4 and MD-2 proteins. Thus, decreased TLR4-MyD88 complex formation with subsequent impairment of IRAK-1 activity may underlie the LPS-tolerant phenotype. C1 Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. RP Vogel, SN (reprint author), Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. FU NIAID NIH HHS [AI18797, AI44936, AIP0150305]; NIGMS NIH HHS [R01GM54060] NR 66 TC 208 Z9 216 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2002 VL 169 IS 9 BP 5209 EP 5216 PG 8 WC Immunology SC Immunology GA 607DY UT WOS:000178777400065 PM 12391239 ER PT J AU Tryniszewska, E Nacsa, J Lewis, MG Silvera, P Montefiori, D Venzon, D Hel, Z Parks, RW Moniuszko, M Tartaglia, J Smith, KA Franchini, G AF Tryniszewska, E Nacsa, J Lewis, MG Silvera, P Montefiori, D Venzon, D Hel, Z Parks, RW Moniuszko, M Tartaglia, J Smith, KA Franchini, G TI Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; STRUCTURED TREATMENT INTERRUPTIONS; I MOLECULE MAMU-A-ASTERISK-01; ANTIVIRAL IMMUNE-RESPONSES; CELL RESPONSES; HIV-INFECTION; CD8(+) LYMPHOCYTES; PERIPHERAL-BLOOD; RHESUS MACAQUES AB A cohort of rhesus macaques with long-standing SIVmac251 infection (greater than or equal to5 mo) was treated with continuous antiretroviral therapy (ART). A group of eight macaques was vaccinated with or without simultaneous administration of low dose IL-2 with the highly attenuated poxvirus vector (NYVAC) vaccine candidate expressing the SIVmac structural gag-pol-env (gpe) genes and a novel, chimeric fusion protein derived from the rev-tat-nef (rtn) regulatory genes. Control groups consisted of mock-vaccinated macaques or animals treated only with IL-2. Vaccination significantly expanded both virus-specific CD4(+) and CD8(+) T cell responses, and IL-2 further increased the vaccine-induced response to an immunodominant Gag epitope. Following antiretroviral treatment interruption, the viral set point was significantly lower in vaccinated than in control macaques for at least 4 consecutive mo, and viral containment was inversely correlated with vaccine-induced, virus-specific CD4(+) and CD8(+) T cell responses. These data provide the proof of concept that therapeutic vaccination before cessation of ART may be a feasible approach in the clinical management of HIV-1 infection. C1 NCI, Sect Anim Models & Retroviral Vaccines, Ctr Canc Res, NIH,Basic Res Lab, Bethesda, MD 20892 USA. Med Acad Bialystok, Dept Pediat 3, Bialystok, Waszyngtona, Poland. So Res Inst, Frederick, MD 21701 USA. Duke Univ, Med Ctr, Ctr AIDS Res, Durham, NC 27710 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Aventis Pasteur, Toronto, ON, Canada. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Sect Anim Models & Retroviral Vaccines, Ctr Canc Res, NIH,Basic Res Lab, 41 Lib Dr,Bldg 41, Room D804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; OI Hel, Zdenek/0000-0002-4923-4794 FU NIAID NIH HHS [AI85343, N01-AI-15451] NR 56 TC 74 Z9 76 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 NOV 1 PY 2002 VL 169 IS 9 BP 5347 EP 5357 PG 11 WC Immunology SC Immunology GA 607DY UT WOS:000178777400082 PM 12391256 ER PT J AU Choi, EH Lee, HJ Yoo, T Chanock, SJ AF Choi, EH Lee, HJ Yoo, T Chanock, SJ TI A common haplotype of interleukin-4 gene IL4 is associated with severe respiratory syncytial virus disease in Korean children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INFECTION; ASTHMA; MICE; ILLNESS; CELLS; ATOPY; IL-4 AB Respiratory syncytial virus (RSV) is a major health problem in young children, and host response to severe disease favors a Th2 immune response. To investigate the genetic basis for RSV disease severity, linked variants of 3 Th2 cytokine genes, IL4, IL13, and IL5 (which are clustered on chromosome 5q31.1) were characterized in 105 children who were hospitalized with severe RSV infection and 315 Korean control subjects in a pilot study. A common IL4 haplotype defined at 5 loci, which includes the -589T promoter variant, previously shown to be associated with increased interleukin (IL)-4 transcriptional activity and predisposition to asthma, was overrepresented in patients with severe RSV disease (odds ratio, 1.63; P = .02). These results support the hypothesis that severe RSV disease might be related to increased Th2 response, which is perhaps mediated by overexpression of IL-4, and provide preliminary evidence for a genetic link between severe RSV disease and subsequent wheezing. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, Gaithersburg, MD 20877 USA. Seoul Natl Univ, Coll Med, Dept Pediat, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Family Med, Seoul, South Korea. Seoul Natl Univ Hosp, Virus Res Ctr, Clin Res Inst, Seoul 110744, South Korea. RP Chanock, SJ (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, 8717 Grovemont Cir, Gaithersburg, MD 20877 USA. RI Choi, Eun Hwa/J-5691-2012; Lee, Hoan Jong/J-5616-2012 NR 22 TC 102 Z9 109 U1 0 U2 1 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 NOV 1 PY 2002 VL 186 IS 9 BP 1207 EP 1211 DI 10.1086/344310 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 603TY UT WOS:000178577500002 PM 12402189 ER PT J AU Marovich, MA Mascola, JR Eller, MA Louder, MK Caudrelier, PA El-Habib, R Ratto-Kim, S Cox, JH Currier, JR Levine, BL June, CH Bernstein, WB Robb, ML Schuler-Thurner, B Steinman, RM Birx, DL Schlesinger-Frankel, S AF Marovich, MA Mascola, JR Eller, MA Louder, MK Caudrelier, PA El-Habib, R Ratto-Kim, S Cox, JH Currier, JR Levine, BL June, CH Bernstein, WB Robb, ML Schuler-Thurner, B Steinman, RM Birx, DL Schlesinger-Frankel, S TI Preparation of clinical-grade recombinant canarypox-human immunodeficiency virus vaccine-loaded human dendritic cells SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Conference on Retroviruses and Opportunistic Infections CY FEB 04-08, 2001 CL CHICAGO, ILLINOIS ID NECROSIS-FACTOR-ALPHA; CHEMOKINE RECEPTOR EXPRESSION; PERIPHERAL LYMPHOID ORGANS; HERPES-SIMPLEX VIRUS; T-CELLS; PROTEASOME REGULATOR; IMMUNE-RESPONSES; LARGE NUMBERS; ALVAC-HIV; MATURATION AB Preclinical data are reported that support a human immunodeficiency virus (HIV) vaccine strategy using recombinant canarypox-HIV vectors (ALVAC-HIV) to load human dendritic cells (DCs) with HIV antigens. Clinical-grade DCs were infected with good manufacturing practice-grade ALVAC-HIV vaccine constructs. ALVAC infection, HIV gene expression, and DC viability and function were monitored by use of immunohistochemistry, flow cytometry, blastogenesis assays, antigen-specific interferon (IFN)-gamma enzyme-linked immunospot assay, and enzyme-linked immunosorbent assay protein detection. The vaccines infected both immature and mature DCs, and intracellular HIV-1 Gag protein was detected within hours. ALVAC-HIV induced DC maturation that was mediated by tumor necrosis factor-alpha and induced DC apoptosis that was directly related to the length of vaccine exposure. Of importance, the infected DCs remained functional in T cell stimulation assays and induced HIV antigen-specific CD8(+) T cell production of IFN-gamma from cells of HIV-1-infected individuals. These data support an ongoing HIV vaccine trial comparing conventional vaccine delivery routes with ex vivo vaccine-loaded autologous DCs for immunogenicity in HIV-1-uninfected volunteers. C1 US Mil HIV Res Program, Div Retrovirol, Rockville, MD 20850 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Penn, Abramson Family Canc Res Inst, Ctr Canc, Philadelphia, PA 19104 USA. Rockefeller Univ, New York, NY 10021 USA. IDM Biotech, Montreal, PQ, Canada. Aventis Pasteur, Lyon, France. Univ Hosp Erlangen, Erlangen, Germany. RP Marovich, MA (reprint author), US Mil HIV Res Program, Div Retrovirol, 13 Taft Ctr,Ste 200, Rockville, MD 20850 USA. RI Levine, Bruce/D-1688-2009; Steinman, Ralph/F-7729-2012 NR 47 TC 22 Z9 23 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 NOV 1 PY 2002 VL 186 IS 9 BP 1242 EP 1252 DI 10.1086/344302 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 603TY UT WOS:000178577500006 PM 12402193 ER PT J AU Cooper, PJ Schwartz, LB Irani, AM Awadzi, K Guderian, RH Nutman, TB AF Cooper, PJ Schwartz, LB Irani, AM Awadzi, K Guderian, RH Nutman, TB TI Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MAST-CELL ACTIVATION; SYSTEMIC MASTOCYTOSIS; LYMPH-NODES; ANAPHYLAXIS; SKIN; PATHOGENESIS; CHEMOTHERAPY; EXPRESSION; BASOPHILS; VOLVULUS AB To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups of Onchocerca volvulus-infected subjects after ivermectin treatment. After treatment, an increase in tryptase levels was observed concurrent with the onset of blood eosinopenia and preceding the appearance of plasma eosinophil-derived neurotoxin (EDN) and interleukin-5. Tryptase levels were correlated with development of peripheral eosinopenia and markers of eosinophil activation and degranulation. Dermal mast cell numbers increased transiently at 24 h after treatment, preceding the onset of dermal eosinophil infiltration and the development of clinically apparent inflammation. Local reactions were strongly correlated with levels of plasma tryptase and EDN, and the severity of systemic reactions was correlated with levels of tryptase, EDN, and interleukin-5. The data indicate that mast cells play a role in initiation of tissue inflammatory reactions after ivermectin treatment of onchocerciasis. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Div Rheumatol Allergy & Immunol, Richmond, VA USA. Hohoe Hosp, Onchocerciasis Chemotherapy Res Ctr, Hohoe, Ghana. Hosp Vozandes, Dept Clin Invest, Quito, Ecuador. RP Cooper, PJ (reprint author), St George Hosp, Sch Med, Dept Infect Dis, London SW17 0RE, England. FU NIAID NIH HHS [AI-20487, AI-27517]; NIAMS NIH HHS [AR-45441] NR 28 TC 14 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2002 VL 186 IS 9 BP 1307 EP 1313 DI 10.1086/344318 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 603TY UT WOS:000178577500013 PM 12402200 ER PT J AU Ikewaki, K Zech, LA Brewer, HB Rader, DJ AF Ikewaki, K Zech, LA Brewer, HB Rader, DJ TI Comparative in vivo metabolism of apolipoproteins E2 and E4 in heterozygous apoE2/4 subjects SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID E POLYMORPHISM; LIPOPROTEINS AB Apolipoprotein E (apoE) exists in three common forms in humans: the wild-type apoE3 and two common genetic variants, apoE2 and apoE4. Although previous studies have examined the metabolism of the different apoE isoforms in human subjects, they have not involved direct comparison of two different isoforms in subjects heterozygous for the same two isoforms. We conducted this study to directly compare the catabolism of apoE2 and apoE4 in heterozygous E2/4 subjects in vivo. Iodine 131-labeled apoE2 and iodine 125-labeled apoE4 were simultaneously injected into three E4/2 heterozygous subjects. The mean residence time of apoE4 (0.40 +/- 0.01 day) was found to be one-third that of apoE2 (1.20 +/- 0.18 day). ApoE2 was present primarily in high-density lipoprotein, whereas apoE4 was present equally in very low density and high-density lipoprotein. In all lipoprotein subfractions, apoE4 was catabolized at a much faster rate than apoE2. In conclusion, E4 is catabolized three times faster than apoE2 in heterozygous E2/4 subjects, indicating that these two apoE isoproteins have distinct metabolic pathways. C1 Jikei Univ, Sch Med, Dept Cardiol, Tokyo, Japan. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Rader, DJ (reprint author), Univ Penn, Med Ctr, 654 BRB2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. NR 13 TC 13 Z9 13 U1 2 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD NOV PY 2002 VL 140 IS 5 BP 369 EP 374 DI 10.1067/mlc.2002.129066 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 618XJ UT WOS:000179442600010 PM 12434139 ER PT J AU Kazerouni, N Schairer, C Friedman, HB Lacey, JV Greene, MH AF Kazerouni, N Schairer, C Friedman, HB Lacey, JV Greene, MH TI Family history of breast cancer as a determinant of the risk of developing endometrial cancer: a nationwide cohort study SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; YOUNG-WOMEN; ADJUVANT TAMOXIFEN; SYNDROME-II; EPIDEMIOLOGY; CARCINOMA; ASSOCIATION; OVARIAN; TUMOR; AGE C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Greene, MH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Room 7022,Execut Plaza S,6120 Execut Blvd, Rockville, MD 20852 USA. NR 61 TC 9 Z9 10 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2002 VL 39 IS 11 BP 826 EP 832 DI 10.1136/jmg.39.11.826 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 614UC UT WOS:000179208400009 PM 12414823 ER PT J AU Castle, PE Schiffman, M Gravitt, PE Kendall, H Fishman, S Dong, H Hildesheim, A Herrero, R Bratti, MC Sherman, ME Lorincz, A Schussler, JE Burk, RD AF Castle, PE Schiffman, M Gravitt, PE Kendall, H Fishman, S Dong, H Hildesheim, A Herrero, R Bratti, MC Sherman, ME Lorincz, A Schussler, JE Burk, RD TI Comparisons of HPV DNA detection by MY09/11 PCR methods SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HPV; MY09/11 PCR; PGMY09/11; PCR ID HUMAN-PAPILLOMAVIRUS INFECTION; CERVICAL-CANCER; COSTA-RICA; WOMEN; EPIDEMIOLOGY; WORLDWIDE; SPECIMENS; NEOPLASIA; AGREEMENT AB Two modifications to the original L1 consensus primer human papillomavirus (HPV) PCR method, MY09-MY011, using AmpliTaq DNA polymerase (MY-Taq), were evaluated for HPV DNA detection on clinical specimens from a cohort study of cervical cancer in Costa Rica. First, HPV DNA testing of 2978 clinical specimens by MY09-MY011 primer set, using AmpliTaq Gold DNA polymerase (MY-Gold) were compared with MY-Taq testing. There was 86.8% total agreement (kappa = 0.72, 95%CI = 0.70-75) and 69.6% agreement among positives between MY-Gold and MY-Taq. MY-Gold detected 38% more HPV infections (P < 0.0001) and 45% more cancer-associated (high-risk) HPV types (P < 0.0001) than MY-Taq, including 12 of the 13 high-risk HPV types. Analyses of discordant results using cytologic diagnoses and detection of HPV DNA by the Hybrid Capture 2 Test suggested that MY-Gold preferentially detected DNA positive specimens with lower HPV viral loads compared with MY-Taq. In a separate analysis, PGMY09-PGMY11 (PGMY-Gold), a redesigned MY09/11 primer set, was compared with MY-Gold for HPV DNA detection (n = 439). There was very good agreement between the two methods (kappa = 0.83; 95%CI = 0.77-0-88) and surprisingly no significant differences in HPV detection (P = 0.41). In conclusion, we found MY-Gold to be a more sensitive assay for the detection of HPV DNA than MY-Taq. Our data also suggest that studies reporting HPV DNA detection by PCR need to report the type of polymerase used, as well as other assay specifics, and underscore the need for worldwide standards of testing. (C) 2002 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Proyecto Epidemiol, Guanacaste, Costa Rica. Digene Corp, Gaithersburg, MD USA. Informat Managment Serv, Silver Spring, MD USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. FU NCI NIH HHS [N0ICP21081, N0ICP31061, R01CA78527] NR 19 TC 118 Z9 122 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD NOV PY 2002 VL 68 IS 3 BP 417 EP 423 DI 10.1002/jmv.10220 PG 7 WC Virology SC Virology GA 597RD UT WOS:000178233800018 PM 12226831 ER PT J AU Yu, J Cadet, JL Angulo, JA AF Yu, J Cadet, JL Angulo, JA TI Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE methamphetamine; neurokinin-1 receptor; neurotoxicity; Parkinson's disease; striatum; substance P ID TACHYKININ NK1 RECEPTOR; SUBSTANCE-P; RAT STRIATUM; MESSENGER-RNA; GLUTAMATE RELEASE; NUCLEUS-ACCUMBENS; TRANSGENIC MICE; NULL MUTATION; AMPHETAMINE; EXPRESSION AB Methamphetamine (METH) is an addictive substance that also causes extensive neural degeneration in the central nervous system. Because METH augments striatal substance P (SP) levels, we hypothesized that this neuropeptide plays a role in methamphetamine-induced toxicity and neural damage in the striatum. In this study we present evidence demonstrating that signaling through the neurokinin-1 (NK-1) receptor by SP plays an important role in methamphetamine-induced toxicity in the striatum. We tested the effects of the selective NK-1 receptor antagonists WIN-51,708 and L-733,060 on several markers of dopaminergic terminal toxicity in the mouse striatum. Administration of NK-1 receptor antagonist prevented the loss of dopamine transporters assessed by autoradiography and western blotting, the loss of tissue dopamine assessed by high-pressure liquid chromatography, and the loss of tyrosine hydroxylase, as well as the induction of glial fibrillary acidic protein determined by western blotting. Pre-treatment with NK-1 receptor antagonist had no effect on METH-induced hyperthermia. Pre-exposure of mice to either of the NK-1 receptor antagonists alone was without effect on all of these neurochemical markers. These results provide the first evidence that tachykinins, particularly SP, acting through NK-1 receptors, play a crucial role in the pathogenesis of nigrostriatal dopaminergic terminal degeneration induced by METH. This finding could lead to novel therapeutic strategies to offset drug addictions as well as in the treatment of a number of disorders including Parkinson's and Huntington's diseases. C1 CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. NIDA, Mol Neuropsychiat Sect, Div Intramural Res, NIH, Baltimore, MD USA. RP Angulo, JA (reprint author), CUNY Hunter Coll, Dept Biol Sci, 695 Pk Ave,Rm 927HN, New York, NY 10021 USA. FU NIDA NIH HHS [DA 12136]; NINDS NIH HHS [NS 410973] NR 44 TC 30 Z9 30 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2002 VL 83 IS 3 BP 613 EP 622 DI 10.1046/j.1471-4159.2002.01155.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 605KJ UT WOS:000178676800014 PM 12390523 ER PT J AU Milhavet, O Martindale, JL Camandola, S Chan, SL Gary, DS Cheng, A Holbrook, NJ Mattson, MP AF Milhavet, O Martindale, JL Camandola, S Chan, SL Gary, DS Cheng, A Holbrook, NJ Mattson, MP TI Involvement of Gadd153 in the pathogenic action of presenilin-1 mutations SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; apoptosis; eIF2 alpha; ER stress; Gadd153; presenilin-1 ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED-PROTEIN RESPONSE; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; CALCIUM HOMEOSTASIS; CA2+ CONCENTRATION; PRECURSOR PROTEIN; UP-REGULATION; PC12 CELLS; DNA-DAMAGE AB Mutations in the presenilin-1 (PS1) gene cause early onset familial Alzheimer's disease (FAD) by a mechanism believed to involve perturbed endoplasmic reticulum (ER) function and altered proteolytic processing of the amyloid precursor protein. We investigated the molecular mechanisms underlying cell death and ER dysfunction in cultured cells and knock-in mice expressing FAD PS1 mutations. We report that PS1 mutations cause a marked increase in basal protein levels of the pro-apoptotic transcription factor Gadd153. PS1 mutations increase Gadd153 protein translation without affecting mRNA levels, while decreasing levels of the anti-apoptotic protein Bcl-2. Moreover, an exaggerated Gadd153 response to stress induced by ER stress agents was observed in PS1 mutant cells. Cell death in response to ER stress is enhanced by PS1 mutations, and this endangering effect is attenuated by anti-sense-mediated suppression of Gadd153 production. An abnormality in the translational regulation of Gadd153 may sensitize cells to the detrimental effects of ER stress and contribute to the pathogenic actions of PS1 mutations in FAD. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, La Cellular & Mol Biol, Gerontol Res Ctr, Baltimore, MD 21224 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 42 TC 50 Z9 58 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2002 VL 83 IS 3 BP 673 EP 681 DI 10.1046/j.1471-4159.2002.01165.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 605KJ UT WOS:000178676800020 PM 12390529 ER PT J AU Qin, LY Liu, YX Cooper, C Liu, B Wilson, B Hong, JS AF Qin, LY Liu, YX Cooper, C Liu, B Wilson, B Hong, JS TI Microglia enhance beta-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE beta-amyloid; cortical neurons; mesencephalic neurons; microglia; nicotinamide-adenine dinucleotide phosphate; oxidase ID RESPIRATORY BURST ACTIVITY; NITRIC-OXIDE PRODUCTION; ALZHEIMERS-DISEASE; SUPEROXIDE PRODUCTION; PROTEIN TOXICITY; BRAIN; ACTIVATION; CELLS; NEUROTOXICITY; MECHANISMS AB The purpose of this study was to assess and compare the toxicity of beta-amyloid (Abeta) on primary cortical and mesencephalic neurons cultured with and without microglia in order to determine the mechanism underlying microglia-mediated Abeta-induced neurotoxicity. Incubation of cortical or mesencephalic neuron-enriched and mixed neuron-glia cultures with Abeta(1-42) over the concentration range 0.1-6.0 muM caused concentration-dependent neurotoxicity. High concentrations of Abeta (6.0 muM for cortex and 1.5-2.0 muM for mesencephalon) directly injured neurons in neuron-enriched cultures. In contrast, lower concentrations of Abeta (1.0-3.0 muM for cortex and 0.25-1.0 muM for mesencephalon) caused significant neurotoxicity in mixed neuron-glia cultures, but not in neuron-enriched cultures. Several lines of evidence indicated that microglia mediated the potentiated neurotoxicity of Abeta, including the observations that low concentrations of Abeta activated microglia morphologically in neuron-glia cultures and that addition of microglia to cortical neuron-glia cultures enhanced Abeta-induced neurotoxicity. To search for the mechanism underlying the microglia-mediated effects, several proinflammatory factors were examined in neuron-glia cultures. Low doses of Abeta significantly increased the production of superoxide anions, but not of tumor necrosis factor-alpha, interleukin-1beta or nitric oxide. Catalase and superoxide dismutase significantly protected neurons from Abeta toxicity in the presence of microglia. Inhibition of NADPH oxidase activity by diphenyleneiodonium also prevented Abeta-induced neurotoxicity in neuron-glia mixed cultures. The role of NADPH oxidase-generated superoxide in mediating Abeta-induced neurotoxicity was further substantiated by a study which showed that Abeta caused less of a decrease in dopamine uptake in mesencephalic neuron-glia cultures from NADPH oxidase-deficient mutant mice than in that from wild-type controls. This study demonstrates that one of the mechanisms by which microglia can enhance the neurotoxicity of Abeta is via the production of reactive oxygen species. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Truman State Univ, Div Sci, Kirksville, MO USA. RP Qin, LY (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 46 TC 196 Z9 203 U1 2 U2 9 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2002 VL 83 IS 4 BP 973 EP 983 DI 10.1046/j.1471-4159.2002.01210.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 611YR UT WOS:000179046200025 PM 12421370 ER PT J AU Tonelli, L Kramer, P Webster, JI Wray, S Listwak, S Sternberg, E AF Tonelli, L Kramer, P Webster, JI Wray, S Listwak, S Sternberg, E TI Lipopolysaccharide-induced oestrogen receptor regulation in the paraventricular hypothalamic nucleus of Lewis and Fischer rats SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE CRH; HPA axis; inbred rats; neuroendocrine; neuroimmune ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; ESTROGEN-RECEPTOR; INDEPENDENT ACTIVATION; GENE-EXPRESSION; BRAIN; BETA; ALPHA; ESTRADIOL; RESPONSES AB Oestrogen receptor (ER) regulation of gene transcription in neurosecretory and pituitary cells has been proposed as an important mechanism for increased hypothalamic-pituitary-adrenal (HPA) axis responses in females of several mammalian species, including humans. Inbred female Fischer (F344/N) and Lewis (LEW/N) rats have similar oestrogen levels, although Fischer rats exhibit hyper- and Lewis rats hypo-HPA axis responses. The blunted HPA axis response of Lewis rats has been associated with their blunted hypothalamic corticotropin releasing hormone (CRH) expression. To determine if the female CRH expression deficiency in Lewis rats is associated with defective ER expression and regulation, hypothalamic paraventricular nucleus (PVN) transcript levels of CRH and ER were determined under basal conditions and after immune challenge. Microdissected PVN were obtained from control and lipopolysaccharide (LPS) treated Lewis and Fischer rats and CRH, ERalpha and beta mRNA levels were determined by semiquantitative reverse-transcriptase-polymerase chain reaction. In addition, ERalpha and beta protein levels were determined by semiquantitative Western blots. ERalpha and beta mRNA and protein levels in the PVN of control Fischer rats were significantly higher than in control Lewis rats. ERalpha and beta mRNA and protein levels in Fischer rats were reduced by LPS administration at the time of maximal CRH mRNA levels but did not change in Lewis rats, an effect independent of oestrogen levels. These data indicate that defective neuroendocrine HPA axis responses are associated with defective ER expression and regulation in Lewis PVN despite oestrogen concentrations. C1 NIMH, SNIB, Bethesda, MD 20892 USA. Texas A&M Univ Syst Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX USA. NINDS, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA. RP Tonelli, L (reprint author), 36 Convent Dr MSC 4020,Bldg 36,Room 1A21, Bethesda, MD 20892 USA. RI Webster Marketon, Jeanette/H-5613-2011; OI Webster Marketon, Jeanette/0000-0002-3627-1094; Kramer, Phillip/0000-0003-0117-542X; wray, susan/0000-0001-7670-3915 NR 35 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD NOV PY 2002 VL 14 IS 11 BP 847 EP 852 DI 10.1046/j.1365-2826.2002.00841.x PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 611YA UT WOS:000179044400002 PM 12421337 ER PT J AU Garrido, GEJ Furuie, SS Buchpiguel, CA Bottino, CMC Almeida, P Cid, CG Camargo, CHP Castro, CC Glabus, MF Busatto, GF AF Garrido, GEJ Furuie, SS Buchpiguel, CA Bottino, CMC Almeida, P Cid, CG Camargo, CHP Castro, CC Glabus, MF Busatto, GF TI Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer's disease: a combined MRI and SPECT study SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID CEREBRAL BLOOD-FLOW; VOXEL-BASED MORPHOMETRY; EVENT-RELATED FMRI; GRAY-MATTER LOSS; HIPPOCAMPAL ATROPHY; EMISSION TOMOGRAPHY; RECOGNITION MEMORY; VERBAL MEMORY; DEMENTIA; ACTIVATION AB Objective: To investigate the relation between atrophy of the hippocampal region and brain functional patterns during episodic memory processing in Alzheimer's disease. Patients and methods: Whole brain structural magnetic resonance imaging (MRI) data and single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF) were obtained during a verbal recognition memory task in nine subjects with mild Alzheimer's disease and 10 elderly healthy controls. Using the statistical parametric mapping approach, voxel based comparisons were made on the MRI data to identify clusters of significantly reduced grey matter concentrations in the hippocampal region in the Alzheimer patients relative to the controls. The mean grey matter density in the voxel cluster of greatest hippocampal atrophy was extracted for each Alzheimer subject. This measure was used to investigate, on a voxel by voxel basis, the presence of significant correlations between the degree of hippocampal atrophy and the rCBF SPECT measures obtained during the memory task. Results: Direct correlations were detected between the hippocampal grey matter density and rCBF values in voxel clusters located bilaterally in the temporal neocortex, in the left medial temporal region, and in the left posterior cingulate cortex during the memory task in the Alzheimer's disease group (p < 0.001). Conversely, measures of hippocampal atrophy were negatively correlated with rCBF values in voxel clusters located in the frontal lobes, involving the right and left inferior frontal gyri and the insula (p < 0.001). Conclusions: Hippocampal atrophic changes in Alzheimer's disease are associated with reduced functional activity in limbic and associative temporal regions during episodic memory processing, but with increased activity in frontal areas, possibly on a compensatory basis. C1 Univ Sao Paulo, Sch Med, Div Informat, InCor, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Radiol, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Western Australia, Dept Psychiat & Behav Sci, Nedlands, WA 6009, Australia. NIH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, Bethesda, MD USA. RP Garrido, GEJ (reprint author), USP, Ctr Med Nucl, Rua Dr Ovidio Pires de Campos S-N, BR-05403010 Sao Paulo, Brazil. RI Furuie, Sergio/A-7219-2008; Buchpiguel, Carlos/C-3774-2012; Almeida, Osvaldo/A-4925-2008; Castro, Claudio/J-3139-2012; Busatto, Geraldo/D-4431-2009 OI Furuie, Sergio/0000-0002-1557-3018; Buchpiguel, Carlos/0000-0003-0956-2790; Castro, Claudio/0000-0002-3531-4232; NR 55 TC 53 Z9 60 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 2002 VL 73 IS 5 BP 508 EP 516 DI 10.1136/jnnp.73.5.508 PG 9 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 612UK UT WOS:000179093700011 PM 12397142 ER PT J AU Jeong, BH Jin, JK Choi, EK Lee, EY Meeker, HC Kozak, CA Carp, RI Kim, YS AF Jeong, BH Jin, JK Choi, EK Lee, EY Meeker, HC Kozak, CA Carp, RI Kim, YS TI Analysis of the expression of endogenous murine leukemia viruses in the brains of senescence-accelerated mice (SAMP8) and the relationship between expression and brain histopathology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE aging; Akv; astrocytosis; degeneration; murine leukemia virus; senescence-accelerated mouse; SAMP8 ID AGE-RELATED-CHANGES; MOUSE SAM; MULTIPLE-SCLEROSIS; ENDOTHELIAL-CELLS; RETROVIRUS; SEQUENCES; MEMORY; INFECTION; INDUCTION; STRAINS AB Many studies have explored the premature aging of accelerated senescence-prone (SAMP8) mice. However, the cause of premature aging in this strain remains unknown. We analyzed the expression of ecotropic, xenotropic, and polytropic marine leukemia viruses (MuLVs) in the brains of accelerated senescence-resistant (SAMR1) and SAMP8 mice. No ecotropic mRNA was detected in SAMR1 mice, and only Akv-type ecotropic MuLV mRNA was detected in SAMP8 mice. Restriction mapping of the full-length infectious E-MuLV genome from SAMP8 confirmed its identity as Akv. mRNAs corresponding to a prototypical polytropic MuLV,and to an unusual xenotropic MULV were detected at equal levels in SAMP8 and SAMR1 mice, but no infectious virus of either host range type was detected.. In order to determine the cellular localization of Akv expression in SAMP8 mice, we used immunohistochemistry and electron microscopy to, detect expression of the E-MuLV capsid gag (CAgag) gene in striatum, brainstem, hippocampus, and cerebellum of 12-month-old SAMR1 and SAMP8 mice. The CAgag antigen was seen in the neurons, oligodendroglia, and vascular endothelium of these brain regions of SAMP8 mice, but not in SAMR1 mice. To evaluate the correlation between activation of astrocytes and expression of Akv, we performed double-immunohistochemical staining for both glial fibrillary acidic protein (GFAP) and CAgag in SAMR1 and SAMP8 mice. Strong astrocytic activation and extensive vacuolation were observed around CAgag-positive neurons in SAMP8 mice, whereas in SAMR1 mice neither astrocytosis nor. vacuolation were present. CAgag antigen was also localized in astrocytes of the hippocampus region of SAMP8 mice. Electron micrography showed that a number of vacuoles were found in the cytoplasm of MuLV-positive neurons and the extracellular space surrounding these neurons showed lytic changes. These results suggest that endogenous Akv provirus is expressed in neurons, astrocytes, vascular endothelium, and oligodendroglia in the brains of SAMP8 and that this virus could play an important role in the brain aging processes in this mouse strain. C1 Hallym Univ, Coll Med, Dept Microbiol, Chunchon, South Korea. Hallym Univ, Coll Med, Ilsong Inst Life Sci, Chunchon, South Korea. Chungbuk Natl Univ, Coll Med, Dept Anat, Cheongju, South Korea. NYS Inst Basic Res Dev Disabil, Dept Virol, Staten Isl, NY USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, YS (reprint author), Hallym Univ, Hallym Acad Sci, Coll Med,Ilsong Inst Life Sci, Dongan Gu, 1605-4 Gwanyang Dong, Anyang 431060, Kyounggi Do, South Korea. NR 47 TC 12 Z9 13 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2002 VL 61 IS 11 BP 1001 EP 1012 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 612AN UT WOS:000179051200008 PM 12430717 ER PT J AU Del Negro, CA Koshiya, N Butera, RJ Smith, JC AF Del Negro, CA Koshiya, N Butera, RJ Smith, JC TI Persistent sodium current, membrane properties and bursting behavior of pre-Botzinger complex inspiratory neurons in vitro SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RESPIRATORY RHYTHM GENERATION; PACEMAKER NEURONS; PREBOTZINGER COMPLEX; NETWORK; MAMMALS; MODELS; RAT; MODULATION; CHANNELS; SLICES AB We measured persistent Na(+) current and membrane properties of bursting-pacemaker and nonbursting inspiratory neurons of the neonatal rat pre-Botzinger complex (pre-BotC) in brain stem slice preparations with a rhythmically active respiratory network in vitro. In whole-cell recordings, slow voltage ramps (less than or equal to100 mV/s) inactivated the fast, spike-generating Na(+) current and yielded N-shaped current-voltage relationships with nonmonotonic, negative-slope regions between -60 and -35 mV when the voltage-sensitive component was isolated. The underlying current was a TTX-sensitive persistent Na(+) current (I(NaP)) since the inward current was present at slow voltage ramp speeds (3.3-100 mV/s) and the current was blocked by 1 muM TTX. We measured the biophysical properties of I(NaP) after subtracting the voltage-insensitive "leak" current (I(Leak)) in the presence of Cd(2+) and in some cases tetraethylammonium (TEA). Peak I(NaP) ranged from -50 to -200 pA at a membrane potential of -30 mV. Decreasing the speed of the voltage ramp caused time-dependent I(NaP) inactivation, but this current was present at ramp speeds as low as 3.3 mV/s. I(NaP) activated at -60 mV and obtained half-maximal activation near -40 mV. The subthreshold voltage dependence and slow inactivation kinetics of I(NaP), which closely resemble those of I(NaP) mathematically modeled as a burst-generation mechanism in pacemaker neurons of the pre-BotC, suggest that I(NaP) predominantly influences bursting dynamics of pre-BotC inspiratory pacemaker neurons in vitro. We also found that the ratio of persistent Na(+) conductance to leak conductance (g(NaP)/g(Leak)) can distinguish the phenotypic subpopulations of bursting pacemaker and nonbursting inspiratory neurons: pacemaker neurons showed g(NaP) /g(Leak) > g(NaP) / g(Leak) in nonpacemaker cells (P < 0.0002). We conclude that I(NaP) is ubiquitously expressed by pre-BotC inspiratory neurons and that bursting pacemaker behavior within the heterogeneous population of inspiratory neurons is achieved with specific ratios of these two conductances, g(NaP) and g(Leak). C1 NINDS, Cellular & Syst Neurobiol Sect, Lab Neural Control, NIH, Bethesda, MD 20892 USA. Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. Georgia Inst Technol, Inst Bioengn & Biosci, Lab Neuroengn, Atlanta, GA 30332 USA. RP Smith, JC (reprint author), 49 Convent Dr,Room 3A50, Bethesda, MD 20892 USA. EM jsmith@helix.nih.gov RI Del Negro, Ciro/K-3451-2013; OI Butera, Robert/0000-0002-1806-0621 NR 26 TC 152 Z9 153 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2002 VL 88 IS 5 BP 2242 EP 2250 DI 10.1152/jn.00081.2002 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 612MW UT WOS:000179080900009 PM 12424266 ER PT J AU Oz, M Renaud, LP AF Oz, M Renaud, LP TI Angiotensin AT(1)-receptors depolarize neonatal spinal motoneurons and other ventral horn neurons via two different conductances SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RECEPTOR ACTIVATION; 2 CONDUCTANCES; II RECEPTORS; K+ CHANNEL; RAT EMBRYO; G-PROTEINS; VASOPRESSIN; CORD; MODULATION; PEPTIDES AB Angiotensin receptors are highly expressed in neonatal spinal cord. To identify their influence on neuronal excitability, we used patch-clamp recordings in spinal cord slices to assess responses of neonatal rat (5-12 days) ventral horn neurons to bath-applied angiotensin II (ANG II; 1 muM). In 14/34 identified motoneurons tested under current clamp, ANG II induced a slowly rising and prolonged membrane depolarization, blockable with Losartan (n = 5) and (Sar(1), Val(5), Ala(8))-ANG II (Saralasin, n = 4) but not PD123319 (1 muM each; n = 4). Under voltage clamp (V-H -65 mV), 7/22 motoneurons displayed an ANG-II-induced tetrodotoxin-resistant inward current (-128 +/- 31 pA) with a similar time course, an associated reduction in membrane conductance and net current reversal at -98.8 +/- 3.9 mV. Losartan-sensitive ANG II responses were also evoked in 27/78 tested ventral horn "interneurons." By contrast with motoneurons, their ANG-II-induced inward current was smaller (-39.9 +/- 5.2 pA) and analysis of their I-V plots revealed three patterns. In eight cells, membrane conductance decreased with net inward current reversing at -103.8 +/- 4.1 mV. In seven cells, membrane conductance increased with net current reversing at -37.9 +/- 3.6 mV. In 12 cells, I-V lines remained parallel with no reversal within the current range tested. Intracellular dialysis with GTP-gamma-S significantly prolonged the ANG II effect in seven responsive interneurons and GDP-beta-S significantly reduced the ANG II response in four other cells. Peak inward currents were significantly reduced in all 13 responding neurons recorded in slices incubated in pertussis toxin (5 mug/ml) for 12-18 h or in 12 neurons perfused with N-ethylmaleimide. Of 29 interneurons sensitive to pertussis toxin or N-ethylmaleimide treatment, 9 cells displayed a decrease in membrane conductance that reversed at -101.3 +/- 3.8 mV. In eight cells, membrane conductance increased and reversed at -38.7 +/- 3.4 mV. In 12 cells, the I-V lines remained parallel with no reversal within the current range tested, suggesting that both conductances are modulated by pertussis toxin-sensitive G proteins. These observations reveal a direct, G-protein-mediated depolarizing action of ANG II on neonatal rat ventral horn neurons. They also imply involvement of two distinct conductances that are differentially distributed among different cell types. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. RP Oz, M (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Oz, Murat/E-2148-2012 NR 36 TC 10 Z9 10 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2002 VL 88 IS 5 BP 2857 EP 2863 DI 10.1152/jn.00978.2001 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 612MW UT WOS:000179080900061 PM 12424318 ER PT J AU Mueller, KL Jacques, BE Kelley, MW AF Mueller, KL Jacques, BE Kelley, MW TI Fibroblast growth factor signaling regulates pillar cell development in the organ of Corti SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cochlea; auditory system; hair cell; p75(ntr); ear; FGFR3 ID SUPERNUMERARY HAIR-CELLS; MESSENGER-RNA EXPRESSION; MOUSE INNER-EAR; RAT COCHLEA; MAMMALIAN COCHLEA; BALANCE EPITHELIA; FACTOR RECEPTOR; RETINOIC ACID; DIFFERENTIATION; ORGANOGENESIS AB One of the most striking aspects of the cellular pattern within the sensory epithelium of the mammalian cochlea is the presence of two rows of pillar cells in the region between the single row of inner hair cells and the first row of outer hair cells. The factors that regulate pillar cell development have not been determined; however, previous results suggested a key role for fibroblast growth factor receptor 3 (FGFR3). To examine the specific effects of FGFR3 on pillar cell development, we inhibited receptor activation in embryonic cochlear explant cultures. Results indicated that differentiation of pillar cells is dependent on continuous activation of FGFR3. Moreover, transient inhibition of FGFR3 did not inhibit the pillar cell fate permanently, because reactivation of FGFR3 resulted in the resumption of pillar cell differentiation. The effects of increased FGFR3 activation were determined by exposing cochlear ex-plants to FGF2, a strong ligand for several FGF receptors. Treatment with FGF2 led to a significant increase in the number of pillar cells and to a small increase in the number of inner hair cells. These effects were not dependent on cellular proliferation, suggesting that additional pillar cells and inner hair cells were a result of increased recruitment into the prosensory domain. These results indicate that FGF signaling plays a critical role in the commitment and differentiation of pillar cells. Moreover, the position of the pillar cells appears to be determined by the activation of FGFR3 in a subset of the progenitor cells that initially express this receptor. C1 Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA. RP Kelley, MW (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, 5 Res Court,Romm 2B-44, Rockville, MD 20850 USA. NR 44 TC 88 Z9 90 U1 0 U2 0 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 NOV 1 PY 2002 VL 22 IS 21 BP 9368 EP 9377 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 611RM UT WOS:000179031600027 PM 12417662 ER PT J AU Bilak, MM Becerra, SP Vincent, AM Moss, BH Aymerich, MS Kuncl, RW AF Bilak, MM Becerra, SP Vincent, AM Moss, BH Aymerich, MS Kuncl, RW TI Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyotrophic lateral sclerosis; motor neurons; neurodegeneration; neuroprotection; neurotrophic factor; peptide; pigment epithelium-derived factor; serpin; spinal cord ID CEREBELLAR GRANULE CELLS; SERINE-PROTEASE INHIBITOR; FACTOR PEDF; NEUROTROPHIC ACTIVITY; NONINHIBITORY SERPIN; NEURITE OUTGROWTH; BOVINE EYES; NEXIN-I; DEATH; EXPRESSION AB Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor (serpin) family, is a survival factor for various types of neurons. We studied the mechanisms by which human PEDF protects motor neurons from degeneration, with the goal of eventually conducting human clinical trials. We first searched for a molecular region of human PEDF essential to motor neuron protection. Using a spinal cord culture model of chronic glutamate toxicity, we show herein that a synthetic 44 mer peptide from an N- terminal region of the human PEDF molecule that lacks the homologous serpin- reactive region contains its full neuroprotective activity. We also investigated the presence and distribution of PEDF receptors in the spinal cord. Using a fluoresceinated PEDF probe, we show that spinal motor neurons contain specific binding sites for PEDF. Kinetics analyses using a radiolabeled PEDF probe demonstrate that purified rat motor neurons contain a single class of saturable and specific binding sites. This study indicates that a small peptide fragment of the human PEDF molecule could be engineered to contain all of its motor neuron protective activity, and that the neuroprotective action is likely to be mediated directly on motor neurons via a single class of PEDF receptors. The data support the pharmacotherapeutic potential of PEDF as a neuroprotectant in human motor neuron degeneration. C1 Bryn Mawr Coll, Dept Biol, Bryn Mawr, PA 19010 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. RP Kuncl, RW (reprint author), Bryn Mawr Coll, Dept Biol, Taylor Hall,1st Floor,101 N Merion Ave, Bryn Mawr, PA 19010 USA. NR 46 TC 77 Z9 78 U1 0 U2 1 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 NOV 1 PY 2002 VL 22 IS 21 BP 9378 EP 9386 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 611RM UT WOS:000179031600028 PM 12417663 ER PT J AU Vorel, SR Asbhy, CR Paul, M Liu, XH Hayes, R Hagan, JJ Middlemiss, DN Stemp, G Gardner, EL AF Vorel, SR Asbhy, CR Paul, M Liu, XH Hayes, R Hagan, JJ Middlemiss, DN Stemp, G Gardner, EL TI Dopamine D-3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; addiction; dopamine; mesolimbic; mesocorticolimbic; D-3 receptor; D-3 antagonist; brain stimulation reward; BSR; self-stimulation; ICSS; conditioned place preference; CPP; self-administration; reinstatement; relapse ID CONDITIONED PLACE PREFERENCE; INTRACRANIAL SELF-STIMULATION; BASAL EXTRACELLULAR DOPAMINE; D-AMPHETAMINE; ADMINISTERED COCAINE; NUCLEUS-ACCUMBENS; PARTIAL AGONIST; EXCITOTOXIC LESIONS; INTRAVENOUS COCAINE; SQUIRREL-MONKEYS AB The dopamine D-3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D-3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D-3 receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D-3 receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D-3 receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D-3 receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction. C1 St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10461 USA. Eon Labs, Laurelton, NY 11413 USA. GlaxoSmithKline, Psychiat Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England. RP Asbhy, CR (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, 8000 Utopia Pkwy, Jamaica, NY 11439 USA. NR 90 TC 205 Z9 208 U1 1 U2 8 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 NOV 1 PY 2002 VL 22 IS 21 BP 9595 EP 9603 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 611RM UT WOS:000179031600049 PM 12417684 ER PT J AU Watson, JB Khorasani, H Persson, A Huang, KP Huang, FL O'Dell, TJ AF Watson, JB Khorasani, H Persson, A Huang, KP Huang, FL O'Dell, TJ TI Age-related deficits in long-term potentiation are insensitive to hydrogen peroxide: Coincidence with enhanced autophosphorylation of Ca2+/calmodulin-dependent protein kinase II SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE LTP; age; oxidative stress; hydrogen peroxide; CaMKII ID MEMBRANE CA-ATPASE; SYNAPTIC PLASTICITY; OXIDATIVE STRESS; GLUTATHIONE-PEROXIDASE; ALZHEIMERS-DISEASE; NMDA RECEPTOR; FREE-RADICALS; INCREASED SUSCEPTIBILITY; CALMODULIN; HIPPOCAMPUS AB Reactive oxygen species (ROS) can have deleterious effects for both normal aging and Alzheimer's disease (AD). We examined the hypothesis that synapses undergoing long-term potentiation (LTP) are preferentially at risk for ROS-mediated oxidative stress during aging. We observed age-dependent deficits in LTP induced by a high-frequency stimulation (HFS) protocol in the CA1 region of hippocampus from C57BL/6 mice. There was a significant difference between LTP measured over 60 min in young (1-2 months) and old (23-26 months) mice. In oxidative stress studies, exogenous H2O2 (580 muM) significantly inhibited LTP in young mice; a similar dose of H2O2 failed to inhibit LTP in slices from adult (2-4 months) or from old mice. The results show that there are significant deficits in LTP in aging mice, but such deficits are insensitive to H2O2. Western immunoblotting studies in young mice show that the relative levels of autophosphorylated alpha-Ca2+/calmodulin-dependent protein kinase 11 (CaMKII) are unchanged in hippocampal CA1 treated with H2O2 relative to untreated controls. However with aging, there is a significant enhancement in the levels of autophosphorylated CaMKII in H2O2-treated CA1 of older mice. Phosphorylation of RC3/neurogranin (Ng) by protein kinase C (PKC) is decreased in CA1 in response to H2O2 treatment, irrespective of age. We propose that, during aging, enhanced local release of H2O2 from mitocohondria may induce a compensatory "ceiling" effect at synapses, so that the levels of auto phosphorylated alphaCaMKII are aberrantly saturated, leading to alterations in synaptic plasticity. (C) 2002 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Physiol, Sch Med, Los Angeles, CA 90024 USA. RP Watson, JB (reprint author), Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,47-429 NPI, Los Angeles, CA 90024 USA. NR 72 TC 29 Z9 37 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 2002 VL 70 IS 3 BP 298 EP 308 DI 10.1002/jnr.10422 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 608EL UT WOS:000178832200007 PM 12391589 ER PT J AU Oldfield, EH AF Oldfield, EH TI Cerebellar tonsils and syringomyelia SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID CHIARI-I MALFORMATION; PATHOPHYSIOLOGY; MANAGEMENT C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD USA. NR 11 TC 11 Z9 12 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2002 VL 97 IS 5 BP 1009 EP 1010 DI 10.3171/jns.2002.97.5.1009 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 613BC UT WOS:000179109800001 PM 12450018 ER PT J AU Yamanaka, R Yajima, N Tsuchiya, N Honma, J Tanaka, R Ramsey, J Blaese, M Xanthopoulos, KG AF Yamanaka, R Yajima, N Tsuchiya, N Honma, J Tanaka, R Ramsey, J Blaese, M Xanthopoulos, KG TI Administration of interleukin-12 and-18 enhancing the antitumor immunity of genetically modified dendritic cells that had been pulsed with Semliki Forest virus-mediated tumor complementary DNA SO JOURNAL OF NEUROSURGERY LA English DT Article DE dendritic cell; Semliki Forest virus; immunogene therapy; malignant glioma; interleukin-12; interleukin-18 ID GAMMA-INDUCING FACTOR; CYTOTOXIC T-LYMPHOCYTES; NATURAL-KILLER-CELLS; IFN-GAMMA; INTERFERON-GAMMA; MURINE TUMORS; SINDBIS VIRUS; GENE-THERAPY; IN-VIVO; IL-12 AB Object. Immunogene therapy for malignant gliomas was further investigated in this study to improve its therapeutic efficacy. Methods. Dendritic cells (DCs) were isolated from bone marrow and pulsed with phosphate-buffered saline or Semliki Forest virus (SFV)-mediated 203 glioma complementary (c)DNA with or without systemic administration of interleukin (IL)-12 and IL-18 to treat mice bearing the 203 glioma. To study the immune mechanisms involved in tumor regression, the authors investigated tumor growth of an implanted 203 glioma model in T cell subset-depleted mice and in interferon (IFN) gamma-neutralized mice. To examine the protective immunity produced by tumor inoculation, a repeated challenge of 203 glioma cells was given by injecting the cells into the left thighs of surviving mice and the growth of these cells was monitored. The authors demonstrated that the combined administration of SFV-cDNA, IL-12, and IL-18 produced significant antitumor effects against the growth of murine glioma cells in vivo and also can induce specific antitumor immunity. The synergic effects of the combination of SFV-cDNA, IL-12, and IL-18 in vivo were also observed to coincide with markedly augmented IFNgamma production. The antitumor effects of this combined therapy are mediated by CD4(+) and CD8(+) T cells and by NK cells. These results indicate that the use of IL-18 and IL-12 in DC-based immunotherapy for malignant glioma is beneficial. Conclusions. Immunogene therapy combined with DC therapy, IL-12, and IL-18 may be an excellent candidate in the development of a new treatment protocol. The self-replicating SFV system may therefore provide a novel approach for the treatment of malignant gliomas. C1 Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 9518585, 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 9518585, Japan. NR 52 TC 22 Z9 23 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2002 VL 97 IS 5 BP 1184 EP 1190 DI 10.3171/jns.2002.97.5.1184 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 613BC UT WOS:000179109800029 PM 12450042 ER PT J AU Tulenko, TN Sumner, AE AF Tulenko, TN Sumner, AE TI The physiology of lipoproteins SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; TRIGLYCERIDE-RICH LIPOPROTEINS; VERY-LOW-DENSITY; HEART-DISEASE; APOLIPOPROTEIN-B; ATHEROGENIC LIPOPROTEIN; CHOLESTEROL TRANSPORT; PARTICLE-SIZE; RISK AB The seminal studies of Brown and Goldstein (Science 1986;232:34-47) coupled with the findings of the Framingham study revolutionized our understanding of the metabolic basis for vascular disease. These studies led to the widespread use of the coronary risk lipid profile, which uses the total cholesterol/high-density lipoprotein (HDL) ratio (or low-density lipoprotein [LDL]/HDL ratio) in predicting risk for vascular disease and as a tool for therapeutic management of patients at risk for vascular disease. However, although these methods are predictive of coronary artery disease (CAD) in general, it is also well known that the extent of occlusive disease and CAD varies greatly between individuals with similar cholesterol and HDL lipid profiles. For this reason, the National Cholesterol Education Program Expert Panel revised these guidelines and now recommends monitoring LDL and HDL cholesterol in the context of coronary heart disease risk factors and "risk equivalents." In addition, more recent findings indicate that specific alterations in individual lipoprotein subclasses may account for the variations in CAD in subjects with similar lipid profiles. For example, a preponderance of small, dense LDL particles correlates with a marked increase in risk for myocardial infarction independent of LDL levels. In particular, the association of small, dense LDL with elevated triglycerides (large, less dense VLDL) and reduced HDL has been defined as the atherogenic lipoprotein profile, and the key metabolic defect driving this profile may be elevated levels of triglycerides, specifically large, less dense VLDL. In an attempt to explain the physiologic basis for lipoprotein variations, this review describes the basic metabolic scheme underlying the traditional view of lipoprotein metabolism and physiology. It then examines the identity and role of the various lipoprotein subfractions in an attempt to distill a working model of how lipoprotein abnormalities might account for vascular disease in general and the metabolic syndrome in particular. C1 Thomas Jefferson Univ, Coll Med, Dept Surg, Philadelphia, PA 19107 USA. NIH, Diabet Branch, Bethesda, MD 20892 USA. RP Tulenko, TN (reprint author), Thomas Jefferson Univ, Coll Med, Dept Surg, 1025 Walnut St,Suite 605, Philadelphia, PA 19107 USA. FU NHLBI NIH HHS [HL-66273] NR 63 TC 45 Z9 51 U1 0 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD NOV-DEC PY 2002 VL 9 IS 6 BP 638 EP 649 DI 10.1067/mnc.2002.128959 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 627VV UT WOS:000179957600012 PM 12466789 ER PT J AU Bacharach, SL Sundaram, SK AF Bacharach, SL Sundaram, SK TI F-18-FDG in cardiology and oncology: The bitter with the sweet SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; MYOCARDIAL GLUCOSE-UPTAKE; FLUORODEOXYGLUCOSE; TIME C1 NIH, Bethesda, MD 20892 USA. RP Bacharach, SL (reprint author), NIH, Bldg 10,Room 1C401, Bethesda, MD 20892 USA. RI Sundaram, Senthil/B-3905-2013 OI Sundaram, Senthil/0000-0002-0382-0536 NR 13 TC 11 Z9 12 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2002 VL 43 IS 11 BP 1542 EP 1544 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 613BX UT WOS:000179112100020 PM 12411557 ER PT J AU Aziz, NM AF Aziz, NM TI Cancer survivorship research: Challenge and opportunity SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS DE cancer; survivorship; sequelae; research; paradigm ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; QUALITY-OF-LIFE; RECEIVING ADJUVANT CHEMOTHERAPY; HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER; PHYSICAL-ACTIVITY; CRANIAL IRRADIATION; CHILDHOOD-CANCER; MALIGNANT NEOPLASMS AB With continued advances in strategies to detect cancer early and treat it effectively along with the aging of the population, the number of individuals living years beyond a cancer diagnosis can be expected to continue to increase. This paper reviews current prevalence data for cancer survivors; discusses definitional issues; examines cancer survivorship as a scientific research area; provides an overview of medical and psychosocial sequelae of cancer diagnosis and treatment experienced by survivors, gaps in knowledge and emerging research priorities; explores the role of weight, nutrition and physical activity as key variables carrying the potential to affect physiologic or psychosocial sequelae of cancer and its treatment; and discusses the evolving paradigm of cancer survivorship research. A large and growing community of cancer survivors is one of the major achievements of cancer research over the past three decades. Both length and quality of survival are important end points. Many cancer survivors are at risk for and develop physiologic and psychosocial late and long-term effects of cancer treatment that may lead to premature mortality and morbidity. Interventions-therapeutic and lifestyle-carry the potential to treat or ameliorate these late effects and must be developed, examined and disseminated if found effective. Diet, weight and physical activity interventions hold considerable promise for ameliorating multiple adverse sequelae of cancer and its treatment and should be investigated in larger populations of cancer survivors, those who are long-term survivors, those with understudied cancer sites and ethnocultural minority or medically underserved groups. C1 NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. RP Aziz, NM (reprint author), NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. NR 93 TC 73 Z9 74 U1 1 U2 6 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3494S EP 3503S PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200009 PM 12421876 ER PT J AU Sinha, R AF Sinha, R TI Carcinogens in cooked meats and human cancer SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3536S EP 3537S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200025 ER PT J AU Wright, ME Mayne, ST Alavanja, MCR AF Wright, ME Mayne, ST Alavanja, MCR TI Low fruit and vegetable intake exacerbates the risk of lung cancer associated with residential radon exposure SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3542S EP 3542S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200039 ER PT J AU Gallardo-Williams, MT Maronpot, RR King, PE Moser, GJ Golsworthy, TL Morrison, JP Chapin, RE AF Gallardo-Williams, MT Maronpot, RR King, PE Moser, GJ Golsworthy, TL Morrison, JP Chapin, RE TI Boron supplementation reduces proliferative activity and local expression of IGF-I in human prostate adenocarcinoma (LNCaP) tumors in nude mice SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. ILS, Res Triangle Pk, NC USA. Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3543S EP 3544S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200043 ER PT J AU Gallardo-Williams, MT Harris, MW Maronpot, RR AF Gallardo-Williams, MT Harris, MW Maronpot, RR TI Variability in sensitivity to the antiproliferative effects of boric acid in the human prostate cancer cell lines LNCaP and PC-3. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3543S EP 3543S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200042 ER PT J AU Jardim, BC Galindo, FL Couto, SG Figueredo, MS Rangel, RDB Pereira, RA Marins, VMR AF Jardim, BC Galindo, FL Couto, SG Figueredo, MS Rangel, RDB Pereira, RA Marins, VMR TI Dietary factors associated with breast and prostate cancer development. A review SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 NCI, Bethesda, MD 20892 USA. Univ Fed Fluminense, Nutr Coll, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Inst Nutr, Rio De Janeiro, Brazil. RI Pereira, Rosangela/D-8830-2013 OI Pereira, Rosangela/0000-0002-9886-9796 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3544S EP 3545S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200047 ER PT J AU Huang, WY Hayes, RB Fouad, MN AF Huang, WY Hayes, RB Fouad, MN TI Obesity and colorectal adenoma. Data from the prostate, lung, colorectal, and ovarian cancer screening trial SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 Univ Alabama, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3546S EP 3546S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200052 ER PT J AU Mai, V Katki, H Clevidence, B Hursting, S Harmsen, H Schatzkin, A AF Mai, V Katki, H Clevidence, B Hursting, S Harmsen, H Schatzkin, A TI Changes in the fecal flora composition of human volunteers in a double-blind randomized black tea feeding study SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT International Research Conference on Food, Nutrition and Cancer CY JUL 11-12, 2002 CL WASHINGTON, D.C. SP BASF Aktiengesell, California Dried Plum Board, Campbell Soup Co, Danisco Cultor, Galileo Labs Inc, Mead Johnson Nutr, Roche Vitamins Inc, Yamanouchi, Shaklee, INOBYS C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. Univ Groningen, Groningen, Netherlands. RI Katki, Hormuzd/B-4003-2015 NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2002 VL 132 IS 11 SU S BP 3551S EP 3551S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 614PU UT WOS:000179199200068 ER PT J AU Bhathena, SJ Ali, AA Mohamed, AI Hansen, CT Velasquez, MT AF Bhathena, SJ Ali, AA Mohamed, AI Hansen, CT Velasquez, MT TI Differential effects of dietary flaxseed protein and soy protein on plasma triglyceride and uric acid levels in animal models SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE cholesterol; flaxseed; hypertriglyceridemia; hyperuricemia; plasma lipids; soy protein ID ALPHA-LINOLENIC ACID; CARDIOVASCULAR RISK-FACTORS; HYPERCHOLESTEROLEMIC ATHEROSCLEROSIS; SERUM-LIPIDS; UNDIGESTED FRACTION; INSULIN-RESISTANCE; DEFATTED FLAXSEED; SOYBEAN PROTEIN; BLOOD-PRESSURE; CORPULENT RAT AB The effect of dietary soy protein and flaxseed meal on metabolic parameters was studied in two animal models, F344 rats with normal lipid levels and obese SHR/N-cp rats with elevated levels of cholesterol and triglyceride. The rats were fed AIN 93 diet differing only in the source of protein. The rats were fed either 20% casein, 20% soy protein or 20% flaxseed meal. Plasma was analyzed for cholesterol, triglyceride, uric acid, blood urea nitrogen (BUN), creatinine and total protein. In both strains of rats, flaxseed meal significantly decreased plasma cholesterol and triglyceride concentrations. The effect of soy protein on lipids was not as striking as that of flaxseed meal. Flaxseed meal also lowered uric acid in F344 rats and BUN in SHRIN-cp rats. Since cholesterol, triglyceride and uric acid are independent risk factors for cardiovascular disorders, our data show that both flaxseed meal and soy protein may have beneficial effects. Which chemical constituent(s) of flaxseed meal or soybean is (are) responsible for the beneficial effects need to be identified. Published by Elsevier Science Inc. All rights reserved. C1 ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. Ain Shams Univ, Cairo, Egypt. Virginia State Univ, Peterburg, VA USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. NIH, Anim Genet Resource, Bethesda, MD 20892 USA. RP Bhathena, SJ (reprint author), ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. NR 44 TC 28 Z9 32 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD NOV PY 2002 VL 13 IS 11 BP 684 EP 689 AR PII S0955-2863(02)00227-9 DI 10.1016/S0955-2863(02)00227-9 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 620VW UT WOS:000179554300007 ER PT J AU Wang, ML Nesti, LJ Tuli, R Lazatin, J Danielson, KG Sharkey, PF Tuan, RS AF Wang, ML Nesti, LJ Tuli, R Lazatin, J Danielson, KG Sharkey, PF Tuan, RS TI Titanium particles suppress expression of osteoblastic phenotype in human mesenchymal stem cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE mesenchymal stem cell; differentiation; wear particles; titanium; zirconia ID BONE SIALOPROTEIN; MARROW; DIFFERENTIATION; DEBRIS; RESORPTION; SEQUENCE; ADHESION; DOMAIN; MOUSE; CDNA AB Long-term stability of arthroplasty prosthesis depends on the integration between osseous tissue and the implant biomaterial. Integrity of the osseous tissue requires the contribution of mesenchymal stem cells and their continuous differentiation into an osteoblastic phenotype. This study aims to investigate the hypothesis that exposure to wear debris particles derived from orthopaedic biomaterials affects the osteoblastic differentiation of human mesenchymal stem cells (hMSC). Upon in vitro culture in the presence of osteogenic supplements (OS), we observe that cultures of hMSCs isolated from femoral head bone marrow are capable of osteogenic differentiation, expressing alkaline phosphatase, osteocalcin, and bone sialoprotein (BSP), in addition to producing collagen type I and BSP accompanied by extracellular matrix mineralization. Exposure of OS-treated hMSCs to submicron commercially pure titanium (cpTi) particles suppresses BSP gene expression, reduces collagen type I and BSP production, decreases cellular proliferation and viability, and inhibits matrix mineralization. In comparison, exposure to zirconium oxide (ZrO2) particles of similar size did not alter osteoblastic gene expression and resulted in only a moderate decrease in cellular proliferation and mineralization. Confocal imaging of cpTi-treated hMSC cultures revealed patchy groups of cells displaying disorganized cytoskeletal architecture and low levels of extracellular BSP. These in vitro findings suggest that chronic exposure of marrow cells to titanium wear debris in vivo may contribute to decreased bone formation at the bone/implant interface by reducing the population of viable hMSCs and compromising their differentiation into functional osteoblasts. Understanding the nature of hMSC bioreactivity to orthopaedic wear debris should provide additional insights into mechanisms underlying aseptic loosening. Published by Elsevier Science Ltd. on behalf of Orthopaedic Research Society. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bldg 50,Room 1503,50 South Dr, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR45181, AR44501]; NIDCR NIH HHS [DE12864] NR 32 TC 67 Z9 73 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD NOV PY 2002 VL 20 IS 6 BP 1175 EP 1184 AR PII S0736-0266(02)00076-1 DI 10.1016/S0736-0266(02)00076-1 PG 10 WC Orthopedics SC Orthopedics GA 618CP UT WOS:000179400800007 PM 12472226 ER PT J AU Earthman, CP Reid, PM Harper, IT Ravussin, E Howell, WH AF Earthman, CP Reid, PM Harper, IT Ravussin, E Howell, WH TI Body cell mass repletion and improved quality of life in HIV-infected individuals receiving oxandrolone SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN GROWTH-HORMONE; PLACEBO-CONTROLLED TRIAL; WEIGHT-LOSS; DOUBLE-BLIND; OF-LIFE; MEGESTROL-ACETATE; EUGONADAL MEN; NANDROLONE DECANOATE; RESISTANCE EXERCISE AB Background: The aim of this study was to measure changes in body cell mass (BCM) and quality of life in HIV-infected individuals undergoing oxandrolone therapy. Previous studies on oxandrolone have neither quantified changes in BCM using criterion methods nor quality of life using an HIV-specific instrument. Methods: Twenty-five HIV-infected patients (15 with an AIDS diagnosis) on standard antiretroviral and nutrition management were studied before and an average of 18.6 weeks after the initiation of oxandrolone therapy, as prescribed by their primary care physician for the treatment of weight loss. BCM was estimated from intracellular water measured by multiple dilution. Lean soft tissue mass (LTM) was measured by dual-energy X-ray absorptiometry. Quality of life was evaluated by the Functional Assessment of HIV Infection (FAHI) questionnaire. Results: Significant gains in body weight (2.6 +/- 3.0 kg; p < .0001), BCM (3.6 +/- 3.0 kg; p < .0001), and LTM (3.0 +/- 2.9 kg; p < .0001) occurred over an average course of 18.6 weeks of treatment. Overall quality of life improved (p = .056) and appetite improved (p = .032), both of which were positively associated with weight gain (p = .040 and p = .022, respectively). Conclusions: This is the first study involving oxandrolone therapy in HIV infection to document changes in quality of life and BCM, the metabolically active component of lean body mass that reflects nutritional status better than other more global body composition parameters. Nutritional status and quality of life can improve in HIV-infected individuals receiving a combined therapeutic approach that includes oxandrolone. C1 Virginia Tech, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA. Univ Arizona, Dept Nutr Sci, Tucson, AZ USA. NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Earthman, CP (reprint author), Virginia Tech, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA. NR 63 TC 23 Z9 23 U1 0 U2 3 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD NOV-DEC PY 2002 VL 26 IS 6 BP 357 EP 365 DI 10.1177/0148607102026006357 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 655JU UT WOS:000181548900009 PM 12405647 ER PT J AU Weiss, A King, JE Enns, RM AF Weiss, A King, JE Enns, RM TI Subjective well-being is heritable and genetically correlated with dominance in chimpanzees (Pan troglodytes) SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article ID RESTRICTED MAXIMUM-LIKELIHOOD; VARIANCE-COMPONENTS; MAJOR DEPRESSION; NEGATIVE AFFECT; ANIMAL-MODELS; SELF-ESTEEM; PERSONALITY; HAPPINESS; EXTROVERSION; ENVIRONMENTS AB The hypothesis that subjective well-being (SWB) is heritable and genetically correlated with Dominance was tested using 128 zoo chimpanzees. Dominance was a chimpanzee-specific personality factor including items reflecting Extroversion and low Neuroticism. SWB was measured with a 4-item scale. The best behavior genetic model included additive genetic and nonshared environmental effects for SWB and Dominance, marginal maternal effects for SWB, a high genetic correlation, and a loco nonshared environmental correlation. Results indicated that the shared variance between SWB and Dominance was a consequence of common genes and that the unique variance between SWB and Dominance was a consequence of the nonshared environment. These findings indicate that common genes may underlie the correlation between human personality factors and SWB. C1 Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP Weiss, A (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 75 TC 62 Z9 65 U1 0 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD NOV PY 2002 VL 83 IS 5 BP 1141 EP 1149 DI 10.1037//0022-3514.83.5.1141 PG 9 WC Psychology, Social SC Psychology GA 607LK UT WOS:000178792900009 PM 12416918 ER PT J AU Igarashi, H Ito, T Pradhan, TK Mantey, SA Hou, W Coy, DH Jensen, RT AF Igarashi, H Ito, T Pradhan, TK Mantey, SA Hou, W Coy, DH Jensen, RT TI Elucidation of the vasoactive intestinal peptide pharmacophore for VPAC(2) receptors in human and rat and comparison to the pharmacophore for VPAC(1) receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CYCLASE-ACTIVATING POLYPEPTIDE; PIG PANCREATIC ACINI; VIP RECEPTORS; CELL-LINES; IN-VITRO; EXPRESSION; GROWTH; AGONIST; PHARMACOLOGY; RO-25-1553 AB Vasoactive intestinal peptide (VIP) functions as a neurotransmitter involved in a number of physiological and pathological conditions. The actions of VIP are mediated through VPAC(1) and VPAC(2). In contrast to VPAC(1), which has been extensively studied, little is known about the pharmacology of VPAC(2). In this study we investigated the VIP pharmacophore for VPAC(2) by using alanine and D-amino acid scanning. We found significant species differences, and the human VPAC(2) (hVPAC(2)) expressed in Chinese hamster ovary (CHO) cells, which have been used in previous studies, differed significantly from the native hVPAC(2) in Sup T-1 cells and hVPAC(2) expressed in PANC1 cells. There was a close agreement between binding affinities and potencies for VPAC(2) activation. The amino acids whose backbone or side chain orientations were most important for high affinity potency are Asp(3), Phe(6), Thr(7), Tyr(10), Arg(12), Tyr(22), and Leu(23), whereas the side chains of Ser(2), Asp(8), Asn(9), Gln(16), Val(19), Lys(20), Lys(21), Asn(24), and Ser(25) are not essential. Comparison of the VIP pharmacophore between hVPAC(1) and hVPAC(2) demonstrated that the side chains of Thr(7), Tyr(10), Thr(11), and Tyr(22) were much more critical for high affinity for the hVPAC(2) than the hVPAC(1). In contrast, the orientation of the side chain of Asn(24) was more important for high affinity for the hVPAC(1). This study shows that in assessing the pharmacophore of VIP analogs for the VPAC(2), important species differences need to be considered as well as the expression system used. These results of our study should be useful for designing VPAC subtype-selective analogs, simplified analogs, and possibly metabolically stable analogs. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA 70118 USA. RP NIDDK, NIH, DDB, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 41 TC 26 Z9 30 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2002 VL 303 IS 2 BP 445 EP 460 DI 10.1124/jpet.102.038075 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 605NW UT WOS:000178684800002 PM 12388623 ER PT J AU Esaki, T Itoh, Y Shimoji, K Cook, M Jehle, J Sokoloff, L AF Esaki, T Itoh, Y Shimoji, K Cook, M Jehle, J Sokoloff, L TI Effects of dopamine receptor blockade on cerebral blood flow response to somatosensory stimulation in the unanesthetized rat SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HALOPERIDOL; METABOLISM; ARTERIES; BRAIN; DOG AB Local cerebral blood flow (CBF) was determined in 30 cerebral structures, including four structures of the whisker-to-barrel cortex sensory pathway, by the quantitative autoradiographic [C-14] iodoantipyrine method during unilateral vibrissal stimulation in rats administered 0.1 or 1.0 mg/kg haloperidol or its control vehicle intravenously. The low dose of haloperidol had no significant effects on resting CBF or its enhancement by vibrissal stimulation. By standard t tests, the high dose statistically significantly lowered baseline CBF in frontal and visual cortex, hippocampus, dentate gyrus, inferior olive, cerebellar cortex, and the ventral posteromedial (VPM) thalamic nucleus on the unstimulated side, and raised baseline CBF in the lateral habenula; however, these changes lost statistical significance after Bonferroni correction for multiple comparisons. Neither dose had any effects on the increases in CBF evoked by vibrissal stimulation in the principal sensory trigeminal nucleus and barrel cortex, but the higher dose statistically significantly enhanced the percent increases in CBF due to the sensory stimulation in the spinal trigeminal nucleus and VPM thalamic nucleus. These results do not support a role for direct dopaminergic vasoactive mechanisms in the increases in CBF associated with neuronal functional activation. C1 NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, NIH, Bldg 36,1A-07,36 Convent Dr MSC 4030, Bethesda, MD 20892 USA. NR 20 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2002 VL 303 IS 2 BP 497 EP 502 DI 10.1124/jpet.102.039081 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 605NW UT WOS:000178684800007 PM 12388628 ER PT J AU Unger, EL Mazzola-Pomietto, P Murphy, DL Andrews, AM AF Unger, EL Mazzola-Pomietto, P Murphy, DL Andrews, AM TI 2 '-NH2-MPTP [1-methyl-4-(2 '-aminophenyl)-1,2,3,6-tetrahydropyridine] depletes serotonin and norepinephrine in rats: A comparison with 2 '-CH3-MPTP [1-methyl-4-(2 '-methylphenyl)-1,2,3,6-tetrahydropyridine] SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VESICULAR MONOAMINE TRANSPORTER; DOPAMINERGIC NEUROTOXIN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; HIPPOCAMPAL SEROTONIN; SPECIES SENSITIVITY; MPTP NEUROTOXICITY; KNOCKOUT MICE; IN-VIVO; 1-METHYL-4-PHENYLPYRIDINIUM AB The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) analog, 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2 MPTP), depletes brain serotonin and norepinephrine in mice without affecting striatal dopamine. The present study was conducted to determine whether 2'-NH2-MPTP would be similarly neurotoxic to rats. Four injections of 20 mg/kg 2'-NH2-MPTP caused 80 to 90% depletions in serotonin and norepinephrine in frontal cortex and hippocampus in rats 1 week post-treatment. A lower dose of 2'-NH2-MPTP (4 x 15 mg/kg) also produced large decrements in serotonin and norepinephrine levels and in serotonin transporter density measured 3 weeks after neurotoxin administration. Furthermore, this lower dose of 2'-NH2-MPTP altered functional serotonin neurotransmission as evidenced by a 2-fold potentiation of 1-(3-chlorophenyl)-piperazine.2HCl-induced hyperthermia, an index of serotonergic denervation supersensitivity. At both doses, 2'-NH2-MPTP was without effect on striatal dopamine. For comparison, additional rats were treated with a second 2'-substituted analog of MPTP, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP), at 2 x 20 mg/kg. This dosing regimen causes substantial striatal dopamine depletion in mice. 2'-CH3 MPTP had no effect on brain levels of serotonin, norepinephrine, or dopamine in rats. Together, these results demonstrate that rats are sensitive to the toxic effects of 2'-NH2-MPTP but not to 2'-CH3-MPTP at doses known to cause neurotoxicity in mice. Moreover, this study clearly shows that 2'-NH2-MPTP can be utilized in rats as a tool to study the serotonergic and noradrenergic neurotransmitter systems. C1 Penn State Univ, Dept Chem, Davey Lab 152, University Pk, PA 16802 USA. INSERM, F-13258 Marseille, France. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Andrews, AM (reprint author), Penn State Univ, Dept Chem, Davey Lab 152, University Pk, PA 16802 USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 47 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2002 VL 303 IS 2 BP 527 EP 533 DI 10.1124/jpet.102.037614 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 605NW UT WOS:000178684800011 PM 12388632 ER PT J AU Broom, DC Nitsche, JF Pintar, JE Rice, KC Woods, JH Traynor, JR AF Broom, DC Nitsche, JF Pintar, JE Rice, KC Woods, JH Traynor, JR TI Comparison of receptor mechanisms and efficacy requirements for delta-agonist-induced convulsive activity and antinociception in mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DIFFERENTIAL ANTAGONISM; OPIOID RECEPTORS; NALTRINDOLE 5'-ISOTHIOCYANATE; MEDIATED ANTINOCICEPTION; SQUIRREL-MONKEYS; BW373U86; SUBTYPES; BINDING; SNC-80; ANALOG AB delta-Opioid receptor-selective agonists produce antinociception and convulsions in several species, including mice. This article examines two hypotheses in mice: 1) that antinociception and convulsive activity are mediated through the same type of delta-receptor and 2) that greater delta-agonist efficacy is required for antinociception than for convulsive activity. delta-Mediated antinociception was evaluated in the acetic acid-induced abdominal constriction assay, which involves a low-intensity noxious stimulus; convulsive activity was indicated as a mild tonic-clonic convulsive episode followed by a period of catalepsy. In delta-opioid receptor knockout mice [DOR-1(-/-)], the nonpeptidic delta-agonists (+/-)-4-[( R*)-[(2S*, 5R*)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-( 3-hydroxyphenyl) methyl]- N,N- diethylbenzamide hydrochloride (BW373U86) and (+)-4-[(R)-[(2S, 5R)-2,5-dimethyl- 4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl) methyl]- N, N-diethylbenzamide (SNC80) failed to produce convulsive behavior demonstrating the absolute involvement of DOR-1 in this effect. In NIH Swiss mice expressing delta-opioid receptors, BW373U86 produced both antinociception and convulsive activity. These effects were antagonized by the putative delta(1)-receptor-selective antagonist 7-benzylidenenaltrexone and the putative delta(2)-receptor-selective antagonist naltriben. Tolerance developed to both the convulsive and antinociceptive effects of BW373U86. Tolerance to the convulsive, but not the antinociceptive, effects of BW373U86 was largely prevented when the antagonist naltrindole was given 20 min after each dose of the agonist in a 3-day treatment paradigm. The convulsive action of BW373U86 was also less sensitive than the antinociceptive action to treatment with the irreversible delta-antagonist naltrindole isothiocyanate. Collectively, these data suggest that the convulsive and antinociceptive activities of delta-agonists are mediated through the same receptor but that the receptor reserve for delta-mediated convulsive activity is greater than for delta-mediated antinociceptive activity. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Psychol, Ann Arbor, MI USA. Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Traynor, JR (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1150 W Med Ctr Dr,1301 Med Sci Res Bldg 3, Ann Arbor, MI 48109 USA. FU NIDA NIH HHS [DA 00254, DA 059501, DA 09040, F32 DA 05964, T32 DA 07267]; NIGMS NIH HHS [GM 07767]; NIMH NIH HHS [T32 MH/AG 19957] NR 32 TC 45 Z9 45 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2002 VL 303 IS 2 BP 723 EP 729 DI 10.1124/jpet.102.036525 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 605NW UT WOS:000178684800036 PM 12388657 ER PT J AU Knepper, MA Masilamani, S Brooks, HL Turban, S Nielsen, J Beutler, K Packer, RK AF Knepper, MA Masilamani, S Brooks, HL Turban, S Nielsen, J Beutler, K Packer, RK TI Antibody-based targeted proteomic analysis of renal tubule sodium transporter regulation: role of angiotensin II SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract CT Meeting of the Physiological-Society CY SEP 10-12, 2002 CL UNIV LEEDS, LEEDS, ENGLAND SP Physiol Soc HO UNIV LEEDS ID KIDNEY C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 2002 VL 544 SU S BP 8S EP 8S PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 631JP UT WOS:000180164600232 ER PT J AU Stewart, GS Fenton, RA Thevenod, F Smith, CP AF Stewart, GS Fenton, RA Thevenod, F Smith, CP TI Phloretin-inhibitable urea transport in the mouse colon SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract CT Meeting of the Physiological-Society CY SEP 10-12, 2002 CL UNIV LEEDS, LEEDS, ENGLAND SP Physiol Soc HO UNIV LEEDS C1 Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 2002 VL 544 SU S BP 94P EP 94P PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 631JP UT WOS:000180164600176 ER PT J AU Sudweeks, SN van Hooft, JA Yakel, JL AF Sudweeks, SN van Hooft, JA Yakel, JL TI Serotonin 5-HT3 receptors in rat CA1 hippocampal interneurons: functional and molecular characterization SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GATED ION CHANNELS; NICOTINIC ACH RECEPTORS; 2 SPLICE VARIANTS; FREELY MOVING RAT; NG108-15 CELLS; 5-HYDROXYTRYPTAMINE(3) RECEPTOR; ACETYLCHOLINE-RECEPTOR; PYRAMIDAL CELLS; NERVE-TERMINALS; GUINEA-PIG AB The molecular makeup of the serotonin 5-HT3 receptor (5-HT3R) channel was investigated in rat hippocampal CA1 interneurons in slices using single-cell RT-PCR and patch-clamp recording techniques. We tested for the expression of the 5-HT3A (both short and long splice variants) and 5-HT3B subunits, as well as the expression of the alpha4 subunit of the neuronal nicotinic ACh receptors (nAChRs), the latter of which has been shown to co-assemble with the 5-HT3A subunit in heterologous expression systems. Both the 5-HT3A-short and alpha4-nAChR subunits were expressed in these interneurons, but we could not detect any expression of either the 5-HT3B or the 5-HT3A-long subunits. Furthermore, there was a strong tendency for the 5-HT3A-short and a4-nAChR subunits to be co-expressed in individual interneurons. To assess whether there was any functional evidence for co-assembly between the 5-HT3A-short and alpha4-nAChR subunits, we used the sulphydryl agent 2-aminoethyl methanethiosulphonate (MTSEA), which has previously been shown to modulate expressed 5-HT(3)Rs that contain the alpha4-nAChR subunit. In half of the interneurons examined, MTSEA significantly enhanced the amplitude of the 5-HT3R-mediated responses, which is consistent with the notion that the alpha4-nAChR subunit co-assembles with the 5-HT3A Subunit to form a native heteromeric 5-HT3R channel in rat CA1 hippocampal interneurons in vivo. In addition, the single-channel properties of the 5-HT3R were investigated in outside-out patches. No resolvable single-channel currents were observed. Using non-stationary fluctuation analysis, we obtained an estimate of the single-channel conductance of 4 pS, which is well below that expected for channels containing both the 5-HT3A and 5-HT3B subunits. C1 Univ Amsterdam, Swammerdam Inst Life Sci, Neurobiol Sect, NL-1090 GB Amsterdam, Netherlands. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 55 TC 29 Z9 29 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 2002 VL 544 IS 3 BP 715 EP 726 DI 10.1113/jphysiol.2002.029736 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 615ZD UT WOS:000179276500006 PM 12411518 ER PT J AU Webster, JI Carlstedt-Duke, J AF Webster, JI Carlstedt-Duke, J TI Involvement of multidrug resistance proteins (MDR) in the modulation of glucocorticoid response SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE multidrug resistance; P-glycoprotein; ABC transporter proteins; glucocorticoid response; receptor modulation ID RECEPTOR-BETA-ISOFORM; PRODUCT P-GLYCOPROTEIN; CYCLOSPORINE-A; GENE FAMILY; IMMUNOSUPPRESSANTS FK506; PROGESTERONE-RECEPTOR; TISSUE DISTRIBUTION; INDUCED APOPTOSIS; CMOAT MRP2; CELL-LINES AB Glucocorticoid resistance is a problem in the treatment of many diseases. One possible factor involved in the modulation of a glucocorticoid response is the export of glucocorticoids out of the cell. It has been shown that multidrug resistance protein I (MDR1, ABCB1), a member of the ABC family, is capable of transporting some glucocorticoids. This paper uses a mouse cell line, LMCAT in which the glucocorticoid response can be modulated by inhibitors of multidrug resistance proteins. Glucocorticoids fall into three categories. Firstly, those that are transported by an Abcb1a/Abcb1b transporter and whose transport can be inhibited by inhibitors of ABCB1 activity. Functional Abcb1a/Abcb1b was detected by inhibition of rhodamine efflux by these drugs and mRNA for Abcb1a and Abcb1b were detected in these cells. Secondly, those that are not transported. Finally, those that are transported by an Abcc1a transporter. Calcein transport out of these cells was blocked by treatment with probenecid indicating a functional Abcc I a transporter. Abcc I a mRNA was also detected in these cells. Thus, this paper provides insight into the mechanisms of glucocorticoid transport in cells and demonstrates a diversity of two independent mechanisms of transport of glucocorticoids by Abcb1a/Abcb1b and Abcc I a with individual patterns of steroid specificity. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Huddinge Univ Hosp, Karolinska Inst, Novum, Dept Med Nutr, S-14186 Huddinge, Sweden. RP Webster, JI (reprint author), NIMH, NIH, Bldg 36,Rm 1A21,36 Convent Dr,MSC 4020, Bethesda, MD 20892 USA. RI Webster Marketon, Jeanette/H-5613-2011 OI Webster Marketon, Jeanette/0000-0002-3627-1094 NR 83 TC 39 Z9 44 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 2002 VL 82 IS 4-5 BP 277 EP 288 AR PII S0960-0760(02)00227-3 DI 10.1016/S0960-0760(02)00227-3 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 653AB UT WOS:000181412100002 PM 12589934 ER PT J AU Taylor, SC Kelly, AP Dupree, NE Kimball, AB Lawrence, RC AF Taylor, SC Kelly, AP Dupree, NE Kimball, AB Lawrence, RC TI Health disparities in arthritis and musculoskeletal and skin diseases - The dermatology session: National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, December 15-16, 2000 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB The National Institute of Arthritis and Musculoskeletal and Skin Diseases hosted a diverse group of physicians and scientists to discuss health disparities in arthritis, musculoskeletal, and skin diseases. This article discusses the cutaneous disease portion of the conference. Speakers described a history of scarce information on cutaneous diseases in skin of color, problems with the data that do exist, and inappropriate use of dermatologic data. Basic descriptive data on the structure and function of skin in people of color is needed. For specific cutaneous diseases, information must be collected on their epidemiology, clinical presentation, natural history, complications, and therapeutics. Researchers are standardizing methods for studying keloidal scars, and are developing and validating measurement tools for cutaneous diseases in skin of color, such as atypical nevi, psoriasis, and hand dermatitis, but more is needed. C1 St Lukes Roosevelt Hosp, Skin Color Ctr, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Dermatol, New York, NY USA. King Drew Med Ctr, Div Dermatol, Los Angeles, CA USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Planning Banch, Natl Hlth & Nutr Examinat Survey, Hyattsville, MD 20782 USA. Stanford Univ, Med Ctr, Dept Dermatol, Stanford, CA 94305 USA. NIAMSD, Bethesda, MD 20892 USA. RP Lawrence, RC (reprint author), NIAMS, Bldg 45,Room 5AS-37G, Bethesda, MD 20892 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2002 VL 47 IS 5 BP 770 EP 773 DI 10.1067/mjd.2002.124691 PG 4 WC Dermatology SC Dermatology GA 609FM UT WOS:000178893000018 PM 12399772 ER PT J AU Shavers, VL Shankar, S Alberg, AJ AF Shavers, VL Shankar, S Alberg, AJ TI Perceived access to health care and its influence on the prevalence of behavioral risks among urban African Americans SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE health care access; behaxioral risks; cancer screening utilization; cigarette smoking; alcohol consumption; barriers to care; health disparities ID PREVENTIVE SERVICES; UNITED-STATES; FIRST-EVER; BREAST; PHYSICIAN; BARRIERS; ADULTS; STROKE; RATES; WOMEN AB Introduction: Individuals who have difficulty gaining access to health care may delay seeking and obtaining treatment, underutilize preventive health care services, and may hove a high prevalence of chronic disease risks. This report examines participant perception of the level of difficulty encountered when obtaining medical care and its influence on the prevalence of chronic disease behavioral risks among urban African Americans. Results: We found a significantly higher prevalence of current cigarette smoking and alcohol consumption among African Americans who reported that they experienced difficulty in obtaining medical care than among those who did not. Compared to those who experienced no difficulty obtaining care, participants who perceived a high level of difficulty in obtaining care were less likely to have had a physical exam in the past year and to have seen the some doctor when services were obtained. Conclusion: The perception of a high level of difficulty obtaining health care may be associated with a higher prevalence of behavioral risks for chronic disease. The limited data suggest a need to more closely examine the perception of health care accessibility and its relationship to health services utilization and the prevalence of chronic disease behavioral risks. C1 Johns Hopkins Univ, Dept Epidemiol, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. FU NCI NIH HHS [K07 CA61807-94, T32CA09314-19, CA73790, R03 CA77184-01] NR 39 TC 8 Z9 10 U1 1 U2 3 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD NOV PY 2002 VL 94 IS 11 BP 952 EP 962 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 614JA UT WOS:000179183800003 PM 12442998 ER PT J AU Lovelady, CA Dewey, KG Picciano, MF Dermer, A AF Lovelady, CA Dewey, KG Picciano, MF Dermer, A TI Guidelines for collection of human milk samples for monitoring and research of environmental chemicals SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article; Proceedings Paper CT Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States CY FEB 15-17, 2002 CL PENN STATE UNIV COLL MED, MILTON S HERSHEY MED CTR, HERSHEY, PENNSYLVANIA HO PENN STATE UNIV COLL MED, MILTON S HERSHEY MED CTR ID BREAST-MILK; FECAL EXCRETION; FED INFANTS; LACTATION; EXPOSURE AB This article addresses sample collection protocols for monitoring and research of environmental chemicals in human milk. The process of milk synthesis and secretion and variations in contents of constituents that may impact measurement of environmental chemicals are presented. Possible sources of variation include parity, stage of lactation, method of sampling, maternal nutritional status, and dietary intake. General principles regarding how and when to collect milk samples are provided. For any previously unstudied environmental chemical in milk, all sources of variance must be assessed before a meaningful sampling protocol can be devised. C1 Univ N Carolina, Dept Nutr, Greensboro, NC 27410 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Family Practice Ctr, Old Bridge, NJ USA. RP Lovelady, CA (reprint author), Univ N Carolina, Dept Nutr, POB 26170, Greensboro, NC 27410 USA. NR 18 TC 13 Z9 14 U1 3 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD NOV PY 2002 VL 65 IS 22 BP 1881 EP 1891 DI 10.1080/00984100290071775 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 609PY UT WOS:000178915200006 PM 12470492 ER PT J AU Gummuluru, S KewalRamani, VN Emerman, M AF Gummuluru, S KewalRamani, VN Emerman, M TI Dendritic cell-mediated viral transfer to T cells is required for human immunodeficiency virus type 1 persistence in the face of rapid cell turnover SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; DC-SIGN; INTRAVAGINAL INOCULATION; ANTIRETROVIRAL THERAPY; IMMUNOLOGICAL SYNAPSE; PRODUCTIVE INFECTION; ENDOTHELIAL-CELLS; LYMPHOID-TISSUE; SOLUBLE CD4; LYMPHOCYTES AB Human immunodeficiency virus type 1 (HIV-1)-infected and activated CD4(+) T cells have short half-lives in vivo (<2 days). We have established an in vitro culture system in which infected T cells are turned over frequently to provide a model system that examines this important facet of in vivo HIV-1 replication. We observed that virus replication in T cells under rapid-turnover conditions was possible only when immature dendritic cells or DC-SIGN-expressing cells mediated HIV-1 transmission to T cells. Virus replication was initiated more rapidly in T cells infected with the cell-associated form of virus compared to infection by the cell-free route. This accelerated transfer of virus required adhesion molecule-mediated interactions between the virus-presenting cell and T cell, but surprisingly, HIV-1 transfer could occur independently of DC-SIGN (DC-specific intracellular adhesion molecule 3 [ICAM-3]-grabbing nonintegrin)in the dendritic-cell-T-cell cocultures. These results suggest that dendritic cell-mediated transmission of HIV-1 enables virus replication under conditions of rapid cell turnover in vivo. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Emerman, M (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, Mailstop C2-023,1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA. OI Gummuluru, Suryaram/0000-0002-8606-8481 FU NIAID NIH HHS [R01 AI030927, R01 AI30927] NR 59 TC 49 Z9 49 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 21 BP 10692 EP 10701 DI 10.1128/JVI.76.21.10692-10701.2002 PG 10 WC Virology SC Virology GA 602NX UT WOS:000178512300012 PM 12368311 ER PT J AU Kenyon, TK Cohen, JI Grose, C AF Kenyon, TK Cohen, JI Grose, C TI Phosphorylation by the varicella-zoster virus ORF47 protein serine kinase determines whether endocytosed viral gE traffics to the trans-Golgi network or recycles to the cell membrane SO JOURNAL OF VIROLOGY LA English DT Article ID FC RECEPTOR GE; GLYCOPROTEIN-GPI; CYTOPLASMIC TAIL; INFECTED CELL; VZV; EXPRESSION; DOMAIN; REPLICATION; ENVELOPMENT; SPREAD AB Like all alphaherpesviruses, varicella-zoster virus (VZV) infection proceeds by both cell-cell spread and virion production. Virions are enveloped within vacuoles located near the trans-Golgi network (TGN), while in cell-cell spread, surface glycoproteins fuse cells into syncytia. In this report, we delineate a potential role for serine/threonine phosphorylation of the cytoplasmic tail of the predominant VZV glycoprotein, gE, in these processes. The fact that VZV gE (formerly called gpI) is phosphorylated has been documented (E. A. Montalvo and C. Grose, Proc. Nati. Acad. Sci. USA 83:8967-8971, 1986), although respective roles of viral and cellular protein kinases have never been delineated. VZV ORF47 is a viral serine protein kinase that recognized a consensus sequence similar to that of casein kinase II (CKII). During open reading frame 47 (ORF47)-specific in vitro kinase assays, ORF47 phosphorylated four residues in the cytoplasmic tail of VZV gE (S593, S595, T596, and T598), thus modifying the known phosphofurin acidic cluster sorting protein 1 domain. CKII phosphorylated gE predominantly on the two threonine residues. In wild-type-virus-infected cells, where ORF47-mediated phosphorylation predominated, gE endocytosed and relocalized to the TGN. In cells infected with a VZV ORF47-null mutant, internalized VZV gE recycled to the plasma membrane and did not localize to the TGN. The mutant virus also formed larger syncytia than the wild-type virus, linking CKII-mediated gE phosphorylation with increased cell-cell spread. Thus, ORF47 and CKII behaved as "team players" in the phosphorylation of VZV gE. Taken together, the results showed that phosphorylation of VZV gE by ORF47 or CKII determined whether VZV infection proceeded toward a pathway likely involved with either virion production or cell-cell spread. C1 Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. NIAID, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Univ Hosp, 2501 JCP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM charles-grose@uiowa.edu FU NIAID NIH HHS [AI36884, AI22795, R01 AI022795] NR 51 TC 40 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 21 BP 10980 EP 10993 DI 10.1128/JVI.76.21.10980-10993.2002 PG 14 WC Virology SC Virology GA 602NX UT WOS:000178512300042 PM 12368341 ER PT J AU Sato, H Callanan, LD Pesnicak, L Krogmann, T Cohen, JI AF Sato, H Callanan, LD Pesnicak, L Krogmann, T Cohen, JI TI Varicella-zoster virus (VZV) ORF17 protein induces RNA cleavage and is critical for replication of VZV at 37 degrees C but not 33 degrees C SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; HOST SHUTOFF PROTEIN; TRANSCRIPTIONAL REGULATORY PROTEIN; MESSENGER-RNA; VHS PROTEIN; BOVINE HERPESVIRUS-1; PSEUDORABIES VIRUS; GENE-EXPRESSION; IN-VITRO; DNA AB Varicella-zoster virus (VZV) open reading frame 17 (ORF17) is homologous to herpes simplex virus (HSV) UL41, which encodes the viral host shutoff protein (vhs). HSV vhs induces degradation of mRNA and rapid shutoff of host protein synthesis. An antibody to ORF17 protein detected a 46-kDa protein in VZV-infected cells. While HSV vhs is located in virions, VZV ORF17 protein was not detectable in virions. ORF17 protein induced RNA cleavage, but to a substantially lesser extent than HSV-1 vhs. Expression of ORF17 protein did not inhibit expression from a P-galactosidase reporter plasmid, while HSV type 1 vhs abolished reporter expression. Two VZV ORF17 deletion mutants were constructed to examine the role of ORF17 in virus replication. While the ORF17 VZV mutants grew to peak titers that were similar to those of the parental virus at 33degreesC, the ORF17 mutants grew to 20- to 35-fold-lower titers than parental virus at 37degreesC. ORF62 protein was distributed in a different pattern in the nuclei and cytoplasm of cells infected with an ORF17 deletion mutant at 37degreesC compared to 33degreesC. Inoculation of cotton rats with the ORF17 deletion mutant resulted in a level of latent infection similar to that produced by inoculation with the parental virus. The importance of ORF17 protein for viral replication at 37degreesC but not at 33degreesC suggests that this protein may facilitate the growth of virus in certain tissues in vivo. C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bldg 10,Rm 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 48 TC 27 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 21 BP 11012 EP 11023 DI 10.1128/JVI.76.21.11012-11023.2002 PG 12 WC Virology SC Virology GA 602NX UT WOS:000178512300045 PM 12368344 ER PT J AU Muriaux, D Mirro, J Nagashima, K Harvin, D Rein, A AF Muriaux, D Mirro, J Nagashima, K Harvin, D Rein, A TI Murine leukemia virus nucleocapsid mutant particles lacking viral RNA encapsidate ribosomes SO JOURNAL OF VIROLOGY LA English DT Article ID BASIC RESIDUES; ZINC-FINGER; P-PROTEINS; VIRION; RETROVIRUSES; EXPRESSION; SEQUENCE; DOMAIN AB A single retroviral protein, termed Gag, is sufficient for assembly of retrovirus-like particles in mammalian cells. Gag normally selects the genomic RNA of the virus with high specificity; the nucleocapsid (NC) domain of Gag plays a crucial role in this selection process. However, encapsidation of the viral RNA is completely unnecessary for particle assembly. We previously showed that mutant murine leukemia virus (MuLV) particles that lack viral RNA because of a deletion in the cis-acting packaging signal ("Psi") in the genomic RNA compensate for the loss of the viral RNA by incorporating cellular mRNA. The RNA in wild-type and Psi(-)particles was also found to be necessary for virion core structure. In the present work, we explored the role of RNA in MuLV particles that lack genomic RNA because of mutations in the NC domain of Gag. Using a fluorescent dye assay, we observed that NC mutant particles contain the same amount of RNA that wild-type virions do. Surprisingly enough, these particles contained large amounts of rRNAs. Furthermore, ribosomall proteins were detected by immunoblotting, and ribosomes were observed inside the particles by electron microscopy. The biological significance of the presence of ribosomes in NC mutant particles lacking genomic RNA is discussed. C1 NCI Frederick, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. NCI Frederick, Image Anal Lab, Ft Detrick, MD 21702 USA. RP Muriaux, D (reprint author), NCI Frederick, HIV Drug Resistance Program, POB B, Ft Detrick, MD 21702 USA. EM dmuriaux@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 26 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11405 EP 11413 DI 10.1128/JVI.76.22.11405-11413.2002 PG 9 WC Virology SC Virology GA 608AF UT WOS:000178822400025 PM 12388701 ER PT J AU Baig, J Levy, DB McKay, PF Schmitz, JE Santra, S Subbramanian, RA Kuroda, MJ Lifton, MA Gorgone, DA Wyatt, LS Moss, B Huang, Y Chakrabarti, BK Xu, L Kong, WP Yang, ZY Mascola, JR Nabel, GJ Carville, A Lackner, AA Veazey, RS Letvin, NL AF Baig, J Levy, DB McKay, PF Schmitz, JE Santra, S Subbramanian, RA Kuroda, MJ Lifton, MA Gorgone, DA Wyatt, LS Moss, B Huang, Y Chakrabarti, BK Xu, L Kong, WP Yang, ZY Mascola, JR Nabel, GJ Carville, A Lackner, AA Veazey, RS Letvin, NL TI Elicitation of simian immunodeficiency virus-specific cytotoxic T lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination SO JOURNAL OF VIROLOGY LA English DT Article ID I-PEPTIDE COMPLEX; SIV INFECTION; VIREMIA; AIDS; CTL; MAMU-A-ASTERISK-01; REPLICATION; PREVENTION; CHALLENGE; MACAQUES AB Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymphocytes (CTL) specific for simian immunodeficiency virus (SIV) and simian HIV can be reproducibly sampled from intestinal mucosal tissue of rhesus monkeys obtained under endoscopic guidance. These lymphocytes recognize peptide-major histocompatibility complex class I complexes and express gamma interferon on exposure to peptide antigen. Interestingly, systemic immunization of monkeys with plasmid DNA immunogens followed by live recombinant attenuated poxviruses or adenoviruses with genes deleted elicits high-frequency SIV-specific CTL responses in these mucosal tissues. These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Tulane Reg Primate Res Ctr, Covington, LA 70433 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med, 330 Brookline Ave,RE-113, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA050139, CA50139]; NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [AI28147, AI48394, P30 AI028691, R37 AI020729, U01 AI028147, R01 AI048394, AI20729, R01 AI020729, AI85343, AI28691, U19 AI028147, P01 AI028147] NR 30 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11484 EP 11490 DI 10.1128/JVI.76.22.11484-11490.2002 PG 7 WC Virology SC Virology GA 608AF UT WOS:000178822400034 PM 12388710 ER PT J AU Viard, M Parolini, I Sargiacomo, M Fecchi, K Ramoni, C Ablan, S Ruscetti, FW Wang, JM Blumenthal, R AF Viard, M Parolini, I Sargiacomo, M Fecchi, K Ramoni, C Ablan, S Ruscetti, FW Wang, JM Blumenthal, R TI Role of cholesterol in human immunodeficiency virus type 1 envelope protein-mediated fusion with host cells SO JOURNAL OF VIROLOGY LA English DT Article ID PLASMA-MEMBRANE DOMAINS; LIPID RAFTS; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; CHEMOKINE RECEPTORS; SURFACE ASSOCIATION; SYNCYTIUM FORMATION; HIV-1 INFECTION; 6-HELIX BUNDLE; GP120 BINDING AB In this study we examined the effects of target membrane cholesterol depletion and cytoskeletal changes on human immunodeficiency virus type 1 (HIV-1) Env-mediated membrane fusion by dye redistribution assays. We found that treatment of peripheral blood lymphocytes (PBL) with methyl-beta-cyclodextrin (MOCD) or cytochalasin reduced their susceptibility to membrane fusion with cells expressing HIV-1 Env that utilize CXCR4 or CCR5. However, treatment of human osteosarcoma (HOS) cells expressing high levels of CD4 and coreceptors with these agents did not affect their susceptibility to HIV-1 Env-mediated membrane fusion. Removal of cholesterol inhibited stromal cell-derived factor-1alpha- and macrophage inflammatory protein 1beta-induced chemotaxis of both PBL and HOS cells expressing CD4 and coreceptors. The fusion activity as well as the chemotactic activity of PBL was recovered by adding back cholesterol to these cells. Confocal laser scanning microscopy analysis indicated that treatment of lymphocytes with MbetaCD reduced the colocalization of CD4 or of CXCR4 with actin presumably in microvilli. These findings indicate that, although cholesterol is not required for HIV-1 Env-mediated membrane fusion per se, its depletion from cells with relatively low coreceptor densities reduces the capacity of HIV-1 Env to engage coreceptor clusters required to trigger fusion. Furthermore, our results suggest that coreceptor clustering may occur in microvilli that are supported by actin polymerization. C1 NCI, Canc Res Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. NCI, Canc Res Ctr, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. NCI, Canc Res Ctr, Basic Res Lab, NIH, Frederick, MD 21702 USA. Ist Super Sanita, Dept Hematol Oncol, I-00161 Rome, Italy. Ist Super Sanita, Dept Immunol, I-00161 Rome, Italy. RP Blumenthal, R (reprint author), NCI, Canc Res Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RI parolini, Isabella/J-9955-2016; OI Parolini, Isabella/0000-0001-9863-1051 NR 82 TC 116 Z9 122 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11584 EP 11595 DI 10.1128/JVI.76.22.11584-11595.2002 PG 12 WC Virology SC Virology GA 608AF UT WOS:000178822400043 PM 12388719 ER PT J AU Katz, E Wolffe, E Moss, B AF Katz, E Wolffe, E Moss, B TI Identification of second-site mutations that enhance release and spread of vaccinia virus SO JOURNAL OF VIROLOGY LA English DT Article ID EXTRACELLULAR ENVELOPED VIRUS; ACTIN-CONTAINING MICROVILLI; TO-CELL SPREAD; INTRACELLULAR MOVEMENT; PROGENY VACCINIA; TAIL FORMATION; A33R GENE; PROTEIN; GLYCOPROTEIN; MEMBRANE AB The spread of most strains of vaccinia virus in cell monolayers occurs predominantly via extracellular enveloped virions that adhere to the tips of actin-containing microvilli and to a lesser extent via diffusion of released virions. The mechanism by which virions adhere to the cell surface is unknown, although several viral proteins may be involved. The present investigation was initiated with the following premise: spontaneous mutations that increase virus release will be naturally selected by propagating a virus unable to spread by means of actin tails. Starting with an A36R deletion mutant that forms small, round plaques, five independent virus clones with enhanced spread due to the formation of comet or satellite plaques were isolated. The viral membrane glycoprotein genes of the isolates were sequenced; four had mutations causing C-terminal truncations of the A33R protein, and one had a serine replacing proline 189 of the 13511 protein. The comet-forming phenotype was specifically reproduced or reversed by homologous recombination using DNA containing the mutated or natural sequence, respectively. Considerably more extracellular enveloped virus was released into the medium by the second-site mutants than by the parental A36R deletion mutant, explaining their selection in tissue culture as well as their comet-forming phenotype. The data suggest that the 13511 protein and the C-terminal region of the A33R protein are involved in adherence of cell-associated enveloped virions to cells. In spite of their selective advantage in cultured cells, the second-site mutants were not delectably more virulent than the A36R deletion mutant when administered to mice by the intranasal route. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Virol, IL-91010 Jerusalem, Israel. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. NR 43 TC 28 Z9 29 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11637 EP 11644 DI 10.1128/JVI.76.22.11637-11644.2002 PG 8 WC Virology SC Virology GA 608AF UT WOS:000178822400048 PM 12388724 ER PT J AU Stevceva, L Alvarez, X Lackner, AA Tryniszewska, E Kelsall, B Nacsa, J Tartaglia, J Strober, W Franchini, G AF Stevceva, L Alvarez, X Lackner, AA Tryniszewska, E Kelsall, B Nacsa, J Tartaglia, J Strober, W Franchini, G TI Both mucosal and systemic routes of immunization with the live, attenuated NYVAC/simian immunodeficiency virus SIVgpe recombinant vaccine result in gag-specific CD8(+) T-Cell responses in mucosal tissues of macaques SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-RESPONSES; LAMINA PROPRIA; FLOW-CYTOMETRY; GAMMA-INTERFERON; RHESUS-MONKEYS; LYMPHOCYTES; INFECTION; ANTIGEN; PROTECTION; INDUCTION AB As most human immunodeficiency virus (HIV) infection occurs via mucosal surfaces, an important goal of vaccination may be the induction of virus-specific immune responses at mucosal sites to contain viral infection early on. Here we designed a study in macaques carrying the major histocompatibility complex class I Mamu-A*01 molecule to assess the capacity of the highly attenuated poxvirus NWAC/simian immunodeficiency virus (SIV) SIVgpe vaccine candidate administered by the intranasal, intramuscular, or intrarectal route to induce mucosal immunity. All macaques, including one naive macaque, were exposed to SIVmac251 by the intrarectal route and sacrificed 48 h after infection. The kinetics of immune response at various time points following immunization with NWAC/SIVgpe and the anamnestic response to SIVmac251 at 48 h after challenge were assessed in blood, in serial rectal and vaginal biopsy samples, and in tissues at euthanasia with an SIVmac Gag-specific tetramer. In addition, at euthanasia, antigen-specific cells producing gamma interferon or tumor necrosis factor alpha from the jejunum lamina propria were quantified in all macaques. Surprisingly, antigenspecific CD8+ T cells were found in the mucosal tissues of all immunized macaques regardless of whether the vaccine was administered by a mucosal route (intranasal or intrarectal) or systemically. In addition, following mucosal SIVmac251 challenge, antigen-specific responses were mainly confined to mucosal tissues, again regardless of the route of immunization. We conclude that immunization with a live vector vaccine results in the appearance of CD8(+) T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Aventis Pasteur, Toronto, ON M2R 3T4, Canada. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Comparat Pathol, Southborough, MA 01772 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. FU NCRR NIH HHS [P51 RR000168, RR00168, P51 RR000164, RR00164, K26 RR000168] NR 54 TC 63 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11659 EP 11676 DI 10.1128/JVI.76.22.11659-11676.2002 PG 18 WC Virology SC Virology GA 608AF UT WOS:000178822400050 PM 12388726 ER PT J AU De, SK Devadas, K Notkins, AL AF De, SK Devadas, K Notkins, AL TI Elevated levels of tumor necrosis factor alpha (TNF-alpha) in human immunodeficiency virus type 1-transgenic mice: Prevention of death by antibody to TNF-alpha SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; HUMAN CHORIONIC-GONADOTROPIN; HIV-1 TRANSGENIC MICE; LONG TERMINAL REPEAT; RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; PLASMA-LEVELS; IN-VITRO; ACTIVATION AB Homozygous human immunodeficiency virus type I (HIV-1)-transgenic mice (Tg26) appear normal at birth but die within 3 to 4 weeks. The skin of these animals shows diffuse scaling and high-level expression of both HIV-1 mRNA and gp120. Previous experiments showed that treatment with human chorionic gonadatropin (hCG) prevented death and the expression of HIV-1 mRNA and gp120. The present experiments were initiated to study the role of tumor necrosis factor alpha (TNF-alpha) in HIV-1-induced pathology. Examination of the sera of Tg26 mice revealed a 50-fold increase in TNF-alpha levels compared to those in nontransgenic mice. Treatment with antibody to TNF-alpha prevented death, resulted in near normal growth, and produced a marked decrease in skin lesions and a profound reduction in the expression of HIV-1 mRNA and gp120. Both TNF-alpha antibody and hCG reduced TNF-alpha levels in sera by approximately 75%. We conclude that TNF-alpha contributes in a major way to HIV-1-induced pathology in transgenic mice and that both hCG and antibody to TNF-alpha prevent the development of pathology by suppressing the level of TNF-alpha. C1 NIDCR, Expt Med Sect, Oral Immun & Infect Branch, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), NIDCR, Expt Med Sect, Oral Immun & Infect Branch, NIH, Bldg 30,Room 121,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. NR 41 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11710 EP 11714 DI 10.1128/JVI.76.22.11710-11714.2002 PG 5 WC Virology SC Virology GA 608AF UT WOS:000178822400054 PM 12388730 ER PT J AU Feng, YX Li, T Campbell, S Rein, A AF Feng, YX Li, T Campbell, S Rein, A TI Reversible binding of recombinant human immunodeficiency virus type 1 Gag protein to nucleic acids in virus-like particle assembly in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; IN-VITRO; NUCLEOCAPSID PROTEIN; RNA; RETROVIRUS; PHENOTYPE; IMMATURE; DOMAIN; MUTANT AB Recombinant human immunodeficiency virus type I (HIV-1) Gag protein can assemble into virus-like particles (VLPs) in suitable buffer conditions with nucleic acid. We have explored the role of nucleic acid in this assembly process. HIV-1 nucleocapsid protein, a domain of Gag, can bind to oligodeoxynucleotides with the sequence d(TG)(n) with more salt resistance than to d(A)(n) oligonucleotides. We found that assembly of VLPs on d(TG)(n) oligonucleotides was more salt resistant than assembly on d(A)(n); thus, the oligonucleotides do not simply neutralize basic residues in Gag but provide a binding surface upon which Gag molecules assemble into VLPs. We also found that Gag molecules could be "trapped" on internal d(TG)(n) sequences within 40-base oligonucleotides, rendering them unable to take part in assembly. Thus, assembly on oligonucleotides requires that Gag proteins bind near the ends of the nucleic acid, and binding of Gag to internal d(TG)(n) sequences is apparently cooperative. Finally, we showed that nucleic acids in VLPs can exchange with nucleic acids in solution; there is a hierarchy of preferences in these exchange reactions. The results are consistent with an equilibrium model of in vitro assembly and may help to explain how Gag molecules in vivo select genomic RNA despite the presence in the cell of a vast excess of cellular mRNA molecules. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, POB B, Frederick, MD 21702 USA. NR 24 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11757 EP 11762 DI 10.1128/JVI.76.22.11757-11762.2002 PG 6 WC Virology SC Virology GA 608AF UT WOS:000178822400062 PM 12388738 ER PT J AU Arking, R Novoseltseva, J Hwangbo, DS Novoseltsev, V Lane, M AF Arking, R Novoseltseva, J Hwangbo, DS Novoseltsev, V Lane, M TI Different age-specific demographic profiles are generated in the same normal-lived Drosophila strain by different longevity stimuli SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID EXTENDED LIFE-SPAN; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; STRESS RESISTANCE; OXIDATIVE DAMAGE; PARAQUAT RESISTANCE; SURVIVAL-DATA; HEAT-SHOCK; SELECTION; MELANOGASTER AB We review the empirical data obtained with our normal-lived Ra control strain of Drosophila and show that this one genome is capable of invoking at least three different responses to external stimuli that induce the animal to express one of three different extended longevity phenotypes, each of which arises from one of three different antagonistic molecular mechanisms of stress resistance. The phenotypes are distinguished by different age-specific mortality patterns. Depending on the selected mechanism, the genome may respond by expressing a delayed onset of senescence (type 1), an increased early survival (type 2), or an increased late survival (type 3) phenotype, suggesting their different demographic effects. We suggest that the different demographic effects stem in part from the differential ability of each selection regime to reallocate the organism's energy from reproduction to somatic maintenance. These data document the complexity of the aging process and argue for a relationship between molecular mechanisms and longevity phenotypes. C1 Wayne State Univ, Coll Sci, Dept Biol Sci, Detroit, MI 48202 USA. Russian Acad Sci, Inst Control Sci, Moscow, Russia. NIA, Nutr & Mol Physiol Unit, NIH, Baltimore, MD 21224 USA. RP Arking, R (reprint author), Wayne State Univ, Coll Sci, Dept Biol Sci, Biol Sci Bldg, Detroit, MI 48202 USA. RI Novoseltseva, Janna/B-9482-2017 NR 68 TC 9 Z9 12 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2002 VL 57 IS 11 BP B390 EP B398 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 614PQ UT WOS:000179198900002 PM 12403794 ER PT J AU de Leon, CFM Guralnik, JM Bandeen-Roche, K AF de Leon, CFM Guralnik, JM Bandeen-Roche, K TI Short-term change in physical function and disability: The women's health and aging study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID LOWER-EXTREMITY FUNCTION; SOCIAL NETWORK CHARACTERISTICS; ACTIVITY RESTRICTION SCALE; PERFORMANCE-BASED MEASURES; LIVING OLDER PERSONS; SUBSEQUENT DISABILITY; DEPRESSIVE SYMPTOMS; DISABLEMENT PROCESS; ELDERLY PERSONS; SELF-REPORT AB Objectives. Although measures of physical function are predictive of future disability, little is known about the short-term impact of changes in physical function on disability. Methods. Data from 93 of the 102 women who participated in the Weekly Substudy of the Women's Health and Aging Study (WHAS) were used to explore the association of changes in physical function with disability. The WHAS Substudy included 24 weekly assessments of three standard performance tests and self-reported disability in activities of daily living (ADLs) and basic mobility. Results. Using random-effects models, we found small but significant (ps < .01) changes in ADL and mobility disability during weekly follow-up. Baseline performance scores were significantly associated with both ADL and mobility disability (ps < .001), accounting for 27% and 36% of the between-person variability in each type of disability, respectively. After adjustment for baseline scores, change in performance scores was significantly associated with ADL disability (beta = 0.08, p < .01) and mobility disability (P = 0. 12, p < .001), but accounted only for a small proportion (<10%) of the variability in the rate of change in disability outcomes. There was no evidence for an additional effect on either type of disability because of having a single episode of a higher or lower than usual performance score, or because of periods of at least 4 consecutive higher or lower than usual performance test scores. Discussion. Basic physical functions account for a substantial proportion of the heterogeneity in ADL and mobility disability among older disabled women, but have a relatively small impact on short-term changes in either type of disability. Effective prevention of disability may require attention to a wider array of risk factors than just limitations in basic physical functions. C1 Rush Presbyterian St Lukes Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP de Leon, CFM (reprint author), Rush Presbyterian St Lukes Med Ctr, Rush Inst Healthy Aging, 1645 W Jackson Blvd,Suite 675, Chicago, IL 60612 USA. NR 62 TC 23 Z9 23 U1 3 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2002 VL 57 IS 6 BP S355 EP S365 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 613BW UT WOS:000179112000017 ER PT J AU Leclerc, D Boutros, M Suh, D Wu, Q Palacin, M Ellis, JR Goodyer, P Rozen, R AF Leclerc, D Boutros, M Suh, D Wu, Q Palacin, M Ellis, JR Goodyer, P Rozen, R TI SLC7A9 mutations in all three cystinuria subtypes SO KIDNEY INTERNATIONAL LA English DT Article DE amino acid; transport; inherited disorder; genetics; kidney; stone; mutation; microcrystals ID AMINO-ACID-TRANSPORT; EXPRESSION CLONING; KIDNEY CDNA; RAT-KIDNEY; GENE; SEQUENCES; SLC3A1 AB Background. Cystinuria is an inherited disorder of cystine and dibasic amino acid transport in kidney. Subtypes are defined by the urinary cystine excretion patterns of the obligate heterozygous parents: Type I/N (fully recessive or silent); Type II/N (high excretor); Type III/N (moderate excretor). The first gene implicated in cystinuria (SLC3A1 ) is associated with the Type I urinary phenotype. A second cystinuria gene (SLC7A9 ) was recently isolated, and mutations of this gene were associated with dominant (non-Type I) cystinuria alleles. Here we report genotype-phenotype studies of SLC7A9 mutations in a cohort of well-characterized cystinuria probands and their family members. Methods. Individual exons of the SLC7A9 gene were screened by single strand conformation polymorphism (SSCP) analysis and sequencing of abnormally migrating fragments. Results. Seven mutations were identified. A single bp insertion (799insA) was present in four patients: on Type III alleles in two patients and on Type II alleles in two patients. These results suggest that Type II and Type III may be caused by the same mutation and, therefore, other factors must influence urinary cystine excretion. A 4bp deletion in intron 12 (IVS12+4delAGTA) and a missense mutation (1245G-->A, A354T) were identified on Type III alleles. A nonsense codon (1491G-->T, E436X) and a possible splicing mutation (IVS9-17G-->A) were seen in a Type I/III patient, but the mutations could not be assigned to particular alleles. Of additional interest were two missense mutations (316T-->C, I44T and 967C-->T, P261L) linked to Type I alleles. Conclusion. Our results provide evidence that some SLC7A9 mutations may be associated with fully recessive (Type I) forms of cystinuria. We also demonstrate SLC7A9 mutations in dominant Types II and III cystinuria. The finding of SLC7A9 mutations in all three subtypes underscores the complex interactions between specific cystinuria genes and other factors influencing cystine excretion. A simpler phenotypic classification scheme (recessive and dominant) for cystinuria is warranted. C1 McGill Univ, Montreal Childrens Hosp, Res Inst, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Montreal Childrens Hosp, Dept Pediat, Montreal, PQ H3Z 2Z3, Canada. Univ Barcelona, Dept Biochem, Barcelona, Spain. Univ Barcelona, Dept Mol Biol, Barcelona, Spain. NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD 20892 USA. RP Rozen, R (reprint author), McGill Univ, Montreal Childrens Hosp, Res Inst, Dept Human Genet, 4060 St Catherine St W,Rm 200, Montreal, PQ H3Z 2Z3, Canada. EM rima.rozen@mcgill.ca RI Leclerc, Daniel/B-6375-2012 NR 22 TC 31 Z9 32 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2002 VL 62 IS 5 BP 1550 EP 1559 DI 10.1046/j.1523-1755.2002.00602.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 602BC UT WOS:000178484000015 PM 12371955 ER PT J AU Muramatsu, Y Tsujie, M Kohda, Y Pham, B Perantoni, AO Zhao, H Jo, SK Yuen, PST Craig, L Hu, XZ Star, RA AF Muramatsu, Y Tsujie, M Kohda, Y Pham, B Perantoni, AO Zhao, H Jo, SK Yuen, PST Craig, L Hu, XZ Star, RA TI Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury SO KIDNEY INTERNATIONAL LA English DT Article DE ischemia; reperfusion; cyr61; biomarker; kidney injury ID IMMEDIATE-EARLY GENE; TISSUE GROWTH-FACTOR; HUMAN SKIN FIBROBLASTS; CELL-SURFACE; FAILURE; EXPRESSION; ADHESION; PRODUCT; MICE; FAMILY AB Background. Acute renal failure (ARF) has a high morbidity and mortality. Many therapies have worked in animals but were unsuccessful in clinical trials. The inability to diagnose ARF early may have impaired the success of these trials. Method. We screened a subtraction library to search for potential disease markers that would be induced rapidly after renal injury. Mice and rats were subjected to 30 to 40 minutes of bilateral ischemia. Results. mRNA for Cyr61 , a secreted growth factor-inducible immediate early gene, was markedly up-regulated at two hours in the kidney but not other organs following renal ischemia. In situ hybridization studies suggested Cyr61 was synthesized in the proximal straight tubule. Cyr61 protein was analyzed by capture with heparin beads followed by Western blotting. Induction of Cyr61 protein could be detected in the kidney within one hour, peaked at four to eight hours, and remained elevated for at least 24 hours following ischemia. Cyr61 protein was detected in urine at three to six hours and peaked at six to nine hours after renal injury. Cyr61 was not detected after volume depletion, which is often difficult to differentiate from ARF. Conclusions. The secreted, cysteine-rich, heparin binding protein Cyr61 is rapidly induced in proximal straight tubules following renal ischemia, and excreted in the urine where it might serve as an early biomarker of renal injury. C1 NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21701 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. RP Star, RA (reprint author), NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bldg 10,Room 3N108,10 Ctr Dr MSC 1268, Bethesda, MD 20892 USA. RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU NIDDK NIH HHS [DK-45923] NR 49 TC 92 Z9 108 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2002 VL 62 IS 5 BP 1601 EP 1610 DI 10.1046/j.1523-1755.2002.00633.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 602BC UT WOS:000178484000020 PM 12371960 ER PT J AU Trespalacios, FC Taylor, AJ Agodoa, LY Abbott, KC AF Trespalacios, FC Taylor, AJ Agodoa, LY Abbott, KC TI Incident acute coronary syndromes in chronic dialysis patients in the United States SO KIDNEY INTERNATIONAL LA English DT Article DE cholesterol; angiotensin-converting enzyme inhibitors; beta blockers; aspirin; HMG-CoA reductase inhibitors; calcium channel blockers; USRDS; age; phosphorous; calcium; parathyroid hormone; blood pressure ID CHRONIC-HEMODIALYSIS PATIENTS; RISK-FACTORS; MYOCARDIAL-INFARCTION; PARATHYROID-HORMONE; PLAQUE MORPHOLOGY; MORTALITY RISK; FOLLOW-UP; CALCIFICATION; ASSOCIATION; TRANSPLANT AB Background. Patients on dialysis have a disproportionately high rate of cardiovascular disease (CVD). However, the incidence and risk factors for incident acute coronary syndromes (ACS) have not been previously assessed in dialysis patients. Methods. We analyzed the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave II in a historical cohort study of ACS. Data from 3374 patients who started dialysis in 1996 with valid follow-up times were available for analysis, censored at the time of renal transplantation and followed until March 2000. Cox regression analysis was used to model factors associated with time to first hospitalization for ACS (ICD9 code 410.x or 411.x) adjusted for comorbidities, demographic factors, baseline laboratory values, blood pressures and cholesterol levels, type of vascular access, dialysis adequacy, and cardioprotective medications (angiotensin-converting enzyme inhibitors, calcium channel blockers, HMG-CoA reductase inhibitors (statins), beta blockers, and aspirin). Follow-up was 2.19 +/- 1.14 years. Results. The incidence of ACS was 29/1000 person-years. Factors associated with ACS were older age, the extreme high and low ranges of serum cholesterol level, history of coronary heart disease (CHD), male gender, and diabetes. No cardioprotective medications including statins had a significant association with ACS in this study. However, medications known to reduce mortality after ACS were used in less than 50% of patients with known CHD at the start of the study, and statins were used in less than 10% of patients with CHD. Conclusions. Dialysis patients had similar risk factors for ACS compared to the general population. Cardioprotective medications were not associated with a significant benefit, possibly due to their striking underutilization in this at-risk population. 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, Serv Cardiol, Washington, DC 20307 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 29 TC 67 Z9 68 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2002 VL 62 IS 5 BP 1799 EP 1805 DI 10.1046/j.1523-1755.2002.00638.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 602BC UT WOS:000178484000042 PM 12371982 ER PT J AU McGuffey, LH McCully, CL Bernacky, BJ Blaney, SM AF McGuffey, LH McCully, CL Bernacky, BJ Blaney, SM TI Incorporation of an enrichment program into a study protocol involving long-term restraint in macaques SO LAB ANIMAL LA English DT Article AB Nonhuman primates might experience stress during periods of restraint associated with research procedures. In an attempt to minimize such stress, the authors describe an enrichment program they designed for use with restrained adult male rhesus macaques. C1 Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. NCI, NIH, Dept Expt Therapeut, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX 78602 USA. RP McGuffey, LH (reprint author), 6621 Fannin MC3-3320, Houston, TX 77030 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2002 VL 31 IS 10 BP 37 EP 39 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 629DX UT WOS:000180036100007 PM 12404014 ER PT J AU Weickert, TW Terrazas, A Bigelow, LB Malley, JD Hyde, T Egan, MF Weinberger, DR Goldberg, TE AF Weickert, TW Terrazas, A Bigelow, LB Malley, JD Hyde, T Egan, MF Weinberger, DR Goldberg, TE TI Habit and skill learning in schizophrenia: Evidence of normal striatal processing with abnormal cortical input SO LEARNING & MEMORY LA English DT Article ID EMISSION COMPUTERIZED-TOMOGRAPHY; CAUDATE-NUCLEUS LESIONS; MULTIPLE MEMORY-SYSTEMS; TEMPORAL-LOBE LESIONS; DOUBLE DISSOCIATION; TARDIVE-DYSKINESIA; COGNITIVE SKILL; WORKING-MEMORY; BASAL GANGLIA; HUMAN-BRAIN AB Different forms of nondeclarative learning involve regionally specific striatal circuits. The motor circuit (involving the putamen) has been associated with motor-skill learning and the dorsolateral prefrontal cortex (DLPFC) circuit (involving the caudate) has been associated with cognitive-habit learning. Efforts to differentiate functional striatal circuits within patient samples have been limited. Previous studies have provided mixed results regarding striatal-dependent nondeclarative learning deficits in patients with schizophrenia. In this study, a cognitive-habit learning task (probabilistic weather prediction) was used to assess the DLPFC circuit and a motor-skill learning task (pursuit rotor) was used to assess the motor circuit in 35 patients with schizophrenia and 35 normal controls. Patients with schizophrenia displayed significant performance differences from controls on both nondeclarative tasks; however, cognitive-habit learning rate in patients did not differ from controls. There were performance and learning-rate differences on the motor-skill learning task between the whole sample of patients and controls, however, analysis of a subset of patients and controls matched on general intellectual level eliminated learning rate differences between groups. The abnormal performance offset between patients with schizophrenia and controls in the absence of learning rate differences suggests that abnormal cortical processing provides altered input to normal striatal circuitry. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Weickert, TW (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 85 TC 74 Z9 76 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD NOV-DEC PY 2002 VL 9 IS 6 BP 430 EP 442 DI 10.1101/lm.49102 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 621PL UT WOS:000179598400010 PM 12464703 ER PT J AU Kuramoto, K Ban, S Oda, K Tanaka, H Kimura, A Suzuki, G AF Kuramoto, K Ban, S Oda, K Tanaka, H Kimura, A Suzuki, G TI Chromosomal instability and radiosensitivity in myelodysplastic syndrome cells SO LEUKEMIA LA English DT Article DE myelodysplastic syndrome; chromosomal instability; radiosensitivity ID FRAGMENT-LENGTH-POLYMORPHISMS; POLYMERASE CHAIN-REACTION; ATOMIC-BOMB SURVIVORS; MYELOPROLIFERATIVE DISORDERS; GENETIC INSTABILITY; MICRONUCLEUS METHOD; IONIZING-RADIATION; DNA-DAMAGE; LYMPHOCYTES; PATHOGENESIS AB Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells. To investigate whether chromosomal instability and/or DNA repair defects are involved in the development of MDS, we measured the micronucleus (MN) frequency in peripheral blood lymphocytes exposed to various doses of X-rays, using a cytokinesis-block micronucleus assay. The spontaneous MN frequencies in RAEB and RAEB-T patients were significantly higher than those in normal individuals (P = 0.0224, P = 0.008, respectively). Also, the X-ray-induced MN frequencies in RA/RARS, RAEB, and RAEB-T patients were significantly higher than those in normal individuals (P = 0.007, P = 0.003, P = 0.003, respectively, at 2 Gy). In order to elucidate the cause of unusual radiosensitivity, we measured the expression levels of nucleotide excision repair (NER) genes in peripheral blood mononuclear cells using a RTPCR method. Reduction of NER gene expression was found in only one of 10 patients with low risk MDS, but in four of 11 patients with high risk MDS. Our data suggest that chromosomal instability and DNA repair defects may be involved in the pathophysiology of disease progression of MDS. C1 Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Hematol & Oncol, Hiroshima, Japan. Hiroshima City Hosp, Dept Internal Med, Hiroshima, Japan. Natl Inst Radiol Sci, Frontier Res Ctr, Chiba 260, Japan. Radiat Effects Res Fdn, Dept Clin Studies, Hiroshima, Japan. RP Kuramoto, K (reprint author), NIH, Bldg 10-7C,210,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 18 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2002 VL 16 IS 11 BP 2253 EP 2258 DI 10.1038/sj.leu.2402703 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 614MF UT WOS:000179193400012 PM 12399970 ER PT J AU Geissler, E Hecht, AM Rochas, C Horkay, F Bley, F Livet, F AF Geissler, E Hecht, AM Rochas, C Horkay, F Bley, F Livet, F TI Structure and dynamics of silica-filled polymers by SANS and coherent SAXS SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 20th Conference on Scattering Methods for the Investigation of Polymers CY JUL 09-12, 2001 CL PRAGUE, CZECH REPUBLIC ID LIGHT-SCATTERING; ANGLE AB Random crosslinking in elastomers gives birth to local variations in the crosslink density. When the network is swollen in a low-molecular-weight solvent, competition between the osmotic pressure and the local elastic constraints transforms these variations into differences in polymer concentration, the range and amplitude of which can be measured by small-angle X-ray or neutron scattering (SAXS or SANS). In filled systems, the distribution both of the polymer and of the elastic constraints is modified. By varying the proportion of deuterated solvent in the network, the scattering function of the polymer can be distinguished from that of the filler using SANS. Such measurements yield not only the internal surface area of the filler particles but also the fraction of that surface in contact with the polymer. The recently developed technique of quasi-elastic SAXS detects slow dynamic processes at wave vectors larger than those accessible with visible light lasers. This technique is used to investigate the dynamics of filler particles in uncrosslinked polymer melts. It is directly shown that the structural reorganization process of the filler following an external mechanical perturbation is diffusion-controlled. C1 Univ Grenoble 1, Spectrometrie Phys Lab, CNRS, UMR 5588, F-38402 St Martin Dheres, France. NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Inst Natl Polytech Grenoble, CNRS, UMR 4777, Thermodynam & Physicochim Met Lab, F-38402 St Martin Dheres, France. RP Geissler, E (reprint author), Univ Grenoble 1, Spectrometrie Phys Lab, CNRS, UMR 5588, BP87, F-38402 St Martin Dheres, France. NR 13 TC 0 Z9 0 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD NOV PY 2002 VL 190 BP 23 EP 32 DI 10.1002/masy.200290016 PG 10 WC Polymer Science SC Polymer Science GA 642EQ UT WOS:000180791600004 ER PT J AU Leach, RE Duniec-Dmuchowski, ZM Pesole, G Tanaka, TS Ko, MSH Armant, DR Krawetz, SA AF Leach, RE Duniec-Dmuchowski, ZM Pesole, G Tanaka, TS Ko, MSH Armant, DR Krawetz, SA TI Identification, molecular characterization, and tissue expression of OVCOV1 SO MAMMALIAN GENOME LA English DT Article ID HUMAN CYTOTROPHOBLAST DIFFERENTIATION; ENDOVASCULAR INVASION; MOUSE; PREECLAMPSIA; PREGNANCY; PATTERNS; GENE; TRANSCRIPTS; PLACENTA; DISPLAY AB Key to the maternal-embryonic dialogue during early implantation are the extra embryonic trophoblast cells that play several critical roles including invasion of the maternal decidua. Cytotrophoblast proliferation and differentiation along an invasive pathway is regulated by a positive gradient of oxygen tension. We have employed transcript profiling to characterize the extra-embryonic tissues during early human implantation. We probed a cDNA library isolated from the ectoplacental cone region of stage 7.5 days post coitus mouse embryos with cDNA from hypoxic cultured human trophoblast cells. This identified the pattern of expression of a series of previously unknown genes that correlate to day 20 of human embryonic development. One EST was selected for further analysis since it is identical to the 1588-bp CGI-15 sequence assembled in silico. The human gene is organized into 10 exons 2063 bp in length. The open reading frame contains 1272 bp predicting protein composed of 365 amino acids. This gene is expressed in many tissues including those found in the reproductive tract. Its expression is regulated by oxygen tension and is unaffected by estradiol or progesterone treatment. C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Sch Med, Inst Comp Sci, Detroit, MI USA. NIA, Gerontol Res Ctr, Genet Lab, Baltimore, MD 21224 USA. Dipartimento Fisiol Biochim Gen, Milan, Italy. RP Leach, RE (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RI Ko, Minoru/B-7969-2009; Pesole, Graziano/C-1408-2009; Pesole, Graziano/E-9051-2014; OI Ko, Minoru/0000-0002-3530-3015; Pesole, Graziano/0000-0003-3663-0859; Pesole, Graziano/0000-0003-3663-0859; Armant, D. Randall/0000-0001-5904-9325 FU NICHD NIH HHS [HD 36512, HD 98004] NR 21 TC 4 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 2002 VL 13 IS 11 BP 619 EP 624 DI 10.1007/s00335-002-2185-4 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 621XL UT WOS:000179616200003 PM 12461647 ER PT J AU Soules, MR Parrott, E Rebar, R Santoro, N Sherman, S Utian, W Woods, NF AF Soules, MR Parrott, E Rebar, R Santoro, N Sherman, S Utian, W Woods, NF TI Untitled - Reply SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Letter C1 Univ Washington, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Seattle, WA 98195 USA. NICHHD, Reprod Med Gynecol Program, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Soules, MR (reprint author), Univ Washington, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Seattle, WA 98195 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2002 VL 9 IS 6 BP 464 EP 465 DI 10.1097/00042192-200211000-00014 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 614JN UT WOS:000179185100014 ER PT J AU Mintz, KP Moskovitz, J Wu, H Fives-Taylor, PM AF Mintz, KP Moskovitz, J Wu, H Fives-Taylor, PM TI Peptide methionine sulfoxide reductase (MsrA) is not a major virulence determinant for the oral pathogen Actinobacillus actinomycetemcomitans SO MICROBIOLOGY-SGM LA English DT Article DE adhesion; oxidative stress; periodontal disease ID ESCHERICHIA-COLI; OXIDATIVE STRESS; NEISSERIA-GONORRHOEAE; HELICOBACTER-PYLORI; ANTIOXIDANT DEFENSE; PERIODONTAL-DISEASE; SHUTTLE PLASMIDS; EXPRESSION; PROTEINS; GENE AB Actinobacillus actinomycetemcomitans is an oral pathogen that is a causative agent for periodontal disease as well as other non-oral infections. The chronic inflammation associated with periodontal diseases suggests that the bacterium must be able to neutralize oxygen intermediates to survive in the host tissues. Methionine sulfoxide reductase (MsrA) is an enzyme that has been demonstrated to have a role in protection against oxidative damage and has also been identified to be required for the proper expression or maintenance of functional adhesins on the surface of several pathogenic bacteria. The A. actinomycetemcomitans homologue of msrA has been isolated and a chromosomal insertion mutant constructed by allele replacement mutagenesis. Inactivation of the gene led to a complete loss of enzymic activity toward a synthetic substrate. However, the isogenic mutant was not more sensitive to oxidative stress or less adherent to epithelial cells as compared with the parent strain. These data suggest that this strain of A. actinomycetemcomitans has redundant systems that compensate for the MsrA activities ascribed for other organisms. C1 Univ Vermont, Dept Microbiol & Mol Genet, Burlington, VT 05405 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Mintz, KP (reprint author), Univ Vermont, Dept Microbiol & Mol Genet, Burlington, VT 05405 USA. FU NIDCR NIH HHS [DE09760, R01-DE13824] NR 54 TC 12 Z9 13 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD NOV PY 2002 VL 148 BP 3695 EP 3703 PN 11 PG 9 WC Microbiology SC Microbiology GA 617LN UT WOS:000179363300041 PM 12427959 ER PT J AU Ravi, V Ramachandran, S Thompson, RW Andersen, JF Neva, FA AF Ravi, V Ramachandran, S Thompson, RW Andersen, JF Neva, FA TI Characterization of a recombinant immunodiagnostic antigen (NIE) from Strongyloides stercoralis L3-stage larvae SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE antibodies; basophils; histamine; immunodiagnosis; Strongyloides stercoralis ID LINKED IMMUNOSORBENT-ASSAY; CDNA CLONES; IDENTIFICATION; INFECTIONS; SEQUENCE; PROTEINS; ELISA AB Due to the process of internal autoinfection, even chronic asymptomatic infections with Strongyloides stercoralis have the potential to become severe disseminated disease with fatal outcome. Intermittent and scanty larval excretion makes parasitologic diagnosis difficult. Serodiagnosis is helpful, but antigen preparation from infective larvae requires access to patients or immunosuppressed experimental animals. For these reasons, attention has turned to recombinant antigens for immunodiagnosis. A 31-kDa candidate antigen (NIE) derived from an L3 cDNA library is described in this report. Multiple alignment of the deduced amino acid sequence of NIE showed approximately 12-18% identity with various other organisms, including 17.9% of Asp1 of Ancylostoma caninum, 12.6% of Hemonchus contortus, and 17.6% of insect venom allergen 5 of yellow jacket. By ELISA, antibodies to the purified recombinant NIE antigen were demonstrated in 87.5% of 48 sera from strongyloides-infected patients and in only 6.5% of sera from presumed normal controls. Immunoreactivity of purified NIE antigen with parasite-specific IgE from sera of strongyloides-infected patients indicated its potential use as an immediate sensitivity skin test antigen. This application of the NIE antigen was supported by its capacity to trigger release of histamine upon in vitro exposure to blood from strongyloides-infected patients and its failure to produce histamine release from blood of normal controls. (C) 2002 Published by Elsevier Science B.V. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Neva, FA (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 126, Bethesda, MD 20892 USA. OI Varatharajalu, Ravi/0000-0001-6773-1922 NR 24 TC 34 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV-DEC PY 2002 VL 125 IS 1-2 BP 73 EP 81 AR PII S0166-6851(02)00214-1 DI 10.1016/S0166-6851(02)00214-1 PG 9 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 626FR UT WOS:000179862000007 PM 12467975 ER PT J AU Takala, S Branch, O Escalante, AA Kariuki, S Wootton, J Lal, AA AF Takala, S Branch, O Escalante, AA Kariuki, S Wootton, J Lal, AA TI Evidence for intragenic recombination in Plasmodium falciparum: identification of a novel allele family in block 2 of merozoite surface protein-1: Asembo Bay Area Cohort Project XIV SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE merozoite protein; genetic diversity; vaccine; recombination; Plasmodium; allele family ID MEMBRANE ANTIGEN-1 AMA-1; HUMAN MALARIA PARASITE; NATURAL-SELECTION; ENZYMATIC AMPLIFICATION; LINKAGE DISEQUILIBRIUM; SEQUENCE DIVERSITY; DNA-POLYMERASE; GENE; MSP-1; PCR AB We have investigated intragenic recombination in Block 2 of the merozoite surface protein-1 (MSP-1), where three allele-specific families: K1, Mad20, and 8033 were previously known. Using parasites from western Kenya, we have found a fourth Block 2 allele type, which is a recombinant between Mad20 and 8033 alleles. These recombinant alleles, which we have termed MR, contain sequence from the 5' region of Mad20 and the 3' region of RO33. The results of this study provide new data on the complexity of the MSP-1 antigen gene, which is a candidate vaccine antigen, and further support the importance of intragenic recombination in generating genetic variability in Plasmodium falciparum parasites in nature. (C) 2002 Elsevier Science B.V. All tights reserved. C1 Ctr Dis Control & Prevent, Mol Vaccine Sect, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. NIH, Natl Ctr CBI, Bethesda, MD USA. Inst Venezolano Invest Cient, Caracas, Venezuela. Kenya Govt Med Res Ctr, Ctr Vector Biol & Control Res, Kisumu, Kenya. RP Lal, AA (reprint author), Ctr Dis Control & Prevent, Mol Vaccine Sect, Div Parasit Dis, Natl Ctr Infect Dis, Mail Stop F12,4770 Buford Hwy, Atlanta, GA 30341 USA. FU NIGMS NIH HHS [R01 GM60740, R01 GM060740] NR 35 TC 22 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV-DEC PY 2002 VL 125 IS 1-2 BP 163 EP 171 AR PII S0166-6851(02)00237-2 DI 10.1016/S0166-6851(02)00237-2 PG 9 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 626FR UT WOS:000179862000015 PM 12467983 ER PT J AU Greenblatt, CL Schnur, LF Bar-Gal, GK Ermolaev, H Peleg, N Barrett, MP AF Greenblatt, CL Schnur, LF Bar-Gal, GK Ermolaev, H Peleg, N Barrett, MP TI Polymorphism among alleles of the 6-Phosphogluconate dehydrogenase gene from Leishmania major and Leishmania tropica SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE 6-phosphogluconate dehydrogenase; Leishmania major; L. tropica; electrophoretic variants; zymodemes; cyanobacterial lineage ID PENTOSE-PHOSPHATE PATHWAY; TRYPANOSOMA-BRUCEI; OLD-WORLD; ISOENZYMES; COENZYME; PARASITE C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Parasitol, Kuvin Ctr Study Infect & Trop Dis, IL-91120 Jerusalem, Israel. NCI, Lab Genom Divers, NIH, Frederick, MD 21702 USA. Univ Glasgow, Inst Biomed & Life Sci, Div Infect & Immun, Glasgow, Lanark, Scotland. RP Greenblatt, CL (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Parasitol, Kuvin Ctr Study Infect & Trop Dis, IL-91120 Jerusalem, Israel. NR 17 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV-DEC PY 2002 VL 125 IS 1-2 BP 185 EP 188 AR PII S0166-6851(02)00213-X DI 10.1016/S0166-6851(02)00213-X PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 626FR UT WOS:000179862000017 PM 12467985 ER PT J AU Hirt, RP Harriman, N Kajava, AV Embley, TM AF Hirt, RP Harriman, N Kajava, AV Embley, TM TI A novel potential surface protein in Trichomonas vaginalis contains a leucine-rich repeat shared by micro-organisms from all three domains of life SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Trichomonas vaginalis; parasitic protozoa; BspA-like protein; leucine-rich repeats; surface proteins; horizontal gene transfer; evolution; molecular modelling ID COMPLETE GENOME SEQUENCE; MOLECULAR CHARACTERIZATION; STREPTOCOCCUS-PNEUMONIAE; MECHANISMS; MOTIF; CYTOADHERENCE; LOCALIZATION; PATHOGENESIS; FIBRONECTIN; EVOLUTION C1 Nat Hist Museum, Dept Zool, London SW7 5BD, England. NIH, Ctr Mol Modelling, CIT, Bethesda, MD 20892 USA. RP Embley, TM (reprint author), Nat Hist Museum, Dept Zool, Cromwell Rd, London SW7 5BD, England. RI Kajava, Andrey/E-1107-2014; OI Kajava, Andrey/0000-0002-2342-6886; Embley, Thomas Martin/0000-0002-1484-340X FU NIAID NIH HHS [1-R01-AI46516-01A1] NR 35 TC 20 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV-DEC PY 2002 VL 125 IS 1-2 BP 195 EP 199 AR PII S0166-6851(02)00211-6 DI 10.1016/S0166-6851(02)00211-6 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 626FR UT WOS:000179862000019 PM 12467987 ER PT J AU Kuwata, T Gongora, C Kanno, Y Sakaguchi, K Tamura, T Kanno, T Basrur, V Martinez, R Appella, E Golub, T Ozato, K AF Kuwata, T Gongora, C Kanno, Y Sakaguchi, K Tamura, T Kanno, T Basrur, V Martinez, R Appella, E Golub, T Ozato, K TI Gamma interferon triggers interaction between ICSBP (IRF-8) and TEL, recruiting the histone deacetylase HDAC3 to the interferon-responsive element SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; TRANSCRIPTION FACTOR PU.1; REGULATORY FACTORS; IN-VIVO; GENE; EXPRESSION; MACROPHAGES; COMPLEX; FAMILY; DNA AB ICSBP (IRF-8) is a transcription factor of the IRF family expressed only in the immune system. It is induced in macrophages by gamma interferon (IFN-gamma) and contributes to macrophage functions. By interacting with Ets family protein PU.1, ICSBP binds to the IRF/Ets composite element and stimulates transcription. ICSBP binds to another DNA element, the IFN-stimulated response element (ISRE), a common target of the IRF family. Limited knowledge as to how ICSBP and other IRF proteins regulate ISRE-dependent transcription in WN-y-activated macrophages is available. By mass-spectrometric analysis of ISRE-bound proteins in macrophages, we identified TEL, another Ets member, as a factor recruited to the element in an IFN-y-dependent manner. In vitro analysis with recombinant proteins indicated that this recruitment is due to a direct interaction between ICSBP and TEL, which is enhanced by the presence of ISRE. Significantly, the interaction with TEL in turn resulted in the recruitment of the histone deacetytase HDAC3 to the ISRE, causing increased repression of IFN-y-mediated reporter activity through the ISRE. This repression may provide a negative-feedback mechanism operating after the initial transcriptional activation by IFN-y. By associating with two different Ets family proteins, ICSBP exerts a dual function in IFN-y-dependent gene regulation in an immune system-specific manner. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 2A01,6 Ctr Dr,MSC-2753, Bethesda, MD 20892 USA. RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 61 TC 37 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2002 VL 22 IS 21 BP 7439 EP 7448 DI 10.1128/MCB.22.21.7439-7448.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 603XQ UT WOS:000178586900008 PM 12370291 ER PT J AU Zhang, ZB Sapiro, R Kapfhamer, D Bucan, M Bray, J Chennathukuzhi, V McNamara, P Curtis, A Zhang, M Blanchette-Mackie, EJ Strauss, JF AF Zhang, ZB Sapiro, R Kapfhamer, D Bucan, M Bray, J Chennathukuzhi, V McNamara, P Curtis, A Zhang, M Blanchette-Mackie, EJ Strauss, JF TI A sperm-associated WD repeat protein orthologous to Chlamydomonas PF20 associates with Spag6, the mammalian orthologue of Chlamydomonas PF16 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID OUTER-ARM DYNEIN; INNER-ARM; INTERMEDIATE CHAIN; BINDING PROTEIN; 22S DYNEIN; FLAGELLA; MUTANTS; REINHARDTII; MICROTUBULES; TRANSLIN AB cDNAs were cloned for the murine and human orthologues of Chlamydomonas PF20, a component of the alga axoneme central apparatus that is required for flagellar motility. The mammalian genes encode transcripts of 1.4 and 2.5 kb that are highly expressed in testis. The two transcripts appear to arise from alternative transcription start sites. The murine Pf20 gene was mapped to chromosome 1, syntenic with the location of the human gene on chromosome 2. An antibody generated against an N-terminal sequence of mouse Pf20 recognized a 71-kDa protein in sperm and testis extracts. Immunocytochemistry localized Pf20 to the tails of permeabilized sperm; electron microscope immunocytochemistry showed that Pf20 was located in the axoneme central apparatus. A murine Pf20-green fluorescent protein fusion protein expressed in Chinese hamster ovary cells accumulated in the cytoplasm. When coexpressed with Spag6, the mammalian orthologue of Chlamydomonas PF16, Pf2O was colocalized with Spag6 on polymerized microtubules. Yeast two-hybrid assays demonstrated interaction of the Pf20 WD repeats with Spag6. Pf20 was markedly reduced in sperm collected from mice lacking Spag6, which are infertile due to a motility defect. Our observations provide the first evidence for an association between mammalian orthologues of two Chlamydomonas proteins known to be critical for axoneme structure and function. C1 Univ Penn, Ctr Med, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. NIDDKD, NIH, Lipid Cell Biol Sect, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. RP Strauss, JF (reprint author), Univ Penn, Ctr Med, Ctr Res Reprod & Womens Hlth, 1354 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. FU FIC NIH HHS [D43-TW/HD00671]; NICHD NIH HHS [R01 HD037416, R01-HD37416-02, T32 HD007305, T32-HD07305]; NIDDK NIH HHS [DK19525, P30 DK019525] NR 38 TC 48 Z9 57 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2002 VL 22 IS 22 BP 7993 EP 8004 DI 10.1128/MCB.22.22.7993-8004.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 610HB UT WOS:000178953700024 PM 12391165 ER PT J AU Arudchandran, A Cerritelli, SM Bowen, NJ Chen, XF Krause, MW Crouch, RJ AF Arudchandran, A Cerritelli, SM Bowen, NJ Chen, XF Krause, MW Crouch, RJ TI Multiple ribonuclease H-encoding genes in the Caenorhabditis elegans genome contrasts with the two typical ribonuclease H-encoding genes in the human genome SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE ribonuclease H; splicing; multiple genes; Caenorhabditis elegans; human; genome; double-stranded RNA; RNA-DNA hybrids ID PROKARYOTIC RNASE HII; SACCHAROMYCES-CEREVISIAE; C-ELEGANS; BACILLUS-SUBTILIS; LEADER SEQUENCE; MESSENGER-RNA; ELEMENTS; IDENTIFICATION; RETROVIRUSES; DELETIONS AB Database searches of the Caenorhabditis elegans and human genomic DNA sequences revealed genes encoding ribonuclease HI (RNase HI) and RNase H2 in each genome. The human genome contains a single copy of each gene, whereas C. elegans has four genes encoding RNase HI-related proteins and one gene for RNase H2. By analyzing the mRNAs produced from the C. elegans genes, examining the amino acid sequence of the predicted protein, and expressing the proteins in Esherichia coli we have identified two active RNase H1-like proteins. One is similar to other eukaryotic RNases H1, whereas the second RNase H (rnh-1.1) is unique. The rnh-1.0 gene is transcribed as a dicistronic message with three dsRNA-binding domains; the mature mRNA is transspliced with SL2 splice leader and contains only one dsRNA-binding domain. Formation of RNase HI is further regulated by differential cis-splicing events. A single rnh-2 gene, encoding a protein similar to several other eukaryotic RNase H2L's, also has been examined. The diversity and enzymatic properties of RNase H homologues are other examples of expansion of protein families in C. elegans. The presence of two RNases HI in C. elegans suggests that two enzymes are required in this rather simple organism to perform the functions that are accomplished by a single enzyme in more complex organisms. Phylogenetic analysis indicates that the active C. elegans RNases HI are distantly related to one another and that the C. elegans RNase HI is more closely related to the human RNase HI. The database searches also suggest that RNase H domains of LTR-retrotransposons in C. elegans are quite unrelated to cellular RNases HI, but numerous RNase H domains of human endogenous retroviruses are more closely related to cellular RNases H. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Biol Computat, NIH, Bethesda, MD 20892 USA. NICHHD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP NICHHD, Genet Mol Lab, NIH, Bldg 6B,Room 2B-231,6 Ctr Dr MSC 2790, Bethesda, MD 20892 USA. EM robert_crouch@nih.gov RI Bowen, Nathan/F-3132-2010; OI Bowen, Nathan/0000-0002-1609-6698; Krause, Michael/0000-0001-6127-3940 NR 41 TC 6 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD NOV PY 2002 VL 19 IS 11 BP 1910 EP 1919 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 617NF UT WOS:000179367200009 PM 12411600 ER PT J AU Engbring, JA AF Engbring, JA TI A metastasis-promoting site on laminin-1 binds a heparan sulfate/chondroitin sulfate-containing proteoglycan on B16-F10 melanoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 21 BP 5A EP 5A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100022 ER PT J AU Lum, L Yao, S Von Kessler, D Mozer, B Beachy, P AF Lum, L Yao, S Von Kessler, D Mozer, B Beachy, P TI Identification of novel Hh and Wg pathway components using a high-throughput RNAi approach in Drosophila cell culture SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NIH, Lab Biochem Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 25 BP 5A EP 6A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100026 ER PT J AU Ling, SM Kasper, CE Taub, D Galban, C Spencer, R Abernethy, D AF Ling, SM Kasper, CE Taub, D Galban, C Spencer, R Abernethy, D TI Serum levels are poor predictors of muscle levels of interleukin (IL)-6 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIA, Intramural Res Program, Clin Invest Lab, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Immunol Lab, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Clin Invest Lab, NMR Unit, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 134 BP 25A EP 25A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100134 ER PT J AU Cho, H Kamijo, K Miki, T Kehrl, JH AF Cho, H Kamijo, K Miki, T Kehrl, JH TI RGS14, a nuclear-cytoplasmic shuttling protein localizes to centrosomes in a cell cycle-dependent manner to regulate cell cycle progression SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, NIH, Immunoregulat Lab, B Cell Mol Immunol Sect, Bethesda, MD 20892 USA. NCI, NIH, Basic Res Lab, Mol Tumor Biol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 160 BP 29A EP 29A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100160 ER PT J AU Kamijo, K Saito, S Kapoor, V Lee, J Miki, T AF Kamijo, K Saito, S Kapoor, V Lee, J Miki, T TI The Rho exchange factor ECT2 regulates the terminal phase of cytokinesis through the BRCT-repeat SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Mol Tumor Biol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 163 BP 29A EP 30A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100163 ER PT J AU Carroll, S Herrera, AH Horowits, R AF Carroll, S Herrera, AH Horowits, R TI N-RAP super repeats organize actin filaments during myofibril assembly in cultured chick cardiomyocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 192 BP 35A EP 35A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100192 ER PT J AU Rzadzinska, AK Schneider, MI Belyantseva, I Kachar, B AF Rzadzinska, AK Schneider, MI Belyantseva, I Kachar, B TI Rapid renewal of auditory sensory stereocilia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 206 BP 37A EP 37A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100206 ER PT J AU Gilk, SD Raviv, Y Devore, N Beckers, C Ward, GE AF Gilk, SD Raviv, Y Devore, N Beckers, C Ward, GE TI Photosensitized labeling with I-125-5-iodonapthalene-1-azide (I-125-INA) identification of the protein anchoring the toxoplasma gondii MyosinA motor to the plasma membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Vermont, Burlington, VT 05405 USA. NCI, SAIC, Lab Computat & Expt Biol, Intramural Res Support Program, Frederick, MD 21701 USA. Univ Alabama, Div Geog Med, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 219 BP 39A EP 39A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100219 ER PT J AU O'Connell, KF Kopish, KR Caron, C Kemphues, KJ White, JG AF O'Connell, KF Kopish, KR Caron, C Kemphues, KJ White, JG TI Analysis of the C-elegans ZYG-1 kinase, a mitotic and meiotic regulator of centrosome duplication SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, NIH, Lab Biochem & Genet, Bethesda, MD USA. Univ Wisconsin, Mol Biol Lab, Madison, WI 53706 USA. Cornell Univ, Genet & Dev Sect, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 274 BP 49A EP 49A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100274 ER PT J AU Dougherty, GW Adler, HJ Merritt, RC Rzadzinska, A de Azevedo, R Frolenkov, GI Belyantseva, IA Pompeia, C Kachar, B AF Dougherty, GW Adler, HJ Merritt, RC Rzadzinska, A de Azevedo, R Frolenkov, GI Belyantseva, IA Pompeia, C Kachar, B TI Couplin, a novel 27 kDa protein, links prestin to the actin-spectrin cytoskeleton in sensory hair cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 308 BP 55A EP 55A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100308 ER PT J AU Herrmann, H Wedig, T Aebi, U Parry, DA Marekov, LN Steinert, PM AF Herrmann, H Wedig, T Aebi, U Parry, DA Marekov, LN Steinert, PM TI Evidence that the head and rod domain segments of vimentin interact SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 German Canc Res Ctr, Div Cell Biol, D-6900 Heidelberg, Germany. Univ Basel, Maurice Muller Inst, CH-4003 Basel, Switzerland. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NIAMS, NIH, Skin Biol Lab, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 341 BP 61A EP 61A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100341 ER PT J AU Paik, J Chae, S Cowan, AE Proia, RL Hla, T AF Paik, J Chae, S Cowan, AE Proia, RL Hla, T TI Role of g protein-coupled receptor induced cell-cell junctions in vascular maturation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Ctr Biomed Imaging Technol, Farmington, CT USA. NIDDK, NIH, Genet Dis & Dev Branch, Bethesda, MD USA. RI Proia, Richard/A-7908-2012; Hla, Timothy/G-5873-2012 OI Hla, Timothy/0000-0001-8355-4065 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 418 BP 75A EP 75A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100418 ER PT J AU Hu, J Reyes-Cruz, G Spiegel, AM AF Hu, J Reyes-Cruz, G Spiegel, AM TI Identification of acidic residues in the extracellular loops of the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+ and a positive allosteric modulator SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCD, NIH, Mol Pathophysiol Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 441 BP 79A EP 79A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100441 ER PT J AU Szuchet, S de Velasco, JM Ericson, VR Hudson, LD AF Szuchet, S de Velasco, JM Ericson, VR Hudson, LD TI OTMP: the gene, its encoded protein and the mouse ortholog SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NINDS, NIH, Lab Dev Neurogenet, Bethesda, MD 20892 USA. Univ Chicago, Brain Res Inst, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 455 BP 81A EP 81A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100455 ER PT J AU Hailey, DW Wakabayashi, Y Arias, IM Lippincott-Schwartz, J AF Hailey, DW Wakabayashi, Y Arias, IM Lippincott-Schwartz, J TI Expression of hepatocellular bile acid transporters NTCP and SPGP/BSEP/ABCA11 in five non-polarized MDCK cells: implications for bile canalicular biogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, Cell Biol & Metab Branch, Bethesda, MD USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 497 BP 88A EP 88A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100497 ER PT J AU Palmieri, D Suchar, A Henkel, V Wulfkuhle, JD Petricoin, EF Steeg, PS AF Palmieri, D Suchar, A Henkel, V Wulfkuhle, JD Petricoin, EF Steeg, PS TI Altered expression of lipid and vesicle trafficking proteins in human breast ductal carcinoma in situ SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Pathol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. NCI, Pathol Lab, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, US FDA, CBER, Clin Proteom Program, Bethesda, MD 20892 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 509 BP 91A EP 91A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100509 ER PT J AU Weigert, R Backer, JM Donaldson, JG AF Weigert, R Backer, JM Donaldson, JG TI In vitro characterization of heterotypic fusion between non-clathrin and clathrin-derived endosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 517 BP 92A EP 92A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100517 ER PT J AU Stoddart, A Dykstra, ML Brown, BK Song, W Pierce, SK Brodsky, FM AF Stoddart, A Dykstra, ML Brown, BK Song, W Pierce, SK Brodsky, FM TI Lipid rafts unite signaling cascades with clathrin to regulate B cell antigen receptor internalization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Calif San Francisco, George Williams Hooper Fdn, San Francisco, CA 94143 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Univ Maryland, Dept Cell & Mol Genet, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 524 BP 93A EP 93A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100524 ER PT J AU Yim, Y Zhang, F Greene, L Eisenberg, E AF Yim, Y Zhang, F Greene, L Eisenberg, E TI Hsc70 and auxilin uncoat clathrin from clatrhin coated pits in permeabilized tissue culture cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 520 BP 93A EP 93A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100520 ER PT J AU Dhanvantari, S Shen, F Adams, T Snell, CR Zhang, C Mackin, RB Loh, YP AF Dhanvantari, S Shen, F Adams, T Snell, CR Zhang, C Mackin, RB Loh, YP TI Carboxypeptidase E mediates the sorting of proinsulin to the regulated secretory pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, NIH, Bethesda, MD USA. Medivir UK Ltd, Cambridge, England. Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. RI Dhanvantari, Savita/B-5362-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 541 BP 96A EP 97A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100541 ER PT J AU Rodriguez, YM Cawley, NX Zhang, C Loh, YP AF Rodriguez, YM Cawley, NX Zhang, C Loh, YP TI Residues Arg255 and Lys260 in the prohormone sorting receptor, carboxypeptidase E, are essential for targeting pro-opiomelanocortin to the regulated secretory pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, NIH, LDN, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 542 BP 97A EP 97A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100542 ER PT J AU Pompeia, C Belyantseva, IA Wistow, G Gao, J Beisel, K Kachar, B AF Pompeia, C Belyantseva, IA Wistow, G Gao, J Beisel, K Kachar, B TI Analysis of gene expression in the maturating organ of Corti based on a cDNA database SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCD, NIH, Bethesda, MD USA. NEI, NIH, Sect Mol Struct & Funct, Bethesda, MD 20892 USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 580 BP 103A EP 104A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100580 ER PT J AU Thiriet, N Taylor, M Cadet, J AF Thiriet, N Taylor, M Cadet, J TI Ecstasy (MDMA) modulates the JAK/STAT pathway in the rat brain SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 578 BP 103A EP 103A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100578 ER PT J AU Golestaneh, NC Fan, J Chepelinsky, AB AF Golestaneh, NC Fan, J Chepelinsky, AB TI Activation of the lens MIP/aquaporin 0 gem promoter by FGF2 in differentiating lens epithelia explants SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 585 BP 104A EP 105A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100585 ER PT J AU Jones, JM Kelley, MW AF Jones, JM Kelley, MW TI A potential role for Id proteins in the development of the cochlea SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 632 BP 113A EP 113A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100632 ER PT J AU Philp, DD AF Philp, DD TI Thymosin beta 4 and an internal actin binding peptide promote wound repair and hair regeneration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 641 BP 114A EP 114A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100641 ER PT J AU Kanungo, J Kozmik, Z Swamynathan, SK Piatigorsky, J AF Kanungo, J Kozmik, Z Swamynathan, SK Piatigorsky, J TI Gelsolin, an abundant corneal protein in zebrafish is a dorsalizing factor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 653 BP 116A EP 116A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100653 ER PT J AU Rodgers, EE Hammond, JM Donaldson, JG Randazzo, PA Vitale, N Theibert, AB AF Rodgers, EE Hammond, JM Donaldson, JG Randazzo, PA Vitale, N Theibert, AB TI Centaurin alpha, an Arf6 interacting protein, affects secretion in PC12 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Alabama, Birmingham, AL USA. NHLBI, NIH, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ Strasbourg, Lab Neurotransmiss & Secret Neuroendocrine, Strasbourg, France. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 697 BP 124A EP 124A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100696 ER PT J AU Love, DC Cathey, RL Shin, S Hanover, JA AF Love, DC Cathey, RL Shin, S Hanover, JA TI Nucleocytoplasmic and mitochondrial targeting of O-linked GlcNAc transferase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 712 BP 127A EP 127A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100711 ER PT J AU Jurkovicova, D Gioio, AE Kalra, SK Kaplan, BB AF Jurkovicova, D Gioio, AE Kalra, SK Kaplan, BB TI Novel mitochondrial-associated protein is preferentially expressed in squid neurons and is enriched in presynaptic nerve terminals SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 730 BP 130A EP 130A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100729 ER PT J AU Ishikawa, T Maurizi, MR Steven, AC AF Ishikawa, T Maurizi, MR Steven, AC TI Clp protein-degradation machines: Mechanisms of ATP-dependent proteolysis revealed by cryo-electron microscopy and image analysis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAMS, LSBR, NIH, Bethesda, MD USA. NCI, LCB, NIH, Bethesda, MD 20892 USA. RI Ishikawa, Takashi/E-5023-2017 OI Ishikawa, Takashi/0000-0002-1976-7477 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 775 BP 138A EP 138A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100774 ER PT J AU Kwik, J Margolis, L Boyle, S Sheetz, MP Edidin, M AF Kwik, J Margolis, L Boyle, S Sheetz, MP Edidin, M TI Membrane cholesterol, lateral diffusion of membrane proteins and the PI(4,5)P2-dependent organization of cell actin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Columbia Univ, New York, NY 10027 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 792 BP 142A EP 142A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100791 ER PT J AU Sharrow, M DiPietrantonio, AM Davidson, FF AF Sharrow, M DiPietrantonio, AM Davidson, FF TI Opsin point mutations in Drosophila melanogaster and the one-hit model of neuronal degeneration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, NIH, Biochem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 821 BP 147A EP 147A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100820 ER PT J AU Agarwal, R Rangel, LB D'Souza, T Pizer, ES Alo, PL Schwartz, DR Cho, KR Morin, PJ AF Agarwal, R Rangel, LB D'Souza, T Pizer, ES Alo, PL Schwartz, DR Cho, KR Morin, PJ TI Expression of tight junction proteins claudin-3 and claudin-4 in ovarian cancer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIA, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Univ Fed Rio de Janeiro, Inst Biomed Sci, Dept Basic & Clin Pharmacol, BR-21941 Rio De Janeiro, Brazil. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Rome, Italy. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 886 BP 158A EP 158A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100885 ER PT J AU Bae, M Song, B AF Bae, M Song, B TI Critical role of c-Jun N-terminal protein kinase activation in troglitazone-induced apoptosis of human HepG2 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 913 BP 163A EP 163A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100912 ER PT J AU Wei, K Clark, AB Wong, E Kane, MF Mazur, D Parris, T Kolas, N Russell, R Kneitz, B Kunkel, TA Kolodner, RD Cohen, PE Edelmann, W AF Wei, K Clark, AB Wong, E Kane, MF Mazur, D Parris, T Kolas, N Russell, R Kneitz, B Kunkel, TA Kolodner, RD Cohen, PE Edelmann, W TI Mutation of exonuclease 1 results in DNA mismatch repair defects, male and female sterility and increased cancer susceptibility in older mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Ludwig Inst Canc Res, La Jolla, CA USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 948 BP 169A EP 169A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100947 ER PT J AU Kerscher, O AF Kerscher, O TI Nups, Mads and Bubs: A connection between nucleoporins, kinetochores and spindle checkpoint proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 971 BP 173A EP 173A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100970 ER PT J AU Carter, CD Basrai, MA AF Carter, CD Basrai, MA TI Transcriptome analysis or checkpoint-dependent spindle/kinetochore regulatory networks in Saccharomyces cerevisiae SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 974 BP 174A EP 174A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100973 ER PT J AU Joseph, J Tan, S Karpova, TS McNally, JG Dasso, M AF Joseph, J Tan, S Karpova, TS McNally, JG Dasso, M TI SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, NIH, Lab Gene Regulat & Dev, Bethesda, MD USA. NCI, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 986 BP 176A EP 176A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100985 ER PT J AU Skupsky, R Nossal, R AF Skupsky, R Nossal, R TI Phosphoinositide cycles, mathematical modeling, and chemotaxis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Maryland, NICHD, NIH, LIMB, Bethesda, MD USA. NICHD, NIH, LIMB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1086 BP 193A EP 193A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101085 ER PT J AU Suzuki, N Ichikawa, N Kasai, S Nishi, N Utani, A Yamashita, H Kitagawa, Y Matthew, HP Nomizu, M AF Suzuki, N Ichikawa, N Kasai, S Nishi, N Utani, A Yamashita, H Kitagawa, Y Matthew, HP Nomizu, M TI Syndecan binding site on the laminin alpha-1 chian G domain SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Hokkaido Univ, Grad Sch EES, Sapporo, Hokkaido 060, Japan. Chiba Univ, Dept Dermatol, Chiba, Japan. Nagoya Univ, Grad Sch Bioagr Sci, Nagoya, Aichi, Japan. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1140 BP 202A EP 203A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101139 ER PT J AU Ledee, DR Zelenka, PS AF Ledee, DR Zelenka, PS TI Muskelin, a regulator of spreading on thrombospondin, interacts specifically with the CDK5 activating protein, p39 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1143 BP 203A EP 203A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101142 ER PT J AU Fan, J Donovan, AK Ledee, DR Zelenka, PS Chepelinsky, AB AF Fan, J Donovan, AK Ledee, DR Zelenka, PS Chepelinsky, AB TI Protein-protein interactions of lens MIP/Aquaporin 0 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NEI, NIH, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1237 BP 220A EP 220A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101236 ER PT J AU Greene, L Wu, X Zhao, X Eisenberg, E AF Greene, L Wu, X Zhao, X Eisenberg, E TI Adaptor and clathrin exchange at the plasma membrane and trans-Golgi network SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1272 BP 227A EP 227A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101271 ER PT J AU Snapp, EL Reinhart, G Bogert, B Hegde, R AF Snapp, EL Reinhart, G Bogert, B Hegde, R TI Ribosomes organize and maintain fully assembled translocons at the mammalian endoplasmic reticulum SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1311 BP 233A EP 233A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101310 ER PT J AU Fons, RD Kim, S Bogert, BA Hedge, RS AF Fons, RD Kim, S Bogert, BA Hedge, RS TI Dissection of the pathway of Prion protein topogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, NIH, Cell Biol & Metab Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1314 BP 234A EP 234A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101313 ER PT J AU Novoradovskaya, N Perou, C Whitfield, M Basehore, S Pesich, R Aprelikova, O Fero, M Brown, PO Botstein, D Braman, J AF Novoradovskaya, N Perou, C Whitfield, M Basehore, S Pesich, R Aprelikova, O Fero, M Brown, PO Botstein, D Braman, J TI Universal human, mouse and rat reference RNA as standards for microarray experiments SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Stanford Univ, Stanford, CA 94305 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1355 BP 241A EP 241A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101354 ER PT J AU Rangel, L Sherman-Baust, CA Schwartz, DR Cho, KR Morin, PJ AF Rangel, L Sherman-Baust, CA Schwartz, DR Cho, KR Morin, PJ TI Characterization of novel ovarian-specific genes identified by serial analysis of gene expression (SAGE) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIA, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Univ Fed Rio de Janeiro, Dept Basic & Clin Pharmacol, BR-21941 Rio De Janeiro, Brazil. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1353 BP 241A EP 241A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101352 ER PT J AU Parada, LA McQueen, PG Munson, PJ Misteli, T AF Parada, LA McQueen, PG Munson, PJ Misteli, T TI Conservation of relative chromosome positioning in normal and cancer cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, NIH, Bethesda, MD 20892 USA. CIT, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1382 BP 246A EP 246A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101381 ER PT J AU Roix, JJ Parada, LA McQueen, PG Munson, PJ Misteli, T AF Roix, JJ Parada, LA McQueen, PG Munson, PJ Misteli, T TI Nuclear positioning of gene loci in Burkitt's lymphoma SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, NIH, Bethesda, MD 20892 USA. CIT, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1383 BP 246A EP 246A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101382 ER PT J AU Elliott, BL Kreppel, LK Kimmel, AR AF Elliott, BL Kreppel, LK Kimmel, AR TI Investigating the role of nicastrin and presenilin function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, NIH, LCDB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1427 BP 254A EP 254A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101426 ER PT J AU Frescas, D DeLotto, R Iida, T Lippincott-Schwartz, J AF Frescas, D DeLotto, R Iida, T Lippincott-Schwartz, J TI ER and Golgi dynamics in the developing Drosophila melanogaster embryo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Copenhagen, Dept Genet, DK-1168 Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1470 BP 261A EP 261A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101469 ER PT J AU Snapp, EL Hedge, R Lippincott-Schwartz, J Borgese, N AF Snapp, EL Hedge, R Lippincott-Schwartz, J Borgese, N TI Self-organization of stacked cisternae from ER membranes in living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Milan, Consiglio Nazl Ric Cellular & Mol Pharmacol Ctr, I-20122 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1476 BP 262A EP 262A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101475 ER PT J AU Lorenz, H Patterson, GH Tiwari, S Weissman, AM Lippincott-Schwartz, J AF Lorenz, H Patterson, GH Tiwari, S Weissman, AM Lippincott-Schwartz, J TI Monitoring ER-associated degradation (ERAD) in single live cells using photoactivatable-GFP labeled CD36 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHHD, NIH, Bethesda, MD 20892 USA. NCI, Regulat Prot Funct Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1490 BP 264A EP 265A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101489 ER PT J AU Liu, W Phair, R Duden, R Lippincott-Schwartz, J AF Liu, W Phair, R Duden, R Lippincott-Schwartz, J TI In vivo dynamics of GFP-tagged ARFGAP1, Arf1 and coatmer on Golgi membranes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. BioInformat Serv, Rockville, MD USA. Univ Cambridge, Cambridge CB2 1TN, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1501 BP 266A EP 266A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101500 ER PT J AU Padilla, PP Chang, M Pacheco-Rodriguez, G Adamik, R Moss, J Vaughan, M AF Padilla, PP Chang, M Pacheco-Rodriguez, G Adamik, R Moss, J Vaughan, M TI Modification of BIG1 and BIG2 binding to cell membranes by the immunosuppressive drug, FK506 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1504 BP 267A EP 267A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101503 ER PT J AU Porter-Kelley, JM Gerald, N Engel, J Ghedin, E Dwyer, DM AF Porter-Kelley, JM Gerald, N Engel, J Ghedin, E Dwyer, DM TI Arf 1 is transiently associated with the Golgi in Leishmania donovani SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, VAMC, Dept Pathol, San Francisco, CA 94143 USA. TIGR, Dept Eukaryot Genom, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1503 BP 267A EP 267A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101502 ER PT J AU Hirschberg, K Phair, RD Polischchuk, R Gerlich, D Patterson, GH Lippincott-Schwartz, J AF Hirschberg, K Phair, RD Polischchuk, R Gerlich, D Patterson, GH Lippincott-Schwartz, J TI Secretory transport from the Golgi is a mass action process and involves cargo-based membrane partitioning SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Tel Aviv Univ, Sackler Sch Med, Dept Pathol, IL-69978 Tel Aviv, Israel. BioInformat Serv, Rockville, MD USA. NIH, Cell Biol & Metab Branch, Rockville, MD USA. German Canc Res Ctr, D-6900 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1510 BP 268A EP 268A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101509 ER PT J AU Goldberg, IG Swedlow, JR Sorger, P AF Goldberg, IG Swedlow, JR Sorger, P TI A software framework for computational cell biology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ Dundee, Div Gene Regulat & Express, Dundee DD1 4HN, Scotland. MIT, Dept Biol, Boston, MA USA. RI Goldberg, Ilya/H-5307-2011 OI Goldberg, Ilya/0000-0001-8514-6110 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1550 BP 275A EP 275A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101549 ER PT J AU Agarwal, R Tang, Z Yu, H Cohen-fix, O AF Agarwal, R Tang, Z Yu, H Cohen-fix, O TI The role of Pds1 phosphorylation in the DNA damage induced checkpoint arrest SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1579 BP 281A EP 281A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101578 ER PT J AU Altan-Bonnet, N Lippincott-Schwartz, J AF Altan-Bonnet, N Lippincott-Schwartz, J TI Coupling chromosome segregation, cytokinesis and organelle division: a novel role for the Golgi complex SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1583 BP 282A EP 282A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101582 ER PT J AU Kulp, KS Montgomery, JL Latham, ER Felton, JS Bennett, LM AF Kulp, KS Montgomery, JL Latham, ER Felton, JS Bennett, LM TI Dietary constituents affect estrogen receptor activation and cell proliferation in MCF-7 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Lawrence Livermore Natl Lab, Biol & Biotechnol Program, Livermore, CA USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1616 BP 288A EP 288A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101615 ER PT J AU Cai, D AF Cai, D TI Down-regulation of the phosphorylation of serine-threonine protein kinase Akt in the thirteen-lined ground squirrel during hibernation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1658 BP 295A EP 295A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101657 ER PT J AU Zhou, J Farris, RN Zelenka, PS AF Zhou, J Farris, RN Zelenka, PS TI Synergy of EGF signaling and 12(S)hydroxyeicosatetraenoate (12(S)HETE) on PKC beta activation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1660 BP 295A EP 296A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101659 ER PT J AU Yong-Gonzalez, V Strunnikov, A AF Yong-Gonzalez, V Strunnikov, A TI The sumoylation pathway and its role in chromatin integrity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, NIH, LGRD, Unit Chromosome Struct & Funct, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1678 BP 298A EP 298A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101677 ER PT J AU Murakami, MS Morrison, DK AF Murakami, MS Morrison, DK TI Morphogenesis during vertebrate gastrulation requires Wee1 mediated inhibition of cell proliferation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Regulat Cell Growth Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1687 BP 300A EP 300A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101686 ER PT J AU Barsony, J Chun, RF Adams, JS AF Barsony, J Chun, RF Adams, JS TI Heat shock proteins influence uptake mid subcellular targeting of vitamin D SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA. Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. RI Adams, John/I-3365-2013 OI Adams, John/0000-0001-9607-5020 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1699 BP 302A EP 302A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101698 ER PT J AU Eisenberg, ML Mohiddin, SA Fananapazir, L Bierer, BA AF Eisenberg, ML Mohiddin, SA Fananapazir, L Bierer, BA TI Role of sorcin in calcium homeostasis and signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Lab Lymphocyte Biol, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1709 BP 304A EP 304A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101708 ER PT J AU Shin, S AF Shin, S TI Overexpression of O-linked N-acetylglucosamine transferase (OGT) triggers apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, LCBB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1712 BP 304A EP 305A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101711 ER PT J AU Zhang, P Mattson, MM AF Zhang, P Mattson, MM TI Molecular mechanism of the anti-apoptotic function of TERT SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1723 BP 306A EP 307A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101722 ER PT J AU Wang, B Strunnikov, AV AF Wang, B Strunnikov, AV TI Characterization of chromatin targeting by condensin in budding yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, LGRD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1746 BP 310A EP 310A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101745 ER PT J AU Bai, R Rabow, AA Jung, MK Covell, DG Hamel, E AF Bai, R Rabow, AA Jung, MK Covell, DG Hamel, E TI Disruption of intracellular microtubules by multiple cytotoxic drugs that do not interact with tubulin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Screening Technol Branch, Frederick, MD 21701 USA. NCI, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1873 BP 333A EP 333A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101872 ER PT J AU Brown, FD Donaldson, JG AF Brown, FD Donaldson, JG TI Identification anal characterization of three novel Arf6-specific guanine nucleotide exchange factors SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1896 BP 336A EP 337A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101895 ER PT J AU Takino, T Yamada, KM AF Takino, T Yamada, KM TI A scaffold protei in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and tyrosine-phosphorylated SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Kanazawa Univ, Canc Res Inst, Div Mol Virol & Oncol, Kanazawa, Ishikawa 920, Japan. Natl Inst Dent & Craniofacial Res, NIH, Cranofacial Dev Biol & Regenerat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1906 BP 338A EP 339A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101905 ER PT J AU Wang, H Katagiri, Y Geller, HM AF Wang, H Katagiri, Y Geller, HM TI Cytokine regulation of astrocyte sulfotransferases and CSPG production SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1925 BP 342A EP 342A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101924 ER PT J AU Jaeger, RG Freitas, VM Scheremeta, B Hoffman, MP AF Jaeger, RG Freitas, VM Scheremeta, B Hoffman, MP TI Laminin-1, SIKVAV a laminin-1-derived peptide, and alpha 3 beta 1 integrin, regulate the morphology and protease activity of a human salivary gland adenoid cystic carcinoma cell line SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Sao Paulo, Inst Biomed Sci, BR-05508 Sao Paulo, Brazil. Univ Penn, University Pk, PA USA. NIDCR, NIH, Bethesda, MD USA. RI Jaeger, Ruy/G-8230-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1941 BP 345A EP 345A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101940 ER PT J AU Phair, RD Chasson, AK Presley, JF Hirschberg, K Lippincott-Schwartz, J AF Phair, RD Chasson, AK Presley, JF Hirschberg, K Lippincott-Schwartz, J TI Quantitative testing of mechanistic hypotheses concerning Arf1 and COPI cycling in Golgi membrane traffic SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 BioInformat Serv, Rockville, MD USA. Integrat BioInformat Inc, Mountain View, CA USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2006 BP 356A EP 356A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102005 ER PT J AU Yang, J Lee, SY Gao, M Bourgoin, S Randazzo, PA Premont, RT Hsu, VW AF Yang, J Lee, SY Gao, M Bourgoin, S Randazzo, PA Premont, RT Hsu, VW TI ARFGAP1 functions a component of the COPI coat complex to promote vesicle formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Quebec, Ctr Hosp, St Foy, PQ G1V 2M3, Canada. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2005 BP 356A EP 356A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102004 ER PT J AU Wasiak, S Legendre-Guillemin, V Puertollano, R Blondeau, F Girard, M de Heuvel, E Boismenu, D Bell, AW Bonifacino, JS McPherson, PS AF Wasiak, S Legendre-Guillemin, V Puertollano, R Blondeau, F Girard, M de Heuvel, E Boismenu, D Bell, AW Bonifacino, JS McPherson, PS TI Enthoprotin, a novel clathrin-associated protein identified through subcellular proteomics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada. McGill Univ, Montreal Proteom Ctr, Montreal, PQ H3A 2T5, Canada. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2063 BP 366A EP 366A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102062 ER PT J AU Fu, H Lin, C Bouhassira, EE Aladjem, MI AF Fu, H Lin, C Bouhassira, EE Aladjem, MI TI Orientation dependent replication timing alternation and histone acetylation/methylation of inserted gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2092 BP 371A EP 371A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102091 ER PT J AU Grieshaber, NA Fischer, E Mead, D Dooley, C Hackstadt, T AF Grieshaber, NA Fischer, E Mead, D Dooley, C Hackstadt, T TI Chlamydial histone - DNA interactions are disrupted by a small metabolite in the non-mevalonate pathway of isoprenoid biosynthesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, Rocky Mt Labs, LICP, NIH,Host Parasite Interact Sect, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, RMMB, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2096 BP 372A EP 372A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102095 ER PT J AU Partridge, JJ Latterich, M Indig, FE AF Partridge, JJ Latterich, M Indig, FE TI DNA damage modulates nucleolar interaction of the Werner protein with the AAA ATPase p97/VCP SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Illumina Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2121 BP 376A EP 376A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102120 ER PT J AU Platani, M Goldberg, I Lamond, AI Swedlow, JR AF Platani, M Goldberg, I Lamond, AI Swedlow, JR TI Cajal body dynamics and association with chromatin are ATP-dependent SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Dundee, Div Gene Regulat & Express, Dundee DD1 4HN, Scotland. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Goldberg, Ilya/H-5307-2011 OI Goldberg, Ilya/0000-0001-8514-6110 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2119 BP 376A EP 376A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102118 ER PT J AU Ramos, C Melikov, K Zaitseva, E Wilson, KL Chernomordik, LV AF Ramos, C Melikov, K Zaitseva, E Wilson, KL Chernomordik, LV TI Using protein-free vesicles and quantitative fluorimetric assays to study the early stages of nuclear envelope assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, LCMB, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21218 USA. RI Melikov, Kamran/A-6604-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2145 BP 380A EP 380A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102144 ER PT J AU Segura-Totten, M Lee, K Kowalski, AK Craigie, R Wilson, KL AF Segura-Totten, M Lee, K Kowalski, AK Craigie, R Wilson, KL TI Barrier-to-Autointegration Factor (BAF), a protein involved in chromatin decondensation and nuclear assembly, interacts with 'BAF-like', a related protein with distinct biochemical properties SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2158 BP 383A EP 383A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102157 ER PT J AU Sadler, PL Golden, A Shakes, DC AF Sadler, PL Golden, A Shakes, DC TI Hypomorphic mutations in the C. elegans APC/C cause meiotic defects that disrupt zygotic development SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, NIH, Lab Biochem & Genet, Bethesda, MD USA. Coll William & Mary, Dept Biol, Williamsburg, VA 23185 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2176 BP 386A EP 386A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102175 ER PT J AU Chen, H Beck, HN Hoffer, BJ Lein, PJ AF Chen, H Beck, HN Hoffer, BJ Lein, PJ TI Regulation of dendritic growth in cultured sympathetic neurons by target-derived BMPs SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDA, IRP, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2192 BP 389A EP 389A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102191 ER PT J AU Aguirre, A Chittajallu, R Belachew, S Yuan, X Gallo, V AF Aguirre, A Chittajallu, R Belachew, S Yuan, X Gallo, V TI Lineage origin and phenotypic characterization of immature and differentiated hippocampal neurons expressing the CNP gene in the adult dentate gyrus SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Childrens Natl Med Ctr, Childrens Res Inst, Ctr Neurosci Res, Washington, DC 20010 USA. NICHD, NIH, Lab Cell Syn Neurophysyol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2221 BP 394A EP 394A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102220 ER PT J AU Mayer, D Mu, J Feng, X Su, X Miller, LH AF Mayer, D Mu, J Feng, X Su, X Miller, LH TI Polymorphisms in a "Plasmodium falciparum" erythrocyte-binding ligand change its receptor specificity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, NIH, LMVR, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. RI feng, xiaorong/G-4811-2010 OI feng, xiaorong/0000-0001-8410-3020 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2268 BP 402A EP 402A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102267 ER PT J AU Drecktrah, D Galbraith, K Steele-Mortimer, O AF Drecktrah, D Galbraith, K Steele-Mortimer, O TI Akt activation in macrophages by Salmonella enterica serovar Typhimurium: SigD-dependent and -independent pathways SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2272 BP 403A EP 403A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102271 ER PT J AU Galbraith, KM Steele-Mortimer, O AF Galbraith, KM Steele-Mortimer, O TI Identification of Akt substrates in Salmonella enterica serovar Typhimurium infected epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2273 BP 403A EP 403A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102272 ER PT J AU Carabeo, RA Mead, DJ Hackstadt, T AF Carabeo, RA Mead, DJ Hackstadt, T TI The Chlamydial inclusion preferentially interacts with the Golgi-dependent pathway of cholesterol and sphingomyelin transport SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH,Host Parasite Sect, Hamilton, MT 59840 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2279 BP 404A EP 404A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102278 ER PT J AU Clifton, DR Mead, DJ Fischer, ER Hackstadt, T AF Clifton, DR Mead, DJ Fischer, ER Hackstadt, T TI Identification of tyrosine phosphorylated proteins in response to in vitro infection by Chlamydia trachomatis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2278 BP 404A EP 404A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102277 ER PT J AU Grieshaber, SS Grieshaber, NA Hackstadt, T AF Grieshaber, SS Grieshaber, NA Hackstadt, T TI Chlamydia trachomatis uses least cell dynein to traffic to the MTOC in a dynactin independent process SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH,Host Parasites Interact Sect, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2277 BP 404A EP 404A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102276 ER PT J AU Dombroski, D Takesono, A Schwartzberg, PL AF Dombroski, D Takesono, A Schwartzberg, PL TI siRNA as a viable model to study T lymphocyte cell biology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2311 BP 410A EP 410A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102310 ER PT J AU Barr, VA Bunnell, SC Samelson, LE AF Barr, VA Bunnell, SC Samelson, LE TI Dynamic movement of SLP-76 in activated Jurkat T cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2347 BP 417A EP 417A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102346 ER PT J AU Gopal, TV Winitsky, S Hassanzadeh, S Epstein, ND AF Gopal, TV Winitsky, S Hassanzadeh, S Epstein, ND TI A Sca1-fraction of cells from murine adult skeletal muscle differentiates into beating cardiomyocytes in vitro SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2353 BP 418A EP 418A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102352 ER PT J AU Smith, GH Wagner, K Boulanger, C AF Smith, GH Wagner, K Boulanger, C TI Identifying multilineage mammary epithelial progenitors, in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, BRL, CCR, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Eppley Inst, Omaha, NE 68182 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2352 BP 418A EP 418A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102351 ER PT J AU Puertollano, R van der Well, NN Green, LE Eisenberg, E Peters, PJ Bonifacino, J AF Puertollano, R van der Well, NN Green, LE Eisenberg, E Peters, PJ Bonifacino, J TI In vivo visualization and functional characterization of GGA-coated vesicles SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Netherlands Canc Inst, Div Tumour Biol, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2366 BP 420A EP 420A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102365 ER PT J AU Verges, M Luton, F Reinders, L Huang, L Burlingame, AL Haft, CR Mostov, KE AF Verges, M Luton, F Reinders, L Huang, L Burlingame, AL Haft, CR Mostov, KE TI Association of the polymeric immunoglobulin receptor with the mammalian retromer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. CNRS, Sophia Antipolis, France. NIH, Diabet Branch, Bethesda, MD 20892 USA. RI Huang, Lan/C-3618-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2369 BP 421A EP 421A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102368 ER PT J AU Tang, DC Zhu, J Chin, K Rodgers, GP AF Tang, DC Zhu, J Chin, K Rodgers, GP TI The small GTPase, SAR-e, induced by hydroxyurea, plays a role in cell cycle control in human erythroid cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2443 BP 434A EP 434A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102442 ER PT J AU Farina, A Dey, A Hattori, M Minato, N Ozato, K AF Farina, A Dey, A Hattori, M Minato, N Ozato, K TI The bromodomain protein Brd4 interacts with the GTPase activating protein Spa1 and affects its activity and subcellular localization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, LMGR, NIH, Bethesda, MD USA. Kyoto Univ, Fac Med, Dept Immunol & Cell Biol, Kyoto 606, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2448 BP 435A EP 435A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102447 ER PT J AU Sedelnikova, OA Horikawa, I Filipski, MJ Redon, CE Pilch, DR Newrock, KM Bonner, WM Barrett, JC AF Sedelnikova, OA Horikawa, I Filipski, MJ Redon, CE Pilch, DR Newrock, KM Bonner, WM Barrett, JC TI DNA double-strand breaks and cellular senescence SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Mol Pharmacol Lab, NIH, CCR, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, NIH, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2482 BP 441A EP 441A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102481 ER PT J AU Latterich, M Indig, FE Lin, A AF Latterich, M Indig, FE Lin, A TI Cdc48p functions in cytokinesis through a novel interaction with septin proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Illumina Inc, Proteom, San Diego, CA USA. Salk Inst Biol Studies, La Jolla, CA USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2507 BP 445A EP 445A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102506 ER PT J AU Golomb, E Preston, YA Shoham, N Conti, M Buxton, DB Adelstein, RS AF Golomb, E Preston, YA Shoham, N Conti, M Buxton, DB Adelstein, RS TI Expression of cytoplasmic myosin II-C in vivo and in vitro SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NIAMS, Arthritis & Rheumatism Branch, Genet Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2560 BP 454A EP 455A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102559 ER PT J AU Ma, X Kawamoto, S Liu, C Hara, Y Adelstein, RS AF Ma, X Kawamoto, S Liu, C Hara, Y Adelstein, RS TI Mice with an R709C mutation in nonmuscle myosin heavy chain II-B show brain, heart, and intestinal abnormalities SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2558 BP 454A EP 454A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102557 ER PT J AU Shu, S Liu, X Korn, ED AF Shu, S Liu, X Korn, ED TI The assembly domain of Dictyostelium myosin II (DdMII) localizes to the cleavage furrow of dividing cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2555 BP 454A EP 454A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102554 ER PT J AU Wei, Q Liu, C Yu, Z Adelstein, RS AF Wei, Q Liu, C Yu, Z Adelstein, RS TI Specific ablation of nonmuscle myosin heavy chain II-B in the mouse nervous system SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2559 BP 454A EP 454A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102558 ER PT J AU Limouze, J Sakamoto, T Mitchison, TJ Straight, AF Ostap, EM Sellers, JR AF Limouze, J Sakamoto, T Mitchison, TJ Straight, AF Ostap, EM Sellers, JR TI Blebbistatin, a myosin II inhibitor with interesting photochemical properties SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2562 BP 455A EP 455A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102561 ER PT J AU Takeda, K Kishi, H Yu, Z Ma, X Lin, S Kawamoto, S Adelstein, RS AF Takeda, K Kishi, H Yu, Z Ma, X Lin, S Kawamoto, S Adelstein, RS TI Expression of nonmuscle myosin heavy chain II-C in the lung and heart SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2561 BP 455A EP 455A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102560 ER PT J AU Sakamoto, T Schmitz, S Molloy, JE Veigel, C Wang, F Sellers, JR AF Sakamoto, T Schmitz, S Molloy, JE Veigel, C Wang, F Sellers, JR TI Effect of myosin V neck length on processivity and working stroke SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. Natl Inst Med Res, London NW7 1AA, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2572 BP 457A EP 457A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102571 ER PT J AU Lu, Z Zaal, KJ Bugnard, E Ploug, T Capetanaki, Y Ralston, E AF Lu, Z Zaal, KJ Bugnard, E Ploug, T Capetanaki, Y Ralston, E TI Perturbation of ER exit sites, Golgi complex, and microtubule organization in muscle fibers from desmin null mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NINDS, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD 20892 USA. Univ Copenhagen, Panum Inst, Dept Med Physiol, DK-2200 Copenhagen, Denmark. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2596 BP 461A EP 461A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102595 ER PT J AU Boukari, H Watts, NR Schuck, P Nossal, R Sackett, DL AF Boukari, H Watts, NR Schuck, P Nossal, R Sackett, DL TI Tubulin-cryptophycin-1 complexes are very stable, homogeneous rings of 8 tubulin dimers, each with two unequal points of curvature SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, LIMB, NIH, Bethesda, MD USA. NIAMS, NIH, Bethesda, MD USA. NIH, OD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2607 BP 463A EP 463A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102606 ER PT J AU Satpute-Krishnan, PS Greer, JB Reese, TS Bearer, EL AF Satpute-Krishnan, PS Greer, JB Reese, TS Bearer, EL TI Anterograde transport of human herpes simplex virus: A role for host cell Golgi proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CA SP Amer Soc Cell Biol C1 Brown Univ, Providence, RI 02912 USA. NINDS, NIH, Bethesda, MD 20892 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2674 BP 475A EP 475A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102673 ER PT J AU Sameni, M Dosescu, J List, K Bugge, TH Sloane, BF AF Sameni, M Dosescu, J List, K Bugge, TH Sloane, BF TI Expression of cathepsin B, urokinase and urokinase receptor in colon tumor cells and stromal cells modulates extracellular matrix degradation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Wayne State Univ, Detroit, MI 48202 USA. NIDCR, NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. RI Sloane, Bonnie/A-1050-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2745 BP 487A EP 487A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102744 ER PT J AU Kasai, S Yamada, M Ichikawa, N Mochizuki, M Nishi, N Kadoya, Y Kleinman, HK Yamada, Y Nomizu, M AF Kasai, S Yamada, M Ichikawa, N Mochizuki, M Nishi, N Kadoya, Y Kleinman, HK Yamada, Y Nomizu, M TI Amyloid-like fibril formation of laminin active peptides SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 060, Japan. Kitasato Univ, Sch Med, Sagamihara, Kanagawa 228, Japan. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2748 BP 488A EP 488A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102747 ER PT J AU Ben-Yosef, T Belyantseva, L Saunders, TL Hughes, ED Kawamoto, K Halsey, K Dootz, G Dolan, DF Gardner, DJ Wilcox, ER Forge, A Raphael, Y Camper, SA Friedman, TB AF Ben-Yosef, T Belyantseva, L Saunders, TL Hughes, ED Kawamoto, K Halsey, K Dootz, G Dolan, DF Gardner, DJ Wilcox, ER Forge, A Raphael, Y Camper, SA Friedman, TB TI Claudin 14 tight junction protein knockout mice are deaf due to cochlear hair cell degeneration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CA SP Amer Soc Cell Biol C1 NIDCD, Mol Genet Lab, NIH, Rockville, MD USA. Univ Michigan, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Kresge Hearing Res Inst, Ann Arbor, MI 48109 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. UCL, Ctr Auditory Res, London WC1E 6BT, England. UCL, Inst Laryngol & Otol, London WC1E 6BT, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2800 BP 497A EP 497A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102799 ER PT J AU Weerasinghe, GR Seemann, R Rapoport, SI Bosetti, F AF Weerasinghe, GR Seemann, R Rapoport, SI Bosetti, F TI Reduction by chronic lithium of brain phospholipase A(2) (PLA(2)) activity is not mediated by a decrease in the fractional phosphorylation of cytosolic PLA(2) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol ID RAT-BRAIN C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2812 BP 499A EP 500A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102811 ER PT J AU Puri, N Roche, PA AF Puri, N Roche, PA TI Lipid raft association of SNAP-23 and other SNARE proteins: implications for regulated exocytosis from RBL mast cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2849 BP 506A EP 506A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102848 ER PT J AU Wakabayashi, Y Lippincott-Schwartz, J Phair, RD Atias, JM AF Wakabayashi, Y Lippincott-Schwartz, J Phair, RD Atias, JM TI Dynamics and kinetics of constitutive apical bile salt export pump recycling between the canalicular membrane and Rab11-associated endosomes in polarized WIF-B9 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. NICHD, Cell Biol & Metab Branch, Bethesda, MD USA. BioInformat Serv, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2851 BP 507A EP 507A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102850 ER PT J AU Chen, X Matsumoto, H Hinck, CS Al-Hasani, H Whiteheart, SW Cushman, SW AF Chen, X Matsumoto, H Hinck, CS Al-Hasani, H Whiteheart, SW Cushman, SW TI Expression of a dominant-negative ATPase-deficient NSF reduces cell-surface GLUT4 by interfering with intracellular trafficking of GLUT4 to the insulin-responsive compartment in rat adipose cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, EDMNS DB, NIH, Bethesda, MD USA. Univ Cologne, Inst Biochem, D-5000 Cologne 41, Germany. Univ Kentucky, Coll Med, Lexington, KY 40506 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2860 BP 508A EP 508A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102859 ER PT J AU Hepp, R Roche, PA AF Hepp, R Roche, PA TI Regulation of SNAP-23 phosphorylation during exocytosis in mast cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2863 BP 509A EP 509A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102862 ER PT J AU Fan, J Cheadle, C Becker, KG Gorospe, M AF Fan, J Cheadle, C Becker, KG Gorospe, M TI High-throughput analysis of the relative changes in gene transcription and mRNA turnover during T cell activation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIA, Gerontol Res Ctr, LCMB, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, DNA Array Unit, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2933 BP 521A EP 521A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102932 ER PT J AU Kim, M Levin, H AF Kim, M Levin, H TI A retrotransposon of Schizosacchromyces pombe possesses residues in Gag that regulate nuclear localization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2951 BP 524A EP 524A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102950 ER PT J AU Plafker, SM Weissman, AM Macara, IG AF Plafker, SM Weissman, AM Macara, IG TI The enzymatic activation and nuclear transport of a class III E2 ubiquitin enzyme are coupled SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Virginia, Ctr Cell Signaling, Charlottesville, VA 22903 USA. NCI, Ctr Canc Res, Regulat Prot Funct Lab, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2971 BP 528A EP 528A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102970 ER PT J AU Steinberg, ZL Kidder, BL Larsen, M Kleinman, HK Hoffman, MP AF Steinberg, ZL Kidder, BL Larsen, M Kleinman, HK Hoffman, MP TI FGFs and BMPs regulate branching morphogenesis of mouse submandibular glands in vitro SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, NIDCR, CDBRB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2981 BP 529A EP 529A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102980 ER PT J AU Zhao, L Melenhorst, JJ Cheng, J Stewart, C Hennigahusen, L AF Zhao, L Melenhorst, JJ Cheng, J Stewart, C Hennigahusen, L TI gp130 mediated signaling pathways are involved in mammary gland involution SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDDK, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3012 BP 535A EP 535A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103011 ER PT J AU Lavezzari, G McCallum, J Gerfen, J Roche, KW AF Lavezzari, G McCallum, J Gerfen, J Roche, KW TI Differential endocytic sorting of NMDA receptor NR2 subunits SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NINDS, NIH, RBU, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3019 BP 536A EP 536A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103018 ER PT J AU Sans, NA Prybylowski, K Petralia, RS Chang, K Wang, Y Racca, C Vicini, S Wenthold, RJ AF Sans, NA Prybylowski, K Petralia, RS Chang, K Wang, Y Racca, C Vicini, S Wenthold, RJ TI NMDA receptor trafficking through an interaction between the MAGUKs and the exocyst complex SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3021 BP 536A EP 536A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103020 ER PT J AU Standley, S Petralia, RS Gravell, M Hamilton, R Tsay, M Wang, YX Schubert, M Wenthold, RJ AF Standley, S Petralia, RS Gravell, M Hamilton, R Tsay, M Wang, YX Schubert, M Wenthold, RJ TI Protein interactions with the NMDA receptor C-terminal domains along the secretory pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIDCD, NIH, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3020 BP 536A EP 536A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103019 ER PT J AU Phillips, AW Major, EO AF Phillips, AW Major, EO TI A human neuroglial cell line, SVG, differentially secretes neurotrophins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Howard Univ, Dept Biol, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3031 BP 538A EP 538A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103030 ER PT J AU Scotto-Lavina, Z Lockard, JM Jurkovicova, D Kalra, SK Tessema, M Gioio, AE Kaplan, BB AF Scotto-Lavina, Z Lockard, JM Jurkovicova, D Kalra, SK Tessema, M Gioio, AE Kaplan, BB TI Isolation and characterization of a novel phosphotyrosine-binding protein expressed in the squid and mouse nervous systems SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3028 BP 538A EP 538A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103027 ER PT J AU Kim, T Arnaoutova, I Loh, P AF Kim, T Arnaoutova, I Loh, P TI Mechanisms of dense-core secretory granule biogenesis mediated by chromogranin A in endocrine cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3037 BP 539A EP 539A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103036 ER PT J AU Catalfamo, ML Karpova, T McNally, J Costes, S Lockett, SJ Boss, E Peters, P Henkart, PA AF Catalfamo, ML Karpova, T McNally, J Costes, S Lockett, SJ Boss, E Peters, P Henkart, PA TI CD8+ and CD4+ T cells store RANTES in a unique secretory compartment and release it rapidly after TcR stimulation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, SAIC, Microscopy & Image Anal Lab, NIH, Frederick, MD 21701 USA. Netherlands Canc Inst, Amsterdam, Netherlands. RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3041 BP 540A EP 540A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103040 ER PT J AU Huizing, M Patterson, G Lippincott-Schwartz, J Gahl, WA AF Huizing, M Patterson, G Lippincott-Schwartz, J Gahl, WA TI Hermansky-Pudlak syndrome real-time fluorescent imaging evidence of abnormal vesicle formation and trafficking SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NHGRI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3043 BP 540A EP 540A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103042 ER PT J AU Moriyama, K AF Moriyama, K TI Pallidin is a component of a multi-protein complex involved in the biogenesis of lysosome-related organelles SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3042 BP 540A EP 540A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103041 ER PT J AU Patterson, GH Lippincott-Schwartz, J AF Patterson, GH Lippincott-Schwartz, J TI Photoactivatable green fluorescent protein SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 NIH, Cell Biol & Metab Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3105 BP 551A EP 551A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103104 ER PT J AU Kim, SJ Hegde, RS AF Kim, SJ Hegde, RS TI Cotranslational partitioning of nascent prion protein into multiple populations at the translocation channel SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; SIGNAL SEQUENCE; TRANSMEMBRANE DOMAIN; DISULFIDE-ISOMERASE; SECRETORY PROTEINS; BIOGENESIS; DISEASES; RIBOSOME; TOPOLOGY; CONTAINS AB The decisive events that direct a single polypeptide such as the prion protein (PrP) to be synthesized at the endoplasmic reticulum in both fully translocated and transmembrane forms are poorly understood. In this study, we demonstrate that the topological heterogeneity of PrP is determined cotranslationally, while at the translocation channel. By evaluating sequential intermediates during PrP topogenesis, we find that signal sequence-mediated initiation of translocation results in an interaction between nascent PrP and endoplasmic reticulum chaperones, committing the N terminus to the lumen. Synthesis of the transmembrane domain before completion of this step allows it to direct the generation of (PrP)-Pr-Ctm, a transmembrane form with its N terminus in the cytosol. Thus, segregation of nascent PrP into different topological configurations is critically dependent on the precise timing of signal-mediated initiation of N-terminus translocation. Consequently, this step could be experimentally tuned to, modify PrP topogenesis, including complete reversal of the elevated (PrP)-Pr-Ctm caused by disease-associated mutations in the transmembrane domain. These results delineate the sequence of events involved in PrP biogenesis, explain the mechanism of action of (PrP)-Pr-Ctm-favoring mutations associated with neurodegenerative disease, and more generally, reveal that translocation substrates can be cotranslationally partitioned into multiple populations at the translocon. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Liberty Dr,Bldg 18,Room 101, Bethesda, MD 20892 USA. OI Hegde, Ramanujan/0000-0001-8338-852X NR 39 TC 56 Z9 59 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 IS 11 BP 3775 EP 3786 DI 10.1091/mbc.E02-05-0293 PG 12 WC Cell Biology SC Cell Biology GA 621BK UT WOS:000179568500002 PM 12429823 ER PT J AU Gao, C Negash, S Guo, HT Ledee, D Wang, HS Zelenka, P AF Gao, C Negash, S Guo, HT Ledee, D Wang, HS Zelenka, P TI CDK5 regulates cell adhesion and migration in corneal epithelial cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; NEURONAL-SPECIFIC ACTIVATOR; DIRECTED PROTEIN-KINASE; NEURITE OUTGROWTH; INITIAL BINDING; KDA SUBUNIT; STEM-CELLS; IN-VIVO; EXPRESSION; PHOSPHORYLATION AB CDK5 and its activator, p35, are expressed in mouse corneal epithelium and can be coimmunoprecipited from corneal epithelial cell lysates. Immunostaining shows CDK5 and p35 in all layers of the corneal epithelium, especially along the basal side of the basal cells. Stable transfection of corneal epithelial cells with CDK5, which increases CDK5 kinase activity by approximately 33%, also increases the number of cells adhering to fibronectin and the strength of adhesion. CDK5 kinase activity seems to be required for this effect, because the kinase inactive mutation, CDK5-T33, either reduces adhesion or has no significant effect, depending on the level of expression. Using an in vitro scrape wound in confluent cultures of stably transfected cells to examine the effect of CDK5 on cell migration, we show that reoccupation of the wound area is significantly decreased by CDKS and increased by CDK5-T33. These findings indicate that CDK5 may be an important regulator of adhesion and migration of corneal epithelial cells. C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Taipei 112, Taiwan. RP Zelenka, P (reprint author), NEI, NIH, Room 214,Bldg 6,6 Ctr Dr MSC 2730, Bethesda, MD 20892 USA. EM zelenkap@intra.nei.nih.gov NR 77 TC 44 Z9 46 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2002 VL 1 IS 1 BP 12 EP 24 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 659HZ UT WOS:000181772400003 PM 12496365 ER PT J AU Kim, S Dougherty, ER Shmulevich, I Hess, KR Hamilton, SR Trent, JM Fuller, GN Zhang, W AF Kim, S Dougherty, ER Shmulevich, I Hess, KR Hamilton, SR Trent, JM Fuller, GN Zhang, W TI Identification of combination gene sets for glioma classification SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MOLECULAR CLASSIFICATION; EXPRESSION; PREDICTION AB One goal for the gene expression profiling of cancer tissues is to identify signature genes that robustly distinguish different types or grades of tumors. Such signature genes would ideally provide a molecular basis for classification and also yield insight into the molecular events underlying different cancer phenotypes. This study applies a recently developed algorithm to identify not only single classifier genes but also gene sets (combinations) for use as glioma classifiers. Classifier genes identified by this algorithm are shown to be strong features by conservatively and collectively considering the misclassification errors of the feature sets. Applying this approach to a test set of 25 patients, we have identified the best single genes and two- to three-gene combinations for distinguishing four types of glioma: (a) oligodendroglioma; (b) anaplastic oligodendroglioma; (c) anaplastic astrocytoma; and (d) glioblastoma multiforme. Some of the identified genes, such as insulin-like growth factor-binding protein 2, have been confirmed to be associated with one of the tumor types. Using combinations of genes, the classification error rate can be significantly lowered. In many instances, neither of the individual genes of a two-gene set performs well as an accurate classifier, but the combination of the two genes forms a robust classifier with a small error rate. Two-gene and three-gene combinations thus provide robust classifiers possessing the potential to translate expression microarray results into diagnostic histopathological assays for clinical utilization. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Canc Genom Core Lab, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, W (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Canc Genom Core Lab, Box 85,1515 Holcombe Blvd, Houston, TX 77030 USA. OI Fuller, Gregory/0000-0001-9447-2647 NR 17 TC 96 Z9 99 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2002 VL 1 IS 13 BP 1229 EP 1236 PG 8 WC Oncology SC Oncology GA 616ZA UT WOS:000179332700009 PM 12479704 ER PT J AU Banerjee-Basu, S Baxevanis, AD AF Banerjee-Basu, S Baxevanis, AD TI Molecular modeling of mutations in the DNA-binding domain of the oncoprotein Qin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PROTEIN-FOLD RECOGNITION; CEREBRAL HEMISPHERES; FORK HEAD; SEQUENCE; ONCOGENE; ADJACENT; MOTIF; BF-1 AB The retroviral oncogene qin, homologue of mammalian brain factor 1 (FOXG1B), belongs to the family of winged helix transcription factors. Oncogenic transformation by Qin requires sequence-specific DNA binding. Missense mutations in the forkhead domain of Qin modulate its oncogenic transforming ability in chicken embryonic fibroblasts. We used homology model building (threading) techniques to generate;atomic structures of wild-type c-Qin and c-Qin mutants, using the solution structure of the forkhead domain of the adipocyte transcription factor as a template (M. J. van Dongen et ah, J. Mol. Biol., 296: :351-359, 2000). Energy calculations indicate that the Qin forkhead structure is stabilized primarily by hydrophobic interactions between residues at the helical interface. None of the missense mutations analyzed here were responsible for maintaining the most critical pairwise interactions holding the forkhead domain together. The mutated proteins form the overall structure of the forkhead domain, but the mutations do interfere with DNA binding. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD NOV PY 2002 VL 1 IS 13 BP 1237 EP 1241 PG 5 WC Oncology SC Oncology GA 616ZA UT WOS:000179332700010 PM 12479705 ER PT J AU Flores, KG McAllister, KA Greer, PK Wiseman, RW Hale, LP AF Flores, KG McAllister, KA Greer, PK Wiseman, RW Hale, LP TI Thymic model for examining BRCA2 expression and function SO MOLECULAR CARCINOGENESIS LA English DT Article DE BRCA2; thymus; apoptosis; DNA damage; proliferation; Brca2 knockout ID CANCER SUSCEPTIBILITY GENE; APOPTOSIS; BREAST; CELLS; MICE; MUTATION AB Mutations in the human BRC42 breast cancer susceptibility gene are associated with increased risks of breast, ovarian, and other cancers. BRCA2 has been hypothesized to function in processes of DNA damage/breakage repair, cell proliferation, and apoptosis. These processes continually occur in the thymus during thymocyte development, and BRCA2 mRNA is highly expressed in thymus relative to most other organs. We therefore used the thymus as a model system to study BRCA2 expression and function. Quantitative reverse transcription polymerase chain reaction experiments showed that highly activated immature CD4(+) CD8(+) double-positive human thymocytes that exhibited high levels of proliferation and apoptosis had increased BRCA2 mRNA levels relative to other thymocyte subsets. BRCA2 mRNA levels were upregulated in thymocytes treated with the DNA-damaging agent etoposide. Only modest increases were associated with proliferation in human peripheral lymphocytes in response to concanavalin A (ConA) mitogen. Mice homozygous for a targeted mutation in Brca2 exon 27 (Brca2(Delta27/Delta27)) showed normal thymic architecture but had 18% decreased thymocyte cellularity compared with wild-type mice. Thymocytes from these Brca2(Delta27/Delta27) mice displayed decreased apoptosis in response to etoposide-induced DNA damage compared with wildtype thymocytes. These studies suggest that BRC42 mRNA levels are modulated during DNA damage and may be important during apoptosis. (C) 2002 Wiley-Liss, Inc. C1 Duke Univ, Med Ctr, Dept Pathol, DUMC 3712, Durham, NC 27710 USA. Duke Univ, Cell & Mol Biol Program, Durham, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Hale, LP (reprint author), Duke Univ, Med Ctr, Dept Pathol, DUMC 3712, M213A Davison Bldg, Durham, NC 27710 USA. FU NIA NIH HHS [AG16826] NR 17 TC 5 Z9 5 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 2002 VL 35 IS 3 BP 103 EP 109 DI 10.1002/mc.10081 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 611RD UT WOS:000179030800001 PM 12410562 ER PT J AU Kugoh, H Nakamoto, H Inoue, J Funaki, K Barrett, JC Oshimura, M AF Kugoh, H Nakamoto, H Inoue, J Funaki, K Barrett, JC Oshimura, M TI Multiple human chromosomes carrying tumor-suppressor functions for the mouse melanoma cell line B16-F10, identified by microcell-mediated chromosome transfer SO MOLECULAR CARCINOGENESIS LA English DT Article DE chromosome transfer; senescence; tumor suppressor; microcell; B16-F10 ID MALIGNANT-MELANOMA; SENESCENCE GENE; METASTASIS; REGION; TUMORIGENICITY; HETEROGENEITY; EXPRESSION; PATHWAYS; CANCER; NEVI AB Many tumor-suppressor genes are involved in the development and progression of cellular malignancy. To understand the functional role of tumor-suppressor genes in melanoma and to identify the human chromosome that carries these genes, we transferred individually each normal human chromosome, except for the Y chromosome, into the mouse melanoma cell line B16-F10, by microcell fusion. We examined the tumorigenicity of hybrid cells in nude mice and their in vitro growth properties. The introduction of human chromosomes 1 and 2 elicited a remarkable change in cell morphologic features, and cellular senescence was induced at seven to 10 population doublings. The growth rates of tumors derived from microcell hybrid clones containing introduced human chromosome 5, 7, 9, 10, 11, 13, 14, 15, 16, 19, 20, 21, 22, or X were significantly slower than that of the parental B16-F10 cells, whereas the introduction of other human chromosomes had no effect on the tumorigenicity of these cells. The majority of microcell hybrid clones that exhibited suppressed tumorigenicity also showed a moderate reduction in doubling time compared with B16-F10 cells. Microcell hybrid clones with an introduced human chromosome 5 showed complete suppression of in vitro-transformed phenotypes, including cell growth, saturation density, and colony-forming efficiency in soft agar. Thus, these results indicated the presence of many cell senescence-related genes and putative tumor-suppressor genes for the mouse melanoma cell line B16-F10 and showed in vitro that many tumor-suppressor genes control the phenotypes of transformed cells in the multistep process of neoplastic development. (C) 2002 Wiley-Liss, Inc. C1 Tottori Univ, Fac Med, Sch Life Sci, Dept Mol & Cell Genet, Tottori 6838503, Japan. Shimane Univ, Fac Educ, Dept Sci Educ, Izumo, Shimane, Japan. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Oshimura, M (reprint author), Tottori Univ, Fac Med, Sch Life Sci, Dept Mol & Cell Genet, 86 Nishimachi, Tottori 6838503, Japan. NR 36 TC 5 Z9 5 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 2002 VL 35 IS 3 BP 148 EP 156 DI 10.1002/mc.10080 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 611RD UT WOS:000179030800005 PM 12410566 ER PT J AU Kunkel, TA Diaz, M AF Kunkel, TA Diaz, M TI Enzymatic cytosine deamination: Friend AND foe SO MOLECULAR CELL LA English DT Editorial Material ID B MESSENGER-RNA; DNA AB AID and Apobec proteins have several, normally beneficial cellular functions. It has now been discovered that they act as DNA mutators in E. coli by deaminating cytosine in DNA. Thus, they may produce genome instability in mammals if not controlled. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2002 VL 10 IS 5 BP 962 EP 963 DI 10.1016/S1097-2765(02)00750-5 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619AJ UT WOS:000179450600002 PM 12453402 ER PT J AU Komissarova, N Becker, J Solter, S Kireeva, M Kashlev, M AF Komissarova, N Becker, J Solter, S Kireeva, M Kashlev, M TI Shortening of RNA : DNA hybrid in the elongation complex of RNA polymerase is a prerequisite for transcription termination SO MOLECULAR CELL LA English DT Article ID 3.3 ANGSTROM RESOLUTION; ESCHERICHIA-COLI; NASCENT RNA; TERNARY COMPLEXES; OPERON ATTENUATOR; MECHANISM; RELEASE; STABILITY; HAIRPIN; MODEL AB Passage of E. coli RNA polymerase through an intrinsic transcription terminator, which encodes an RNA hairpin followed by a stretch of uridine residues, results in quick dissociation of the elongation complex. We show that folding of the hairpin disrupts the three upstream base pairs of the 8 bp RNA:DNA hybrid, a major stability determinant in the complex. Shortening the weak rU:dA hybrid from 8 nt to 5 nt causes dissociation of the complex. During termination, the hairpin does not directly compete for base pairing with the 8 bp hybrid. Thus, melting of the hybrid seems to result from spatial restrictions in RNA polymerase that couple the hairpin formation with the disruption of the hybrid immediately downstream from the stem. Our results suggest that a similar mechanism disrupts elongation complexes of yeast RNA polymerase II in vitro. C1 NCI, Ctr Canc Res, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Goucher Coll, Baltimore, MD 21204 USA. RP Komissarova, N (reprint author), NCI, Ctr Canc Res, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 50 TC 83 Z9 87 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2002 VL 10 IS 5 BP 1151 EP 1162 DI 10.1016/S1097-2765(02)00738-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619AJ UT WOS:000179450600022 PM 12453422 ER PT J AU Ferrand, PE Fujimoto, T Chennathukuzhi, V Parry, S Macones, GA Sammel, M Kuivaniemi, H Romero, R Strauss, JF AF Ferrand, PE Fujimoto, T Chennathukuzhi, V Parry, S Macones, GA Sammel, M Kuivaniemi, H Romero, R Strauss, JF TI The CARD15 2936insC mutation and TLR4 896 A > G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM) SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE CARD15; gene mutation; polymorphism; PPROM; TLR4 ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; NOD2; SUSCEPTIBILITY; ENDOTOXIN; APOPTOSIS; PREGNANCY; PATHOGENS; IMMUNITY; WOMEN AB Infection is believed to be a leading cause of preterm premature rupture of membranes (PPROM). The bacterial cell wall component, lipopolysaccharide (LPS), is thought to initiate tissue responses leading to PPROM in the setting of Gram negative infection. LPS is recognized by the innate immune system, including the proteins encoded by the CARD15 and TLR4 genes. A recently described mutation (2936insC) in CARD15 and a polymorphism in TLR4 896 A>G impair responses to LPS. The objective of this study was to determine if African Americans, who have a higher incidence of PPROM than Caucasians, have different frequencies of the mutant CARD15 allele and the TLR4 hyporesponsive variant, and if risk of PPROM is influenced by fetal carriage of these alleles. The allele frequencies for the CARD15 mutation and the TLR4 896G variant in African Americans were similar to those reported for Caucasians. There was no association between the TLR4 alleles examined and PPROM. However, the CARD15 mutation was only detected in controls and not in PPROM cases. We conclude that the CARD15 mutation and hyporesponsive TLR4 allele do not contribute to ethnic variation in the incidence of PPROM. C1 Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Hutzel Hosp, Perinatol Res Branch, NICHHD, Detroit, MI 48201 USA. RP Strauss, JF (reprint author), Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. OI Kuivaniemi, Helena/0000-0001-5753-8766 FU FIC NIH HHS [D43/TWO1272]; NICHD NIH HHS [HD34612, HDO1265] NR 27 TC 31 Z9 31 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD NOV PY 2002 VL 8 IS 11 BP 1031 EP 1034 DI 10.1093/molehr/8.11.1031 PG 4 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 614ZM UT WOS:000179221400009 PM 12397216 ER PT J AU Yavuz, AS Monson, NL Yavuz, S Grammer, AC Longo, N Girschick, HJ Lipsky, PE AF Yavuz, AS Monson, NL Yavuz, S Grammer, AC Longo, N Girschick, HJ Lipsky, PE TI Different patterns of bcl-6 and p53 gene mutations in tonsillar B cells indicate separate mutational mechanisms SO MOLECULAR IMMUNOLOGY LA English DT Article DE human; B lymphocytes; T lymphocytes; oncogenes ID CHRONIC LYMPHOCYTIC-LEUKEMIA; GERMINAL-CENTER FORMATION; TUMOR-SUPPRESSOR GENE; REED-STERNBERG CELLS; SOMATIC HYPERMUTATION; RHEUMATOID-ARTHRITIS; HODGKINS-DISEASE; SYNOVIAL TISSUE; T-CELLS; EXPRESSION AB Mutations within the 5'-non-coding region of the bcl-6 gene can occur in lymphomas that originate from germinal centers (GCs), as well as in normal memory and GC B cells. Mutations in the p53 gene occur in 50% of human cancers. Since both bcl-6 and p53 can be mutated in certain circumstances, we investigated the accumulation of mutations in these genes in individual tonsillar B and T cells to determine whether the mutations exhibited a pattern anticipated from the B-cell hypermutation machinery. In tonsillar GC B cells, the overall mutational frequencies in the 5'-non-coding region of the bcl-6 gene was 0.85 x 10(-3)/bp. In contrast, there were no mutations in a region 2.8 kb downstream of the promoter. RGYW (purine, guanine, pyrimidine, A/T) targeting and a significantly lower mutational frequency in naive B and GC founder B cells compared with GC B cells suggested that a similar mutator mechanism was active on Ig genes and this non-Ig gene. The mutational frequency in the exon-7-region of p53 was similar in the GC, memory and naive B-cell subsets (1.02 x 10(-3) to 1.25 x 10(-3)/bp). RGYW/WRCY motifs were not targeted preferentially in the p53 gene. Moreover, a comparable mutational frequency of p53 was noted in tonsillar B and T cells. Hence, mutations in p53 do not appear to be the result of the B-cell hypermutational mechanism. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Res Ctr, Dallas, TX USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. NR 37 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD NOV PY 2002 VL 39 IS 7-8 BP 485 EP 493 AR PII S0161-5890(02)00117-7 DI 10.1016/S0161-5890(02)00117-7 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 617VN UT WOS:000179381700012 PM 12413700 ER PT J AU Majdalani, N Hernandez, D Gottesman, S AF Majdalani, N Hernandez, D Gottesman, S TI Regulation and mode of action of the second small RNA activator of RpoS translation, RprA SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; CAPSULAR POLYSACCHARIDE; SALMONELLA-TYPHIMURIUM; ERWINIA-AMYLOVORA; EXPRESSION; DSRA; GENE; RCSB; HFQ; IDENTIFICATION AB Translation of the stationary phase sigma factor RpoS is stimulated by at least two small RNAs, DsrA and RprA. DsrA disrupts an inhibitory secondary structure in the rpoS leader mRNA by pairing with the upstream RNA. Mutations in rprA and compensating mutations in the rpoS leader demonstrate that RprA interacts with the same region of the RpoS leader as DsrA. This is the first example of two different small RNAs regulating a common target. Regulation of these RNAs differs. DsrA synthesis is increased at low temperature. We find that RprA synthesis is regulated by the RcsC/RcsB phosphorelay system, previously found to regulate capsule synthesis and promoters of ftsZ and osmC. An rcsB null mutation abolishes the basal level, whereas mutations in rcsC that activate capsule synthesis also activate expression of the rprA promoter. An essential site with similarity to other RcsB-regulated promoters was defined in the rprA promoter. Activation of the RcsC/RcsB system leads to increased RpoS synthesis, in an RprA-dependent fashion. This work suggests a new signal for RpoS translation and extends the global regulation effected by the RcsC/RcsB system to coregulation of RpoS with capsule and FtsZ. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 43 TC 197 Z9 202 U1 3 U2 11 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2002 VL 46 IS 3 BP 813 EP 826 DI 10.1046/j.1365-2958.2002.03203.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 610PD UT WOS:000178968400020 PM 12410838 ER PT J AU Li, YF Sergueev, K Austin, S AF Li, YF Sergueev, K Austin, S TI The segregation of the Escherichia coli origin and terminus of replication SO MOLECULAR MICROBIOLOGY LA English DT Article ID CHROMOSOME DIMER RESOLUTION; FACTORY MODEL; CELL-DIVISION; DNA; RECOMBINATION; LOCALIZATION; ORGANIZATION; MECHANISMS; MOVEMENT; BACTERIA AB Escherichia coli chromosome replication forks are tethered to the cell centre. Two opposing models describe how the chromosomes segregate. In the extrusion-capture model, newly replicated DNA is fed bi-directionally from the forks toward the cell poles, forming new chromosomes in each cell half. Starting with the origins, chromosomal regions segregate away from their sisters progressively as they are replicated. The termini segregate last. In the sister chromosome cohesion model, replication produces sister chromosomes that are paired along much of their length. The origins and most other chromosomal regions remain paired until late in the replication cycle, and all segregate together. We use a combination of microscopy and flow cytometry to determine the relationship of origin and terminus segregation to the cell cycle. Origin segregation frequently follows closely after initiation, in strong support of the extrusion-capture model. The spatial disposition of the origin and terminus sequences also fits this model. Terminus segregation occurs extremely late in the cell cycle as the daughter cells separate. As the septum begins to invaginate, the termini of the completed sister chromosomes are transiently held apart at the cell centre, on opposite sides of the cell. This may facilitate the resolution of topological linkages between the chromosomes. C1 NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NR 32 TC 93 Z9 94 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2002 VL 46 IS 4 BP 985 EP 995 DI 10.1046/j.1365-2958.2002.03234.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 618CQ UT WOS:000179400900007 PM 12421305 ER PT J AU Deng, XL Jayanthi, S Ladenheim, B Krasnova, IN Cadet, JL AF Deng, XL Jayanthi, S Ladenheim, B Krasnova, IN Cadet, JL TI Mice with partial deficiency of c-Jun show attenuation of methamphetamine-induced neuronal apoptosis SO MOLECULAR PHARMACOLOGY LA English DT Article ID DISMUTASE TRANSGENIC MICE; INDUCED NEUROTOXICITY; NULL MUTATION; MOUSE-BRAIN; SYMPATHETIC NEURONS; OXIDATIVE STRESS; GENE-EXPRESSION; DEVELOPING RATS; CELL-DEATH; DOPAMINE AB The regional distribution of c-Jun expression and of the number of apoptotic cells was compared in various brain areas after methamphetamine administration to mice. Our results showed that there was methamphetamine-induced overexpression of c-Jun in the cortex and striatum but not in the cerebellar cortex. There was an almost totally similar regional appearance of methamphetamine-induced apoptotic cells in the mouse brain; no apoptosis was present in the cerebellum. Additionally, in the neocortical area, more positive signals for c-Jun immunoreactivity were observed in the piriform cortex, an area that also showed more positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) signals than the frontal and parietal cortices. These observations suggested that c-Jun might be involved in methamphetamine-induced apoptosis. This idea was confirmed by using heterozygous c-Jun knockout mice that showed much less apoptosis than wild-type controls. In addition, we found that the majority of TUNEL-positive cells were also positive for c-Jun-like immunoreactivity in both genotypes. Moreover, methamphetamine-induced caspase-3 activity and PARP cleavage were also reduced in c-Jun heterozygous knockout mice. In contrast, methamphetamine-induced hyperthermia was essentially identical in the two genotypes. When taken together, our data support the hypothesis that c-Jun is involved in methamphetamine-induced apoptosis. C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 48 TC 38 Z9 38 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2002 VL 62 IS 5 BP 993 EP 1000 DI 10.1124/mol.62.5.993 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 606QR UT WOS:000178745100005 PM 12391261 ER PT J AU Duttaroy, A Gomeza, J Gan, JW Siddiqui, N Basile, AS Harman, WD Smith, PL Felder, CC Levey, AI Wess, J AF Duttaroy, A Gomeza, J Gan, JW Siddiqui, N Basile, AS Harman, WD Smith, PL Felder, CC Levey, AI Wess, J TI Evaluation of muscarinic agonist-induced analgesia in muscarinic acetylcholine receptor knockout mice SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT SPINAL-CORD; DORSAL-ROOT GANGLIA; DENDROASPIS-ANGUSTICEPS; SUBSTANTIA-GELATINOSA; CHOLINERGIC RECEPTORS; CHO CELLS; ANTINOCICEPTION; SUBTYPES; PAIN; MORPHINE AB Centrally active muscarinic agonists display pronounced analgesic effects. Identification of the specific muscarinic acetylcholine receptor (mAChR) subtype(s) mediating this activity is of considerable therapeutic interest. To examine the roles of the M-2 and M-4 receptor subtypes, the two G(i)/G(o)-coupled mAChRs, in mediating agonist-dependent antinociception, we generated a mutant mouse line deficient in both M-2 and M-4 mAChRs [M-2/M-4 double-knockout (KO) mice]. In wild-type mice, systemic, intrathecal, or intracerebroventricular administration of centrally active muscarinic agonists resulted in robust analgesic effects, indicating that muscarinic analgesia can be mediated by both spinal and supraspinal mechanisms. Strikingly, muscarinic agonist-induced antinociception was totally abolished in M-2/M-4 double-KO mice, independent of the route of application. The nonselective muscarinic agonist oxotremorine showed reduced analgesic potency in M-2 receptor single-KO mice, but retained full analgesic activity in M-4 receptor single-KO mice. In contrast, two novel muscarinic agonists chemically derived from epibatidine, CMI-936 and CMI-1145, displayed reduced analgesic activity in both M-2 and M-4 receptor single-KO mice, independent of the route of application. Radioligand binding studies indicated that the two CMI compounds, in contrast to oxotremorine, showed >6-fold higher affinity for M-4 than for M-2 receptors, providing a molecular basis for the observed differences in agonist activity profiles. These data provide unambiguous evidence that muscarinic analgesia is exclusively mediated by a combination of M-2 and M-4 mAChRs at both spinal and supraspinal sites. These findings should be of considerable relevance for the development of receptor subtype-selective muscarinic agonists as novel analgesic drugs. C1 NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Chem, Charlottesville, VA USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.govf RI Levey, Allan/F-2104-2011 OI Levey, Allan/0000-0002-3153-502X NR 63 TC 86 Z9 92 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2002 VL 62 IS 5 BP 1084 EP 1093 DI 10.1124/mol.62.5.1084 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 606QR UT WOS:000178745100015 PM 12391271 ER PT J AU He, ML Koshimizu, TA Tomic, M Stojilkovic, SS AF He, ML Koshimizu, TA Tomic, M Stojilkovic, SS TI Purinergic P2X(2) receptor desensitization depends on coupling between ectodomain and C-terminal domain SO MOLECULAR PHARMACOLOGY LA English DT Article ID NUCLEOTIDE-GATED CHANNELS; METHYL-D-ASPARTATE; SYNAPTIC TRANSMISSION; KAINATE RECEPTORS; PROTEIN-KINASE; AMPA RECEPTORS; SUBUNIT; ACTIVATION; IDENTIFICATION; INACTIVATION AB The wild-type P2X(2) purinergic receptor (P2X(2a)R) and its splice form lacking the intracellular Val(370)-Gln(438) C-terminal sequence (P2X(2b)R) respond to ATP stimulation with comparable EC50 values and peak current/calcium responses but desensitize in a receptor-specific manner. P2X(2a)R desensitizes slowly and P2X(2b)R desensitizes rapidly. We studied the effects of different agonists, and of substituting the ectodomain, on the pattern of calcium signaling by P2X(2a)R and P2X(2b)R. Both receptors showed similar EC50 values (estimated from the peak calcium response) and IC50 values (estimated from the rate of calcium signal desensitization) for agonists, in the order 2-MeS-ATP less than or equal to ATP less than or equal to ATPgammaS < BzATP << αβ-meATP, and the IC50 values for agonists were shifted to the right compared with their EC50 values. Furthermore, the ATP-induced receptor-subtype specific pattern of desensitization was mimicked by high- but not by low-efficacy agonists, suggesting a ligand-specific desensitization pattern. To test this hypothesis, we generated chimeric P2X(2a)R and P2X(2b)R containing the Val(60)-Phe(301) ectodomain sequence of P2X(3)R and Val(61)-Phe(313) ectodomain sequence of P2X(7)R instead the native Ile(66)-Tyr(310) sequence. The mutated P2X(2a)+X3R and P2X(2b)+X3R exhibited comparable EC50 values for ATP, BzATP, and αβ-meATP in the submicromolar concentration range and desensitized in a receptor-specific and ligand-nonspecific manner. On the other hand, the chimeric P2X(2)+X7R exhibited decreased sensitivity for ATP and desensitized in a receptor-nonspecific manner. These results suggest that efficacy of agonists for the ligand-binding domain of P2X(2)Rs reflects the strength of desensitization controlled by their C-terminal structures. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, SCS, ERRB, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. RI Tomic, Melanija/C-3371-2016 NR 42 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2002 VL 62 IS 5 BP 1187 EP 1197 DI 10.1124/mol.62.5.1187 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 606QR UT WOS:000178745100027 PM 12391283 ER PT J AU Waldo, GL Corbitt, J Boyer, JL Ravi, G Kim, HS Ji, XD Lacy, J Jacobson, KA Harden, TK AF Waldo, GL Corbitt, J Boyer, JL Ravi, G Kim, HS Ji, XD Lacy, J Jacobson, KA Harden, TK TI Quantitation of the P2Y(1) receptor with a high affinity radiolabeled antagonist SO MOLECULAR PHARMACOLOGY LA English DT Article ID ATP BINDING-SITES; P-2Y PURINOCEPTOR; ENDOTHELIAL-CELLS; AGONIST; DERIVATIVES; SELECTIVITY; BRAIN; IDENTIFICATION; TRIPHOSPHATES; NUCLEOTIDES AB 2-Chloro-N-6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate (MRS2279) was developed previously as a selective high-affinity, non-nucleotide P2Y(1) receptor (P2Y1-R) antagonist (J Med Chem 43: 829-842, 2002; Br J Pharmacol 135:2004-2010, 2002). We have taken advantage of the N-6-methyl substitution in the adenine base to incorporate [H-3] methylamine into the synthesis of [H-3] MRS2279 to high (89 Ci/mmol) specific radioactivity and have used this molecule as a radioligand for the P2Y1-R. [H-3] MRS2279 bound to membranes from Sf9 insect cells expressing recombinant human P2Y1-R but not to membranes from wild-type Sf9 cells or Sf9 cells expressing high levels of recombinant P2Y(2) or P2Y(12) receptors. Equilibrium binding of [H-3] MRS2279 to P2Y1-R expressed in Sf9 membranes was with a high affinity (K-d = 8 nM) essentially identical to the apparent affinity of MRS2279 determined previously in studies of P2Y1-R-promoted inositol phosphate accumulation or platelet aggregation. A kinetically derived K-d calculated from independent determinations of the rate constants of association (7.15 x 10(7) M-1 min(-1)) and dissociation (0.72 min(-1))of [H-3] MRS2279 also was in good agreement with the K-d derived from equilibrium binding studies. Competition binding assays with [H-3] MRS2279 and P2Y1-R expressing Sf9 cell membranes revealed K-i values for the P2Y1-R antagonists MRS2279 (K-i = 13 nM), N-6-methyl-2'-deoxyadenosine-3',5'-bisphosphate (MRS2179; K-i = 84 nM), adenosine-3',5'-bisphosphate (K-i = 900 nM), and pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (K-i = 6 muM) that were in good agreement with antagonist activities of these molecules previously determined at the P2Y1-R in intact tissues. Moreover, [H-3] MRS2279 also bound with high affinity (K-d = 4-8 nM) to Chinese hamster ovary (CHO) or 1321N1 human astrocytoma cells stably expressing the human P2Y1-R, but specific binding was not observed in wild-type CHO or 1321N1 cells. [H-3] MRS2279 bound with high affinity (K-d = 16 nM) to a binding site on out-dated human platelets (5-35 receptors/platelet) and rat brain membranes (210 fmol/mg protein) that fit the expected drug selectivity of a P2Y1-R. Taken together, these results indicate that [H-3] MRS2279 is the first broadly applicable antagonist radioligand for a P2Y receptor. C1 Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. NIDDKD, Mol Recognit Sect, NIH, Bethesda, MD USA. Perkin Elmer Corp, Life Sci, Receptor Ligand Biol, Boston, MA USA. RP Harden, TK (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, CB 7365, Chapel Hill, NC 27599 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999]; NHLBI NIH HHS [HL54889, R01 HL054889, R29 HL054889]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 35 TC 49 Z9 50 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2002 VL 62 IS 5 BP 1249 EP 1257 DI 10.1124/mol.62.5.1249 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 606QR UT WOS:000178745100033 PM 12391289 ER PT J AU Raben, N Jatkar, T Lee, A Lu, N Dwivedi, S Nagaraju, K Plotz, PH AF Raben, N Jatkar, T Lee, A Lu, N Dwivedi, S Nagaraju, K Plotz, PH TI Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme SO MOLECULAR THERAPY LA English DT Article DE transgenic; knockout; acid alpha-glucosidase; Pompe disease; myopathy ID DISEASE TYPE-II; LYSOSOMAL STORAGE DISEASES; HIGH-LEVEL PRODUCTION; REPLACEMENT THERAPY; GENE-EXPRESSION; RABBIT MILK; MUCOPOLYSACCHARIDOSIS-I; TARGETED DISRUPTION; MAMMALIAN-CELLS; INFANTILE AB Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosiclase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease. We have addressed the issue of reversibility of the disease in the Gaa(-/-) mouse model. We have made transgenic lines expressing human GAA in skeletal and cardiac muscle of Gaa(-/-) mice, and we turned the transgene on at different stages of disease progression by using a tetracycline-controllable system. We have demonstrated that levels of 20-30% of normal activity are indeed sufficient to clear glycogen in the heart of young Gaa(-/-) mice, but not in older mice with a considerably higher glycogen load. However, in skeletal muscle-a major organ affected in infantile and in milder, late-onset variants in humans-induction of GAA expression in young Gaa(-/-) mice to levels greatly exceeding wildtype values did not result in full phenotypic correction, and some muscle fibers showed little or no glycogen clearance. The results demonstrate that complete reversal of pathology in skeletal muscle or long-affected heart muscle will require much more enzyme than previously expected or a different approach. C1 NIAMSD, Arthrit & Rheumat Branch, NIH, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMSD, Arthrit & Rheumat Branch, NIH, Bethesda, MD 20892 USA. NR 35 TC 48 Z9 49 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 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2002 VL 6 IS 5 BP 601 EP 608 DI 10.1006/mthe.2002.0716 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 615RN UT WOS:000179260600012 PM 12409258 ER PT J AU Evidente, VGH Advincula, J Esteban, R Pasco, P Alfon, JA Natividad, FF Cuanang, J San Luis, A Gwinn-Hardy, K Hardy, J Hernandez, D Singleton, A AF Evidente, VGH Advincula, J Esteban, R Pasco, P Alfon, JA Natividad, FF Cuanang, J San Luis, A Gwinn-Hardy, K Hardy, J Hernandez, D Singleton, A TI Phenomenology of "Lubag" or X-linked dystonia-parkinsonism SO MOVEMENT DISORDERS LA English DT Article DE dystonia; Lubag; XDP; parkinsonism ID MOVEMENT DISORDER; MYORHYTHMIA AB X-linked dystonia-parkinsonism (XDP), or Lubag syndrome, is known to cause progressive dystonia, with or without parkinsonism, among Filipino male adults with maternal roots from the Philippine island of Panay. We present cinematographic material of I I cases of Lubag carrying the XDP haplotypes who manifest with a wide spectrum of movement disorders, including dystonia, tremor, parkinsonism, myoclonus, chorea, and myorhythmia. Because of overlapping features, Lubag patients are commonly misdiagnosed as idiopathic dystonia, essential tremor, Parkinson's disease, or Parkinson's-plus syndromes. Thus, it is imperative to elicit an exhaustive family history in any Filipino male adult who presents with a movement disorder. (C) 2002 Movement Disorder Society. C1 Mayo Clin, Dept Neurol, Scottsdale, AZ 85259 USA. St Lukes Hosp, Inst Neurosci, Quezon City, Philippines. Western Visayas State Univ, Med Ctr, Iloilo, Philippines. Philippine Gen Hosp, Dept Neurol, Manila, Philippines. St Lukes Hosp, Res & Biotechnol Div, Quezon City, Philippines. Univ E Ramon Magsaysay, Mem Med Ctr, Quezon City, Philippines. NIH, Bethesda, MD 20892 USA. RP Evidente, VGH (reprint author), Mayo Clin, Dept Neurol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; OI Gwinn, Katrina/0000-0002-8277-651X NR 16 TC 35 Z9 35 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2002 VL 17 IS 6 BP 1271 EP 1277 DI 10.1002/mds.10271 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 618FV UT WOS:000179408800018 PM 12465067 ER PT J AU Hardy, J AF Hardy, J TI Genetically dissecting neurodegenerative disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT Joint PSP-Association/Alzheimers-Society-International-Medical Workshop CY OCT 22-23, 2001 CL BUCKINGHAMSHIRE, ENGLAND SP PSP Assoc, Alzheimers Soc Int Med C1 NIA, Neurogenet Lab, 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2002 VL 17 IS 6 BP 1403 EP 1403 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 618FV UT WOS:000179408800056 ER PT J AU Lewis, J AF Lewis, J TI Tau transgenic mouse models and their relevance to progressive supranuclear palsy and Alzheimer's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT Joint PSP-Association/Alzheimers-Society-International-Medical Workshop CY OCT 22-23, 2001 CL BUCKINGHAMSHIRE, ENGLAND SP PSP Assoc, Alzheimers Soc Int Med C1 NIA, Neurogenet Lab, 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2002 VL 17 IS 6 BP 1404 EP 1404 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 618FV UT WOS:000179408800058 ER PT J AU Litvan, I AF Litvan, I TI Discussion of day 1 proceedings SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT Joint PSP-Association/Alzheimers-Society-International-Medical Workshop CY OCT 22-23, 2001 CL BUCKINGHAMSHIRE, ENGLAND SP PSP Assoc, Alzheimers Soc Int Med C1 NINDS, Cognit Neuropharmacol Unit, 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2002 VL 17 IS 6 BP 1406 EP 1406 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 618FV UT WOS:000179408800062 ER PT J AU Hardy, J AF Hardy, J TI Genetically dissecting neurodegenerative disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT Joint PSP-Association/Alzheimers-Society-International-Medical Workshop CY OCT 22-23, 2001 CL BUCKINGHAMSHIRE, ENGLAND SP PSP Assoc, Alzheimers Soc Int Med C1 NIA, Neurogenet Lab, 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2002 VL 17 IS 6 BP 1407 EP 1408 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 618FV UT WOS:000179408800068 ER PT J AU Luciano, CA Russell, JW Banerjee, TK Quirk, JM Scott, LJC Dambrosia, JM Barton, NW Schiffmann, R AF Luciano, CA Russell, JW Banerjee, TK Quirk, JM Scott, LJC Dambrosia, JM Barton, NW Schiffmann, R TI Physiological characterization of neuropathy in Fabry's disease SO MUSCLE & NERVE LA English DT Article DE Fabry's disease; nerve conduction studies; quantitative sensory testing; small-fiber neuropathy; thermal sensation ID SYMPATHETIC SKIN-RESPONSE; ALPHA-GALACTOSIDASE; QUANTITATIVE-ANALYSIS; DIABETIC NEUROPATHY; CARPAL-TUNNEL; MEDIAN NERVE; POTENTIALS; CONDUCTION; DYSFUNCTION; SUDOMOTOR AB Fabry's disease is commonly associated with a painful, debilitating neuropathy. Characterization of the physiological abnormalities is an important step in evaluating response to specific therapies. Twenty-two patients with Fabry's disease, and with relatively preserved renal function, underwent conventional and near-nerve conduction studies, electromyography, sympathetic skin responses, and quantitative sensory testing (QST). Nerve conduction studies were mostly normal except for an increased frequency of median nerve entrapment at the wrist in 6 (27%) patients. Sympathetic skin responses were preserved in 19 of 20 (95%) of the patients. The QST showed increased or immeasurable cold and warm detection thresholds in patients, significantly different from controls (n = 28) in the hand (P < 0.001, P = 0.04, respectively) and foot (P < 0.001 for both). Cold thresholds were more often abnormal than were warm thresholds. Vibration thresholds were normal in the feet and, in some patients, elevated in the hand only, probably due to frequent median nerve entrapment at the wrist. Our findings suggest that the neuropathy of Fabry's disease is characterized by an increased prevalence of median nerve entrapment at the wrist and by thermal afferent fiber dysfunction in a length -dependent fashion, with greater impairment of cold than warm sensation. (C) 2002 Wiley Periodicals, Inc. C1 Univ Puerto Rico, Sch Med, Div Neurol, San Juan, PR 00936 USA. NIH, NINDS, Dev & Metab Neurol Branch, Bethesda, MD USA. NIH, NINDS, Biostat Branch, Bethesda, MD USA. NIH, NINDS, Electromyog Sect, Bethesda, MD 20892 USA. RP Luciano, CA (reprint author), Univ Puerto Rico, Sch Med, Div Neurol, San Juan, PR 00936 USA. FU NCRR NIH HHS [1P20RR11126]; NINDS NIH HHS [1U54NS43011] NR 48 TC 70 Z9 71 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD NOV PY 2002 VL 26 IS 5 BP 622 EP 629 DI 10.1002/mus.10236 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 611QK UT WOS:000179029100004 PM 12402283 ER PT J AU Yang, ST Kuo, C Bisi, JE Kim, MK AF Yang, ST Kuo, C Bisi, JE Kim, MK TI PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2 SO NATURE CELL BIOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; RETINOIC ACID; RAR-ALPHA; SUPPRESSES GROWTH; CANCER CELLS; CHK2; PROTEIN; PATHWAY; P53; EXPRESSION AB The promyelocytic leukaemia (PML) gene is translocated in most acute promyelocytic leukaemias and encodes a tumour suppressor protein. PML is involved in multiple apoptotic pathways and is thought to be pivotal in gamma irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after gamma irradiation. In addition, gamma irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates gamma irradiation-induced apoptosis in a p53-independent manner through an ataxia telangiectasia-mutated (ATM)-hCds1/Chk2-PML pathway. Our results provide the first evidence of a functional relationship between PML and a checkpoint kinase in gamma irradiation-induced apoptosis. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Dept Cellular Genom, Res Triangle Pk, NC 27709 USA. RP Yang, ST (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 41 TC 163 Z9 167 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2002 VL 4 IS 11 BP 865 EP 870 DI 10.1038/ncb869 PG 6 WC Cell Biology SC Cell Biology GA 613NE UT WOS:000179137700015 PM 12402044 ER PT J AU Wilson, SM Bhattacharyya, B Rachel, RA Coppola, V Tessarollo, L Householder, DB Fletcher, CF Miller, RJ Copeland, NG Jenkins, NA AF Wilson, SM Bhattacharyya, B Rachel, RA Coppola, V Tessarollo, L Householder, DB Fletcher, CF Miller, RJ Copeland, NG Jenkins, NA TI Synaptic defects in ataxia mice result from a mutation in Usp14, encoding a ubiquitin-specific protease SO NATURE GENETICS LA English DT Article ID NEUROMUSCULAR-JUNCTION; RECEPTORS; SUSCEPTIBILITY; MONOUBIQUITIN; LOCUS AB Mice that are homozygous with respect to a mutation (ax J) in the ataxia (ax) gene develop severe tremors by 2-3 weeks of age followed by hindlimb paralysis and death by 6-10 weeks of age(1). Here we show that ax encodes ubiquitin-specific protease 14 (Usp14). Ubiquitin proteases are a large family of cysteine proteases that specifically cleave ubiquitin conjugates. Although Usp14 can cleave a ubiquitin-tagged protein in vitro, it is unable to process polyubiquitin 2, which is believed to be associated with the protein aggregates seen in Parkinson disease 3, spinocerebellar ataxia type 1 (SCA1; ref. 4) and gracile axonal dystrophy (GAD)(5). The physiological substrate of Usp14 may therefore contain a mono-ubiquitin side chain, the removal of which would regulate processes such as protein localization 6 and protein activity(7,8). Expression of Usp14 is significantly altered in ax(J)/ax(J) mice as a result of the insertion of an intracisternal-A particle (IAP) into intron 5 of Usp14. In contrast to other neurodegenerative disorders such as Parkinson disease and SCA1 in humans and GAD in mice, neither ubiquitin-positive protein aggregates nor neuronal cell loss is detectable in the central nervous system (CNS) of ax(J) mice. Instead, ax(J) mice have defects in synaptic transmission in both the central and peripheral nervous systems. These results suggest that ubiquitin proteases are important in regulating synaptic activity in mammals. C1 NCI, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. Northwestern Univ, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA. Novartis Fdn, Genom Inst, San Diego, CA USA. RP Jenkins, NA (reprint author), NCI, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. RI Coppola, Vincenzo/E-2917-2011 OI Coppola, Vincenzo/0000-0001-6163-1779 NR 30 TC 171 Z9 178 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2002 VL 32 IS 3 BP 420 EP 425 DI 10.1038/ng1006 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 611TX UT WOS:000179034800020 PM 12368914 ER PT J AU Khong, HT Restifo, NP AF Khong, HT Restifo, NP TI Natural selection of tumor variants in the generation of "tumor escape" phenotypes SO NATURE IMMUNOLOGY LA English DT Review ID DENDRITIC CELL MATURATION; ENDOTHELIAL GROWTH-FACTOR; HUMAN-MELANOMA CELLS; EXPRESS FAS LIGAND; REGULATORY T-CELLS; CLASS-I PHENOTYPES; HUMAN NK CELLS; MHC CLASS-I; LEUKOCYTE ANTIGEN; DOWN-REGULATION AB The idea that tumors must "escape" from immune recognition contains the implicit assumption that tumors can be destroyed by immune responses either spontaneously or as the result of immunotherapeutic intervention. Simply put, there is no need for tumor escape without immunological pressure. Here, we review evidence supporting the immune escape hypothesis and critically explore the mechanisms that may allow such escape to occur. We discuss the idea that the central engine for generating immunoresistant tumor cell variants is the genomic instability and dysregulation that is characteristic of the transformed genome. "Natural selection" of heterogeneous tumor cells results in the survival and proliferation of variants that happen to possess genetic and epigenetic traits that facilitate their growth and immune evasion. Tumor escape variants are likely to emerge after treatment with increasingly effective immunotherapies. C1 Natl Canc Inst, NIH, Bethesda, MD 20892 USA. RP Khong, HT (reprint author), Natl Canc Inst, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 100 TC 581 Z9 600 U1 11 U2 52 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2002 VL 3 IS 11 BP 999 EP 1005 DI 10.1038/ni1102-999 PG 7 WC Immunology SC Immunology GA 612KE UT WOS:000179073000004 PM 12407407 ER PT J AU Yewdell, JW Hill, AB AF Yewdell, JW Hill, AB TI Viral interference with antigen presentation SO NATURE IMMUNOLOGY LA English DT Review ID MHC CLASS-I; HERPES-SIMPLEX VIRUS; CYTOTOXIC T-LYMPHOCYTES; MOUSE CYTOMEGALOVIRUS GLYCOPROTEIN; MURINE CYTOMEGALOVIRUS; CELL RESPONSES; IMMUNE-EVASION; ENDOPLASMIC-RETICULUM; NATURAL-KILLER; HEAVY-CHAINS AB CD8(+) T cells play an important role in immunity to viruses. just how important these cells are is demonstrated by the evolution of viral strategies for blocking the generation or display of peptide-major histocompatibility complex class I complexes on the surfaces of virus-infected cells. Here, we focus on viral interference with antigen presentation; in particular we consider the importance (and difficulty) of establishing the evolutionary significance (that is, the ability to enhance viral transmission) of viral gene products that interfere with antigen presentation in vitro. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 80 TC 161 Z9 165 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2002 VL 3 IS 11 BP 1019 EP 1025 DI 10.1038/ni1102-1019 PG 7 WC Immunology SC Immunology GA 612KE UT WOS:000179073000007 PM 12407410 ER PT J AU Sacks, D Sher, A AF Sacks, D Sher, A TI Evasion of innate immunity by parasitic protozoa SO NATURE IMMUNOLOGY LA English DT Review ID FALCIPARUM-INFECTED ERYTHROCYTES; LEISHMANIA-MAJOR PROMASTIGOTES; HUMAN DENDRITIC CELLS; PROTEIN-KINASE-C; TRYPANOSOMA-BRUCEI-RHODESIENSE; TOXOPLASMA-GONDII TACHYZOITES; COMPLEMENT REGULATORY PROTEIN; CD4(+) T-CELLS; PLASMODIUM-FALCIPARUM; DONOVANI INFECTION AB Parasitic protozoa are a major cause of global infectious disease. These eukaryotic pathogens have evolved with the vertebrate immune system and typically produce long-lasting chronic infections. A critical step in their host interaction is the evasion of innate immune defenses. The ability to avoid attack by humoral effector mechanisms, such as complement lysis, is of particular importance to extracellular parasites, whereas intracellular protozoa must resist killing by lysosomal enzymes and toxic metabolites. They do so by remodeling the phagosomal compartments in which they reside and by interfering with signaling pathways that lead to cellular activation. In addition, there is growing evidence that protozoan pathogens modify the antigen-presenting and immunoregulatory functions of dendritic cells, a process that facilitates their evasion of both innate and adaptive immunity. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 81 TC 199 Z9 213 U1 3 U2 37 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2002 VL 3 IS 11 BP 1041 EP 1047 DI 10.1038/ni1102-1041 PG 7 WC Immunology SC Immunology GA 612KE UT WOS:000179073000010 PM 12407413 ER PT J AU Migueles, SA Laborico, AC Shupert, WL Sabbaghian, MS Rabin, R Hallahan, CW Van Baarle, D Kostense, S Miedema, F McLaughlin, M Ehler, L Metcalf, J Liu, SY Connors, M AF Migueles, SA Laborico, AC Shupert, WL Sabbaghian, MS Rabin, R Hallahan, CW Van Baarle, D Kostense, S Miedema, F McLaughlin, M Ehler, L Metcalf, J Liu, SY Connors, M TI HIV-specific CD8(+) T cell proliferation is coupled to perforin expression and is maintained in nonprogressors SO NATURE IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM NONPROGRESSORS; ANTIRETROVIRAL THERAPY; LYMPHOCYTE RESPONSES; CYTOKINE PRODUCTION; TYPE-1 INFECTION; IMMUNE-RESPONSES; EFFECTOR; MEMORY; HLA AB It is unclear why immunological control of HIV replication is incomplete in most infected individuals. We examined here the CD8(+)T cell response to HIV-infected CD4(+)T cells in rare patients with immunological control of HIV. Although high frequencies of HIV-specific CD8(+)T cells were present in nonprogressors and progressors, only those of nonprogressors maintained a high proliferative capacity. This proliferation was coupled to increases in perforin expression. These results indicated that nonprogressors were differentiated by increased proliferative capacity of HIV-specific CD8(+)T cells linked to enhanced effector function. In addition,the relative absence of these functions in progressors may represent a mechanism by which HIV avoids immunological control. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20205 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. CLB Sanquin, Dept Clin Viroimmunol, Amsterdam, Netherlands. RP Connors, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20205 USA. NR 49 TC 659 Z9 677 U1 0 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2002 VL 3 IS 11 BP 1061 EP 1068 DI 10.1038/ni845 PG 8 WC Immunology SC Immunology GA 612KE UT WOS:000179073000013 PM 12368910 ER PT J AU Sharp, R Recio, JA Jhappan, C Otsuka, T Liu, SQ Yu, YL Liu, WJ Anver, M Navid, F Helman, LJ DePinho, RA Merlino, G AF Sharp, R Recio, JA Jhappan, C Otsuka, T Liu, SQ Yu, YL Liu, WJ Anver, M Navid, F Helman, LJ DePinho, RA Merlino, G TI Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis SO NATURE MEDICINE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; SKELETAL-MUSCLE DIFFERENTIATION; BHLH PROTEIN TWIST; CELL-CYCLE ARREST; TUMOR-SUPPRESSOR; SATELLITE CELLS; MYOGENIC DIFFERENTIATION; GENE-EXPRESSION; MET AB Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet molecular events associated with the genesis and progression of this potentially fatal disease are largely unknown. For the molecules and pathways that have been implicated, genetic validation has been impeded by lack of a mouse model of RMS. Here we show that simultaneous loss of Ink4a/Arf function and disruption of c-Met signaling in Ink4a/Arf(-/-) mice transgenic for hepatocyte growth factor/scatter factor (HGF/SF) induces RMS with extremely high penetrance and short latency. In cultured myoblasts, c-Met activation and Ink4a/Arf loss suppress myogenesis in an additive fashion. Our data indicate that human c-MET and INK4a/ARF, situated at the nexus of pathways regulating myogenic growth and differentiation, represent critical targets in RMS pathogenesis. The marked synergism in mice between aberrant c-Met signaling and Ink4a/Arf inactivation, lesions individually implicated in human RMS, suggests a therapeutic combination to combat this devastating childhood cancer. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Frederick Canc Res & Dev Ctr, SAIC, Pathol Histotechnol Lab, Frederick, MD USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol Med & Genet, Boston, MA 02115 USA. RP Merlino, G (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. OI Recio, Juan Angel/0000-0002-7320-3832 FU NCI NIH HHS [U01CA84313-04] NR 39 TC 112 Z9 114 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2002 VL 8 IS 11 BP 1276 EP 1280 DI 10.1038/nm787 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 614ZK UT WOS:000179221200034 PM 12368906 ER PT J AU Heemskerk, J Tobin, AJ Ravina, B AF Heemskerk, J Tobin, AJ Ravina, B TI From chemical to drug: neurodegeneration drug screening and the ethics of clinical trials SO NATURE NEUROSCIENCE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SPINAL MUSCULAR-ATROPHY; HUNTINGTONS-DISEASE; MOUSE MODELS; GABAPENTIN; EQUIPOISE C1 NINDS, Technol Dev Program, NIH, Bethesda, MD 20892 USA. NINDS, Clin Trials Program, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Heemskerk, J (reprint author), NINDS, Technol Dev Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jill_heemskerk@ninds.nih.gov NR 20 TC 27 Z9 29 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2002 VL 5 BP 1027 EP 1029 DI 10.1038/nn931 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 611WT UT WOS:000179041300005 PM 12403977 ER PT J AU Finkelstein, R Miller, T Baughman, R AF Finkelstein, R Miller, T Baughman, R TI The challenge of translational research - a perspective from the NINDS SO NATURE NEUROSCIENCE LA English DT Article C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Finkelstein, R (reprint author), NINDS, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. RI Baughman, Robert/O-9078-2014 OI Baughman, Robert/0000-0002-8557-9458 NR 0 TC 10 Z9 10 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2002 VL 5 SU S BP 1029 EP 1030 DI 10.1038/nn933 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 611WT UT WOS:000179041300006 PM 12403978 ER PT J AU Khaled, AR Durum, SK AF Khaled, AR Durum, SK TI Lymphocide: Cytokines and the control of lymphoid homeostasis SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID T-CELL DEVELOPMENT; RECEPTOR-DEFICIENT MICE; NA+/H+ EXCHANGER ISOFORM-1; ACTIVATED PROTEIN-KINASE; FAMILY MEMBER BIM; BCL-2 FAMILY; CYTOCHROME-C; INTERLEUKIN-7 RECEPTOR; TRANSGENIC MICE; IN-VIVO AB In a human, about 10(11) excess peripheral lymphocytes die every day. This death process maintains a constant lymphocyte population size in the face of a continuous influx of new lymphocytes and the homeostatic proliferation of old ones. Death is triggered when a lymphocyte fails to acquire signals from survival factors, the availability of which, therefore, determines the size of the pool of lymphocytes. A lymphocyte acquires survival signals through receptors for cytokines, antigens, hormones and probably other extracellular factors. Here, we discuss current concepts of the intracellular signalling pathways for survival versus death that establish cytokine-regulated lymphocyte homeostasis. C1 NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. NR 156 TC 118 Z9 123 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2002 VL 2 IS 11 BP 817 EP 830 DI 10.1038/nri931 PG 14 WC Immunology SC Immunology GA 636DR UT WOS:000180439700015 PM 12415306 ER PT J AU Sacks, D Noben-Trauth, N AF Sacks, D Noben-Trauth, N TI The immunology of susceptibility and resistance to Leishmania major in mice SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID CELL-MEDIATED-IMMUNITY; CD4(+) T-CELLS; EXPERIMENTAL CUTANEOUS LEISHMANIASIS; NITRIC-OXIDE PRODUCTION; INTERFERON-GAMMA; BALB/C MICE; DENDRITIC CELLS; TH2 RESPONSE; DEFICIENT MICE; PROTECTIVE IMMUNITY AB Established models of T-helper-2-cell dominance in BALB/c mice infected with Leishmania major - involving the early production of interleukin-4 by a small subset of Leishmania-specific CD4(+) T cells - have been refined by accumulating evidence that this response is not sufficient and, under some circumstances, not required to promote susceptibility. In addition, more recent studies in L. major-resistant mice have revealed complexities in the mechanisms responsible for acquired immunity, which necessitate the redesign of vaccines against Leishmania and other pathogens that require sustained cell-mediated immune responses. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Immunol, Washington, DC 20037 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 140 TC 669 Z9 679 U1 3 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2002 VL 2 IS 11 BP 845 EP 858 DI 10.1038/nri933 PG 14 WC Immunology SC Immunology GA 636DR UT WOS:000180439700017 PM 12415308 ER PT J AU Guarne, A Zhao, QH Ghirlando, R Yang, W AF Guarne, A Zhao, QH Ghirlando, R Yang, W TI Insights into negative modulation of E-coli replication initiation from the structure of SeqA-hemimethylated DNA complex SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID ELECTRON-DENSITY MAPS; ESCHERICHIA-COLI; 2 SITES; PROTEIN; CHROMOSOME; SEQUESTRATION; METHYLATION; BACTERIAL; TOPOLOGY; BINDING AB The SeqA protein binds clusters of fully methylated or hemimethylated GATC sequences at oriC and negatively modulates the initiation of DNA replication. We find that SeqA can be proteolytically cleaved into an N-terminal multimerization and a C-terminal DNA-binding domain and have determined the crystal structure of the C-terminal domain in complex with a hemimethylated GATC site. SeqA makes direct hydrogen bonds and van der Waals contacts with the hemimethylated A-T base pair in addition to interactions with the surrounding bases and DNA backbone. The tetrameric protein-DNA complex found in the crystal suggests that SeqA binds multiple GATC sites on separate DNA duplexes, altering the overall DNA topology and sequestering oriC from replication initiation. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ghirlando, Rodolfo/A-8880-2009; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 35 TC 29 Z9 31 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD NOV PY 2002 VL 9 IS 11 BP 839 EP 843 DI 10.1038/nsb857 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 609CH UT WOS:000178884700014 PM 12379844 ER PT J AU Frank, MK Dyda, F Dobrodumov, A Gronenborn, AM AF Frank, MK Dyda, F Dobrodumov, A Gronenborn, AM TI Core mutations switch monomeric protein GB1 into an intertwined tetramer SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID IMMUNOGLOBULIN-BINDING DOMAIN; HETERONUCLEAR NMR-SPECTROSCOPY; MACROMOLECULAR STRUCTURES; STRUCTURAL INTEGRITY; CRYSTAL-STRUCTURES; DIFFRACTION DATA; PROGRAM PACKAGE; RESTRAINTS; CRYSTALLOGRAPHY; STABILITY AB The structure of a mutant immunoglobulin- binding B1 domain of streptococcal protein G (GB1), which comprises five conservative changes in hydrophobic core residues, was determined by NMR spectroscopy and X-ray crystallography. The oligomeric state and quaternary structure of the mutant protein are drastically changed from the wild type protein. The mutant structure consists of a symmetric tetramer, with intermolecular strand exchange involving all four units. Four of the five secondary structure elements present in the monomeric wild type GB1 structure are retained in the tetrameric structure, although their intra- and intermolecular interactions are altered. Our results demonstrate that through the acquisition of a moderate number of pivotal point mutations, proteins such as GB1 are able to undergo drastic structural changes, overcoming reduced stability of the monomeric unit by multimerization. The present structure is an illustrative example of how proteins exploit the breadth of conformational space. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gronenborn@nih.gov OI Gronenborn, Angela M/0000-0001-9072-3525 NR 41 TC 41 Z9 41 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD NOV PY 2002 VL 9 IS 11 BP 877 EP 885 DI 10.1038/nsb854 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 609CH UT WOS:000178884700020 ER PT J AU Hardy, J AF Hardy, J TI Testing times for the "amyloid cascade hypothesis" SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID ONSET ALZHEIMERS-DISEASE; PRECURSOR PROTEIN LOCUS; CHROMOSOME-10; A-BETA-42; MODEL; TAU C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10,6C103, Bethesda, MD 20892 USA. RI Hardy, John/C-2451-2009 NR 11 TC 48 Z9 48 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 2002 VL 23 IS 6 BP 1073 EP 1074 AR PII S0197-4580(02)00042-8 DI 10.1016/S0197-4580(02)00042-8 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 630CH UT WOS:000180089600011 PM 12470803 ER PT J AU Savory, J Ghribi, O Herman, MM AF Savory, J Ghribi, O Herman, MM TI Is amyloid beta-peptide neurotoxic or neuroprotective and what is its role in the binding of metal ions? SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID INDUCED NEUROFIBRILLARY DEGENERATION; ALZHEIMERS-DISEASE; A-BETA; ENDOPLASMIC-RETICULUM; SENILE PLAQUE; ALUMINUM; APOPTOSIS; PROTEIN; RABBITS; COPPER C1 Univ Virginia, Dept Pathol, Ctr Hlth Sci, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NIMH, IRP, NIH, Bethesda, MD 20892 USA. RP Savory, J (reprint author), Univ Virginia, Dept Pathol, Ctr Hlth Sci, POB 168, Charlottesville, VA 22908 USA. NR 28 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 2002 VL 23 IS 6 BP 1089 EP 1092 AR PII S0197-4580(02)00037-4 DI 10.1016/S0197-4580(02)00037-4 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 630CH UT WOS:000180089600015 PM 12470807 ER PT J AU Ungerleider, LG Doyon, J Karni, A AF Ungerleider, LG Doyon, J Karni, A TI Imaging brain plasticity during motor skill learning SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article; Proceedings Paper CT 7th Conference on the Neurobiology of Learning and Memory CY NOV 07-09, 2001 CL IRVINE, CALIFORNIA DE motor sequence learning; motor cortex; procedural memory; consolidation; fMRI; humans ID POSITRON EMISSION TOMOGRAPHY; LONG-TERM POTENTIATION; HORIZONTAL CONNECTIONS; POSTERIOR PARIETAL; FORELIMB CORTEX; RAT; MEMORY; REPRESENTATIONS; CONSOLIDATION; PERFORMANCE AB The search for the neural substrates mediating the incremental acquisition of skilled motor behaviors has been the focus of a large body of animal and human studies in the past decade. Much less is known, however, with regard to the dynamic neural changes that occur in the motor system during the different phases of learning. In this paper, we review recent findings, mainly from our own work using fMRI, which suggest that: (i) the learning of sequential finger movements produces a slowly evolving reorganization within primary motor cortex (M I) over the course of weeks and (ii) this change in M1 follows more dynamic, rapid changes in the cerebellum, striatum, and other motor-related cortical areas over the course of days. We also briefly review neurophysiological and psychophysical evidence for the consolidation of motor skills, and we propose a working hypothesis of its underlying neural substrate in motor sequence learning. (C) 2002 Elsevier Science (USA). C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. Univ Haifa, Fac Sci, IL-31999 Haifa, Israel. Univ Haifa, Fac Educ, IL-31999 Haifa, Israel. RP Ungerleider, LG (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr,Bldg 10,Room 4C104, Bethesda, MD 20892 USA. NR 36 TC 291 Z9 296 U1 2 U2 36 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD NOV PY 2002 VL 78 IS 3 BP 553 EP 564 DI 10.1006/nlme.2002.4091 PG 12 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 620HL UT WOS:000179527900007 PM 12559834 ER PT J AU Schmidt, PJ Raju, J Danaceau, M Murphy, DL Berlin, RE AF Schmidt, PJ Raju, J Danaceau, M Murphy, DL Berlin, RE TI The effects of gender and gonadal steroids on the neuroendocrine and temperature response to m-chlorophenylpiperazine in leuprolide-induced hypogonadism in women and men SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE estradiol; progesterone; testosterone; serotonin; prolactin; humans ID MESSENGER-RNA EXPRESSION; MENSTRUAL-CYCLE PHASE; FEMALE RAT-BRAIN; POSTMENOPAUSAL WOMEN; PROLACTIN SECRETION; PREMENSTRUAL-SYNDROME; BEHAVIORAL-RESPONSES; PROGESTIN RECEPTORS; HEALTHY-VOLUNTEERS; PLASMA TRYPTOPHAN AB Studies of the effects of gender and gonadal steroids on serotonergic activity in humans are few in number and often contradictory. We examined the neuroendocrine anti core temperature response to a serotonergic stimulus, m-chlorophenylpiperazine (m-CPP) (0.08 mg/kg body weight, IV), in asymptomatic female and male volunteers during induced hypogonadism (leuprolide acetate) and hormone replacement (estradiol (E2) or progesterone (P4) in women; testosterone (T) in men). Compared with the hypogonadal state, basal prolactin (PRL) secretion was significantly higher during both P4 and E2 replacement (p <.05) in women and during T replacement in men (p <.05). m-CPP stimulated PRL secretion was significantly greater only during P4 (p <.05) but not E2 (women) or T (men) replacement, compared with hypogonadism. Basal but not stimulated plasma growth hormone (GH) levels were significantly higher during P4 in women and T in men (p <.05), and no significant differences in basal or m-CPP stimulated plasma levels of ACTH or cortisol were observed. Finally, basal core temperatures were significantly higher during P4 replacement compared with either E2 replacement or the hypogonadal condition (p <.01) in women, with no differences observed in men. Comparisons of measures by gender (and matched for baseline plasma T levels) revealed that during the hypogonadal state m-CPP-stimulated GH secretion was significantly greater (p <.01) and m-CPP-stimulated ACTH (p <.05) and cortisol (P <.01) significantly less in wonzen compared with men. Although our data arc limited to those components of the central serotonergic system influenced by m-CPP administration, our findings suggest the following: the regulatory effects of gonadal steroids on serotonergic function are modest in humans during leuprolide-induced hypogonadism; menstrual cycle phase effects of serotonergic agents on PRL secretion may reflect both the effects of P4 and E2; the effects of P4 in humans may occur without E2 priming of the progesterone receptor; and gender differences in GH secretion occur independent of the presence of gonadal steroids. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NIMH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3N238,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. EM Peter.Schmidt@NIH.GOV NR 62 TC 8 Z9 8 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2002 VL 27 IS 5 BP 800 EP 812 AR PII S0893-133X(02)00334-2 DI 10.1016/S0893-133X(02)00334-2 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 604DG UT WOS:000178600100011 PM 12431854 ER PT J AU Atkinson, AJ Sjoqvist, F AF Atkinson, AJ Sjoqvist, F TI Bo Holmstedt, 1919-2002 - In memoriam SO NEUROPSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Karolinska Inst, S-10401 Stockholm, Sweden. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2002 VL 27 IS 5 BP 884 EP 885 AR PII S0893-133X(02)00401-3 DI 10.1016/S0893-133X(02)00401-3 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 604DG UT WOS:000178600100023 ER PT J AU Jett, DA Beckles, RA Navoa, RV McLemore, GL AF Jett, DA Beckles, RA Navoa, RV McLemore, GL TI Increased high-affinity nicotinic receptor-binding in rats exposed to lead during development SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE nicotinic receptor; epibatidine; lead (Pb); brain; neurodevelopment ID METHYL-D-ASPARTATE; ACETYLCHOLINE-RECEPTORS; CHOLINERGIC RECEPTORS; HIPPOCAMPAL-NEURONS; MUSCARINIC RECEPTORS; BRAIN; CELLS; SYNAPTOSOMES; MODULATION; RELEASE AB Receptor autoradiography and membrane radioligand-binding assays were used to determine the expression of nicotinic cholinergic receptors in the brains of weanling rats exposed to low-levels of lead (Pb) during development. Nicotinic receptors were identified with the frog toxin epibatidine (EB) that binds with high affinity to a variety of receptors containing alpha and beta subunits. Rat pups were exposed to Pb from their mothers given 750-ppm Pb in the diet beginning on gestational day 0 through postnatal day (PN)21. Blood Pb levels ranged from 36.5 to 46.5 mug/dl in the PN21 pups, and this exposure did not alter their body weight when compared to control rats. Several brain regions identified by autoradiographic studies as having significant binding of EB were dissected from control and Pb-treated pups and used in saturation-binding experiments with membrane preparations to determine the affinity constant (K-d) and maximal-binding capacity (B-max) of [H-3]EB. Results indicate that the B-max of [H-3]EB was increased in several brain regions in Pb-treated rat pups, without a significant effect on K-d estimates. [H-3]EB-binding to membranes from untreated rats was not affected by in vitro exposure to 20-muM Pb, indicating that the effect of Ph on [H-3]EB-binding in vivo was not likely due to direct influence of free Ph remaining in the tissue at the time of assay. The data therefore suggest that expression of nicotinic receptors that bind [H-3]EB were increased by developmental exposure to Pb. Several possible mechanisms for these effects and the potential toxicological significance are discussed. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Morgan State Univ, Baltimore, MD 21251 USA. RP Jett, DA (reprint author), NINDS, NIH, 6001 Execut Blvd,NSC,Suite 2149,MSC 9535, Bethesda, MD 20892 USA. NR 42 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 2002 VL 24 IS 6 BP 805 EP 811 AR PII S0892-0362(02)00314-8 DI 10.1016/S0892-0362(02)00314-8 PG 7 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 630CJ UT WOS:000180089700012 PM 12460663 ER PT J AU Basser, PJ Jones, DK AF Basser, PJ Jones, DK TI Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review SO NMR IN BIOMEDICINE LA English DT Review DE diffusion; tensor; MRI; methods ID ECHO-PLANAR IMAGES; ANISOTROPIC WATER DIFFUSION; CURRENT-INDUCED ARTIFACTS; EDDY-CURRENT ARTIFACTS; HUMAN BRAIN; WEIGHTED MRI; SPIN-ECHO; SELF-DIFFUSION; NERVOUS-SYSTEM; B-MATRIX AB This article treats the theoretical underpinnings of diffusion-tensor magnetic resonance imaging (DT-MRI), as well as experimental design and data analysis issues. We review the mathematical model underlying DT-MRI, discuss the quantitative parameters that are derived from the measured effective diffusion tensor, and describe artifacts thet arise in typical DT-MRI acquisitions. We also discuss difficulties in identifying appropriate models to describe water diffusion in heterogeneous tissues, as well as in interpreting experimental data obtained in such issues. Finally, we describe new statistical methods that have been developed to analyse DT-MRI data, and their potential uses in clinical and multi-site studies. Copyright (C) 2002 John Wiley Sons, Ltd. C1 NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. Inst Psychiat, Sect Old Psychiat, London, England. RP Basser, PJ (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RI Jones, Derek/D-1460-2009; Basser, Peter/H-5477-2011; OI Jones, Derek/0000-0003-4409-8049 NR 107 TC 714 Z9 734 U1 10 U2 102 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD NOV-DEC PY 2002 VL 15 IS 7-8 BP 456 EP 467 DI 10.1002/nbm.783 PG 12 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 631KC UT WOS:000180166100003 PM 12489095 ER PT J AU Eckelman, WC AF Eckelman, WC TI Accelerating drug discovery and development through in vivo imaging SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Review DE receptor; fluorine-18; drug; knockout mice ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; RAT-BRAIN; COMPUTED-TOMOGRAPHY; BINDING; M2; INVIVO; COMPETITION; SUBTYPES; DEMENTIA; SPECT C1 NIH, Bethesda, MD 20892 USA. RP Eckelman, WC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 30 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 2002 VL 29 IS 8 BP 777 EP 782 AR PII S0969-8051(02)00345-1 DI 10.1016/S0969-8051(02)00345-1 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 621AB UT WOS:000179565400001 PM 12453585 ER PT J AU Kim, I Kobayashi, H Yoo, TM Kim, MK Le, N Han, ES Wang, QC Pastan, I Carrasquillo, JA Paik, CH AF Kim, I Kobayashi, H Yoo, TM Kim, MK Le, N Han, ES Wang, QC Pastan, I Carrasquillo, JA Paik, CH TI Lowering of pI by acylation improves the renal uptake of Tc-99m-labeled anti-Tac dsFv: effect of different acylating reagents SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Tc-99m-MAG3-dsFv; isoelectric point; enhanced renal clearance ID SINGLE-CHAIN-FV; MONOCLONAL-ANTIBODY; AMINO-ACIDS; FRAGMENT; BIODISTRIBUTION; TC-99M; BINDING; SELECTIVITY; CATABOLISM; IN-111 AB Anti-Tac disulfide-stabilized variable region fragment (dsFv) was labeled with Tc-99m by a preformed chelate approach using Tc-99m-MAG3-trifluorophenyl (TFP) ester. Simultaneously it was acylated with TFP-lactate or succinic anhydride to decrease the isoelectric point of dsFv (pI 10). Acylation of dsFv (0.04 mM) with the lactate at a 73 times molar excess reduced the pI to 5.0-6.7, whereas acylation with succinic anhydride at a 30 times molar excess reduced the pI to 4.9-8.7. Comparative biodistribution studies performed in mice (n = 5) showed the reduced renal accumulation of the Tc-99m proportional to the pI reduction. The effect of the pI on the reduced renal uptake was especially pronounced at 15 min postinjection. The reduced renal uptake was also reflected in the reduced whole-body retention, indicating that lowering the pI inhibited the tubular reabsorption of the labeled dsFv. Published by Elsevier Science Inc. All rights reserved. C1 NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Paik, CH (reprint author), NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 39 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 2002 VL 29 IS 8 BP 795 EP 801 AR PII S0969-8051(02)00341-4 DI 10.1016/S0969-8051(02)00341-4 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 621AB UT WOS:000179565400004 PM 12453588 ER PT J AU Primack, A AF Primack, A TI Future of obesity and disease management in health care: The government perspective SO OBESITY RESEARCH LA English DT Article; Proceedings Paper CT Task Force on Developing Obesity Outcomes and Learning Standards Symposium (TOOLS) CY JUN 11-13, 1999 CL WARRENTON, VIRGINIA C1 Fogarty Int Ctr, NIH, Hlth Care Financing Adm, Ctr Medicare, Bethesda, MD 20892 USA. Fogarty Int Ctr, NIH, Hlth Care Financing Adm, Ctr Medicaid, Bethesda, MD 20892 USA. RP Primack, A (reprint author), Fogarty Int Ctr, NIH, Hlth Care Financing Adm, Ctr Medicare, Bldg 31,Rm B2C39,31 Ctr Dr, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD NOV PY 2002 VL 10 SU 1 BP 82S EP 83S DI 10.1038/oby.2002.196 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 619DX UT WOS:000179460000016 PM 12446865 ER PT J AU Bada, HS Das, A Bauer, CR Shankaran, S Lester, B Wright, LL Verter, J Smeriglio, VL Finnegan, LP Maza, PL AF Bada, HS Das, A Bauer, CR Shankaran, S Lester, B Wright, LL Verter, J Smeriglio, VL Finnegan, LP Maza, PL TI Gestational cocaine exposure and intrauterine growth: Maternal lifestyle study SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FETAL GROWTH; PRENATAL COCAINE; BIRTH-WEIGHT; ALCOHOL-USE; DRUG-USE; RETARDATION; PREGNANCY; INFANTS; CARE; ASSOCIATION AB OBJECTIVE: To estimate the effects of cocaine exposure on intrauterine growth and to investigate at what point in gestation growth deviation would be manifested. METHODS: This is a secondary analysis of data from a multicenter project, the Maternal Lifestyle Study, designed to determine infant outcomes of in utero cocaine or opiates exposure. Four centers of the National Institute of Child Health and Human Development Neonatal Research Network enrolled 11,811 maternal-infant dyads. A total of 1072 infants were cocaine exposed, 7565 were cocaine negative by maternal history and meconium results, and 3174 were excluded from analysis because of unconfirmed negative exposure. Outcome measures included birth weight, length, and head circumference. RESULTS: Percentile estimates for birth weight, length, and head circumference revealed growth deceleration in cocaine-exposed infants evident after 32 weeks' gestation. There was significant interaction between cocaine and gestational age. After controlling for confounders, at 40 weeks' gestation, cocaine exposure was estimated to be associated with a decrease of 151 g, 0.71 cm, and 0.43 cm in birth weight, length, and head circumference, respectively. Smoking had a negative impact on all growth measurements, with some indication of a dose-effect relationship. Heavy alcohol use was associated with decrease in weight and length only. Opiates had significant effect only on birth weight. CONCLUSION: In utero cocaine exposure is associated with growth deceleration involving all measurements, becoming more pronounced with advancing gestation. (C) 2002 by The American College of Obstetricians and Gynecologists. C1 Univ Kentucky, Albert B Chandler Med Ctr, Dept Pediat, Lexington, KY 40536 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ Miami, Miami, FL 33152 USA. Wayne State Univ, Detroit, MI USA. Brown Univ, Providence, RI 02912 USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. Natl Inst Drug Abuse, Bethesda, MD USA. Ctr Subst Abuse Treatment, Rockville, MD USA. Adm Children Youth & Families, Washington, DC USA. RP Bada, HS (reprint author), Univ Kentucky, Albert B Chandler Med Ctr, Dept Pediat, Room MS-473,800 Rose St, Lexington, KY 40536 USA. FU NICHD NIH HHS [U10HD27856, U10HD21397, U10HD21385, U01HD36790, U10HD27904, U01HD19897] NR 40 TC 46 Z9 48 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2002 VL 100 IS 5 BP 916 EP 924 AR PII S0029-7844(02)02199-3 DI 10.1016/S0029-7844(02)02199-3 PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 610XC UT WOS:000178986400016 PM 12423853 ER PT J AU Morrissey, K Idriss, N Nieman, L Winkel, C Stratton, P AF Morrissey, K Idriss, N Nieman, L Winkel, C Stratton, P TI Dysmenorrhea after bilateral tubal ligation: A case of retrograde menstruation SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID STERILIZATION; ENDOMETRIOSIS AB BACKGROUND: Endometriosis, arising de novo, is believed to be uncommon in women who have undergone bilateral tubal ligation because the occluded tube prevents outflow of blood and menses. CASE: A woman 10-year status-post bilateral tubal ligation suffered from dysmenorrhea and menorrhagia that began within 1 year after sterilization. At the time of bilateral tubal ligation, no endometriosis was observed. A recent magnetic resonance imaging scan showed no pelvic abnormalities, and the patient underwent a diagnostic laparoscopy in anticipation of finding endometriosis, yet none was found. At laparoscopy performed on day 3 of her menstrual cycle, the proximal segments of her occluded fallopian tubes were dilated with blood. As this was the only abnormality found, we postulated that her dysmenorrhea might be related to the dilated proximal tubal stumps. We evacuated the bloody fluid and occluded die proximal tube at the cornua with Filshie dips. One year after surgery, the patient remains asymptomatic. CONCLUSION: This case is unique because bilateral tubal ligation combined with retrograde menstrual flow appears to have caused dysmenorrhea. Women who have undergone tubal ligation and who have dysmenorrhea may benefit from a diagnostic laparoscopy during menstruation to evaluate the possibility of retrograde menstruation dilating the proximal tubal stumps. (C) 2002 by The American College of Obstetricians and Gynecologists. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Gynecol Consult Serv, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Stratton, P (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, Gynecol Consult Serv, 10 Ctr Dr,MSC 1583,Bldg 10,Room 9D42, Bethesda, MD 20892 USA. NR 8 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2002 VL 100 IS 5 SU S BP 1065 EP 1067 AR PII S0029-7844(02)01991-9 DI 10.1016/S0029-7844(02)01991-9 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 612FV UT WOS:000179064600003 PM 12423806 ER PT J AU Trimble, EL Schoenfeldt, M Cornelison, TL Wright, J Kolker, A Christian, M AF Trimble, EL Schoenfeldt, M Cornelison, TL Wright, J Kolker, A Christian, M TI Referral resource SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. Ovarian Canc Natl Alliance, Washington, DC USA. RP Trimble, EL (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2002 VL 16 IS 11 BP 1498 EP + PG 13 WC Oncology SC Oncology GA 620VR UT WOS:000179553800015 PM 12469928 ER PT J AU Dias, L Manny, RE Hyman, L Fern, K AF Dias, L Manny, RE Hyman, L Fern, K CA COMET Grp TI The relationship between self-esteem of myopic children and ocular and demographic characteristics SO OPTOMETRY AND VISION SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol DE myopia; children; self-esteem; clinical trials; visual symptoms ID PERCEPTION PROFILE; GENDER DIFFERENCES; NHLBI GROWTH; HEALTH; AGE; DEPRESSION; COMPETENCE; COHORT; GIRLS AB Purpose. To evaluate self-esteem and its relationship with various ocular and demographic characteristics in 469 myopic children participating in the Correction of Myopia Evaluation Trial (COMET), an ongoing, randomized, multicenter clinical trial designed to evaluate the effects of progressive addition lenses vs. single vision lenses on the progression of juvenile-onset myopia. Methods. Baseline data collection included demographic information, refractive error measurements, parent-reported myopia history, child-reported visual symptoms, and self-esteem in several areas (scholastic/athletic competence, physical appearance, social acceptance, behavioral conduct, and global self-worth) as measured by the Self-Perception Profile for Children. Univariate and multiple regression analyses were used to identify factors associated with self-esteem. Results. The Self-Perception Profile for Children is a reliable measure of self-esteem in COMET children as indicated by the high internal consistency reliabilities (0.74 to 0.81) obtained for the various domains. COMET children's mean self-esteem scores ranged from 2.72 +/- 0.69 for athletic competence to 3.36 +/- 0.56 for global self-worth and were similar to normative samples. Multiple regression analyses showed that less symptomatic children had higher self-esteem in all areas (p < 0.05), except athletic competence, after adjusting for other ocular and demographic characteristics. Self-esteem also varied significantly by age, gender, and ethnicity (p < 0.05). Conclusions. Baseline self-esteem is associated with visual symptoms, age, gender, and ethnicity, but not with magnitude of refractive error. Follow-up reports will assess whether there are changes in self-esteem associated with myopia progression and lens assignment. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Alabama, Sch Optometry, Birmingham, AL 35294 USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. New England Coll Optometry, Boston, MA USA. Univ Houston, Coll Optometry, Houston, TX USA. RP Dias, L (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Dept Prevent Med, HSC L-3,Room 086, Stony Brook, NY 11794 USA. FU NEI NIH HHS [EY11754, EY11805, EY11756, U10 EY011805, EY11752, EY11740, EY11755] NR 35 TC 9 Z9 9 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD NOV PY 2002 VL 79 IS 11 BP 688 EP 696 DI 10.1097/00006324-200211000-00006 PG 9 WC Ophthalmology SC Ophthalmology GA 618AF UT WOS:000179394000003 PM 12462537 ER PT J AU Sankar, V Baccaglini, L Sawdey, M Wheeler, CJ Pillemer, SR Baum, BJ Atkinson, JC AF Sankar, V Baccaglini, L Sawdey, M Wheeler, CJ Pillemer, SR Baum, BJ Atkinson, JC TI Salivary gland delivery of pDNA-cationic lipoplexes elicits systemic immune responses SO ORAL DISEASES LA English DT Article DE plasmid DNA; cationic liposomes; gene transfer; vaccination; salivary ID MEDIATED GENE-TRANSFER; DNA VACCINE; IN-VIVO; IMMUNIZATION; INJECTION; MUCOSAL; PROTECTION; SECRETION; INFLUENZA; COMPLEXES AB OBJECTIVE: To test the ability of two cationic lipoplexes, Vaxfectin and GAP-DLRIE/DOPE, to facilitate transfection and elicit immune responses from plasmid DNAs (pDNAs) after retrograde instillation into salivary glands. METHODS: Two pDNA expression vectors encoding either the influenza NP protein or human growth hormone (hGH) were complexed with the cationic lipid transfection reagents, GAP-DLRIE/DOPE or Vaxfectin, and delivered to the submandibular glands of rats. Samples from rats receiving the influenza NP protein pDNA and cationic lipoplexes were analyzed for anti-influenza NP-specific IgG1, IgG2a, and IgG2b in serum, and IgA in saliva, by an enzyme-linked immunosorbent assay (ELISA). Cytotoxic T-cell lymphocyte (CTL) assays were also performed. Transgene protein expression (hGH) was determined from extracts of submandibular glands of rats receiving hGH lipoplexes. RESULTS: Serum antibodies (IgG) against the NP protein developed and were highest in all rats vaccinated with GAP-DLRIE/DOPE or Vaxfectin. The major serum IgG subclass stimulated by this route of immunization was IgG2b, followed by IgG2a. CTL assay results showed statistically significantly higher percentage killing in the Vaxfectin group than controls (P < 0.05). No rats developed IgA antibodies to NP protein in saliva. Animals receiving plasmid encoding hGH and either lipoplex expressed significantly higher amounts of hGH compared with those receiving the hGH plasmid and water. Although hGH expression was higher in the animals receiving pDNA/Vaxfectin (&SIM;30- fold > pDNA/water), the difference with those receiving pDNA/GAP-DLRIE/DOPE (similar to10-fold > pDNA/water) was not significant. CONCLUSIONS: Retrograde instillation of pDNA complexed with Vaxfectin into the salivary glands can stimulate cytotoxic and humoral responses to the influenza NP protein antigen. Optimization of the conditions required to stimulate humoral and secretory antibody formation may facilitate use of this tissue for specific clinical applications of pDNA immunization. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. Vical Inc, Dept Cell Biol, San Diego, CA USA. Vical Inc, Dept Chem, San Diego, CA USA. Univ Maryland, Off Clin Affairs, Baltimore, MD 21201 USA. RP Sankar, V (reprint author), NIDCR, GTTB, NIH, Bldg 10,Room 1N-113,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. NR 23 TC 12 Z9 13 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1354-523X J9 ORAL DIS JI Oral Dis. PD NOV PY 2002 VL 8 IS 6 BP 275 EP 281 DI 10.1034/j.1601-0825.2002.02856.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 615JB UT WOS:000179241100001 PM 12477057 ER PT J AU Akintoye, SO Brennan, MT Graber, CJ McKinney, BE Rams, TE Barrett, AJ Atkinson, JC AF Akintoye, SO Brennan, MT Graber, CJ McKinney, BE Rams, TE Barrett, AJ Atkinson, JC TI A retrospective investigation of advanced periodontal disease as a risk factor for septicemia in hematopoietic stem cell and bone marrow transplant recipients SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Association-of-Dental-Research CY MAR 08-10, 2001 CL CHICAGO, ILLINOIS SP Amer Assoc Dent Res ID BACTEREMIA; BACT/ALERT; CHEMOTHERAPY; LEUKEMIA; SYSTEM; CAPNOCYTOPHAGA; ASSOCIATION; RECOVERY; PATIENT; CANCER AB Objective. Septicemia is a cause of death in hematopoietic stem cell transplant (HSCT) recipients. Extraction of teeth with advanced periodontitis has been advocated before HSCT to prevent septicemia in myeloablated hosts. The primary aim of the present study was to determine impact of chronic periodontitis, as measured by radiographic alveolar bone loss, on septicemia and transplant mortality. Study design. A retrospective design was used to study 77 subjects who received pretransplant dental evaluation, panoramic radiography, and full myeloablative allogeneic HSCT to treat hematologic malignancies. Radiographic crestal alveolar bone loss was measured with a Schei ruler on all teeth. Microorganisms isolated from positive blood cultures within the first 100 days after transplant were categorized as of likely origin from periodontal, oral, or any body sites. Spearman correlation and logistic regression analysis assessed associations between positive blood cultures, mean subject whole-mouth percent radiographic crestal alveolar bone loss, and 100-day survival. Results. Radiographic crestal alveolar bone loss per study subject averaged 13% +/- 7%, with 18.2% exhibiting bone loss of 20% or greater. During the initial 100 days after transplant, 63.6% subjects yielded septicemia-associated positive blood cultures, with Staphylococcus epidermidis, Streptococcus mitis, Enterococcus faecalis, Streptococcus sanguis, Staphylococcus aureus, and Escherichia coli as the most common isolates recovered. No statistically significant associations were found between mean subject radiographic alveolar bone loss and septicemia of likely periodontal or oral origin. Conclusions. In this preliminary study, no relationship was found between radiographic periodontal status and septicemia or mortality within the initial 100 days after transplant. A larger-sized, prospective study is warranted to further delineate the risk of septicemia from periodontal and other oral diseases in immunocompromised patients. C1 NIDCR, Clin Res Core, DIR, NIH, Bethesda, MD 20892 USA. Carolinas Med Ctr, Charlotte, NC USA. Univ Washington, Dept Med, Seattle, WA USA. Temple Univ, Sch Dent, Dept Periodontol, Philadelphia, PA USA. Temple Univ, Sch Dent, Oral Microbiol Testing Serv Lab, Philadelphia, PA USA. NR 36 TC 22 Z9 25 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD NOV PY 2002 VL 94 IS 5 BP 581 EP 588 DI 10.1067/moe.2002.128960 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 613XT UT WOS:000179157400013 PM 12424452 ER PT J AU Grigolo, B Roseti, L Neri, S Gobbi, P Jensen, P Major, EO Facchini, A AF Grigolo, B Roseti, L Neri, S Gobbi, P Jensen, P Major, EO Facchini, A TI Human articular chondrocytes immortalized by HPV-16 E6 and E7 genes: Maintenance of differentiated phenotype under defined culture conditions SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE human chondrocytes; immortalization; HPV-16 E6-E7; collagen II ID HUMAN-PAPILLOMAVIRUS TYPE-16; EXPRESSION; CELL; CARTILAGE; KERATINOCYTES; COLLAGEN; INVITRO; TRANSFORMATION; FIBROBLASTS; PROLIFERATION AB Objective: To establish an immortalized normal human articular chondrocyte line which could be useful for a better understanding of cell molecular mechanisms relevant for the development of new therapeutic approaches in rheumatic diseases. Design: Chondrocytes from human adult articular healthy cartilage were transfected in primary culture with a plasmid containing two human papilloma virus type 16 (HPV-16) early function genes: E6 and E7, using the highly efficient cationic liposome-mediated (lipofection) procedure. The transfection was verified by reverse transcriptase-polymerase chain reaction analysis of E7 mRNA and by immunofluorence localization of the E7 protein in the cell cytoplasm. The established chondrocyte cell line was examined in monolayer and in two culture conditions that were described to re-induce differentiated characteristics: culturing in a serum-free defined medium supplemented with an insulin-containing serum substitute and seeding on a hyaluronan-based non-woven structured biomaterial. The expression of markers characteristic of cartilage was shown in the mRNA by reverse transcriptase-polymerase chain reaction. Immunohistological staining and Western blotting analysis were performed to evaluate type II collagen synthesis. Proteoglycans deposition was detected by Alcian Blue staining. A Field Emission In Lens Scanning Microscopy was used to look at the morphology of the immortalized cells at very high magnification. Results: Normal human articular chondrocytes were efficiently transfected leading to the establishment of an immortalized cell line as confirmed by HPV-16 E7 mRNA and protein detection. These cells were able to re-express type II collagen both at mRNA and protein levels under the two defined cultured conditions we used, still maintaining type I collagen expression. Collagen IX mRNA was present only in early primary culture while collagen type X and aggrecan transcripts were always detected. Alcian Blue staining showed a proteoglycan-rich matrix production. The ultrastructural analysis of the immortalized cells revealed that their morphology strictly resembled that of normal chondrocytes. Conclusions:The cell line that we obtained may be a useful tool for increasing our knowledge of the genetic and biochemical events involved in the processes of cartilage growth and differentiation. Moreover, it appears to be a suitable model for pharmacological and toxicological studies related to rheumatic diseases relevant to humans. (C) 2002 OsteoArthritis Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 IOR, Lab Immunol & Genet, Ist Ricerca Codivilla Putti, I-40136 Bologna, Italy. Univ Bologna, Dipartimento Sci Anat Umane & Fisiopatol Apparto, I-40126 Bologna, Italy. NIH, NINDS, Lab Mol Med & Neurosci, Bethesda, MD USA. Univ Bologna, Dipartimento Med Interna & Gastroenterol, I-40139 Bologna, Italy. RP Facchini, A (reprint author), IOR, Lab Immunol & Genet, Ist Ricerca Codivilla Putti, Via Barbiano 1-10, I-40136 Bologna, Italy. EM labimge@alma.unibo.it RI Gobbi, Pietro/J-2566-2012; Grigolo, Brunella/J-5417-2016 OI Gobbi, Pietro/0000-0003-4705-0833; Grigolo, Brunella/0000-0002-3990-6745 NR 45 TC 30 Z9 32 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD NOV PY 2002 VL 10 IS 11 BP 879 EP 889 DI 10.1053/joca.2002.0836 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 620QH UT WOS:000179543700009 PM 12435333 ER PT J AU Scher, AI Petterson, B Blair, E Ellenberg, JH Grether, JK Haan, E Reddihough, DS Yeargin-Allsopp, M Nelson, KB AF Scher, AI Petterson, B Blair, E Ellenberg, JH Grether, JK Haan, E Reddihough, DS Yeargin-Allsopp, M Nelson, KB TI The risk of mortality or cerebral palsy in twins: A collaborative population-based study SO PEDIATRIC RESEARCH LA English DT Article ID LINKING VITAL RECORDS; GESTATIONAL-AGE; CHANGING PATTERN; MULTIPLE BIRTHS; UNITED-STATES; REPRODUCTIVE HISTORIES; PERINATAL-MORTALITY; INFANT-MORTALITY; EASTERN DENMARK; FOLLOW-UP AB The purpose of the paper was to describe demographic and clinical factors associated with fetal or neonatal death or cerebral palsy (CP) in twins. Vital statistics from five populations in the United States and Australia, which included information on CP diagnosed after 1 y of age. Information on zygosity was not available. In 1,141,351 births, 25,772 of whom were twins, significant secular trends from 1980 to 1989 included increasing prevalence of twins, increasing proportion of unlike-sex twins, and increasing maternal age. Overall, twins were at an approximately 5-fold increased risk of fetal death, 7-fold increased risk of neonatal death, and 4-fold increased risk of CP compared with singletons. However, at birth weight <2500 g, twins generally did better than singletons, both with respect to mortality and to CP rates. Second-born twins and twins from same-sex pairs were at increased risk of early death but not of CP. Twins from growth-discordant pairs and twins whose co-twin died were at increased risk of both mortality and CP. The highest rates of CP were in surviving twins whose co-twin was still-born (4.7%), died shortly after birth (6.3%) or had CP (11.8%). In this large data set spanning a 10-y period, overall rates of death or cerebral palsy were higher in twins than singletons, although small twins generally did better than small singletons. Co-twin death was a strong predictor of CP in surviving twins. This risk was the same for same- and different-sex pairs, and observed both for preterm and term infants. C1 NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. Child Hlth Res, Subiaco, WA, Australia. Univ Western Australia, Dept Anat & Human Biol, Nedlands, WA 6009, Australia. Inst Child Hlth Res, Nedlands, WA, Australia. WESTAT Corp, Rockville, MD 20850 USA. Calif Birth Defects Monitoring Program, Emeryville, CA USA. Womens & Childrens Hosp, S Australian Cerebral Palsy Register, Adelaide, SA, Australia. Royal Childrens Hosp, Melbourne, Vic, Australia. Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. RP Scher, AI (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Suite 3C-309,MSC 9205, Bethesda, MD 20892 USA. NR 58 TC 111 Z9 116 U1 0 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2002 VL 52 IS 5 BP 671 EP 681 DI 10.1203/01.PDR.0000032159.88318.5B PG 11 WC Pediatrics SC Pediatrics GA 610TP UT WOS:000178977200010 PM 12409512 ER PT J AU Kimm, SYS Obarzanek, E AF Kimm, SYS Obarzanek, E TI Childhood obesity: A new pandemic of the new millennium SO PEDIATRICS LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; ENERGY-EXPENDITURE; NHLBI GROWTH; NATIONAL-HEALTH; US CHILDREN; WHITE GIRLS; ADOLESCENTS; OVERWEIGHT; CHOLESTEROL; RACE C1 Univ Pittsburgh, Sch Med, Dept Family Med, Pittsburgh, PA 15261 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Kimm, SYS (reprint author), Univ Pittsburgh, Sch Med, Dept Family Med, 3518 5th Ave, Pittsburgh, PA 15261 USA. RI Loureiro, Nuno/I-6400-2012 OI Loureiro, Nuno/0000-0002-1166-3219 NR 47 TC 129 Z9 136 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2002 VL 110 IS 5 BP 1003 EP 1007 DI 10.1542/peds.110.5.1003 PG 5 WC Pediatrics SC Pediatrics GA 610QK UT WOS:000178971800037 PM 12415042 ER PT J AU MacDonald, H AF MacDonald, H CA Comm Fetus Newborn TI Perinatal care at the threshold of viability SO PEDIATRICS LA English DT Article ID LOW-BIRTH-WEIGHT; CESAREAN DELIVERY; INFANTS; SURVIVAL; OUTCOMES; CHILDREN; AGE; MORBIDITY; SECTION AB In the United States, an increase in the number of births of extremely preterm infants and in their survival potential has occurred over the last decade. Determining the survival prognosis for the infant of a pregnancy with threatened preterm delivery between 22 and 25 completed weeks of gestation remains problematic. Many physicians and families encounter the difficulty of making decisions regarding the institution and continuation of life support for an infant born within this threshold period. This report addresses the process of counseling, assisting, and supporting families faced with the dilemma of an extremely preterm delivery. C1 Amer Acad Pediat, Comm Fetus & Newborn, Elk Grove Village, IL 60007 USA. Amer Nurses Assoc, Washington, DC 20024 USA. Assoc Womens Hlth Obstet & Neonatal Nurses, Washington, DC 20036 USA. Natl Assoc Neonatal Nurses, Glenview, IL 60025 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20090 USA. NICHHD, Bethesda, MD 20892 USA. RP MacDonald, H (reprint author), Amer Acad Pediat, Comm Fetus & Newborn, Elk Grove Village, IL 60007 USA. NR 26 TC 147 Z9 152 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2002 VL 110 IS 5 BP 1024 EP 1027 DI 10.1542/peds.110.5.1024 PG 4 WC Pediatrics SC Pediatrics GA 610QK UT WOS:000178971800042 PM 12415047 ER PT J AU Newman, TB Klebanoff, M AF Newman, TB Klebanoff, M TI 33 272 infants, 7-year follow-up: Total serum bilirubin, transfusions reexamined SO PEDIATRICS LA English DT Letter C1 Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Newman, TB (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2002 VL 110 IS 5 BP 1032 EP 1032 DI 10.1542/peds.110.5.1032 PG 1 WC Pediatrics SC Pediatrics GA 610QK UT WOS:000178971800051 PM 12415054 ER PT J AU Kimm, SYS Barton, BA Obarzanek, E McMahon, RP Kronsberg, SS Waclawiw, MA Morrison, JA Schreiber, GB Sabry, ZI Daniels, SR AF Kimm, SYS Barton, BA Obarzanek, E McMahon, RP Kronsberg, SS Waclawiw, MA Morrison, JA Schreiber, GB Sabry, ZI Daniels, SR TI Obesity development during adolescence in a biracial cohort: The NHLBI growth and health study SO PEDIATRICS LA English DT Article DE race; adolescence; body mass index; obesity; overweight; prevalence rates; females ID NUTRITION EXAMINATION SURVEYS; BLOOD-INSTITUTE GROWTH; OVERWEIGHT PREVALENCE; NATIONAL-HEALTH; TRENDS; GIRLS; BLACK; HEART; MATURATION; ADULTS AB Objective. The National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) is a 10-year study to investigate the development of obesity in black and white girls during adolescence and its environmental and psychosocial correlates. The purpose of this report was to examine changes in the annual prevalence rates of overweight and obesity in the NGHS cohort from ages 9 to 19 years. Participants and Setting. A total of 2379 black and white girls, aged 9 to 10 years, were recruited from schools in Richmond, California, and Cincinnati, Ohio, and from families enrolled in a health maintenance organization in the Washington, DC area. Participant eligibility was limited to girls and their parents who declared themselves as being either black or white and who lived in racially concordant households. Design and Statistical Analysis. The NGHS is a multicenter prospective study of a biracial cohort followed annually from ages 9 to 10 years through 18 to 19 years. The prevalence of overweight and obesity was based on age-specific greater than or equal to85th and greater than or equal to95th percentile values, respectively, for body mass index based on the 1960-1965 National Health Examination Survey reference population. Main Outcome Measures. The main outcome measures were body mass index (weight in kilograms divided by height in meters, squared) and proportions of girls who were "overweight" and "obese" by age and race. Results. The prevalence of overweight was 37% higher in blacks as compared with whites (30.6% vs 22.4%) even by age 9. The rate of overweight almost doubled in both groups during the 10-year period. By age 19, the rate of overweight was 56.9% in black and 41.3%, in white girls. The prevalence of obesity was 17.7% in black and 7.7% in white girls at 9 years old, and the rates also doubled during the study period. Conclusions. The doubling in the prevalence of overweight and obesity during adolescence in black and white NGHS girls was surprising. By age 19, more than half of black girls were overweight and more than one third were obese. Almost half of white girls were overweight and almost 1 of 5 girls were obese. These findings should sound an alarm for all primary care physicians and public health professionals to take heed of what is happening to our youth. C1 Univ Pittsburgh, Sch Med, Dept Family Med, Pittsburgh, PA 15261 USA. Maryland Med Res Inst, Baltimore, MD USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. Childrens Hosp, Med Ctr, Div Cardiol, Cincinnati, OH 45229 USA. Westat Corp, Rockville, MD USA. Univ Calif Berkeley, Sch Publ Hlth, Dept Nutr, Berkeley, CA 94720 USA. RP Kimm, SYS (reprint author), Univ Pittsburgh, Sch Med, Dept Family Med, 3518 5th Ave, Pittsburgh, PA 15261 USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [N0-HC55023-26, U01-HL48941-44] NR 19 TC 69 Z9 72 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2002 VL 110 IS 5 AR e54 DI 10.1542/peds.110.5.e54 PG 5 WC Pediatrics SC Pediatrics GA 610QK UT WOS:000178971800004 PM 12415060 ER PT J AU O'Grady, NP Alexander, M Dellinger, P Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA AF O'Grady, NP Alexander, M Dellinger, P Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA TI Guidelines for the prevention of intravascular catheter-related infections SO PEDIATRICS LA English DT Review DE catheter-related bloodstream infections; intensive care unit; central venous catheter; peripherally inserted central catheter; guidelines ID CENTRAL VENOUS CATHETER; BLOOD-STREAM INFECTION; INTENSIVE-CARE-UNIT; TOTAL PARENTERAL-NUTRITION; RANDOMIZED CONTROLLED TRIAL; CRITICALLY ILL PATIENTS; PERIPHERAL INTRAVENOUS CATHETERS; RESISTANT STAPHYLOCOCCUS-AUREUS; PULMONARY-ARTERY CATHETERS; IN-LINE FILTRATION AB These guidelines have been developed for practitioners who insert catheters and for persons responsible for surveillance and control of infections in hospital, outpatient, and home health-care settings. This report was prepared by a working group comprising members from professional organizations representing the disciplines of critical care medicine, infectious diseases, health-care infection control, surgery, anesthesiology, interventional radiology, pulmonary medicine, pediatric medicine, and nursing. The working group was led by the Society of Critical Care Medicine (SCCM), in collaboration with the Infectious Disease Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), Surgical Infection Society (SIS), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), American Society of Critical Care Anesthesiologists (ASCCA), Association for Professionals in Infection Control and Epidemiology (APIC), Infusion Nurses Society (INS), Oncology Nursing Society (ONS), Society of Cardiovascular and Interventional Radiology (SCVIR), American Academy of Pediatrics (AAP), and the Healthcare Infection Control Practices Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention (CDC) and is intended to replace the Guideline for Prevention of Intravascular Device-Related Infections published in 1996. These guidelines are intended to provide evidence-based recommendations for preventing catheter-related infections. Major areas of emphasis include 1) educating and training health-care providers who insert and maintain catheters; 2) using maximal sterile barrier precautions during central venous catheter insertion; 3) using a 2% chlorhexidine preparation for skin antisepsis; 4) avoiding routine replacement of central venous catheters as a strategy to prevent infection; and 5) using antiseptic/antibiotic impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (ie, education and training, maximal sterile barrier precautions, and 2% chlorhexidine for skin antisepsis). These guidelines also identify performance indicators that can be used locally by health-care institutions or organizations to monitor their success in implementing these evidence-based recommendations. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Infus Nurses Soc, Cambridge, MA USA. Univ Washington, Seattle, WA 98195 USA. CDC, Off Director, Atlanta, GA 30333 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Wisconsin, Sch Med, Madison, WI USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Rhode Isl Hosp, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Childrens Hosp, Boston, MA 02115 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Rush Med Coll, Chicago, IL 60612 USA. RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, 9000 Rockville Pike,Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. NR 286 TC 143 Z9 150 U1 2 U2 27 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2002 VL 110 IS 5 AR e51 DI 10.1542/peds.110.5.e51 PG 24 WC Pediatrics SC Pediatrics GA 610QK UT WOS:000178971800001 PM 12415057 ER PT J AU Izenwasser, S French, D AF Izenwasser, S French, D TI Tolerance and sensitization to the locomotor-activating effects of cocaine are mediated via independent mechanisms SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; locomotor activity; behavior; chronic treatment ID TIME-DEPENDENT CHANGES; RAT NUCLEUS-ACCUMBENS; DOPAMINE TRANSPORTER; EXTRACELLULAR DOPAMINE; BEHAVIORAL SENSITIZATION; CONTINUOUS-INFUSION; REVERSE TOLERANCE; RECEPTOR FUNCTION; WITHDRAWAL; BRAIN AB Tolerance or sensitization to the locomotor-activating effects of cocaine occurs depending upon the treatment regimen that is used. When cocaine is injected on a daily basis, sensitization occurs, whereas continuously infused cocaine leads to tolerance. Male Sprague-Dawley rats were treated for 7 days with continuous cocaine (50 mg/kg/day) via subcutaneously implanted osmotic minipumps, after which the pumps were removed. Locomotor activity was measured for I h each day. Some rats were challenged with an injection of cocaine (7.5, 15 or 30 mg/kg) either 2 or 9 days after pump removal. Two days after the pumps were removed (Day 10), there were no significant differences between cocaine- or saline-treated rats in the amount of locomotor activity produced by the challenge injections. However, cocaine-treated rats challenged with cocaine 9 days after pumps were removed (Day 17) exhibited significant tolerance, as evidenced by a shift downward of the cocaine curve, as compared to saline controls. When the rats were injected again on the next day (Day 18), the activity levels of both groups increased, as compared to the effects observed on Day 17. Thus, although the cocaine-treated rats were still tolerant compared to the saline-treated rats, they were sensitized compared to their previous response to a challenge injection, These findings indicate that tolerance and sensitization to the locomotor-activating effects of cocaine can exist simultaneously, which suggests that they are mediated by separate mechanisms. (C) 2002 Elsevier Science Inc, All tights reserved. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. NIDA, Psychobiol Sect, Div Intramural Res, Baltimore, MD 21224 USA. RP Izenwasser, S (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci, 1695 NW 9th Ave,Room 3302 D-21, Miami, FL 33136 USA. RI Izenwasser, Sari/G-9193-2012 FU NIDA NIH HHS [DA 11960] NR 26 TC 22 Z9 23 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 2002 VL 73 IS 4 BP 877 EP 882 AR PII S0091-3057(02)00942-5 DI 10.1016/S0091-3057(02)00942-5 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 597CU UT WOS:000178205200018 PM 12213534 ER PT J AU Krieg, RC Messmann, H Rauch, J Seeger, S Knuechel, R AF Krieg, RC Messmann, H Rauch, J Seeger, S Knuechel, R TI Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID DELTA-AMINOLEVULINIC-ACID; HUMAN BLADDER-CARCINOMA; HIGH-GRADE DYSPLASIA; PHOTODYNAMIC THERAPY; IN-VITRO; BARRETTS-ESOPHAGUS; PORPHOBILINOGEN DEAMINASE; PORPHYRIN BIOSYNTHESIS; FLUORESCENCE DETECTION; ADENOCARCINOMA CELLS AB 5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) fluorescence has been shown to have high tumor cell selectivity in various organs, including the gastrointestinal (GI) tract. To better understand and to possibly find new approaches to therapeutic application, we investigated the uptake kinetics and consequent metabolism of ALA and PPIX, respectively. Three colon carcinoma (CaCo2, HT29, SW480) and a stromal cell line (fibroblast, CCD18) were chosen to mimic important aspects of malignant mucosa of the GI tract. Because differential PPIX concentrations in these cell lines represented the in vivo observations (ratio tumor vs normal 10:1-20:1), we analyzed the ALA uptake, mitochondrial properties and key molecules of PPIX metabolism (porphobilinogen deaminase [PBGD], ferrochelatase [FC], iron content, transferrin receptor content). The tumor-preferential PPIX accumulation is strongly influenced, but not solely determined, by activity differences between the PPIX-producing PBGD and the PPIX-converting FC, when compared with fibroblasts. Tumor-specific PPIX accumulation is generated by ALA conversion rather than by initial ALA uptake because no significant overall difference in uptake (about 0.6 mug ALA/mg protein) of ALA is seen. In conclusion, further research of tumor cell selectivity of PPIX fluorescence should focus on the mechanisms responsible for an altered PPIX metabolism to find tumor-specific target molecules, thus leading to an improved clinical practicability of ALA application and consequent endoscopy. C1 Univ Regensburg, Inst Pathol, D-93042 Regensburg, Germany. NCI, NIH, Bethesda, MD 20892 USA. Univ Regensburg, Dept Internal Med 1, D-93042 Regensburg, Germany. Univ Zurich, Inst Phys Chem, CH-8057 Zurich, Switzerland. RP Knuechel, R (reprint author), Univ Regensburg, Inst Pathol, Franz Josef Str Allee 11, D-93042 Regensburg, Germany. NR 46 TC 63 Z9 67 U1 0 U2 10 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV PY 2002 VL 76 IS 5 BP 518 EP 525 DI 10.1562/0031-8655(2002)076<0518:MCOTCS>2.0.CO;2 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 617NX UT WOS:000179368700009 PM 12462647 ER PT J AU Castonguay, TW Beaulieu, S Eskay, RL Barden, N Kamara, K Khozin, S Lustberg, L Brown, L AF Castonguay, TW Beaulieu, S Eskay, RL Barden, N Kamara, K Khozin, S Lustberg, L Brown, L TI The effects of adrenalectomy and aldosterone replacement in transgenic mice expressing antisense RNA to the type 2 glucocorticoid receptor SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE corticusterone; aldosterone; obesity; glucocorticoid receptor; leptin; body composition ID OB-OB MICE; TREATED OBESE MICE; ENERGY-BALANCE; BODY-WEIGHT; FATTY RAT; CORTICOSTERONE; LEPTIN; DEXAMETHASONE; ZUCKER; DIET AB Bilateral adrenalectomy (ADX) either prevents or attenuates obesity in several animal models. Mice that express an antisense RNA to the glucocorticoid receptor (GCR) are obese. The present study was conducted to examine the effects of ADX and aldosterone (ALDO) replacement on the rate of weight gain and body composition of mice bearing an antisense GCR gene construct. Twenty-eight male transgenic mice bearing the antisense GCR construct and 16 male B6C/3FI mice were either bilaterally ADX or given sham operations. At the time of surgery, some of the ADX mice and all of the sham-operated mice were implanted with 100-mg cholesterol (CHOL) pellets inserted subcutaneously in the subscapular region. The remaining ADX mice were implanted with 100-mg 1% w/w ALDO pellets using CHOL as vehicle. All mice were returned to their home cages for 2 weeks. They were then decapitated and the blood was collected for corticosterone, ALDO, insulin, and leptin radioimmunoassay. Carcasses were eviscerated and prepared for gravimetric analyses, including bomb calorimetry. ADX resulted in a significant drop in carcass fat in both transgenic and wildtype groups. ALDO prevented the decrease in carcass fat in both groups. Two weeks after ADX, transgenic mice were as fat as sham-operated wildtype controls, whereas both sham-operated and ALDO-treated transgenic groups were significantly fatter. Despite observing a reliable decrease in carcass fat following ADX, no corresponding decrease in circulating leptin was found. (C) 2002 Published by Elsevier Science Inc. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD USA. Laval Univ Hosp, Dept Anat & Physiol, Neurosci Sect, St Foy, PQ, Canada. RP Castonguay, TW (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. OI Castonguay, Thomas/0000-0003-1176-5095 NR 39 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD NOV PY 2002 VL 77 IS 2-3 BP 417 EP 423 AR PII S0031-9384(02)00881-8 DI 10.1016/S0031-9384(02)00881-8 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 614CL UT WOS:000179170700027 PM 12419418 ER PT J AU Li, YF Austin, S AF Li, YF Austin, S TI The P1 plasmid in action: time-lapse photomicroscopy reveals some unexpected aspects of plasmid partition SO PLASMID LA English DT Article DE P1 plasmid; partition; DNA segregation; cell division ID ESCHERICHIA-COLI; SEGREGATION; CHROMOSOME; MECHANISMS AB The prophage of bacteriophage P I is a low copy number plasmid in Escherichia coli and is segregated to daughter cells by an active partition system. The dynamics of the partition process have now been successfully followed by time-lapse photomicroscopy. The process appears to be fundamentally different from that previously inferred from statistical analysis of fixed cells. A focus containing several plasmid copies is captured at the cell center. Immediately before cell division, the copies eject bi-directionally along the long axis of the cell. Cell division traps one or more plasmid copies in each daughter cell. These copies are free to move, associate, and disassociate. Later, they are captured to the new cell center to re-start the cycle. Studies with mutants suggest that the ability to segregate accurately at a very late stage in the cell cycle is dependent on a novel ability of the plasmid to control cell division. Should segregation be delayed, cell division is also delayed until segregation is successfully completed. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NCI, Gene Regulat & Chromosome Biol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Div Basic Sci, Frederick, MD 21702 USA. NR 9 TC 22 Z9 22 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 0147-619X J9 PLASMID JI Plasmid PD NOV PY 2002 VL 48 IS 3 BP 174 EP 178 AR PII S0147-619X(02)00104-X(02) DI 10.1016/S0147-619X(02)00104-X PG 5 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 625NZ UT WOS:000179823700002 PM 12460532 ER PT J AU Neeley, YC McDonagh, KT Overwijk, WW Restifo, NP Sanda, MG AF Neeley, YC McDonagh, KT Overwijk, WW Restifo, NP Sanda, MG TI Antigen-specific tumor vaccine efficacy in vivo against prostate cancer with low class I MHC requires competent class II MHC SO PROSTATE LA English DT Article DE prostate cancer; T lymphocytes; tumor antigens; vaccinia; immunotherapy ID CYTOTOXIC T-LYMPHOCYTES; DEFICIENT MICE; CELL CONTROL; EXPRESSION; RECOMBINANT; RESPONSES; MODEL; BETA-2-MICROGLOBULIN; IMMUNOTHERAPY; IMMUNIZATION AB BACKGROUND. Cancers can escape immune recognition by means of evading class I major histocompatibility complex (MHC) -mediated recognition by cytotoxic T lymphocytes. However, immunization strategies targeting defined tumor-associated antigens have not been extensively characterized in murine prostate cancer models. Therefore, we evaluated antigenspecific, antitumor immunity after antigen-encoding vaccinia immunization against mouse prostate cancer cells expressing a model tumor-associated antigen (beta-galactosidase) and exhibiting partially deficient class I MHC. METHODS AND RESULTS. Low class I MHC expression in P-galactosidase-expressing D7RM-1 prostate cancer cells was shown by fluorescence activated cell sorting, and deficient class I MHC-mediated antigen presentation was shown in resistance of D7RM-1 to cytolysis by beta-galactosidase-specific cytotoxic T lymphocytes (CTL). Despite partially deficient class I MHC presenting function, immunization with vaccinia encoding P-galactosidase conferred antigen-specific protection against D7RM-1 cancer. Antigen-specific immunity was recapitulated in beta(2)m knockout mice (with deficient class I MHC and CTL function), confirming that class I MHC antigen presentation was not required for immunity against tumor partially deficient in class I MHC. Conversely, antigen-specific antitumor immunity was abrogated in A(b)beta knockout mice (with deficient class II MHC and helper T cell function), demonstrating a requirement for functional class II MHC. Resistant tumors from the otherwise effectively immunized beta(2)m knockout mice (among which tumor progression had been reduced or delayed) showed reduced target antigen expression, corroborating antigen-specificity (and showing an alternative immune escape mechanism), whereas antigen expression (like tumor growth) was unaffected among A(b)beta knockout mice. CONCLUSION. Our results demonstrate that class I MHC-restricted antigen presentation and CTL activity is neither necessary nor sufficient for antigen-encoding vaccinia immunization to induce protective immunity against class I MHC-low tumors, whereas host class II MHC-mediated antigen presentation facilitates antigen-specific immunity against prostate cancer in vivo. Reduced expression of the target antigen developed rapidly in vivo as an immune escape mechanism for such cancers. C1 Univ Michigan, Taubman Ctr 2916, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Sanda, MG (reprint author), Univ Michigan, Taubman Ctr 2916, Dept Urol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Restifo, Nicholas/A-5713-2008; Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [R01 CA082419, R01-CA82419-01] NR 33 TC 7 Z9 7 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 0270-4137 J9 PROSTATE JI Prostate PD NOV 1 PY 2002 VL 53 IS 3 BP 183 EP 191 DI 10.1002/pros.10136 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 610PN UT WOS:000178969500003 PM 12386918 ER PT J AU Kloczkowski, A Ting, TL Jernigan, RL Garnier, J AF Kloczkowski, A Ting, TL Jernigan, RL Garnier, J TI Combining the GOR V algorithm with evolutionary information for protein secondary structure prediction from amino acid sequence SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE GOR algorithm; protein secondary structure; secondary structure prediction; PSI-BLAST; multiple sequence alignment; information theory ID HOMOLOGOUS SEQUENCES; GLOBULAR PROTEINS; ALIGNMENT; ACCURACY; RECOGNITION; IMPROVEMENT; PARAMETERS; REGIONS; SEARCH; PHD AB We have modified and improved the GOR algorithm for the protein secondary structure prediction by using the evolutionary information provided by multiple sequence alignments, adding triplet statistics, and optimizing various parameters. We have expanded the database used to include the 513 non-redundant domains collected recently by Cuff and Barton (Proteins 1999;34:508519; Proteins 2000;40:502-511). We have introduced a variable size window that allowed us to include sequences as short as 20-30 residues. A significant improvement over the previous versions of GOR algorithm was obtained by combining the PSI-BLAST multiple sequence alignments with the GOR method. The new algorithm will form the basis for the future GOR V release on an online prediction server. The average accuracy of the prediction of secondary structure with multiple sequence alignment and full jack-knife procedure was 73.5%. The accuracy. of the prediction increases to 74.2% by limiting the prediction to 375 (of 513) sequences having at least 50 PSI-BLAST alignments. The average accuracy of the prediction of the new improved program without using multiple sequence alignments was 67.5%. This is approximately a 3% improvement over the preceding GOR IV algorithm (Garnier J, Gibrat JF, Robson B. Methods Enzymol 1996;266:540-553; Kloczkowski A, Ting K-L, Jernigan RL, Garnier J. Polymer 2002;43:441-449). We have discussed alternatives to the segment overlap (Sov) coefficient proposed by Zemla et al. (Proteins 1999;34:220-223). (C) 2002 Wiley-Liss, Inc.*. C1 NIH, Math & Stat Comp Lab, CIT, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Jernigan, RL (reprint author), Iowa State Univ Sci & Technol, Laurence H Baker Ctr Bioinformat & Biol Studies, Ames, IA 50011 USA. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 50 TC 78 Z9 83 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 1 PY 2002 VL 49 IS 2 BP 154 EP 166 DI 10.1002/prot.10181 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 598HC UT WOS:000178269300002 PM 12210997 ER PT J AU Keskin, O Ji, X Blaszcyk, J Covell, DG AF Keskin, O Ji, X Blaszcyk, J Covell, DG TI Molecular motions and conformational changes of HPPK SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE conformational changes; coarse grained network model; 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK); normal mode analysis ID NORMAL-MODE ANALYSIS; DYNAMICS SIMULATIONS; PROTEIN DYNAMICS; 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN PYROPHOSPHOKINASE; CRYSTAL-STRUCTURE; DOMAIN MOTIONS; HIV-1 PROTEASE; HEN LYSOZYME; FLUCTUATIONS; SYNTHETASE AB 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) belongs to a class of catalytic enzymes involved in phosphoryl transfer and is a new target for the development of novel antimicrobial agents. In the present study, the fundamental consideration is to view the overall structure of HPPK as a network of interacting residues and to extract the most cooperative collective motions that define its global dynamics. A coarse-grained model, harmonically constrained according to HPPK`s crystal structure is used. Four crystal structures of HPPK (one apo and three holo forms with different nucleotide and pterin analogs) are studied with the goal of providing insights about the function-dynamic correlation and ligand induced conformational changes. The dynamic differences are examined between HPPK's apo- and holo-forms, because they are involved in the catalytic reaction steps. Our results indicate that the palm-like structure of HPPK is nearly rigid, whereas the two flexible loops: L2 (residues 43-53) and L3 (residues 82-92) exhibit the most concerted motions for ligan recognition and presumably, catalysis. These two flexible loops are involved in the recognition of HPPKs nucleotide and pterin ligands, whereas the rigid palm region is associated with binding of these cognate ligands. Six domains of collective motions are identified, comprised of structurally close but not necessarily sequential residues. Two of these domains correspond to the flexible loops (L2 and L3), whereas the remaining domains correspond to the rigid part of the molecule. (C) 2002 Wiley-Liss, Inc.*. C1 NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21701 USA. Koc Univ, Dept Chem, Coll Arts & Sci, Istanbul, Turkey. NCI, Comp Technol Lab, Screening Technol Branch, Dev Therapeut Program,NIH, Frederick, MD 21701 USA. RP Keskin, O (reprint author), Ft Detrick Bldg,430,Room 215, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 NR 47 TC 13 Z9 13 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 0887-3585 J9 PROTEINS JI Proteins PD NOV 1 PY 2002 VL 49 IS 2 BP 191 EP 205 DI 10.1002/prot.10205 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 598HC UT WOS:000178269300005 PM 12211000 ER PT J AU Miyaji, T Hewitt, SM Liotta, LA Star, RA AF Miyaji, T Hewitt, SM Liotta, LA Star, RA TI Frozen protein arrays: A new method for arraying and detecting recombinant and native tissue proteins SO PROTEOMICS LA English DT Article DE arrays; kidney ischemia; NaK-ATPase; prostate specific antigen; protein arrays ID MICROARRAY TECHNOLOGY; CANCER; MICROCHIPS; SPECIMENS; DNA AB DNA microarrays are powerful tools for high throughput analysis of gene expression; however, they do not measure protein expression. Current methods for producing protein arrays require sophisticated equipment or extensive protein modification. We developed a low overhead, customizable assay platform called frozen protein arrays that can detect native proteins in protein lysates. Frozen protein arrays were formed from a block of frozen histologic embedding compound containing an array of wells. wells were filled with samples, which freeze and bond to the block. Cryosections were cut and transferred to nitrocellulose-coated slides. The reproducibility, linearity, and sensitivity was confirmed using frozen protein arrays filled with prostate specific antigen. Frozen protein arrays could detect native tissue proteins. The alpha1 subunit of NaK-ATPase was detected in rat kidneys with a coefficient of variation of 4.3-6.6%. Frozen protein array analysis indicated that the protein abundance decreased by 48.7% following renal ischemia, similar to the 40% decrease by Western blotting. We conclude that frozen protein arrays are a low cost, moderate size platform for arraying samples including protein lysates. Production of many identical frozen protein arrays is easy, inexpensive, and requires only small sample volumes. The method is gentle on proteins as they remain frozen during production. C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr Room 3N108, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 16 TC 14 Z9 15 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD NOV PY 2002 VL 2 IS 11 BP 1489 EP 1493 DI 10.1002/1615-9861(200211)2:11<1489::AID-PROT1489>3.0.CO;2-8 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622RW UT WOS:000179661600002 PM 12442248 ER PT J AU Ruiz-Padial, E Sanchez, MB Thayer, JF Vila, J AF Ruiz-Padial, E Sanchez, MB Thayer, JF Vila, J TI Non-conscious modulation of the cardiac defense response by phobic pictures. SO PSICOTHEMA LA Spanish DT Article ID FEAR-RELEVANT STIMULI; STARTLE REFLEX; MASKED STIMULI; EMOTION; ATTENTION; HUMANS; PROBE AB Non-conscious modulation of the cardiac defense response by phobic pictures. This study examined the effect of viewing a phobic versus a non phobic picture on the modulation of the cardiac defense response elicited by an intense auditory stimulus. 48 women with fear of spiders were examined using a factorial design with two independent groups (non-effective backward masking and effective backward masking) and two presentations of the auditory stimulus preceded by a visual image (one phobic and one non phobic). The dependent variable was second-by-second heart rate analyzed for 80 seconds after the auditory stimulus. 6 subjects of the effective masking group were able to identify one of the two visual stimuli and were excluded from the statistical analysis. The results of the analysis with the remaining subjects showed the expected emotional modulation: the phobic picture, as compared to the non phobic picture, potentiated the cardiac defense response. The same effects were observed in both the conscious and the non-conscious groups. The results are discussed in the context of Peter Lang's motivational priming and Arne Ohman's preattentional fear processing theories. C1 Univ Jaen, Fac Psicol, Jaen 23071, Spain. Univ Granada, E-18071 Granada, Spain. NIA, Baltimore, MD 21224 USA. RP Ruiz-Padial, E (reprint author), Univ Jaen, Fac Psicol, Jaen 23071, Spain. RI Vila, Jaime/F-9719-2010; Ruiz Padial, Elisabeth/G-8962-2011 OI Vila, Jaime/0000-0002-1767-8606; NR 32 TC 3 Z9 3 U1 0 U2 0 PU COLEGIO OFICIAL DE PSICOLOGOS DE ASTURIAS PI OVIEDO PA ILDEFONSO S. DEL RIO, 4-1 B, 33001 OVIEDO, SPAIN SN 0214-9915 J9 PSICOTHEMA JI Psicothema PD NOV PY 2002 VL 14 IS 4 BP 739 EP 745 PG 7 WC Psychology, Multidisciplinary SC Psychology GA 607FX UT WOS:000178782400008 ER PT J AU Schmidt, PJ Murphy, JH Haq, N Danaceau, MA St Clair, LS AF Schmidt, PJ Murphy, JH Haq, N Danaceau, MA St Clair, LS TI Basal plasma hormone levels in depressed perimenopausal women SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE perimenopause; depression; estrogens; androgens; DHEA ID GABA-A RECEPTOR; DEHYDROEPIANDROSTERONE-SULFATE; POSTMENOPAUSAL WOMEN; DIURNAL-VARIATION; STEROID-HORMONES; MENOPAUSAL WOMEN; THYROID-HORMONE; ESTROGEN-LEVELS; HEALTHY WOMEN; MIDLIFE WOMEN AB Background: An association between abnormal changes in reproductive endocrine function during the perimenopause and the onset of depression in some women has been suggested but remains controversial. Methods: We examined basal plasma hormone levels in two samples of women with well characterized, first onset depression (major or minor) during the perimenopause and matched comparison groups of asymptomatic women. Results were compared by analysis of variance. Results: No significant diagnosis-related differences were observed in plasma hormone measures of the following: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), estrone (E1), total (T) or free testosterone (FT), or the E2/LH ratio. We did identify significantly lower morning plasma dehydroepiandrosterone (DHEA) and its sulphated metabolite DHEA-S (but not cortisol) levels in the depressed women compared to the non-depressed comparison group. Women with hot flushes (regardless of the presence of depression) were significantly older than women without flushes, had significantly higher plasma levels of FT, LH and FSH, and had significantly lower E2/LH ratios. Conclusions: Women with first onset depression during the perimenopause are not distinguished from controls on the basis of basal hormone measures of ovarian estrogens, testosterone, or gonadotropins. However, perimenopause-related changes in E2 may interact with low levels of DHEA in some women to increase their vulnerability to develop depression. In contrast to perimenopause-related vasomotor symptoms, depression during the perimenopause is not associated with a simple hormone deficiency state. The relatively low levels of E2 and El in the depressed women may have met statistical significance in a much larger and homogenous sample. Published by Elsevier Science Ltd. C1 NIMH, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Bldg 10,Room 3N-238,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. NR 58 TC 68 Z9 72 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 2002 VL 27 IS 8 BP 907 EP 920 AR PII S0306-4530(02)00004-5 DI 10.1016/S0306-4530(02)00004-5 PG 14 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 621QG UT WOS:000179600500003 PM 12383452 ER PT J AU Xi, ZX Stein, EA AF Xi, ZX Stein, EA TI Blockade of ionotropic glutamatergic transmission in the ventral tegmental area reduces heroin reinforcement in rat SO PSYCHOPHARMACOLOGY LA English DT Article DE heroin; glutamate; reinforcement; self-administration; NMDA receptors; AMPA receptors ID CONDITIONED PLACE PREFERENCE; SELF-ADMINISTRATION BEHAVIOR; METHYL-D-ASPARTATE; NUCLEUS-ACCUMBENS; DOPAMINE NEURONS; MORPHINE; COCAINE; RECEPTORS; MK-801; AMPHETAMINE AB Rationale: While the role of the mesocorticolimbic (MCL) dopamine (DA) system in mediating the reinforcing properties of drugs of abuse has been well established, how and where other neurotransmitter systems interact to modify this system is less well understood. Objectives: The present study sought to assess whether blockade of ionotropic glutamate receptors in the ventral tegmental area (VTA) would modulate heroin self-administration (SA) behavior in rats. Methods: The effects of systemic or regional administration of ionotropic glutamate receptor antagonists into the VTA on the maintenance of heroin SA were assessed. Rats were reinforced each time they responded on a lever with a single injection of intravenous heroin. To determine the specificity of their effects on heroin SA, the ability of these antagonists to modify locomotion and food-reinforced behavior was also examined. Results: Systemic or regional administration of the non-competitive NMDA antagonist dizocilpine into the VTA significantly increased the rate of heroin SA and shifted the heroin dose-response curve to the right. Similarly, when systemically administered, ketamine, another non-competitive NMDA antagonist, also increased the rate of heroin SA. However, when administered directly into the VTA, ketamine or AP5 [D-(-)-2-amino-5-phosphonopentanoic acid, a competitive NMDA antagonist], dose-dependently blocked heroin SA. In contrast, 6,7-dinitroquinoxaline-2,3-dione (DNQX), an AMPA/kainate receptor antagonist, significantly increased heroin SA. Conclusion: These data suggest that ionotropic glutamate receptors in the VTA, presumably by modulating MCL DA efferents and/or tegmental interneurons, modulate opiate reinforcement. C1 Med Coll Wisconsin, Dept Cell Biol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Neurobiol & Anat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA. Natl Inst Drug Abuse, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD 21224 USA. RP Stein, EA (reprint author), Med Coll Wisconsin, Dept Cell Biol, Milwaukee, WI 53226 USA. RI Stein, Elliot/C-7349-2008 FU NIDA NIH HHS [DA09465] NR 53 TC 34 Z9 35 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2002 VL 164 IS 2 BP 144 EP 150 DI 10.1007/s00213-002-1190-3 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 620LM UT WOS:000179534900003 PM 12404076 ER PT J AU Grillon, C Baas, JMP AF Grillon, C Baas, JMP TI Comments on the use of the startle reflex in psychopharmacological challenges: impact of baseline startle on measurement of fear-potentiated startle SO PSYCHOPHARMACOLOGY LA English DT Letter ID HUMANS; ALPRAZOLAM; ANXIETY C1 NIH, NIMH MAP, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIH, NIMH MAP, 15K N Dr,Rm 113,MSC 2670, Bethesda, MD 20892 USA. NR 12 TC 21 Z9 21 U1 3 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2002 VL 164 IS 2 BP 236 EP 238 DI 10.1007/s00213-002-1164-5 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 620LM UT WOS:000179534900016 PM 12481758 ER PT J AU Broadbear, JH Winger, G Rice, KC Woods, JH AF Broadbear, JH Winger, G Rice, KC Woods, JH TI Antalarmin, a putative CRH-RI antagonist, has transient reinforcing effects in rhesus monkeys SO PSYCHOPHARMACOLOGY LA English DT Article DE CRH antagonist; antalarmin; Macaca mulatta; schedule controlled responding; HPA axis; cortisol; ACTH ID RECEPTOR ANTAGONIST; NONPEPTIDE ANTAGONIST; CP-154,526; STRESS; RESPONSES; RATS; NEUROENDOCRINE AB Rationale: During the course of our investigation of antalarmin, a corticotropin-releasing hormone (CRH) antagonist, in rhesus monkeys, we noticed that large, intravenous doses of antalarmin resulted in behavioral changes that resembled intoxication. Objectives: Antalarmin was evaluated in rhesus monkeys for its reinforcing effectiveness as well as for its effects on hypothalamic-pituitary-adrenal (HPA) axis activity. Methods: Twelve monkeys, each with a surgically implanted indwelling venous catheter, were trained to respond for and receive the short-acting barbiturate, methohexital. Monkeys responded on one of two schedules: a fixed ratio (FR) 10 (30 or 100), timeout (TO) 10 s schedule on which they received methohexital, antalarmin, vehicle or saline injections; or an FR30, TO 45 s during which saline, vehicle, or four different doses of methohexital or antalarmin were available. Each dose was available during a 25-min period separated by a 10-min TO. Blood samples were obtained from three monkeys before, during and after the self-administration sessions and assayed for ACTH and cortisol. Results: Antalarmin initially served as a reinforcer in I I of 12 monkeys, although its reinforcing effects dissipated after three to four exposures under both operant schedules. Self-injection of antalarmin did not produce any change in cortisol levels, although methohexital did attenuate ACTH and cortisol release. Conclusions: This study provides the first evidence for transient reinforcing properties of a putative centrally acting CRH-R1 selective antagonist. C1 Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. NIDDK, NIH, Med Chem Lab, Bethesda, MD 20892 USA. RP Woods, JH (reprint author), Univ Michigan, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. RI Broadbear, Jillian/A-6864-2011 FU NIDA NIH HHS [DA 09161] NR 19 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2002 VL 164 IS 3 BP 268 EP 276 DI 10.1007/s00213-002-1187-y PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 624UD UT WOS:000179779200004 PM 12424550 ER PT J AU Daly, S Mills, JL Molloy, AM Conley, M McPartlin, J Lee, YJ Young, PB Kirke, PN Weir, DG Scott, JM AF Daly, S Mills, JL Molloy, AM Conley, M McPartlin, J Lee, YJ Young, PB Kirke, PN Weir, DG Scott, JM TI Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Article ID NEURAL-TUBE DEFECTS; MICROBIOLOGICAL ASSAY; RISK FACTOR; SERUM; DISEASE; FOLATE; FORTIFICATION; VITAMIN-B-12; PREGNANCY AB Background: Ongoing clinical trials are investigating whether lowering plasma homocysteine reduces the risk of vascular disease. If so, food fortification with folic acid will be the likely result, and sub-optimal amounts are likely to be preferred, for safety reasons. Dose-finding studies are needed before the outcomes of these trials, to establish the benefits and risks of folic acid consumption over the widest intake range likely to be encountered. Aim: To find the lowest dose of folic acid that effectively reduces plasma homocysteine in premenopausal women. Design: Double-blind, randomized placebo-controlled trial. Methods: Women of child-bearing age (n=95) were randomly allocated to 0, 100, 200, or 400 mug/day of folic acid. Red-cell folate and plasma homocysteine were measured at baseline and after 10 weeks supplementation. Results: Median red cell folate levels increased significantly in the 200 mug (p=0.0001) and 400 mug (p=0.0001) groups; but not in the placebo (0 mug) (p=0.25) or the 100 mug (p=0.5) groups. Only the 200 mug and the 400 mug groups had significant decreases in plasma homocysteine, (p=0.04 and p=0.0008, respectively). However, when subjects whose initial plasma homocysteine was <8 mumol/l (already optimally low) were removed from the analysis, there were significant plasma homocysteine decreases in all three treatment groups, but not the placebo group. Discussion: In this sub-population, low doses of folic acid significantly lower plasma homocysteine. This could be achieved safely by fortification. C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. Coombe Womens Hosp, Dublin, Ireland. NICHD, Epidemiol Branch, NIH, Bethesda, MD USA. NICHD, Branch Stat, NIH, Bethesda, MD USA. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Vet Sci Div, Dept Biochem, Belfast, Antrim, North Ireland. Hlth Res Board, Dublin, Ireland. RP Scott, JM (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. NR 23 TC 18 Z9 18 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD NOV PY 2002 VL 95 IS 11 BP 733 EP 740 DI 10.1093/qjmed/95.11.733 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 608BN UT WOS:000178825400004 PM 12391385 ER PT J AU Miller, DL Balter, S Noonan, PT Georgia, JD AF Miller, DL Balter, S Noonan, PT Georgia, JD TI Minimizing radiation-induced skin injury in interventional radiology procedures SO RADIOLOGY LA English DT Article DE fluoroscopy, technology; radiations, exposure to patients and personnel; radiations, injurious effects; radiations, measurement; radiology and radiologists, How I Do It ID FLUOROSCOPICALLY GUIDED PROCEDURES; REAL-TIME MEASUREMENT; EXPOSURE; PATIENT; FILTRATION AB Skin injury is a deterministic effect of radiation. Once a threshold dose has been exceeded, the severity of the radiation effect at any point on the Skin increases with increasing dose. Peak skin close is defined as the highest dose delivered to any portion of the patient's skin. Reducing peak skin dose can reduce the likelihood and type of skin injury. Unfortunately, peak skin dose is difficult to measure in real time, and most currently available fluoroscopic systems do not provide the operator with sufficient information to minimize skin dose. Measures that reduce total radiation dose will reduce peak skin dose, as well as dose to the operator and assistants. These measures include minimizing fluoroscopy time, the number of images obtained, and dose by controlling technical factors. Specific techniques-dose spreading and collimation-reduce both peak skin dose and the size of skin area subjected to peak skin dose. For optimum effect, real-time knowledge of skin-dose distribution is invaluable. A trained operator using well-maintained state-of-the art equipment can minimize peak skin dose in all fluoroscopically guided procedures. C1 USN, Natl Med Ctr, Dept Radiol, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol & Nucl Med, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. NCI, Med Oncol Clin Res Unit, Canc Res Ctr, Bethesda, MD 20892 USA. Lenox Hill Hosp, Dept Med, New York, NY 10021 USA. RP Miller, DL (reprint author), USN, Natl Med Ctr, Dept Radiol, Wisconsin Ave, Bethesda, MD 20889 USA. NR 20 TC 92 Z9 96 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2002 VL 225 IS 2 BP 329 EP 336 DI 10.1148/radiol.2252011414 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608AG UT WOS:000178822500005 PM 12409563 ER PT J AU Summers, RM Jerebko, AK Franaszek, M Malley, JD Johnson, CD AF Summers, RM Jerebko, AK Franaszek, M Malley, JD Johnson, CD TI Colonic polyps: Complementary role of computer-aided detection in CT Colonography SO RADIOLOGY LA English DT Article DE colon, CT; colon neoplasms; colonoscopy; computers, diagnostic aid ID VIRTUAL BRONCHOSCOPY; FEASIBILITY; SEGMENTATION; DIAGNOSIS; DISPLAY AB PURPOSE: To apply a computer-aided detection (CAD) algorithm to supine and prone multisection helical computed tomographic (CT) colonographic images to confirm if there is any added benefit provided by CAD over that of standard clinical interpretation. MATERIALS AND METHODS: CT colonography (with patients in both supine and prone positions) was performed with a multisection helical CT scanner in 40 asymptomatic high-risk patients. There were two consecutive series of patients, 20 of whom had at least one polyp 1.0 cm in size or larger and 20 of whom had normal colons at conventional colonoscopy performed the same day. The CT colonographic images were interpreted with an automated CAD algorithm and by two radiologists who were blinded to colonoscopy findings RESULTS: For 25 polyps at least 1.0 cm in size ("large" polyps), sensitivity for detection by at least one radiologist was 48% (12 of 25). The sensitivity of CAD for detecting large polyps was also 48% (12 of 25), but the CAD algorithm detected four of 13 large polyps that were not detected by either radiologist (31%, 95% two-sided Cl: 9, 61), increasing,the potential sensitivity to 64% (16 of 25). For polyps identifiable retrospectively, sensitivity of CAD was 67% (12 of 18), and sensitivity of the combination of detection with the CAD algorithm or by at least one radiologist was 89% (161 of 18). There were an average of 11 false-positive detections per patient for CAD. CONCLUSION: In this series, of patients in whom radiologists had difficulties detecting polyps (compared with sensitivities of 75%-90% reported in the literature), this CAD algorithm played a complementary role to conventional interpretation of CT colonographic images by detecting a number of large polyps missed by trained observers. (C) RSNA, 2002. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. RP Summers, RM (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, 10 Ctr Dr,MSC 1182,Bldg 10,Rm 1C660, Bethesda, MD 20892 USA. EM rms@nih.gov FU NCI NIH HHS [R01CA75333] NR 26 TC 104 Z9 104 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2002 VL 225 IS 2 BP 391 EP 399 DI 10.1148/radiol.2252011619 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608AG UT WOS:000178822500013 PM 12409571 ER PT J AU Avila, NA Dwyer, AJ AF Avila, NA Dwyer, AJ TI Diurnal variation in size of lymphangioleiomyomas? Response SO RADIOLOGY LA English DT Letter C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10,Room 1C-660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2002 VL 225 IS 2 BP 609 EP 610 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608AG UT WOS:000178822500048 ER PT J AU Johnson, L Staub, C Silge, RL Harris, MW Chapin, RE AF Johnson, L Staub, C Silge, RL Harris, MW Chapin, RE TI The pesticide methoxychlor given orally during the perinatal/juvenile period, reduced the spermatogenic potential of males as adults by reducing their Sertoli cell number SO REPRODUCTION NUTRITION DEVELOPMENT LA English DT Article DE methoxychlor; estrogenic; oral exposure; Sertoli cell number ID DAILY SPERM PRODUCTION; LACTATIONAL EXPOSURE; ESTROGENIC ACTIVITY; TESTICULAR SIZE; MALE-RATS; ANDROGENIC STATUS; FISCHER RATS; EFFICIENCY; HORMONE; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN AB Perinatal and juvenile oral treatment of rats with the insecticide, methoxychlor (MXC), reduced testicular size and other reproductive indices including the number of epididymal spermatozoa in those animals as adults [6]. The objective was to determine if these males exposed during development had fewer Sertoli cells which might explain these testicular effects. Rat dams were gavaged with MXC at 0, 5, 50, or 150 mg.kg(-1).day(-1) for the week before and after they gave birth. Resulting male pups (15/group) then were dosed directly from postnatal day 7 to 42. Testes were fixed in Bouin's and in OsO4, embedded in Epon and sectioned at 0.5 mum, stained with toluidine blue, and evaluated stereologically or cut at 20 mm to measure Sertoli cell nuclei with Nomarski optics. Sertoli cell number was calculated as the volume density of the nucleus times the parenchymal weight (90% of testicular weight) divided by the volume of a single Sertoli cell nucleus. Across dose groups, there were no changes in the nuclear volume density, the volume of a single nucleus, or the number of Sertoli cells per g parenchyma. There were highly significant dose-related changes in the volume of Sertoli cell nuclei per testis and the number of Sertoli cells per testis. Reduced testicular weight (r = 0.94) and reduced numbers of epididymal spermatozoa (r = 0.43) were significantly (p < 0.01) correlated to reduced number of Sertoli cells per testis. Hence, perinatal and juvenile oral exposure to MXC can reduce spermatogenic potential of males as adults by reducing their number of Sertoli cells. C1 Texas A&M Univ, Ctr Environm & Rural Hlth, Dept Vet Anat & Publ Hlth, College Stn, TX 77843 USA. NIEHS, Reprod Toxicol Grp, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Johnson, L (reprint author), Texas A&M Univ, Ctr Environm & Rural Hlth, Dept Vet Anat & Publ Hlth, College Stn, TX 77843 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NICHD NIH HHS [N01-HD-8-3281]; NIEHS NIH HHS [N01-ES-15307, R25-ES-10735, R25-ES-10443] NR 54 TC 6 Z9 8 U1 1 U2 3 PU E D P SCIENCES PI LES ULIS CEDEXA PA 7, AVE DU HOGGAR, PARC D ACTIVITES COURTABOEUF, BP 112, F-91944 LES ULIS CEDEXA, FRANCE SN 0926-5287 J9 REPROD NUTR DEV JI Reprod. Nutr. Dev. PD NOV-DEC PY 2002 VL 42 IS 6 BP 573 EP 580 DI 10.1051/rnd:2002043 PG 8 WC Developmental Biology; Nutrition & Dietetics; Reproductive Biology; Zoology SC Developmental Biology; Nutrition & Dietetics; Reproductive Biology; Zoology GA 648XU UT WOS:000181177400005 PM 12625421 ER PT J AU Devasahayam, N Murugesan, R Yamada, K Reijnders, K Mitchell, JB Subramanian, S Krishna, MC Cook, JA AF Devasahayam, N Murugesan, R Yamada, K Reijnders, K Mitchell, JB Subramanian, S Krishna, MC Cook, JA TI Evaluation of a high-speed signal-averager for sensitivity enhancement in radio frequency Fourier transform electron paramagnetic resonance imaging SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID DATA-ACQUISITION SYSTEM; SPECTROMETER; SPECTROSCOPY; EPR; MICE; ESR AB A commercially available high-speed, digital signal-averager is integrated into an existing time-domain radio frequency (rf) electron paramagnetic resonance (EPR) spectrometer/imager. Sensitivity enhancement by the integrated system is estimated by coherent averaging of free induction decay signals, obtained from narrow-line EPR spin probes, and its performance is compared with that of an existing custom-built averager. For the existing custom-built "Analytek" averager, the minimum realizable trigger rate was 50 kHz, whereas for the commercial EG&G 9826 system, due the spectrometer constraints, we set the retrigger rate to 133 kHz. Very short summing and down loading times of the latter enable good temporal resolution in phantom as well as in vivo rf Fourier transform EPR images, obtained by the single point imaging (SPI) modality. For two-dimensional and three-dimensional imaging using the SPI mode, a saving of time by a factor of >2 could be achieved with the EG&G system compared with the Analytek. (C) 2002 American Institute of Physics. C1 NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RI Yamada, Ken-ichi/E-6318-2012 NR 25 TC 4 Z9 4 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD NOV PY 2002 VL 73 IS 11 BP 3920 EP 3925 DI 10.1063/1.1511792 PG 6 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 607YK UT WOS:000178818200034 ER PT J AU Ott, DE AF Ott, DE TI Potential roles of cellular proteins in HIV-1 SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; UBIQUITIN-DEPENDENT DEGRADATION; ELONGATION-FACTOR EF-1-ALPHA; MURINE LEUKEMIA-VIRUS; HLA CLASS-II; CYCLOPHILIN-A; GAG POLYPROTEIN; TARGET-CELLS; IN-VIVO; BINDING PROTEIN AB Human immunodeficiency virus type-1 particles contain host proteins, both on their surface and interior. This review summarises the cellular proteins found in these virions and covers some of their potential roles in the viral life cycle and pathogenesis. For most proteins studied, their role and function are either unknown or in the hypothesis stage. This reflects the relatively recent emphasis given to these proteins by the HIV-1 field as well as the incomplete understanding of their function in the cell. The study of cellular proteins in HIV-1 promises to help us better understand the interaction of this virus with the cell, the immune system, and the whole human host as well as to shed light on the nature of AIDS and suggest more targets for therapeutic intervention. Finally, many of the cell systems themselves are still poorly understood. The extensive study of HIV-1 has already brought increased attention to the fields of immunology and vaccine science and, in the same way, might assist our understanding of the cellular pathways themselves. Published in 2002 by John Wiley Sons, Ltd. C1 NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Ott, DE (reprint author), NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. FU PHS HHS [N01-C0-12400] NR 89 TC 82 Z9 87 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD NOV-DEC PY 2002 VL 12 IS 6 BP 359 EP 374 DI 10.1002/rmv.367 PG 16 WC Virology SC Virology GA 614MU UT WOS:000179194600003 PM 12410528 ER PT J AU Dalakas, MC AF Dalakas, MC TI Muscle biopsy findings in inflammatory myopathies SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID INCLUSION-BODY MYOSITIS; CELL RECEPTOR REPERTOIRE; INFILTRATING T-CELLS; MHC CLASS-I; POLYMYOSITIS; EXPRESSION; DERMATOMYOSITIS; LYMPHOCYTES; SIMILARITIES; EXPANSION AB The inflammatory myopathies encompass a heterogeneous group of acquired muscle diseases characterized clinically, by muscle weakness, and histologically, by inflammatory infiltrates within the skeletal muscles. The group of these myopathies comprise three major and discrete subsets: polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Each subset retains its characteristic clinical, immunopathologic, and morphologic features regardless of whether it occurs separately or in connection with other systemic diseases. Although the diagnosis of these disorders is based on the combination of clinical examination, electromyographic data, serum muscle enzyme levels, various autoantibodies, and the muscle biopsy findings, the muscle biopsy offers the most definitive diagnostic information in the majority of the cases. This article summarizes the main histologic features that characterize PM, DM, or IBM and emphasizes the main pitfalls associated with interpretation of the biopsies. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. NR 47 TC 72 Z9 81 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 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2002 VL 28 IS 4 BP 779 EP + AR PII S0889-857X(02)00030-3 DI 10.1016/S0889-857X(02)00030-3 PG 21 WC Rheumatology SC Rheumatology GA 626TA UT WOS:000179888300004 PM 12506772 ER PT J AU Nagaraju, K Plotz, PH AF Nagaraju, K Plotz, PH TI Animal models of myositis SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID EXPERIMENTAL AUTOIMMUNE MYOSITIS; EXPERIMENTAL ALLERGIC MYOSITIS; FAMILIAL CANINE DERMATOMYOSITIS; B1-INDUCED MURINE POLYMYOSITIS; INCLUSION-BODY MYOPATHY; TRANSFER-RNA SYNTHETASE; TRANSGENIC MICE; SKELETAL-MUSCLE; DENDRITIC CELLS; SJL/J MICE AB Animal models have greatly contributed to our understanding of immunopathogenetic mechanisms in various autoimmune diseases. Recently, several animal models of muscle inflammation have been described. This article outlines various spontaneous, induced, and transgenic models of muscle inflammation with an emphasis on their phenotypic resemblance to human autoimmune muscle diseases. Although the existing models may not exactly represent all the phenotypic variations of the human disease, they facilitate our knowledge of mechanisms of muscle inflammation and allow us to evaluate various therapeutic interventions to suppress muscle inflammation in the search for safer and more effective treatments for myositis. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21205 USA. RP Plotz, PH (reprint author), NIAMSD, NIH, Bldg 10-9N244, Bethesda, MD 20892 USA. NR 77 TC 11 Z9 14 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2002 VL 28 IS 4 BP 917 EP + AR PII S0889-857X(02)00026-1 DI 10.1016/S0889-857X(02)00026-1 PG 19 WC Rheumatology SC Rheumatology GA 626TA UT WOS:000179888300010 PM 12506778 ER PT J AU Rider, LG AF Rider, LG TI Outcome assessment in the adult and juvenile idiopathic inflammatory myopathies SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID INTERSTITIAL LUNG-DISEASE; ELEVATED SERUM LEVELS; MAGNETIC-RESONANCE SPECTROSCOPY; ISOMETRIC MUSCLE FORCE; VON-WILLEBRAND-FACTOR; SOLUBLE INTERLEUKIN-2 RECEPTORS; HEALTH ASSESSMENT QUESTIONNAIRE; SYSTEMIC LUPUS-ERYTHEMATOSUS; INTRAVENOUS GAMMA-GLOBULIN; INCLUSION-BODY MYOSITIS AB Significant progress has been achieved in developing international consensus regarding outcome assessment of the idiopathic inflammatory myopathies. This article describes the development and preliminary validation of new measures to evaluate disease activity, damage, and health-related quality of life for the adult and juvenile myositis syndromes. The discussion focuses on the core set measures that have been recommended by multidisciplinary collaborative study groups for the assessment of each of these domains. Alternative or novel approaches, that are not as fully validated or developed, but may be important tools in the evaluation of certain patients with myositis, are also reviewed. The use of standardized, validated approaches to assess myositis disease activity and damage and health-related quality of life should enhance the ability to compare therapeutic trials and increase their efficiency in the future. C1 NIEHS, NIH, Bethesda, MD 20892 USA. RP Rider, LG (reprint author), NIEHS, NIH, 9 Mem Dr,Room 1W107,MSC 0958, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458 NR 212 TC 30 Z9 30 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2002 VL 28 IS 4 BP 935 EP + AR PII S0889-857X(02)00027-3 DI 10.1016/S0889-857X(02)00027-3 PG 44 WC Rheumatology SC Rheumatology GA 626TA UT WOS:000179888300011 PM 12506779 ER PT J AU Kumon, Y Suehiro, T Faulkes, DJ Hosakawa, T Ikeda, Y Woo, P Sipe, JD Hashimoto, K AF Kumon, Y Suehiro, T Faulkes, DJ Hosakawa, T Ikeda, Y Woo, P Sipe, JD Hashimoto, K TI Transcriptional regulation of serum amyloid A1 gene expression in human aortic smooth muscle cells involves CCAAT/enhancer binding proteins (C/EBP) and is distinct from HepG2 cells SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID C-REACTIVE PROTEIN; ACUTE-PHASE; RHEUMATOID-ARTHRITIS; INDUCTION; APOLIPOPROTEIN; IDENTIFICATION; INTERLEUKIN-6; CHOLESTEROL; ACTIVATION; MORTALITY AB Regulation of acute-phase serum amyloid A (A-SAA) synthesis by proinflammatory cytokines and steroid hormones in human aortic smooth muscle cells (HASMCs) is distinct from that in HepG2 cells. To study the cis- and trans-activating promoter element involved in the SAA1 gene expression by HASMCs and HepG2 cells, we constructed plasmid vectors for luciferase reporter gene assay with varying lengths of SAA1 upstream regulatory region (up to 1431 bp), and examined their response to proinflammatory cytokines and/or steroid hormones. The corresponding vectors with the SAA4 upstream regulatory region served as controls. The presence of proposed transcriptional regulatory factors binding to these regions was confirmed immunohistochemically. The sequences of 1478 and 1836bp of the SAA1 and SAA4 5'-flanking regions were determined, respectively. SAA1 promoter transcription in cultured HASMCs was upregulated not by proinflammatory cytokines, but rather by glucocorticoids. This differed from HepG2 cells, in which SAA1 promoter transcription was upregulated synergistically by proinflammatory cytokines and glucocorticoids. The promoter activity of a series of truncated SAA1 promoter constructs measured using the reporter gene assay showed that the 5'-region from -252 to -175, containing a consensus site for CCAAT/enhancer binding proteins alpha,beta (C/EBPalpha,beta), was essential for SAA1 induction in HASMCs. In HepG2 cells, the 5'-region from - 119 to -79, containing a nuclear factor kappa-B (NFkappaB) consensus sequence, was essential for the induction. The functional significance of the C/EBP site as indicated by the immunohistochemical result was that in HASMCs anti-C/EBPbeta reactivity was shifted from the cytoplasm to the nuclei. We have, therefore, demonstrated that the region containing the C/EBPalpha,beta consensus binding site between the bases -252 and - 175 is important for the glucocorticoid-induced SAA1 gene expression in HASMCs but not in HepG2 cells. C1 Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kochi 7838505, Japan. UCL, Sch Med, Dept Mol Pathol, London W1N 8AA, England. NIH, Musculoskeletal & Dent Sci IRG, Ctr Sci Review, Bethesda, MD 20892 USA. RP Kumon, Y (reprint author), Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kohasu Okoh Cho, Kochi 7838505, Japan. EM kumony@kochi-ms.ac.jp NR 26 TC 12 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD NOV PY 2002 VL 56 IS 5 BP 504 EP 511 DI 10.1046/j.1365-3083.2002.01169.x PG 8 WC Immunology SC Immunology GA 610NL UT WOS:000178966600010 PM 12410800 ER PT J AU Vawter, MP Crook, JM Hyde, TM Kleinman, JE Weinberger, DR Becker, KG Freed, WJ AF Vawter, MP Crook, JM Hyde, TM Kleinman, JE Weinberger, DR Becker, KG Freed, WJ TI Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE microarray; schizophrenia; genomics; gene expression; postmortem; prefrontal cortex ID IONOTROPIC GLUTAMATE RECEPTORS; MEDIAL TEMPORAL-LOBE; CDNA MICROARRAYS; MESSENGER-RNAS; BINDING; BRAIN; CELLS; HALOPERIDOL; APOPTOSIS; PROTEINS AB Microarray studies can be used to examine expression levels for large numbers of genes simultaneously and may be applied to identify genes involved in schizophrenia. A microarray with 1127 brain-relevant genes was used to screen relative gene expression in the dorsolateral prefrontal cortex (DLPFC) from three pools of patients with schizophrenia (n = 15) and three matched control pools (n = 15). Pooling of tissue samples was employed as a strategy to detect changes in gene expression that are consistently found across individual cases of schizophrenia. Differences in gene expression were examined by z-ratios in addition to traditional normalized ratios. Three genes that showed consistently decreased expression in schizophrenia by both z-ratio differences and decreased normalized numerical ratios were identified. These were histidine triad nucleotide-binding protein (HINT), ubiquitin conjugating enzyme E2N (UBE2N) and glutamate receptor, ionotropic, AMPA 2 (GRIA2). Moreover, HINT gene expression was decreased to a similar degree in a prior study. In addition, a decrease in AMPA receptor expression is consistent with a decrease in glutamate synaptic function. These results are subject to limitations based on variations inherent to human subjects and tissue samples, possible effects of neuroleptic treatment, and the requirement for verification using independent techniques. Published by Elsevier Science B.V. C1 NIDA, Cellular Neurobiol Res Branch, Baltimore, MD 21224 USA. Univ Calif Irvine, Irvine, CA 92697 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIA, DNA Array Unit, Res Resources Branch, Baltimore, MD 21224 USA. RP Freed, WJ (reprint author), NIDA, Cellular Neurobiol Res Branch, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 27 TC 189 Z9 195 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 1 PY 2002 VL 58 IS 1 BP 11 EP 20 AR PII S0920-9964(01)00377-2 DI 10.1016/S0920-9964(01)00377-2 PG 10 WC Psychiatry SC Psychiatry GA 605AV UT WOS:000178654000002 PM 12363385 ER PT J AU Xing, GQ Chavko, M Zhang, LX Yang, ST Post, RM AF Xing, GQ Chavko, M Zhang, LX Yang, ST Post, RM TI Decreased calcium-dependent constitutive nitric oxide synthase (cNOS) activity in prefrontal cortex in schizophrenia and depression SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cNOS activity; prefrontal cortex; schizophrenia; affective disorders ID METHYL-D-ASPARTATE; NADPH-DIAPHORASE; CORTICAL DEVELOPMENT; MAJOR DEPRESSION; CARBON-DIOXIDE; FRONTAL-LOBE; EXPRESSION; NEURONS; BRAIN; ABNORMALITIES AB To further understand the potential role of nitric oxide synthase (NOS) in schizophrenia and affective disorders, we determined the calcium-dependent constitutive NOS (cNOS) enzymatic activity and protein levels in the prefrontal cortex of postmortem brains of patients with unipolar, bipolar, and schizophrenic disorders and non-psychiatric controls (n = 15 for each group). Protein levels of two NOS isoforms, nNOS and eNOS, were not significantly different from the non-psychiatric controls in any of the patient groups. However, cNOS activity was significantly lower in schizophrenic patients (mean +/- S.E. = 19.1 +/- 3.2 cpm/mug/45 min) than in the control group (28.5 +/- 3.4, P < 0.05). Trends of lower cNOS activity were found in unipolar (20.3 +/- 2.6, P = 0.062) and bipolar patients (20.8 +/- 3.0, P = 0.079). Males had significantly higher NOS activity (25.4 +/- 2, n = 36, P = 0.01) than females (17.3 +/- 1.9, n = 24), but no significant diagnosis and gender interactions were found. To minimize potential effects of extended postmortem interval (PMI) on NOS activity and proteins, the PMI was limited to 30 h and the data (n = 38) were re analyzed. cNOS activity was significantly (P<0.05) lower in patients with schizophrenia (15.8 +/- 5.6, P = 0.026) and unipolar depression (18.8 +/- 3.2, P = 0.042) but not in patients with bipolar illness (22.9 +/- 3.4, P = 0.21) than in the control group (29.5 +/- 3.7). cNOS activity was significantly correlated with brain pH in the total sample (r = 0.28, P < 0.05, n = 60) and in the PMI controlled subgroup (r = 0.43, P < 0.01, n = 38). Our data provide evidence of reduced cNOS activity in the postmortem brains of patients with schizophrenia and depression. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. USN, Med Res Ctr, Silver Spring, MD 20910 USA. NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Xing, GQ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 50 TC 59 Z9 61 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 1 PY 2002 VL 58 IS 1 BP 21 EP 30 AR PII S0920-9964(01)00388-7 DI 10.1016/S0920-9964(01)00388-7 PG 10 WC Psychiatry SC Psychiatry GA 605AV UT WOS:000178654000003 PM 12363386 ER PT J AU Selkoe, DJ Hardy, J AF Selkoe, DJ Hardy, J TI The search for an amyloid solution - Response SO SCIENCE LA English DT Letter ID BETA-PROTEIN-PRECURSOR; ALZHEIMERS-DISEASE; MOUSE MODEL; PEPTIDE; PATHOLOGY; MUTATION; CELLS; BRAIN; DIMER C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Selkoe, DJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. RI Hardy, John/C-2451-2009 NR 18 TC 8 Z9 8 U1 2 U2 14 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 NOV 1 PY 2002 VL 298 IS 5595 BP 963 EP 964 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 609XQ UT WOS:000178932000032 ER PT J AU Biragyn, A Ruffini, PA Leifer, CA Klyushnenkova, E Shakhov, A Chertov, O Shirakawa, AK Farber, JM Segal, DM Oppenheim, JJ Kwak, LW AF Biragyn, A Ruffini, PA Leifer, CA Klyushnenkova, E Shakhov, A Chertov, O Shirakawa, AK Farber, JM Segal, DM Oppenheim, JJ Kwak, LW TI Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2 SO SCIENCE LA English DT Article ID INNATE IMMUNITY; ANTITUMOR IMMUNITY; COMPLEXES; PROTEIN; CD14; LPS AB beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens. C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. Sci Applicat Int Corp, Prot Chem Lab, Frederick, MD 21702 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Biragyn, A (reprint author), NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. FU NCI NIH HHS [N0L-CO-12400] NR 20 TC 615 Z9 680 U1 3 U2 28 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 NOV 1 PY 2002 VL 298 IS 5595 BP 1025 EP 1029 DI 10.1126/science.1075565 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 609XQ UT WOS:000178932000057 PM 12411706 ER PT J AU Scott, PA Pancioli, AM Davis, LA Frederiksen, SM Eckman, J AF Scott, PA Pancioli, AM Davis, LA Frederiksen, SM Eckman, J TI Prevalence of atrial fibrillation and antithrombotic prophylaxis in emergency department patients SO STROKE LA English DT Article DE anticoagulants; atrial fibrillation; stroke prevention ID HEALTH-CARE PROFESSIONALS; TISSUE-PLASMINOGEN ACTIVATOR; AMERICAN-HEART-ASSOCIATION; ACUTE ISCHEMIC STROKE; THERAPY; MANAGEMENT; PREVENTION; STATEMENT; COMMUNITY; RISK AB Background and Purpose-The emergency department (ED), as the point of first medical contact for many complaints referable to atrial fibrillation (AF) and a common source of primary care, occupies a unique position to identify AF patients at risk of stroke. This study evaluates that potential by determining the prevalence of AF in an ED population and assessing antithrombotic use in those patients with recurrent AF. Methods-This was a multicenter, retrospective, cross-sectional study of consecutive records of ED patients with AF identified by ECG between January and June 1998. American Heart Association and modified Stroke Prevention in Atrial Fibrillation criteria established high-risk patients and contraindications to anticoagulation, respectively. Results-We identified 866 records with ECG-proven AF in 78 787 patient visits for an estimated prevalence of 1.10% (95% CI, 1.03 to 1.17). We found that 556 records had a prior history of AF; of these, 221 (40%) used warfarin alone, 155 (28%) had antiplatelet therapy alone, 28 (5%) used both, and 152 (27%) had no antithrombotic therapy identified. Sixty-eight patients (12%; 95% CI, 0.10 to 0.15) were warfarin eligible and without antithrombotic therapy. An additional 64 (12%; 95% CI, 0.09 to 0.14) had antiplatelet therapy alone. In warfarin-eligible patients, no differences were identified between the anticoagulated and nonanticoagulated groups on the basis of age, sex, or race. Of patients on warfarin with a measured international normalized ratio, 61% (95% CI, 0.55 to 0.67) were outside the AHA-recommended range of 2.0 to 3.0. Conclusions-AF is a common finding in an ED population. Many are warfarin eligible and untreated or under-treated. Methods to increase anticoagulant use in this at-risk population warrant further investigation. C1 Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA. Univ Cincinnati, Cincinnati, OH USA. NINDS, NIH, Div Diagnost & Therapeut, Bethesda, MD 20892 USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. RP Scott, PA (reprint author), Univ Michigan, Dept Emergency Med, 1500 E Med Ctr Dr,TC B 1354,Box 0303, Ann Arbor, MI 48109 USA. NR 30 TC 35 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2002 VL 33 IS 11 BP 2664 EP 2669 DI 10.1161/01.STR.0000035260.70403.88 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 612LE UT WOS:000179076100022 PM 12411658 ER PT J AU Rathore, SS Hinn, AR Cooper, LS Tyroler, HA Rosamond, WD AF Rathore, SS Hinn, AR Cooper, LS Tyroler, HA Rosamond, WD TI Characterization of incident stroke signs and symptoms - Findings from the atherosclerosis risk in communities study SO STROKE LA English DT Article DE cerebrovascular disorders; epidemiology; pathology; stroke ID TRENDS; MORTALITY; SEVERITY; DISEASE AB Background and Purpose-Although patterns of stroke occurrence and mortality have been well studied, few epidemiological data are available regarding the clinical characteristics of stroke events. Methods-We evaluated hospitalized stroke events reported in the Atherosclerosis Risk in Communities (ARIC) Study to describe the clinical characteristics of incident stroke. Confirmed stroke cases (n=474) were evaluated for stroke symptoms (headache, vertigo, gait disturbance, convulsions) and stroke signs (hemianopia, diplopia, speech deficits, paresis, paresthesia/sensory deficits) and their univariate associations with race, sex, and stroke subtype. Results-Over 9.2 years of follow-up, 402 (85%) ischemic and 72 (15%) hemorrhagic strokes occurred. Frequency of stroke symptoms (95% CIs) were as follows: headache (27.4%; 23.4% to 31.4%), gait disturbance (10.8%; 7.9% to 13.6%), convulsions (4.4%; 2.6% to 6.3%), and vertigo (2.1%; 0.8% to 3.4%). Speech deficits occurred in 24.0% (20.2% to 27.9%), hemianopia in 14.6% (11.4% to 17.7%), and diplopia in 5.5% (3.4% to 7.5%) of cases. Most cases involved paresis (81.6%; 78.1% to 85.1%), while fewer cases experienced sensory deficits (44.5%; 40.0% to 49.0%). Blacks were more likely than whites to experience paresis (85.4% versus 78.2%; P=0.044). Men were more likely than women to experience a gait disturbance (14.4% versus 6.7%; P=0.007). Persons with hemorrhagic strokes had a higher proportion of headaches (55.6% versus 22.4%; P=0.001) and convulsions (11.1% versus 3.2%; P=0.003) than those with ischemic events, while speech and sensory deficits were more common in ischemic strokes (26.1% versus 12.5%, P=0.013, and 49.0% versus 19.4%, P=0.001, respectively). Conclusions-We present epidemiological data concerning the clinical characteristics of incident stroke in a populationbased cohort. Although minor differences by race, sex, and stroke subtype were observed, data from additional follow-up are required to confirm observed variations. C1 Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Bank Amer Ctr, Chapel Hill, NC 27514 USA. Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Internal Med, New Haven, CT USA. Univ N Carolina, Div Neurol, Dept Med, Sch Med, Chapel Hill, NC USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Rosamond, WD (reprint author), Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Bank Amer Ctr, 137 E Franklin St,suite 306, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [N01-HC-55022, N01-HC-55015, N01-HC-55021, N01-HC-55020, N01-HC-55019, N01-HC-55018, N01-HC-55016] NR 11 TC 98 Z9 103 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2002 VL 33 IS 11 BP 2718 EP 2721 DI 10.1161/01.STR.0000035286.87503.31 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 612LE UT WOS:000179076100031 PM 12411667 ER PT J AU Yamada, K Flippen-Anderson, JL Jacobson, AE Rice, KC AF Yamada, K Flippen-Anderson, JL Jacobson, AE Rice, KC TI Probes for narcotic receptor mediated phenomena; 29: Synthesis of rac(4R,6aR,11bR)-3-methyl-2,3,4,5,6,6a-hexahydro-1H-4,11b-methanobenzo-f uro[3,2-d]azocin-10-ol, the para-a oxide-bridged phenylmorphan isomer, and a new route to rac-(4R,6aR,11bR)-3-methyl-2,3,4,5,6,6a-hexahydro-1H-4,11b-methanobenzof uro[3,2-d]azocin-8-ol, the ortho-a oxide-bridged phenylmorphan isomer SO SYNTHESIS-STUTTGART LA English DT Article DE phenylmorphan; narcotic antagonist; drugs; ring closure; heterocycles ID PARKINSONISM; SELECTIVITY; LIGANDS AB A six-step synthesis of the para-a oxide-bridged phenylmorphan isomer rac-(4R,6aR,11bR)-3-methyl-2,3,4,5,6,6a-hexahydro-IH-4,11b-methanobenzofuro[3,2-d]azocin-10-ol (4), was achieved using Okahara's reagent, 3-chloro-2-methoxymethoxy-propene, to prepare the key intermediate 8. Bromination was directed at the desired carbon atom via the correctly positioned ketone moiety in 8. O-Demethylation followed by subsequent displacement of the bromine by the phenolic ion in situ gave ketone 9 that, after reduction to the alcohol and conversion to the bis-mesylate, could be reduced to obtain the desired product. The structure of was unequivocally determined by an X-ray spectroscopic study. A similar sequence of reactions provided a novel, much shorter synthetic route to the known ortho-a oxide-bridged phenylmorphan isomer. C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, Bldg 8,Rm B1-23, Bethesda, MD 20892 USA. EM kr21f@nih.gov NR 21 TC 18 Z9 18 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0039-7881 J9 SYNTHESIS-STUTTGART JI Synthesis PD NOV PY 2002 IS 16 BP 2359 EP 2364 PG 6 WC Chemistry, Organic SC Chemistry GA 618AB UT WOS:000179393600008 ER PT J AU Tofler, GH D'Agostino, RB Jacques, PF Bostom, AG Wilson, PWF Lipinska, I Mittleman, MA Selhub, J AF Tofler, GH D'Agostino, RB Jacques, PF Bostom, AG Wilson, PWF Lipinska, I Mittleman, MA Selhub, J TI Association between increased homocysteine levels and impaired fibrinolytic potential: Potential mechanism for cardiovascular risk SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE homocysteine; cardiovascular disease; thrombosis ID TISSUE-PLASMINOGEN-ACTIVATOR; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; VONWILLEBRAND-FACTOR; HEART-DISEASE; THROMBOSIS; HYPERHOMOCYSTEINEMIA; DEATH AB Background: Elevated homocysteine levels increase cardiovascular risk although the mechanism is not well understood. Since thrombosis plays an important role in plaque development and acute coronary syndromes, hyperhomocysteinemia may increase risk by increasing the thrombotic potential. Methods and Results: Hemostatic risk factors were measured in 3216 individuals (1451 men and 1765 women) free of cardiovascular disease who participated in cycle 5 of the Framingham Offspring Study. An increase in homocysteine level was associated with a rise in plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (TPA) antigen, von Willebrand factor and fibrinogen level. After regression analyses adjusting for covariates, there remained significant associations between homocysteine and PAI-1 and TPA antigen. Conclusion: Increasing homocysteine levels are associated with impaired fibrinolytic potential, as indicated by increased PAI-1 and TPA antigen levels. These data suggest that folic acid and other homocysteine lowering therapies may decrease cardiac events through a reduction in thrombotic tendency. C1 Royal N Shore Hosp, St Leonards, NSW 2065, Australia. Boston Univ, Dept Math, Boston, MA 02215 USA. Tufts Univ, USDA, Human Nutr Res Ctr, Ctr Aging, Medford, MA 02155 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Tofler, GH (reprint author), Royal N Shore Hosp, St Leonards, NSW 2065, Australia. FU NHLBI NIH HHS [R01-HL-48157] NR 46 TC 36 Z9 48 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD NOV PY 2002 VL 88 IS 5 BP 799 EP 804 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 615LD UT WOS:000179245900018 PM 12428097 ER PT J AU Suzuki, H Willingham, MC Cheng, SY AF Suzuki, H Willingham, MC Cheng, SY TI Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: A mouse model of thyroid carcinogenesis SO THYROID LA English DT Article ID SECRETING PITUITARY-TUMOR; RET/PTC1 ONCOGENE; HEPATOCELLULAR-CARCINOMA; GENERALIZED RESISTANCE; PAPILLARY CARCINOMAS; TARGETED EXPRESSION; TRANSGENIC MICE; LIGAND-BINDING; V-ERBA; GROWTH AB The molecular genetic basis of thyroid carcinogenesis is not well understood. Most of the existing models of thyroid cancer only rarely show metastases, and this has limited progress in the understanding of the molecular events in thyroid cancer invasion and metastasis. We have recently generated a mutant mouse by introducing a dominant negative mutant thyroid hormone nuclear receptor gene, TRbetaPV, into the TRbeta gene locus. In this TRbetaPV mouse, the regulation of the thyroid-pituitary axis is disrupted, leading to a mouse with high levels of circulating thyroid-stimulating hormone and extensive hyperplasia of follicular epithelium within the thyroid. As TRbeta(PV/PV) mice, but not TRbeta(PV/+) mice, aged, metastatic thyroid carcinoma developed. Histologic evaluation of thyroids of 5-14-month-old mice showed capsular invasion (91%), vascular invasion (74%), anaplasia (35%), and metastasis to the lung and heart (30%). Previous models of thyroid cancer have focused on genes that control initial carcinogenesis, but this model provides an unusual opportunity to study the alterations in gene regulation that occur with clinically relevant changes during progression and metastasis in a predictable fashion. C1 NCI, Mol Biol Lab, Gene Regulat Sect, Ctr Canc Res, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Gene Regulat Sect, Ctr Canc Res, 37 Convent Dr,Room 5128,MSC 4264, Bethesda, MD 20892 USA. NR 26 TC 134 Z9 136 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2002 VL 12 IS 11 BP 963 EP 969 DI 10.1089/105072502320908295 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 620MZ UT WOS:000179538300005 PM 12490073 ER PT J AU Nyska, A Kohen, R AF Nyska, A Kohen, R TI Oxidation of biological systems: Oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Toxicologic-Pathologists CY JUN, 2000 CL PHOENIX, ARIZONA SP Soc Toxicol Pathologists DE antioxidants; pro-oxidant; reducing power; cyclic voltammetry; oxidative damage markers ID CLOSED-HEAD INJURY; MOLECULAR-WEIGHT ANTIOXIDANTS; NITRIC-OXIDE SYNTHASE; FREE-RADICAL THEORY; HUMAN-BLOOD-PLASMA; NF-KAPPA-B; DNA-DAMAGE; VITAMIN-E; CYCLIC VOLTAMMETRY; LIPID-PEROXIDATION AB Reactive oxygen species (ROS) and other radicals are involved in a variety of biological phenomena, such as mutation, carcinogenesis, degenerative and other diseases, inflammation, aging, and development. ROS are well recognized for playing a dual role as deleterious and beneficial species. The objectives of this review are to describe oxidative stress phenomena, terminology, definitions, and basic chemical characteristics of the species involved; examine the biological targets susceptible to oxidation and the defense mechanisms of the organism against these reactive metabolites; and analyze methodologies, including immunohistochemical markers, used in toxicological pathology in the visualization of oxidative stress phenomena. Direct detection of ROS and other free radicals is difficult, because these molecules are short-lived and highly reactive in a nonspecific manner. Ongoing oxidative damage is, thus, generally analyzed by measurement of secondary products including derivatives of amino acids, nuclei acids, and lipid peroxidation. Attention has been focused on electrochemical methods based on voltammetry measurements for evaluating the total reducing power of biological fluids and tissues. This approach can function as a tool to assess the antioxidant-reducing profile of a biological site and follow changes in pathological situations. This review thus includes different topics essential for understanding oxidative stress phenomena and provides tools for those intending to conduct study and research in this field. C1 Hebrew Univ Jerusalem, Fac Med, Dept Pharmaceut, Sch Pharm, IL-91120 Jerusalem, Israel. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Kohen, R (reprint author), Hebrew Univ Jerusalem, Fac Med, Dept Pharmaceut, Sch Pharm, POB 12065, IL-91120 Jerusalem, Israel. NR 273 TC 787 Z9 816 U1 21 U2 112 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2002 VL 30 IS 6 BP 620 EP 650 DI 10.1080/01926230290166724 PG 31 WC Pathology; Toxicology SC Pathology; Toxicology GA 615KB UT WOS:000179243400002 ER PT J AU Rao, GN AF Rao, GN TI Diet and kidney diseases in rats SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Toxicologic-Pathologists CY JUN, 2000 CL PHOENIX, ARIZONA SP Soc Toxicol Pathologists DE nephropathy; nephrocalcinosis; protein; Ca : P ratio; cardiomyopathy; control of nephropathy; prevention of nephrocalcinosis; control of cardiomyopathy ID COMMERCIAL RODENT DIETS; FISCHER-344 RATS; NTP-2000; NEPHROCALCINOSIS; TOXICOLOGY; TOXICITY; GROWTH; MICE AB Diet-associated kidney diseases of rats includes nephropathy in both sexes and nephrocalcinosis in females. High protein content of diets appears to be the major cause for severe nephropathy and changing the source of protein to one such as soy protein, restricting caloric intake, or modifying the diet to decrease protein consumption could decrease the severity of nephropathy. The NTP-2000 diet with lower protein content than most diets decreases the severity of nephropathy and increases the survival of Fischer 344 rats without substantial changes in growth patterns and body weights. Nephrocalcinosis, characterized by mineralization of renal tubules at the corticomedullary junction, has been reported in young and adult female rats of most strains and stocks suggesting a major contribution of female sex hormones to the development of this lesion. Calcium (Ca), phosphorous ( P), magnesium (Mg), and chloride ( Cl) imbalances, especially a Ca: P ratio of less than 1.0 in diet, are considered to be associated with this lesion. Most commercial diets commonly used for toxicology studies have a Ca: P molar ratio of less than 1.0. Increasing the Ca: P molar ratio to more than 1.0 and closer to 1.3 in the AIN-93 purified diet and NTP-2000 nonpurified diet prevents the development of this lesion. Genetics will predispose rats to some diseases and environmental factors will influence the severity of these diseases. Diet is one of the most important environmental factors. Diets balanced for nutrients without excesses could markedly improve the health of rats used in chronic studies leading to substantial increases in survival and thereby accomplish the objective of chronic toxicity and carcinogenicity studies. C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Rao, GN (reprint author), NIEHS, Natl Toxicol Program, MD B3-08,POB 12233, Res Triangle Pk, NC 27709 USA. NR 21 TC 28 Z9 28 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2002 VL 30 IS 6 BP 651 EP 656 DI 10.1080/01926230290166733 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 615KB UT WOS:000179243400003 PM 12512864 ER PT J AU Seely, JC Haseman, JK Nyska, A Wolf, DC Everitt, JI Hailey, JR AF Seely, JC Haseman, JK Nyska, A Wolf, DC Everitt, JI Hailey, JR TI The effect of chronic progressive nephropathy on the incidence of renal tubule cell neoplasms in control male F344 rats SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Toxicologic-Pathologists CY JUN, 2000 CL PHOENIX, ARIZONA SP Soc Toxicol Pathologists DE kidney; nephropathy; neoplasia; males; Fischer 344 rat; National Toxicology Program ID SPRAGUE-DAWLEY RATS; FISCHER-344 RATS; B6C3F(1) MICE; CARCINOGENICITY; PROLIFERATION; MECHANISMS; KIDNEY; HYDROQUINONE; TOXICITY; NTP-2000 AB Chronic progressive nephropathy (CPN) is the most frequently diagnosed lesion in the rat kidney. It has many components including degeneration and regeneration of renal tubule (RT) epithelium, glomerular lesions and interstitial inflammation and fibrosis. The incidence and severity of CPN is strain, age, and sex dependent and may be altered by a number of factors including exposure to xenobiotics. In National Toxicology Program (NTP) 2-year bioassays, xenobiotic-associated increased severity ( exacerbation) of CPN often occurs in association with a marginal increased incidence of renal tubule cell neoplasms (RTCN). The relationship between CPN and RTCN development has not been definitively determined. The present study evaluated the association between severity of CPN and the occurrence of RTCN in control male F344 rats. A slight but statistically significant increase in CPN severity was present in those animals with RTCN compared to aged-matched controls without RTCN. Although these data suggest there is a positive correlation between CPN and RTCN, cause and effect were not determined. This marginal association suggests that the number of RTCNs that may develop secondary to chemically exacerbated nephropathy would be few. C1 Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. US EPA, Div Environm Carcinogenesis, NHEERL, ORD, Res Triangle Pk, NC USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC USA. RP Seely, JC (reprint author), Expt Pathol Labs Inc, POB 12766, Res Triangle Pk, NC 27709 USA. OI Everitt, Jeffrey/0000-0003-0273-6284 NR 39 TC 31 Z9 33 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2002 VL 30 IS 6 BP 681 EP 686 DI 10.1080/01926230290166779 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 615KB UT WOS:000179243400008 PM 12512869 ER PT J AU Long, PH Herbert, RA AF Long, PH Herbert, RA TI Epithelial-induced intrapulpal Denticles in B6C3F1 mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE mice; teeth; incisor; pulp; denticle; dysplasia; malformation; pathology ID RATS AB Multiple intrapulpal denticles were observed in maxillary incisors of control and treated B6C3F1 mice used in a chronic inhalation study. Histologically, the denticles originated from multiple small budlike projections emanating from the epithelial sheath, immediately adjacent to the pulp chamber. The denticles were round to ovoid in shape with a central cavity surrounded by tubular dentin. Immature denticles contained epithelial cells within the central cavity, whereas mature denticles were either devoid of cells or contained cell fragments. A layer of columnar odontoblasts surrounded the outer surface of each denticle. Denticles advanced in a coronal direction as the incisors grew. With continued incisor growth, some denticles impacted the tooth wall and were associated with defects in dentinogenesis, altered tooth shape, and microfractures. Some denticles became partly or entirely incorporated into the dentin of the tooth. Intrapulpal denticle formation may represent a previously unidentified alteration that could contribute to the development of dental dysplasia in mice by interfering with normal tooth development and predisposing affected teeth to malformation and biomechanical failure with fracture. C1 Pathol Associates Inc, W Chester, OH 45069 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Long, PH (reprint author), Pathol Associates Inc, 6217 Ctr Pk Dr, W Chester, OH 45069 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2002 VL 30 IS 6 BP 744 EP 748 DI 10.1080/01926230290166832 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 615KB UT WOS:000179243400015 PM 12512876 ER PT J AU Foster, PMD Gray, LE AF Foster, PMD Gray, LE TI Endocrine active agents: Implications of adverse and non-adverse changes - Response SO TOXICOLOGIC PATHOLOGY LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. Schering Plough Corp, Res Inst, Lafayette, NJ 07848 USA. US EPA, NHEERL, Res Triangle Pk, NC 27711 USA. RP Foster, PMD (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 2002 VL 30 IS 6 BP 757 EP 757 DI 10.1080/01926230290166869 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 615KB UT WOS:000179243400018 ER PT J AU Waalkes, MP Liu, J AF Waalkes, MP Liu, J TI Purine nucleoside phosphorylase: A fortuitous cytosolic arsenate reductase? SO TOXICOLOGICAL SCIENCES LA English DT Article ID MONOMETHYLARSONOUS ACID; ARSENITE; METHYLATION; METABOLISM; TOXICITY; RATS AB The articles highlighted in this issue are this issue are "Purine Nucleoside Phosphorylase as a Cytosolic Arsenate Reductase" by Zoltan Gregus and Balazs Nemeti (pp. 4-12) and "Reduction of Arsenate to Arsenite in Hepatic Cytosol" by Balazs Nemeti and Zoltan Gregus (pp. 13-19). C1 NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 13 TC 4 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2002 VL 70 IS 1 BP 1 EP 3 DI 10.1093/toxsci/70.1.1 PG 3 WC Toxicology SC Toxicology GA 608AQ UT WOS:000178823300001 PM 12388828 ER PT J AU Nyska, A Moomaw, CR Foley, JF Maronpot, RR Malarkey, DE Cummings, CA Peddada, S Moyer, CF Allen, DG Travlos, G Chan, PC AF Nyska, A Moomaw, CR Foley, JF Maronpot, RR Malarkey, DE Cummings, CA Peddada, S Moyer, CF Allen, DG Travlos, G Chan, PC TI The hepatic endothelial carcinogen riddelliine induces endothelial apoptosis, mitosis, S phase, and p53 and hepatocytic vascular endothelial growth factor expression after short-term exposure SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-of-Toxicology CY MAR, 2002 CL NASHVILLE, TENNESSEE SP Society Toxicol DE pyrrolizidine alkaloid; endothelium; hemangiosarcoma; cytotoxicity; vascular endothelial growth factor; VEGFR2; BrdU; factor VIII-related antigen; von Willebrand factor; p53 ID TUMOR-SUPPRESSOR GENE; MONOCROTALINE PYRROLE; MOLECULAR EPIDEMIOLOGY; CELL-PROLIFERATION; VINYL-CHLORIDE; ANGIOGENESIS; RATS; MUTATIONS; GLUTATHIONE; HYPOXIA AB Riddelliine is a naturally occurring pyrrolizidine alkaloid found in certain poisonous rangeland plants of the western United States. In National Toxicology Program 2-year studies, riddelliine induced high incidences of hemangiosarcoma in the liver of F344/N rats (both sexes) and B6C3F1 mice (males). To understand this pathogenesis, we tested short-term effects of riddelliine. Three groups (control; 1.0 mg/kg/day, high dose used in the 2-year study; and 2.5 mg/kg/day) of seven male F344/N rats per group were terminated after 8 consecutive doses and 30 doses (6 weeks, excluding weekends). Serum vascular endothelial growth factor (VEGF), histological, immunohistochemical [factor VIII-related antigen/von Willebrand factor (fVIII-ra/vWf)], VEGF, VEGF receptor-2 (VEGFR2), glutathione S-transferase-pi, S-phase (BrdU), p53, apoptosis, and ultrastructural evaluations were performed on the liver. Following 8 doses of 1.0 and 2.5 mg/kg/day, increased numbers of apoptotic and S-phase nuclei appeared in hepatocytes and endothelial cells. Following 30 doses of 1.0 and 2.5 mg/kg/day, hepatocytes exhibited reduced mitosis, fewer S-phase nuclei, increased hypertrophy, and fatty degeneration, while endothelial cells showed karyomegaly, cytomegaly, decreased apoptosis, more S-phase nuclei, and p53 positivity. Hepatocytes of treated animals expressed higher VEGF immunopositivity. That altered endothelial cells were fVIII-ra/vWf and VEGFR2 positive confirmed their identity. These changes may have promoted hemangiosarcoma development upon long-term exposure through endothelial adduct formation, apoptosis, proliferation of endothelial cells having undamaged and/or damaged DNA, and mutation. Endothelial proliferation may also have been promoted through endothelial arrest at S phase, which was associated with endothelial karyo- and cytomegaly, resulting in hepatocytic hypoxia, triggering VEGF induction. 2002 Elsevier Science (USA). C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. A Charles River Co, Pathol Associates, Durham, NC 27713 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. RI Peddada, Shyamal/D-1278-2012 NR 56 TC 14 Z9 15 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2002 VL 184 IS 3 BP 153 EP 164 DI 10.1006/taap.2002.9485 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 615HL UT WOS:000179239700004 PM 12460743 ER PT J AU Stroncek, DF Rainer, T Sharon, V Byrne, KM Noguchi, CT Klein, HG Schechter, AN Leitman, SF AF Stroncek, DF Rainer, T Sharon, V Byrne, KM Noguchi, CT Klein, HG Schechter, AN Leitman, SF TI Sickle Hb polymerization in RBC components from donors with sickle cell trait prevents effective WBC reduction by filtration SO TRANSFUSION LA English DT Article ID BLOOD COMPONENTS; ERYTHROCYTES; HEMOGLOBIN; DISEASE AB Background: RBC components collected from donors with sickle cell trait frequently occlude WBC-reduction filters. In vitro, sickle trait RBCs have the potential for sickle Hb (Hb S) polymerization at low oxygen saturations and high Hb concentrations. Study design and method: To determine if the low pH and high osmolarity of the CP2D used in the collection contributed to filter failures, the filterability of sickle trait donor RBCs collected in CP2D was compared with RBCs from the same donors collected in heparin. Results: Five of six sickle trait components collected in CP2D did not complete filtration, but all six RBC components collected in heparin filtered completely. RBC components collected in CP2D from four other sickle trait donors were divided in two, and one-half was treated with carbon monoxide to convert Hb S to its liganded form to prevent Hb S polymerization. All four carbon monoxide-treated components filtered within 9 minutes, but only one untreated component filtered completely. RBC components collected by apheresis contained less CP2D, and five of seven sickle trait apheresis components filtered completely; four of the five filtered rapidly (<15 min) and one filtered in 100 minutes. Hb oxygen saturation was greater in the four rapidly filtering apheresis RBC components (68&PLUSMN;9%) than in the three that filtered slowly or incompletely (37&PLUSMN;5%, p=0.03). Conclusions: Hb S polymerization appears responsible for RBC WBC-reduction filter failures. Citrate anticoagulant and low oxygen saturation are responsible in part for Hb S polymerization in this setting. C1 NIDDKD, Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIDDKD, Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bldg 10,Room 1C711,10 Ctr Dr,MSC-1184, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 20 TC 16 Z9 17 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2002 VL 42 IS 11 BP 1466 EP 1472 DI 10.1046/j.1537-2995.2002.00206.x PG 7 WC Hematology SC Hematology GA 613ZE UT WOS:000179161000012 PM 12421220 ER PT J AU Stenland, CJ Lee, DC Brown, P Petteway, SR Rubenstein, R AF Stenland, CJ Lee, DC Brown, P Petteway, SR Rubenstein, R TI Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma SO TRANSFUSION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; BLOOD COMPONENTS; INFECTIVITY AB Background: Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrPvCJD), human sporadic CJD (PrPsCJD) and Gerstmann-Straussler-Scheinker (PPpGSS) syndrome was compared to the partitioning of hamster scrapie (PrPSc) in three plasma protein purification steps. Sheep scrapie (PrPSc) was similarly evaluated. Study design and methods: The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrPvCJD, human PrPsCJD, human PrPGSS, sheep PrPSc, and hamster 263K PrPSc. The partitioning of the pathogenic form of the PrP was analyzed. Results: Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrPSc. A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (greater than or equal to3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. Conclusions: These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model. C1 NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. New York State Inst Basic Res Dev Disabil, Lab Mol & Biochem Neurovirol, Staten Isl, NY USA. RP Stenland, CJ (reprint author), Bayer Corp, Dept Pathogen Safety Res, Bayer Biol Prod, POB 13887,85 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 11 TC 42 Z9 43 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2002 VL 42 IS 11 BP 1497 EP 1500 DI 10.1046/j.1537-2995.2002.00216.x PG 4 WC Hematology SC Hematology GA 613ZE UT WOS:000179161000016 PM 12421224 ER PT J AU Bux, J Stroncek, D AF Bux, J Stroncek, D TI Human neutrophil antigens SO TRANSFUSION LA English DT Letter ID AUTOIMMUNE NEUTROPENIA; TRANSFUSION C1 Univ Giessen, Inst Clin Immunol & Transfus Med, D-6300 Giessen, Germany. NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Bux, J (reprint author), Univ Giessen, Inst Clin Immunol & Transfus Med, Langhansstr 7, D-6300 Giessen, Germany. NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2002 VL 42 IS 11 BP 1523 EP 1523 DI 10.1046/j.1537-2995.2002.00265.x PG 1 WC Hematology SC Hematology GA 613ZE UT WOS:000179161000020 PM 12421228 ER PT J AU Silva, JC Kondrashov, AS AF Silva, JC Kondrashov, AS TI Patterns in spontaneous mutation revealed by human-baboon sequence comparison SO TRENDS IN GENETICS LA English DT Article ID NUCLEOTIDE SUBSTITUTION; REGULATORY ELEMENTS; MOUSE GENOME; RATES; EVOLUTION; CHROMATIN; ISOCHORES; REGIONS; RODENTS; DAMAGE AB We have analyzed the alignment of a long homologous region of the human and baboon genomes (similar to1.5 Mb). We show that the frequency of gaps between aligned segments decreases slowly with gap length, indicating that several successive nucleotides are often deleted or inserted in one event. By contrast, runs of consecutive mismatches decrease rapidly in frequency with increasing length, following an exponential distribution, indicating that nucleotides are mostly substituted one at a time. Nucleotide substitutions are clumped at the scales of <10 and 1000-10 000 nucleotides, but show almost no aggregation at the scales of 10-100 and over similar to50 000 nucleotides. Apparently, two rather different factors make the substitution rate not exactly uniform along the DNA sequence. Comparison of regions of very similar genomes that are approximately selectively neutral makes it possible to study spontaneous mutation at a new level of resolution. C1 Inst Genom Res, Rockville, MD 20850 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Silva, JC (reprint author), Inst Genom Res, Med Ctr Dr, Rockville, MD 20850 USA. NR 23 TC 49 Z9 51 U1 2 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV PY 2002 VL 18 IS 11 BP 544 EP 547 AR PII S0168-9525(02)02757-9 DI 10.1016/S0168-9525(02)02757-9 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 607MX UT WOS:000178796300002 PM 12414177 ER PT J AU Le, YY Murphy, PM Wang, JM AF Le, YY Murphy, PM Wang, JM TI Formyl-peptide receptors revisited SO TRENDS IN IMMUNOLOGY LA English DT Review ID N-FORMYLPEPTIDE RECEPTOR; LOCALIZED JUVENILE PERIODONTITIS; PROTEIN-COUPLED RECEPTOR; ASPIRIN-TRIGGERED 15-EPI-LXA(4); LIPOXIN A(4) RECEPTORS; NEUTROPHIL CHEMOTAXIS; POTENT INHIBITORS; ESCHERICHIA-COLI; GENE-CLUSTER; ANNEXIN-I AB Leukocytes accumulate at sites of inflammation and microbial infection in direct response to locally produced chemotactic factors, which signal through specific G protein-coupled receptors. The first chemotactic factors to be structurally defined were the N-formyl peptides. Unlike other leukocyte chemoattractants, N-formyl peptides could originate from either an endogenous source, such as the mitochondrial proteins of ruptured host cells, or an exogenous source, such as the proteins of invading pathogens. This suggests that the formyl-peptide receptor (FPR) and its variant FPRL1 (FPR-like 1) are involved in host defense against bacterial infection and in the clearance of damaged cells. Recently, additional, more complex, roles for these receptors have been proposed because FPR, and to a greater extent FPRL1, have been found to interact with a menagerie of structurally diverse pro- and anti-inflammatory ligands associated with different diseases, including amyloidosis, Alzheimer's disease, prion disease and HIV How these receptors recognize such diverse ligands, which are the most important in vivo, and how they contribute to disease pathogenesis and host defense are basic questions currently under investigation that could lead to new therapeutic targets. C1 NCI, CCR, LMI, Frederick, MD 21702 USA. NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. RP Wang, JM (reprint author), NCI, CCR, LMI, Bldg 560,Room 31-40, Frederick, MD 21702 USA. NR 64 TC 367 Z9 380 U1 3 U2 20 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD NOV PY 2002 VL 23 IS 11 BP 541 EP 548 AR PII S1471-4906(02)02316-5 DI 10.1016/S1471-4906(02)02316-5 PG 8 WC Immunology SC Immunology GA 610AG UT WOS:000178938100007 PM 12401407 ER PT J AU Banks, DJ Beres, SB Musser, JM AF Banks, DJ Beres, SB Musser, JM TI The fundamental contribution of phages to GAS evolution, genome diversification and strain emergence SO TRENDS IN MICROBIOLOGY LA English DT Review ID GROUP-A STREPTOCOCCI; SCARLET FEVER TOXIN; MITOGENIC FACTOR MF; SHOCK-LIKE SYNDROME; ERYTHROMYCIN RESISTANCE; PYOGENES; GENE; EXPRESSION; MACROLIDE; BACTERIOPHAGES AB The human bacterial pathogen group A Streptococcus (GAS) causes many different diseases including pharyngitis, tonsillitis, impetigo, scarlet fever, streptococcal toxic shock syndrome, necrotizing fasciitis and myositis, and the post-infection sequelae glomerulonephritis and rheumatic fever. The frequency and severity of GAS infections increased in the 1980s and 1990s, but the cause of this increase is unknown. Recently, genome sequencing of serotype M1, M3 and M 18 strains revealed many new proven or putative virulence factors that are encoded by phages or phage-like elements. Importantly, these genetic elements account for an unexpectedly large proportion of the difference in gene content between the three strains. These new genome-sequencing studies have provided evidence that temporally and geographically distinct epidemics, and the complex array of GAS clinical presentations, might be related in part to the acquisition or evolution of phage-encoded virulence factors. We anticipate that new phage-encoded virulence factors will be identified by sequencing the genomes of additional GAS strains, including organisms non-randomly associated with particular clinical syndromes. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Banks, DJ (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 54 TC 130 Z9 134 U1 1 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD NOV PY 2002 VL 10 IS 11 BP 515 EP 521 AR PII S0966-842X(02)02461-7 DI 10.1016/S0966-842X(02)02461-7 PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 613NA UT WOS:000179137300013 PM 12419616 ER PT J AU Mocellin, S Panelli, M Wang, E Rossi, CR Marincola, FM AF Mocellin, S Panelli, M Wang, E Rossi, CR Marincola, FM TI Tumor microenvironment: What have we learned studying the immune response in this puzzling battlefield? SO TUMORI LA English DT Review DE immunotherapy; melanoma; microenvironment; vaccination ID CD8(+) T-CELLS; MHC CLASS-I; METASTATIC MELANOMA; INFILTRATING LYMPHOCYTES; HISTAMINE DIHYDROCHLORIDE; INTERLEUKIN-2 THERAPY; ANTIGEN EXPRESSION; PERIPHERAL-BLOOD; HIGH-FREQUENCIES; GENE-EXPRESSION AB Recent developments hallmark the progress in the understanding of tumor immunology and related therapeutic strategies. The administration of interleukin-2 (IL-2) to patients with cancer has shown that immune manipulation can mediate the regression of established cancers. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing against these antigens has opened new avenues for the development of active immunization of patients with cancer. However, an efficient immune response against tumor comprises an intricate molecular network still poorly understood. Only when the code governing immune responsiveness of cancer will be deciphered, new therapeutic strategies could be designed to fit biologically defined mechanisms of immune rejection of cancer. In this review, we propose that the mechanisms regulating tumor rejection in response to vaccination will be more efficiently identified by following the evolution of treatment induced events within the tumor microenvironment taking advantage of recently developed technological tools. As a model, we will discuss the observed immune response to tumor antigen-specific immunization and its relationship with the systemic administration of IL-2. C1 NIH, Immunogenet Sect, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Padua, Dept Oncol & Surg Sci, Surg Branch, I-35100 Padua, Italy. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Ctr Clin, Dept Transfus Med, Bldg 10,Room 1C-711,10 Ctr Dr MSC, Bethesda, MD 20892 USA. RI Rossi, Carlo Riccardo/A-7685-2010 OI Rossi, Carlo Riccardo/0000-0001-7875-5655 NR 76 TC 2 Z9 2 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD NOV-DEC PY 2002 VL 88 IS 6 BP 437 EP 444 PG 8 WC Oncology SC Oncology GA 649QA UT WOS:000181218400001 PM 12597134 ER PT J AU Zhang, ZJ Huckle, J Francomano, CA Spencer, RGS AF Zhang, ZJ Huckle, J Francomano, CA Spencer, RGS TI The influence of pulsed low-intensity ultrasound on matrix production of chondrocytes at different stages of differentiation: An explant study SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE cartilage; chondrocyte; ultrasound; ossification ID X COLLAGEN-SYNTHESIS; AGGRECAN GENE-EXPRESSION; CHICK STERNAL CARTILAGE; ARTICULAR-CARTILAGE; GROWTH-PLATE; IN-VITRO; OSTEOARTHRITIS; CALCIFICATION; MODEL AB The proximal and distal parts of sterna of chick embryos represent cartilage undergoing endochondral ossification and hyaline cartilage, respectively. Cartilage explants from both regions were exposed for 20 min to pulsed low-intensity ultrasound (PLIUS) with an intensity of 30 mW.cm(-2) (spatial average-temporal average) at a frequency of 1.5 MHz, with a pulse burst frequency of 1 kHz and burst duration of 200 mus. Histological and imnunohistochemical analysis was performed on days 1, 3, 5 and 7 after treatment. An anabolic effect of PLIUS on matrix production was shown by an increase of up to 10% to 20% in quantitative immunohistochemical staining for type II collagen and aggrecan in the two parts of the sternum. PLIUS also increased type X collagen staining by up to 10% in certain regions of the proximal part of the sternum. Staining for type X collagen was negative in the distal part of the sternum in both PLIUS and control groups. These results suggest that PLIUS may stimulate bone formation by increasing hypertrophy of chondrocytes directed to terminal differentiation. However, PLIUS did not induce hypertrophy in hyaline cartilage; moreover, increased matrix synthesis indicates a potential role in cartilage repair. (E-mail: spencer@helix.nih.gov) Published by Elsevier Science Inc. on behalf of World Federation for Ultrasound in Medicine Biology. C1 NIA, NIH, Baltimore, MD 21224 USA. Smith & Nephew Grp Res Ctr, York, N Yorkshire, England. RP Spencer, RGS (reprint author), NIA, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 44 Z9 53 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD NOV-DEC PY 2002 VL 28 IS 11-12 BP 1547 EP 1553 AR PII S0301-5629(02)00659-2 DI 10.1016/S0301-5629(02)00659-2 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 629GF UT WOS:000180041500020 PM 12498950 ER PT J AU Kurtkaya-Yapicier, O Scheithauer, BW Carney, JA Kovacs, K Horvath, E Stratakis, CA Vidal, S Vella, A Young, WF Atkinson, JLD Lloyd, RV Kontogeorgos, G AF Kurtkaya-Yapicier, O Scheithauer, BW Carney, JA Kovacs, K Horvath, E Stratakis, CA Vidal, S Vella, A Young, WF Atkinson, JLD Lloyd, RV Kontogeorgos, G TI Pituitary adenoma in Carney complex: An immunohistochemical, ultrastructural, and immunoelectron microscopic study SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE Carney complex; immunoelectron microscopy; pituitary adenoma; ultrastructure ID SPOTTY SKIN PIGMENTATION; PSAMMOMATOUS MELANOTIC SCHWANNOMA; MCCUNE-ALBRIGHT SYNDROME; ENDOCRINE OVERACTIVITY; GROWTH-HORMONE; REVERSIBLE TRANSDIFFERENTIATION; INSITU HYBRIDIZATION; REGULATORY SUBUNIT; CUSHING-SYNDROME; CARDIAC MYXOMAS AB First described in 1985, Carney complex is a rare, heritable disorder featuring abnormal skin pigmentation, cardiac and cutaneous myxoma, melanotic schwannoma of psammomatous type, and endocrine abnormalities, including pituitary adenomas. Patients with the latter present with elevated growth hormone (GH) levels and acromegaly or gigantism. Prolactin (PRL) elevation may also be seen. The authors have investigated 2 resected pituitary adenomas from patients with Carney complex. One, a 19-year-old female acromegalic with elevated GH, IgF-1, and PRL levels, had a mammosomatotroph adenoma immunoreactive for GH and PRL. Ultrastructurally, GH and PRL were present in the same secretory granules. The second patient, a 27-year-old acromegalic, had a sparsely granulated GH cell adenoma that by immuno-electron microscopy revealed GH immunoreactivity only. The lack of morphologic similarity between the 2 adenomas indicates that pituitary tumors in patients with Carney complex may not exhibit the same phenotype. C1 Mayo Clin, Dept Pathol & Lab Med, Rochester, MN 55905 USA. Univ Toronto, St Michaels Hosp, Dept Lab Med & Pathol, Toronto, ON M5B 1W8, Canada. NICHHD, Endocrinol Branch, Bethesda, MD 20892 USA. Univ Santiago de Compostela, Dept Anat, Lugo, Spain. Mayo Clin, Dept Endocrinol & Metab, Rochester, MN 55905 USA. Mayo Clin, Dept Neurosurg, Rochester, MN 55905 USA. Athens Gen Hosp, Dept Pathol, Athens, Greece. RP Scheithauer, BW (reprint author), Mayo Clin, Dept Pathol & Lab Med, 200 1st St SW, Rochester, MN 55905 USA. NR 37 TC 14 Z9 14 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD NOV-DEC PY 2002 VL 26 IS 6 BP 345 EP 353 DI 10.1080/01913120290104656 PG 9 WC Microscopy; Pathology SC Microscopy; Pathology GA 629LL UT WOS:000180051100001 PM 12537759 ER PT J AU Propert, KJ Payne, C Kusek, JW Nyberg, LM AF Propert, KJ Payne, C Kusek, JW Nyberg, LM TI Pitfalls in the design of clinical trials for interstitial cystitis SO UROLOGY LA English DT Review ID BENIGN PROSTATIC HYPERPLASIA; PENTOSAN POLYSULFATE SODIUM; BACILLUS-CALMETTE-GUERIN; DOUBLE-BLIND; SYMPTOM-INDEX; DATA-BASE; L-ARGININE; PENTOSANPOLYSULFATE; DIAGNOSIS; EFFICACY C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Stanford Univ, Med Ctr, Stanford, CA USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Propert, KJ (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Blockley Hall,6th Floor,423 Guardian Dr, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [R01-DK-59601, U01-DK-54127] NR 43 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD NOV PY 2002 VL 60 IS 5 BP 742 EP 748 AR PII S0090-4295(02001775-2 DI 10.1016/S0090-4295(02)01775-2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 614KU UT WOS:000179188700003 PM 12429288 ER PT J AU Mendez, A Belkaid, Y Seder, RA Sacks, D AF Mendez, A Belkaid, Y Seder, RA Sacks, D TI Optimization of DNA vaccination against cutaneous leishmaniasis SO VACCINE LA English DT Article DE DNA vaccines; Leishmania major; CD8+T cells ID IMMUNE-RESPONSES; CELLULAR-IMMUNITY; MAJOR INFECTION; NATURAL MODEL; IN-VIVO; T-CELLS; ANTIGEN; IMMUNIZATION; PROTEIN; MURINE AB The present studies were designed to examine the requirements of dose, route of inoculation and constituent antigens for the maintenance of complete and long lasting protection against cutaneous leishmaniasis due to Leishmania major conferred by a cocktail DNA vaccine encoding the Leishmania antigens LACK, LmST11 and TSA. Vaccination of C57Bl/6 mice with LACK DNA alone resulted in partial protection, whereas the combination of LmST11 and TSA provided stronger, though still incomplete protection compared to the combination of all three Ag DNAs. When intradermal (i.d.), intramuscular (i.m.), and subcutaneous (s.c.) vaccination routes were compared, i.d. immunization reduced by five-fold the dose necessary to maintain complete protection. In vivo depletion of CD4+ or CD8+ T cells provided direct evidence that both populations are necessary to mediate complete protection. These results establish intradermal vaccination using DNA encoding multiple Leishmania antigens as a way to optimize priming of CD4+ and CD8+ T cells necessary for potent and durable protection against cutaneous leishmaniasis. Published by Elsevier Science Ltd. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Room 126,Bldg 4,Ctr Dr MSC 0425, Bethesda, MD 20892 USA. NR 37 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 1 PY 2002 VL 20 IS 31-32 BP 3702 EP 3708 AR PII S0264-410X(02)00376-6 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 619RA UT WOS:000179489000013 ER PT J AU Villa, LL Bernard, HU Kast, M Hildesheim, A Amestoy, G Franco, EL AF Villa, LL Bernard, HU Kast, M Hildesheim, A Amestoy, G Franco, EL TI Past, present, and future of HPV research: highlights from the 19th International Papillomavirus Conference-HPV2001 SO VIRUS RESEARCH LA English DT Article; Proceedings Paper CT 19th International Papillomavirus Conference CY SEP 01-07, 2001 CL FLORIANOPOLIS, BRAZIL DE human papillomavirus (HPV); epidemiology; biology; immunology; cancer prevention; clinical diagnosis AB This manuscript summarizes the papers presented at. the 19th International Papillomavirus Conference, held in Florianopolis, Brazil, September 1-7, 2001, divided in four main areas: Clinical diagnosis and screening, Epidemiology, Biology and Immunology. It provides an overview of what we know about the biology and life cycle of these viruses, their interaction with human and animal hosts, and the diseases that they cause. Highlights derive from the analysis of more than 500 papers presented at the Conference. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Ludwig Inst Canc Res, Dept Virol, BR-01509010 Sao Paulo, Brazil. Natl Univ Singapore, Inst Cell & Mol Biol, Singapore 117548, Singapore. Loyola Univ, Chicago, IL 60611 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Austral, Buenos Aires, DF, Argentina. McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. RP Villa, LL (reprint author), Ludwig Inst Canc Res, Dept Virol, R Prof Antonio Prudente 109,4th Floor, BR-01509010 Sao Paulo, Brazil. EM llvilla@ludwig.org.br RI ASTAR, IMCB/E-2320-2012; OI Franco, Eduardo/0000-0002-4409-8084 NR 2 TC 5 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD NOV PY 2002 VL 89 IS 2 BP 163 EP 173 AR PII S0168-1702(02)00185-5 DI 10.1016/S0168-1702(02)00185-5 PG 11 WC Virology SC Virology GA 626YZ UT WOS:000179902500002 PM 12445656 ER PT J AU Hildesheim, A Wang, SS AF Hildesheim, A Wang, SS TI Host and viral genetics and risk of cervical cancer: a review SO VIRUS RESEARCH LA English DT Article; Proceedings Paper CT 19th International Papillomavirus Conference CY SEP 01-07, 2001 CL FLORIANOPLIS, BRAZIL DE HPV; HLA; variants; cervical neoplasia ID HUMAN-PAPILLOMAVIRUS TYPE-16; SQUAMOUS-CELL CARCINOMA; LONG CONTROL REGION; HLA-ASSOCIATED RISK; CLASS-II ALLELES; ANTIGEN CLASS-I; INTRAEPITHELIAL NEOPLASIA; DR-DQ; HUMAN-PAPILLOMAVIRUS-16 E6; ENVIRONMENT INTERACTIONS AB Infection with human papillomaviruses (HPV) is known to play a central role in the development of cervical cancer. Both host and viral genetic factors have been postulated to be important determinants of risk of HPV progression to neoplasia among infected individuals. In this report, we review epidemiological studies that have evaluated the role in cervical cancer pathogenesis of genetic variation in human leukocyte antigen (HLA) genes and in the HPV genome itself. A protective effect of HLA Class 11 DRB1*13/DBQ1*0603 alleles is the most consistent HLA finding in the published literature. A consistent association between HPV 16 non-European variants and risk of disease is also evident from published work. These findings are discussed. Gaps in our understanding and future research needs are also discussed. Published by Elsevier Science B.V. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Hildesheim, A (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7062,EPS-MSC 7234, Rockville, MD 20852 USA. NR 75 TC 178 Z9 191 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD NOV PY 2002 VL 89 IS 2 BP 229 EP 240 AR PII S0168-1702(02)00191-0 DI 10.1016/S0168-1702(02)00191-0 PG 12 WC Virology SC Virology GA 626YZ UT WOS:000179902500008 PM 12445662 ER PT J AU Watanabe, K Nijhawan, R Shimojo, S AF Watanabe, K Nijhawan, R Shimojo, S TI Shifts in perceived position of flashed stimuli by illusory object motion SO VISION RESEARCH LA English DT Article DE motion; shape; occlusion; localization; anorthoscopic perception ID ANORTHOSCOPIC PERCEPTION; LOCALIZATION; EYE AB Moving stimuli cause the position of flashed stimuli to appear shifted in the direction of motion (position capture). To examine whether position capture depends on low-level motion interactions or perception of integrated object motion, we employed a slit-view display. Two line-drawn diamonds translated horizontally in opposite directions, one above and one below the fixation cross, either behind an occluding surface with a narrow slit or without occluding surface. When the diamonds were in vertical alignment, two vertical bars were flashed, one in the center of each diamond. In the slit-view condition, the diamonds were visible through a 4-, 2-, or 1-pixel vertical slit; the width of the flashed bars always matched the width of the slit. Even though the horizontal component of physical motion was greatly reduced or absent in the slit-view conditions, observers perceived diamonds moving behind the occluding surface. Furthermore, the position of the flashed bar was captured by the moving diamonds such that each bar appeared shifted in the direction of perceived motion. We conclude that the position capture reported here has a component based on high-level motion processing that is responsible for dynamically integrating object motion and shape. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 CALTECH, Div Biol, Pasadena, CA 91125 USA. Univ Sussex, Dept Cognit & Comp Sci, Brighton BN1 9QH, E Sussex, England. NTT Corp, Commun Sci Labs, Human & Informat Sci Lab, Atsugi, Kanagawa 2430198, Japan. RP Watanabe, K (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 COnvent Dr, Bethesda, MD 20892 USA. EM kw@lsr.nei.nih.gov NR 19 TC 31 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 EI 1878-5646 J9 VISION RES JI Vision Res. PD NOV PY 2002 VL 42 IS 24 BP 2645 EP 2650 AR PII S0042-6989(02)00296-1 DI 10.1016/S0042-6989(02)00296-1 PG 6 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 631NZ UT WOS:000180175000001 PM 12445850 ER PT J AU Masson, GS Yang, DS Miles, FA AF Masson, GS Yang, DS Miles, FA TI Version and vergence eye movements in humans: open-loop dynamics determined by monocular rather than binocular image speed SO VISION RESEARCH LA English DT Article DE ocular following; disparity-vergence; dynamics; velocity tuning ID LATENCY DISPARITY VERGENCE; OCULAR-FOLLOWING RESPONSES; RANDOM-DOT STEREOGRAMS; DEPTH-PERCEPTION; MOTION; DEPENDENCE; MONKEY AB We examined the velocity dependence of the vergence and version eye movements elicited by motion stimuli that were symmetric or asymmetric at the two eyes. Movements of both eyes were recorded with the scleral search coil technique. Vergence was computed as the difference in the positions of the two eyes (left-right) and version was computed as the average position of the two eyes ((left + right)/2). Subjects faced a large tangent screen onto which two identical random-dot patterns were back-projected. Each pattern was viewed by one eye only using crossed-polarizers and its position was controlled by X/Y mirror galvanometers. Viewing was always binocular and horizontal velocity steps (range, 5-240 deg/s) were applied to one (asymmetric stimulus) or both (symmetric stimulus) patterns similar to50 ins after a centering saccade. With the symmetric stimulus, them motion at the two eyes could be either in the opposite direction (eliciting vergence responses) or in the same direction (eliciting version responses). The asymmetric stimuli elicited both vergence and version. In all cases, minimum response latencies were very short (<90 ms). Velocity tuning curves (based on the changes in vergence and version over the time period, 90-140 ms) were all sigmoidal and peaked when the monocular (i.e., retinal) image velocities were 30-60 deg/s. The vergence (version) responses to symmetric stimuli were linearly related to the vergence (version) responses to asymmetric stimuli when expressed in terms of the monocular rather than the binocular image velocities. We conclude that the dynamical limits for both vergence and version are imposed in the monocular visual pathways, before the inputs from the two eyes are combined. Published by Elsevier Science Ltd. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. CNRS, Ctr Rech Neurosci Cognit, F-13402 Marseille, France. RP Miles, FA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Rm 2A50,49 Convent Dr, Bethesda, MD 20892 USA. RI MASSON, Guillaume/G-4615-2012 FU Intramural NIH HHS [Z01 EY000153-24] NR 31 TC 16 Z9 17 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD NOV PY 2002 VL 42 IS 26 BP 2853 EP 2867 AR PII S0042-6989(02)00334-6 DI 10.1016/S0042-6989(02)00334-6 PG 15 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 631PC UT WOS:000180175300005 PM 12450510 ER PT J AU Read, JCA Parker, AJ Cumming, BG AF Read, JCA Parker, AJ Cumming, BG TI A simple model accounts for the response of disparity-tuned V1 neurons to anticorrelated images SO VISUAL NEUROSCIENCE LA English DT Article DE binocular disparity; stereo correspondence; visual cortex; complex cells; depth perception ID RANDOM-DOT STEREOGRAMS; CATS VISUAL-CORTEX; BINOCULAR DISPARITY; HORIZONTAL-DISPARITY; NEURAL MECHANISMS; SIMPLE CELLS; ENERGY MODELS; COMPLEX CELLS; DEPTH; PERCEPTION AB Disparity-tuned cells in primary visual cortex (VI) are thought to play a significant role in the processing of stereoscopic depth. The disparity-specific responses of these neurons have been previously described by an energy model based on local, feedforward interactions. This model fails to predict the response to binocularly anticorrelated stimuli, in which images presented to left and right eyes have opposite contrasts. The original energy model predicts that anticorrelation should invert the disparity tuning curve (phase difference pi), with no change in the amplitude of the response. Experimentally, the amplitude tends to be reduced with anticorrelated stimuli and a spread of phase differences is observed, although phase differences near pi are the most common. These experimental observations could potentially reflect a modulation of the VI signals by feedback from higher visual areas (because anticorrelated stimuli create a weaker or nonexistent stereoscopic depth sensation). This hypothesis could explain the effects on amplitude, but the spread of phase differences is harder to understand. Here, we demonstrate that changes in both amplitude and phase can be explained by a straightforward modification of the energy model that involves only local processing. Input from each eye is passed through a monocular simple cell, incorporating a threshold, before being combined at a binocular simple cell that feeds into the energy computation. Since this local feedforward model can explain the responses of complex cells to both correlated and anticorrelated stimuli, there is no need to invoke any influence of global stereoscopic matching. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. RP Read, JCA (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. RI Read, Jenny/A-7493-2013; Parker, Andrew/I-7867-2013 OI Read, Jenny/0000-0002-9029-5185; Parker, Andrew/0000-0001-5800-0407 NR 34 TC 54 Z9 55 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD NOV-DEC PY 2002 VL 19 IS 6 BP 735 EP 753 DI 10.1017/S0952523802196052 PG 19 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 659CE UT WOS:000181759000005 PM 12688669 ER PT J AU Tsuyuki, S Kono, M Bloom, ET AF Tsuyuki, S Kono, M Bloom, ET TI Cloning and potential utility of porcine Fas ligand: overexpression in porcine endothelial cells protects them from attack by human cytolytic cells SO XENOTRANSPLANTATION LA English DT Article DE cell surface molecules; cytotoxicity; endothelial cells; T cells; transplantation ID NATURAL-KILLER-CELLS; HUMAN NK CELLS; IMMUNODEFICIENT MOUSE HOSTS; CYTOTOXIC T-LYMPHOCYTES; ANTI-PIG CYTOTOXICITY; XENOGRAFT REJECTION; TARGET-CELLS; IN-VITRO; MEDIATED CYTOTOXICITY; MONONUCLEAR-CELLS AB Endothelial cells (EC) are primary targets of the recipient's immune response to transplanted organs and constitutively express Fas (CD95) ligand (FasL) on their surface. We investigated the role of porcine FasL in the generation of the human anti-pig response in vitro. Porcine aortic endothelial cells (PAEC) lysed a Fas(+) human T-cell line, Jurkat. Anti-human Fas monoclonal antibody (mAb) specifically inhibited this killing in a dose-dependent manner, suggesting that porcine FasL recognizes and binds human Fas to induce apoptosis of human Fas(+) cells. We next cloned porcine FasL, identifying an open reading frame of 849 base pairs predicting a protein of 282 amino acids. The predicted amino acid sequence was 85, 76, and 75% homologous to the predicted amino acid sequences of human, mouse, and rat, respectively, and found that PAEC expressed both FasL mRNA and protein. Transient transfection was used to increase or induce porcine FasL expression in PAEC or COS-7 cells. Transfection of PAEC with a plasmid encoding porcine FasL increased their ability to induce apoptosis in Jurkat cells, fresh human T cells activated with IL-2 and anti-CD3, and fresh IL-2-activated human (natural killer) NK cells. Moreover, porcine Fas L-transfected COS-7 cells induced significant apoptosis in Jurkat cells compared with that induced by mock-transfected COS-7 cells. Finally, the overexpression of porcine FasL in PAEC reduced their susceptibility as target cells to lysis by activated human NK or T cells. These findings suggest that porcine FasL overexpression in EC of vascularized xenografts may provide protection from cellular xenograft rejection. C1 US FDA, CBER, Div Cellular & Gene Therapies, Lab Immunol & Virol, Bethesda, MD 20892 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, CBER, Div Cellular & Gene Therapies, Lab Immunol & Virol, HFM-518,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 11 Z9 13 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2002 VL 9 IS 6 BP 410 EP 421 DI 10.1034/j.1399-3089.2002.01114.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 601YP UT WOS:000178477200009 PM 12371937 ER PT J AU Noetzel, C Chandra, V Perbandt, M Rajashankar, K Singh, T Aleksiev, B Kalkura, N Genov, N Betzel, C AF Noetzel, C Chandra, V Perbandt, M Rajashankar, K Singh, T Aleksiev, B Kalkura, N Genov, N Betzel, C TI Enzymatic activity and inhibition of the neurotoxic complex vipoxin from the venom of Vipera ammodytes meridionalis SO ZEITSCHRIFT FUR NATURFORSCHUNG C-A JOURNAL OF BIOSCIENCES LA English DT Article DE neurotoxin; phospholipase A2; snake venom ID II PHOSPHOLIPASES A(2); MOLECULAR EVOLUTION; SEQUENCE AB Vipoxin from the venom of Vipera ammodytes meridionalis is an unique neurotoxic complex between a toxic phospholipase A2 and a highly homologous non-toxic protein inhibitor. It is an example of evolution of a catalytic and toxic function into inhibitory and non-toxic one. The activity of the V ammodytes meridionalis toxin is 1.7 times higher than that of the closely related (92% sequence identity) neurotoxic complex RV4/RV7 from the venom of Vipera russelli formosensis. The enhanced enzymatic activity of vipoxin is attributed to limited structural changes, in particular to the substitutions G54R and Q78K in the PLA2 subunit of the complex and to the T54R substitution in the inhibitor. Oleyloxyethylphosphocholine, aristolochic acid and vitamin E suppressed the enzymatic activity of vipoxin and its isolated PLA2 subunit. These compounds influence inflammatory processes in which PLA2 is implicated. The peptide Lys-Ala-Ile-Tyr-Ser, which is an integral part of the PLA2 components of the two neurotoxic complexes from V ammodytes meridionalis and V russelli formosensis (sequence 70-74) activated vipoxin increasing its PLA2 activity by 23%. This is in contrast to the inhibitory effect of the respective pentapeptides with 70-74 sequences on other group II PLA2s. Surprisingly, the same peptide inhibited 46% of the V russelli formosensis PLA2 activity. The limited changes in the structure of the two highly homologous neurotoxins lead to considerable differences in their interaction with native peptides. C1 Bulgarian Acad Sci, Inst Organ Chem, BU-1113 Sofia, Bulgaria. DESY, Univ Hosp Eppendorf, Inst Med Biochem & Mol Biol, D-22603 Hamburg, Germany. All India Inst Med Sci, Dept Biophys, New Delhi 110029, India. NCI, Frederick & Brookhaven Natl Lab, Upton, NY 11973 USA. Univ Chem Technol & Met, BU-1756 Sofia, Bulgaria. RP Genov, N (reprint author), Bulgarian Acad Sci, Inst Organ Chem, BU-1113 Sofia, Bulgaria. NR 19 TC 5 Z9 5 U1 0 U2 0 PU VERLAG Z NATURFORSCH PI TUBINGEN PA POSTFACH 2645, W-7400 TUBINGEN, GERMANY SN 0939-5075 J9 Z NATURFORSCH C JI Z.Naturforsch.(C) PD NOV-DEC PY 2002 VL 57 IS 11-12 BP 1078 EP 1083 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 648AM UT WOS:000181126300023 PM 12562098 ER PT J AU Simhadri, S Kramata, P Zajc, B Sayer, JM Jerina, DM Hinkle, DC Wei, CSJ AF Simhadri, S Kramata, P Zajc, B Sayer, JM Jerina, DM Hinkle, DC Wei, CSJ TI Benzo[a]pyrene diol epoxide-deoxyguanosine adducts are accurately bypassed by yeast DNA polymerase zeta in vitro SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE polymerase zeta; benzo[a]pyrene diol epoxide; BPDE; DNA adduct; translesion synthesis ID XERODERMA PIGMENTOSUM VARIANT; PRONE LESION BYPASS; SACCHAROMYCES-CEREVISIAE; TRANSLESION SYNTHESIS; OPTICAL ENANTIOMERS; 7,8-DIOL 9,10-EPOXIDES; INDUCED MUTAGENESIS; NUCLEOSIDE ADDUCTS; CATALYTIC SUBUNIT; EXCISION-REPAIR AB The possible role of bypass DNA polymerase zeta in mutagenic translesion synthesis past benzo[a]pyrene (BP) 7,8-diol-9,10-epoxide (DE) N-2-deoxyguanosine (dG) adducts has been examined. We prepared 59-mer DNA templates containing dG adducts derived from trans opening of enantiomers of BP DE-2, in which the 7-hydroxyl group and epoxide oxygen are trans. The 10S-BP DE-dG and 10R-BP DE-dG adducts derive from the (+)- and (-)-DE-2 enantiomers, respectively. The adducted dG is located at a site identified as a G --> T mutational hotspot in random mutagenesis studies of (+)-BP DE-2 in Chinese hamster V-79 cells. Yeast pol zeta (complex of Gst-Rev3p and Rev7p) formed extension products (total of all lengths) of 71, 74 and 88% of a primer annealed to the 10S-BP DE-dG, 10R-BP DE-dG and non-adducted 59-mer templates, respectively. However, only 18 and 19% of the primer was extended to the full-length product on 10S-BP DE-dG and 10R-BP DE-dG adducted templates compared to 55% of the primer on the non-adducted template. A major 34-mer product corresponding to primer elongation up to and including the base before the adduct indicated that nucleotide incorporation opposite both adducts was strongly blocked. Full-length products were isolated from gels and subjected to PCR amplification and cloning. Sequence analysis of more than 300 clones of these full-length products on each template showed that only the correct dCMP was incorporated opposite both the adducted and non-adducted G-hotspot in the template. This corresponds to a probability of mutation lower than 0.3%, the limit of detection, and demonstrates the remarkable fidelity of yeast pol in translesion synthesis past these BP DB-dG lesions in vitro. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Rutgers State Univ, Susan Lehman Cullman Lab Canc Res, Dept Biol Chem, Coll Pharm, Piscataway, NJ 08854 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Rochester, Dept Biol, Rochester, NY 14627 USA. RP Kramata, P (reprint author), Rutgers State Univ, Susan Lehman Cullman Lab Canc Res, Dept Biol Chem, Coll Pharm, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. FU NCI NIH HHS [CA 76425]; NIEHS NIH HHS [ES 0502] NR 48 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 31 PY 2002 VL 508 IS 1-2 BP 137 EP 145 AR PII S0027-5107(02)00211-7 DI 10.1016/S0027-5107(02)00211-7 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 612GN UT WOS:000179066200014 PM 12379469 ER PT J AU Lin, HJ Shaffer, KM Chang, YH Barker, JL Pancrazio, JJ Stenger, DA Ma, W AF Lin, HJ Shaffer, KM Chang, YH Barker, JL Pancrazio, JJ Stenger, DA Ma, W TI Acute exposure of toluene transiently potentiates p42/44 mitogen-activated protein kinase (MAPK) activity in cultured rat cortical astrocytes SO NEUROSCIENCE LETTERS LA English DT Article DE astrocytes; mitogen-activated protein kinase; toluene; apoptosis; caspase 3; signal transduction ID OXIDATIVE STRESS; DNA-SYNTHESIS; CELLS; GFAP AB It has been shown that the inhalation of toluene in rats can cause neuronal apoptosis in the central nervous system. However, the cellular and molecular effects of toluene directly on astrocytes are relatively unknown. We used primary cultures of astrocytes isolated from the neonatal rat cortex as a model to study the toluene effects on cell outcome and associated signal transduction pathways using immunostaining and Western blotting. We observed that acute toluene exposure significantly induced caspase-dependent cell apoptosis and transiently stimulated the activation of p42/44 mitogen-activated protein kinase (MAPK) in the primary astrocytes. Interestingly, the inhibition of the p42/44 MAPK signaling cascade by PD98059 in conjunction with the toluene treatment evoked more cellular apoptosis than toluene alone, suggesting that the toluene-induced transient MAPK activation may play a role in promoting cell survival during the toluene exposure. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Lin, HJ (reprint author), USN, Res Lab, Ctr Bio Mol Sci & Engn, Code 6910,4555 Overlook Ave SW, Washington, DC 20375 USA. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 14 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 31 PY 2002 VL 332 IS 2 BP 103 EP 106 AR PII S0304-3940(02)00930-8 DI 10.1016/S0304-3940(02)00930-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 608BW UT WOS:000178826100008 PM 12384221 ER PT J AU Levy, D Kenchaiah, S Larson, MG Benjamin, EJ Kupka, MJ Ho, KKL Murabito, JM Vasan, RS AF Levy, D Kenchaiah, S Larson, MG Benjamin, EJ Kupka, MJ Ho, KKL Murabito, JM Vasan, RS TI Long-term trends in the incidence of and survival with heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; CASE-FATALITY; MORTALITY; HYPERTENSION; PREVALENCE; FRAMINGHAM; MORBIDITY; PROGNOSIS; DISEASE; COMMUNITY AB Background: Heart failure is a major public health problem. Long-term trends in the incidence of heart failure and survival after its onset in the community have not been characterized. Methods: We used statistical models to assess temporal trends in the incidence of heart failure and Cox proportional-hazards regression to evaluate survival after the onset of heart failure among subjects in the Framingham Heart Study. Cases of heart failure were classified according to the date of onset: 1950 through 1969 (223 cases), 1970 through 1979 (222), 1980 through 1989 (307), and 1990 through 1999 (323). We also calculated 30-day, 1-year, and 5-year age-adjusted mortality rates for each period. Results: Heart failure occurred in 1075 subjects (51 percent of whom were women). As compared with the rate for the period from 1950 through 1969, the incidence of heart failure remained virtually unchanged among men in the three subsequent periods but declined by 31 to 40 percent among women (rate ratio for the period from 1990 through 1999, 0.69; 95 percent confidence interval, 0.51 to 0.93). The 30-day, 1-year, and 5-year age-adjusted mortality rates among men declined from 12 percent, 30 percent, and 70 percent, respectively, in the period from 1950 through 1969 to 11 percent, 28 percent, and 59 percent, respectively, in the period from 1990 through 1999. The corresponding rates among women were 18 percent, 28 percent, and 57 percent for the period from 1950 through 1969 and 10 percent, 24 percent, and 45 percent for the period from 1990 through 1999. Overall, there was an improvement in the survival rate after the onset of heart failure of 12 percent per decade (P=0.01 for men and P=0.02 for women). Conclusions: Over the past 50 years, the incidence of heart failure has declined among women but not among men, whereas survival after the onset of heart failure has improved in both sexes. Factors contributing to these trends need further clarification. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Clin Res Inst, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. RI Kenchaiah, Satish/A-1519-2016; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1K24 HL04334, N01-HC-25195] NR 43 TC 991 Z9 1043 U1 2 U2 22 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 31 PY 2002 VL 347 IS 18 BP 1397 EP 1402 DI 10.1056/NEJMoa020265 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 609DM UT WOS:000178888400002 PM 12409541 ER PT J AU Althuis, MD Brinton, LA AF Althuis, MD Brinton, LA TI Oral contraceptives and the risk of breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Rockville, MD 20852 USA. RP Althuis, MD (reprint author), NCI, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 3 TC 0 Z9 0 U1 0 U2 0 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 31 PY 2002 VL 347 IS 18 BP 1448 EP 1448 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 609DM UT WOS:000178888400012 PM 12409551 ER PT J AU Popescu, NC Zimonjic, DB AF Popescu, NC Zimonjic, DB TI Chromosome and gene alterations in breast cancer as markers for diagnosis and prognosis as well as pathogenetic targets for therapy SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE breast cancer; genetic alterations; amplification; deletion; chromosome rearrangements; proto-oncogenes; tumor suppressor genes; DNA copy-number imbalances; gene expression profile ID COMPARATIVE GENOMIC HYBRIDIZATION; MOLECULAR CYTOGENETIC ANALYSIS; CELL-LINES; COPY-NUMBER; EXPRESSION PROFILES; CLINICAL IMPLICATIONS; CDNA MICROARRAYS; TUMOR-CELLS; CYCLIN D1; AMPLIFICATION AB Chromosomal abnormalities have been implicated in cancer development since the turn of the last century. Only during the past two decades, with advances in cytogenetics and molecular biology, has the genetic basis of neoplasia been firmly established, however, with chromosomal alterations being recognized as critical in the pathogenesis of human cancer. Recurrent chromosomal alterations provide cytological and molecular markers for the diagnosis and prognosis of disease. They also facilitate the identification of genes that are important in carcinogenesis and, ultimately, may lead to the development of targeted therapy. In breast cancer, the most prevalent malignancy among females, substantial progress has been achieved in identifying genes located at sites of recurrent chromosomal alterations and in profiling gene expression through the application of powerful cytogenetic and functional genomic techniques. Characterization of the molecular pathologic characteristics and gene-expression profiles of breast cancer should provide new clinical tools for the accurate diagnosis and prediction of prognosis as well as new targets for the development of therapeutic agents. Published 2002 Wiley-Liss, Inc.(dagger). C1 NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 3C05,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA. NR 66 TC 17 Z9 17 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 30 PY 2002 VL 115 IS 3 BP 142 EP 149 DI 10.1002/ajmg.10696 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 609ZL UT WOS:000178936200006 PM 12407694 ER PT J AU Payne, SG Milstien, S Spiegel, S AF Payne, SG Milstien, S Spiegel, S TI Sphingosine-1-phosphate: dual messenger functions SO FEBS LETTERS LA English DT Article; Proceedings Paper CT Workshop on Lipid Signalling - Cellular Events and Their Biophysical Mechanisms CY MAY 20-22, 2002 CL JUAN MARCH FDN, MADRID, SPAIN HO JUAN MARCH FDN DE sphingosine-1-phosphate; EDG-1; sphingosine kinase; cell growth; apoptosis ID PROTEIN-COUPLED RECEPTOR; SPHINGOSINE 1-PHOSPHATE RECEPTOR; INDUCED CELL MOTILITY; LYSOPHOSPHATIDIC ACID; GROWTH-FACTOR; INTRACELLULAR SPHINGOSINE-1-PHOSPHATE; SIGNALING PATHWAYS; ENDOTHELIAL-CELLS; APOPTOSIS; KINASE AB The sphingolipid metabolite sphingosine-1-phosphate (S1P) is a serum-borne lipid that regulates many vital cellular processes. S1P is the ligand of a family of five specific G protein-coupled receptors that are differentially expressed in different tissues and regulate diverse cellular actions. Much less is known of the intracellular actions of S1P. It has been suggested that S1P may also function as an intracellular second messenger to regulate calcium mobilization, cell growth and suppression of apoptosis in response to a variety of extracellular stimuli. Dissecting the dual actions and identification of intracellular targets of S1P has been challenging, but there is ample evidence to suggest that the balance between S1P and ceramide and/or sphingosine levels in cells is an important determinant of cell fate. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Med Coll Virginia Campus, Richmond, VA 23298 USA. FU NCI NIH HHS [CA61774]; NIGMS NIH HHS [GM43880] NR 50 TC 142 Z9 148 U1 1 U2 5 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 30 PY 2002 VL 531 IS 1 BP 54 EP 57 AR PII S0014-5793(02)03480-4 DI 10.1016/S0014-5793(02)03480-4 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 611BD UT WOS:000178995800011 PM 12401202 ER PT J AU Foletta, VC Brown, FD Young, WS AF Foletta, VC Brown, FD Young, WS TI Cloning of rat ARHGAP4/Cl, a RhoGAP family member expressed in the nervous system that colocalizes with the Golgi complex and microtubules SO MOLECULAR BRAIN RESEARCH LA English DT Article DE RhoGAP; nervous system; Golgi network; microtubulin; cDNA cloning; in situ hybridization histochemistry and immunofluorescence ID RECEPTOR MESSENGER-RNA; NEPHROGENIC DIABETES-INSIPIDUS; NUCLEOTIDE EXCHANGE FACTOR; BINDING PROTEINS RHOA; P190 RHOGAP; CDC42; CELLS; VASOPRESSIN; BRAIN; GTPASES AB The Rho GTPase family of intracellular molecular switches control multiple cellular functions via the regulation of the actin cytoskeleton. Increasing evidence implicates a critical involvement of these molecules in the nervous system, particularly during neuronal migration and polarity, axon and growth cone guidance, dendritic arborization and synaptic formation. However, the molecules regulating Rho GTPase activities in the nervous system are less known. Here, we present the cloning of rat ARHGAP4, a member of the Rho GTPase activating protein family, and also demonstrate its close linkage to the vasopressin 2 receptor gene. In vitro, recombinant ARHGAP4 stimulated the GTPase activity of three members of Rho GTPases, Racl, Cdc42 and RhoA. ARHGAP4 mRNA expression was observed in multiple tissues with marked expression throughout the developing and adult nervous systems. On closer analysis of protein levels, ARHGAP4 was significantly restricted to specific regions in the nervous system. These included the stratum lucidem in the CA3 area of the hippocampus, neuronal fibers in the ventral region of the brainstem and striatum, and in the cerebellar granule cells. Subcellularly, endogenous ARHGAP4 expression localized to the Golgi complex and could redistribute to the microtubules, for example during mitosis. In addition, distinct protein expression was observed in the tips of differentiating neurites of PC12 cells. Collectively, these results demonstrate that ARHGAP4 is more widely expressed than previously thought but potentially possesses specialized activity in regulating members of the Rho GTPase family in specific cellular compartments of the nervous system. Published by Elsevier Science B.V. C1 NIMH, Sect Neural Gene Express, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, NIH, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 53 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 30 PY 2002 VL 107 IS 1 BP 65 EP 79 AR PII S0169-328x(02)00448-5 DI 10.1016/S0169-328X(02)00448-5 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 619AH UT WOS:000179450500009 ER PT J AU Goldstein, DS Holmes, C Frank, SM Dendi, R Cannon, RO Sharabi, Y Esler, MD Eisenhofer, G AF Goldstein, DS Holmes, C Frank, SM Dendi, R Cannon, RO Sharabi, Y Esler, MD Eisenhofer, G TI Cardiac sympathetic dysantonomia in chronic orthostatic intolerance syndromes SO CIRCULATION LA English DT Article DE catecholamines; nervous system, sympathetic; norepinephrine; dysautonomia ID NEURALLY-MEDIATED SYNCOPE; CHRONIC-FATIGUE-SYNDROME; HUMAN-HEART; NOREPINEPHRINE; DIHYDROXYPHENYLGLYCOL; TACHYCARDIA; 6-FLUORODOPAMINE; HYPOTENSION; HYPOVOLEMIA; DISORDER AB Background-In postural tachycardia syndrome (POTS) and repeated neurocardiogenic presyncope (NCS), orthostatic intolerance occurs without persistent sympathetic neurocirculatory failure. Whether these conditions involve abnormal cardiac sympathetic innervation or function has been unclear. Methods and Results-Patients with POTS or NCS underwent measurements of neurochemical indices of cardiac release, reuptake, and synthesis of the sympathetic neurotransmitter norepinephrine based on entry of norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover), cardiac extraction of circulating H-3-norepinephrine, and cardiac production of dihydroxyphenylalanine and measurement of left ventricular myocardial innervation density using 6-[F-18]fluorodopamine positron emission tomographic scanning. Mean cardiac norepinephrine spillover in POTS (171 +/- 30 pmol/min, N=16) was higher and in NCS (62 +/- 9 pmol/min, N=20) was lower than in a large group of healthy volunteers (102 +/- 9 pmol/min, N=52) and in a subgroup of age-matched healthy women (106 +/- 18 pmol/min, N=11). Both patient groups had normal cardiac extraction of H-3-norepinephrine, normal cardiac production of dihydroxyphenylalanine, and normal myocardial 6-[F-18]fluorodopamine-derived radioactivity. Conclusions-POTS and NCS differ in tonic cardiac sympathetic function, with increased cardiac norepinephrine release in the former and decreased release in the latter. Both groups had normal values for indices of function of the cell membrane norepinephrine transporter, norepinephrine synthesis, and density of myocardial sympathetic innervation. Because POTS and NCS both include specific abnormalities of cardiac sympathetic function, both can be considered forms of dysautonomia. C1 Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. NINDS, Clin Neurocardiol Sect, NIH, Baltimore, MD USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. Baker Med Res Inst, Prahran, Vic 3181, Australia. RP Goldstein, DS (reprint author), Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. NR 30 TC 56 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 29 PY 2002 VL 106 IS 18 BP 2358 EP 2365 DI 10.1161/01.CIR.0000036015.54619.B6 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 611YW UT WOS:000179046600021 PM 12403667 ER PT J AU Kele, P Orbulescu, J Calhoun, TL Gawley, RE Leblanc, RM AF Kele, P Orbulescu, J Calhoun, TL Gawley, RE Leblanc, RM TI Langmuir monolayer and Langmuir-Blodgett film studies of an amphiphilic coumaryl crown ether SO LANGMUIR LA English DT Article ID SCHAEFER FILMS; SENSORS AB As a potential compound for use in optical fiber fluorescence sensor for rapid detection of saxitoxin, 4-(monoaza-18-crown-6-methyl)-7-octadecanoylaminocoumarin (ODAC) was synthesized and the interfacial and spectroscopic properties of its Langmuir monolayers and Langmuir-Blodgett (LB) films were studied. The surface pressure- and surface potential-area isotherms were obtained on a pure water subphase. In situ fluorescence of the ODAC monolayer at the air-water interface showed a fluorescence band centered around 425 nm (lambda(ex) = 332 nm) decreasing in intensity with increasing surface pressure. This observation is due to the self-quenching of the ODAC molecules as the surface concentration per unit area increases and aggregates are formed. To reduce the aggregation phenomenon, mixed monolayers of ODAC with C(18)GlyGlyAlaGlyNH(2) peptidolipid (PL) (PL:ODAC, 20:1 and 100:1) were used to dilute the fluorophore molecules at the air-water interface and diminish the self-quenching. LB films of pure ODAC and PL: ODAC mixed monolayers (100:1) were prepared and tested on saxitoxin dissolved in a phosphate buffer (pH 7.4). Each LB film showed fluorescence increase in the presence of saxitoxin. C1 Univ Miami, Dept Chem, Coral Gables, FL 33124 USA. Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Coral Gables, FL 33124 USA. RP Gawley, RE (reprint author), Univ Miami, Dept Chem, 1301 Mem Dr, Coral Gables, FL 33124 USA. RI Orbulescu, Jhony/D-7829-2012 OI Orbulescu, Jhony/0000-0001-9408-9787 NR 16 TC 22 Z9 22 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD OCT 29 PY 2002 VL 18 IS 22 BP 8523 EP 8526 DI 10.1021/la020531w PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 608HC UT WOS:000178839300037 ER PT J AU Daly, JW Kaneko, T Wilham, J Garraffo, HM Spande, TF Espinosa, A Donnelly, MA AF Daly, JW Kaneko, T Wilham, J Garraffo, HM Spande, TF Espinosa, A Donnelly, MA TI Bioactive alkaloids of frog skin: Combinatorial bioprospecting reveals that pumiliotoxins have an arthropod source SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POISON FROGS; AMPHIBIAN SKIN; DENDROBATIDAE; DECAHYDROQUINOLINES; PYRROLIZIDINES; QUINOLIZIDINES; INDOLIZIDINES; EVOLUTION; COMMON; ANTS AB Nearly 500 alkaloids have been detected in skin extracts from frogs of the family Dendrobatidae. All seem to have been sequestered unchanged into skin glands from alkaloid-containing arthropods. Ants, beetles,and millipedes seem to be the source of decahydroquinolines, certain izidines, coccinellines, and spiropyrrolizidine oximes. But the dietary source for a major group of frog-skin alkaloids, namely the pumiliotoxins (PTXs), alloPTXs, and homoPTXs, remained a mystery. In hopes of revealing an arthropod source for the PTX group, small arthropods were collected from eight different sites on a Panamanian island, where the dendrobatid frog (Dendrobates pumilio) was known to contain high levels of two PTXs. The mixed arthropod collections from several sites, each representing up to 20 arthropod taxa, contained PTX 307A and/or alloPTX 323B. In addition, the mixed arthropod collections from several sites contained a 5,8-disubstituted indolizidine (205A or 235B), representing another class of alkaloids previously unknown from an arthropod. An ant alkaloid, decahydroquinoline 195A, was detected in the mixed arthropod collections from several sites. Thus, "combinatorial bioprospecting" demonstrates that further collection and analysis of individual taxa of leaf-litter arthropods should reveal the taxa from which PTXs, alloPTXs, and 5,8-disubstituted indolizidines are derived. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Panama, Panama City, Panama. Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 26 TC 83 Z9 88 U1 3 U2 17 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 29 PY 2002 VL 99 IS 22 BP 13996 EP 14001 DI 10.1073/pnas.222551599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400008 PM 12381780 ER PT J AU Ma, BY Nussinov, R AF Ma, BY Nussinov, R TI Stabilities and conformations of Alzheimer's beta-amyloid peptide oligomers (A beta(16-22 ') A beta(16-35 ') and A beta(10-35)): Sequence effects SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyloid conformation; beta-sheet; double-layered sheets; molecular dynamics simulation; protein folding ID SOLID-STATE NMR; FIBRILS; PROTEIN; FRAGMENT; TOXICITY; FIBRILLOGENESIS; AGGREGATION; INHIBITION; MECHANISM; PARALLEL AB Previously, we have studied the minimal oligomer size of an aggregate amyloid seed and the mechanism of seed growth with a multilayer beta-sheet model. Under high temperature simulation conditions, our approach can test the stability of possible amyloid forms. Here, we report our study of oligomers of Alzheimer's amyloid beta-peptide (Abeta) fragments 16-22, 16-35, and 10-35 (abbreviated Abeta(16-22), Abeta(16-35), and Abeta(10-35), respectively). Our simulations indicate that an antiparallel beta-sheet orientation is the most stable for the Abeta16-22, in agreement with a solid state NMR-based model [Balbach, J. J., Ishii, Y., Antzutkin, O. N., Leapman, R. D., Rizzo, N. W., et al. (2000) Biochemistry 39,13748-13759]. A model with twenty-four Abeta(16-22) strands indicates a highly twisted fibril. Whereas the short Abeta(16-22) and Abeta(24-36) may exist in fully extended form, the linear parallel beta-sheets for Abeta(16-35) appear impossible, mainly because of the polar region in the middle of the 16-35 sequence. However, a bent double-layered hairpin-like structure (called hook) with the polar region at the turn forms parallel p-sheets with higher stability. An intra-strand salt-bridge (D23-K28) stabilizes the bent hairpin-like hook structure. The bent double-beta-sheet model for the Abeta(10-35) similarly offers oligomer stability. C1 Sci Applicat Int Corp, Lab Expt & Computat Biol, NCI, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, NCI, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Sci Applicat Int Corp, Intramural Res Support Program, NCI, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 30 TC 323 Z9 330 U1 6 U2 53 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 29 PY 2002 VL 99 IS 22 BP 14126 EP 14131 DI 10.1073/pnas.212206899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400031 PM 12391326 ER PT J AU Chen, L Segal, D Hukriede, NA Podtelejnikov, AV Bayarsaihan, D Kennison, JA Ogryzko, VV Dawid, IB Westphal, H AF Chen, L Segal, D Hukriede, NA Podtelejnikov, AV Bayarsaihan, D Kennison, JA Ogryzko, VV Dawid, IB Westphal, H TI Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to regulate development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HISTONE ACETYLASE COMPLEX; WING MARGIN ENHANCER; ACTIVITY IN-VIVO; HOMEODOMAIN PROTEINS; HOMEOBOX GENES; DROSOPHILA; CHIP; EXPRESSION; ZEBRAFISH; TETRAMER AB The LIM-domain-binding protein Ldb1 is a key factor in the assembly of transcriptional complexes involving LIM-homeodomain proteins and other transcription factors that regulate animal development. We identified Ssdp proteins (previously described as sequence-specific, sing le-stranded-DNA-binding proteins) as components of Ldb1-associated nuclear complexes in HeLa cells. Ssdp proteins are associated with Ldb1 in a variety of additional mammalian cell types. This association is specific, does not depend on the presence of nucleic acids, and is functionally significant. Genes encoding Ssdp proteins are well conserved in evolution from Drosophila to humans. Whereas the vertebrate Ssdp gene family has several closely related members, the Drosophila Ssdp gene is unique. In Xenopus, Ssdp encoded by Drosophila Ssdp or mouse Ssdp1 mRNA enhances axis induction by Ldb1 in conjunction with the LIM-homeobox gene Xlim1. Furthermore, we were able to demonstrate an interaction between Ssdp and Chip (the fly homolog of Ldb1) in Drosophila wing development. These findings indicate functional conservation of Ssdp as a cofactor of Ldb1 during invertebrate and vertebrate development. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20814 USA. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20814 USA. Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. Univ So Denmark, Prot Interact Lab, DK-5230 Odense, Denmark. MDS Proteom, DK-5230 Odense, Denmark. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. CNRS, Inst Andre Lwoff, Unite Propre Rech 9079, F-94801 Villejuif, France. RP Westphal, H (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20814 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 37 TC 46 Z9 50 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 29 PY 2002 VL 99 IS 22 BP 14320 EP 14325 DI 10.1073/pnas.212532399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400065 PM 12381786 ER PT J AU Hoyer, KK French, SW Turner, DE Nguyen, MTN Renard, M Malone, CS Knoetig, S Qi, CF Su, TT Cheroutre, H Wall, R Rawlings, DJ Morse, HC Teitell, MA AF Hoyer, KK French, SW Turner, DE Nguyen, MTN Renard, M Malone, CS Knoetig, S Qi, CF Su, TT Cheroutre, H Wall, R Rawlings, DJ Morse, HC Teitell, MA TI Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AIDS-RELATED LYMPHOMAS; PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE; ATAXIA-TELANGIECTASIA; SOMATIC HYPERMUTATION; ONCOGENE EXPRESSION; TRANSGENIC MICE; S6 KINASE; T-CELLS; ACTIVATION AB The TCL1 protooncogene is overexpressed in many mature B cell lymphomas, especially from AIDS patients. To determine whether aberrant expression promotes B cell transformation, we generated a murine model in which a TCL1 transgene was overexpressed at similar levels in both B and T cells. Strikingly, transgenic mice developed Burkitt-like lymphoma (BLL) and diffuse large B cell lymphoma (DLBCL) with attendant BcI-6 expression and mutated J(H) gene segments at a very high penetrance beginning at 4 months of age. In contrast, only one mouse developed a T cell malignancy at 15 months, consistent with a longer latency for transformation of T cells by TCL1. Activation of premalignant splenic B cells by means of B cell antigen receptor (BCR) engagement resulted in significantly increased proliferation and augmented AKT-dependent signaling, including increased S6 ribosomal protein phosphorylation. Transgenic spleen cells also survived longer than wild-type spleen cells in long-term culture. Together these data demonstrate that TCL1 is a powerful oncogene that, when overexpressed in both B and T cells, predominantly yields mature B cell lymphomas. C1 Univ Calif Los Angeles, Dept Pathol & Lab Med, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol & Immunol, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, AIDS Inst, Sch Med, Los Angeles, CA 90095 USA. NIH, Immunopathol Lab, Bethesda, MD 20892 USA. La Jolla Inst & Allergy & Immunol, San Diego, CA 92121 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Teitell, MA (reprint author), Univ Calif Los Angeles, Dept Pathol & Lab Med, Sch Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA85841, R01 CA081140, R01 CA085841, T32 CA009056, T32 CA009120, T32CA09056]; NICHD NIH HHS [HD37091, R01 HD037091]; NIGMS NIH HHS [GM08042, GM40185, R01 GM040185, T32 GM008042]; PHS HHS [A09120, A81140] NR 46 TC 85 Z9 87 U1 1 U2 6 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 29 PY 2002 VL 99 IS 22 BP 14392 EP 14397 DI 10.1073/pnas.212410199 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400077 PM 12381789 ER PT J AU Bukh, J Pietschmann, T Lohmann, V Krieger, N Faulk, K Engle, RE Govindarajan, S Shapiro, M Claire, MS Bartenschlager, R AF Bukh, J Pietschmann, T Lohmann, V Krieger, N Faulk, K Engle, RE Govindarajan, S Shapiro, M Claire, MS Bartenschlager, R TI Mutations that permit efficient replication of hepatitis C virus RNA in Huh-7 cells prevent productive replication in chimpanzees SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFECTIOUS MOLECULAR CLONE; CDNA CLONE; IN-VIVO; GENOTYPE 1B; HCV RNA; CULTURE; PROTEIN; 5A; INTERFERON-ALPHA-2B; TRANSCRIPTS AB The development of a subgenomic replicon derived from the hepatitis C virus (HCV) strain Coni enabled the study of viral RNA replication in Huh-7 cells. The level of replication of replicons, as well as full-length Con1 genomes, increased significantly by a combination of two adaptive mutations in NS3 (E1202G and T1280l) and a single mutation in NS5A (S2197P). However, these cell culture-adaptive mutations influenced in vivo infectivity. After intrahepatic transfection of chimpanzees, the wild-type Conl genome was infectious and produced viral titers similar to those produced by other infectious HCV clones. Repeated independent transfections with RNA transcripts of a Conl genome containing the three adaptive mutations failed to achieve active HCV infection. Furthermore, although a chimpanzee transfected with RNA transcripts of a Con1 genome with only the NS5A mutation became infected, this mutation was detected only in virus genomes recovered from serum at day 4; viruses recovered at day 7 had a reversion back to the original Conl sequence. Our study demonstrates that mutations that are adaptive for replication of HCV in cell culture may be highly attenuating in vivo. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Mainz, Inst Virol, D-55131 Mainz, Germany. Univ Heidelberg, Inst Hyg, Dept Mol Virol, D-69120 Heidelberg, Germany. Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pietschmann, Thomas/E-9241-2015; Bartenschlager, Ralf/L-2582-2015; OI Pietschmann, Thomas/0000-0001-5138-6239; Lohmann, Volker/0000-0001-8719-7608 NR 44 TC 173 Z9 184 U1 3 U2 11 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 29 PY 2002 VL 99 IS 22 BP 14416 EP 14421 DI 10.1073/pnas.212532699 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400081 PM 12391335 ER PT J AU Daelemans, D Afonina, E Nilsson, J Werner, G Kjems, J De Clercq, E Pavlakis, GN Vandamme, AM AF Daelemans, D Afonina, E Nilsson, J Werner, G Kjems, J De Clercq, E Pavlakis, GN Vandamme, AM TI A synthetic HIV-1 Rev inhibitor interfering with the CRM1-mediated nuclear export SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS TYPE-1 REV; LEPTOMYCIN-B; INTRACELLULAR TRAFFICKING; TRANSPORT FACTOR; RRE INTERACTION; MESSENGER-RNA; PROTEIN; CRM1; RAN; CYTOPLASM AB The HIV-1 Rev protein is an essential regulator of the HIV-1 mRNA expression that promotes the export of unspliced and partially spliced mRNA. The export receptor for the leucine-rich nuclear export signal (NES) of Rev has recently been recognized as CRM1. We identified a low molecular weight compound PKF050-638 as an inhibitor of HIV-1 Rev. This drug inhibits in a dose-dependent fashion Rev-dependent mRNA expression in a cellular assay for Rev function. We show that PKF050-638 is an inhibitor of the CRM1-mediated Rev nuclear export. By using a quantitative in vitro CRM1-NES cargo-binding assay, we could demonstrate that PKF050-638 disrupts CRM1-NES interaction. This mode of action is confirmed in cell culture because the drug reversibly interferes with the colocalization of CRM1 and Rev in the nucleolus of the cell. In addition, we prove that the inhibition is through direct interaction of the compound with Cys-539 of CRM1. These effects are similar to those of the known CRM1 inhibitor leptomycin B and suggest that the inhibitory effect of the compound is caused by binding to CRM1 at a similar site. The compound displayed strict structural requirements for its activity, as its enantiomer was inactive in all assays tested. These results show that we identified a drug that interferes with the CRM1-mediated nuclear export of Rev through inhibition of the CRM1-NES complex formation. The reversibility of its binding to CRM1 and its availability through chemical synthesis could make it useful for studying CRM1-mediated export pathways. C1 Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. NCI, Human Retrovirus Sect, Frederick, MD 21702 USA. Aarhus Univ, Dept Mol & Struct Biol, DK-8000 Aarhus, Denmark. Novartis Res Inst, A-1090 Vienna, Austria. RP Vandamme, AM (reprint author), Minderbroedersstr 10, B-3000 Louvain, Belgium. RI Vandamme, Anne Mieke/I-4127-2012; OI Vandamme, Anne Mieke/0000-0002-6594-2766; Nilsson, Jakob/0000-0003-4100-1125; Kjems, Jorgen/0000-0003-4128-9317 NR 32 TC 80 Z9 88 U1 1 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 29 PY 2002 VL 99 IS 22 BP 14440 EP 14445 DI 10.1073/pnas.212285299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400085 PM 12374846 ER PT J AU Dreher, JC Berman, KF AF Dreher, JC Berman, KF TI Fractionating the neural substrate of cognitive control processes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE prefrontal; cingulate; executive processes; task switching; inhibition ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; PREFRONTAL CORTEX; WORKING-MEMORY; INHIBITORY MECHANISMS; RHESUS-MONKEY; HUMAN BRAIN; TASK-SET; ATTENTION; SWITCH AB Psychological and neurobiological theories of cognitive control must account for flexible, seemless transitions among cognitive operations. When subjects switch between tasks, they must both inhibit the previous task and re-engage in a different task. Inhibition of the disengaged task remains active for a period of time and has to be overcome when re-engaging in the same task. Here we used a task-switching paradigm that allows distinction of two control processes: overcoming the inhibition of a previously performed task when re-engaging it and restarting a sequence of tasks after a period of interruption. Behaviorally, these processes were reflected in the facts that: (i) switching to a recently performed task, that is thus unlikely to have fully recovered from inhibition, takes longer than switching to a task less recently performed and (ii) re-engaging in a sequence of tasks after a period of interruption transiently increases response time. Using event-related functional MRI, we found that these two behavioral effects were accompanied by a double dissociation: the right lateral prefrontal cortex was more activated when switching to a task recently performed compared to a task less recently performed, while the anterior cingulate cortex was recruited when a sequence of tasks was initiated. These results provide insights into the functional organization of the frontal lobe in humans and its role in distinct processes involved in cognitive control. C1 NIMH, Clin Brain Disorders Branch, Unit Integrat Neuroimaging, Intramural Res Program,NIH, Bethesda, MD 20892 USA. RP Dreher, JC (reprint author), NIMH, Clin Brain Disorders Branch, Unit Integrat Neuroimaging, Intramural Res Program,NIH, Bethesda, MD 20892 USA. NR 45 TC 102 Z9 102 U1 4 U2 13 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 29 PY 2002 VL 99 IS 22 BP 14595 EP 14600 DI 10.1073/pnas.222193299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400111 PM 12391312 ER PT J AU LeRoith, D AF LeRoith, D TI beta-cell dysfunction and insulin resistance in type 2 diabetes: Role of metabolic and genetic abnormalities SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Will Using Exogenouos Insulin Earlier in Disease Progression Prevent Didease in Diabetes CY JUN 25, 2001 CL PHILADELPHIA, PENNSYLVANIA ID SKELETAL-MUSCLE TRIGLYCERIDE; RISK-FACTORS; MELLITUS; OBESITY; SECRETION; PATHOGENESIS; SENSITIVITY; GLUCOSE; TRANSLOCATION; TROGLITAZONE AB Defects in insulin action and insulin secretion are both present in type 2 diabetes, and both are believed to be genetically predetermined. In the absence of a defect in beta-cell function, individuals can compensate indefinitely for insulin resistance with appropriate hyperinsulinemia, as observed even in obese populations such as the Pima Indians of Arizona. However, loss of beta-cell function leads eventually to the postprandial and fasting hyperglycemia that characterizes type 2 diabetes. This progression occurs despite initially effective antidiabetic therapies, a situation clearly demonstrated by the United Kingdom Prospective Diabetes Study (UKPDS). External factors (access to high-calorie foods, lack of exercise, weight gain), the increased insulin requirements imposed by insulin resistance, and toxicities from hyperglycemia and elevated free fatty acids may all contribute to beta-cell deterioration. Free fatty acids, resistin, and tumor necrosis factor (TNF)-alpha potentially worsen the insulin resistance. beta-Cell dysfunction resulting from glucose toxicity and lipotoxicity is potentially reversible with restoration of metabolic control. Therefore, attention to these toxicities may delay the deterioration of beta-cell function and suggest new approaches to the management of type 2 diabetes. C1 NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 48 TC 99 Z9 100 U1 2 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 28 PY 2002 VL 113 SU 6A BP 3S EP 11S AR PII S0002-9343(02)01276-7 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 614YL UT WOS:000179219000002 PM 12431757 ER PT J AU Miller, FG Rosenstein, DL AF Miller, FG Rosenstein, DL TI Reporting of ethical issues in publications of medical research SO LANCET LA English DT Article ID PLACEBO-CONTROLLED TRIALS; PSYCHIATRIC RESEARCH; INFORMED CONSENT AB Clinical investigators rarely describe the rationale for ethically controversial features of study design or procedures instituted to enhance the protection of patients taking part in research, or how they ensured informed consent. We recommend a policy of extensive reporting of pertinent ethical issues to promote public accountability for clinical research. Guidelines are presented, and possible objections to this recommended policy are addressed. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. NIH, Psychiat Consultat Liaison Serv, Bethesda, MD USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1c118, Bethesda, MD 20892 USA. NR 21 TC 30 Z9 30 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 26 PY 2002 VL 360 IS 9342 BP 1326 EP 1328 DI 10.1016/S0140-6736(02)11346-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 608CH UT WOS:000178827200032 PM 12414226 ER PT J AU Ablonczy, Z Crouch, RK Goletz, PW Redmond, TM Knapp, DR Ma, JX Rohrer, B AF Ablonczy, Z Crouch, RK Goletz, PW Redmond, TM Knapp, DR Ma, JX Rohrer, B TI 11-cis-retinal reduces constitutive opsin phosphorylation and improves quantum catch in retinoid-deficient mouse rod photoreceptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRIC ANALYSIS; MULTIPLE PHOSPHORYLATION; CONGENITAL AMAUROSIS; VERTEBRATE RETINA; RECEPTOR KINASE; DARK-ADAPTATION; VISUAL PIGMENT; RHODOPSIN; LIGHT; RPE65 AB Rpe65(-/-) mice produce minimal amounts of 11-cis-retinal, the ligand necessary for the formation of photosensitive visual pigments. Therefore, the apoprotein opsin in these animals has not been exposed to its normal ligand. The Rpe65(-/-) mice contain less than 0.1% of wild type levels of rhodopsin. Mass spectrometric analysis of opsin from Rpe65(-/-) mice revealed unusually high levels of phosphorylation in dark-adapted mice but no other structural alterations. Single flash and flicker electroretinograms (ERGs) from 1-month-old animals showed trace rod function but no cone response. B-wave kinetics of the single-flash ERG are comparable with those of dark-adapted wild type mice containing a full compliment of rhodopsin. Application (intraperitoneal injection) of 11-cis-retinal to Rpe65(-/-) mice increased the rod ERG signal, increased levels of rhodopsin, and decreased opsin phosphorylation. Therefore, exogenous 11-cis-retinal improves photoreceptor function by regenerating rhodopsin and removes constitutive opsin phosphorylation. Our results indicate that opsin, which has not been exposed to 11-cis-retinal, does not generate the activity generally associated with the bleached apoprotein. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. FU NEI NIH HHS [EY 12231, EY 04939, EY 08239, EY 13520] NR 41 TC 59 Z9 59 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 2002 VL 277 IS 43 BP 40491 EP 40498 DI 10.1074/jbc.M205507200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 607KU UT WOS:000178791400044 PM 12176991 ER PT J AU Hsi, LC Wilson, LC Eling, TE AF Hsi, LC Wilson, LC Eling, TE TI Opposing effects of 15-lipoxygenase-1 and-2 metabolites on MAPK signaling in prostate - Alteration in peroxisome proliferator-activated receptor gamma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN BREAST-CANCER; GROWTH-FACTOR-I; KINASE-MEDIATED PHOSPHORYLATION; HUMAN COLORECTAL-CANCER; CELL-CYCLE ARREST; PPAR-GAMMA; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; INHIBIT GROWTH; MAMMALIAN LIPOXYGENASES AB Human prostate tumors have elevated levels of 15-lipoxygenase-1 (15-LOX-1) and data suggest that 15-LOX-1 may play a role in the development of prostate cancer. In contrast, 15-LOX-2 expression is higher in normal rather than in tumor prostate tissue and appears to suppress cancer development. We recently reported that 13-(S)-HODE, the 15-LOX-1 metabolite, up-regulates the MA-P kinase signaling pathway and subsequently down-regulates PPARgamma in human colorectal carcinoma cells. To determine whether this mechanism is applicable to prostate cancer and what the effects of 15-LOX-2 are, we investigated the effect of 15-LOX-1, 15-LOX-2, and their metabolites on epidermal growth factor (EGF)- and insulin-like growth factor (IGF)-1 signaling in prostate carcinoma cells. In PC3 cells, 13-(S)-HODE, a 15-LOX-1 metabolite, upregulated MAP kinase while in contrast 15-(S)-HETE, a 15-LOX-2 metabolite, down-regulated MAP kinase. As a result, 13-(S)-HODE increased PPARgamma phosphorylation while a subsequent decrease in PPARgamma phosphorylation was observed with 15-(S)-HETE. Thus, 15-LOX metabolites have opposing effects on the regulation of the MAP kinase signaling pathway and a downstream target of MAP kinase signaling like PPARgamma. In addition to the EGF signaling pathway, the IGF signaling pathway appears to be linked to prostate cancer. 13-(S)-HODE and 15-(S)-HETE up-regulate or down-regulate, respectively, both the MAPK and Akt pathways after activation with IGF-1. Thus, the effect of these lipid metabolites is not solely restricted to EGF signaling and not solely restricted to MAPK signaling. These results provide a plausible mechanism to explain the apparent opposing effects 15-LOX-1 and 15-LOX-2 play in prostate cancer. C1 NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 42 TC 94 Z9 96 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 2002 VL 277 IS 43 BP 40549 EP 40556 DI 10.1074/jbc.M203522200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 607KU UT WOS:000178791400052 PM 12189136 ER PT J AU Opresko, PL von Kobbe, C Laine, JP Harrigan, J Hickson, ID Bohr, VA AF Opresko, PL von Kobbe, C Laine, JP Harrigan, J Hickson, ID Bohr, VA TI Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNDROME CELLS; DNA HELICASE; SYNDROME FIBROBLASTS; RECQ FAMILY; WRN; REPLICATION; EXONUCLEASE; INTERACTS; REPEATS; REPAIR AB Werner syndrome is a human premature aging disorder displaying cellular defects associated with telomere maintenance including genomic instability, premature senescence, and accelerated telomere erosion. The yeast homologue of the Werner protein (WRN), Sgs1, is required for recombination-mediated lengthening of telomeres in telomerase-deficient cells. In human cells, we report that WRN co-localizes and physically interacts with the critical telomere maintenance protein TRF2. This interaction is mediated by the RecQ conserved G terminal region of WRN. In vitro, TRF2 demonstrates high affinity for WRN and for another RecQ family member, the Bloom syndrome protein (BLM). TRF2 interaction with either WRN or BLM results in a notable stimulation of their helicase activities. Furthermore, the WRN and BLM helicases, partnered with replication protein A, actively unwind long telomeric duplex regions that are pre-bound by TRF2. These results suggest that TRF2 functions with WRN, and possibly BLM, in a common pathway at telomeric ends. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Strasbourg 1, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. Univ Oxford, John Radcliffe Hosp, Inst Mol Med, Imperial Canc Res Fund Labs, Oxford OX3 9DS, England. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Opresko, Patricia/0000-0002-6470-2189 NR 51 TC 259 Z9 269 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 2002 VL 277 IS 43 BP 41110 EP 41119 DI 10.1074/jbc.M205396200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 607KU UT WOS:000178791400121 PM 12181313 ER PT J AU Courselaud, B Pigeon, C Inoue, Y Inoue, J Gonzalez, FJ Leroyer, P Gilot, D Boudjema, K Guguen-Guillouzo, C Brissott, P Loreal, O Ilyin, G AF Courselaud, B Pigeon, C Inoue, Y Inoue, J Gonzalez, FJ Leroyer, P Gilot, D Boudjema, K Guguen-Guillouzo, C Brissott, P Loreal, O Ilyin, G TI C/EBP alpha regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BINDING-PROTEIN; LIVER-SPECIFIC GENE; HEREDITARY HEMOCHROMATOSIS; INNATE IMMUNITY; KNOCKOUT MICE; MOUSE LIVER; EXPRESSION; TISSUE; BETA; DIFFERENTIATION AB Originally identified as a gene up-regulated by iron overload in mouse liver, the HEPC gene encodes hepcidin, the first mammalian liver-specific antimicrobial peptide and potential key regulator of iron metabolism. Here we demonstrate that during rat liver development, amounts of HEPC transcripts were very low in fetal liver, strongly and transiently increased shortly after birth, and reappeared in adult liver. To gain insight into mechanisms that regulate hepatic expression of hepcidin, 5'-flanking regions of human and mouse HEPC genes were isolated and analyzed by functional and DNA binding assays. Human and mouse HEPC promoter-luciferase reporter vectors exhibited strong basal activity in hepatoma HuH-7 and mouse hepatocytes, respectively, but not in non-hepatic U-2OS cells. We found that CCAAT/enhancer-binding protein alpha (C/EBPalpha) and C/EBPbeta were respectively very potent and weak activators of both human and mouse promoters. In contrast, co-expression of hepatocyte nuclear factor 4alpha (HNF4alpha) failed to induce HEPC promoter activity. By electrophoretic mobility shift assay we demonstrated that one putative C/EBP element found in the human HEPC promoter (-250/-230) predominantly bound C/EBPalpha from rat liver nuclear extracts. Hepatic deletion of the C/EBPalpha gene resulted in reduced expression of HEPC transcripts in mouse liver. In contrast, amounts of HEPC transcripts increased in liver-specific HNF4alpha-null mice. Decrease of hepcidin mRNA in mice lacking hepatic C/EBPalpha was accompanied by iron accumulation in periportal hepatocytes. Finally, iron overload led to a significant increase of C/EBPalpha protein and HEPC transcripts in mouse liver. Taken together, these data demonstrate that C/EBPalpha is likely to be a key regulator of HEPC gene transcription and provide a novel mechanism for cross-talk between the C/EBP pathway and iron metabolism. C1 CHRU Pontchaillou, INSERM U522, F-35033 Rennes, France. NCI, Lab Metab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. CHRU Pontchaillou, Serv Malad Foie, F-35033 Rennes, France. RP Ilyin, G (reprint author), CHRU Pontchaillou, INSERM U522, F-35033 Rennes, France. RI Loreal, Olivier/G-3366-2013 NR 39 TC 180 Z9 190 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 2002 VL 277 IS 43 BP 41163 EP 41170 DI 10.1074/jbc.M202653200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 607KU UT WOS:000178791400127 PM 12183449 ER PT J AU Dudley, ME Wunderlich, JR Robbins, PF Yang, JC Hwu, P Schwartzentruber, DJ Topalian, SL Sherry, R Restifo, NP Hubicki, AM Robinson, MR Raffeld, M Duray, P Seipp, CA Rogers-Freezer, L Morton, KE Mavroukakis, SA White, DE Rosenberg, SA AF Dudley, ME Wunderlich, JR Robbins, PF Yang, JC Hwu, P Schwartzentruber, DJ Topalian, SL Sherry, R Restifo, NP Hubicki, AM Robinson, MR Raffeld, M Duray, P Seipp, CA Rogers-Freezer, L Morton, KE Mavroukakis, SA White, DE Rosenberg, SA TI Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes SO SCIENCE LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; T-CELL CLONES; ADOPTIVE IMMUNOTHERAPY; METASTATIC MELANOMA; IN-VIVO; INTERLEUKIN-2; RESPONSES; THERAPY; RECIPIENTS; INFECTION AB We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus related acquired immunodeficiency syndrome and other infectious diseases. C1 NCI, Surg Branch, NIH, Bethesda, MD 20902 USA. NEI, NIH, Bethesda, MD 20902 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20902 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20902 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 27 TC 1708 Z9 1767 U1 7 U2 91 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 25 PY 2002 VL 298 IS 5594 BP 850 EP 854 DI 10.1126/science.1076514 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 607KR UT WOS:000178791200066 PM 12242449 ER PT J AU Yamada, KM Clark, K AF Yamada, KM Clark, K TI Cell biology - Survival in three dimensions SO NATURE LA English DT Editorial Material ID EXPRESSION; GROWTH C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 10 TC 34 Z9 36 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 24 PY 2002 VL 419 IS 6909 BP 790 EP 791 DI 10.1038/419790a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 607BD UT WOS:000178769800025 PM 12397336 ER PT J AU Lawrence, NS Ross, TJ Stein, EA AF Lawrence, NS Ross, TJ Stein, EA TI Cognitive mechanisms of nicotine on visual attention SO NEURON LA English DT Article ID INFORMATION-PROCESSING PERFORMANCE; POSITRON EMISSION TOMOGRAPHY; SHORT-TERM-MEMORY; SUSTAINED ATTENTION; HUMAN BRAIN; WORKING-MEMORY; SUBCUTANEOUS NICOTINE; TRANSDERMAL NICOTINE; ALZHEIMERS-DISEASE; CIGARETTE-SMOKING AB Understanding nicotine's neurobiological and cognitive mechanisms may help explain both its addictive properties and potential therapeutic applications. As such, functional MRI was used to determine the neural substrates of nicotine's effects on a sustained attention (rapid visual information-processing) task. Performance was associated with activation in a fronto-parietal-thalamic network in both smokers and nonsmokers. Along with subtle behavioral deficits, mildly abstinent smokers showed less task-induced brain activation in the parietal cortex and caudate than did nonsmokers. Transdermal nicotine replacement improved task performance in smokers and increased task-induced brain activation in the parietal cortex, thalamus, and caudate, while nicotine induced a generalized increase in occipital cortex activity. These data suggest that nicotine improves attention in smokers by enhancing activation in areas traditionally associated with visual attention, arousal, and motor activation. C1 Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Cellular Biol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Biophys Res Inst, Milwaukee, WI 53226 USA. RP Stein, EA (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Ross, Thomas/B-7469-2008; Stein, Elliot/C-7349-2008; Lawrence, Natalia/A-1588-2010 OI Ross, Thomas/0000-0002-7745-3572; FU NIDA NIH HHS [DA09465]; PHS HHS [M01 00058] NR 51 TC 205 Z9 214 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 24 PY 2002 VL 36 IS 3 BP 539 EP 548 DI 10.1016/S0896-6273(02)01004-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 608ZE UT WOS:000178877700021 PM 12408855 ER PT J AU Staudt, LM AF Staudt, LM CA Lymphoma Leukemia Molecular Profil TI Molecular profiling of lymphoma - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 24 PY 2002 VL 347 IS 17 BP 1376 EP 1377 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 607FK UT WOS:000178781300017 ER PT J AU Fan, FY Jin, SQ Amundson, SA Tong, T Fan, WH Zhao, HC Zhu, XC Mazzacurati, L Li, XX Petrik, KL Fornace, AJ Rajasekaran, B Zhan, QM AF Fan, FY Jin, SQ Amundson, SA Tong, T Fan, WH Zhao, HC Zhu, XC Mazzacurati, L Li, XX Petrik, KL Fornace, AJ Rajasekaran, B Zhan, QM TI ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth SO ONCOGENE LA English DT Article DE ATF3; p53; DNA damage; gene regulation ID TRANSCRIPTIONAL REPRESSOR ATF3; GENOTOXIC-STRESS; MOLECULAR-BIOLOGY; CYCLE CHECKPOINT; ARREST GENES; UV-RADIATION; C-FOS; GADD45; P53; APOPTOSIS AB Mammalian cells have a remarkable diverse repertoire of response to genotoxic stress that damage DNA. Cellular responses to DNA damaging agents will initially exhibit gene induction, which is regulated by complex mechanism(s) and probably involves multiple signaling pathways. In this paper, we demonstrate that induction of ATF3 protein, a member of the ATF/CREB family of transcription factors, by ionizing radiation (IR) requires normal cellular p53 function. In contrast, induction of ATF3 after UV radiation (UV) or Methyl methanesulphonate (MMS) is independent of p53 status. Induction of ATF3 by DNA damage is rapid, transient, and through a transcriptional mechanism. The ATF3 promoter is induced by UV and MMS, but not by IR. In addition, ATF3 promoter can be activated by MEKK1, an upstream activator of the ERK and JNK kinase pathway, but not induced following p53 expression. Those results indicate that regulation of ATF3 induction after DNA damage utilizes both the p53-dependent and independent pathways, and may also involve MAP kinase signaling pathways. Using the tetracycline-inducible system (tet-off), we have found that overexpression of ATF3 protein moderately suppresses cell growth. Interestingly, over-expression of ATF3 protein is able to slow down progression of cells from G1 to S phase, indicating that ATF3 protein might play a negative role in the control of cell cycle progression. C1 Univ Pittsburgh, Sch Med, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. Chinese Acad Med Sci, Inst Canc, Natl Lab Mol Oncol, Beijing 100021, Peoples R China. NCI, Lab Basic Sci, NIH, Bethesda, MD 20892 USA. RP Zhan, QM (reprint author), Univ Pittsburgh, Sch Med, Inst Canc, Dept Radiat Oncol, BST W-945,200 Lothrop St, Pittsburgh, PA 15213 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 50 TC 119 Z9 125 U1 0 U2 10 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 24 PY 2002 VL 21 IS 49 BP 7488 EP 7496 DI 10.1038/sj.onc.1205896 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 604JX UT WOS:000178618200004 PM 12386811 ER PT J AU Li, WK Chen, SN Fabricant, D Angerhofer, CK Fong, HHS Farnsworth, NR Fitzloff, JF AF Li, WK Chen, SN Fabricant, D Angerhofer, CK Fong, HHS Farnsworth, NR Fitzloff, JF TI High-performance liquid chromatographic analysis of Black Cohosh (Cimicifuga racemosa) constituents with in-line evaporative light scattering and photodiode array detection SO ANALYTICA CHIMICA ACTA LA English DT Article DE Black Cohosh; Cimicifuga racemosa; triterpene glycosides; phenolic acids; flavonoids; HPLC; PDA; ELSD ID TRITERPENE GLYCOSIDES; SEQUENCE VARIATION; SIMPLEX WORMSK; RHIZOME; RANUNCULACEAE; PHYLOGENY; EXTRACTS; EFFICACY; ACTAEA; SAFETY AB A validated and reproducible high-performance liquid chromatography (HPLC) method with in-line evaporative light scattering and photodiode array detection was developed for the analysis of major constituents in Black Cohosh (Cimicifuga racemosa L.). The method is based on the baseline chromatographic separation of 18 compounds reported to be present in Black Cohosh on a C-18 column (5 mum, 4.6 mm, x 250 nun) with water (0.05% trifluoroacetic acid, TFA)-acetonitrile-water as the mobile phase, and their in-line detection using photodiode array detector (PDA) and evaporative light scattering detector (ELSD). Sixteen of these (caffeic acid, ferulic acid, isoferulic acid, cimicifugoside H-1, cimiracemoside A, cimicifugoside H-2, (26R)-actein, 26-deoxycimicifugoside, (26S)-actein, 23-epi-26-deoxyactein, 23-OAc-shengmanol-3-O-beta-D-xyloside, 26-deoxyactoin, 25-OAc-cimigenol-3-O-alpha-L-arabinoside, 25-OAc-cimigenol-3-O-beta-D-xyloside, cimigenol-3-O-alpha-L-arabinoside, cimigenol-3-O-beta-D-xyloside) were detected to be present and quantifiable. The reputed two flavonoid constituents (kaempferol and formononetin) were not detectable. The validation of the method included tests for sensitivity, linearity, reproducibility, recovery and stability. The detection limits were found to be in the range of 26-55 ng (10 mul per injection) in ELSD for the 16 constituents of Black Cohosh. The exponential linear calibration curves were observed for all the constituents tested with r(2) being >0.99. The reproducibility of the method was evaluated by analyzing three sets of controls on three consecutive days (n = 3) with R.S.D. (%) and relative error (%) <8.14 and 11.27%, respectively. The observed recovery rates were better than 91.75%. The stability of Black Cohosh methanolic sample solution was assessed by consecutively analyzing the methanolic solutions prepared from liquid extract (Sample A), powered extract (Sample B), milled plant material (Sample Q and one of the commercial product (Sample D I) for the content of 16 major constituents with the relative standard deviations (R.S.D., %) <6.39%, indicating the sample matrix of Black Cohosh is stable. Contrary to literature reports, kaempferol and formononetin were not detected in either our field collected plant materials or commercial products of Black Cohosh in the current assay. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Funct Food Hlth Core Analyt Lab, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. Toms Maine Corp, Lafayette Ctr, Kennebunk, ME 04043 USA. RP Fitzloff, JF (reprint author), Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, M-C 877,833 S Wood St, Chicago, IL 60612 USA. NR 34 TC 42 Z9 44 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD OCT 23 PY 2002 VL 471 IS 1 BP 61 EP 75 AR PII S0003-2670(02)00776-6 DI 10.1016/S0003-2670(02)00776-6 PG 15 WC Chemistry, Analytical SC Chemistry GA 603NJ UT WOS:000178565700007 ER PT J AU Yamada, M Kadoya, Y Kasai, S Kato, K Mochizuki, M Nishi, N Watanabe, N Kleinman, HK Yamada, Y Nomizu, M AF Yamada, M Kadoya, Y Kasai, S Kato, K Mochizuki, M Nishi, N Watanabe, N Kleinman, HK Yamada, Y Nomizu, M TI Ile-Lys-Val-Ala-Val (IKVAV)-containing laminin alpha 1 chain peptides form amyloid-like fibrils SO FEBS LETTERS LA English DT Article DE amyloid-like fibril; synthetic peptide; laminin; cell attachment; neurite outgrowth ID CELL-BINDING SEQUENCES; CONGO RED; A-CHAIN; SYNTHETIC PEPTIDES; NEURITE OUTGROWTH; BETA-SHEET; GLOBULAR DOMAIN; IKVAV SEQUENCE; IDENTIFICATION; PROTEIN AB The Ile-Lys-Val-Ala-Val (IKVAV) sequence derived from laminin-1 promotes cell adhesion, neurite outgrowth, and tumor growth and metastasis. Here, we examined amyloid formation of an IKVAV-containing peptide (LAM-L: AASIK-VAVSADR, mouse laminin alpha1 chain 2097-2108). The LAM-L peptide was stained with Congo red and exhibited fibrils in electron microscopy with a characteristic cross-beta X-ray diffraction pattern. Further, infrared spectra of LAM-L suggested a beta-sheet structure. These results indicate that LAM-L forms amyloid-like fibrils. We also examined amyloid-like fibril formation of LAM-L analogs. The neurite outgrowth activity of the LAM-L analogs was closely related to their amyloid-like fibril formation. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Hokkaido Univ, Grad Sch Environm Earth Sci, Div Biosci, Kita Ku, Sapporo, Hokkaido 0600810, Japan. Kitasato Univ, Sch Med, Dept Anat, Sagamihara, Kanagawa 2288555, Japan. Hokkaido Univ, Grad Sch Sci, Div Biol Sci, Sapporo, Hokkaido 0600810, Japan. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Nomizu, M (reprint author), Hokkaido Univ, Grad Sch Environm Earth Sci, Div Biosci, Kita Ku, Kita 10 Nishi 5, Sapporo, Hokkaido 0600810, Japan. NR 43 TC 34 Z9 35 U1 0 U2 1 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 23 PY 2002 VL 530 IS 1-3 BP 48 EP 52 AR PII S0014-5793(02)03393-8 DI 10.1016/S0014-5793(02)03393-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 608PZ UT WOS:000178856900009 PM 12387864 ER PT J AU Wan, HH Wootton, JC AF Wan, HH Wootton, JC TI Algorithms for computing lengths of chains in integral partition lattices SO THEORETICAL COMPUTER SCIENCE LA English DT Article DE algorithm; length; chain; partition lattice; majorization; nearby shift; distant shift ID SEQUENCE DATABASES; PROTEIN SEQUENCES; COMPLEXITY AB Let P-1,P-n denote the partition lattice of 1 with n parts, ordered by Hardy-Littlewood-Polya majorization. For any two comparable elements x and y of P-1,P-n we denote by M(x, y), m(x, y), f(x, y), and F(x, y), respectively, the sizes of four typical chains between x and y: the longest chain, the shortest chain, the lexicographic chain, and the counter-lexicographic chain. The covers u=(u(1),...,u(n)) > v=(v(1),...,v(n)) in P-1,P-n are of two types: N-shift (nearby shift) where v(i)=u(i) - 1, v(i)+1 = u(i+1) + 1 for some i; and D-shift (distant shift) where u(i) - 1 = v(i) = v(i+1) = ... = v(j) = u(j) + 1 for some i and j. An N-shift (a D-shift) is pure if it is not a D-shift (an N-shift). We develop linear algorithms for calculating M(x, y), m(x, y), f (x, y), and F(x, y), using the leftmost pure N-shift first search, the rightmost pure D-shift first search, the leftmost N-shift first search, and the rightmost D-shift first search, respectively. Those algorithms have significant applications in complexity analysis of biological sequences. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Comp Biol Branch, NIH, Bethesda, MD 20894 USA. RP Wan, HH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Comp Biol Branch, NIH, Bldg 38A,8th Floor,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 29 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3975 J9 THEOR COMPUT SCI JI Theor. Comput. Sci. PD OCT 23 PY 2002 VL 289 IS 1 BP 783 EP 800 AR PII S0304-3975(01)00392-9 DI 10.1016/S0304-3975(01)00392-9 PG 18 WC Computer Science, Theory & Methods SC Computer Science GA 611CR UT WOS:000178999300033 ER PT J AU Watts, NR Cheng, NQ West, W Steven, AC Sackett, DL AF Watts, NR Cheng, NQ West, W Steven, AC Sackett, DL TI The cryptophycin-tubulin ring structure indicates two points of curvature in the tubulin dimer SO BIOCHEMISTRY LA English DT Article ID MICROTUBULE DYNAMICS; VINCA DOMAIN; DENSITY MAPS; BETA-TUBULIN; RESOLUTION; BINDING; DOLASTATIN-10; MECHANISM; STABILIZATION; MICROGRAPHS AB Cryptophycin-1 is the parent compound of a group of cyclic peptides with potent antineoplastic activity. Cryptophycins are thought to function by modulating the dynamic instability of spindle microtubules, and in vitro are known to bind in an equimolar ratio to the beta-tubulin subunit and to induce the formation of ring-like complexes. However, the detailed mechanisms whereby the cryptophycins interact with tubulin are not known. We have investigated the origin of the conformational changes in tubulin both biochemically and by electron microscopy and image analysis. Cryptophycin was found to protect both alpha- and beta-tubulin against proteolysis by trypsin, indicating conformational changes in specific regions of both subunits. The ring mass was determined to be similar to0.81 MDa by sedimentation velocity combined with dynamic light scattering and by STEM, indicating a complex of eight alphabeta dimers. Statistical analysis of rings imaged by cryoelectron microscopy revealed 16-fold symmetry, corresponding to eight dimers. Computational averaging based on this symmetry yielded an image of a 24 nm diameter ring, at 2.6 nm resolution, that clearly distinguishes intradimer contacts from interdimer contacts, and allows discrimination of alpha-subunits from beta-subunits. Fitting of the tubulin dimer crystal structure into this projected density map indicates two points of curvature: a 13degrees intradimer bend and a 32degrees interdimer bend. We conclude that drug binding to one subunit (beta) results in two bends per dimer, affecting both subunits. C1 NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Sackett, DL (reprint author), NIH, Bldg 12A,Rm 2041, Bethesda, MD 20892 USA. FU NCRR NIH HHS [P41-RR01777] NR 39 TC 31 Z9 34 U1 0 U2 0 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 22 PY 2002 VL 41 IS 42 BP 12662 EP 12669 DI 10.1021/bi020430x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605TW UT WOS:000178694000011 PM 12379108 ER PT J AU Sun, GY Kurti, J Kertesz, M Baughman, RH AF Sun, GY Kurti, J Kertesz, M Baughman, RH TI Dimensional changes as a function of charge injection for trans-polyacetylene: A density functional theory study SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DOPED POLYACETYLENE; ELECTRON CORRELATION; NEUTRON-DIFFRACTION; CORRELATION-ENERGY; DIMERIZATION; GRAPHITE; POLYMERS; GEOMETRY; EXCHANGE AB Charge-induced dimensional changes allow conducting polymers and single walled carbon nanotubes to function as electromechanical actuators. The unit cell of the prototypical conducting polymer, trans-polyacetylene, was calculated as a function of charge injection using density functional theory in combination with ultrasoft pseudopotentials using the solid-state Vienna ab initio simulation package. Test calculations on the charged pyridinium molecular ion give results in good agreement with the experimental geometry. Strain versus charge relationships are predicted from dimensional changes calculated using a uniform background charge ("jellium") for representing the counterions, which we show provides results consistent with experiment for doped polyacetylenes. These jellium calculations are consistent with further presented calculations that include specific counterions, showing that hybridization between the guest dopant ions and the host polyacetylene chains is unimportant. The lack of guest-host orbital hybridization allows a qualitative rigid band interpretation of the amount of charge transfer for both acceptor and donor doping. For polyacetylene, asymmetry of strain along the chain with respect to the sign of the charge is predicted: negative charge elongates and positive charge shortens the polymer. For charge less than 0.05e per carbon, an approximately linear dependence is obtained for the dependence of chain-direction strain on the amount of injected charge. (C) 2002 American Institute of Physics. C1 Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Univ Texas, Nano Tech Inst, Richardson, TX 75083 USA. Univ Texas, Dept Chem, Richardson, TX 75083 USA. RP NCI, Med Chem Lab, NIH, 376 Boyles St, Ft Detrick, MD 21702 USA. EM kertesz@georgetown.edu RI Kertesz, Miklos/E-7122-2010 OI Kertesz, Miklos/0000-0002-7930-3260 NR 44 TC 16 Z9 16 U1 0 U2 5 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 22 PY 2002 VL 117 IS 16 BP 7691 EP 7697 DI 10.1063/1.1509052 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 602AW UT WOS:000178483400031 ER PT J AU Hecht, AM Horkay, F Schleger, P Geissler, E AF Hecht, AM Horkay, F Schleger, P Geissler, E TI Thermal fluctuations in polymer gels investigated by neutron spin echo and dynamic light scattering SO MACROMOLECULES LA English DT Article ID NETWORK AB Measurements are described involving neutron spin echo and quasi-elastic light scattering in an end-linked polyfluorosilicone (PFS) gel swollen in acetone as well as in the equivalent solution. Small-angle elastic neutron scattering measurements were performed on the same system. For the PFS-acetone system, both dynamic light scattering and neutron spin echo yield similar results for the characteristic relaxation rates and for the intensity scattered by concentration fluctuations. It is shown that the relaxing part of the spin echo decay is described by the same thermodynamic concentration fluctuations that define the osmotic modulus of the system. Both the collective diffusion coefficient and the intensity of the dynamically scattered light are found to be greater in the gel than in the solution. This difference indicates that the polymer solvent friction coefficient in the cross-linked network is lower than in the un-cross-linked solution. C1 Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Inst Max Von Laue Paul Langevin, F-38042 Grenoble, France. RP Geissler, E (reprint author), Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, BP 87, F-38402 St Martin Dheres, France. NR 12 TC 20 Z9 20 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD OCT 22 PY 2002 VL 35 IS 22 BP 8552 EP 8555 DI 10.1021/ma020507p PG 4 WC Polymer Science SC Polymer Science GA 606MP UT WOS:000178738000040 ER PT J AU Sawaki, L Cohen, LG Classen, J Davis, BC Butefisch, CM AF Sawaki, L Cohen, LG Classen, J Davis, BC Butefisch, CM TI Enhancement of use-dependent plasticity by D-amphetamine SO NEUROLOGY LA English DT Article ID MOTOR CORTEX; FATIGUE; MOVEMENT; RECOVERY AB In healthy individuals, motor training can elicit use-dependent plasticity. Here the authors studied six subjects in whom training alone failed to elicit this effect. Administration of a single dose of 10 mg Of D-amphetamine preceding training led to use-dependent plasticity in a subgroup of these subjects. Using pharmacologic interventions to enhance the effects of motor training might help rehabilitative efforts in patients in whom training alone fails. C1 Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bldg 10,Rm 5N 226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 9 TC 47 Z9 49 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 22 PY 2002 VL 59 IS 8 BP 1262 EP 1264 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 606GR UT WOS:000178726700029 PM 12391362 ER PT J AU Katz, BZ Miyamoto, S Teramoto, H Zohar, M Krylov, D Vinson, C Gutkind, JS Yamada, KM AF Katz, BZ Miyamoto, S Teramoto, H Zohar, M Krylov, D Vinson, C Gutkind, JS Yamada, KM TI Direct transmembrane clustering and cytoplasmic dimerization of focal adhesion kinase initiates its tyrosine phosphorylation SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE FAK; tyrosine phosphorylation; clustering; dimerization; MAP kinase ID INTEGRIN-MEDIATED ACTIVATION; CELL-CYCLE PROGRESSION; GTP-BINDING PROTEINS; SIGNAL-TRANSDUCTION; CYTOSKELETAL; RAS; MIGRATION; DOMAIN; MATRIX; LOCALIZATION AB We investigated mechanisms for inducing focal adhesion kinase (FAK) tyrosine phosphorylation and their ability to trigger MAP kinase signaling using transmembrane chimeras that localize FAK and its mutants to the plasma membrane. We tested whether tyrosine phosphorylation was triggered by FAK transmembrane aggregation using antibodies against the chimeric extracellular domain. Experimental clustering of chimeras containing integrin p cytoplasmic domains or FAK induced FAK tyrosine phosphorylation and trans-phosphorylation of endogenous FAK, as well as strong ERK activation. Next, we examined whether lower-order molecular proximity, namely dimerization, could regulate FAK tyrosine phosphorylation. We found that even relatively low-affinity FAK dimerization (K-d = 3.9 x 10(-5) M), in either of two different orientations, could induce FAK tyrosine phosphorylation. However, this cytoplasmic FAK dimerization could not induce MAP kinase activation or trans-phosphorylation of endogenous FAK. We conclude that dimerization of FAK is sufficient to induce its tyrosine phosphorylation, but that higher-order molecular proximity (clustering) at the cell membrane is apparently needed for additional biochemical events. This study identifies a proximity mechanism for regulating the initiation of FAK-mediated biochemical signaling. Published by Elsevier Science B.V. C1 NIH, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Katz, BZ (reprint author), Tel Aviv Med Ctr & Sch Med, Inst Hematol, 6 Weizman St, Tel Aviv, Israel. RI Gutkind, J. Silvio/A-1053-2009; OI Yamada, Kenneth/0000-0003-1512-6805 NR 50 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT 21 PY 2002 VL 1592 IS 2 BP 141 EP 152 AR PII S0167-4889(02)00308-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 607ZY UT WOS:000178821700006 PM 12379477 ER PT J AU Han, SQ Hamel, E Bastow, KF McPhail, AT Brossi, A Lee, KH AF Han, SQ Hamel, E Bastow, KF McPhail, AT Brossi, A Lee, KH TI Antitumor agents. Part 215: Antitubulin effects of cytotoxic B-ring modified allocolchicinoids SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID METHYL-ETHER; THIOCOLCHICINE; ANALOGS AB N-Acetylcolchinol methyl ether 1 served as the starting material to prepare the chloroacetamide (3) and epoxide (5) analogues. Both 3 and 5 were potent inhibitors of tubulin polymerization in vitro. Compound 3 was also 4-fold more cytotoxic than colchicine against the 1A9 tumor cell line and showed a unique cross-resistance profile. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA. NCI Frederick, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. Duke Univ, Dept Chem, Paul M Gross Chem Lab, Durham, NC 27708 USA. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA17525] NR 9 TC 8 Z9 8 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 21 PY 2002 VL 12 IS 20 BP 2851 EP 2853 AR PII S0960-894X(02)00635-2 DI 10.1016/S0960-894X(02)00635-2 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 601MJ UT WOS:000178450000012 PM 12270161 ER PT J AU Michaud, DS Pietinen, P Taylor, PR Virtanen, M Virtamo, J Albanes, D AF Michaud, DS Pietinen, P Taylor, PR Virtanen, M Virtamo, J Albanes, D TI Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study SO BRITISH JOURNAL OF CANCER LA English DT Article DE vitamins; carotenoids; fruit; vegetables; bladder cancer; cohort studies; epidemiology ID FINNISH FOODS; BETA-CAROTENE; SUPPLEMENTS; CONSUMPTION; RETINOIDS; PRODUCTS; MEN AB We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27111 male smokers aged 5069 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk = 1.28; 95% confidence intervals CI: 0.89 - 1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to nonsmokers. (C) 2002 Cancer Research UK. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Rockville, MD USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Canc Res Ctr, Rockville, MD USA. RP Michaud, DS (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-320 MSC 7232, Bethesda, MD 20892 USA. RI Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN045035, N01 CN045165] NR 32 TC 77 Z9 84 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 21 PY 2002 VL 87 IS 9 BP 960 EP 965 DI 10.1038/sj.bjc.6600604 PG 6 WC Oncology SC Oncology GA 614FT UT WOS:000179178200006 PM 12434284 ER PT J AU Scheinecker, C McHugh, R Shevach, EM Germain, RN AF Scheinecker, C McHugh, R Shevach, EM Germain, RN TI Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE antigen-presenting cells; autoimmune disease; gastritis; autoantigen; CD11c antigen ID CLASS-II COMPLEXES; THYMECTOMY AUTOIMMUNE GASTRITIS; IMMUNOLOGICAL SELF-TOLERANCE; EPIDERMAL LANGERHANS CELLS; MYELIN BASIC-PROTEIN; REACTIVE T-CELLS; IN-VIVO; MONOCLONAL-ANTIBODY; B-CELLS; EFFICIENT PRESENTATION AB The major histocompatibility complex (MHC)-dependent presentation of processed tissue-specific self-antigens can contribute to either peripheral (extrathymic) tolerance or the differentiation of autoreactive T cells. Here, we have studied the MHC class II molecule presentation of gastric parietal cell (PC)-specific H+/K+-ATPase, which induces a destructive autoimmune gastritis in BALB/c mice lacking CD4(+) CD25(+) regulatory T cells. Immunofluorescence microscopy showed physical association of CD11c(+) dendritic cells (DCs) with PCs in the gastric mucosa. H+/K+-ATPase protein was found within vesicular compartments of a few CD11c(+) DCs only in the draining gastric lymph node (LN) and these antigen-containing DCs increased markedly in number with the onset of tissue destruction in autoimmune animals. Both CD8alpha(hi) and CD8alpha(lo) gastric DCs, but not peripheral or inesenteric DCs, showed evidence of constitutive in vivo processing and presentation of H+/K+-ATPase. These data provide direct support for a widely held model of local tissue antigen uptake and trafficking by DCs in normal animals and demonstrate that DCs in the draining LN can present a tissue-specific self-antigen under noninflammatory conditions without fully deleting autoreactive T cells or inducing active autoimmunity. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 10 Ctr Dr MSC-1892,Bldg 10,Room 11N311, Bethesda, MD 20892 USA. EM rgermain@nih.gov NR 66 TC 279 Z9 283 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 21 PY 2002 VL 196 IS 8 BP 1079 EP 1090 DI 10.1084/jem.20020991 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 609FN UT WOS:000178893100009 PM 12391019 ER PT J AU Tasaki, I AF Tasaki, I TI Spread of discrete structural changes in synthetic polyanionic gel: A model of propagation of a nerve impulse SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID FIBERS; CELLS AB Thin fibers of cross-linked polyacrylate gel were prepared by inducing polymerization reaction inside long glass or Tygon tubings. By immersing these gel fibers in salt solutions containing both Ca(2+) and Na(+) at varying ratios, a discontinuous transition from the swollen state to the shrunken was demonstrated. A very sharp boundary was observed between the swollen and shrunken portions of the gel fiber. It was found possible to displace this sharp boundary continuously by application of a weak electric current. Based on the similarity in swelling behavior between nerve fibers and synthetic gel fibers, a non-myelinated nerve fiber carrying an impulse was treated as a cylindrical gel layer consisting of two distinct portions, a swollen (active) portion connected directly to the remaining shrunken (resting) portion. By applying the cable theory to this model of the nerve fiber, mathematical expressions describing the conduction velocity, the maximum rate of potential rise, etc. in terms of the electric parameters of the fiber were derived. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NICHD, LIMB, NIH, Bethesda, MD 20892 USA. NIMH, LCMR, NIH, Bethesda, MD 20892 USA. RP Tasaki, I (reprint author), NICHD, LIMB, NIH, Bethesda, MD 20892 USA. EM itasaki@erols.com NR 19 TC 13 Z9 15 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD OCT 21 PY 2002 VL 218 IS 4 BP 497 EP 505 DI 10.1006/jtbi.2002.3095 PG 9 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 613FC UT WOS:000179120800009 PM 12384052 ER PT J AU Alavanja, MCR AF Alavanja, MCR TI Biologic damage resulting from exposure to tobacco smoke and from radon: implication for preventive interventions SO ONCOGENE LA English DT Review DE lung cancer; radon; smoking; pathologic mechanism ID OXIDATIVE DNA-DAMAGE; LUNG-CANCER RISK; S-TRANSFERASE M1; SISTER-CHROMATID EXCHANGES; P53 MUTATION HOTSPOT; ALPHA-PARTICLES; MAMMALIAN-CELLS; CIGARETTE-SMOKE; FREE-RADICALS; UNITED-STATES AB Cigarette smoking and residential radon are, respectively, the first and second leading cause of lung cancer in the United States today. Of the approximately 157000 lung deaths occurring in 2000, approximately 90% can be attributed to cigarette smoking and 30% 4 the lung cancer deaths among non-smokers can be attributed to residential radon exposure. Although dwarfed by cigarette related lung cancer, lung cancer among lifetime non-smokers is a leading cause of death in the United States, and many other countries, accounting for approximately 16000 deaths per year in the US. Laboratory studies and epidemiological investigations, particularly those conducted in the past decade, are yielding evidence that tobacco smoke and radon may share important elements of lung cancer's pathologic mechanism(s). Lung cancer prevention among smokers, ex-smokers and lifetime nonsmokers can be enhanced as we learn more about the etiologic mechanism(s) of lung cancer resulting from these and other exposures including diet, non-malignant respiratory diseases, occupational exposures, and susceptibility-gene. In this article we review both laboratory and epidemiologic data that gives insight into the biologic damage done to the lung from these exposures. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8000, Rockville, MD 20892 USA. NR 134 TC 22 Z9 23 U1 0 U2 1 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 21 PY 2002 VL 21 IS 48 BP 7365 EP 7375 DI 10.1038/sj.onc.1205798 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 604JW UT WOS:000178618000009 PM 12379879 ER PT J AU Antman, E Cooper, H Domanski, M Feinstein, S Gersh, B Gibler, WB Haigney, M Hochman, J McKinlay, S Norman, J Opie, L Rogers, W Rosenberg, Y Woods, K Mills, P Rosenberg, Y Assmann, S Woods, K Nannicelli, J Scott, J Oakleaf, K Singh, S Davis, B Hallstrom, A Levine, R Robertson, R Norman, J Gretton, V Scott, K Dolan, S Brown, M Ewart, A Hendriks, R Jeffrey, I Newman, R Quinn, W Rankin, J Russell, A Singh, B Waites, J Ziffer, R Smetana, R Col, J Bruno, P Evrard, P Massart, PE Vrabevski, M Andreev, N Benov, H Boichev, B Daskalov, T Dzhurdzhev, A Elenkova, A Gateva, S Genov, S Georgiev, S Hergeldzhieva, V Kaloyanova, A Karaassenoy, M Kozhuharov, C Krastev, A Lovdzhicva, S Margaritov, V Mateeva, D Mihov, A Milanov, S Nachev, C Naidenova, L Ninova, M Penkoy, N Perchev, I Popov, A Raev, D Staykov, I Tanev, T Taneva, I Toneva, L Todorov, T Vassileva, T Lazarenko, G Lubelsky, B Senaratne, MPJ Garber, P Ringuette, G Auersberg, E Noseworthy, R Corbalan, R Betancourt, R Potthoff, S Kobulia, B Tsintsadze, G Khabeishvilli, G Paposhvili, K Chapidze, G Khintibidze, I Melia, A Mamatsashvilli, M Keltai, M Toth, K Janosi, A Papp, A Tarjan, J Konya, L Katona, A Zoltan, L Poor, F Varadi, A Soltesz, P Mohacsi, A Lupkovics, G Bartal, G Szaboki, F Tahy, A Fenyvesi, T Shechter, M Hod, H Lotan, C Weiss, AT van der Heijden, MY van Hessen, MWJ van de Moer, WMM van der Heijden, R Jochemsen, GM White, H Rankin, R Hedley, JM Hamer, A Abdul-Gaffar, N Hills, M Sebastian, C Varshavsky, S Zavolozin, S Kosouhov, A Timofeev, A Kalinina, S Gordienko, T Ermoshkina, L Tarasov, N Sitnikova, V Shulman, V Nechepurenko, G Sumin, A Vertkin, A Lyusoy, V Emelyanov, I Baranov, E Strekalovsky, A Fotianov, S Goryachkin, I Barbarich, V Rifel, A Belenky, D Lapin, O Pavlov, A Yakovlev, O Kharkov, A Petrov, D Bzhelyanskaya, V Repin, M Stefanenko, M Vishnevsky, A Klenina, I Khankoeva, A Yakusheva, S Shlyakhto, E Goloshchekin, B Sorokin, L Vorochnina, S Zverev, D Deryugin, M Belekhov, G Shwarts, Y Orlikova, O Novoghenina, A Maximov, I Stefanenko, M Shalaev, S Pomogalova, O Yakusevish, V Hrustalev, O Sergeeva, M Boyarkin, M Mogilevsky, A Grinshtein, Y Mogilevsky, A Moiseev, V Saiganov, S Striouck, R Kots, Y Antonova, T Demko, A Susharin, L Ishmurzin, G Khramov, V Miller, MS Battle, RW Akosah, K Grossman, D Lader, E Pollack, ML Mezei, LE Hull, W Jenny, D Ghahramani, AR Linz, PE Kutscher, AH Cannon, JD Keedy, D O'Gara, PT Scaggs, TR Basu, D Kmetzo, JJ Rubin, A Rubinstein, R Rivera, E Schachter, DT DiBlasi, SL Meyers, D Heltne, CE Hanovich, G Arouni, A Slater, J Malik, S Harchelroad, F Genovely, HC Alpert, M Reese, S Holland, S McClure, JM Priest, M Dixon, D Herzog, W Ford, JK Rave, M Mahrer, P Eisenberg, S Ringham, J Mattern, A Hall, DM Ramalanjaona, G Walter, G Bhalla, R Hosny, A Baber, Z Wadhwani, J Mikhail, M Paul, TO Lopez, F Watkins, JW Soloff, L Tri, TB Aliabadi, DG Tice, P Denny, DM Bertolet, BD Oschwald, CJ Silverman, R Varriale, P Wilson, J Ramamurti, S Jenny, D Pappas, JD Beattie, JR Rosenblatt, A Courtade, D Pond, MS Fritz, RM Siegel, RM Tran, TP Wright, RS Hodsden, JE Teichholz, L Cox, JM Munyak, J Kippperman, RM Vergne, R Ghali, JK Hudson, J Rabbani, LE Greenberg, R McKendall, G Mohan, K Forker, AD Hanley, HG Brodsky, MA Kluger, J Blanda, M Longo, J Samadi, RR Ziady, G Young, SP Liu, CY Shapiro, M Mamuya, W Bowling, LS Carrillo, E Morr, I Briceno, E AF Antman, E Cooper, H Domanski, M Feinstein, S Gersh, B Gibler, WB Haigney, M Hochman, J McKinlay, S Norman, J Opie, L Rogers, W Rosenberg, Y Woods, K Mills, P Rosenberg, Y Assmann, S Woods, K Nannicelli, J Scott, J Oakleaf, K Singh, S Davis, B Hallstrom, A Levine, R Robertson, R Norman, J Gretton, V Scott, K Dolan, S Brown, M Ewart, A Hendriks, R Jeffrey, I Newman, R Quinn, W Rankin, J Russell, A Singh, B Waites, J Ziffer, R Smetana, R Col, J Bruno, P Evrard, P Massart, PE Vrabevski, M Andreev, N Benov, H Boichev, B Daskalov, T Dzhurdzhev, A Elenkova, A Gateva, S Genov, S Georgiev, S Hergeldzhieva, V Kaloyanova, A Karaassenoy, M Kozhuharov, C Krastev, A Lovdzhicva, S Margaritov, V Mateeva, D Mihov, A Milanov, S Nachev, C Naidenova, L Ninova, M Penkoy, N Perchev, I Popov, A Raev, D Staykov, I Tanev, T Taneva, I Toneva, L Todorov, T Vassileva, T Lazarenko, G Lubelsky, B Senaratne, MPJ Garber, P Ringuette, G Auersberg, E Noseworthy, R Corbalan, R Betancourt, R Potthoff, S Kobulia, B Tsintsadze, G Khabeishvilli, G Paposhvili, K Chapidze, G Khintibidze, I Melia, A Mamatsashvilli, M Keltai, M Toth, K Janosi, A Papp, A Tarjan, J Konya, L Katona, A Zoltan, L Poor, F Varadi, A Soltesz, P Mohacsi, A Lupkovics, G Bartal, G Szaboki, F Tahy, A Fenyvesi, T Shechter, M Hod, H Lotan, C Weiss, AT van der Heijden, MY van Hessen, MWJ van de Moer, WMM van der Heijden, R Jochemsen, GM White, H Rankin, R Hedley, JM Hamer, A Abdul-Gaffar, N Hills, M Sebastian, C Varshavsky, S Zavolozin, S Kosouhov, A Timofeev, A Kalinina, S Gordienko, T Ermoshkina, L Tarasov, N Sitnikova, V Shulman, V Nechepurenko, G Sumin, A Vertkin, A Lyusoy, V Emelyanov, I Baranov, E Strekalovsky, A Fotianov, S Goryachkin, I Barbarich, V Rifel, A Belenky, D Lapin, O Pavlov, A Yakovlev, O Kharkov, A Petrov, D Bzhelyanskaya, V Repin, M Stefanenko, M Vishnevsky, A Klenina, I Khankoeva, A Yakusheva, S Shlyakhto, E Goloshchekin, B Sorokin, L Vorochnina, S Zverev, D Deryugin, M Belekhov, G Shwarts, Y Orlikova, O Novoghenina, A Maximov, I Stefanenko, M Shalaev, S Pomogalova, O Yakusevish, V Hrustalev, O Sergeeva, M Boyarkin, M Mogilevsky, A Grinshtein, Y Mogilevsky, A Moiseev, V Saiganov, S Striouck, R Kots, Y Antonova, T Demko, A Susharin, L Ishmurzin, G Khramov, V Miller, MS Battle, RW Akosah, K Grossman, D Lader, E Pollack, ML Mezei, LE Hull, W Jenny, D Ghahramani, AR Linz, PE Kutscher, AH Cannon, JD Keedy, D O'Gara, PT Scaggs, TR Basu, D Kmetzo, JJ Rubin, A Rubinstein, R Rivera, E Schachter, DT DiBlasi, SL Meyers, D Heltne, CE Hanovich, G Arouni, A Slater, J Malik, S Harchelroad, F Genovely, HC Alpert, M Reese, S Holland, S McClure, JM Priest, M Dixon, D Herzog, W Ford, JK Rave, M Mahrer, P Eisenberg, S Ringham, J Mattern, A Hall, DM Ramalanjaona, G Walter, G Bhalla, R Hosny, A Baber, Z Wadhwani, J Mikhail, M Paul, TO Lopez, F Watkins, JW Soloff, L Tri, TB Aliabadi, DG Tice, P Denny, DM Bertolet, BD Oschwald, CJ Silverman, R Varriale, P Wilson, J Ramamurti, S Jenny, D Pappas, JD Beattie, JR Rosenblatt, A Courtade, D Pond, MS Fritz, RM Siegel, RM Tran, TP Wright, RS Hodsden, JE Teichholz, L Cox, JM Munyak, J Kippperman, RM Vergne, R Ghali, JK Hudson, J Rabbani, LE Greenberg, R McKendall, G Mohan, K Forker, AD Hanley, HG Brodsky, MA Kluger, J Blanda, M Longo, J Samadi, RR Ziady, G Young, SP Liu, CY Shapiro, M Mamuya, W Bowling, LS Carrillo, E Morr, I Briceno, E CA MAGIC Trial Investigators TI Early administration of intravenous magnesium to high-risk patients with acute myocardial infarction in the Magnesium in Coronaries (MAGIC) Trial: a randomised controlled trial SO LANCET LA English DT Article ID THROMBOLYTIC THERAPY; NATIONAL REGISTRY; CLINICAL-TRIALS; SULFATE; ARRHYTHMIAS; SIZE; INFUSION; LIMIT-2; SCORE; MI AB Background The benefits of supplemental administration of intravenous magnesium in patients with ST-elevation myocardial infarction (STEMI) are controversial. Despite promising results from work in animals and the ready availability of this simple, inexpensive treatment, conflicting results have been reported in clinical trials. Our aim was to compare short-term mortality in patients with STEMI who received either intravenous magnesium sulphate or placebo. Methods We did a randomised, double-blind trial in 6213 patients with acute STEMI who were assigned a 2 g intravenous bolus of magnesium sulphate administered over 15 min, followed by a 17 g infusion of magnesium sulphate over 24 h (n=3113), or matching placebo (n=3100). Our primary endpoint was 30-day all-cause mortality. At randomisation, patients were stratified by their eligibility for reperfusion therapy. The first stratum included patients who were aged 65 years or older and eligible for reperfusion therapy, and the second stratum included patients of any age who were not eligible for reperfusion therapy. Analysis was by intention-to-treat. Findings At 30 days, 475 (15.3%) patients in the magnesium group and 472 (15.2%) in the placebo group had died (odds ratio 1.0, 95% CI 0.9-1.2, p=0.96). No benefit or harm of magnesium was observed in eight prespecified subgroup analyses of patients and in 15 additional exploratory subgroup analyses. After adjustment for factors shown to effect mortality risk in a multivariate regression model, no benefit of magnesium was observed (1.0, 0.8-1.1, p=0.53). Interpretation Early administration of magnesium in high-risk patients with STEMI has no effect on 30-day mortality. In view of the totality of the available evidence, in current coronary care practice there is no indication for the routine administration of intravenous magnesium in patients with STEMI. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Antman, E (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 35 TC 104 Z9 106 U1 1 U2 4 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 19 PY 2002 VL 360 IS 9341 BP 1189 EP 1196 DI 10.1016/S0140-6736(02)11278-5 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 605ZZ UT WOS:000178708100007 ER PT J AU Leach, RE Romero, R Kim, YM Chaiworapongsa, T Kilbum, B Das, SK Dey, SK Johnson, A Qureshi, F Jacques, S Armant, DR AF Leach, RE Romero, R Kim, YM Chaiworapongsa, T Kilbum, B Das, SK Dey, SK Johnson, A Qureshi, F Jacques, S Armant, DR TI Pre-eclampsia and expression of heparin-binding EGF-like growth factor SO LANCET LA English DT Article ID PREECLAMPSIA; APOPTOSIS; PLACENTATION; CYTOTROPHOBLASTS; IMPLANTATION; PREGNANCIES; INVASION; UTERINE AB Background Pre-eclampsia is a disorder of pregnancy associated with poor extravillous cytotrophoblast invasion and above-normal rates of apoptosis in the trophoblast. Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) has strong cytoprotective activity and is an important signalling protein that regulates trophoblast invasion during early placentation. We aimed to establish whether HB-EGF expression is altered in placentae of pre-eclamptic women. Methods We assessed the expression of HB-EGF mRNA and protein by in-situ hybridisation and immunohistochemical techniques, respectively, in archived placental tissues from pregnancies terminated at around 20 weeks of gestation, and from women delivering between weeks 19 and 35 of gestation with preterm labour, small for gestational age infants, or pre-eclampsia. Findings HB-EGF mRNA and protein were expressed in villous and extravillous cytotrophoblast cells up to week 35 of gestation in placentae from women who delivered preterm. Similar levels of HB-EGF protein were found in the placentae of women who were not in labour. HB-EGF expression was reduced about five-fold (p=0.0001) in pre-eclamptic pregnancies. Fetal growth retardation, which has been linked with shallow trophoblast invasion and moderate apoptosis, was associated with placentae expressing intermediate levels of HB-EGF. Interpretation In pre-eclampsia, deficient HB-EGF signalling during placental development could impair trophoblast survival, differentiation, and invasion, leading to poor placental perfusion and hypertension. C1 Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Dept Anat & Cell Biol, Detroit, MI USA. Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Dept Pathol, Detroit, MI USA. NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Div Reprod & Dev Biol, Nashville, TN 37232 USA. RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Mott Ctr, 275 E Hancock Ave, Detroit, MI 48201 USA. OI Armant, D. Randall/0000-0001-5904-9325 FU NIAAA NIH HHS [AA12057]; NICHD NIH HHS [HD12304, HD33994, HD36764, HD37500, HD37830, HD98004] NR 27 TC 60 Z9 65 U1 2 U2 4 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 19 PY 2002 VL 360 IS 9341 BP 1215 EP 1219 DI 10.1016/S0140-6736(02)11283-9 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 605ZZ UT WOS:000178708100011 PM 12401248 ER PT J AU Sklar, PA Ward, DJ Baker, RK Wood, KC Gafoor, Z Alzola, CF Moormanm, AC Holmberg, SD AF Sklar, PA Ward, DJ Baker, RK Wood, KC Gafoor, Z Alzola, CF Moormanm, AC Holmberg, SD CA HOPS Investigators TI Prevalence and clinical correlates of HIV viremia ('blips') in patients with previous suppression below the limits of quantification SO AIDS LA English DT Article DE transient viremia; viral load; highly active antiretroviral therapy; CD4; cohort study; HIV infections; prevalence ID THERAPY; LOAD AB Objective: To examine the prevalence and clinical correlates of subsequently measurable viremia in HIV-infected patients who have achieved viral suppression below the limits of quantification (< 50 copies/ml). Design: Non-randomized dynamic cohort study of ambulatory HIV patients in nine HIV clinics in eight cities. Patients: Patients had two consecutive HIV-1 RNA levels < 50 copies/ml (minimum, 2 months apart) that were followed by at least two more viral level determinations while remaining on the same antiretroviral therapy (ART) between January 1997 and June 2000 (median 485 days). Transiently viremic patients were defined having a subsequently measurable viremia but again achieved suppression < 50 copies/ml. Results: Of the 448 patients, 122 (27.2%) had transient viremia, 19 (4.2%) had lasting low-level viremia and 33 (7.4%) had lasting high-level viremia (defined as 50400 and > 400 copies/ml, respectively). Only 16 (13.1%) of those who had transient viremia later had persistent viremia > 50 copies/ml. The occurrence of transient viremia did not vary with whether the patient was ART naive or experienced (P = 0.31), or currently taking protease inhibitors or not (P = 0.08). On consistent ART, the median percentage increase in CD4 cell count was statistically different between subgroups of our cohort (Kruskal-Wallis, P = 0.002). Conclusions: Transiently detectable viremia, usually 50-400 copies/ml, was frequent among patients who had two consecutive HIV-1 RNA levels below the limits of quantification. In this analysis, such viremia did not appear to affect the risk of developing lasting viremia. Caution is warranted before considering a regimen as 'failing' and changing medications. (C) 2002 Lippincott Williams Wilkins. C1 George Washington Univ, Div Infect Dis, Washington, DC USA. Dupont Circle Phys Grp, Washington, DC USA. Cerner Corp, Vienna, VA USA. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. RP Sklar, PA (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr, Bethesda, MD 20892 USA. OI Moorman, Anne/0000-0003-2411-2798 FU ODCDC CDC HHS [UC64/CCU5096889-03] NR 11 TC 69 Z9 69 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 18 PY 2002 VL 16 IS 15 BP 2035 EP 2041 DI 10.1097/00002030-200210180-00008 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 612FR UT WOS:000179064300008 PM 12370502 ER PT J AU Kino, T Tsukamoto, M Chrousos, GP AF Kino, T Tsukamoto, M Chrousos, GP TI Transcription factor TFIIH components enhance the GR coactivator activity but not the cell cycle-arresting activity of the human immunodeficiency virus type-1 protein Vpr SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE CDK7; cyclin H; MAT1; coactivator; cell cycle arrest ID HIV-1 PREINTEGRATION COMPLEX; ACTIVATING KINASE CAK; RNA-POLYMERASE-II; DNA-REPAIR; T-CELLS; IN-VIVO; RECEPTOR; INTERACTS; PHOSPHORYLATION; REQUIREMENT AB The human immunodeficiency virus type-1 (HIV-1)-accessory protein Vpr interacts with and potentiates the activity of the glucocorticoid receptor (GR) and arrests the host cell cycle at the G2/M boundary. Here we report that three core components of the general transcription factor (TF) IIH, CDK7, Cyclin H, and MAT1, enhance Vpr's GR coactivator activity but inhibit its cell cycle-arresting function. A CDK7 mutant defective in kinase activity for the C-terminal tail of RNA polymerase II, which cannot form a functional TFIIH complex, did not enhance Vpr coactivator activity. Overexpression of all three TFIIH components and p300 cooperatively enhanced Vpr coactivator activity, whereas TFIIH overexpression did not potentiate the transcriptional activity of a Vpr mutant, which does not bind p300/CBP. These findings suggest that TFIIH participates in Vpr's GR coactivating activity, at a step beyond its interaction with p300/CBP. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 43 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 18 PY 2002 VL 298 IS 1 BP 17 EP 23 AR PII S0006-291X(02)02442-7 DI 10.1016/S0006-291X(02)02442-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 607LF UT WOS:000178792500004 PM 12379213 ER PT J AU Hurley, JH Wendland, B AF Hurley, JH Wendland, B TI Endocytosis: Driving membranes around the bend SO CELL LA English DT Review ID ENTH DOMAIN; CLATHRIN; BINDING; AP180 AB When a nascent vesicle buds, the membrane must curve. Several mechanisms have been proposed for curvature creation or stabilization. Structural analysis of the ENTH domain of the endocytic protein epsin has suggested a new mechanism, in which the ENTH domain pushes its way into membranes, thus bending them into shape. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 19 TC 41 Z9 43 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 18 PY 2002 VL 111 IS 2 BP 143 EP 146 DI 10.1016/S0092-8674(02)01044-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 606UX UT WOS:000178753500001 PM 12408856 ER PT J AU Greenstone, HL Santoro, F Lusso, P Berger, EA AF Greenstone, HL Santoro, F Lusso, P Berger, EA TI Human herpesvirus 6 and measles virus employ distinct CD46 domains for receptor function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEMBRANE COFACTOR PROTEIN; DECAY-ACCELERATING FACTOR; RECOMBINANT VACCINIA VIRUS; MONOCLONAL-ANTIBODIES; CELLULAR RECEPTOR; COMPLEMENT ACTIVATION; MULTIPLE ISOFORMS; BINDING DOMAINS; MCP; SITES AB We employed a quantitative cell fusion assay to identify structural domains of CD46 required for its function as a receptor for human herpesvirus 6 (HHV-6). We examined the activities of recombinant variants of CD46, including different isoforms as well as engineered truncations and molecular chimeras with decay-accelerating factor, a related protein in the family of regulators of complement activation (RCA). We observed strong receptor activity for all four CD46 isoforms, which differ in the membrane-proximal extracellular and cytoplasmic domains, indicating that the critical determinants for HHV-6 receptor activity reside outside the C-terminal portion of CD46. Analysis of the short consensus repeat (SCR) regions that comprise most of the extracellular portion of CD46 indicated a strong dependence on SCRs 2 and 3 and no requirement for SCRs 1 or 4. Fusion-inhibition studies with SCR-specific monoclonal antibodies supported the essential role of SCRs 2 and 3 in HHV-6 receptor activity. These findings contrast markedly with fusion mediated by measles virus glycoproteins for which we observed a strict dependence on SCRs 1 and 2, consistent with previous reports. These results expand the emerging notion that CD46 and other members of the RCA family are co-opted in distinct manners by different infectious pathogens. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. San Raffaele Sci Inst, Dept Biol & Technol Res, Unit Human Virol, I-20132 Milan, Italy. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Rm 237, Bethesda, MD 20892 USA. NR 54 TC 41 Z9 44 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 18 PY 2002 VL 277 IS 42 BP 39112 EP 39118 DI 10.1074/jbc.M206488200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605EA UT WOS:000178662500009 PM 12171934 ER PT J AU Szymkiewicz, I Kowanetz, K Soubeyran, P Dinarina, A Lipkowitz, S Dikic, I AF Szymkiewicz, I Kowanetz, K Soubeyran, P Dinarina, A Lipkowitz, S Dikic, I TI CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-RECEPTOR; PROTEIN C-CBL; ADAPTER PROTEIN; NEGATIVE REGULATION; EGF RECEPTOR; PLASMA-MEMBRANE; CELL-ADHESION; SH3 DOMAINS; A431 CELLS; UBIQUITINATION AB The Cbl family of ubiquitin ligases in mammals contains three members, Cbl, Cbl-b, and Chl-3, that are involved in down-regulation of receptor tyrosine kinases (RTKs) by mediating receptor ubiquitination and degradation. More recently, a novel pathway has been identified whereby Cbl promotes internalization of EGF receptor via a CIN85/endophilin pathway that is functionally separable from the ubiquitin ligase activity of Cbl (1). Here we show that Cbl-b, but not Chl-3, utilize the same mechanism to down-regulate multiple RTKs. CIN85 was shown to bind to the minimal binding domain identified in the carboxyl terminus of Cbl-b. Ligand-induced phosphorylation of Cbl-b further increased their interactions and led to a rapid and sustained recruitment of CIN85 in the complex with EGF or PDGF receptors. Inhibition of binding between CIN85 and Cbl-b was sufficient to impair Cbl-b-mediated internalization of EGF receptors, while being dispensable for Cbl-b-directed polyubiquitination of EGF receptors. Moreover, CIN85 and Cbl/Cbl-b were constitutively associated with activated PDGF, EGF, or c-Kit receptors in several tumor cell lines. Our data reveal a common pathway utilized by Cbl and Cbl-b that may have an important and redundant function in negative regulation of ligand-activated as well as oncogenically activated RTKs in vivo. C1 Ludwig Inst Canc Res, S-75124 Uppsala, Sweden. NCI, Canc Genet Branch, Ctr Canc Res, Gaithersburg, MD 20899 USA. RP Dikic, I (reprint author), Ludwig Inst Canc Res, Box 595,Husargatan 3, S-75124 Uppsala, Sweden. RI Dikic, Ivan/O-4650-2015 OI Dikic, Ivan/0000-0001-8156-9511 NR 46 TC 89 Z9 96 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 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 18 PY 2002 VL 277 IS 42 BP 39666 EP 39672 DI 10.1074/jbc.M205535200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605EA UT WOS:000178662500079 PM 12177062 ER PT J AU Zhou, MI Wang, HM Ross, JJ Kuzmin, I Xu, CG Cohen, HT AF Zhou, MI Wang, HM Ross, JJ Kuzmin, I Xu, CG Cohen, HT TI The von Hippel-Lindau tumor suppressor stabilizes novel plant homeodomain protein Jade-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RENAL-CELL CARCINOMA; FACTOR MESSENGER-RNA; GENE-PRODUCT; KINASE-C; GROWTH; VHL; MUTATIONS; DISEASE; BINDING; FINGER AB The von Hippel-Lindau disease gene (VHL) is the causative gene for most adult renal cancers. However, the mechanism by which VHL protein functions as a renal tumor suppressor remains largely unknown. To identify low occupancy VHL protein partners with potential relevance to renal cancer, we screened a human kidney library against human VHL p30 using a yeast two-hybrid approach. Jade-1 (gene for Apoptosis and Differentiation in Epithelia) encodes a previously uncharacterized 64-kDa protein that interacts strongly with VHL protein and is most highly expressed in kidney. Jade-1 protein is short-lived and contains a candidate destabilizing (PEST) motif and plant homeodomains that are not required for the VHL interaction. Jade-1 is abundant in proximal tubule cells, which are clear-cell renal cancer precursors, and expression increases with differentiation. Jade-1 is expressed in cytoplasm and the nucleus diffusely and in speckles, where it partly colocalizes with VHL. VHL reintroduction into renal cancer cells increases endogenous Jade-1 protein abundance up to 10-fold. Furthermore, VHL increases Jade-1 protein half-life up to 3-fold. Thus, direct protein stabilization is identified as a new VHL function. Moreover, Jade-1 protein represents a novel candidate regulatory factor in VHL-mediated renal tumor suppression. C1 Boston Univ, Med Ctr, Evans Biomed Res Ctr, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Nephrol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Hematol Oncol Sect, Boston, MA 02118 USA. NCI, Frederick Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Cohen, HT (reprint author), Boston Univ, Med Ctr, Evans Biomed Res Ctr, X-535,650 Albany St, Boston, MA 02118 USA. OI Cohen, Herbert/0000-0003-1900-8718 FU NCI NIH HHS [F32-CA79133, R01 CA079830, R01-CA79830]; NIDDK NIH HHS [T32-DK07053] NR 68 TC 58 Z9 61 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 18 PY 2002 VL 277 IS 42 BP 39887 EP 39898 DI 10.1074/jbc.M205040200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605EA UT WOS:000178662500106 PM 12169691 ER PT J AU Chu, R Takei, J Knowlton, JR Andrykovitch, M Pei, WH Kajava, AV Steinbach, PJ Ji, XH Bai, YW AF Chu, R Takei, J Knowlton, JR Andrykovitch, M Pei, WH Kajava, AV Steinbach, PJ Ji, XH Bai, YW TI Redesign of a four-helix bundle protein by phage display coupled with proteolysis and structural characterization by NMR and X-ray crystallography SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE phage-display; four-helix bundle protein; proteolysis; NMR structure; X-ray structure ID DE-NOVO DESIGN; APOCYTOCHROME B(562); MOLECULAR GRAPHICS; HYDROGEN-EXCHANGE; STABLE PROTEINS; HEME-BINDING; COILED-COIL; STABILITY; SELECTION; DYNAMICS AB To test whether it is practical to use phage display coupled with proteolysis for protein design, we used this approach to convert a partially unfolded four-helix bundle protein, apocytochrome b(562), to a stably folded four-helix bundle protein. Four residues expected to form a hydrophobic core were mutated. One residue was changed to Trp to provide a fluorescence probe for studying the protein's physical properties and to partially fill the void left by the heme. The other three positions were randomly mutated. In addition, another residue in the region to be redesigned was substituted with Arg to provide a specific cutting site for protease Arg-c. This library of mutants was displayed on the surface of phage and challenged with protease Arg-c to select stably folded proteins. The consensus sequence that emerged from the selection included hydrophobic residues at only one of the three positions and non-hydrophobic residues at the other two. Nevertheless, the selected proteins were thermodynamically very stable. The structure of a selected protein was characterized using multi-dimensional NMR. All four helices were formed in the structure. Further, site-directed mutagenesis was used to change one of the two non-hydrophobic residues to a hydrophobic residue, which increased the stability of the protein, indicating that the selection result was not based solely on the protein's global stability and that local structural characteristics may also govern the selection. This conclusion is supported by the crystal structure of another mutant that has two hydrophobic residues substituted for the two non-hydrophobic residues. These results suggest that the hydrophobic interactions in the core are not sufficient to dictate the selection and that the location of the cutting site of the protease also influences the selection of structures. (C) 2002 Published by Elsevier Science Ltd. C1 NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Ctr Mol Modeling, Bethesda, MD 20892 USA. RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, NIH, Bldg 539,Room 124, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012; Kajava, Andrey/E-1107-2014 OI Ji, Xinhua/0000-0001-6942-1514; Kajava, Andrey/0000-0002-2342-6886 NR 48 TC 29 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE 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 18 PY 2002 VL 323 IS 2 BP 253 EP 262 DI 10.1016/S0022-2836(02)00884-7 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 610TH UT WOS:000178976500008 PM 12381319 ER PT J AU Fields, RD Stevens-Graham, B AF Fields, RD Stevens-Graham, B TI Neuroscience - New insights into neuron-glia communication SO SCIENCE LA English DT Review ID OLIGODENDROCYTE PRECURSOR CELLS; MYELIN-ASSOCIATED GLYCOPROTEIN; CALCIUM WAVES; NEUROMUSCULAR-JUNCTION; TRANSMITTER RELEASE; ADHESION MOLECULE; SYNAPTIC EFFICACY; PROGENITOR CELLS; SODIUM-CHANNELS; SCHWANN-CELLS AB Two-way communication between neurons and nonneural cells called glia is essential for axonal conduction, synaptic transmission, and information processing and thus is required for normal functioning of the nervous system during development and throughout adult life. The signals between neurons and glia include ion fluxes, neurotransmitters, cell adhesion molecules, and specialized signaling molecules released from synaptic and nonsynaptic regions of the neuron. In contrast to the serial flow of information along chains of neurons, glia communicate with other glial cells through intracellular waves of calcium and via intercellular diffusion of chemical messengers. By releasing neurotransmitters and other extracellular signaling molecules, glia can affect neuronal excitability and synaptic transmission and perhaps coordinate activity across networks of neurons. C1 NICHHD, Neurocytol & Physiol Sect, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHHD, Neurocytol & Physiol Sect, Bethesda, MD 20892 USA. EM elds@helix.nih.gov FU NICHD NIH HHS [Z01 HD000713-11] NR 95 TC 533 Z9 567 U1 7 U2 53 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 18 PY 2002 VL 298 IS 5593 BP 556 EP 562 DI 10.1126/science.298.5593.556 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RL UT WOS:000178634800030 PM 12386325 ER PT J AU Cope, GA Suh, GSB Aravind, L Schwarz, SE Zipursky, SL Koonin, EV Deshaies, RJ AF Cope, GA Suh, GSB Aravind, L Schwarz, SE Zipursky, SL Koonin, EV Deshaies, RJ TI Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1 SO SCIENCE LA English DT Article ID MODULATE AP-1 ACTIVITY; SCF UBIQUITIN-LIGASE; COP9 SIGNALOSOME; FISSION YEAST; COMPLEX; JAB1; ZINC; TRANSCRIPTION; PURIFICATION; P27(KIP1) AB COP9 signalosome (CSN) cleaves the ubiquitin-like protein Nedd8 from the Cul1 subunit of SCF ubiquitin ligases. The Jab1/MPN domain metalloenzyme (JAMM) motif in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity. JAMM is found in proteins from archaea, bacteria, and eukaryotes, including the Rpn11 subunit of the 26 S proteasome. Metal chelators and point mutations within JAMM abolished CSN-dependent cleavage of Nedd8 from Cul1, yet had little effect on CSN complex assembly. Optimal SCF activity in yeast and both viability and proper photoreceptor cell ( R cell) development in Drosophila melanogaster required an intact Csn5 JAMM domain. We propose that JAMM isopeptidases play important roles in a variety of physiological pathways. C1 CALTECH, Dept Biol, Pasadena, CA 91125 USA. Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Deshaies, RJ (reprint author), CALTECH, Dept Biol, Pasadena, CA 91125 USA. RI Deshaies, Raymond/B-8354-2014 OI Deshaies, Raymond/0000-0002-3671-9354 NR 33 TC 429 Z9 443 U1 1 U2 11 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 18 PY 2002 VL 298 IS 5593 BP 608 EP 611 DI 10.1126/science.1075901 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RL UT WOS:000178634800043 PM 12183637 ER PT J AU Verma, R Aravind, L Oania, R McDonald, WH Yates, JR Koonin, EV Deshaies, RJ AF Verma, R Aravind, L Oania, R McDonald, WH Yates, JR Koonin, EV Deshaies, RJ TI Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome SO SCIENCE LA English DT Article ID S-PHASE; UBIQUITIN; YEAST; GENE; SIGNAL; TRANSCRIPTION; PROTEOLYSIS; RECOGNITION; ACTIVATION; PARTICLE AB The 26 S proteasome mediates degradation of ubiquitin-conjugated proteins. Although ubiquitin is recycled from proteasome substrates, the molecular basis of deubiquitination at the proteasome and its relation to substrate degradation remain unknown. The Rpn11 subunit of the proteasome lid subcomplex contains a highly conserved Jab1/MPN domain associated metalloisopeptidase (JAMM) motif EXnHXHX10D. Mutation of the predicted active-site histidines to alanine (rpn11AXA) was lethal and stabilized ubiquitin pathway substrates in yeast. Rpn11(AXA) mutant proteasomes assembled normally but failed to either deubiquitinate or degrade ubiquitinated Sic1 in vitro. Our findings reveal an unexpected coupling between substrate deubiquitination and degradation and suggest a unifying rationale for the presence of the lid in eukaryotic proteasomes. C1 CALTECH, Dept Biol, Pasadena, CA 91125 USA. CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Scripps Res Inst, Dept Cell Biol, San Diego, CA 92037 USA. RP Deshaies, RJ (reprint author), CALTECH, Dept Biol, Pasadena, CA 91125 USA. RI Deshaies, Raymond/B-8354-2014; McDonald, W. Hayes/B-4109-2016 OI Deshaies, Raymond/0000-0002-3671-9354; McDonald, W. Hayes/0000-0002-3510-426X FU NCRR NIH HHS [RR11823-05-01] NR 31 TC 569 Z9 585 U1 6 U2 25 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 18 PY 2002 VL 298 IS 5593 BP 611 EP 615 DI 10.1126/science.1075898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RL UT WOS:000178634800044 PM 12183636 ER PT J AU Eells, JB Lipska, BK Yeung, SK Misler, JA Nikodem, VM AF Eells, JB Lipska, BK Yeung, SK Misler, JA Nikodem, VM TI Nurr1-null heterozygous mice have reduced mesolimbic and mesocortical dopamine levels and increased stress-induced locomotor activity SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Nurr1; schizophrenia; dopamine; stress; amphetamine ID RECEPTOR-DEFICIENT MICE; NGFI-B; TYROSINE-HYDROXYLASE; TARGETED DISRUPTION; PARKINSONS-DISEASE; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; TRANSPORTER GENE; 2 PARTS; NEURONS AB Nurr1, an orphan nuclear receptor, is essential for the differentiation of the midbrain dopamine (DA) neurons; however, its function in adult midbrain DA neurons has not been determined. The present study compared regional brain levels of catecholamines and spontaneous and pharmacologically induced locomotor behaviors between mice heterozygous for the Nurr1-null allele (+/-) and wild type (+/+) littermates. The Nurr1 +/- mice had significantly lower levels of DA in whole brain, midbrain, prefrontal cortex and nucleus accumbens, although no significant differences were observed in the striatum, olfactory bulb or hippocampus. Nurr1 +/- mice displayed significantly greater locomotor activity in a novel open field and after saline injection with no significant difference in activity after treatment with amphetamine (2.5 or 5.0 mg/kg) or MK 801 (0.2 or 0.4 mg/ kg). A similar elevation in locomotor activity was observed in Nurr1 +/- mice at 35 days old as was found in 70 days old adults. These data demonstrate that the loss of a single Nurr1 allele results in reduced DA levels in mesolimbic and mesocortical pathways and increased locomotor activity in response to mild stress. The involvement of Nurr1 in DA neurotransmission and the implications for schizophrenia are discussed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Nikodem, VM (reprint author), NIDDKD, NIH, 10 Ctr Dr,MSC 1766, Bethesda, MD 20892 USA. RI Lipska, Barbara/E-4569-2017; OI Eells, Jeffrey/0000-0002-6381-1666 NR 40 TC 61 Z9 62 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD OCT 17 PY 2002 VL 136 IS 1 BP 267 EP 275 AR PII S0166-4328(02)00185-7 DI 10.1016/S0166-4328(02)00185-7 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 607DM UT WOS:000178776300029 PM 12385813 ER PT J AU Capelluto, DGS Kutateladze, TG Habas, R Finkielstein, CV He, X Overduin, M AF Capelluto, DGS Kutateladze, TG Habas, R Finkielstein, CV He, X Overduin, M TI The DIX domain targets dishevelled to actin stress fibres and vesicular membranes SO NATURE LA English DT Article ID PLANAR CELL POLARITY; INTRACELLULAR-LOCALIZATION; PROTEIN INTERACTIONS; CORTICAL ROTATION; WNT PATHWAY; XENOPUS; AXIN; PHOSPHORYLATION; EMBRYOGENESIS; GASTRULATION AB Colorectal cancer results from mutations in components of the Wnt pathway that regulate beta-catenin levels(1). Dishevelled (Dvl or Dsh) signals downstream of Wnt receptors and stabilizes beta-catenin during cell proliferation(1) and embryonic axis formation(2). Moreover, Dvl contributes to cytoskeletal reorganization during gastrulation(3-5) and mitotic spindle orientation during asymmetric cell division(6). Dvl belongs to a family of eukaryotic signalling proteins that contain a conserved 85-residue module of unknown structure and biological function called the DIX domain(7). Here we show that the DIX domain mediates targeting to actin stress fibres and cytoplasmic vesicles in vivo. Neighbouring interaction sites for actin and phospholipid are identified between two helices by nuclear magnetic resonance spectroscopy (NMR). Mutation of the actin-binding motif abolishes the cytoskeletal localization of Dvl, but enhances Wnt/beta-catenin signalling and axis induction in Xenopus. By contrast, mutation of the phospholipid interaction site disrupts vesicular association of Dvl, Dvl phosphorylation, and Wnt/beta-catenin pathway activation. We propose that partitioning of Dvl into cytoskeletal and vesicular pools by the DIX domain represents a point of divergence in Wnt signalling. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol,Div Neurosci, Boston, MA 02115 USA. NICHHD, Genet Mol Lab, Bethesda, MD 20892 USA. RP Overduin, M (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, 4200 E 9th Ave, Denver, CO 80262 USA. OI Overduin, Michael/0000-0002-3114-6585; finkielstein, carla/0000-0002-8417-4643 NR 30 TC 139 Z9 140 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 17 PY 2002 VL 419 IS 6908 BP 726 EP 729 DI 10.1038/nature01056 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604JF UT WOS:000178615200042 PM 12384700 ER PT J AU Schuler, B Lipman, EA Eaton, WA AF Schuler, B Lipman, EA Eaton, WA TI Probing the free-energy surface for protein folding with single-molecule fluorescence spectroscopy SO NATURE LA English DT Article ID TRANSFER CONFOCAL MICROSCOPY; COLD-SHOCK PROTEIN; DIFFUSING MOLECULES; THERMOTOGA-MARITIMA; BETA-SHEET; DYNAMICS; PEPTIDES; MODEL; DENATURATION; DEPENDENCE AB Protein folding is inherently a heterogeneous process because of the very large number of microscopic pathways that connect the myriad unfolded conformations to the unique conformation of the native structure. In a first step towards the long-range goal of describing the distribution of pathways experimentally, Forster resonance energy transfer(1) (FRET) has been measured on single, freely diffusing molecules(2-4). Here we use this method to determine properties of the free-energy surface for folding that have not been obtained from ensemble experiments. We show that single-molecule FRET measurements of a small cold-shock protein expose equilibrium collapse of the unfolded polypeptide and allow us to calculate limits on the polypeptide reconfiguration time. From these results, limits on the height of the free-energy barrier to folding are obtained that are consistent with a simple statistical mechanical model, but not with the barriers derived from simulations using molecular dynamics. Unlike the activation energy, the free-energy barrier includes the activation entropy and thus has been elusive to experimental determination for any kinetic process in solution. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Lipman, Everett/D-1696-2009; Schuler, Benjamin/E-7342-2011 OI Schuler, Benjamin/0000-0002-5970-4251 NR 31 TC 607 Z9 618 U1 20 U2 179 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 17 PY 2002 VL 419 IS 6908 BP 743 EP 747 DI 10.1038/nature01060 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604JF UT WOS:000178615200046 PM 12384704 ER PT J AU Fisher, B Anderson, S Bryant, J Margolese, RG Deutsch, M Fisher, ER Jeong, J Wolmark, N AF Fisher, B Anderson, S Bryant, J Margolese, RG Deutsch, M Fisher, ER Jeong, J Wolmark, N TI Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AXILLARY DISSECTION; RADICAL-MASTECTOMY; RADIATION; MANAGEMENT; THERAPY AB Background: In 1976, we initiated a randomized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer. Methods: A total of 1851 women for whom follow-up data were available and nodal status was known underwent randomly assigned treatment consisting of total mastectomy, lumpectomy alone, or lumpectomy and breast irradiation. Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained. Results: The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation, as compared with 39.2 percent in the women who underwent lumpectomy without irradiation (P<0.001). No significant differences were observed among the three groups of women with respect to disease-free survival, distant-disease-free survival, or overall survival. The hazard ratio for death among the women who underwent lumpectomy alone, as compared with those who underwent total mastectomy, was 1.05 (95 percent confidence interval, 0.90 to 1.23; P=0.51). The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation, as compared with those who underwent total mastectomy, was 0.97 (95 percent confidence interval, 0.83 to 1.14; P=0.74). Among the lumpectomy-treated women whose surgical specimens had tumor-free margins, the hazard ratio for death among the women who underwent postoperative breast irradiation, as compared with those who did not, was 0.91 (95 percent confidence interval, 0.77 to 1.06; P=0.23). Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer. This decrease was partially offset by an increase in deaths from other causes. Conclusions: Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained. C1 NSABP, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Fisher, B (reprint author), NSABP, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. OI Anderson, Stewart/0000-0001-8948-0650; Jeong, Jong/0000-0003-0596-2201 FU NCI NIH HHS [U10-CA-69651, U10-CA-69974, U10-CA-37377] NR 27 TC 2494 Z9 2661 U1 17 U2 100 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 17 PY 2002 VL 347 IS 16 BP 1233 EP 1241 DI 10.1056/NEJMoa022152 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 604CP UT WOS:000178598300004 PM 12393820 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Institutional review board reform SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 1 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 17 PY 2002 VL 347 IS 16 BP 1285 EP 1286 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 604CP UT WOS:000178598300027 PM 12393832 ER PT J AU Rockwood, LD Torrey, TA Kim, JS Coleman, AE Kovalchuk, AL Xiang, S Ried, T Morse, HC Janz, S AF Rockwood, LD Torrey, TA Kim, JS Coleman, AE Kovalchuk, AL Xiang, S Ried, T Morse, HC Janz, S TI Genomic instability in mouse Burkitt lymphoma is dominated by illegitimate genetic recombinations, not point mutations SO ONCOGENE LA English DT Article DE in vivo mutant rates; MYC; mutator phenotype; B-cell neoplasia; genomic instability ID DOUBLE TRANSGENIC MICE; IN-VIVO MUTATIONS; DNA; SELECTION; TARGET; MODEL AB lambda-MYC-induced mouse Burkitt lymphoma (BL) harboring the shuttle vector pUR288, which includes a lacZ reporter gene to study mutagenesis, was employed to assess genomic instability associated with MYC deregulation. The frequency of lacZ mutations in lymphomas was elevated only 1.75-fold above that in normal tissue, indicating that mouse BL does not exhibit a phenotype of hypermutability. However, the nature of lacZ mutations was strikingly different in normal tissues and lymphomas. While point mutations comprised approximately 75% of the mutations found in normal tissues, apparent translocations, deletions and inversions constituted the majority of mutations (similar to65%) in lymphomas. Genomic instability in mouse BL thus seems characterized by a preponderance of illegitimate genetic rearrangements in the context of near-background mutant frequencies. SKY analyses of cell lines from primary BL tumors revealed substantial changes in chromosomal structure, confirming the lacZ studies. Bi-allelic deletions of the tumor suppressor p16(Ink4a) were detected in six out of 16 cell lines, illustrating cellular selection of advantageous mutations. Together, these approaches indicate that MYC may contribute to lymphomagenesis through the dominant mutator effect of inducing chromosomal instability. The results further suggest that a phenotype of hypermutability (elevated mutant frequency) may not always be required for oncogenesis to occur. C1 NCI, Genet Lab, CCR, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. NCI, Genet Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, Genet Lab, CCR, Bldg 37,Room 2B10, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 19 TC 20 Z9 20 U1 0 U2 0 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 17 PY 2002 VL 21 IS 47 BP 7235 EP 7240 DI 10.1038/sj.onc.1205697 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 602KN UT WOS:000178504600012 PM 12370814 ER PT J AU Malek, RL Irby, RB Guo, QBM Lee, K Wong, S He, M Tsai, J Frank, B Liu, ET Quackenbush, J Jove, R Yeatman, TJ Lee, NH AF Malek, RL Irby, RB Guo, QBM Lee, K Wong, S He, M Tsai, J Frank, B Liu, ET Quackenbush, J Jove, R Yeatman, TJ Lee, NH TI Identification of Src transformation fingerprint in human colon cancer SO ONCOGENE LA English DT Article DE Src; colon cancer; expression profiling; microarray ID PROTEIN-KINASE ACTIVITY; ROUS-SARCOMA VIRUS; NIH 3T3 CELLS; C-SRC; GENE-EXPRESSION; V-SRC; BINDING PROTEIN; MESSENGER-RNA; DNA-SEQUENCE; DRS GENE AB We used a classical rodent model of transformation to understand the transcriptional processes, and hence the molecular and cellular events a given cell undergoes when progressing from a normal to a transformed phenotype. Src activation is evident in 80% of human colon cancer, yet the myriad of cellular processes effected at the level of gene expression has yet to be fully documented. We identified a Src 'transformation fingerprint' within the gene expression profiles of Src-transformed rat 3Y1 fibroblasts demonstrating a progression in transformation characteristics. To evaluate the role of this gene set in human cancer development and progression, we extracted the orthologous genes present on the Affymetrix Hu95A GeneChip(TM) (12k named genes) and compared expression profiles between the Src-induced rodent cell line model of transformation and staged colon tumors where Src is known to be activated. A similar gene expression pattern between the cell line model and staged colon tumors for components of the cell cycle, cytoskeletal associated proteins, transcription factors and lysosomal proteins suggests the need for co-regulation of several cellular processes in the progression of cancer. Genes not previously implicated in tumorigenesis were detected, as well as a set of 14 novel, highly conserved genes with here-to-fore unknown function. These studies define a set of transformation associated genes whose up-regulation has implications for understanding Src mediated transformation and strengthens the role of Src in the development and progression of human colon cancer. Supportive Supplemental Data can be viewed at http:// pga.tigr.org/PGApubs.shtml. C1 Univ S Florida, Coll Med, Dept Surg, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Oncol, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Biochem & Mol Biol, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. Johns Hopkins Canc Ctr, Div Canc Biol, Baltimore, MD 21231 USA. Inst Genom Res, Dept Funct Genom, Rockville, MD 20850 USA. NCI, Div Clin Sci, Med Branch,Mol Signaling & Oncogenesis Sect, Dept Canc & Cell Biol, Bethesda, MD 20892 USA. RP Yeatman, TJ (reprint author), Univ S Florida, Coll Med, Dept Surg, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA77049-02, CA85052-A1, CA85429-01]; NHLBI NIH HHS [HL59781]; PHS HHS [6120-119-L0-A] NR 54 TC 60 Z9 61 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 17 PY 2002 VL 21 IS 47 BP 7256 EP 7265 DI 10.1038/sj.onc.1205900 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 602KN UT WOS:000178504600015 PM 12370817 ER PT J AU George, L Mills, JL Johansson, ALV Nordmark, A Olander, B Granath, F Cnattingius, S AF George, L Mills, JL Johansson, ALV Nordmark, A Olander, B Granath, F Cnattingius, S TI Plasma foliate levels and risk of spontaneous abortion SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NEURAL-TUBE DEFECTS; EARLY-PREGNANCY LOSS; ACID SUPPLEMENTATION; BIRTH-DEFECTS; FOLATE LEVELS; MISCARRIAGE; PREVENTION; FORTIFICATION; HOMOCYSTEINE; TERATHANASIA AB Context Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies. Objective To study the association between plasma folate levels and the risk of spontaneous abortion. Design, Setting, and Population Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks. Main Outcome Measure Risk of spontaneous abortion vs maternal plasma folate level. Results Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (less than or equal to2.19 ng/mL [less than or equal to 4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and greater than or equal to6.17 ng/mL [greater than or equal to14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% Cl, 0.59-1.20; and OR, 0.74; 95% Cl, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% Cl, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% Cl, 0.55-2.24) or unknown (OR, 1.45; 95% Cl, 0.90-2.33). Conclusion Low plasma folate levels were associated with an increased risk of early spontaneous abortion. C1 Karolinska Inst, Huddinge Univ Hosp, Dept Med Epidemiol, Stockholm, Sweden. Karolinska Inst, Huddinge Univ Hosp, Dept Med Lab Sci & Technol, Stockholm, Sweden. NICHHD, Pediat Epidemiol Sect, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Danderyd Hosp, Karolinska Lab, Dept Clin Chem, Stockholm, Sweden. RP Cnattingius, S (reprint author), Karolinska Inst, Dept Med Epidemiol, POB 281, SE-17177 Stockholm, Sweden. NR 38 TC 117 Z9 124 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 16 PY 2002 VL 288 IS 15 BP 1867 EP 1873 DI 10.1001/jama.288.15.1867 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 604EU UT WOS:000178604200025 PM 12377085 ER PT J AU Whelton, PK He, J Appel, LJ Cutler, JA Havas, S Kotchen, TA Roccella, EJ Stout, R Vallbona, C Winston, MC Karimbakas, J AF Whelton, PK He, J Appel, LJ Cutler, JA Havas, S Kotchen, TA Roccella, EJ Stout, R Vallbona, C Winston, MC Karimbakas, J CA Natl High Blood Pressure Educ Prog TI Primary prevention of hypertension - Clinical and public health advisory from the National High Blood Pressure Education Program SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; REDUCED DIETARY-SODIUM; N-3 FATTY-ACIDS; CARDIOVASCULAR-DISEASE; WEIGHT-LOSS; METAANALYSIS; RISK; REDUCTION; MEN; MORTALITY AB The National High Blood Pressure Education Program Coordinating Committee published its first statement on the primary prevention of hypertension in 1993. This article updates the 1993 report, using new and further evidence from the scientific literature. Current recommendations for primary prevention of hypertension involve a population-based approach and an intensive targeted strategy focused on individuals at high risk for hypertension. These 2 strategies are complementary and emphasize 6 approaches with proven efficacy for prevention of hypertension: engage in moderate physical activity; maintain normal body weight; limit alcohol consumption; reduce sodium intake; maintain adequate intake of potassium; and consume a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat. Applying these approaches to the general population as a component of public health and clinical practice can help prevent blood pressure from increasing and can help decrease elevated blood pressure levels for those with high normal blood pressure or hypertension. C1 NHLBI, Natl High Blood Pressure Educ Program, Off Prevent Educ & Control, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Epidemiol & Med, New Orleans, LA 70118 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. Johns Hopkins Med Inst, Dept Internal Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Int Hlth, Baltimore, MD 21205 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Med Coll Wisconsin, Dept Med, Div Endocrinol Metab & Clin Nutr, Milwaukee, WI 53226 USA. Procter & Gamble Co, Hlth Care Res Ctr, Mason, OH USA. Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. Amer Heart Assoc, Dallas, TX USA. Amer Inst Res Hlth Program, Silver Spring, MD USA. RP Roccella, EJ (reprint author), NHLBI, Natl High Blood Pressure Educ Program, Off Prevent Educ & Control, NIH, 31 Ctr Dr,MSC 2480, Bethesda, MD 20892 USA. NR 45 TC 651 Z9 685 U1 10 U2 47 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 16 PY 2002 VL 288 IS 15 BP 1882 EP 1888 DI 10.1001/jama.288.15.1882 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 604EU UT WOS:000178604200027 PM 12377087 ER PT J AU Preston, DL Ron, E Yonehara, S Kobuke, T Fujii, H Kishikawa, M Tokunaga, M Tokuoka, S Mabuchi, K AF Preston, DL Ron, E Yonehara, S Kobuke, T Fujii, H Kishikawa, M Tokunaga, M Tokuoka, S Mabuchi, K TI Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; INTERNATIONAL CASE-CONTROL; BRAIN-TUMORS; INTRACRANIAL MENINGIOMAS; IONIZING-RADIATION; SURVIVORS; CHILDHOOD; CANCER; RADIOTHERAPY; MORTALITY AB Background: The risk of developing nervous system tumors following exposure to ionizing radiation is not well quantified. We characterized the incidence of nervous system tumors among atomic bomb survivors as a function of radiation dose. Methods: Tumors of the nervous system and pituitary gland diagnosed between 1958 and 1995 among 80160 atomic bomb survivors were ascertained using the Hiroshima and Nagasaki tumor registries, medical records, and death certificates. Pathologists reviewed slides and medical records to provide histologic diagnoses. Poisson regression analyses were used to characterize radiation effects on tumor incidence, which are expressed as excess relative risk per sievert (ERRSv). All statistical tests were two-sided. Results: A statistically significant dose-related excess of nervous system tumors was observed in the cohort (ERRSv = 1.2, 95% confidence interval [CI] = 0.6 to 2.1). The highest ERRSv was seen for schwannoma (4.5, 95% CI = 1.9 to 9.2). The risk for all other nervous system tumors as a group is also statistically significantly elevated (ERRSv = 0.6, 95% CI = 0.1 to 1.3). Risk increases, although not statistically significant, were seen for meningiomas (ERRSv = 0.6, 95% CI = -0.01 to 1.8), gliomas (ERRSv = 0.6, 95 % CI = -0.2 to 2.0), other nervous system tumors (ERRSv = 0.5, 95% CI = <--0.2 to 2.2), and pituitary tumors (ERRSv = 1.0, 95% CI = <--0.2 to 3.5). The dose-response relationships were linear. For nervous system tumors other than schwannoma, excess risks were higher for men than for women and for those exposed during childhood than for those exposed during adulthood. Conclusions: A statistically significant dose response was observed for all nervous system tumors combined and for schwannoma considered separately, indicating that exposure to even moderate doses (i.e., < 1 Sv) of radiation is associated with an elevated incidence of nervous system tumors. C1 Radiat Effects Res Fdn, Dept Stat, Minami Ku, Hiroshima 7320815, Japan. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Hiroshima Univ, Sch Med, Dept Pathol 2, Hiroshima, Japan. Koseiren Onomichi Hosp, Div Clin Res Labs, Onomichi, Japan. Nagasaki Chuo Natl Hosp, Div Clin Res Labs, Nagasaki, Japan. Nagasaki Univ, Sch Med, Sci Data Ctr Atom Bomb Disaster, Nagasaki 852, Japan. Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima 7320815, Japan. RP Preston, DL (reprint author), Radiat Effects Res Fdn, Dept Stat, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. EM preston@rerf.or.jp FU NCI NIH HHS [N01-CP-21028] NR 47 TC 146 Z9 149 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT 16 PY 2002 VL 94 IS 20 BP 1555 EP 1563 PG 9 WC Oncology SC Oncology GA 603MF UT WOS:000178562900010 PM 12381708 ER PT J AU Okin, PM Devereux, RB Fabsitz, RR Lee, ET Galloway, JM Howard, BV AF Okin, PM Devereux, RB Fabsitz, RR Lee, ET Galloway, JM Howard, BV TI Quantitative assessment of electrocardiographic strain predicts increased left ventricular mass: The strong heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HYPERTENSIVE PATIENTS; AMERICAN-INDIANS; CARDIOVASCULAR MORTALITY; ALL-CAUSE; HYPERTROPHY; LIFE; IMPACT; PRODUCTS; GEOMETRY; DISEASE AB OBJECTIVES This study was designed to examine the relation of computer-measured ST depression (STdep) in the lateral precordial leads to the presence of left ventricular hypertrophy (LVH). BACKGROUND Qualitative abnormalities of repolarization in the lateral precordial. leads of the electrocardiogram, as manifested by the strain pattern of T-wave inversion and STdep, are markers for LVH and adverse prognosis. However, the independent relationship of increased left ventricular (LV) mass to quantitative measures of STdep in these leads remains unclear. METHODS Electrocardiograms and echocardiograms were examined in the second Strong Heart Study examination in 1,595 American Indian participants without evident coronary disease. The absolute magnitude of ST segment deviation above or below isoelectric baseline was measured by computer in leads V-5 and V-6 and participants were grouped according to gender-specific quartiles of maximal STdep. Left ventricular hypertrophy was defined by indexed LV mass >49.2 g/m(2.7) in men and >46.7 g/m(2.7) in women. RESULTS Increasing STdep was associated with older age, greater pulse pressure, serum fibrinogen levels and urinary albumin/creatinine ratios, and with stepwise increases in LV mass (145 +/- 28 vs. 150 +/- 33 vs. 156 +/- 36 vs. 164 +/- 43 p < 0.001), indexed LV mass (38.2 +/- 7.7 vs. 39.3 +/- 8.7 vs. 40.5 +/- 9.4 vs. 44.0 +/- 11.0 g/m(2.7) p < 0.001), and prevalence of LVH (11.6 vs. 19.1 vs. 21.5 vs. 31.2%, p < 0.001). After controlling for clinical differences, increasing STdep remained strongly associated with increased prevalence of LVH (p = 0.0001). CONCLUSIONS In the absence of evidence of coronary disease, increasing STdep in the lateral precordial leads is associated with increasing LV mass and increased prevalence of anatomic LVH. (J Am Coll Cardiol 2002;40:1395-400). (C) 2002 by the American College of Cardiology Foundation. C1 Cornell Med Ctr, Div Cardiol, Dept Med, New York, NY 10021 USA. NHLBI, Bethesda, MD 20892 USA. Univ Oklahoma, Ctr Hlth Sci, Coll Publ Hlth, Oklahoma City, OK USA. Univ Arizona, Tucson, AZ USA. Medstar Res Inst, Washington, DC USA. RP Okin, PM (reprint author), Cornell Med Ctr, Div Cardiol, Dept Med, 525 E 68th St, New York, NY 10021 USA. FU NCRR NIH HHS [M10RR0047-34]; NHLBI NIH HHS [HL-41642, HL-41654, HL-65521, HL-41652] NR 31 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 16 PY 2002 VL 40 IS 8 BP 1395 EP 1400 AR PII S0735-1097(02)02171-X DI 10.1016/S0735-1097(02)02171-X PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 604DF UT WOS:000178600000004 PM 12392827 ER PT J AU Haider, AW Wilson, PWF Larson, MG Evans, JC Michelson, EL Wolf, PA O'Donnell, CJ Levy, D AF Haider, AW Wilson, PWF Larson, MG Evans, JC Michelson, EL Wolf, PA O'Donnell, CJ Levy, D TI The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease - A prospective study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; FUTURE MYOCARDIAL-INFARCTION; CHRONIC INFECTION; ARTERY DISEASE; ATHEROSCLEROSIS; POPULATION; MORTALITY; TWAR; IGG; ANTIBODIES AB OBJECTIVES We sought to determine whether seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus (CMV) is an independent predictor of incident cardiovascular disease. BACKGROUND Recent reports have suggested that infections may contribute to risk of cardiovascular disease. However, prospective studies of these associations in a free-living population are lacking. METHODS We measured serum H. pylori IgG, C pneumoniae IgG and IgA, and CMV IgG levels in Framingham Heart Study cohort participants. Blood samples were drawn during the 16th biennial examination cycle (1979 to 1982) from 1,187 participants free of cardiovascular disease (mean age 69 years) and stored at -20degreesC. A pooled primary end point of myocardial infarction, atherothrombotic stroke, and coronary heart disease deaths was studied in relation to serology. Using a Cox model, hazard ratios (HR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender, and established risk factors. RESULTS Seropositivity to H. pylori IgG, C pneumoniae IgG, C pneumoniae IgA, and CMV IgG was 60%, 45%, 11%, and 69%, respectively. During 10 years of follow-up, incident cardiovascular disease occurred in 199 participants (16.8%). In age- and gender-adjusted models, H. pylori IgG (HR 1.09, 95% CI 0.81 to 1.46), C. pneumoniae IgG (HR 0.91, 95% CI 0.68 to 1.20), C pneumoniae IgA (HR 0.65, 95% CI 0.39 to 1.07), and CMV IgG (HR 0.84, 95% CI 0.62 to 1.12) were not associated with incident cardiovascular disease. These associations were further attenuated after adjustment for risk factors including body mass index, total and high-density lipoprotein cholesterol, diabetes mellitus, smoking, and hypertension. These estimates did not change for the individual components of cardiovascular disease, and seropositivity to more than one organism did not alter these risk estimates substantially. CONCLUSIONS In this elderly cohort, chronic H. pylori, C pneumoniae, and CMV infections, as evidenced by seropositivity, were not associated with increased risk for cardiovascular disease. Additional studies are needed to determine the relations of chronic infections to cardiovascular disease risk in younger persons. (J Am Coll Cardiol 2002;40:1408-13). (C) 2002 by the American College of Cardiology Foundation. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA. MCP Hahnemann Univ Hosp, Div Cardiol, Philadelphia, PA USA. AstraZeneca, Wayne, PA USA. Beth Israel Hosp, Div Cardiol & Clin Epidemiol, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 37 TC 67 Z9 69 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 16 PY 2002 VL 40 IS 8 BP 1408 EP 1413 AR PII S0735-1097(02)02272-6 DI 10.1016/S0735-1097(02)02272-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 604DF UT WOS:000178600000006 PM 12392829 ER PT J AU Moak, JP Bailey, JJ Makhlouf, FT AF Moak, JP Bailey, JJ Makhlouf, FT TI Simultaneous heart rate and blood pressure variability analysis: Insight into mechanisms underlying neurally mediated cardiac syncope in children SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID UP TILT TEST; VASOVAGAL SYNCOPE; UNEXPLAINED SYNCOPE; RESPONSES AB OBJECTIVES The purpose of our investigation was to examine serial changes in autonomic nervous system activity along with measurements of hemodynamics and cardiac contractility, in assessing the mechanism(s) that underlie neurally mediated cardiac syncope (NMCS) in children. BACKGROUND Previous research that used heart rate variability analysis alone to understand changes in autonomic activity that result in NMCS has provided conflicting results. We performed simultaneous heart rate and blood pressure variability analyses to characterize dynamic alterations in sympathetic and vagal tone during tilt-table testing in 23 children with a history of syncope or frequent dizziness. METHODS Power spectra of heart rate and blood pressure variability were analyzed using autoregressive modeling. Maximum dP/dT of systolic blood pressure and the electrical-mechanical activation time were used to assess cardiac contractility. RESULTS Tilt-table testing was positive in 12 children and negative in 11. Syncope was associated with decreased heart rate, blood pressure and low-frequency (LF) power. Before episodes of syncope, systolic blood pressure dP/dT decreased, and the electrical-mechanical activation time was prolonged. The decrease in blood pressure LF power exceeded and occurred before the decrease in heart rate LF power. Despite similar early increases in LF power to the initial stress of upright tilting, no significant decline in LF power (heart rate or blood pressure) was observed during negative tilt-table tests. CONCLUSIONS All of these changes considered in total provide evidence supporting the hypothesis of sympathetic withdrawal/failure, resulting in a decrease in peripheral vascular tone and cardiac contractility, which results in profound hypotension in children with NMCS. (J Am Coll Cardiol 2002;40:1466-74). (C) 2002 by the American College of Cardiology Foundation. C1 Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. Ctr Informat Technol, NIH, Bethesda, MD USA. American Univ, Dept Stat, Washington, DC 20016 USA. RP Moak, JP (reprint author), Childrens Natl Med Ctr, Dept Cardiol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 33 TC 15 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 16 PY 2002 VL 40 IS 8 BP 1466 EP 1474 AR PII S0735-1097(02)02273-8 DI 10.1016/S0735-1097(02)02273-8 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 604DF UT WOS:000178600000015 PM 12392838 ER PT J AU Clegg, LX Feuer, EJ Midthune, DN Fay, MP Hankey, BF AF Clegg, LX Feuer, EJ Midthune, DN Fay, MP Hankey, BF TI Impact of reporting delay and reporting error on cancer incidence rates and trends SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURVEILLANCE DATA; AIDS INCIDENCE; REGRESSION AB Background: Cancer incidence rates and trends are a measure of the cancer burden in the general population. We studied the impact of reporting delay and reporting error on incidence rates and trends for cancers of the female breast, colorectal, lung/bronchus, prostate, and melanoma. Methods: Based on statistical models, we obtained reporting-adjusted (i.e., adjusted for both reporting delay and reporting error) case counts for each diagnosis year beginning in 1981 using reporting information for patients diagnosed with cancer in 1981-1998 from nine cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Joinpoint linear regression was used for trend analysis. All statistical tests are two-sided. Results: Initial incidence case counts (i.e., after the standard 2-year delay) accounted for only 88%-97% of the estimated final counts; it would take 4-17 years for 99% or more of the cancer cases to be reported. The percent change between reporting-adjusted and unadjusted cancer incidence rates for the 1998 diagnosis year ranged from 3% for colorectal cancers to 14% for melanoma in whites and for prostate cancer in black males. Reporting-adjusted current incidence trends for breast cancer and lung/bronchus cancer in white females showed statistically significant increases (estimated annual percent change [EAPC] = 0.6%, 95% confidence interval [CI] = 0.1% to 1.2%) and 1.2%, 95% CI = 0.7% to 1.6%, respectively), whereas trends for these cancers using unadjusted incidence rates were not statistically significantly different from zero (EAPC = 0.4%, 95% CI = -0.1% to 0.9% and 0.5%, 95% CI = -0.1% to 1.1%, respectively). Reporting-adjusted melanoma incidence rates for white males showed a statistically significant increase since 1981 (EAPC = 4.1%, 95% CI = 3.8% to 4.4%) in contrast to the unadjusted incidence rate, which was most consistent with a flat or downward trend (EAPC = -4.2%, 95% CI = -11.1% to 3.3%) after 1996. Conclusions: Reporting-adjusted cancer incidence rates are valuable in precisely determining current cancer incidence rates and trends and in monitoring the timeliness of data collection. Ignoring reporting delay and reporting error may produce downwardly biased cancer incidence trends, particularly in the most recent diagnosis years. C1 NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Clegg, LX (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, 6116 Execut Blvd,MSC 8316,Suite 504,Rm 5011, Bethesda, MD 20892 USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 9 TC 147 Z9 148 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 2002 VL 94 IS 20 BP 1537 EP 1545 PG 9 WC Oncology SC Oncology GA 603MF UT WOS:000178562900008 PM 12381706 ER PT J AU Ernster, VL Ballard-Barbash, R Barlow, WE Zheng, YY Weaver, DL Cutter, G Yankaskas, BC Rosenberg, R Carney, PA Kerlikowske, K Taplin, SH Urban, N Geller, BM AF Ernster, VL Ballard-Barbash, R Barlow, WE Zheng, YY Weaver, DL Cutter, G Yankaskas, BC Rosenberg, R Carney, PA Kerlikowske, K Taplin, SH Urban, N Geller, BM TI Detection of ductal carcinoma in situ in women undergoing screening mammography SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INVASIVE BREAST-CARCINOMA; SURGICAL ADJUVANT BREAST; IN-SITU; RISK-FACTORS; CANCER DETECTION; NATIONAL BREAST; FAMILY HISTORY; NEW-MEXICO; FOLLOW-UP; AGE AB Background: With the large number of women having mammography-an estimated 28.4 million U.S. women aged 40 years and older in 1998-the percentage of cancers detected as ductal carcinoma in situ (DCIS), which has an uncertain prognosis, has increased. We pooled data from seven regional mammography registries to determine the percentage of mammographically detected cancers that are DCIS and the rate of DCIS per 1000 mammograms. Methods: We analyzed data on 653 833 mammograms from 540 738 women between 40 and 84 years of age who underwent screening mammography at facilities participating in the National Cancer Institute's Breast Cancer Surveillance Consortium (BCSC) throughout 1996 and 1997. Mammography results were linked to population-based cancer and pathology registries. We calculated the percentage of screen-detected breast cancers that were DCIS, the rate of screen-detected DCIS per 1000 mammograms by age and by previous mammography status, and the sensitivity of screening mammography. Statistical tests were two-sided. Results: A total of 3266 cases of breast cancer were identified, 591 DCIS and 2675 invasive breast cancer. The percentage of screen-detected breast cancers that were DCIS decreased with age (from 28.2% [95% confidence interval (CI) = 23.9% to 32.5%] for women aged 4049 years to 16.0% [95% CI = 13.3% to 18.7%] for women aged 70-84 years). However, the rate of screen-detected DCIS cases per 1000 mammograms increased with age (from 0.56 [95% CI = 0.41 to 0.70] for women aged 40-49 years to 1.07 [95% CI = 0.87 to 1.27] for women aged 70-84 years). Sensitivity of screening mammography in all age groups combined was higher for detecting DCIS (86.0% [95% CI = 83.2% to 88.8%]) than it was for detecting invasive breast cancer (75.1% [95% CI = 73.5% to 76.8%]). Conclusions: Overall, approximately 1 in every 1300 screening mammography examinations leads to a diagnosis of DCIS. Given uncertainty about the natural history of DCIS, the clinical significance of screen-detected DCIS needs further investigation. C1 Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT USA. Univ Vermont, Coll Med, Burlington, VT USA. Univ Nevada, Ctr Res Design & Stat Methods, Reno, NV 89557 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Lebanon, NH USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Seattle, WA 98104 USA. RP Ballard-Barbash, R (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. FU NCI NIH HHS [U01CA63740, U01CA63731, U01CA63736, U01CA69976, U01CA70013, U01CA70040, U01CA86076, U01CA86082] NR 50 TC 315 Z9 327 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 2002 VL 94 IS 20 BP 1546 EP 1554 PG 9 WC Oncology SC Oncology GA 603MF UT WOS:000178562900009 PM 12381707 ER PT J AU Petricoin, EF Ornstein, DK Paweletz, CP Ardekani, A Hackett, PS Hitt, BA Velassco, A Trucco, C Wiegand, L Wood, K Simone, CB Levine, PJ Linehan, WM Emmert-Buck, MR Steinberg, SM Kohn, EC Liotta, LA AF Petricoin, EF Ornstein, DK Paweletz, CP Ardekani, A Hackett, PS Hitt, BA Velassco, A Trucco, C Wiegand, L Wood, K Simone, CB Levine, PJ Linehan, WM Emmert-Buck, MR Steinberg, SM Kohn, EC Liotta, LA TI Serum proteomic patterns for detection of prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROTEIN BIOCHIP; ANTIGEN AB Pathologic states within the prostate may be reflected by changes in serum proteomic patterns. To test this hypothesis, we analyzed serum proteomic mass spectra with a bioinformatics tool to reveal the most fit pattern that discriminated the training set of sera of men with a histopathologic diagnosis of prostate cancer (serum prostate-specific antigen [PSA] greater than or equal to 4 ng/mL) from those men without prostate cancer (serum PSA level < 1 ng/mL). Mass spectra of blinded sera (N = 266) from a test set derived from men with prostate cancer or men without prostate cancer were matched against the discriminating pattern revealed by the training set. A predicted diagnosis of benign disease or cancer was rendered based on similarity to the discriminating pattern discovered from the training set. The proteomic pattern correctly predicted 36 (95%, 95% confidence interval [CI] = 82% to 99%) of 38 patients with prostate cancer, while 177 (78%, 95% CI = 72% to 83%) of 228 patients were correctly classified as having benign conditions. For men with marginally elevated PSA levels (4-10 ng/mL; n = 137), the specificity was 71%. If validated in future series, serum proteomic pattern diagnostics may be of value in deciding whether to perform a biopsy on a man with an elevated PSA level. C1 US FDA, NCI, CBER, Dept Therapeut,Clin Proteom Program, Bethesda, MD USA. Univ N Carolina, Div Urol, Chapel Hill, NC USA. NCI, US FDA, Clin Proteom Program, Dept Therapeut Prot,CBER,NIH, Bethesda, MD USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Correl Syst Inc, Bethesda, MD USA. Catholic Univ Chile, Dept Urol, Santiago, Chile. Simone Protect Canc Inst, Lawrenceville, NJ USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), Bldg 29A,Rm 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 501 Z9 535 U1 3 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 2002 VL 94 IS 20 BP 1576 EP 1578 PG 3 WC Oncology SC Oncology GA 603MF UT WOS:000178562900013 PM 12381711 ER PT J AU Morshedi-Meibodi, A Larson, MG Levy, D O'Donnell, CJ Vasan, RS AF Morshedi-Meibodi, A Larson, MG Levy, D O'Donnell, CJ Vasan, RS TI Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RATE-VARIABILITY; MYOCARDIAL-INFARCTION; MORTALITY; COHORT; ASSOCIATION; POPULATION; PREDICTORS; ECG AB A delayed heart rate (HR) recovery after graded exercise testing has been associated with increased all-cause mortality in clinic-based samples. No prior study has examined the association of HR recovery after exercise with the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) events. We evaluated 2,967 Framingham study subjects (1,400 men, mean age 43 years) who were free of CVD and underwent a treadmill exercise test (Bruce protocol) at a routine examination. We examined the relations of HR recovery indexes (decrease in HR from peak exercise) to the incidence of a first CHD or CVD event and all-cause mortality, adjusting for established CVD risk factors. During follow-up (mean 15 years), 214 subjects experienced a CHD event (156 men), 312 developed a CVD event (207 men), and 167 died (105 men). In multivariable models, continuous HR recovery indexes were not associated with the incidence of CHD or CVD events, or with all-cause mortality. However, in models evaluating quintile-based cut points, the top quintile of HR recovery (greatest decline in HR) at 1-minute after exercise was associated with a lower risk of CHD (hazards ratio vs bottom 4 quintiles 0.54, 95% confidence interval [CI], 0.32 to 0.93) and CVD (hazards ratio 0.61, 95% CI 0.41 to 0.93), but not all-cause mortality (hazards ratio 0.99, 95% CI 0.60 to 1.62). In our community-based sample, HR recovery indexes were not associated with all-cause mortality. A very rapid HR recovery immediately after exercise was associated with lower risk of CHD and CVD events. These findings should be confirmed in other settings. (C) 2002 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol & Clin Epidemiol,Beth Israel Hosp, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K24-HL 04334-01A1, N01-HC-25195] NR 21 TC 104 Z9 111 U1 0 U2 7 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2002 VL 90 IS 8 BP 848 EP 852 AR PII S0002-9149(02)02706-6 DI 10.1016/S0002-9149(02)02706-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 603NF UT WOS:000178565400006 PM 12372572 ER PT J AU Saydah, SH Eberhardt, MS Loria, CM Brancati, FL AF Saydah, SH Eberhardt, MS Loria, CM Brancati, FL TI Age and the burden of death attributable to diabetes in the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diabetes mellitus; mortality ID MORTALITY; US; CERTIFICATES; POPULATION; PREVALENCE; GLUCOSE; ADULTS; INDEX AB Diabetes is a well-established cause of cardiovascular disease (CVD) and all-cause mortality. The burden of death attributable to diabetes in the United States is not well quantified, particularly with regard to age. The authors analyzed data from the Second National Health and Nutrition Examination Survey (NHANES 11) (19761980) and the NHANES II Mortality Study, in which a nationally representative cohort of 9,250 adults aged 3075 years was followed for 12-16 years, to determine all-cause and cause-specific mortality. Overall, between 1976 and 1980, the prevalence of diagnosed diabetes was 4.3%. By 1992, the relative hazard of all-cause mortality was 1.9 (95% confidence interval: 1.5, 2.3), and the population attributable risk (PAR) was 3.6%. The relative hazard of CVD mortality was 2.3 (95% confidence interval: 1.8, 2.8), and the PAR was 5.2%. Including participants with undiagnosed diabetes in the estimates increased the PAR for all-cause mortality to 5.1% and that for CVD mortality to 6.8%. Women had a higher prevalence of diagnosed diabetes than men and a greater relative hazard of death than nondiabetic women, leading to a higher PAR for women (3.8% for all causes and 7.3% for CVD) versus men (3.3% for all causes and 3.8% for CVD). These data suggest that diabetes accounts for at least 3.6% of all deaths and 5.2% of CVD deaths in US adults. Improvements in diabetes prevention and treatment should produce noticeable effects on US life expectancy. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Ctr Dis Control & Prevent, Off Anal Epidemiol & Hlth Promot, Natl Ctr Hlth Stat, Atlanta, GA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Brancati, FL (reprint author), Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [T32 HL07024-26] NR 29 TC 99 Z9 104 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2002 VL 156 IS 8 BP 714 EP 719 DI 10.1093/aje/kwf111 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 605AH UT WOS:000178652900004 PM 12370159 ER PT J AU Maki, PM AF Maki, PM TI Re: "Prospective assessment of estrogen replacement therapy and cognitive functioning: Atherosclerosis risk in communities study" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID MEMORY C1 NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Maki, PM (reprint author), NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2002 VL 156 IS 8 BP 785 EP 785 DI 10.1093/aje/kwf116 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 605AH UT WOS:000178652900012 PM 12385341 ER PT J AU Biesecker, LG AF Biesecker, LG TI Polydactyly: How many disorders and how many genes? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE malformations; genetic heterogeneity; medical diagnosis; pleiotropism ID BARDET-BIEDL-SYNDROME; PALLISTER-HALL-SYNDROME; SMITH-LEMLI-OPITZ; MUTATIONS; GLI3; GENETICS; INHERITANCE AB Disorders that include polydactyly as a manifestation are diverse and numerous. Cataloging these disorders by phenotype and genotype demonstrates numerous overlapping phenotypes, genetic heterogeneity of phenotypes, and distinct phenotypes generated from mutations in single genes. To assess these issues, a list of disorders with polydactyly has been compiled from several sources. Among 119 disorders, 39 disorders are associated with mutations in genes, and among these, genotypic and phenotypic overlap is demonstrated. These issues highlight the need for a diagnostic system that catalogs both genotype and phenotype. Published 2002 Wiley-Liss, Inc(dagger). C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, NIH, Bldg 49,Room 4A80, Bethesda, MD 20892 USA. NR 21 TC 25 Z9 25 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 15 PY 2002 VL 112 IS 3 BP 279 EP 283 DI 10.1002/ajmg.10779 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 599DH UT WOS:000178318500007 PM 12357471 ER PT J AU Everman, DB Bartels, CF Yang, Y Yanamandra, N Goodman, FR Mendoza-Londono, JR Savarirayan, R White, SM Graham, JM Gale, RP Svarch, E Newman, WG Kleckers, AR Francomano, CA Govindaiah, V Singh, L Morrison, S Thomas, JT Warman, ML AF Everman, DB Bartels, CF Yang, Y Yanamandra, N Goodman, FR Mendoza-Londono, JR Savarirayan, R White, SM Graham, JM Gale, RP Svarch, E Newman, WG Kleckers, AR Francomano, CA Govindaiah, V Singh, L Morrison, S Thomas, JT Warman, ML TI The mutational spectrum of brachydactyly type C SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE brachydactyly type C; growth/differentiation factor 5; cartilage-derived morphogenetic protein 1 ID TGF-BETA-SUPERFAMILY; LOCUS HETEROGENEITY; MEMBERS; BONE; PROTEIN-1; CDMP1 AB Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5. (C) 2002 Wiley-Liss, Inc. C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ctr Human Genet, Cleveland, OH 44106 USA. Univ Illinois, Coll Med, Peoria, IL 61656 USA. Inst Child Hlth, Mol Med Unit, London, England. Baylor Coll Med, Dept Genet, Houston, TX 77030 USA. Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. Cedars Sinai Med Ctr, Dept Med Genet, Ahmanson Dept Pediat, Steven Spielberg Pediat Res Ctr,Burns & Allen Res, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. Inst Hematol & Immul, Havana, Cuba. St Marys Hosp, Dept Clin Genet, Manchester M13 0JH, Lancs, England. NIA, Genet Lab, Baltimore, MD 21224 USA. Ctr DNA Finger Printing & Diagnost, Hyderabad, Andhra Pradesh, India. Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. Cleveland Clin Fdn, Cleveland, OH 44195 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. RP Warman, ML (reprint author), Case Western Reserve Univ, Dept Genet, Room BRB-719,2109 Adelbert Rd, Cleveland, OH 44106 USA. OI Mendoza-Londono, Roberto/0000-0003-3542-8106; Newman, William/0000-0002-6382-4678 FU NIAMS NIH HHS [AR 45687]; NICHD NIH HHS [HD 07518, HD 07104, HD22657]; NIGMS NIH HHS [GM08243] NR 28 TC 56 Z9 60 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 15 PY 2002 VL 112 IS 3 BP 291 EP 296 DI 10.1002/ajmg.10777 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 599DH UT WOS:000178318500009 PM 12357473 ER PT J AU Gottdiener, JS McClelland, RL Marshall, R Shemanski, L Furberg, CD Kitzman, DW Cushman, M Polak, J Gardin, JM Gersh, BJ Aurigemma, GP Manolio, TA AF Gottdiener, JS McClelland, RL Marshall, R Shemanski, L Furberg, CD Kitzman, DW Cushman, M Polak, J Gardin, JM Gersh, BJ Aurigemma, GP Manolio, TA TI Outcome of congestive heart failure in elderly persons: Influence of left ventricular systolic function - The cardiovascular health study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HOSPITAL CARDIAC-ARREST; LONG-TERM PROGNOSIS; EJECTION FRACTION; OLDER ADULTS; DIASTOLIC DYSFUNCTION; MYOCARDIAL-INFARCTION; PULMONARY-EDEMA; V-HEFT; MORTALITY; PREVALENCE AB Background: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function. Objective: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons. Design: Population-based longitudinal study of coronary heart disease and stroke. Setting: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland. Participants: 5888 persons who were at least 65 years of age and were recruited from the community. Measurements: Total mortality and cardiovascular morbidity and mortality. Results: Of 5532 participants, 269 (4.9%) had congestive heart failure. Among these, left ventricular function was normal in 63%, borderline decreased in 15%, and overtly impaired in 22%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category. Conclusions: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure. C1 St Francis Hosp, Div Cardiol, Roslyn, NY 11576 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Univ Washington, Seattle, WA 98195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Vermont, Burlington, VT USA. Tufts New England Med Ctr, Boston, MA USA. St John Hosp & Med Ctr, Detroit, MI USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Gottdiener, JS (reprint author), St Francis Hosp, Div Cardiol, 100 Port Washington Blvd, Roslyn, NY 11576 USA. FU NHLBI NIH HHS [N01-HC-85084, N01-HC-15103, N01-HC-85079-85086, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85085, N01-HC-85086] NR 54 TC 259 Z9 270 U1 0 U2 5 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 15 PY 2002 VL 137 IS 8 BP 631 EP 639 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 604WL UT WOS:000178644000001 PM 12379062 ER PT J AU Bruno, ME Borchers, CH Dial, JM Walker, NJ Hartis, JE Wetmore, BA Barrett, JC Tomer, KB Merrick, BA AF Bruno, ME Borchers, CH Dial, JM Walker, NJ Hartis, JE Wetmore, BA Barrett, JC Tomer, KB Merrick, BA TI Effects of TCDD upon I kappa B and IKK subunits localized in microsomes by proteomics SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE I kappa B; IKK; liver; microsomes; NF-kappa B; proteomics; rat; TCDD ID OXIDATIVE STRESS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; POTENTIAL MECHANISM; BINDING PROTEIN; AH RECEPTOR; RAT-LIVER; ACTIVATION; CELLS; BETA AB Biochemical studies have shown that microsomes represent an important subcellular fraction for determining 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) effects. Proteomic analysis by two-dimensional gel-mass spectrometry of liver microsomes was undertaken to gain new insight into the actions of TCDD in male and female rats. Proteomic analysis showed TCDD induced several xenobiotic metabolism enzymes as well as a protein at 90 kDa identified by mass spectrometry as IkappaB kinase beta/IKK2. This observation led to the discovery of other NF-kappaB binding proteins and kinases in microsomes and effects by TCDD. Western blotting for IKK and ikappaB family members in microsomes showed a distinct pattern from cytosol. IKK1 and IKK2 were both present in microsomes and were catalytically active although, unlike cytosol, IKKgamma/NEMO was not detectable. TCDD exposure produced an elevation in cytosolic and microsomal IKK activity of both genders. The NF-kappaB binding proteins IkappaBbeta and IkappaBgamma were prevalent in microsomes, while IkappaBalpha and IkappaBepsilon proteins were absent. TCDD treatment produced hyperphosphorylation of microsomal IkappaBbeta in both sexes with females being most sensitive. In cytosol, IkappaBalpha, IkappaBbeta, and IkappaBepsilon, but not IkappaBgamma, were clearly observed but were not changed by TCDD. Overall, proteomic analysis indicated the presence of NF-kappaB pathway members in microsomes, selectively altered by dioxin, which may influence immune and inflammatory responses within the liver. Published by Elsevier Science (USA). C1 NIEHS, Proteom Grp, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. NIEHS, Inst Spectrometry Grp, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Merrick, BA (reprint author), NIEHS, Proteom Grp, Natl Ctr Toxicogenom, POB 12233, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012; Tomer, Kenneth/E-8018-2013 OI Walker, Nigel/0000-0002-9111-6855; NR 51 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 15 PY 2002 VL 406 IS 2 BP 153 EP 164 AR PII S0003-9861(02)00452-6 DI 10.1016/S0003-9861(02)00452-6 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 605GX UT WOS:000178670500002 PM 12361703 ER PT J AU Radfar, L Kleiner, DE Fox, PC Pillemer, SR AF Radfar, L Kleiner, DE Fox, PC Pillemer, SR TI Prevalence and clinical significance of lymphocytic foci in minor salivary glands of healthy volunteers SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE focus score; prevalence; healthy volunteer; lymphocytic foci ID SJOGRENS-SYNDROME; DIAGNOSIS; BIOPSY; SIALADENITIS; INVOLVEMENT; SARCOIDOSIS; CRITERIA; DISEASE; MODEL AB Objective. To determine the prevalence and severity of focal lymphocytic sialadenitis in minor salivary glands of healthy, asymptomatic individuals, in whom Sjogren's syndrome (SS) has been excluded. Methods. Charts of 54 healthy volunteers who had salivary gland biopsies at the National Institutes of Health from January 1992 to August 1998 were reviewed. The healthy volunteers served as control subjects in various studies of salivary dysfunction. Significant medical conditions including SS were excluded. A biopsy with a focus score (FS) > 1 was regarded as positive. Descriptive statistics were used to summarize the population's characteristics. Results. The frequency of focal lymphocytic infiltration in the healthy volunteers was about 15% (8 of 54). None of these individuals had subjective xerostomia or dry eyes. The positive FS ranged from 2 to 6. FS did not correlate with age, smoking, serologic findings, or salivary flow in these patients. Conclusion. Lymphocytic infiltration in minor salivary glands is not uncommon among individuals without a history of salivary gland dysfunction. This finding is in agreement with the result of a previous autopsy survey study, indicating that focal sialadenitis may occur in the absence of SS. C1 SUNY Buffalo, Sch Dent Med, Buffalo, NY 14214 USA. NIDCR, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. Amarillo Biosci Inc, Rockville, MD USA. RP Radfar, L (reprint author), SUNY Buffalo, Sch Dent Med, Squire Hall,Room 355,3435 Main St, Buffalo, NY 14214 USA. OI Kleiner, David/0000-0003-3442-4453 NR 26 TC 42 Z9 44 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 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD OCT 15 PY 2002 VL 47 IS 5 BP 520 EP 524 DI 10.1002/art.10668 PG 5 WC Rheumatology SC Rheumatology GA 606BZ UT WOS:000178714400010 PM 12382301 ER PT J AU Takei, J Pei, WH Vu, D Bai, YW AF Takei, J Pei, WH Vu, D Bai, YW TI Populating partially unfolded forms by hydrogen exchange-directed protein engineering SO BIOCHEMISTRY LA English DT Article ID ISOTOPICALLY ENRICHED PROTEINS; BACKBONE DYNAMICS; NMR-SPECTROSCOPY; CHEMICAL-SHIFTS; N-15; INTERMEDIATE; APOMYOGLOBIN; RELAXATION; STATE; MODEL AB The native-state hydrogen exchange of a redesigned apocytochrome b(562) suggests that at least two partially unfolded forms (PUFs) exist for this four-helix bundle protein under native conditions. The more stable PUF has the N-terminal helix unfolded. To verify the conclusion further and obtain more detailed structural information about this PUF, five hydrophobic core residues in the N-terminal helix were mutated to Gly and Asp to destabilize the native state selectively and populate the PUF for structural studies. The secondary structure and the backbone dynamics of this mutant were characterized using multidimensional NMR. Consistent with the prediction, the N-terminal region of the mutant was found to be unfolded while other parts of the proteins remained folded. These results suggest that native-state hydrogen exchange-directed protein engineering can be a useful approach to populating partially unfolded forms for detailed structural studies. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6114E, Bethesda, MD 20892 USA. NR 27 TC 34 Z9 34 U1 0 U2 0 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 15 PY 2002 VL 41 IS 41 BP 12308 EP 12312 DI 10.1021/bi026491c PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602FD UT WOS:000178494400005 PM 12369818 ER PT J AU Pine, DS Charney, DS AF Pine, DS Charney, DS TI Children, stress, and sensitization: An integration of basic and clinical research on emotion? SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; INDIVIDUAL-DIFFERENCES; CORTISOL; TRANSMISSION; TEMPERAMENT; GENERATIONS; ADOLESCENTS; DISORDERS; BEHAVIOR; ANXIETY C1 NIMH, NIH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, NIH, Mood & Anxiety Disorder Program, 15K North Dr,Room 110,MSC 2670, Bethesda, MD 20892 USA. NR 20 TC 17 Z9 17 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2002 VL 52 IS 8 BP 773 EP 775 AR PII S0006-3223(02)01569-X DI 10.1016/S0006-3223(02)01569-X PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 601BE UT WOS:000178425600001 PM 12372648 ER PT J AU Leverich, GS AF Leverich, GS TI Early Physical and Sexual Abuse Associated with an Adverse Course of Bipolar Illness - Reply SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID RISK-FACTORS; CHILD; NEGLECT C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA. Univ Texas, SW Med Ctr, Bipolar Disorder Clin, Dallas, TX USA. Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA. Univ Utrecht, Med Ctr, Utrecht, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Los Angeles, CA 90024 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20829 USA. RP Leverich, GS (reprint author), NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RI Nolen, Willem/E-9006-2014 NR 11 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2002 VL 52 IS 8 BP 843 EP 845 DI 10.1016/S0006-3223(02)01493-2 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 601BE UT WOS:000178425600010 ER PT J AU Schmidt, M Zickler, P Hoffmann, G Haas, S Wissler, M Muessig, A Tisdale, JF Kuramoto, K Andrews, RG Wu, T Kiem, HP Dunbar, CE von Kalle, C AF Schmidt, M Zickler, P Hoffmann, G Haas, S Wissler, M Muessig, A Tisdale, JF Kuramoto, K Andrews, RG Wu, T Kiem, HP Dunbar, CE von Kalle, C TI Polyclonal long-term repopulating stem cell clones in a primate model SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; IN-VIVO; HEMATOPOIETIC-CELLS; QUANTITATIVE ASSAY; NONHUMAN-PRIMATES; SCID/SCID MICE; PROGENITOR; EXPANSION; KINETICS; DNA AB Hematopoietic bone marrow stem cells generate differentiated blood cells and, when transplanted, may contribute to other organs, such as the brain, heart, and liver. An understanding of in vivo clonal behavior of stem cells will have important implications for cellular and gene therapy. For the first time, we have directly demonstrated the derivation of circulating peripheral blood cells from individual stem cell clones. We analyzed the clonal composition of retrovirus-marked peripheral blood leukocyte populations in 2 different primate models by a novel direct genomic sequencing technique allowing the identification of vector insertion sites. More than 80 contributing long-term hematopoietic clones were identified in individual rhesus macaque peripheral blood transplant recipients and more than 25 different clones in a baboon marrow transplant recipient. Up to 5 insertion sequences from each animal were used to trace the long-term contribution of stem cell clones in these primate models. Continuous and mostly pluripotent contributions of peripheral blood leukocytes from each of the traced clones could be detected for the entire follow-up period of 23 to 33 months. Our study provides direct molecular evidence for a polyclonal, multilineage, and sustained contribution of individual stem cells to primate hematopoiesis. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Dept Internal Med 1, D-7800 Freiburg, Germany. Univ Freiburg, Inst Mol Med & Cell Res, D-7800 Freiburg, Germany. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. Univ Washington, Washington Reg Primate Res Ctr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR 00166]; NHLBI NIH HHS [HL 53750, HL 54881]; NIDDK NIH HHS [DK47754, DK56465] NR 33 TC 167 Z9 174 U1 0 U2 1 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 15 PY 2002 VL 100 IS 8 BP 2737 EP 2743 DI 10.1182/blood-2002-02-0407 PG 7 WC Hematology SC Hematology GA 602RW UT WOS:000178519100013 PM 12351380 ER PT J AU Pedersen, IM Kitada, S Schimmer, A Kim, Y Zapata, JM Charboneau, L Rassenti, L Andreeff, M Bennett, F Sporn, MB Liotta, LD Kipps, TJ Reed, JC AF Pedersen, IM Kitada, S Schimmer, A Kim, Y Zapata, JM Charboneau, L Rassenti, L Andreeff, M Bennett, F Sporn, MB Liotta, LD Kipps, TJ Reed, JC TI The triterpenoid CDDO induces apoptosis in refractory CLL B cells SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACTIVATED RECEPTOR-GAMMA; NITRIC-OXIDE PRODUCTION; MOUSE MACROPHAGES; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; CASPASE ACTIVATION; CYTOCHROME-C; PPAR-GAMMA; CANCER; DEATH AB Chronic lymphocytic leukemia (CLL) cells develop chemo-resistance over time. Most anticancer agents function through induction of apoptosis, and therefore resistance against these agents is likely to be caused by selection for CLL cells with defects in the particular apoptosis pathway that is triggered by these drugs. Anticancer agents that function through alternative apoptotic pathways might therefore be useful in treating chemoresistant CLL. Triterpenoids represent a class of naturally occurring and synthetic compounds with demonstrated antitumor activity. We examined the effects of CDDO (triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid) on CLL B cells in vitro. CDDO induced apoptosis in a dose-dependent manner in all (n=30) CLL samples tested, including previously untreated and chemo-resistant CLL specimens. CDDO induced rapid proteolytic processing of caspase-8, but not caspase-9, in CLL B cells, suggesting activation of a mitochondria-independent pathway. CDDO-incluced apoptosis of CLL B cells was blocked by cytokine response modifier A (CrmA), a suppressor of caspase-8, but not by X-linked inhibitor of apoptosis protein-baculovirus IAP repeat-3 (XIAP-BIR3), a fragment of XIAP, which selectively inhibits caspase-9. Examination of CDDO effects on expression of several apoptosis-relevant genes demonstrated significant reductions in the levels of caspase-8 homolog Fas-ligand interleukin-11-converting enzyme (FLICE)inhibitory protein (c-FLIP), an endogenous antagonist of caspase-8. However, reductions of FLIP achieved by FLIP antisense oligonucleotides were insufficient for triggering apoptosis, indicating that CDDO has other targets in CLL B cells besides FLIP. These data suggest that the synthetic triterpenoid CDDO should be further explored as a possible therapeutic agent for treatment of chemo-resistant CLL. C1 Burnham Inst, La Jolla, CA 92037 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NCI, Tissue Proteom Unit, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. Dartmouth Coll Sch Med, Hanover, NH USA. RP Reed, JC (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Zapata, Juan/J-6304-2014 OI Zapata, Juan/0000-0002-0110-0009 FU NCI NIH HHS [CA-81534, CA-78814] NR 44 TC 97 Z9 104 U1 1 U2 3 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 15 PY 2002 VL 100 IS 8 BP 2965 EP 2972 DI 10.1182/blood-2002-04-1174 PG 8 WC Hematology SC Hematology GA 602RW UT WOS:000178519100042 PM 12351409 ER PT J AU Schop, RFJ Kuehl, WM Van Wier, SA Ahmann, GJ Price-Troska, T Bailey, RJ Jalal, SM Qi, Y Kyle, RA Greipp, PR Fonseca, R AF Schop, RFJ Kuehl, WM Van Wier, SA Ahmann, GJ Price-Troska, T Bailey, RJ Jalal, SM Qi, Y Kyle, RA Greipp, PR Fonseca, R TI Waldenstrom macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; TRANSCRIPTION FACTOR BSAP; IN-SITU HYBRIDIZATION; MULTIPLE-MYELOMA; CHROMOSOMAL-ABNORMALITIES; 3'ALPHA ENHANCER; CYTOGENETIC ABNORMALITIES; HISTOLOGIC SUBTYPES; MOLECULAR ANALYSIS; BONE-MARROW AB Lymphoplasmacytic lymphoma (LPL) is characterized by t(9;14)(p13;q32) in 50% of patients who lack paraproteinemia. Waldenstrom macroglobulinemia (WM), which has an immunoglobulin M (IgM) paraproteinemia, is classified as an LPL. Rare reports have suggested that WM sometimes is associated with 14q23 translocations, deletions of 6q, and t(11;18)(q21; q21). We tested for these abnormalities in the clonal cells of WM patients. We selected patients with clinicopathologic diagnosis of WM (all had IgM levels greater than 1.5 g/dL). Southern blot assay was used to detect legitimate and illegitimate IgH switch rearrangements. In addition to conventional cytogenetic (CC) and multicolor metaphase fluorescence in situ hybridization (M-FISH) analyses, we used interphase FISH to screen fort(9;14)(p13; q32) and other IgH translocations, t(11; 18)(q21;q21), and 6q21 deletions. Genomic stability was also assessed using chromosome enumeration probes for chromosomes 7, 9, 11, 12, 15, and 17 in 15 patients. There was no evidence of either legitimate or illegitimate IgH rearrangements by Southern blot assay (n=12). CC (n=37), M-FISH (n=5), and interphase FISH (n=42) failed to identify IgH or t(11;18) translocations. Although tumor cells from most patients were diploid for the chromosomes studied, deletions of 6q21 were observed in 42% of patients. In contrast to LPL tumors that are not associated with paraproteinemia and that have frequent t(9;14)(p13;q32) translocations, IgH translocations are not found in WM, a form of LPL tumor distinguished by IgM paraproteinemia. However, WM tumor cells, which appear to be diploid or near diploid, often have deletions of 6q21. C1 Mayo Clin & Mayo Fdn, Dept Hematol & Internal Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. NCI, Genet Branch, Bethesda, MD 20892 USA. RP Fonseca, R (reprint author), Mayo Clin & Mayo Fdn, Dept Hematol & Internal Med, Stabile 628, Rochester, MN 55905 USA. OI Fonseca, Rafael/0000-0002-5938-3769 FU NCI NIH HHS [CA21115-25C, P01 CA62242, R01 CA83724-01] NR 52 TC 112 Z9 116 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2002 VL 100 IS 8 BP 2996 EP 3001 DI 10.1182/blood.V100.8.2996 PG 6 WC Hematology SC Hematology GA 602RW UT WOS:000178519100046 PM 12351413 ER PT J AU Raziuddin, A Longo, DL Bennett, M Winkler-Pickett, R Ortaldo, JR Murphy, WJ AF Raziuddin, A Longo, DL Bennett, M Winkler-Pickett, R Ortaldo, JR Murphy, WJ TI Increased bone marrow allograft rejection by depletion of NK cells expressing inhibitory Ly49 NK receptors for donor class I antigens SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; LY-49 MULTIGENE FAMILY; GRAFT-REJECTION; MICE; RECOGNITION; SPECIFICITY; MOLECULES; SUBSETS; IDENTIFICATION; HEMATOPOIESIS AB Natural killer (NK) cells are the major effectors of acute rejection of incompatible bone marrow cell (BMC) grafts in lethally irradiated mice. The immunogenetics of BMC rejection are largely controlled by the coexpression (or not) of inhibitory and stimulatory Ly49 receptors whose ligands are class I major histocompatibility complex (MHC) molecules. The majority of the BMC rejection studies involved low numbers of BMCs that were resisted by host NK cells. In the present study, larger numbers of BMCs were given in which rejection was not detected and the role of different Ly49 NK subsets not presumably involved in the rejection of a particular BMC haplotype was examined. Surprisingly, the data show that the removal of NK cell subsets expressing Ly49 inhibitory receptors for donor class I antigens, which would be predicted to have no effect on the BMC rejection capability, resulted in the marked rejection of BMCs where no resistance was normally seen. These results extend the "missing self" hypothesis to suggest that NK Ly49 inhibitory receptors can both inhibit activation and killing by those cells, but also can in some way influence the function of NK cells that do not express that inhibitory receptor in a cell-cell interaction. This suggests that caution must be exercised before removal of host NK cell subset is applied clinically because enhanced BMC rejection may result. Altering the balance of Ly49 NK subsets may also affect other in vivo activities of these cells. C1 SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NIA, Baltimore, MD 21224 USA. RP Murphy, WJ (reprint author), SAIC Frederick, Intramural Res Support Program, Bldg 567,Room 210, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 37 TC 31 Z9 32 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 15 PY 2002 VL 100 IS 8 BP 3026 EP 3033 DI 10.1182/blood.V100.8.3026 PG 8 WC Hematology SC Hematology GA 602RW UT WOS:000178519100050 PM 12351417 ER PT J AU Pickard, AL Gridley, G Mellemkjae, L Johansen, C Kofoed-Enevoldsen, A Cantor, KP Brinton, LA AF Pickard, AL Gridley, G Mellemkjae, L Johansen, C Kofoed-Enevoldsen, A Cantor, KP Brinton, LA TI Hyperparathyroidism and subsequent cancer risk in Denmark SO CANCER LA English DT Article DE primary hyperparathyroidism; secondary hyperparathyroidism; thyroid; myeloma ID PARATHYROID ADENOMA; THYROID-CARCINOMA; HYPER-PARATHYROIDISM; MULTIPLE-MYELOMA; UREMIC PATIENTS; IRRADIATION; NECK; RADIATION; DISEASE AB BACKGROUND. There is increasing evidence that hyperparathyroidism (HPT), a condition that leads to elevated serum calcium levels, is associated with endocrine and other malignancies, suggesting a possible causal link between HPT and carcinoma. METHODS. To investigate the relation of HPT to subsequent cancer risk, the authors conducted a record-linkage study among 2425 patients who were diagnosed with HPT in Danish hospitals. Patients were identified in hospital discharge records, and records were then linked with the Danish National Cancer Registry for the years 1977-1993 to identify cancer incidence. To estimate cancer risk, standardized incidence ratios (SIRs) were computed. RESULTS. After excluding patients who were diagnosed in the first year of follow-up, a total of 219 malignancies were observed, resulting in an SIR of 1.25 (95% confidence interval [95%CI], 1.1-1.4). Cancer risk among women was higher than among men. Among those with primary (idiopathic) HPT, hematopoetic malignancies were elevated significantly (SIR, 1.88; 95%CI, 1.0-3.2; based on 13 patients), with the excess derived primarily from 4 observed patients with multiple myeloma. Patients with secondary HPT had an insignificantly increased risk of overall cancers. Patients who were diagnosed with other or unspecified types of HPT had significant increases in carcinoma of the urinary tract (SIR, 2.71; 95%Cl, 1.2-5.3; based on 8 patients) and carcinoma of the thyroid gland (SIR, 21.19; 95%Cl, 4.3-61.9; based on 3 patients). CONCLUSIONS. Future studies should monitor whether specific endocrine alterations associated with HPT may affect the long-term risk of hematopoetic, thyroid, and urinary tract carcinomas. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, Carrboro, NC USA. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. RP Brinton, LA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 7068, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 35 TC 31 Z9 33 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2002 VL 95 IS 8 BP 1611 EP 1617 DI 10.1002/cncr.10845 PG 7 WC Oncology SC Oncology GA 602EK UT WOS:000178492600001 PM 12365007 ER PT J AU Feldman, AL Alexander, HR Linehan, WM Eyler, RA Miller, MS Steinberg, SM Libutti, SK AF Feldman, AL Alexander, HR Linehan, WM Eyler, RA Miller, MS Steinberg, SM Libutti, SK TI Prospective analysis of circulating endostatin levels in patients with renal cell carcinoma SO CANCER LA English DT Article DE renal cell carcinoma; endostatin; vascular endothelial growth factor; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS INHIBITOR ENDOSTATIN; ANTIANGIOGENIC GENE-THERAPY; CANCER-PATIENTS; COLLAGEN-XVIII; PLASMA ENDOSTATIN; TUMOR-GROWTH; FACTOR VEGF; SUPPRESSION; METASTASES AB BACKGROUND. The aim of the current study was to assess circulating levels of endogenous endostatin in patients with renal carinoma and to determine the relationship of these levels to circulating levels of vascular endothelial growth factor (VEGF) and prognosis. METHODS. The authors prospectively studied 66 patients (48 male, 18 female; mean age, 50 years) undergoing nephrectomy for renal carcinoma oil clinical trials at the National Cancer Institute. Metastases were present in 51 of 66 patients (77%) at the time of nephrectomy. Preoperative and followup serum endostatin and VEGF levels were determined using competitive enzyme immunoassays and compared to a group of 32 age- and gender-matched healthy controls. Associations between circulating endostatin levels and clinicopathologic variables, including survival, were determined. RESULTS. Preoperative endostatin levels were higher in renal carcinoma patients than in healthy controls (P = 0.05). There was a weak to moderate correlation between pretreatment serum endostatin levels and serum VEGF levels (r = 0.47; P = 0.001), and levels of both proteins increased significantly following nephrectomy (P < 0.0001 and P < 0.0001, respectively; n = 41). In addition, patients whose endostatin levels increased more than twofold after nephrectomy had significantly poorer prognoses than patients without such an increase (P = 0.018). This association was more pronounced when patients without metastases were excluded (P = 0.0037). CONCLUSIONS. Circulating endostatin levels are elevated in patients with renal carcinoma and correlate with circulating VEGF levels. Endostatin levels increase after nephrectomy, and patients with the greatest increases experience shortened survival times. These findings suggest an association between tumor aggressiveness and the production of endogenous endostatin in patients with renal carcinoma. C1 NIH, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NIH, Surg Branch, Ctr Canc Res, Bldg 10,Room 3C428, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 NR 32 TC 47 Z9 54 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2002 VL 95 IS 8 BP 1637 EP 1643 DI 10.1002/cncr.10845 PG 7 WC Oncology SC Oncology GA 602EK UT WOS:000178492600004 PM 12365010 ER PT J AU Gatta, G Capocaccia, R Coleman, MP Ries, LAG Berrino, F AF Gatta, G Capocaccia, R Coleman, MP Ries, LAG Berrino, F TI Childhood cancer survival in Europe and the United States SO CANCER LA English DT Article; Proceedings Paper CT European Conference on Cancer Strategies and Outcomes CY MAR, 2001 CL EDINBURGH, SCOTLAND DE childhood cancer; population-based cancer registries; survival; Europe; United States AB BACKGROUND. Survival rates for most major adult cancers are higher in the United States compared with the survival rates in Europe. The objective of this study was to determine whether transatlantic differences in survival also are present in childhood cancers. METHODS. The authors analyzed 16,148 European patients and 3476 patients in the United States who were diagnosed with malignant disease at age < 15 years during 1985-1989. The patients were obtained from 34 EUROCARE cancer registries in 17 countries and from 9 SEER registries in the United States. The authors considered the major 14 diagnostic categories of the International Classification of Childhood Cancers. To increase the power of comparisons, they also considered all childhood cancers together. Observed survival was calculated by actuarial methods. RESULTS. For all cancers combined, northern Europe had the highest 5-year survival rate at 75% (95% confidence interval [95%CI], 72-78%), and Eastern Europe had the lowest survival rate at 55% (95%CI, 52-58%). The survival rate in the United States was roughly comparable to the survival rates in Italy and other Western European countries at 70%. Northern Europe also had highest survival rate for patients with lymphoid leukemias (83%; 95%CI, 78-88%); whereas Germany, Italy, and the other Western European countries had survival rates similar to the average survival rate for patients in the United States (77%; 95%CI, 74-80%). The survival rate was 7-9% lower in Europe compared with the survival rate in United States for patients with neuroblastoma and Wilms tumors and 8% higher for patients with retinoblastoma (all significant). Small, nonsignificant differences were found for patients with osteosarcoma, ependymoma, and medulloblastorna (with a higher survival rate in the United States) and for patients with acute nonlymphocytic leukemia (with a higher survival rate in Europe). Very similar survival rates among the two populations were found for the other cancers. CONCLUSIONS. Unlike the survival of adults with cancer, the survival of children with cancer in Europe (except Eastern Europe) is very similar to that in the United States. Childhood cancers are generally more responsive to therapy than adult cancers, but these results also may reflect wide accessibility of these treatments for most patients. These results are relevant to the interpretation of differences in adult cancer survival. (C) 2002 American Cancer Society. C1 Ist Nazl Studio & Cura Tumori, Div Epidemiol, I-20133 Milan, Italy. Ist Super Sanita, Dept Epidemiol & Biostat, I-00161 Rome, Italy. London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, Canc & Publ Hlth Unit, London WC1, England. NCI, DCCPS, SRP,Canc Stat Branch, Surveillance Epidemiol & End Results Program, Bethesda, MD 20892 USA. RP Gatta, G (reprint author), Ist Nazl Studio & Cura Tumori, Div Epidemiol, Via Venezian 1, I-20133 Milan, Italy. RI Gatta, Gemma/B-8627-2017; OI Gatta, Gemma/0000-0003-4160-6458; Coleman, Michel/0000-0001-8940-3807 NR 15 TC 163 Z9 167 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2002 VL 95 IS 8 BP 1767 EP 1772 DI 10.1002/cncr.10833 PG 6 WC Oncology SC Oncology GA 602EK UT WOS:000178492600020 PM 12365026 ER PT J AU Yu, Q La Rose, J Zhang, HL Takemura, H Kohn, KW Pommier, Y AF Yu, Q La Rose, J Zhang, HL Takemura, H Kohn, KW Pommier, Y TI UCN-01 inhibits p53 up-regulation and abrogates gamma-radiation-induced G(2)-M checkpoint independently of p53 by targeting both of the checkpoint kinases, Chk2 and Chk1 SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGE CHECKPOINT; CANCER CELL-LINES; HUMAN COLON-CARCINOMA; 7-HYDROXYSTAUROSPORINE UCN-01; PROTEIN-KINASE; RADIOSENSITIZING AGENT; CYCLE CHECKPOINT; INDUCED S; PHOSPHORYLATION; ATM AB UCN-01 (7-hydroxystaurosporine) is a cell-cycle checkpoint abrogator that sensitizes cells to ionizing radiation (IR) and chemotherapeutic agents. It has been shown previously that UCN-01 abrogates DNA-damage-induced G(2) checkpoint most selectively in p53-defective cells, by primarily targeting Chk1. Here we show that UCN-01 prevented IR-induced p53 up-regulation and p53 phosphorylation on serine 20, a site previously identified for Chk2 (or/and Chk1) kinase. We found that in human colon carcinoma HCT116 cells, IR treatment enhanced Chk2 kinase activity, whereas Chk1 activity remained unchanged, which suggested that UCN-01 may interrupt Ir-induced p53 response by inhibiting Chk2 kinase. This conclusion is supported by in vitro kinase assays, showing that UCN-01 inhibits Chk2 immunoprecipitated from HCT116 cells (1C(50), similar to10 nM). In addition, UCN-01 efficiently abrogated both the initiation and maintenance of IR-induced G2 arrest in HCT116 cells and their isogenic p53 (-/-) derivative, indicating that G2 checkpoint abrogation by UCN-01 is p53 independent. In the p53 (-/-) cells, there was no p21(Waf1/Cip1) induction nor UCN-01-induced apoptosis. Taken together, these observations indicate that UCN-01 can modulate both Chk1 and Chk2 in intact cells and enhance IR-induced apoptosis in p53-deficient, and consequently p21-deficient, cells. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. NR 51 TC 124 Z9 134 U1 1 U2 1 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 15 PY 2002 VL 62 IS 20 BP 5743 EP 5748 PG 6 WC Oncology SC Oncology GA 605TP UT WOS:000178693400021 PM 12384533 ER PT J AU Yao, ZS Zhang, ML Axworthy, DB Wong, KJ Garmestani, K Park, L Park, CW Mallett, RW Theodore, LJ Yau, EK Waldmann, TA Brechbiel, MW Paik, CH Pastan, I Carrasquillo, JA AF Yao, ZS Zhang, ML Axworthy, DB Wong, KJ Garmestani, K Park, L Park, CW Mallett, RW Theodore, LJ Yau, EK Waldmann, TA Brechbiel, MW Paik, CH Pastan, I Carrasquillo, JA TI Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and Y-90-labeled 1,4,7,10-tetraazacyclododecane-N,N ',N '',N '''-tetraacetic acid (DOTA)-biotin SO CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY; CARCINOMA XENOGRAFTS; CANCER; Y-90; TOXICITY; BIOTIN AB We investigated the biodistribution of Y-88/In-111-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA)-biotin and therapy with Y-90-labeled DOTA-biotin in tumor-bearing mice after B3- streptavidin antibody conjugate (B3-SA) pretargeting. B3 antibody, recognizing Lewis(y) antigen, was conjugated to streptavidin (B3-SA). For pretargeting, 400 mug of the B3-SA was injected i.v. into mice bearing A431 tumor xenografts. After tumor localization of B3-SA, 100 mug of synthetic clearing agent was injected i.v. to clear the unbound B3-SA from the circulation. Four It later, 1 mug of radiolabeled DOTA-biotin was injected i.v. Radioimmunotherapy was performed with doses of 9.25 to 37 MBq of 90Y-labeled DOTA-biotin. As a result, radiolabeled DOTA-biotin cleared rapidly. All of the normal tissues had <2.6% of the injected dose per gram, whereas tumor uptake reached &SIM;15% ID/g. The total tumor uptake of radioactivity remained similar for 96 h or longer. In the first study, the median survival of the control group was 8 days, whereas it increased to >163 days in the 37 MBq Y-90 group (P < 0.005). In a second therapy group, 7 of 10 mice receiving 37 MBq of 90Y and B3-SA were cured, and remained healthy for >180 days after therapy, compared with control groups, with less than or equal to29.2 days mean survival time (P < 0.001). Tumor pretargeting with B3-SA and radiolabeled DOTA-biotin has shown favorable, specific, and fast targeting that has resulted in good tumor responses and, thus, serves as a rationale for human studies with the B3-SA pretargeting approach. C1 NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NeoRx Corp, Seattle, WA 98119 USA. RP Carrasquillo, JA (reprint author), NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1C-496,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 20 TC 38 Z9 38 U1 0 U2 2 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 15 PY 2002 VL 62 IS 20 BP 5755 EP 5760 PG 6 WC Oncology SC Oncology GA 605TP UT WOS:000178693400023 PM 12384535 ER PT J AU Aarts, WM Schlom, J Hodge, JW AF Aarts, WM Schlom, J Hodge, JW TI Vector-based vaccine/cytokine combination therapy to enhance induction of immune responses to a self-antigen and antitumor activity SO CANCER RESEARCH LA English DT Article ID RECOMBINANT VACCINIA VIRUS; COLONY-STIMULATING FACTOR; TUMOR-ASSOCIATED ANTIGEN; T-CELL COSTIMULATION; REGIONAL LYMPH-NODES; ANTICANCER VACCINES; DIVERSIFIED PRIME; PRESENTING CELLS; DENDRITIC CELLS; PHASE-I AB Many antigens associated with human tumors are overexpressed in tumor cells as compared with normal tissues; these "self" tumor-associated antigens are also expressed during fetal development, and it is, thus, not surprising that they are either weakly immunogenic or functionally nonimmunogenic in the tumor-bearing host. In the studies reported here, we have used different vaccines and vaccine strategies in an attempt to develop antitumor immunity in a stringent animal model. The tumor antigen used was human carcinoembryonic antigen (CEA). The model used was CEA transgenic mice, in which the human CEA transgene is under the control of the endogenous CEA promoter; CEA is expressed in fetal tissues and normal gastrointestinal tissues, and CEA protein is found in sera. Previous studies have shown these CEA transgenic mice to be tolerant to the induction of CEA immunity using CEA protein in adjuvant as an immunogen. CEA-expressing tumor cells were implanted 14 days before vaccine therapy. The vaccines used were recombinant vaccinia virus containing the transgenes for CEA and three T-cell costimulatory molecules [B7-1, ICAM-1, and LFA-3, designated recombinant vaccinia (rV)-CEA/TRICOM], with each transgene under the control of individual poxvirus promoters, and a replication-defective avipox virus (fowlpox; rF) containing the same four transgenes (designated rF-CEA/TRICOM). The results demonstrate that (a) continued boosting with vaccine is required to maintain CEA-specific T-cell responses, and boosting with rF-CEA/TRICOM is superior to boosting with rF-CEA; (b) a diversified vaccination protocol consisting of primary vaccination with rV-CEA/TRICOM followed by boosting with rF-CEA/TRICOM is more efficacious than homogeneous vaccination with rF-CEA/TRICOM in the induction of both CEA-specific T-cell responses and antitumor activity; and (c) the use of cytokines, local granulocyte macrophage colony-stimulating factor (GMCSF) and low-dose systemic interleukin 2, in combination with vaccine is essential in inducing antitumor activity, as compared with the use of cytokines alone, or the use of vaccines without cytokine. Both GM-CSF and interleukin 2 were shown to contribute to the induction of CEA-specific T-cell responses. These studies thus provide a "proof of concept" that potent vaccines and vaccine strategies, in combination with cytokines, may be essential to obtain the level of T-cell responses directed against a self-antigen that is necessary to achieve antitumor responses. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 37 TC 88 Z9 89 U1 0 U2 1 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 15 PY 2002 VL 62 IS 20 BP 5770 EP 5777 PG 8 WC Oncology SC Oncology GA 605TP UT WOS:000178693400025 PM 12384537 ER PT J AU Johnson, BD Shaw, LJ Pepine, CJ McGorray, SP Reis, SE Kelsey, SF Sopko, G Rogers, WJ Mankad, S Merz, CNB AF Johnson, BD Shaw, LJ Pepine, CJ McGorray, SP Reis, SE Kelsey, SF Sopko, G Rogers, WJ Mankad, S Merz, CNB TI Persistent chest pain and future adverse events: The NHLBI-sponsored women's ischemia syndrome evaluation (WISE) study SO CIRCULATION LA English DT Meeting Abstract CT 4th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY OCT 13-14, 2002 CL WASHINGTON, D.C. SP Amer Heart Assoc Councils Cardiovasc Dis Young, Cardiovasc Nursing, Cardio Thorac & Vasc Surg, Amer Coll Cardiol Fdn, Dept Vet Affairs C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Atlanta Cardiovasc Res Inst, Atlanta, GA USA. Univ Florida, Gainesville, FL USA. NHLBI, Bethesda, MD 20892 USA. Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 2002 VL 106 IS 16 MA P117 BP E97 EP E97 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 605NH UT WOS:000178683600126 ER PT J AU Walker, ER Clark, BL AF Walker, ER Clark, BL TI Racial disparities in the duality of care delivered to Mississippi Medicare beneficiaries with type II diabetes mellitus SO CIRCULATION LA English DT Meeting Abstract CT 4th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY OCT 13-14, 2002 CL WASHINGTON, D.C. SP Amer Heart Assoc Councils Cardiovasc Dis Young, Cardiovasc Nursing, Cardio Thorac & Vasc Surg, Amer Coll Cardiol Fdn, Dept Vet Affairs C1 NHLBI, Jackson, MS USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 2002 VL 106 IS 16 MA P239 BP E118 EP E118 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 605NH UT WOS:000178683600227 ER PT J AU Beall, B Besser, J Bisno, A Chuang, IL Craig, AS Facklam, R Fetter, J Gerber, MA Gray, G Hill, H Lepine, L Levine, O McGeer, A Moore, M Pearson, M O'Brien, K Schuchat, A Sewell, M Shulman, S Siegel, J Stevens, DL Strausbaugh, L Van Beneden, C AF Beall, B Besser, J Bisno, A Chuang, IL Craig, AS Facklam, R Fetter, J Gerber, MA Gray, G Hill, H Lepine, L Levine, O McGeer, A Moore, M Pearson, M O'Brien, K Schuchat, A Sewell, M Shulman, S Siegel, J Stevens, DL Strausbaugh, L Van Beneden, C CA Prevention Invasive Grp A Streptoc TI Prevention of invasive group A streptococcal disease among household contacts of case patients and among postpartum and postsurgical patients: Recommendations from the Centers for Disease Control and Prevention SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GROUP-A STREPTOCOCCUS; SURGICAL-WOUND INFECTIONS; HEALTH-CARE WORKERS; PHARYNGEAL CARRIAGE; ERADICATE GROUP; PENICILLIN; OUTBREAK; STRAINS; FAMILY; SUSCEPTIBILITY AB The Centers for Disease Control and Prevention hosted a workshop to formulate recommendations for the control of invasive group A streptococcal (GAS) disease among household contacts of persons with invasive GAS infections and for responding to postpartum and postsurgical invasive GAS infections. Experts reviewed data on the risk of subsequent invasive GAS infection among household contacts of case patients, the effectiveness of chemoprophylactic regimens for eradicating GAS carriage, and the epidemiology of postpartum and postsurgical GAS infection clusters. For household contacts of index patients, routine screening for and chemoprophylaxis against GAS are not recommended. Providers and public health officials may choose to offer chemoprophylaxis to household contacts who are at an increased risk of sporadic disease or mortality due to GAS. One nosocomial postpartum or postsurgical invasive GAS infection should prompt enhanced surveillance and isolate storage, whereas greater than or equal to2 cases caused by the same strain should prompt an epidemiological investigation that includes the culture of specimens from epidemiologically linked health care workers. C1 Ctr Dis Control & Prevent, Resp Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Minnesota Dept Hlth, Minneapolis, MN USA. Miami Vet Affairs Med Ctr, Miami, FL USA. Univ Miami, Sch Med, Coral Gables, FL 33124 USA. CDC, Resp Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Tennessee Dept Hlth, Nashville, TN USA. CDC, Resp Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. CDC, Act Bacterial Core Surveillance Program, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Northside Hosp, Atlanta, GA USA. Assoc Profess Infect Control & Epidemiol, Washington, DC 20005 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Amer Acad Pediat, Elk Grove Village, IL 60007 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Emory Univ, Sch Med, Atlanta, GA USA. NIAID, Bethesda, MD 20892 USA. Univ Toronto, Lab Med & Publ Hlth Sci, Toronto, ON, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. CDC, Epidem Intelligence Serv Program, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. CDC, Epidem Intelligence Serv Program, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. CDC, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. New Mexico Dept Hlth, Santa Fe, NM USA. Council State & Terr Epidemiologists, Atlanta, GA 30341 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Boise VA Med Ctr, Boise, ID USA. Univ Washington, Sch Med, Seattle, WA USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Sch Med, Portland, OR USA. Infect Dis Soc Amer, Alexandria, VA 22314 USA. RP Moore, M (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, 1600 Clifton Rd,Mailstop D-63, Atlanta, GA 30333 USA. RI mcgeer, allison /H-7747-2014 OI mcgeer, allison /0000-0001-5647-6137 NR 60 TC 65 Z9 68 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 15 PY 2002 VL 35 IS 8 BP 950 EP 959 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YC UT WOS:000178303800006 ER PT J AU Anaissie, EJ Stratton, SL Dignani, MC Lee, CK Mahfouz, TH Rex, JH Summerbell, RC Walsh, TJ AF Anaissie, EJ Stratton, SL Dignani, MC Lee, CK Mahfouz, TH Rex, JH Summerbell, RC Walsh, TJ TI Cleaning patient shower facilities: A novel approach to reducing patient exposure to aerosolized Aspergillus species and other opportunistic molds SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BONE-MARROW TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; NEUTROPENIC PATIENTS; FUNGAL-INFECTIONS; EPIDEMIOLOGY; PROPHYLAXIS; WATER AB We previously have demonstrated that the hospital water-distribution system could be a reservoir for airborne molds that leads to secondary aerosolization of these molds in patient shower facilities. In this report, we show that cleaning the floors of patient shower facilities in a bone marrow transplantation unit reduced the mean air concentrations of molds, including Aspergillus species (from 12 cfu/m(3) to 4 cfu/m(3); P = .0047 ). C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma & Transplantat Res Ctr, Myeloma Inst Res & Treatment, Little Rock, AR 72205 USA. Univ Texas, Houston Med Sch, Ctr Infect Dis, Houston, TX USA. NCI, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. Cent Bur Schimmelcultures, NL-3740 AG Baarn, Netherlands. RP Anaissie, EJ (reprint author), Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma & Transplantat Res Ctr, Myeloma Inst Res & Treatment, MS 776,4301 W Markham, Little Rock, AR 72205 USA. NR 15 TC 35 Z9 36 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 15 PY 2002 VL 35 IS 8 BP E86 EP E88 DI 10.1086/342305 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YC UT WOS:000178303800021 PM 12355397 ER PT J AU Kingma, DW Imus, P Xie, XY Jasper, G Sorbara, L Stewart, C Stetler-Stevenson, M AF Kingma, DW Imus, P Xie, XY Jasper, G Sorbara, L Stewart, C Stetler-Stevenson, M TI CD2 is expressed by a subpopulation of normal B cells and is frequently present in mature B-Cell neoplasms SO CYTOMETRY LA English DT Article DE CD2; B-cell lymphoma; leukemia; flow cytometry ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FLOW CYTOMETRIC ANALYSIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; ROSETTE RECEPTOR; LYMPHOMAS; COEXPRESSION; CHILDHOOD; ANTIGENS; LIGHT AB Background: CD2 is expressed by T and natural killer (NK) cells and has been reported in T/NK cell lineage neoplasms as well as in immature B-lymphoblastic and myeloid leukemias. Although CD2+ B-cells have been identified in normal fetal and postnatal thymus, they have not been reported in adults. Methods: We retrospectively reviewed flow cytometric immunophenotypic data on consecutive low-grade B-cell leukemias and lymphomas to investigate the frequency of CD2 expression. We also reviewed samples from normal healthy donors to determine whether there is a normal CD2+ B-cell population. Results: CD2 expression (partial or complete) was observed in 13 of 83 (16%) chronic lymphocytic leukemias (CLL), 16 of 29 (55%) follicle center lymphomas (FCL), 3 of 12 (25%) hairy cell leukemias (HCL), 0 of 6 mantle cell lymphomas (MCL), 8 of 28 (29%) large cell lymphomas (LCL), and in 0 of 5 marginal zone/mucosa-associated lymphoid tissue lymphomas (MZL/MALT). We determined that 5.74+/-2.46% (mean+/-SD) of normal peripheral blood B cells and 6.48+/-1.62% (mean+/-SD) of normal bone marrow B cells coexpress CD2. Conclusions: CD2 expression in B-cell neoplasia is a more prevalent phenomenon than previously appreciated. Normal CD2+ B-cell populations are observed in adults and may represent the nonmalignant counterpart of CD2+ B-cell neoplasms. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Flow Cytometry Dept, Buffalo, NY 14263 USA. RP Stetler-Stevenson, M (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2N-108, Bethesda, MD 20892 USA. NR 24 TC 16 Z9 16 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 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 2002 VL 50 IS 5 BP 243 EP 248 DI 10.1002/cyto.10131 PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 603KR UT WOS:000178559000002 PM 12360573 ER PT J AU Imus, PD Sausville, JE Salloum, R Sorbara, L Kingma, DW Raffeld, M Kreitman, R Venzon, D Stetler-Stevenson, M AF Imus, PD Sausville, JE Salloum, R Sorbara, L Kingma, DW Raffeld, M Kreitman, R Venzon, D Stetler-Stevenson, M TI Minimal residual disease detection in hairy cell leukemia: Comparison of flow cytometric immunophenotyping and clonal analysis employing polymerase chain reaction for the heavy chain gene SO CYTOMETRY LA English DT Meeting Abstract C1 NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 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 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 2002 VL 50 IS 5 MA 8 BP 280 EP 280 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 603KR UT WOS:000178559000015 ER PT J AU Gold, B AF Gold, B TI Acknowledgement SO DRUG DISCOVERY TODAY LA English DT Letter C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Gold, B (reprint author), NCI, Lab Genom Divers, Bldg 560,Room 11-85, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD OCT 15 PY 2002 VL 7 IS 20 BP 1035 EP 1035 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 603WJ UT WOS:000178583800006 ER PT J AU Kong, DC DePamphilis, ML AF Kong, DC DePamphilis, ML TI Site-specific ORC binding, pre-replication complex assembly and DNA synthesis at Schizosaccharomyces pombe replication origins SO EMBO JOURNAL LA English DT Article DE ARS3001; cell cycle; DNA replication origin; origin recognition complex; replication initiation point ID YEAST YARROWIA-LIPOLYTICA; FISSION YEAST; RECOGNITION COMPLEX; SACCHAROMYCES-CEREVISIAE; S-PHASE; ADENINE/THYMINE STRETCHES; CELL-CYCLE; PROTEIN; INITIATION; HOMOLOG AB Previous studies have shown that the Schizo-saccharomyces pombe Orc4 subunit is solely responsible for in vitro binding of origin recognition complex (ORC) to specific AT-rich sites within S.pombe replication origins. Using ARS3001, a S.pombe replication origin consisting of four genetically required sites, we show that, in situ as well as in vitro, Orc4 binds strongly to the Delta3 site, weakly to the Delta6 site and not at all to the remaining sequences. In situ, the footprint over Delta3 is extended during G(1) phase, but only when Cdc18 is present and Mcm. proteins are bound to chromatin. Moreover, this footprint extends into the adjacent Delta2 site, where leading strand DNA synthesis begins. Therefore, we conclude that ARS3001 consists of a single primary ORC binding site that assembles a pre-replication complex and initiates DNA synthesis, plus an additional novel origin element (Delta9) that neither binds ORC nor functions as a centromere, but does bind an as yet unidentified protein throughout the cell cycle. Schizosaccharomyces pombe may be an appropriate paradigm for the complex origins found in the metazoa. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP NICHHD, NIH, Bldg 6,Room 416,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kongd@mail.nih.gov; depamphm@mail.nih.gov NR 56 TC 34 Z9 36 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD OCT 15 PY 2002 VL 21 IS 20 BP 5567 EP 5576 DI 10.1093/emboj/cdf546 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 607QK UT WOS:000178802100026 PM 12374757 ER PT J AU Moshkin, YM Armstrong, JA Maeda, RK Tamkun, JW Verrijzer, P Kennison, JA Karch, F AF Moshkin, YM Armstrong, JA Maeda, RK Tamkun, JW Verrijzer, P Kennison, JA Karch, F TI Histone chaperone ASF1 cooperates with the Brahma chromatin-remodelling machinery SO GENES & DEVELOPMENT LA English DT Article DE ASF1; Brahma; SWI/SNF complex; chromatin assembly; chromatin-remodelling ID TRITHORAX GROUP PROTEINS; POSITION-EFFECT VARIEGATION; DROSOPHILA; COMPLEX; POLYCOMB; DOMAIN; GENES; TRANSCRIPTION; ACTIVATION; PROMOTES AB De novo chromatin assembly into regularly spaced nucleosomal arrays is essential for eukaryotic genome maintenance and inheritance. The Anti-Silencing Function 1 protein (ASF1) has been shown to be a histone chaperone, participating in DNA-replication-coupled nucleosome assembly. We show that mutations in the Drosophila asf1 gene derepress silencing at heterochromatin and that the ASF1 protein has a cell cycle-specific nuclear and cytoplasmic localization. Furthermore, using both genetic and biochemical methods, we demonstrate that ASF1 interacts with the Brahma (SWI/SNF) chromatin-remodelling complex. These findings suggest that ASF1 plays a crucial role in both chromatin assembly and SWI/SNF-mediated chromatin remodelling. C1 Univ Geneva, Dept Zool & Anim Behav, CH-1211 Geneva 4, Switzerland. Univ Calif Santa Cruz, Dept Mol Cellular & Dev Biol, Santa Cruz, CA 95064 USA. Leiden Univ, Dept Mol & Cell Biol, Ctr Med Genet, Ctr Biomed Genet,Med Ctr, NL-2300 RA Leiden, Netherlands. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Karch, F (reprint author), Univ Geneva, Dept Zool & Anim Behav, CH-1211 Geneva 4, Switzerland. FU NIGMS NIH HHS [GM49883, R01 GM049883] NR 31 TC 88 Z9 91 U1 0 U2 2 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 15 PY 2002 VL 16 IS 20 BP 2621 EP 2626 DI 10.1101/gad.231202 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 604XE UT WOS:000178645700003 PM 12381660 ER PT J AU Doruker, P Jernigan, RL Navizet, I Hernandez, R AF Doruker, P Jernigan, RL Navizet, I Hernandez, R TI Important fluctuation dynamics of large protein structures are preserved upon coarse-grained renormalization SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Article DE Gaussian network model; anisotropic fluctuations; vibration dynamics; collective motions; hemagglutinin; xanthine dehyrogenase; beta-galactosidase; myosin ID INFLUENZA-VIRUS; HEMAGGLUTININ; RESOLUTION; REFINEMENT; MODEL; S1 AB The fluctuations and important motions of three large proteins-hemaglutinin, xanthine dehydrogenase, and beta-galactosidase-have been considered with a range of models having various levels of detail to represent the structures. Because the slowest modes of motion are the largest contributors to the total motions, and because these motions depend mainly on the shapes of the structures rather than their details, it is possible to replace the real structures with significantly fewer points, and still retain the essential features of the structure for these modes of motion. We obtain excellent results, both for the magnitudes of the individual motions as well as for the molecular changes occurring during these motions. Similar results are obtained with another completely different approach where the coarse graining is based on invariant regions of structure found by comparing two structures of the same protein, given as an example here for myosin. Results confirm the important coupling of local functional motions with the large-scale motions, implying important functional roles for the entire protein structure. (C) 2002 Wiley Periodicals, Inc. C1 NCI, Canc Res Ctr, Lab Expt & Computat Biol, Mol Struct Sect, Bethesda, MD 20892 USA. Bogazici Univ, Dept Chem Engn, TR-80815 Bebek, Istanbul, Turkey. Bogazici Univ, Ctr Polymer Res, TR-80815 Bebek, Istanbul, Turkey. Inst Biol Physicochim, F-75005 Paris, France. Georgia Inst Technol, Sch Chem & Biochem, Ctr Computat Mol Sci & Technol, Atlanta, GA 30332 USA. RP Jernigan, RL (reprint author), NCI, Canc Res Ctr, Lab Expt & Computat Biol, Mol Struct Sect, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Hernandez, Rigoberto/A-8793-2008; Navizet, Isabelle/M-2113-2016 OI Hernandez, Rigoberto/0000-0001-8526-7414; Navizet, Isabelle/0000-0002-2158-6157 NR 23 TC 17 Z9 18 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7608 J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD OCT 15 PY 2002 VL 90 IS 2 BP 822 EP 837 DI 10.1002/qua.955 PG 16 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA 595UE UT WOS:000178126500036 ER PT J AU Pankov, R Yamada, KM AF Pankov, R Yamada, KM TI Fibronectin at a glance SO JOURNAL OF CELL SCIENCE LA English DT Article ID IDENTIFICATION; INTEGRINS; VARIANTS; BINDING C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Pankov, R (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RI Pankov, Roumen/B-3284-2014; OI Pankov, Roumen/0000-0002-3157-3659; Yamada, Kenneth/0000-0003-1512-6805 NR 15 TC 789 Z9 807 U1 11 U2 81 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 15 PY 2002 VL 115 IS 20 BP 3861 EP 3863 DI 10.1242/jcs.00059 PG 3 WC Cell Biology SC Cell Biology GA 614GK UT WOS:000179179800001 PM 12244123 ER PT J AU von Kobbe, C Bohr, VA AF von Kobbe, C Bohr, VA TI A nucleolar targeting sequence in the Werner syndrome protein resides within residues 949-1092 SO JOURNAL OF CELL SCIENCE LA English DT Article DE Werner syndrome; nucleolar targeting sequence; in vivo localization ID NUCLEAR-LOCALIZATION; SYNDROME GENE; DNA HELICASE; TRANSPORT; CELLS; SYSTEM AB Werner syndrome is a premature aging disorder caused by the lack of an active Werner syndrome protein (WRN). The patients suffer from many, of the ailments seen at a much later stage in the life of normal individuals. WRN is a nuclear protein and contains a nuclear localization signal (NLS) in its C-terminal region. Inside the nucleus, WRN is mainly located in the nucleoli and in nuclear foci. To begin to understand the role of WRN in the nucleolus, we determined the specific regions of the protein that are responsible for this localization. We have cloned different WRN gene domains fused to enhanced green fluorescent protein (EGFP), and analyzed their intracellular distribution in living cells using confocal microscopy. The 3901 region encompassing amino acids 949-1092 of the human WRN, together with the NLS containing amino acids 1358-1432, provides the targeting to the nucleoli. This targeting is observed in three human and one mouse cell line. The NLS-containing region alone is unable to direct EGFP to the nucleoli. The results demonstrate that the human WRN contains a conserved nucleolar targeting sequence residing in a 144 amino acid region (aa 949-1092) and this provides new tools and insight into the biological function of WRN. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 20 TC 56 Z9 57 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 15 PY 2002 VL 115 IS 20 BP 3901 EP 3907 DI 10.1242/jcs.00076 PG 7 WC Cell Biology SC Cell Biology GA 614GK UT WOS:000179179800006 PM 12244128 ER PT J AU Fisher, B Bryant, J Dignam, JJ Wickerham, DL Mamounas, EP Fisher, ER Margolese, RG Nesbitt, L Paik, S Pisansky, TM Wolmark, N AF Fisher, B Bryant, J Dignam, JJ Wickerham, DL Mamounas, EP Fisher, ER Margolese, RG Nesbitt, L Paik, S Pisansky, TM Wolmark, N CA Natl Surg Adjuvant Breast Bowel TI Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL-ADJUVANT-BREAST; RANDOMIZED CLINICAL-TRIAL; RECEPTOR-POSITIVE TUMORS; CARCINOMA IN-SITU; LOCAL RECURRENCE; CONSERVATION THERAPY; RISK-FACTORS; AXILLARY DISSECTION; LYMPH-NODES; RADIOTHERAPY AB Purpose : This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of :5 1 cm, by speculation that tamoxifen (TAM) might be as or more effective than radiation therapy (XRT) in reducing the rate of ipsilateral breast tumor recurrence (IBTR) in such women, and by the thesis that both modalities might be more effective than either alone. Patients and Methods: After lumpectomy, 1,009 women were randomly assigned to TAM (n = 336), XRT and placebo (n = 336), or XRT and TAM (n = 337). Rates of IBTR, distant recurrence, and contralateral breast cancer (CBC) were among the end points for analysis. Cumulative incidence of IBTR and of CBC was computed accounting for competing risks. Results with two-sided P values of .05 or less were statistically significant. Results: XRT and placebo resulted in a 49% lower hazard rate of IBTR than did TAM alone, XRT and TAM resulted in a 63% lower rate than did XRT and placebo. When compared with TAM alone, XRT plus TAM resulted in an 81% reduction in hazard rate of lBTR. Cumulative incidence of IBTR through 8 years was 16.5% with TAM, 9.3% with XRT and placebo, and 2.8% with XRT and TAM. XRT reduced IBTR below the level achieved with TAM alone, regardless of estrogen receptor (ER) status. Distant treatment failures were infrequent and not significantly different among the groups (P =.28). When TAM-treated women were compared with those who received XRT and placebo, there was a significant reduction in CBC (hazard ratio, 0.45; 95% confidence interval, 0.21 to 0.95; P =.039). Survival in the three groups was 93%, 94%, and 93%, respectively (P =.93). Conclusion: In women with tumors less than or equal to 1 cm, IBTR occurs with enough frequency after lumpectomy to justify considering XRT, regardless of tumor ER status, and TAM plus XRT when tumors are ER positive. C1 Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Div Pathol, Pittsburgh, PA USA. Breast Comm, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Aultman Hosp, Ctr Canc, Canton, OH USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. Mayo Clin, Div Radiat Oncol, Rochester, MN USA. RP Fisher, B (reprint author), NSABP, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-12027, U10-CA-37377, U10-CA-69651] NR 43 TC 317 Z9 325 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2002 VL 20 IS 20 BP 4141 EP 4149 DI 10.1200/JCO.2002.11.101 PG 9 WC Oncology SC Oncology GA 604CG UT WOS:000178597600003 PM 12377957 ER PT J AU Gonzales, NR Schuck, P Schlom, J Kashmiri, SVS AF Gonzales, NR Schuck, P Schlom, J Kashmiri, SVS TI Surface plasmon resonance-based competition assay to assess the sera reactivity of variants of humanized antibodies SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE humanized antibody; monoclonal antibody; immunogenicity; sera reactivity; surface plasmon resonance; CC49 ID BIOSPECIFIC INTERACTION ANALYSIS; SPECIFICITY-DETERMINING RESIDUES; MONOCLONAL-ANTIBODY; ANTICARCINOMA ANTIBODY; ANTIGEN-BINDING; PHASE-II; CC49; CANCER; PHARMACOKINETICS; IMMUNOGENICITY AB While clinical trials are the only way to evaluate the immunogenicity, in patients, of murine or genetically engineered humanized variants of a potentially therapeutic or diagnostic monoclonal antibody (MAb), ethical and logistical considerations of clinical trials do not permit the evaluation of variants of a given MAb that are generated to minimize its immunogenicity. The most promising variant could be identified by comparing the reactivities of the parental antibody (Ab) and its variants to the sera of patients containing anti-variable region (anti-VR) Abs to the administered parental Ab. We have developed a surface plasmon resonance (SPR) biosensor-based assay to monitor the binding of the sera anti-VR Abs to the parental Ab and the inhibition of this binding by the variants. SPR biosensors allow the real-time detection and monitoring of the binding between an immobilized protein and its soluble ligand without the need for prior purification and labeling of the mobile analyte. This new assay requires no radiolabeling, is relatively less time-consuming, and uses only small amounts of serum (5-20 mul of diluted serum) through a new microfluidic sample handling technique. To validate the assay, we have tested the relative reactivities of the CDR-grafted anti-carcinoma Ab, HuCC49, and its two variants, designated V5 and V10, to the sera of patients who were earlier administered radiolabeled murine CC49 in a clinical trial. A comparison of IC(50)s (the concentrations of the competitor Abs required for 50% inhibition of the binding of sera to immobilized HuCC49) showed that V5 and V10 were less reactive than HuCC49 to the three patients' sera tested. We have also demonstrated, for the first time, the specific detection and comparison of relative amounts of anti-VR Abs present in the sera of different patients without prior removal of anti-murine Fc Abs and/or circulating antigen. This may facilitate the rapid screening, for the presence of anti-VR Abs, of the sera of patients undergoing clinical trials. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. ORS, OD, Div Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Ctr Canc Res, Lab Tumor Immunol & Biol, NIH, 10 Ctr Dr,Rm 8B09, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 38 TC 28 Z9 29 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD OCT 15 PY 2002 VL 268 IS 2 BP 197 EP 210 AR PII S0022-1759(02)00205-3 DI 10.1016/S0022-1759(02)00205-3 PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 597VL UT WOS:000178241400009 PM 12215388 ER PT J AU Tkaczyk, C Metcalfe, DD Gilfillan, AM AF Tkaczyk, C Metcalfe, DD Gilfillan, AM TI Determination of protein phosphorylation in Fc epsilon RI-activated human mast cells by immunoblot analysis requires protein extraction under denaturing conditions SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE human mast cells; Fc epsilon RI; immunoblot analysis; protein phosphorylation; signal transduction AB The advent of activation state antibodies has greatly facilitated studies aimed at understanding the intracellular signaling cascade following occupancy and/or aggregation of surface receptors. As part of an ongoing study investigating the signal transduction cascade initiated following aggregation of the high affinity receptor for IgE (FcepsilonRI) in human mast cells, we observed substantial differences in responses monitored by these antibodies when cells were extracted either under nonreducing or reducing conditions. This was true even in the presence of high concentrations of protease inhibitors. Although the activation of some proteins such as those of the MAP kinase pathway appeared to be unaffected by the extraction conditions, other signals, including overall tyrosine phosphorylation and activation of phospholipase Cgamma(1), were substantially different. This was due to the significant proteolysis in samples extracted under nondenaturing conditions. When the signaling proteins were extracted rapidly under denaturing conditions, however, there was little evidence of proteolysis of the signaling proteins with a resulting improved recovery of signal. Thus, accurate determination of signaling events utilizing activation state-specific antibodies in human mast cells requires protein extraction under denaturing conditions. The data presented in this report would be applicable to other cell types where high concentrations of proteases are present. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C213,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 6 TC 38 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD OCT 15 PY 2002 VL 268 IS 2 BP 239 EP 243 AR PII S0022-1759(02)00210-7 DI 10.1016/S0022-1759(02)00210-7 PG 5 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 597VL UT WOS:000178241400013 PM 12215392 ER PT J AU Nishikomori, R Usui, T Wu, CY Morinobu, A O'Shea, JJ Strober, W AF Nishikomori, R Usui, T Wu, CY Morinobu, A O'Shea, JJ Strober, W TI Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA PRODUCTION; T-CELLS; IL-12 RECEPTOR; SERINE PHOSPHORYLATION; GENE-EXPRESSION; MICE; REQUIREMENT; RESPONSES; PROTEINS; BINDING AB In this study we demonstrated that CD4(+) T cells from STAT4(-/-) mice exhibit reduced IL-12R expression and poor IL-12R signaling function. This raised the question of whether activated STAT4 participates in Th1 cell development mainly through its effects on IL-12 signaling. In a first approach to this question we determined the capacity of CD4(+) T cells from STAT4(-/-) bearing an IL-12Rbeta2 chain transgene (and thus capable of normal IL-12R expression and signaling) to undergo Th1 differentiation when stimulated by Con A and APCs. We found that such cells were still unable to exhibit IL-12-mediated IFN-gamma production. In a second approach to this question, we created Th2 cell lines (D10 cells) transfected with STAT4-expressing plasmids with various tyrosine-phenylalanine mutations and CD4(+) T cell lines from IL-12beta2(-/-) mice infected with retroviruses expressing similarly STAT4 mutations that nevertheless express surface IL-12Rbeta2 chains. We then showed that constructs that were unable to support STAT4 tyrosine phosphorylation (in D10 cells) as a result of mutation were also incapable of supporting IL-12-induced IFN-gamma production (in IL-12Rbeta2(-/-) cells). Thus, by two complementary approaches we demonstrated that activated STAT4 has an essential downstream role in Th1 cell differentiation that is independent of its role in the support of IL-12Rbeta2 chain signaling. This implies that STAT4 is an essential element in the early events of Th1 differentiation. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Lymphocyte Cell Biol Sect, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 94 Z9 96 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 2002 VL 169 IS 8 BP 4388 EP 4398 PG 11 WC Immunology SC Immunology GA 602NU UT WOS:000178512000042 PM 12370372 ER PT J AU Wigginton, JM Lee, JK Wiltrout, TA Alvord, WG Hixon, JA Subleski, J Back, TC Wiltrout, RH AF Wigginton, JM Lee, JK Wiltrout, TA Alvord, WG Hixon, JA Subleski, J Back, TC Wiltrout, RH TI Synergistic engagement of an ineffective endogenous anti-tumor immune response and induction of IFN-gamma and Fas-ligand-dependent tumor eradication by combined administration of IL-18 and IL-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; INTERLEUKIN-18 IL-18; IN-VIVO; ANTITUMOR; CYTOKINE; CYTOTOXICITY; INHIBITION; ACTIVATION; EXPRESSION; CARCINOMA AB IFN-gamma is a critical component of the endogenous and many cytokine-induced antitumor immune responses. In this study we have shown that the combination of IL-18 and IL-2 (IL-18/IL-2) synergistically enhances IFN-gamma production both in vitro and in vivo, and synergizes in vivo to induce complete durable regression of well-established 3LL tumors in > 80% of treated mice. We have observed a nascent, but ineffective, host immune response against 3LL that depends on endogenous IFN-gamma and IL-12 production and the Fas/Fas ligand (Fas-L) pathway. The combined administration of IL-18/IL-2 engages this endogenous response to induce tumor regression via a mechanism that is independent of NK and NKT cells or IL-12, but is critically dependent on CD8(+) T cells, IFN-gamma, and the Fas/Fas-L pathway. These studies demonstrate the importance of IFN-gamma as well as the Fas/Fas-L pathway in both endogenous and cytokine-driven antitumor immune responses engaged by IL-18/IL-2 and provide preclinical impetus for clinical investigation of this potent anti-tumor combination. C1 Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Data Management Serv, Canc Res Ctr, Bethesda, MD 20892 USA. RP Wigginton, JM (reprint author), NCI, Pediat Oncol Branch, Bldg 560,Room 31-93, Frederick, MD 21702 USA. FU NCI NIH HHS [N01 CO 12400] NR 28 TC 50 Z9 55 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2002 VL 169 IS 8 BP 4467 EP 4474 PG 8 WC Immunology SC Immunology GA 602NU UT WOS:000178512000052 PM 12370382 ER PT J AU Schiffman, M Wheeler, CM Castle, PE AF Schiffman, M Wheeler, CM Castle, PE CA Atypical Squamous Cells Undetermin TI Human papillomavirus DNA remains detectable longer than related cervical cytologic abnormalities SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIGH-RISK; INFECTION; WOMEN; NEOPLASIA; LESIONS; TRIAL AB Cervical human papillomavirus (HPV) infections are at high risk of neoplastic progression if they persist. Persistence can be measured by repeated HPV DNA tests or by cytologic testing. Thus, it is useful to understand the relationship between these 2 measurements. To explore the relative timing of HPV DNA clearance versus cytologic regression, data were analyzed from 840 study participants who were followed-up by repeat thin-layer cytology and HPV testing by a hybrid capture test at 6-month intervals for 2 years. On average, HPV DNA detection persisted longer than related cytologic abnormalities (P < .001). HPV type-specific data from a subset of 448 women with complete polymerase chain reaction test data confirmed that HPV DNA persisted longer than cytologic abnormalities (P < .001). It appears that the natural history of HPV typically includes periods before and after cytologic abnormality, in which HPV DNA is the more sensitive indicator of infection. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 7066,EPS MSC 7234, Bethesda, MD 20892 USA. FU NCI NIH HHS [CN-55154, CN-55156, CN-55153, CN-55159, CN-55158, CN-55157, CN-55105, CN-55155] NR 16 TC 31 Z9 32 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2002 VL 186 IS 8 BP 1169 EP 1172 DI 10.1086/343816 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YK UT WOS:000178304800017 PM 12355370 ER PT J AU Patke, DS Langan, SJ Carruth, LM Keating, SM Sabundayo, BP Margolick, JB Quinn, TC Bollinger, RC AF Patke, DS Langan, SJ Carruth, LM Keating, SM Sabundayo, BP Margolick, JB Quinn, TC Bollinger, RC TI Association of Gag-specific T lymphocyte responses during the early phase of human immunodeficiency virus type 1 infection and lower virus load set point SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTION; VIRAL LOAD; CELL RESPONSES; SEROCONVERSION; VIREMIA; CD4(+) AB T lymphocyte responses to human immunodeficiency virus (HIV) type 1 Gag were measured in 9 patients by interferon-gamma enzyme-linked immunospot assay at 3 time points within 12 months of infection. Patients with early recognition of HIV-1 Gag had lower subsequent HIV-1 load set points, as measured during the first 2 years of infection, compared with those of patients with undetectable Gag-specific responses (median, 4.27 vs. 5.05 log(10) HIV-1 RNA copies/mL, respectively; P = .028). An inverse correlation existed between the magnitude of the Gag-specific responses and the HIV-1 load set point (r = -0.733; P = .025). Early sustained T lymphocyte responses to HIV-1 Gag may be important for the establishment of virus load set point. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Bollinger, RC (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, Ross 1150,720 Rutland Ave, Baltimore, MD 21205 USA. RI Keating, Sheila/B-1652-2013; OI Keating, Sheila/0000-0002-8324-3694 FU FIC NIH HHS [D43 TW 00000]; NIAID NIH HHS [AI 41532] NR 13 TC 24 Z9 24 U1 0 U2 1 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 2002 VL 186 IS 8 BP 1177 EP 1180 DI 10.1086/343811 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YK UT WOS:000178304800019 PM 12355372 ER PT J AU Cabin, DE Shimazu, K Murphy, D Cole, NB Gottschalk, W McIlwain, KL Orrison, B Chen, A Ellis, CE Paylor, R Lu, B Nussbaum, RL AF Cabin, DE Shimazu, K Murphy, D Cole, NB Gottschalk, W McIlwain, KL Orrison, B Chen, A Ellis, CE Paylor, R Lu, B Nussbaum, RL TI Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein SO JOURNAL OF NEUROSCIENCE LA English DT Article DE alpha-synuclein; genetically engineered mice; docked synaptic vesicles; reserve pool; readily releasable pool; hippocampus; amphetamine sensitivity ID I-DEFICIENT MICE; PARKINSONS-DISEASE; SYNAPSIN-I; NEUROTRANSMITTER RELEASE; HIPPOCAMPAL SYNAPSES; EXCITATORY SYNAPSES; LEWY BODIES; BINDING; IDENTIFICATION; PLASTICITY AB Although the mutation of alpha-synuclein, a protein associated with presynaptic vesicles, is implicated in the etiology and pathogenesis of Parkinson's disease, the biological function of the normal protein is unknown. Mice that lack alpha-synuclein have been generated by homologous recombination in embryonic stem cells. Electron microscopic examination of hippocampal synapses revealed a striking selective deficiency of undocked vesicles without affecting docked vesicles. Field recording of CA1 synapses in hippocampal slices from the mutant mice demonstrated normal basal synaptic transmission, paired-pulse facilitation, and response to a brief train of high-frequency stimulation (100 Hz, 40 pulses) that exhausts only docked vesicles. In contrast, the alpha-synuclein knock-out mice exhibited significant impairments in synaptic response to a prolonged train of repetitive stimulation (12.5 Hz, 300 pulses) capable of depleting docked as well as reserve pool vesicles. Moreover, the replenishment of the docked vesicles by reserve pool vesicles after depletion was slower in the mutant synapses. Thus, alpha-synuclein may be required for the genesis and/or maintenance of a subset of presynaptic vesicles, those in the "reserve" or "resting" pools. These results reveal, for the first time, the normal function of endogenous alpha-synuclein in regulating synaptic vesicle mobilization at nerve terminals. C1 NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. NHGRI, Neurodegenerat Cluster, Bethesda, MD 20892 USA. NICHHD, Unit Synapse Dev & Plast, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol Genet, Houston, TX 77030 USA. Primal Inc, Seattle, WA 98104 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, 49-4A72,49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012 NR 45 TC 473 Z9 484 U1 3 U2 26 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 2002 VL 22 IS 20 BP 8797 EP 8807 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 605PQ UT WOS:000178686600004 PM 12388586 ER PT J AU Prybylowski, K Fu, ZY Losi, G Hawkins, LM Luo, JH Chang, K Wenthold, RJ Vicini, S AF Prybylowski, K Fu, ZY Losi, G Hawkins, LM Luo, JH Chang, K Wenthold, RJ Vicini, S TI Relationship between availability of NMDA receptor subunits and their expression at the synapse SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cerebellar granule cells; ifenprodil sensitivity; NMDA-mEPSCs; peak open probability; PDZ binding domain; receptor targeting ID D-ASPARTATE RECEPTOR; CEREBELLAR GRANULE NEURONS; RAT CORTICAL-NEURONS; ER RETENTION SIGNAL; PROTEIN-KINASE-C; POSTSYNAPTIC MEMBRANE; BIOCHEMICAL-EVIDENCE; GLUTAMATE RECEPTORS; AMPA RECEPTORS; NR2B SUBUNIT AB The effect of increasing the expression of NMDA subunits in cerebellar granule cells (CGCs) by transfection was studied to determine how the availability of various NMDA subunits controls both the total pool of functional receptors and the synaptic pool. Overexpression of either NR2A or NR2B, but not splice variants of NR1, by transfection caused a significant increase in the total number of functional NMDA receptors and in surface NR1 subunit cluster density in CGCs in primary culture. These data solidify the central role of NR2 subunit availability in determining the number of cell surface receptors. Overexpression of either NR2A or NR2B significantly altered the deactivation kinetics of NMDA-mediated miniature EPSCs (NMDA-mEPSCs). However, there was no significant effect of NR2 subunit overexpression on the mEPSC amplitude or single-channel conductance. NR2 subunit overexpression did not change the rate of block by MK-801 of NMDA-mediated currents in excised patches from CGCs, indicating that subunit composition does not regulate peak open probability of the channel in CGCs. With the overexpression of a mutant of NR2B lacking the PDZ binding domain, there was an increase in the total number of NMDA receptors without a change in mEPSC kinetics. Therefore, the entry of NMDA receptors into the synapse requires a PDZ binding domain and is limited by means other than receptor subunit availability. C1 Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA. RP Prybylowski, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bldg 50,Room 4140, Bethesda, MD 20892 USA. OI Losi, Gabriele/0000-0001-7796-9299; LOSI, GABRIELE/0000-0002-4931-6167 FU NIMH NIH HHS [MH01680, MH58946] NR 46 TC 103 Z9 109 U1 1 U2 3 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 2002 VL 22 IS 20 BP 8902 EP 8910 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 605PQ UT WOS:000178686600015 PM 12388597 ER PT J AU Moore, JP Shang, E Wray, S AF Moore, JP Shang, E Wray, S TI In situ GABAergic modulation of synchronous gonadotropin releasing hormone-1 neuronal activity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE LHRH; GnRH; GABA; explant culture; development; synchronous pulses; calcium oscillations ID EMBRYONIC OLFACTORY PLACODE; LHRH NEURONS; RHESUS-MONKEY; HYPOTHALAMIC NEURONS; CORTICAL-NEURONS; EXPLANT CULTURES; GABA; BRAIN; RATS; EXPRESSION AB Evidence indicates that gonadotropin releasing hormone-1 [GnRH-1, also known as luteinizing hormone releasing hormone (LHRH)] neurons can exhibit synchronized neuroendocrine secretory activity before entrance into the CNS. In this study, we used calcium imaging to evaluate patterns of activity in individual, embryonic, GnRH-1 neurons as well as population dynamics of GnRH-1 neurons in mouse nasal explants maintained for 1 versus 3 weeks. Independent of age, GnRH-1 neurons displayed significant calcium peaks that synchronized at an interval of similar to20 min across multiple GnRH-1 cells within an explant. Acute tetrodotoxin treatment decreased the amplitude of calcium peaks in individual GnRH-1 neurons and the duration but not the frequency of synchronized activity in the population of GnRH-1 neurons. Acute GABA(B) receptor antagonism increased the frequency of synchronized neuronal activity at both ages, whereas acute GABA(A) receptor antagonism decreased calcium oscillations in individual GNRH-1 cells as well as synchronization of the calcium pulses within the GnRH-1 population at the 1 week time point to background non-GNRH-1 cell levels. These results indicate that developing GnRH-1 neurons rely heavily on GABAergic signaling to initiate synchronized bouts of activity but thereafter, possess an innate capacity for synchronized activity patterns that are modulated by, but not completely dependent on GABAergic signaling. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 36,Room 5A-21, Bethesda, MD 20895 USA. OI wray, susan/0000-0001-7670-3915 NR 39 TC 41 Z9 41 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 2002 VL 22 IS 20 BP 8932 EP 8941 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 605PQ UT WOS:000178686600018 PM 12388600 ER PT J AU Tessitore, A Hariri, AR Fera, F Smith, WG Chase, TN Hyde, TM Weinberger, DR Mattay, VS AF Tessitore, A Hariri, AR Fera, F Smith, WG Chase, TN Hyde, TM Weinberger, DR Mattay, VS TI Dopamine modulates the response of the human amygdala: A study in Parkinson's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Parkinson's disease; dopamine; amygdala; modulating emotions; BOLD fMRI; depression ID BASOLATERAL AMYGDALA; PERCEPTION; DISORDERS; EMOTION; EXPRESSION; CIRCUITRY; BINDING AB In addition to classic motor signs and symptoms, Parkinson's disease (PD) is characterized by neuropsychological and emotional deficits, including a blunted emotional response. In the present study, we explored both the neural basis of abnormal emotional behavior in PD and the physiological effects of dopaminergic therapy on the response of the amygdala, a central structure in emotion processing. PD patients and matched normal controls (NCs) were studied with blood oxygenation level-dependent functional magnetic resonance imaging during a paradigm that involved perceptual processing of fearful stimuli. PD patients were studied twice, once during a relatively hypodopaminergic state (i.e., greater than or equal to12 hr after their last dose of dopamimetic treatment) and again during a dopamine-replete state. The imaging data revealed a robust bilateral amygdala response in NCs that was absent in PD patients during the hypodopaminergic state. Dopamine repletion partially restored this response in PD patients. Our results demonstrate an abnormal amygdala response in PD that may underlie the emotional deficits accompanying the disease. Furthermore, consistent with findings in experimental animal paradigms, our results provide in vivo evidence of the role of dopamine in modulating the response of the amygdala to sensory information in human subjects. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mattay, VS (reprint author), NIMH, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,Room 3C108, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 40 TC 170 Z9 174 U1 0 U2 15 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 2002 VL 22 IS 20 BP 9099 EP 9103 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 605PQ UT WOS:000178686600035 PM 12388617 ER PT J AU Proescholdt, MG Quigley, L Martin, R Herkenham, M AF Proescholdt, MG Quigley, L Martin, R Herkenham, M TI Immunization with a cannabinoid receptor type 1 peptide results in experimental allergic meningocerebellitis in the Lewis rat: A model for cell-mediated autoimmune neuropathology SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE T lymphocytes; autoimmunity; EAE/MS; MHC; neuroimmunology ID PARANEOPLASTIC CEREBELLAR DEGENERATION; MYELIN BASIC-PROTEIN; PROGRESSIVE MULTIPLE-SCLEROSIS; RECOMBINANT YO PROTEIN; CENTRAL-NERVOUS-SYSTEM; LA-TOURETTE-SYNDROME; ANTI-HU ANTIBODY; NEUROPSYCHIATRIC DISORDERS; DENDRITIC CELLS; T-CELLS AB Neuronal elements are increasingly suggested as primary targets of an autoimmune attack in certain neurological and neuropsychiatric diseases. Type 1 cannabinoid receptors (CB1) were selected as autoimmune targets because they are predominantly expressed on neuronal surfaces in brain and display strikingly high protein levels in striatum, hippocampus, and cerebellum. Female Lewis rats were immunized with N-terminally acetylated peptides (50 or 400 mug per rat) of the extracellular domains of the rat CB1 and killed at various time points. Subsequent evaluation using immunohistochemistry and in situ hybridization showed dense infiltration of immune cells exclusively within the cerebellum, peaking 12-16 days after immunization with the CB1 peptide containing amino acids 9-25. The infiltrates clustered in meninges and perivascular locations in molecular and granular cell layers and were also scattered throughout the CB1-rich neuropil. They consisted primarily of CD4(+) and ED1(+) cells, suggestive of cell-mediated autoimmune pathology. There were no inflammatory infiltrates elsewhere in the brain or spinal cord. The results show that neuronal elements, such as neuronal cell-surface receptors, may be recognized as antigenic targets in a cell-mediated autoimmune attack and, therefore, support the hypothesis of cell-mediated antineuronal autoimmune pathology in certain brain disorders. Published 2002 Wiley-Liss, Inc.(dagger) C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Rm 2D15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 79 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 15 PY 2002 VL 70 IS 2 BP 150 EP 160 DI 10.1002/jnr.10424 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 600NG UT WOS:000178396700003 PM 12271464 ER PT J AU Wang, E Struble, E Liu, P Cheung, AP AF Wang, E Struble, E Liu, P Cheung, AP TI A new sensitive HPLC assay for methoxyamine and its analogs SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article; Proceedings Paper CT 12th International Symposium on Pharmaceutical and Biomedical Analysis CY MAY 13-16, 2001 CL MONTEREY, CALIFORNIA DE methoxyamine (MOA); analogs; HPLC assay; development; validation; UV detection; OPA-oxime ID ELECTROCHEMICAL DETECTION; LIQUID-CHROMATOGRAPHY; HYDROXYLAMINE; AMINES; BASE; ELECTROPHORESIS; ELECTRODE AB Methoxyamine (MOA) and its analogs are polymerization regulators, building blocks and intermediates for agrichemicals and pharmaceuticals. MOA induces mutagenesis of nucleic acids and has been considered for anti-cancer and anti-virus therapy. It has been studied as a DNA repair modifier in anti-cancer therapy. HPLC procedures available in the literature for MOA are all based on electrochemical detection, which is not commonly available. This paper describes the development and validation of a HPLC assay with UV detection for MOA and its analogs. The analytes are first reacted with o-phthalaldehyde to form an oxime derivative before chromatography with an ODS column. Detection is achieved by UV at 254 nm. The chromatography resolves MOA from its decomposition products and analogs. The assay is reproducible (R.S.D. < 0.8%), linear (r(2) = 0.9997), and accurate (error < 1%). The method is sensitive and has a lower detection limit of 5 pmol (0.4 ng of MOA.HCl), which is comparable to that of electrochemical detection. (C) 2002 Elsevier Science B.V. All rights reserved. C1 SRI Int, Menlo Pk, CA 94025 USA. NCI, Pharmaceut Resources Branch, DCTD, Bethesda, MD 20892 USA. RP Cheung, AP (reprint author), SRI Int, 333 Ravenswood Ave, Menlo Pk, CA 94025 USA. FU NCI NIH HHS [N01-CM-77104] NR 29 TC 6 Z9 7 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD OCT 15 PY 2002 VL 30 IS 3 BP 415 EP 427 AR PII S0731-7085(01)00557-X DI 10.1016/S0731-7085(01)00557-X PG 13 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 608BZ UT WOS:000178826400004 PM 12367666 ER PT J AU Minagar, A Shapshak, P Fujimura, R Ownby, R Heyes, M Eisdorfer, C AF Minagar, A Shapshak, P Fujimura, R Ownby, R Heyes, M Eisdorfer, C TI The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Review DE macrophage/microglia; astrocytes; HIV-associated dementia; Alzheimer disease; multiple sclerosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; POLYMERASE-CHAIN-REACTION; PROTEIN-KINASE-C; NF-KAPPA-B; SIGNAL-TRANSDUCTION PATHWAYS; IMMUNE-DEFICIENCY-SYNDROME; MESSENGER-RNA EXPRESSION AB Macrophage/microglia (M empty set) are the principal immune cells in the central nervous system (CNS) concomitant with inflammatory brain disease and play a significant role in the host defense against invading microorganisms. Astrocytes, as a significant component of the blood-brain barrier, behave as one of the immune effecter cells in the CNS as well. However, both cell types may play a dual role, amplifying the effects of inflammation and mediating cellular damage as well as protecting the CNS. Interactions of the immune system, M empty set, and astrocytes result in altered production of neurotoxins and neurotrophins by these cells. These effects alter the neuronal structure and function during pathogenesis of HIV-1-associated dementia (HAD), Alzheimer disease (AD), and multiple sclerosis (MS). HAD primarily involves subcortical gray matter, and both HAD and MS affect sub-cortical white matter. AD is a cortical disease. The process of M empty set and astrocytes activation leading to neurotoxicity share similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1-infected M empty set are involved in the pathogenesis of HAD and produce toxic molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M empty set s produce these molecules and are activated by beta-amyloid proteins and related oligopeptides. Demyelination in MS involves M empty set that become lipid laden, spurred by several possible antigens. In these three diseases, cytokine/chemokine communications between M empty set and astrocytes occur and are involved in the balance of protective and destructive actions by these cells. This review describes the role of M empty set and astrocytes in the pathogenesis of these three progressive neurological diseases, examining both beneficent and deleterious effects in each disease. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Louisiana State Univ, Sch Med, Dept Neurol, Shreveport, LA 71130 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33136 USA. Univ Miami, Sch Med, Comprehens Drug Res Ctr, Miami, FL 33136 USA. NIMH, Dept Neuropharmacol, NIH, Bethesda, MD 20014 USA. RP Minagar, A (reprint author), Louisiana State Univ, Sch Med, Dept Neurol, Shreveport, LA 71130 USA. EM aminag@lsuhsc.edu FU NIA NIH HHS [AG 19952]; NIDA NIH HHS [DA 04787, DA 07909, DA 12580, DA 14533]; NINDS NIH HHS [NS 31488, NS 39177, NS 41205] NR 146 TC 339 Z9 357 U1 1 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2002 VL 202 IS 1-2 BP 13 EP 23 AR PII S0022-510X(02)00207-1 DI 10.1016/S0022-510X(02)00207-1 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 598BH UT WOS:000178254900003 PM 12220687 ER PT J AU Kadyrov, FA Drake, JW AF Kadyrov, FA Drake, JW TI Characterization of DNA synthesis catalyzed by bacteriophage T4 replication complexes reconstituted on synthetic circular substrates SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LAGGING-STRAND DNA; LEADING-STRAND; RNA-POLYMERASE; HELICASE; FORK; PROTEINS; RECOMBINATION; MECHANISMS; HOLOENZYME; REMOVES AB Replication complexes were reconstituted using the eight purified bacteriophage T4 replication proteins and synthetic circular 70-, 120- or 240-nt DNA substrates annealed to a leading-strand primer. To differentiate leading strands from lagging strands, the circular parts of the substrates lacked dCMP; thus, no dCTP was required for leading-strand synthesis and no dGTP for lagging-strand synthesis. The size of the substrates was crucial, the longer substrates supporting much more DNA synthesis. Leading and lagging strands were synthesized in a coupled manner. Specifically targeting leading-strand synthesis by decreasing the concentration of dGTP decreased the rate of extension of leading strands. However, blocking lagging-strand synthesis by lowering the dCTP concentration, by omitting dCTP altogether, by adding ddCTP, or with a single abasic site had no immediate effect on the rate of extension of leading strands. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Kadyrov, FA (reprint author), NIEHS, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 35 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 15 PY 2002 VL 30 IS 20 BP 4387 EP 4397 DI 10.1093/nar/gkf576 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 608CC UT WOS:000178826700016 PM 12384585 ER PT J AU Chumakov, I Blumenfeld, M Guerassimenko, O Cavarec, L Palicio, M Abderrahim, H Bougueleret, L Barry, C Tanaka, H La Rosa, P Puech, A Tahri, N Cohen-Akenine, A Delabrosse, S Lissarrague, S Picard, FP Maurice, K Essioux, L Millasseau, P Grel, P Debailleul, V Simon, AM Caterina, D Dufaure, I Malekzadeh, K Belova, M Luan, JJ Bouillot, M Sambucy, JL Primas, G Saumier, M Boubkiri, N Martin-Saumier, S Nasroune, M Peixoto, H Delaye, A Pinchot, V Bastucci, M Guillou, S Chevillon, M Sainz-Fuertes, R Meguenni, S Aurich-Costa, J Cherif, D Gimalac, A Van Duijn, C Gauvreau, D Quelette, G Fortier, I Realson, J Sherbatich, T Riazanskaia, N Rogaev, E Raeymaekers, P Aerssens, J Konings, F Luyten, W Macciardi, F Sham, PC Straub, RE Weinberger, DR Cohen, N Cohen, D AF Chumakov, I Blumenfeld, M Guerassimenko, O Cavarec, L Palicio, M Abderrahim, H Bougueleret, L Barry, C Tanaka, H La Rosa, P Puech, A Tahri, N Cohen-Akenine, A Delabrosse, S Lissarrague, S Picard, FP Maurice, K Essioux, L Millasseau, P Grel, P Debailleul, V Simon, AM Caterina, D Dufaure, I Malekzadeh, K Belova, M Luan, JJ Bouillot, M Sambucy, JL Primas, G Saumier, M Boubkiri, N Martin-Saumier, S Nasroune, M Peixoto, H Delaye, A Pinchot, V Bastucci, M Guillou, S Chevillon, M Sainz-Fuertes, R Meguenni, S Aurich-Costa, J Cherif, D Gimalac, A Van Duijn, C Gauvreau, D Quelette, G Fortier, I Realson, J Sherbatich, T Riazanskaia, N Rogaev, E Raeymaekers, P Aerssens, J Konings, F Luyten, W Macciardi, F Sham, PC Straub, RE Weinberger, DR Cohen, N Cohen, D TI Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN GENOME; HAPLOTYPE FREQUENCIES; SUSCEPTIBILITY GENES; RECEPTOR EXPRESSION; NATURAL-HISTORY; POPULATION; LINKAGE; SEARCH; SEQUENCE AB A map of 191 single-nucleotide polymorphism (SNPs) was built across a 5-Mb segment from chromosome 13q34 that has been genetically linked to schizophrenia. DNA from 213 schizophrenic patients and 241 normal individuals from Canada were genotyped with this marker set. Two 1,400- and 65-kb regions contained markers associated with the disease. Two markers from the 65-kb region were also found to be associated to schizophrenia in a Russian sample. Two overlapping genes G72 and G30 transcribed in brain were experimentally annotated in this 65-kb region. Transfection experiments point to the existence of a 153-aa protein coded by the G72 gene. This protein is rapidly evolving in primates, is localized to endoplasmic reticulum/ Golgi in transfected cells, is able to form multimers and specifically binds to carbohydrates. Yeast two-hybrid experiments with the G72 protein identified the enzyme D-amino acid oxidase (DAAO) as an interacting partner. DAAO is expressed in human brain where it oxidizes D-serine, a potent activator of N-methyl-D-aspartate type glutamate receptor. The interaction between G72 and DAAO was confirmed in vitro and resulted in activation of DAAO. Four SNIP markers from DAAO were found to be associated with schizophrenia in the Canadian samples. Logistic regression revealed genetic interaction between associated SNPs in vicinity of two genes. The association of both DAAO and a new gene G72 from 13q34 with schizophrenia together with activation of DAAO activity by a G72 protein product points to the involvement of this N-methyl-D-aspartate receptor regulation pathway in schizophrenia. C1 Genset SA, F-91030 Evry, France. Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium. Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 113152, Russia. Signalgene Biotechnol, Montreal, PQ H2M 2NG, Canada. Erasmus Univ, NL-3000 DR Rotterdam, Netherlands. Inst Psychiat, London SE5 8AF, England. NIMH, NIH, Bethesda, MD 20892 USA. RP Cohen, D (reprint author), Genset SA, F-91030 Evry, France. EM dcohen@genset.fr RI PUECH, Anne/A-7470-2013; Macciardi, Fabio/N-3768-2014 OI Macciardi, Fabio/0000-0003-0537-4266 NR 49 TC 583 Z9 617 U1 4 U2 34 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 15 PY 2002 VL 99 IS 21 BP 13675 EP 13680 DI 10.1073/pnas.182412499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700062 PM 12364586 ER PT J AU Xue, HH Kovanen, PE Pise-Masison, CA Berg, M Radovich, MF Brady, JN Leonard, WJ AF Xue, HH Kovanen, PE Pise-Masison, CA Berg, M Radovich, MF Brady, JN Leonard, WJ TI IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THYMIC STROMAL LYMPHOPOIETIN; IGM(+) B-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; BETA-CHAIN; IN-VITRO; KINASE; CYTOKINE; PROLIFERATION AB Interleukin (IL)-2 is a type I four-alpha-helical bundle cytokine that plays vital roles in antigen-mediated proliferation of peripheral blood T cells and also is critical for activation-induced cell death. We now demonstrate that IL-2 potently decreases expression of IL-7 receptor alpha chain (IL-7Ralpha) mRNA and protein. The fact that IL-7Ralpha is a component of the receptors for both IL-7 and thymic stromal lymphopoietin (TSLP) suggests that IL-2 can negatively regulate signals by each of these cytokines. Previously it was known that the IL-2 and IL-7 receptors shared the common cytokine receptor gamma chain, gamma(c), which suggested a possible competition between these cytokines for a receptor component. Our findings now suggest a previously unknown type of cross-talk between IL-2 and IL-7 signaling by showing that IL-2 signaling can diminish IL-7Ralpha expression via a phosphatidylinositol 3-kinase/Akt-dependent mechanism. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NCI, Virus Tumor Biol Sect, Lab Receptor Biol & Gene Express, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N252, Bethesda, MD 20892 USA. NR 42 TC 119 Z9 120 U1 1 U2 2 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 15 PY 2002 VL 99 IS 21 BP 13759 EP 13764 DI 10.1073/pnas.212214999 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700076 PM 12354940 ER PT J AU Girnun, GD Smith, WM Drori, S Sarraf, P Mueller, E Eng, C Nambiar, P Rosenberg, DW Bronson, RT Edelmann, W Kucherlapati, R Gonzalez, FJ Spiegelman, BM AF Girnun, GD Smith, WM Drori, S Sarraf, P Mueller, E Eng, C Nambiar, P Rosenberg, DW Bronson, RT Edelmann, W Kucherlapati, R Gonzalez, FJ Spiegelman, BM TI APIC-dependent suppression of colon carcinogenesis by PPAR gamma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; FAMILIAL ADENOMATOUS POLYPOSIS; COLORECTAL-CANCER; BETA-CATENIN; SEQUENCE VARIANTS; DIABETES-MELLITUS; PROTEIN-KINASE; MOUSE MODEL; APC; EXPRESSION AB Activation of PPARgamma by synthetic ligands, such as thiazoliclinediones, stimulates adipogenesis and improves insulin sensitivity. Although thiazolidinediones represent a major therapy for type 2 diabetes, conflicting studies showing that these agents can increase or decrease colonic tumors in mice have raised concerns about the role of PPARgamma in colon cancer. To analyze critically the role of this receptor, we have used mice heterozygous for Ppargamma with both chemical and genetic models of this malignancy. Heterozygous loss of PPARgamma causes an increase in beta-catenin levels and a greater incidence of colon cancer when animals are treated with azoxymethane. However, mice with preexisting damage to Apc, a regulator of beta-catenin, develop tumors in a manner insensitive to the status of PPARgamma. These data show that PPARgamma can suppress beta-catenin levels and colon carcinogenesis but only before damage to the APC/beta-catenin pathway. This finding suggests a potentially important use for PPARgamma ligands as chemopreventative agents in colon cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT 06117 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Harvard Partners Ctr Genet & Genomics, Boston, MA 02115 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NIDDK NIH HHS [F32 DK061313, R01 DK 57670, R01 DK057670, F32 DK 61313] NR 48 TC 168 Z9 175 U1 1 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 15 PY 2002 VL 99 IS 21 BP 13771 EP 13776 DI 10.1073/pnas.162480299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700078 PM 12370429 ER PT J AU Imamichi, H Igarashi, T Imamichi, T Donau, OK Endo, Y Nishimura, Y Willey, RL Suffredini, AF Lane, HC Martin, MA AF Imamichi, H Igarashi, T Imamichi, T Donau, OK Endo, Y Nishimura, Y Willey, RL Suffredini, AF Lane, HC Martin, MA TI Amino acid deletions are introduced into the V2 region of gp120 during independent pathogenic simian immunodeficiency virus/HIV chimeric virus (SHIV) infections of rhesus monkeys generating variants that are macrophage tropic SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR-BINDING; CONFORMATIONAL-CHANGES; ALVEOLAR MACROPHAGES; TYPE-1 ISOLATE; IN-VIVO; HIV; REPLICATION; CELLS; CD4; GLYCOPROTEIN AB Highly pathogenic simian immunodeficiency virus/HIV chimeric viruses (SHIVs) cause extremely rapid, irreversible, and systemic depletions of CD4(+) T lymphocytes in inoculated rhesus monkeys. In the absence of this T cell subset, virus production can be sustained for several months by tissue macrophage. During independent infections of seven animals with uncloned virus stocks, SHIV variants emerged bearing amino acid deletions that affected specific residues of the gp120 V2 loop. Some of these macrophage-phase SHIVs replicated to high levels in alveolar macrophage. C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. NIAID, Labs Immunoregulat, Bethesda, MD 20892 USA. NIH, Ctr Clin, Div Crit Care Med, Bethesda, MD 20892 USA. Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 36 TC 19 Z9 19 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 15 PY 2002 VL 99 IS 21 BP 13813 EP 13818 DI 10.1073/pnas.212511599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700085 PM 12370415 ER PT J AU Graham, MR Smoot, LM Migliaccio, CAL Virtaneva, K Sturdevant, DE Porcella, SF Federle, MJ Adams, GJ Scott, JR Musser, JM AF Graham, MR Smoot, LM Migliaccio, CAL Virtaneva, K Sturdevant, DE Porcella, SF Federle, MJ Adams, GJ Scott, JR Musser, JM TI Virulence control in group A Streptococcus by a two-component gene regulatory system: Global expression profiling and in vivo infection modeling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microarrays; real-time RT-PCR; transcript analysis ID GROUP-A STREPTOCOCCUS; SIGNATURE-TAGGED MUTAGENESIS; HYALURONIC-ACID CAPSULE; STAPHYLOCOCCUS-AUREUS; STREPTOLYSIN-S; MURINE MODEL; PYOGENES; 2-COMPONENT; IDENTIFICATION; PROTEINS AB Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodomase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Baylor Coll Med, Dept Family & Community Med, Houston, TX 77005 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RI Federle, Michael/E-5522-2017 FU NIAID NIH HHS [T32 AI 07470, AI 20723, R01 AI020723, R21 AI020723, R37 AI020723, R56 AI020723, T32 AI007470] NR 44 TC 225 Z9 232 U1 1 U2 16 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 15 PY 2002 VL 99 IS 21 BP 13855 EP 13860 DI 10.1073/pnas.202353699 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700092 PM 12370433 ER PT J AU Spong, CY Auth, J Vink, J Goodwin, K Abebe, DT Hill, JM Brenneman, DE AF Spong, CY Auth, J Vink, J Goodwin, K Abebe, DT Hill, JM Brenneman, DE TI Vasoactive intestinal peptide mRNA and immunoreactivity are decreased in fetal alcohol syndrome model SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 23rd Winter Neuropeptide Conference CY FEB 02-05, 2002 CL BRECKENRIDGE, COLORADO DE vasoactive intestinal peptide; fetal alcohol syndrome ID DEPENDENT NEUROTROPHIC FACTOR; CULTURED MOUSE EMBRYOS; CYCLIC-AMP; NEUROPROTECTIVE PEPTIDE; GROWTH; VIP; POLYPEPTIDE; BLOCKADE; EXPOSURE; BINDING AB Vasoactive intestinal peptide (VIP) regulates growth in the early post-implantation embryo. Previous work has demonstrated that peptide agonists (SALLRSIPA and NAPVSIPQ) from downstream mediators that are regulated by VIP were able to prevent the alcohol-induced fetal death, growth restriction and microcephaly associated with fetal alcohol syndrome. Here we evaluated the role of VIP in this mouse model of fetal alcohol syndrome, to determine if fetal or maternal levels of VIP are altered. In addition, we evaluated whether peptide treatment would alter the effects of alcohol on VIP levels. Treatment groups included control, alcohol, and alcohol +peptides. VIP levels were measured with enzyme immunoassay [EIA] (Peninsula Laboratories, Belmont, CA). Quantitation of VIP expression was measured with rt-PCR using mimic cDNA primers. Embryo: decidual VIP levels were similar in control and alcohol-treated groups 6 h after treatment. However, in the embryo/deciduas at 12 and 24 h, VIP levels were below the EIA's detection limit in the alcohol-treated groups, and significantly lower than the control or peptide-pretreated groups (p < 0.05). Maternal cortex VIP levels were undetectable and significantly lower in the alcohol-treated group than control or peptide+alcohol group at 6 and 12 h (p < 0.001). VIP mRNA expression was quantitated in the embryo and deciduas, with a significant decline noted at 6 h to 58 0 of control levels (p=0.02). Pretreatment with the peptides attenuated the alcohol-induced decrease in VIP mRNA. These studies demonstrate that treatment with alcohol can decrease the expression and immunoreactivity of VIP in both maternal and fetal tissues. This alcohol-induced loss of a recognized regulator of embryonic growth and differentiation may contribute to the sequelae of toxicity observed in fetal alcohol syndrome. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A-38,MSC 4480,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 16 Z9 17 U1 0 U2 4 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 2002 VL 108 IS 2-3 BP 143 EP 147 AR PII S0167-0115(02)00104-0 DI 10.1016/S0167-0115(02)00104-0 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 601TJ UT WOS:000178463800013 PM 12220738 ER PT J AU Wollman, Y Blumberg, S Spungin, A Brenneman, DE Fridkin, M Wollman, J Iaina, A Gozes, I AF Wollman, Y Blumberg, S Spungin, A Brenneman, DE Fridkin, M Wollman, J Iaina, A Gozes, I TI The increased proliferation of cultured neuroblastoma cells treated with vasoactive intestinal peptide is enhanced by simultaneous inhibition of neutral endopeptidase SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 23rd Winter Neuropeptide Conference CY FEB 02-05, 2002 CL BRECKENRIDGE, COLORADO DE neuroblastoma cells; vasoactive intestinal peptide; neutral endopeptidase ID CYCLASE-ACTIVATING PEPTIDE; GROWTH; DIFFERENTIATION; VIP; SURVIVAL; EMBRYOS; MITOSIS; MARROW; MOUSE; GENE AB Vasoactive intestinal peptide (VIP) stimulates the neuroblastoma cell line (NMB) to proliferate. Neuropeptide activity can be inhibited by neutral endopeptidases that function intracellularly and in the extracellular milieu. NMB cells express neutral endopeptidase (NEP) activity that can be specifically inhibited by phosphoramidon (PA). Our data now show that phosphoramidon treatment increases the efficacy of VIP-stimulated neuroblastoma proliferation. These results suggest that membrane endopeptidases modulate VIP-associated cell proliferation and enhancement of endopeptidase activity may serve as a target for cancer therapy. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. Tel Aviv Med Ctr & Sch Med, Dept Nephrol, IL-64239 Tel Aviv, Israel. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 24 TC 6 Z9 6 U1 1 U2 1 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 2002 VL 108 IS 2-3 BP 175 EP 177 AR PII S0167-0115(02)00098-8 DI 10.1016/S0167-0115(02)00098-8 PG 3 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 601TJ UT WOS:000178463800017 PM 12220742 ER PT J AU Simon, R AF Simon, R TI Bayesian subset analysis: application to studying treatment-by-gender interactions SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 9th International Symposium on Long-Term Clinical Trials CY JUN 19-20, 2000 CL LONDON, ENGLAND DE clinical trials; Bayesian methods; subsets; subgroups; gender ID CLINICAL-TRIALS AB Evaluating treatment effects within subsets of patients plays a major part of the analysis of many major clinical trials. Clinicians are often impressed by the heterogeneity of patient populations in clinical trials and hence are interested in examining subset effects. Statisticians generally discourage subset analysis or suggest that clinicians 'do subset analysis but do not believe it'. This advice, however, is a sign of the inadequacy of the analytic methods generally used for subset analysis. Separate analysis of many subsets, and basing conclusions on whether the observed treatment difference achieves significance at the 0.05 level, is likely to yield erroneous conclusions. Making the separate analysis of subsets dependent on demonstration of a statistically significant treatment-by-subset interaction is also not an effective analytic strategy because of the limited power of interaction tests. This paper describes a Bayesian approach to subset analysis developed by Simon, Dixon and Freidlin. The method avoids many of the problems of subset analysis because it is not 'separate' analysis of subsets. Instead, subset-specific treatment effects are estimated as an average of observed within-subset differences and overall differences; the two components are weighted by the a priori estimate of the likelihood of qualitative treatment by subset interactions. Hence, the Bayesian method proposed permits subset analyses incorporating the assumption that qualitative interactions are unlikely. The methodology is applied to the problem of designing and analysing clinical trials to estimate treatment effects for males and females. Copyright (C) 2002 John Wiley Sons, Ltd. C1 NCI, Bethesda, MD 20892 USA. RP Simon, R (reprint author), 6130 Execut Blvd,Room 8134, Bethesda, MD 20892 USA. NR 13 TC 33 Z9 33 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 15 PY 2002 VL 21 IS 19 BP 2909 EP 2916 DI 10.1002/sim.1295 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 599WG UT WOS:000178357700016 PM 12325107 ER EF