FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kant, AK Graubard, BI AF Kant, AK Graubard, BI TI Eating out in America, 1987-2000: trends and nutritional correlates SO PREVENTIVE MEDICINE LA English DT Article DE eating out; body mass index; away-from-home eating; restaurant eating; NHIS; NHANES; energy intake ID US OBESITY; WOMEN; PREVALENCE; EPIDEMIC; DIETARY AB Background. Despite widely held beliefs about increasing popularity of eating away-from-home and its possible contribution to increasing adiposity of the US population, there are little published data on this topic. To address this issue, we examined trends in frequency of consumption of commercially prepared (CP) meals reported by Americans aged greater than or equal to 18 years, and its nutritional correlates. Methods. The data were from the National Health Interview Survey (NHIS) 1987 (n = 21,73 1), NHIS 1992 (n = 11,718), and the National Health and Nutrition Examination Survey (NHANES) 1999-2000 (n = 5,330). The information on CP meal consumption was obtained from questions included in the three surveys. The independent association of reported CP meal frequency with body mass index (BMI), and intakes of energy and macronutrients was examined using multiple linear regression methods. Results. The mean reported number of CP meals per week was 2.5 in 1987 and 1992, and 2.8 in 1999-2000. In 1987, approximately 28% of the population reported 0 or <1 commercially prepared meal per week, decreasing to 24% in 1999-2000 (P for trend <0.0001). However, the proportion of the population reporting three or more weekly CP meals increased from 36% in 1987 to 41% in 1999-2000 (P for trend less than or equal to0.0005). The odds of eating out at least one or more and three or more meals per week were 40% higher (95% CI 1.20-1.70) in 19992000 relative to 1987. The reported number of CP meals per week was positively associated with estimates of energy intake (P less than or equal to 0.0001) in each survey. Self-reported and measured BMI were modestly associated with the reported number of weekly CP meals in women in 19992000 (P less than or equal to 0.05). Conclusion. Our results confirm that in 1999-2000, more Americans ate out, and ate out more frequently than in 1987 and 1992. Higher eating-out frequency was associated with adverse nutritional consequences. (C) 2003 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. EM ashima_kant@qc.edu NR 20 TC 190 Z9 194 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD FEB PY 2004 VL 38 IS 2 BP 243 EP 249 DI 10.1016/j.ypmed.2003.10.004 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 765YT UT WOS:000188319200016 PM 14715218 ER PT J AU McKinney, J Knappskog, PM Pereira, J Ekern, T Toska, K Kuitert, BB Levine, D Gronenborn, AM Martinez, A Haavik, J AF McKinney, J Knappskog, PM Pereira, J Ekern, T Toska, K Kuitert, BB Levine, D Gronenborn, AM Martinez, A Haavik, J TI Expression and purification of human tryptophan hydroxylase from Escherichia coli and Pichia pastoris SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE tryptophan hydroxylase; pichiapastoris; Escherichia coli; recombinant protein production; purification; optimization; L-tryptophan ID HUMAN PHENYLALANINE-HYDROXYLASE; AMINO-ACID HYDROXYLASES; MURINE MAST-CELL; RAT-BRAIN; FUSION PROTEIN; CATALYTIC CORE; ENZYME; SEROTONIN; 5-MONOOXYGENASE; CHROMATOGRAPHY AB Tryptophan hydroxylase (TPH) from several mammalian species has previously been cloned and expressed in bacteria. However, due to the instability of wild type TPH, most successful attempts have been limited to the truncated forms of this enzyme. We have expressed full-length human TPH in large amounts in Escherichia coli and Pichia pastoris and purified the enzyme using new purification protocols. When expressed as a fusion protein in E coli, the maltose-binding protein-TPH (MBP-TPH) fusion protein was more soluble than native TPH and the other fusion proteins and had a 3-fold higher specific activity than the His-Patch-thioredoxin-TPH and 6 x His-TPH fusion proteins. The purified MBP-TPH had a V-max of 296nmol/min/mg and a K-m for L-tryptophan of 7.5 +/- 0.7 muM, compared to 18 +/- 5 muM for the partially purified enzyme from P. pastoris. To overcome the unfavorable properties of TPH, the stabilizing effect of different agents was investigated. Both tryptophan and glycerol had a stabilizing effect, whereas dithiothreitol, (6R)-5,6,7,8,-tetrahydrobiopterin, and Fe2+ inactivated the enzyme. Irrespective of expression conditions, both native TPH expressed in bacteria or yeast, or TPH fusion proteins expressed in bacteria exhibited a strong tendency to aggregate and precipitate during purification, indicating that this is an intrinsic property. of this enzyme. This supports previous observations that the enzyme in vivo may be stabilized by additional interactions. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Bergen, Dept Biochem & Mol Biol, Bergen, Norway. Haukeland Univ Hosp, Ctr Med Genet & Mol Med, Bergen, Norway. Norwegian Univ Sci & Technol, Dept Biotechnol, NTNU, N-7034 Trondheim, Norway. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP McKinney, J (reprint author), Univ Bergen, Dept Biochem & Mol Biol, Bergen, Norway. EM jeffrey.mckinney@student.uib.no OI Martinez, Aurora/0000-0003-1643-6506; Gronenborn, Angela M/0000-0001-9072-3525; Haavik, Jan/0000-0001-7865-2808 NR 37 TC 21 Z9 23 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD FEB PY 2004 VL 33 IS 2 BP 185 EP 194 DI 10.1016/j.pep.2003.09.014 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 766ZT UT WOS:000188414200004 PM 14711505 ER PT J AU Khil, PP Obmolova, G Teplyakov, A Howard, AJ Gilliland, GL Camerini-Otero, RD AF Khil, PP Obmolova, G Teplyakov, A Howard, AJ Gilliland, GL Camerini-Otero, RD TI Crystal structure of the Escherichia coli YjiA protein suggests a GTP-dependent regulatory function SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article ID P-LOOP; GENES; CLASSIFICATION; SEQUENCE; BINDING C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Natl Inst Stand & Technol, Rockville, MD USA. IIT, Biol Chem & Phys Sci Dept, Ctr Synchrotron Radiat Res & Instrumentat, Chicago, IL 60616 USA. RP Khil, PP (reprint author), NIDDK, Genet & Biochem Branch, NIH, 5 Mem Dr, Bethesda, MD 20892 USA. EM pk94j@nih.gov RI ID, IMCACAT/D-5867-2014; OI Khil, Pavel/0000-0002-4903-8777; Teplyakov, Alexey/0000-0003-0296-0016 FU NIGMS NIH HHS [P01-GM57890] NR 15 TC 9 Z9 12 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 0887-3585 J9 PROTEINS JI Proteins PD FEB 1 PY 2004 VL 54 IS 2 BP 371 EP 374 DI 10.1002/prot.10430 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 763AC UT WOS:000188044600020 PM 14696199 ER PT J AU Houtsmuller, EJ Notes, LD Newton, T van Sluis, N Chiang, N Elkashef, A Bigelow, GE AF Houtsmuller, EJ Notes, LD Newton, T van Sluis, N Chiang, N Elkashef, A Bigelow, GE TI Transdermal selegiline and intravenous cocaine: safety and interactions SO PSYCHOPHARMACOLOGY LA English DT Article DE cocaine; selegiline; eldepryl; human; laboratory; subjective; endocrine ID LONG-TERM REDUCTION; NUCLEUS-ACCUMBENS; FRONTAL-CORTEX; RAT-BRAIN; REINFORCING PROPERTIES; BETA-PHENYLETHYLAMINE; DOPAMINE TRANSPORTER; ANTERIOR-PITUITARY; SUBJECTIVE RATINGS; PARKINSONS-DISEASE AB Rationale. Because the dopamine system appears to be involved in both acute and chronic effects of cocaine, medication development efforts for cocaine addiction have focused largely on agents that interact with the dopamine system. Selegiline, a selective monoamine oxidase B inhibitor, indirectly modulates dopamine levels, and research suggests selegiline may modify subjective effects of cocaine. Objectives. To evaluate further the safety and potential of transdermal selegiline as a treatment for cocaine dependence, interactions between transdermal selegiline and intravenous cocaine were studied in cocaine-dependent volunteers. Methods. Pharmacokinetics and subjective, physiological, and endocrinological effects of intravenous cocaine (0,20 and 40 mg) were evaluated both before and during transdermal selegiline treatment (20 mg/day, 10 days) in 12 cocaine-dependent subjects. A transdermal selegiline formulation was used to avoid the risks associated with oral administration of MAO inhibitors. Results. Selegiline attenuated some physiological (systolic blood pressure and heart rate) and subjective (good effects, liking, stimulated, high, desire for cocaine) effects of cocaine. Selegiline did not affect cocaine's pharmacokinetics or cocaine-induced prolactin decrease and growth hormone increase. Conclusions. The combined administration of the transdermal selegiline patch and up to 40 mg cocaine was well tolerated. Selegiline may reduce physiological and subjective effects of cocaine. A randomized trial is needed to evaluate the efficacy of selegiline for cocaine abuse. C1 Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, Bayview Med Ctr, Baltimore, MD 21224 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Natl Inst Drug Abuse, Medicat Dev Div, Rockville, MD USA. RP Houtsmuller, EJ (reprint author), Johns Hopkins Univ, Sch Med, Behav Pharmacol Res Unit, Bayview Med Ctr, 5510 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ehoutsm@jhmi.edu OI newton, thomas/0000-0002-3198-5901 FU NCRR NIH HHS [M01-RR00865]; NIDA NIH HHS [Y01-DA50038, N01-DA78074, K05-DA00050, K08-DA00388, R01-DA0-5196, N01DA-6-8054, N01-DA48306] NR 57 TC 23 Z9 23 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 2004 VL 172 IS 1 BP 31 EP 40 DI 10.1007/s00213-003-1616-6 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 777WL UT WOS:000189206800005 PM 14605792 ER PT J AU Steyn, NP Mann, J Bennett, PH Temple, N Zimmet, P Tuomilehto, J Lindstrom, J Louheranta, A AF Steyn, NP Mann, J Bennett, PH Temple, N Zimmet, P Tuomilehto, J Lindstrom, J Louheranta, A TI Diet, nutrition and the prevention of type 2 diabetes SO PUBLIC HEALTH NUTRITION LA English DT Article; Proceedings Paper CT Joint WHO/FAO Expert Consultation Meeting on Diet, Nutrition and the Prevention of Chronic Diseases CY JAN 28-FEB 01, 2002 CL GENEVA, SWITZERLAND SP WHO, FAO DE diabetes; prevention; dietary intake; overweight; obesity; physical activity ID IMPAIRED GLUCOSE-TOLERANCE; ISCHEMIC-HEART-DISEASE; HIGH-CARBOHYDRATE DIETS; FATTY-ACID COMPOSITION; SKELETAL-MUSCLE PHOSPHOLIPIDS; HEALTH-ORGANIZATION CRITERIA; THRIFTY PHENOTYPE HYPOTHESIS; CARDIOVASCULAR RISK-FACTORS; INSULIN-RESISTANCE; PIMA-INDIANS AB Objectives: The overall objective of this study was to evaluate and provide evidence and recommendations on current published literature about diet and lifestyle in the prevention of type 2 diabetes. Design: Epidemiological and experimental studies, focusing on nutritional intervention in the prevention of type 2 diabetes are used to make disease-specific recommendations. Long-term cohort studies are given the most weight as to strength of evidence available. Setting and subjects: Numerous clinical trials and cohort studies in low, middle and high income countries are evaluated regarding recommendations for dietary prevention of type 2 diabetes. These include, among others, the Finnish Diabetes Prevention Study, US Diabetes Prevention Program, Da Qing Study; Pima Indian Study; Iowa Women's Health Study; and the study of the US Male Physicians. Results: There is convincing evidence for a decreased risk of diabetes in adults who are physically active and maintain a normal body mass index (BMI) throughout adulthood, and in overweight adults with impaired glucose tolerance who lose weight voluntarily. An increased risk for developing type 2 diabetes is associated with overweight and obesity; abdominal obesity; physical inactivity; and maternal diabetes. It is probable that a high intake of saturated fats and intrauterine growth retardation also contribute to an increased risk, while non-starch polysaccharides are likely to be associated with a decreased risk. From existing evidence it is also possible that omega-3 fatty acids, low glycaemic index foods and exclusive breastfeeding may play a protective role, and that total fat intake and trans fatty acids may contribute to the risk. However, insufficient evidence is currently available to provide convincing proof. Conclusions: Based on the strength of available evidence regarding diet and lifestyle in the prevention of type 2 diabetes, it is recommended that a normal weight status in the lower BMI range (BMI 21-23) and regular physical activity be maintained throughout adulthood; abdominal obesity be prevented; and saturated fat intake be less than 7% of the total energy intake. C1 MRC, Chron Dis Lifestyle Unit, Tygerberg, South Africa. Univ Otago, Dept Human Nutr, Dunedin, New Zealand. Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA. Athabasca Univ, Ctr Sci, Athabasca, AB, Canada. Int Diabet Inst, Caulfield, Australia. Natl Publ Hlth Inst, Helsinki, Finland. Univ Kuopio, Dept Clin Nutr, FIN-70211 Kuopio, Finland. RP Steyn, NP (reprint author), MRC, Chron Dis Lifestyle Unit, Tygerberg, South Africa. EM nelia.steyn@mrc.ac.za NR 245 TC 134 Z9 142 U1 3 U2 32 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD FEB PY 2004 VL 7 IS 1A SI SI BP 147 EP 165 DI 10.1079/PHN2003586 PG 19 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 780JL UT WOS:000189377500004 PM 14972058 ER PT J AU Key, T Schatzkin, A Willett, WC Allen, NE Spencer, EA Travis, RC AF Key, T Schatzkin, A Willett, WC Allen, NE Spencer, EA Travis, RC TI Diet, nutrition and the prevention of cancer SO PUBLIC HEALTH NUTRITION LA English DT Article; Proceedings Paper CT Joint WHO/FAO Expert Consultation Meeting on Diet, Nutrition and the Prevention of Chronic Diseases CY JAN 28-FEB 01, 2002 CL GENEVA, SWITZERLAND SP WHO, FAO DE diet; nutrition; cancer; review ID GROWTH-FACTOR-I; DISEASE-SPECIFIC MORTALITY; PROSTATE-CANCER; COLORECTAL-CANCER; BREAST-CANCER; COLON-CANCER; LUNG-CANCER; BETA-CAROTENE; POSTMENOPAUSAL WOMEN; FAT INTAKE AB Objective: To assess the epidemiological evidence on diet and cancer and make public health recommendations. Design: Review of published studies, concentrating on recent systematic reviews, meta-analyses and large prospective studies. Conclusions and recommendations: Overweight/obesity increases the risk for cancers of the oesophagus (adenocarcinoma), colorectum, breast (postmenopausal), endometrium and kidney; body weight should be maintained in the body mass index range of 18.5-25 kg/m(2), and weight gain in adulthood avoided. Alcohol causes cancers of the oral cavity, pharynx, oesophagus and liver, and a small increase in the risk for breast cancer; if consumed, alcohol intake should not exceed 2 units/d. Aflatoxin in foods causes liver cancer, although its importance in the absence of hepatitis virus infections is not clear; exposure to aflatoxin in foods should be minimised. Chinese-style salted fish increases the risk for nasopharyngeal cancer, particularly if eaten during childhood, and should be eaten only in moderation. Fruits and vegetables probably reduce the risk for cancers of the oral cavity, oesophagus, stomach and colorectum, and diets should include at least 400 g/d of total fruits and vegetables. Preserved meat and red meat probably increase the risk for colorectal cancer; if eaten, consumption of these foods should be moderate. Salt preserved foods and high salt intake probably increase the risk for stomach cancer; overall consumption of salt preserved foods and salt should be moderate. Very hot drinks and foods probably increase the risk for cancers of the oral cavity, pharynx and oesophagus; drinks and foods should not be consumed when they are scalding hot. Physical activity, the main determinant of energy expenditure, reduces the risk for colorectal cancer and probably reduces the risk for breast cancer; regular physical activity should be taken. C1 Univ Oxford, Canc Res UK Epidemiol Unit, Oxford, England. Natl Canc Inst, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Key, T (reprint author), Univ Oxford, Canc Res UK Epidemiol Unit, Oxford, England. EM tim.key@cancer.org.uk OI Spencer, Elizabeth/0000-0002-9079-8006 NR 109 TC 284 Z9 294 U1 15 U2 63 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD FEB PY 2004 VL 7 IS 1A SI SI BP 187 EP 200 DI 10.1079/PHN2003588 PG 14 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 780JL UT WOS:000189377500006 PM 14972060 ER PT J AU Mankani, MH Kuznetsov, SA Avila, NA Kingman, A Robey, PG AF Mankani, MH Kuznetsov, SA Avila, NA Kingman, A Robey, PG TI Bone formation in transplants of human bone marrow stromal cells and hydroxyapatite-tricalcium phosphate: Prediction with quantitative CT in mice SO RADIOLOGY LA English DT Article DE animals; bone marrow, transplantation; bones, computed tomography (CT), quantitative; hydroxyapatite; phantoms ID ANORGANIC BOVINE BONE; CRANIOFACIAL SURGERY; DIAGNOSTIC-TESTS; IN-VIVO; HYDROXYLAPATITE; RECONSTRUCTION; DEFECTS; IMPLANTS; QCT; CRANIOPLASTY AB PURPOSE: To determine whether quantitative computed tomography (CT) can be used to estimate the extent of new bone formation in hydroxyapatite-tricalcium phosphate (HA-TCP)-based transplants. MATERIALS AND METHODS: Bone-forming transplants were generated by attacking cultured human bone marrow stromal cells to aliquots of HA-TCP particles and were placed in subcutaneous pockets in immunocompromised mice. After 8 weeks, the transplants were individually imaged; each scan included a phantom. Overall bone mineral density (BMD) of each transplant was obtained. Hematoxylineosin-stained sections of the same transplants were then examined histologically, which is the reference standard for assessing bone formation. The extent of bone in each transplant was scored on a semiquantitative scale ranging from 0 to 4 by three independent blinded observers; the bone score for each transplant was calculated by averaging the three observer scores. BMD was compared with the histologically determined bone score for each transplant. Statistical evaluations included (a) calculation of empiric receiver operating characteristic curves to determine optimum BMD thresholds and (b) determination of the relationship between BMD and bone score, including derivation of Pearson correlation coefficients. RESULTS: One hundred twenty transplants were evaluated. Average BMD of 600 mg/cm(3) K2HPO4 or more was noted in transplants with appreciable bone formation (bone score greater than or equal to 3), while average BMD of less than 600 mg/cm(3) K2HPO4 was seen in transplants with poor bone formation (bone score < 3) (P < .001). Among transplants with appreciable bone formation, the BMD was proportional to the extent of mineralized matrix present in the new bone. CONCLUSION: Use of quantitative CT offers a practical approach for the noninvasive determination of new bone formation in mineralizing bone marrow stromal cells and HA-TCP transplants. ((C))RSNA, 2004. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Dept Surg, Div Plast Surg, San Francisco, CA 94110 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Off Director, Biostat Core, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. RP Mankani, MH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Surg, Div Plast Surg, 1001 Potrero Ave,Ward 3A, San Francisco, CA 94110 USA. EM mmankani@sfghsurg.ucsf.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 37 TC 33 Z9 34 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 FEB PY 2004 VL 230 IS 2 BP 369 EP 376 DI 10.1148/radiol.2302011529 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 767QG UT WOS:000188463700011 PM 14752182 ER PT J AU Bratti, MC Rodriguez, AC Schiffman, M Hildesheim, A Morales, J Alfaro, M Guillen, D Hutchinson, M Sherman, ME Eklund, C Schussler, J Buckland, J Morera, LA Cardenas, F Barrantes, M Perez, E Cox, TJ Burk, RD Herrero, R AF Bratti, MC Rodriguez, AC Schiffman, M Hildesheim, A Morales, J Alfaro, M Guillen, D Hutchinson, M Sherman, ME Eklund, C Schussler, J Buckland, J Morera, LA Cardenas, F Barrantes, M Perez, E Cox, TJ Burk, RD Herrero, R TI Description of a seven-year prospective study of human papillomavirus infection and cervical neoplasia among 10000 women in Guanacaste, Costa Rica SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE carcinoma; papillomavirus; human; precancerous conditions; risk factors; epidemiologic methods; Costa Rica ID HIGH-RISK; POPULATION; CANCER; COLLECTION; SECRETIONS; STRATEGIES; SPECIMENS; SYSTEM; REGION; PCR AB Objective. The Guanacaste study ("Guanacaste Project," or GP), was designed to investigate the role of human papillomavirus (HPV) infection and its cofactors in the development of cervical neoplasia and to evaluate new cervical cancer screening technologies. The follow-up phase of the GP was designed to study why a small proportion of women infected with HPV develop cervical intraepithelial neoplasia grade 2 (CIN 2), CIN 3, or cancer (these three together are globally referred to as greater than or equal to CIN 2, that is, CIN 2 or worse). The purpose of this article is to describe this prospective study in detail and to present the preliminary findings regarding the incidence of cervical neoplasia. Methods. A cohort of 10 049 randomly selected women from 18 to 97 years old from Guanacaste, a province in northwestern Costa Rica, was intensively screened in 1993-1994 and then followed up for seven years after being enrolled. A questionnaire for demographic and risk factors was administered, and a pelvic examination was performed on sexually active women at each follow-up visit in order to obtain samples for screening tests and for research purposes. The final diagnosis given at the end of the enrollment phase categorized women into several groups according to the perceived risk of their developing either high-grade precursors of cancer or cancer. These groups were followed up at different intervals according to the risk of developing greater than or equal to CIN 2. The most active follow-up (every 6-12 months) was concentrated on the women most likely to develop greater than or equal to CIN 2, based on cytology (n = 492). The remainder of the cohort was followed either annually (n = 2 574) or after five to seven years of passive follow-up (n = 3 926). All women with possibly severe lesions detected by any technique were referred to colposcopy for further evaluation and treatment, and they were also censored from the study. Lesions greater than or equal to CIN 2 served as both the censoring outcome and our surrogate for cancer risk. Results. Participation during follow-up was high (near 90%). Suspected greater than or equal to CIN 2 by any screening technique censored 4.6% of women. Most of the women censored because of suspected greater than or equal to CIN 2 came from the large group perceived at entry as being at low risk of developing greater than or equal to CIN 2, but the greatest rates of progression to greater than or equal to CIN 2 were observed among women perceived at entry to be at highest risk of greater than or equal to CIN 2, based on their cytology, virology, or sexual behavior. Conclusions. The GP is the largest population-based longitudinal cohort for the study of HPV and cervical neoplasia in the world, and its results will hopefully let us soon plan future worldwide prevention strategies. Research projects such as this one require the long-term commitment of a large multidisciplinary team and ample financial resources. The intensive effort and expertise applied in all aspects of this study were key factors in its success as a model of cooperative, interdisciplinary cancer research in Latin America. Quality control played an important role at all times during the study and made it possible to adapt new diagnostic and screening technology to Guanacaste. The systematic follow-up of a population-based group of close to 10 000 women in Guanacaste should permit careful, time-dependent evaluation of factors postulated to be linked to the development of cervical cancer as well as the evaluation of clinical markers of disease progression. The study results that have already been published have validated sensitive screening techniques and have also promoted the use of more affordable screening techniques in resource-poor, developing countries. The GP has also contributed to building knowledge for the search for vaccines against HPV as part of the effort to develop an effective tool to reduce the incidence and mortality of cervical cancer worldwide. C1 Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Informat Management Serv Inc, Silver Spring, MD USA. Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Bratti, MC (reprint author), Proyecto Epidemiol Guanacaste, POB 1253-1007, San Jose, Costa Rica. EM mcbratti@amnet.co.cr FU NCI NIH HHS [N01CP 21081, N01CP 33061, N01CP 40542, N01CP 50535, N01CP 81023] NR 33 TC 53 Z9 54 U1 0 U2 2 PU PAN AMERICAN HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD FEB PY 2004 VL 15 IS 2 BP 75 EP 89 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 898HT UT WOS:000227068500002 PM 15030652 ER PT J AU El Sahly, HM Reich, RA Dou, SJ Musser, JM Graviss, EA AF El Sahly, HM Reich, RA Dou, SJ Musser, JM Graviss, EA TI The effect of mannose binding lectin gene polymorphisms on susceptibility to tuberculosis in different ethnic groups SO SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PROTEIN GENE; AFRICANS; POPULATION; MUTATIONS; INFECTION; ALLELE AB In order to investigate the role of MBL gene polymorphisms in susceptibility to tuberculosis ( TB) we genotyped 487 TB cases and 232 controls. Among African-American individuals, the frequency of B allele was lower among controls than cases (p<0.01), but we found no differences between cases and controls of white and Hispanic ethnicity. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Div Infect Dis, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Graviss, EA (reprint author), Baylor Coll Med, Dept Pathol 209E, 1 Baylor Plaza, Houston, TX 77030 USA. EM egraviss@bcm.tmc.edu FU NIAID NIH HHS [N01-AO-02738] NR 12 TC 30 Z9 32 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0036-5548 J9 SCAND J INFECT DIS JI Scand. J. Infect. Dis. PD FEB PY 2004 VL 36 IS 2 BP 106 EP 108 DI 10.1080/00365540310018860 PG 3 WC Infectious Diseases SC Infectious Diseases GA 800YV UT WOS:000220064500004 PM 15061663 ER PT J AU Ryan, AS Ivey, FM Hurlbut, DE Martel, GF Lemmer, JT Sorkin, JD Metter, EJ Fleg, JL Hurley, BF AF Ryan, AS Ivey, FM Hurlbut, DE Martel, GF Lemmer, JT Sorkin, JD Metter, EJ Fleg, JL Hurley, BF TI Regional bone mineral density after resistive training in young and older men and women SO SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS LA English DT Article DE exercise; aging; osteoporosis; strength; menopause ID LEAN TISSUE MASS; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; BODY-COMPOSITION; WEIGHT LIFTERS; RISK-FACTORS; FAT-FREE; STRENGTH; EXERCISE; RESISTANCE AB Purpose: The purpose of this study was to determine the effects of 6 months of whole-body resistive training (RT) on total and regional bone mineral density (BMD) and bone mineral content (BMC) by age and gender in young and older men and women. Methods: Younger men (n = 10) and women (n = 7) aged 20-29 years (25 +/- 1 years) and older men (n = 10) and women (n = 10) aged 65-74 years (69+/-1 years) participated in 6 months of progressive whole-body RT. Upper- and lower-body strength was assessed by the one repetition maximum (IRM) test, and total body fat, lean tissue mass, femoral neck BMD, Ward's triangle BMD, greater trochanter BMD, totalbody BMD, and L-2-L-4 spine BMD were determined by dual-energy X-ray absorptiometry before and after 6 months of RT. Results: Percent body fat decreased only in the young men (P<0.05). Lean tissue mass increased after training in young men and women and older men (P<0.05) but did not change significantly in older women. Upper- and lower-body IRM strength increased in all groups (P<0.01). Overall, there was a significant increase in BMD at the femoral neck, ward's triangle and greater trochanter BMD, as well as total body BMC and leg BMC (P<0.05). Total-body BMD and L2-L4 spine BMD did not change with RT. There were no gender differences in the training response between men and women for any of the BMD regions and no age differences in the training response, except for a trend between young and older subjects for femoral neck (P<0.08). Conclusion: A 6-month RT program increases muscle mass and improves BMD of the femoral region in young and healthy older men and women as a group, with a trend for this to be greater in young subjects. C1 Baltimore Vet Affairs Med Ctr, Div Gerontol, GRECC, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Ryan, AS (reprint author), Baltimore Vet Affairs Med Ctr, Div Gerontol, GRECC, BT-18-GR, Baltimore, MD 21201 USA. EM aryan@grecc.umaryland.edu FU NIA NIH HHS [1T32-AG00219, N01-AG-2148]; PHS HHS [K01-A600747] NR 32 TC 49 Z9 53 U1 2 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-7188 J9 SCAND J MED SCI SPOR JI Scand. J. Med. Sci. Sports PD FEB PY 2004 VL 14 IS 1 BP 16 EP 23 DI 10.1046/j.1600-0838.2003.00328.x PG 8 WC Sport Sciences SC Sport Sciences GA 801JB UT WOS:000220091100003 PM 14723783 ER PT J AU Zhang, GQ Fu, Y Yang, DM Hao, XM Bai, SH Tang, YQ Lakatta, EG Wu, CH Cheng, HP AF Zhang, GQ Fu, Y Yang, DM Hao, XM Bai, SH Tang, YQ Lakatta, EG Wu, CH Cheng, HP TI Contribution of spontaneous L-type Ca2+ channel activation to the genesis of Ca2+ sparks in resting cardiac myocytes SO SCIENCE IN CHINA SERIES C-LIFE SCIENCES LA English DT Article DE Ca2+ sparks; L-type Ca2+ channels; cardiac myocytes; confocal microscopy ID SPATIAL NONUNIFORMITIES; CONFOCAL IMAGES; CALCIUM SPARKS; HEART-MUSCLE; (I); RELEASE; CELLS AB Ca2+ sparks are the elementary events of intracellular Ca2+ release from the sarcoplasmic reticulum in cardiac myocytes. In order to investigate whether spontaneous L-type Ca2+ channel activation contributes to the genesis of spontaneous Ca2+ sparks, we used confocal laser scanning microscopy and fluo-4 to visualize local Ca2+ sparks in intact rat ventricular myocytes. In the presence of 0.2 mmol/L CdCl2 which inhibits spontaneous L-type Ca2+ channel-activation, the rate of occurrence of spontaneous Ca2+ sparks was halved from 4.20 to 2.04 events/(100 mum (.) s), with temporal and spatial properties of individual Ca2+ sparks unchanged. Analysis of the Cd2+-sensitive spark production revealed an open probability of similar to10(-5) for L-type channels at the rest membrane potentials (-80 mV). Thus, infrequent and stochastic openings of sarcolemmal L-type Ca2+ channels in resting heart cells contribute significantly to the production of spontaneous Ca2+ sparks. C1 Beijing Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. China Pharmaceut Univ, Res Div Pharmacol, Nanjing 210009, Peoples R China. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Cheng, HP (reprint author), Beijing Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. EM Chengp@grc.nia.nih.gov NR 12 TC 1 Z9 1 U1 1 U2 7 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1006-9305 J9 SCI CHINA SER C JI Sci. China Ser. C-Life Sci. PD FEB PY 2004 VL 47 IS 1 BP 31 EP 37 DI 10.1360/02yc0234 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 773XR UT WOS:000188951300005 ER PT J AU Kwak, LW Neelapu, SS Bishop, MR AF Kwak, LW Neelapu, SS Bishop, MR TI Adoptive immunotherapy with antigen-specific T cells in myeloma: A model of tumor-specific donor lymphocyte infusion SO SEMINARS IN ONCOLOGY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; BLOOD PROGENITOR-CELL; COLONY-STIMULATING FACTOR; HUMORAL IMMUNE-SYSTEM; MULTIPLE-MYELOMA; RANDOMIZED TRIAL; ALLOGENEIC TRANSPLANTATION; IDIOTYPIC IMMUNOGLOBULIN; COMBINATION CHEMOTHERAPY C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kwak, LW (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 77 TC 13 Z9 13 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 2004 VL 31 IS 1 BP 37 EP 46 DI 10.1053/j.seminoncol.2003.11.001 PG 10 WC Oncology SC Oncology GA 774UZ UT WOS:000189005000006 PM 14970936 ER PT J AU Kohn, EC Lu, YL Wang, HW Yu, QH Yu, SX Hall, H Smith, DL Meric-Bernstam, F Hortobagyi, GN Mills, GB AF Kohn, EC Lu, YL Wang, HW Yu, QH Yu, SX Hall, H Smith, DL Meric-Bernstam, F Hortobagyi, GN Mills, GB TI Molecular therapeutics: Promise and challenges SO SEMINARS IN ONCOLOGY LA English DT Review ID GENE-EXPRESSION PROFILES; GASTROINTESTINAL STROMAL TUMORS; COPY NUMBER ABNORMALITIES; BREAST-CANCER; OVARIAN-CANCER; IN-VITRO; IMATINIB MESYLATE; MUTANT P53; STEM-CELLS; CLINICAL PROTEOMICS C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. RP Mills, GB (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, 1515 Holcombe Blvd,Box 317-T5-3891, Houston, TX 77030 USA. FU NCI NIH HHS [CA83639, CA64602, CA82716] NR 67 TC 19 Z9 19 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 2004 VL 31 IS 1 SU 3 BP 39 EP 53 DI 10.1053/j.seminoncol.2004.01.009 PG 15 WC Oncology SC Oncology GA 808SX UT WOS:000220589900006 PM 15052542 ER PT J AU Srinivasan, R Barrett, J Childs, R AF Srinivasan, R Barrett, J Childs, R TI Allogeneic stem cell transplantation as immunotherapy for nonhematological cancers SO SEMINARS IN ONCOLOGY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; RESTRICTED TISSUE DISTRIBUTION; CHRONIC MYELOID-LEUKEMIA; HOST DISEASE; T-CELLS; MYELOABLATIVE THERAPY; BREAST-CANCER; TUMOR C1 NCI, NHLBI, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NCI, NHLBI, NIH, 9000 Rockville Pike,10-7C103, Bethesda, MD 20892 USA. NR 50 TC 15 Z9 15 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 2004 VL 31 IS 1 BP 47 EP 55 DI 10.1053/j.seminoncol.2003.11.002 PG 9 WC Oncology SC Oncology GA 774UZ UT WOS:000189005000007 PM 14970937 ER PT J AU Fowler, DH Bishop, MR Gress, RE AF Fowler, DH Bishop, MR Gress, RE TI Immunoablative reduced-intensity stem cell transplantation: Potential role of donor Th2 and Tc2 cells SO SEMINARS IN ONCOLOGY LA English DT Review ID GRAFT-VERSUS-HOST; BONE-MARROW-TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; CD8(+) T-CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; TYPE-2 CYTOKINE PRODUCTION; ANTIGEN-PRESENTING CELLS; HEMATOLOGIC MALIGNANCIES; MIXED CHIMERISM; DENDRITIC CELLS C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 100 TC 12 Z9 13 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 2004 VL 31 IS 1 BP 56 EP 67 DI 10.1053/j.seminoncol.2003.11.003 PG 12 WC Oncology SC Oncology GA 774UZ UT WOS:000189005000008 PM 14970938 ER PT J AU Com, SH Elbedawi, M Castro, O Gladwin, M Palestine, A AF Com, SH Elbedawi, M Castro, O Gladwin, M Palestine, A TI Central retinal vein occlusion in sickle cell disease SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE central retinal vein occlusion; protein S deficiency; sickle cell disease ID PROTEIN-C RESISTANCE; ANEMIA; BLOOD; COAGULATION; YOUNG AB Central retinal vein occlusion has not been reported previously in patients with sickle cell anemia. We describe the case of a 31-year-old man with sickle cell anemia who developed this complication. The search for risk factors for central retinal vein occlusion in this young patient revealed protein S deficiency and a history of iron deficiency. He was treated with anticoagulation therapy, and his vision improved gradually. C1 Howard Univ, Ctr Sickle Cell Dis, Metro Retina Consultants PC, Washington, DC 20059 USA. Howard Univ, Dept Med, Metro Retina Consultants PC, Washington, DC 20059 USA. NIH, Ctr Clin, Crit Care Med Sect, Bethesda, MD 20892 USA. RP Com, SH (reprint author), Howard Univ, Ctr Sickle Cell Dis, Metro Retina Consultants PC, 2121 Georgia Ave NW, Washington, DC 20059 USA. EM syedphasan@hotmail.com NR 18 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD FEB PY 2004 VL 97 IS 2 BP 202 EP 204 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 831CY UT WOS:000222171700023 ER PT J AU Mezey, E AF Mezey, E TI On bone marrow stem cells and openmindedness SO STEM CELLS AND DEVELOPMENT LA English DT Article ID TRAUMATIC BRAIN INJURY; RAT SPINAL-CORD; STROMAL CELLS; ADULT MICE; IN-VIVO; FUNCTIONAL RECOVERY; TRANSPLANTATION; FUSION; DIFFERENTIATION; EXPRESSION AB Several lines of evidence support the concept that pluripotent stem cells reside in the hematopoietic system of adults, but each has been questioned for valid reasons. Thus, the results reported to date after infusion of bone marrow stem cells, may be due to cell fusion, non-physiological de-differentiation and subsequent differentiation to lineages directed by the culture environment, microchimerism, or transdifferentiation. Several authors have suggested complex ways of investigating each of these possibilities, but in no case are any of the suggested protocols complete, nor will they rule out other possible causes of the results observed to date. Determining the nature, origin, and characteristics of adult cells is important and interesting, but the important question at this time is not what happens physiologically, but what we can do with these cells therapeutically. Research addressing therapeutic endpoints now takes a pivotal position in studies of nonembryonic stem cells. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, NIH, Bldg 36,Rm 3D-10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mezeye@ninds.nih.gov NR 36 TC 18 Z9 18 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD FEB PY 2004 VL 13 IS 1 BP 147 EP 152 DI 10.1089/154732804773099344 PG 6 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 843CR UT WOS:000223053700014 PM 15068702 ER PT J AU Warach, S Baron, JC AF Warach, S Baron, JC TI Neuroimaging SO STROKE LA English DT Article DE Advances in Stroke; magnetic resonance imaging; stroke; tomography, emission computed ID ACUTE ISCHEMIC-STROKE; POSITRON-EMISSION-TOMOGRAPHY; SILENT BRAIN INFARCTS; CEREBRAL BLOOD-VOLUME; IN-VIVO; HYPERACUTE STROKE; TISSUE; DIFFUSION; HYPERGLYCEMIA; INFLAMMATION C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Neurol, Cambridge CB2 1TN, England. RP Warach, S (reprint author), NINDS, NIH, 10 Ctr Dr,MSC 1063,Bldg 10,Rm B1D733, Bethesda, MD 20892 USA. EM warachs@ninds.nih.gov OI baron, jean-claude/0000-0002-5264-2588 NR 28 TC 6 Z9 8 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 FEB PY 2004 VL 35 IS 2 BP 351 EP 353 DI 10.1161/01.STR.0000115163.59487.FD PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 769VB UT WOS:000188669500005 PM 14757876 ER PT J AU Kwong, PD AF Kwong, PD TI The 447-52D antibody: Hitting HIV-1 where its armor is thickest SO STRUCTURE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; CRYSTAL-STRUCTURE; NEUTRALIZATION; MOLECULES; SITE C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Kwong, PD (reprint author), NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 7 Z9 7 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD FEB PY 2004 VL 12 IS 2 BP 173 EP 174 DI 10.1016/j.str.2004.01.018 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 820ZZ UT WOS:000221430100004 PM 14962377 ER PT J AU Maurizi, MR Xia, D AF Maurizi, MR Xia, D TI Protein binding and disruption by CIp/Hsp100 chaperones SO STRUCTURE LA English DT Review ID ATP-DEPENDENT PROTEASE; SITE-DIRECTED MUTAGENESIS; CLPX-RECOGNITION SIGNALS; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; SUBSTRATE-BINDING; TERMINAL DOMAIN; SUBUNIT INTERACTIONS; MOLECULAR CHAPERONE; MITOCHONDRIAL HSP78 AB Clp/Hsp100 chaperones work with other cellular chaperones and proteases to control the quality and amounts of many intracellular proteins. They employ an ATP-dependent protein unfoldase activity to solubilize protein aggregates or to target specific classes of proteins for degradation. The structural complexity of Clp/Hsp100 proteins combined with the complexity of the interactions with their macromolecular substrates presents a considerable challenge to understanding the mechanisms by which they recognize and unfold substrates and deliver them to downstream enzymes. Fortunately, high-resolution structural data is now available for several of the chaperones and their functional partners, which together with mutational data on the chaperones and their substrates has provided a glimmer of light at the end of the Clp/Hsp100 tunnel. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM mmaurizi@helix.nih.gov NR 77 TC 37 Z9 37 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD FEB PY 2004 VL 12 IS 2 BP 175 EP 183 DI 10.1016/j.str.2004.01.021 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 820ZZ UT WOS:000221430100005 PM 14962378 ER PT J AU Derewenda, U Mateja, A Devedjiev, Y Routzahn, KM Evdokimov, AG Derewenda, ZS Waugh, DS AF Derewenda, U Mateja, A Devedjiev, Y Routzahn, KM Evdokimov, AG Derewenda, ZS Waugh, DS TI The structure of Yersinia pestis V-antigen, an essential virulence factor and mediator of immunity against plague SO STRUCTURE LA English DT Article ID LOW-CA2+ RESPONSE; PROTEIN; LCRV; SECRETION; SURFACE; DOMAIN; CRYSTALLIZATION; REFINEMENT; MECHANISM; MUTATIONS AB The LcrV protein (V-antigen) is a multifunctional virulence factor in Yersinia pestis, the causative agent of plague. LcrV regulates the translocation of cytotoxic effector proteins from the bacterium into the cytosol of mammalian cells via a type III secretion system, possesses antihost activities of its own, and is also an active and passive mediator of resistance to disease. Although a crystal structure of this protein has been actively sought for better understanding of its role in pathogenesis, the wild-type LcrV was found to be recalcitrant to crystallization. We employed a surface entropy reduction mutagenesis strategy to obtain crystals of LcrV that diffract to 2.2 Angstrom and determined its structure. The refined model reveals a dumbbell-like molecule with a novel fold that includes an unexpected coiled-coil motif, and provides a detailed three-dimensional roadmap for exploring structure-function relationships in this essential virulence determinant. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Procter & Gamble Pharmaceut, Hlth Care Res Ctr Discovery, Mason, OH 45040 USA. RP Waugh, DS (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. EM waughd@ncifcrf.gov FU NIGMS NIH HHS [GM62615] NR 30 TC 106 Z9 109 U1 3 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD FEB PY 2004 VL 12 IS 2 BP 301 EP 306 DI 10.1016/j.str.2004.01.010 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 820ZZ UT WOS:000221430100017 PM 14962390 ER PT J AU Nemukhin, AV Grigorenko, BL Rogov, AV Topol, IA Burt, SK AF Nemukhin, AV Grigorenko, BL Rogov, AV Topol, IA Burt, SK TI Modeling of serine protease prototype reactions with the flexible effective fragment potential quantum mechanical/molecular mechanical method SO THEORETICAL CHEMISTRY ACCOUNTS LA English DT Article DE serine protease; reaction path; quantum mechanical/molecular mechanical modeling ID FREE-ENERGY SURFACES; AB-INITIO; FORCE-FIELD; ACTIVE-SITE; CLAISEN REARRANGEMENT; MOLECULAR-DYNAMICS; ALPHA-CHYMOTRYPSIN; CHORISMATE MUTASE; NMR-SPECTROSCOPY; CHEMICAL-SHIFTS AB A complete cycle of chemical transformations for the serine protease prototype reaction is modeled following calculations with the flexible effective fragment quantum mechanical/molecular mechanical (QM/MM) method. The initial molecular model is based on the crystal structure of the trypsin-bovine pancreatic trypsin inhibitor complex including all atoms of the enzyme within approximately 15-18 Angstrom of the oxygen center O-gamma of the catalytic serine residue. Several selections of the QM/MM partitioning are considered. Fractions of the side chains of the residues from the catalytic triad (serine, histidine and aspartic acid) and a central part of a model substrate around the C-N bond to be cleaved are included into the QM subsystem. The remaining part, or the MM subsystem, is represented by flexible chains of small effective fragments, whose potentials explicitly contribute to the Hamiltonian of the QM part, but the corresponding fragment-fragment interactions are described by the MM force fields. The QM/MM boundaries are extended over the C-alpha-C-beta bonds of the peptides assigned to the QM subsystem in the enzyme, C-C and C-N bonds in model substrates. Multiple geometry optimizations have been performed by using the RHF/6-31G method in the QM part and OPLSAA or AMBER sets of MM parameters, resulting in a series of stationary points on the complex potential-energy surfaces. All structures generally accepted for the serine protease catalytic cycle have been located. Energies at the stationary points found have been recomputed at the MP2/6-31+G* level for the QM part in the protein environment. Structural changes along the reaction path are analyzed with special attention to hydrogen-bonding networks. In the case of a model substrate selected as a short peptide CH3(NHCO-CH2)(2)-HN-CO-(CH2-NHCO)CH3 the computed energy profile for the acylation step shows too high activation energy barriers. The energetics of this rate-limiting step is considerably improved, if more realistic model for the substrate is considered, following the motifs of the ThrI11-GlyI12-ProI13-CysI14-LysI15-AlaI16-ArgI17-IleI18-IleI19 sequence of the bovine pancreatic trypsin inhibitor. C1 NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. RP Topol, IA (reprint author), NCI, Adv Biomed Comp Ctr, SAIC Frederick, POB B, Frederick, MD 21702 USA. EM topol@ncifcrf.gov RI Nemukhin, Alexander/P-9662-2015 NR 58 TC 35 Z9 35 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1432-881X J9 THEOR CHEM ACC JI Theor. Chem. Acc. PD FEB PY 2004 VL 111 IS 1 BP 36 EP 48 DI 10.1007/s00214-003-0556-x PG 13 WC Chemistry, Physical SC Chemistry GA 805PG UT WOS:000220377600005 ER PT J AU Helmberg, W Dunivin, R Feolo, M AF Helmberg, W Dunivin, R Feolo, M TI The reagent database at dbMHC SO TISSUE ANTIGENS LA English DT Article DE database; HLA typing; SSO; SSP; typing interpretation ID HLA-A; DNA-SEQUENCES; RESOLUTION AB The reagent database dbMHC was built by the National Center for Biotechnology Information (NCBI) as an open resource for registration and characterization of HLA DNA-typing kits and reagents. Each reagent is uniquely identified as sequence-specific oligonucleotide (SSO) or primer (SSP), SSO mix, or SSP mix. Computerized prediction of allele reactivities, based on annealing stringency, is performed on all submissions to the reagent database. User-specified allele reactivities may be added or deleted independently of the prediction algorithm. Updates of allele reactivities are performed in synchronization with the IMGT/HLA database, in order to account for newly discovered alleles. Probe and primer sequences aligned to allelic sequences can be displayed at any time. Reagents registered in the reagent database are grouped in typing kits. Each kit or kit batch is uniquely identified. Group-specific amplification of alleles can be specified for an entire kit or for sections of each kit. Kits designed to test multiple loci are supported. Kits can be entered and updated via the web or submitted as batches in extensible markup language (XML) format. A tool for online interpretation of typing results is available. Both the reagent database and the typing kit database have been designed to facilitate the exchange of HLA typing based on raw typing data using the unique identifiers of kits or individual reagents. In addition, batch-wise reinterpretation of previous typing data can be performed either using the NCBI web site or by locally using downloaded allele-reactivity lists. Reinterpretation by the NCBI requires submission of raw typing data in XML format. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Helmberg, W (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 45,45 Ctr Dr, Bethesda, MD 20892 USA. NR 19 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD FEB PY 2004 VL 63 IS 2 BP 142 EP 148 DI 10.1111/j.1399-0039.2004.00163.x PG 7 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 760QX UT WOS:000187846700005 PM 14705985 ER PT J AU MacDonald, J French, JE Gerson, RJ Goodman, J Inoue, T Jacobs, A Kasper, P Keller, D Lavin, A Long, G McCullough, B Sistare, FD Storer, R van der Laan, JW AF MacDonald, J French, JE Gerson, RJ Goodman, J Inoue, T Jacobs, A Kasper, P Keller, D Lavin, A Long, G McCullough, B Sistare, FD Storer, R van der Laan, JW TI The utility of genetically modified mouse assays for identifying human carcinogens: A basic understanding and path forward SO TOXICOLOGICAL SCIENCES LA English DT Article DE carcinogenicity; p53(+/-) knockout mouse; regulatory perspective; risk assessment; Tg.rasH2 transgenic mouse; genetically modified mice ID TUMORS AB The Alternatives to Carcinogenicity Testing Committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) conducted a large-scale, multinational collaborative research program to evaluate several genetically modified mouse assays for assessing the human carcinogenic potential of compounds. The data from this testing program have made an important contribution to the general understanding of how these models can be best applied in hazard identification; however, questions still exist regarding methodology and data interpretation. To address these issues, ILSI HESI hosted a February 2003 workshop on the Utility of Transgenic Assays for Risk Assessment. The purpose of this workshop was to reach an understanding of how data from genetically modified mouse models are viewed by different regulatory bodies in the pharmaceutical sector and, based on this understanding, to identify areas in which more experimental work may be needed to increase the utility of data derived from these assays. In the course of discussions, various data gaps related to model selection and protocol issues were identified. Based on the outcome of the workshop, various studies are proposed to provide data to improve the utility of currently available assays for cancer hazard identification and risk assessment purposes. C1 ILSI HESI, Washington, DC 20005 USA. Schering Plough Res Inst, Kenilworth, NJ 07033 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Endo Pharmaceut, Chadds Ford, PA 19352 USA. Michigan State Univ, E Lansing, MI 48824 USA. Natl Inst Hlth Sci, Tokyo 1588501, Japan. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Fed Inst Drugs & Med Devices BfArM, D-53175 Berlin, Germany. Sanofi Synthelabo Res, Malvern, PA 19355 USA. Eli Lilly & Co, Greenfield, IN 46140 USA. Aventis Pharmaceut Inc, Bridgewater, NJ 08807 USA. Merck Res Labs, W Point, PA 19486 USA. Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands. RP Lavin, A (reprint author), ILSI HESI, 1 Thomas Circle,9th Floor, Washington, DC 20005 USA. EM alavin@ilsi.org OI Keller, Douglas/0000-0002-6186-2881 NR 7 TC 43 Z9 45 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 FEB PY 2004 VL 77 IS 2 BP 188 EP 194 DI 10.1093/toxsci/kfh037 PG 7 WC Toxicology SC Toxicology GA 774ML UT WOS:000188987000003 PM 14657512 ER PT J AU Liu, J Xie, YX Ward, JM Diwan, BA Waalkes, MP AF Liu, J Xie, YX Ward, JM Diwan, BA Waalkes, MP TI Toxicogenomic analysis of aberrant gene expression in liver tumors and nontumorous livers of adult mice exposed in utero to inorganic arsenic SO TOXICOLOGICAL SCIENCES LA English DT Article DE inorganic arsenic; transplacental exposure; hepatocellular carcinoma; microarray; real-time RT-PCR ID HEPATOCELLULAR-CARCINOMA; BLACKFOOT DISEASE; CDNA MICROARRAY; DRINKING-WATER; MOUSE-LIVER; DNA-REPAIR; CELL-LINE; CARCINOGENESIS; TRANSFORMATION; METABOLITES AB Arsenic is a known human carcinogen. We have reported that brief exposure of pregnant C3H mice to arsenite in their drinking water during gestation induced hepatocellular carcinoma (HCC) in male offspring after they became adults. Tumor formation is typically associated with multiple gene expression changes, and this study examined aberrant gene expression associated with transplacental arsenic hepatocarcinogenesis. Liver tumors and nontumorous liver samples were taken at necropsy from adult male mice exposed in utero to either 42.5 or 85 ppm arsenic as sodium arsenite or unaltered water from day 8 to 18 of gestation. Total RNA was extracted and subjected to microarray analysis. Among 600 genes, arsenic-induced HCC showed a higher rate of aberrant gene expression (>2-fold and p < 0.05, 14%) than spontaneous tumors (7.8%). Overexpression of alpha-fetoprotein, c-myc, cyclin D1, proliferation-associated protein PAG, and cytokeratin-18 were more dramatic in arsenic-induced HCC than spontaneous tumors. In nontumorous liver samples of arsenic-exposed animals, 60 genes (10%) were differentially expressed, including the increased expression of alpha-fetoprotein, c-myc, insulin-like growth factor binding protein-1, superoxide dismutase, glutathione S-transferases, and CYP2A4, and the depressed expression of CYP7B1. Real-time RT-PCR analysis largely confirmed these findings. This toxicogenomic analysis revealed several aberrant gene expression changes associated with transplacental arsenic carcinogenesis. It is indeed remarkable that expression changes occurred in adulthood even though arsenic exposure ended during gestation. Some of these aberrantly expressed genes could play a role in the development of arsenic-induced tumors, at least in the liver. C1 NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NCI Frederick, Vet & Tumor Pathol Sect, Off Lab Anim Sci, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Liu, J (reprint author), NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, 111 Alexander Dr,Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. EM Liu6@niehs.nih.gov FU NCI NIH HHS [N01-CA-12400] NR 41 TC 55 Z9 61 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2004 VL 77 IS 2 BP 249 EP 257 DI 10.1093/toxsci/kfh055 PG 9 WC Toxicology SC Toxicology GA 774ML UT WOS:000188987000009 PM 14691202 ER PT J AU Morgan, DL Shines, CJ AF Morgan, DL Shines, CJ TI Alveolar macrophage cytotoxicity for normal lung fibroblasts is mediated by nitric oxide release SO TOXICOLOGY IN VITRO LA English DT Article DE alveolar macrophage; lung fibroblast; lipopolysaccharide; cytotoxicity; nitric oxide ID TUMOR-NECROSIS-FACTOR; MOUSE MACROPHAGES; TYROSINE PHOSPHORYLATION; ACTIVATED MACROPHAGES; SYNTHASE GENE; GROWTH-FACTOR; PEROXYNITRITE; ENDOTOXIN; CELLS; LIPOPOLYSACCHARIDE AB Nitric oxide (NO) released by activated alveolar macrophages (AM) can mediate effects on target cells and can also react with superoxide anion (O-2-) to form peroxynitrite (PN), a highly cytotoxic product. The role of NO and PN in AM cytotoxicity for normal lung cells was investigated using co-cultures of rat lung fibroblasts (FB) and rat AM treated with lipopolysaccharide + interferon-gamma (LI). AM and FB, alone and in co-culture, were treated with LI for 5 days and cell viability measured. The culture media was analyzed for NO, TNF-alpha, O-2-, and IL-1beta. A decreased FB viability was correlated with increased NO release by LI-activated AM. Pretreatment of co-cultures with the inducible NOS inhibitor L-NAME caused dose-related decreases in NO release by AM and increases in FB viability. Although TNF-alpha release was increased in co-cultures treated with LI, the viability of FB was not affected when cultures were treated with similar concentrations of TNF-a in the absence of AM. O-2- could not be detected in the media and addition of superoxide dismutase (SOD) did not protect FB. These data suggest that neither O-2- nor PN contributed to the loss of cell viability. Activated AM may kill normal rat lung FB through a NO-mediated pathway that does not involve PN. Published by Elsevier Ltd. C1 NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Morgan, DL (reprint author), NIEHS, Mol Toxicol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM morgand@niehs.nih.gov NR 36 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD FEB PY 2004 VL 18 IS 1 BP 139 EP 146 DI 10.1016/j.tiv.2003.08.007 PG 8 WC Toxicology SC Toxicology GA 763DL UT WOS:000188058900017 PM 14630072 ER PT J AU Bolan, CD Yau, YY Cullis, HC Horwitz, ME Mackall, CL Barrett, AJ Malech, HL Rehak, NN Wayne, AS Leitman, SF AF Bolan, CD Yau, YY Cullis, HC Horwitz, ME Mackall, CL Barrett, AJ Malech, HL Rehak, NN Wayne, AS Leitman, SF TI Pediatric large-volume leukapheresis: a single institution experience with heparin versus citrate-based anticoagulant regimens SO TRANSFUSION LA English DT Article ID BLOOD STEM-CELLS; SMALL CHILDREN; 20 KG; APHERESIS; TRANSPLANTATION; COLLECTION; DONOR; PLATELETPHERESIS; MOBILIZATION; PREDICTS AB BACKGROUND: Anticoagulant-associated toxicity may exert significant effects on the safety and efficacy of large-volume leukapheresis (LVL) in children, however, few studies specifically address management of this issue. STUDY DESIGN AND METHODS: Seventy-four consecutive LVL procedures (mean, 4 blood volumes processed) in children weighing less than or equal to 30 kg (minimum, 10.9 kg) were analyzed. The first 21 procedures were evaluated retrospectively; 11 used heparin alone (Group I) and 10 used heparin plus reduced-dose ACD-A (whole blood to anticoagulant ratio greater than or equal to20:1) (Group II). The next 53 procedures were evaluated prospectively and used full-dose ACD-A (whole blood to anticoagulant ratio less than or equal to 13:1), intravenous divalent cation prophylaxis and no heparin; 11 used calcium alone (Group III) followed by 42 with calcium plus magnesium (Group IV). RESULTS: Seventy-four LVL (56 PBPC and 18 MNC) collections were performed in 38 subjects. One donor in Group I experienced a significant groin hematoma at the site of line placement. One donor each in Groups III and IV had mild paresthesias. Despite a mean citrate infusion rate of 2.6 mg per kg per minute, mean postapheresis serum potassium and ionized magnesium and calcium concentrations in Group IV declined by only 9, 8, and 4 percent, respectively, and stable levels of these variables were maintained 24 hours later. Postapheresis PLT counts declined significantly from baseline preapheresis levels in all groups (mean, 52% decrease). CONCLUSIONS: Use of full-dose citrate anticoagulant with prophylactic intravenous divalent cation infusion offers an effective and safe approach to management of anticoagulant-related toxicity in children undergoing LVL. C1 Amer Fluoroseal Corp, Gaithersburg, MD USA. Walter Reed Army Inst Res, Silver Spring, MD USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIAID, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIAID, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. RP Leitman, SF (reprint author), NIAID, Dept Transfus Med, NIH, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM sleitman@mail.cc.nih.gov NR 25 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2004 VL 44 IS 2 BP 229 EP 238 DI 10.1111/j.1537-2995.2004.00668.x PG 10 WC Hematology SC Hematology GA 775RH UT WOS:000189055900013 PM 14962314 ER PT J AU Raju, R AF Raju, R TI Tracking the 'General': tagging skin-derived dendritic cells SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID FLUORESCEIN ISOTHIOCYANATE; IMMUNIZATION; ANTIGEN AB Dendritic cells (DCs) are the sentinels of the immune system; their migration, maturation and mobilization are fundamental to immunity and tolerance. The recent tracking of DCs from the skin to lymph node (LN) and their enumeration using a Cre/loxP system demonstrate the recruitment of a higher than expected number of DCs to the draining LN after cutaneous administration of DNA-coated gold particles. The longevity of the migrated DCs was also longer than previously reported. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Raju, R (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10 Room 4N252,10 Ctr Dr, Bethesda, MD 20892 USA. EM RajuR@ninds.mh.gov RI Raju, Raghavan/E-9219-2011 NR 12 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD FEB PY 2004 VL 22 IS 2 BP 58 EP 59 DI 10.1016/j.tibtech.2003.11.005 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 774KK UT WOS:000188978500003 PM 14757036 ER PT J AU Seong, E Saunders, TL Stewart, CL Burmeister, M AF Seong, E Saunders, TL Stewart, CL Burmeister, M TI To knockout in 129 or in C57BL/6: that is the question SO TRENDS IN GENETICS LA English DT Article ID MOUSE STRAINS; CELL-LINES; GENE; ESTABLISHMENT; MICE AB Traditionally, knockout experiments are performed in ES cells derived from the 129 mouse strain, followed by backcrossing with the more robust C57BL/6 strain. C57BL/6-derived ES cells have only occasionally been used in this process. We compared C57BL/6- with 129-derived ES cells directly and reviewed the literature. We found that, although some steps are less efficient, the advantages of C57BL/6 mice more than compensate for these drawbacks. C1 Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA. Univ Michigan, Neurosci Program, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Burmeister, M (reprint author), Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA. EM margit@umich.edu RI Burmeister, Margit/A-3157-2013; OI Burmeister, Margit/0000-0002-1914-2434; Saunders, Thom/0000-0003-2015-101X FU NINDS NIH HHS [NS32130] NR 18 TC 75 Z9 81 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 2004 VL 20 IS 2 BP 59 EP 62 DI 10.1016/j.tig.2003.12.006 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 774QM UT WOS:000188994600001 PM 14746984 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI Proteomic approaches in cancer risk and response assessment SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID PROTEIN IDENTIFICATION TECHNOLOGY; TYROSINE KINASE INHIBITOR; IMMOBILIZED PH GRADIENTS; OVARIAN-CANCER; MASS-SPECTROMETRY; BREAST-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; TRASTUZUMAB HERCEPTIN; CLINICAL PROTEOMICS; MYELOID-LEUKEMIA AB Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy. C1 NCI, FDA, Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), NCI, FDA, Clin Proteom Program, Bldg 29A,Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 70 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD FEB PY 2004 VL 10 IS 2 BP 59 EP 64 DI 10.1016/j.molmed.2003.12.006 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 780BE UT WOS:000189350600004 PM 15102358 ER PT J AU Lu, L Hope, BT Shaham, Y AF Lu, L Hope, BT Shaham, Y TI The cystine-glutamate transporter in the accumbens: a novel role in cocaine relapse SO TRENDS IN NEUROSCIENCES LA English DT Article ID DRUG-SEEKING BEHAVIOR; STRESS-INDUCED RELAPSE; NUCLEUS-ACCUMBENS; INDUCED REINSTATEMENT; RATS; TRANSMISSION; ADDICTION; NEUROADAPTATIONS; SENSITIZATION; NEUROBIOLOGY AB Baker et al. have recently studied the potential role of cocaine-induced alterations in accumbens cystine-glutamate transporter activity (which controls basal extracellular glutamate levels) during cocaine-induced relapse to drug seeking in rats. Their data provide new evidence that neuroadaptations induced by repeated exposure to cocaine and subsequent withdrawal can play a causal role in drug relapse. These data also suggest the cystine-glutamate transporter as a novel target for medication that could prevent cocaine relapse. C1 NIDA, IRP, DHHS, Behav Neurosci Branch,NIH, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, IRP, DHHS, Behav Neurosci Branch,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; NR 27 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD FEB PY 2004 VL 27 IS 2 BP 74 EP 76 DI 10.1016/j.tins.2003.11.007 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 775XR UT WOS:000189086400006 PM 15106652 ER PT J AU Andersson, J AF Andersson, J TI Molecular diagnosis of experimental Chagas disease SO TRENDS IN PARASITOLOGY LA English DT Article ID TRYPANOSOMA-CRUZI; AUTOIMMUNITY AB Diagnostic methods for detecting Trypanosoma cruzi infection are important to allow administration of chemotherapy and as an experimental tool when trying to understand the pathogenesis of Chagas disease. A nested polymerase chain reaction (PCR)-based approach was recently used to demonstrate preferential heart and skeletal muscle tropism in mice of a Mexican T cruzi isolate. The authors of this study also demonstrated higher sensitivity for this PCR setup compared with a commercially available enzyme-linked immuno-sorbent assay kit. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Andersson, J (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM jandersson@niaid.nih.gov RI Andersson, John/A-4436-2009; OI Andersson, John/0000-0003-2799-6349 NR 14 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD FEB PY 2004 VL 20 IS 2 BP 52 EP 53 DI 10.1016/j.pt.2003.10.017 PG 2 WC Parasitology SC Parasitology GA 773VH UT WOS:000188944500002 PM 14747014 ER PT J AU Hubbard, JS Rohrmann, S Landis, PK Metter, EJ Muller, DC Andres, R Carter, HB Platz, EA AF Hubbard, JS Rohrmann, S Landis, PK Metter, EJ Muller, DC Andres, R Carter, HB Platz, EA TI Association of prostate cancer risk with insulin, glucose, and anthropometry in the Baltimore longitudinal study of aging SO UROLOGY LA English DT Article ID UNITED-STATES; BODY-SIZE; PHYSICAL-ACTIVITY; FAT DISTRIBUTION; PLASMA-GLUCOSE; SERUM LEVELS; 4.0 NG/ML; POPULATION; LEPTIN; RESISTANCE AB Objectives. To examine the relationship of insulin, glucose, and anthropometry with the subsequent risk of prostate cancer. Methods. The relative risk of prostate cancer by insulin, glucose, and anthropometric measures was evaluated in 823 male participants (87 patients with prostate cancer in 10,737 person-years of follow-up) of the Baltimore Longitudinal Study of Aging who had at least one fasting plasma insulin measurement, which was prediagnostic for those with prostate cancer. Age-adjusted and multivariate-adjusted relative risks were estimated from Cox proportional hazards regression models. Results. Insulin concentrations were in the normal range (defined as less than 20 muU/mL) for 95.1% of participants. Fasting insulin and glucose levels were unrelated to prostate cancer risk in our overall analysis (P for trend = 0.56 and 0.45, respectively). The relative risk of prostate cancer for the second through fourth quartiles of the waist/hip ratio compared with the lowest quartile was 2.10, 1.96, and 2.06, respectively (P for trend = 0.32). Risk was unrelated to waist circumference and body mass index. Conclusions. The results of this study do not conclusively support positive associations of markers of insulin and glucose metabolism and obesity with prostate cancer. Additional larger prospective studies with repeated measure of these parameters are warranted to explore these associations further. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. NIA, Clin Invest Lab, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Carter, HB (reprint author), Johns Hopkins Univ Hosp, James Buchanan Brady Urol Inst, Marburg 403,600 N Wolfe St, Baltimore, MD 21287 USA. RI Rohrmann, Sabine/D-2113-2012 NR 30 TC 62 Z9 65 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 FEB PY 2004 VL 63 IS 2 BP 253 EP 258 DI 10.1016/j.urology.2003.09.060 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 774QU UT WOS:000188995300010 PM 14972466 ER PT J AU Song, CZ Wang, QW Song, CC Bai, ZL AF Song, Chang-Zheng Wang, Qing-Wei Song, Chang-Cheng Bai, Zeng-Liang TI Viral replication modulated by synthetic peptide derived from hepatitis B virus X protein SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article AB AIM: A strategy for viral vaccine design is the use of conserved peptides to overcome the problem of sequence diversity. At present it is still unclear whether conserved peptide is safe as a candidate vaccine. We reported it here for the first time not only to highlight the biohazard issue and safety importance for viral peptide vaccine, but also to explore the effect of a fully conserved peptide on HBV replication within the carboxyl terminus of HBx. METHODS: We synthesized the fully conserved peptide (CP) with nine residues, FVLGGCRHK. HBV-producing 2.2.15 cells were treated with or without 3.5 mu M CP for 36 hours. Quantitative detection of viral DNA was performed by real-time PCR. HBV antigens were determined by enzyme-linked immunoadsorbent assay (ELISA). Quantitative analyses of p53 and Bax proteins were based on immunofluorescence. Flow cytometry was performed to detect cell cycle and apoptosis. RESULTS: Both extracellular and intracellular copies of HBV DNA per ml were significantly increased after incubation with 3.5 mu M of CP. HBsAg and HBeAg in the cultured medium of CP-treatment cells were as abundant as untreated control cells. CP influenced negatively the extracellular viral gene products, and 3.5 mu M CP could significantly inhibit intracellular HBsAg expression. In response to CP, intracellular HBeAg displayed an opposite pattern to that of HBsAg, and 3.5 mu M CP could efficiently increase the level of intracellular HBeAg. Flow cytometric analyses exhibited no significant changes on cell cycle, apoptosis, p53 and Bax proteins in 2.2.15 cells with or without CP. CONCLUSION: Together with the results generated from the synthetic peptide, we address that the conserved region, a domain of HBx, may be responsible for modulating HBV replication. As conserved peptides from infectious microbes are used as immunogens to elicit immune responses, their latent biological hazard for human beings should be evaluated. C1 [Song, Chang-Zheng] Shandong Acad Med Sci, Shandong Res Ctr Med Biotechnol, Project Viral Vaccine, Jinan 250062, Shandong, Peoples R China. [Song, Chang-Zheng; Bai, Zeng-Liang] Shandong Univ, Coll Life Sci, Immunobiol Lab, Jinan 250100, Shandong, Peoples R China. [Wang, Qing-Wei] Shandong Univ, Qilu Hosp, Canc Res Ctr, Jinan 250012, Shandong, Peoples R China. [Song, Chang-Cheng] NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Song, CZ (reprint author), Shandong Acad Med Sci, Shandong Res Ctr Med Biotechnol, Project Viral Vaccine, Jinan 250062, Shandong, Peoples R China. EM songcz@life.sdu.edu.cn NR 29 TC 3 Z9 3 U1 0 U2 1 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD FEB 1 PY 2004 VL 10 IS 3 BP 389 EP 392 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V21RD UT WOS:000208223800017 PM 14760764 ER PT J AU Hu, Y Krausz, K Gelboin, HV Kupfer, D AF Hu, Y Krausz, K Gelboin, HV Kupfer, D TI CYP2C subfamily, primarily CYP2C9, catalyses the enantioselective demethylation of the endocrine disruptor pesticide methoxychlor in human liver microsomes: use of inhibitory monoclonal antibodies in P450 identification SO XENOBIOTICA LA English DT Article ID ENANTIOTOPIC SELECTIVITY; CYTOCHROME-P450 ENZYMES; OXIDATIVE DEMETHYLATION; ESTROGENIC ACTIVITIES; CATECHOL METABOLITE; IN-VITRO; RECEPTOR; RAT; MONOOXYGENASES; GENE AB 1. The endocrine disruptor pesticide methoxychlor undergoes O -demethylation by mammalian liver microsomes forming chiral mono-phenolic (1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane, i.e. mono-OH-M) and achiral bis-phenolic oestrogenic metabolites. Human liver microsomes (HLM) generated primarily the S -mono-OH-M. 2. Inhibitory monoclonal antibodies (MAb) identified those P450s catalysing the enantioselective O -demethylation of methoxychlor. In HLM, O -demethylation was inhibited by MAb anti-2C9 (30-40%), diminishing the per cent of S -mono-OH-M from about 80 to 55-60%. MAb anti-CYP1A2, 2A6, 2B6, 2C8, 2C19, 2D6 and 3A4 did not affect the demethylation rate in HLM. Nevertheless, MAb anti-CYP1A2 decreased the formation of R -mono-OH-M from 21-23 to 10-17%, indicating that CYP1A2 exhibits a role in generating the R -enantiomer. 3. Among cDNA-expressed human P450s (supersomes), CYP2C19 was the most active in demethylation, but in HLM, CYP2C19 appeared inactive (no inhibition by MAb anti-CYP2C19). There was a substantial difference in the per cent inhibition of demethylation by MAb anti-CYP2C9 and anti-rat CYP2C (MAb inhibiting all human CYP2C forms) and in altering the enantioselectivity, suggesting that demethylation by combined CYP2C8, 2C18 and 2C19 was significant (20-30%). 4. Polymorphism of methoxychlor demethylation was examined with supersomes and HLM-expressing CYP2C9 allelic variants. CYP2C9*1 and 2C9*2 were highly active; however, CYP2C9*3 appeared inactive. C1 Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Kupfer, D (reprint author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. EM david.kupfer@umassmed.edu FU NIEHS NIH HHS [ES00834] NR 41 TC 17 Z9 17 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD FEB PY 2004 VL 34 IS 2 BP 117 EP 132 DI 10.1080/00498250310001644535 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 778UC UT WOS:000189258300001 PM 14985143 ER PT J AU Minn, AH Kayton, M Lorang, D Hoffmann, SC Harlan, DM Libutti, SK Shalev, A AF Minn, AH Kayton, M Lorang, D Hoffmann, SC Harlan, DM Libutti, SK Shalev, A TI Insulinomas and expression of an insulin splice variant SO LANCET LA English DT Article ID HUMAN PANCREATIC-ISLETS; TRANSLATIONAL CONTROL; PROINSULIN BIOSYNTHESIS; BETA-CELL; GLUCOSE; GENE; INITIATION; MUTATIONS AB Background Insulinomas are beta-cell tumours characterised by uncontrolled insulin secretion even in the presence of hypoglycaemia. However, the mechanisms allowing such excessive insulin secretion are not known. Insulin secretion can occur only when the beta-cell insulin stores have been replenished by insulin biosynthesis, which is mainly controlled by translation. Such specific translational regulation often involves the 5' untranslated region. We have identified an insulin splice variant in isolated human pancreatic islets of non-diabetic donors that retains 26 bp of intron 1 and thereby changes the 5' untranslated region, but leaves the coding region unchanged. This splice variant has increased translation efficiency in vitro and in vivo compared with native insulin mRNA. However, splice variant expression is less than 1% of native insulin mRNA in normal islets. Methods To test whether this splice variant is involved in insulin production by human insulinomas, we extracted RNA from nine laser-captured surgical insulinoma samples and from isolated islets of nine donors who did not have diabetes. We then determined the ratio of splice variant to native insulin mRNA by quantitative real-time RT-PCR. Findings The mean ratio of the splice variant to native insulin mRNA was increased more than 50-fold in insulinomas compared with normal islets, and this difference was present in all nine human insulinomas. Overexpression of the splice variant therefore seems to be a general characteristic of insulinomas and is estimated to contribute about 90% to insulin synthesis by these tumours. Interpretation Overexpression of the insulin splice variant with increased translation efficiency in insulinomas might explain how these tumours maintain high levels of insulin synthesis and secretion leading to hyperinsulinaemia-the hallmark of this disease. C1 Univ Wisconsin, Dept Med, Endocrinol Sect, Madison, WI 53792 USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. NIDDKD, NIH, DHHS, Bethesda, MD 20892 USA. RP Shalev, A (reprint author), Univ Wisconsin, Dept Med, Endocrinol Sect, H4-526 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. EM as7@medicine.wisc.edu NR 29 TC 16 Z9 18 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 31 PY 2004 VL 363 IS 9406 BP 363 EP 367 DI 10.1016/S0140-6736(04)15438-X PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 768TQ UT WOS:000188590900012 PM 15070567 ER PT J AU Ng, D Johnston, JJ Turner, JT Boudreau, EA Wiggs, EA Theodore, WH Biesecker, LG AF Ng, D Johnston, JJ Turner, JT Boudreau, EA Wiggs, EA Theodore, WH Biesecker, LG TI Gonadal mosaicism in severe Pallister-Hall syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE hypothalamic hamartoma; mental retardation ID HYPOTHALAMIC HAMARTOMAS; GELASTIC SEIZURES; CHILDREN; GENES AB Pallister-Hall syndrome (PHS,MIM#146510) is characterized by central and postaxial polydactyly, hypothalamic hamartoma (HH), bifid epiglottis, imperforate anus, renal abnormalities, and pulmonary segmentation anomalies. It is inherited in an autosomal dominant pattern. Here, we describe a family with two affected children manifesting severe PHS with mental retardation, behavioral problems, and intractable seizures. Both parents are healthy, with normal intelligence, and have no malformations on physical, laryngoscopic, and cranial MRI exam. The atypical presentation of these children and the absence of parental manifestations suggested an autosomal recessive mode of inheritance or gonadal mosaicism. Sequencing of GLI3 revealed a two nucleotide deletion in exon 15 (c.3385(-)3386delTT) predicting a frameshift and premature stop at codon 1129 (p.F1129X) in the children while both parents have wild type alleles. Genotyping with GLI3 intragenic markers revealed that both children inherited the abnormal allele from their mother thus supporting gonadal mosaicism as the underlying mechanism of inheritance (paternity was confirmed). This is the first reported case of gonadal mosaicism in PHS. The severe CNS manifestations of these children are reminiscent of children with non-syndromic HH who often have progressive mental retardation with behavioral problems and intractable seizures. We conclude that the phenotypic spectrum of PHS can include severe CNS manifestations and that recurrence risks for PHS should include a proviso for gonadal mosaicism, though the frequency cannot be calculated from a single case report. Published 2003 Wiley-Liss, Inc(dagger). C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Ng, D (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49,Room 4C72, Bethesda, MD 20892 USA. EM davidng@nhgri.nih.gov NR 14 TC 16 Z9 16 U1 1 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 A JI Am. J. Med. Genet. A PD JAN 30 PY 2004 VL 124A IS 3 BP 296 EP 302 DI 10.1002/ajmg.a.20338 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 761GN UT WOS:000187893300012 PM 14708104 ER PT J AU Alves, VS Pimenta, DC Sattlegger, E Castilho, BA AF Alves, VS Pimenta, DC Sattlegger, E Castilho, BA TI Biophysical characterization of Gir2, a highly acidic protein of Saccharomyces cerevisiae with anomalous electrophoretic behavior SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Gir2; highly acidic; anomalous behavior; natively unfolded ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; DODECYL-SULFATE; CHEMICAL-MODIFICATION; IDENTIFICATION; SEQUENCES; RESIDUES; DOMAIN AB Gir2 is an uncharacterized protein of Saccharomyces cerevisiae, containing a RWD/GI domain. In this work, we report the biophysical characterization of Gir2. His-tagged Gir2, expressed and purified from Escherichia coli, showed an abnormally slow migration on SDS-PAGE. The yeast expressed protein behaves similarly. Using mass spectrometry and peptide mass fingerprinting we demonstrated that the protein has the expected molecular mass (34 kDa). EDC modification of carboxylate groups reverted the anomalous migration on SDS-PAGE. Size exclusion chromatography showed that Gir2 has a Stokes radius larger than expected. Gir2 is thermostable and lacks extensive structure, as determined by CD analysis. Based on these findings, we suggest that Gir2 is a representative of the growing group of "natively unfolded" proteins. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, Brazil. Ctr Toxincol Aplicada, CAT, CEPID, Inst Butantan, Sao Paulo, SP, Brazil. NICHHD, NIH, Bethesda, MD 20892 USA. RP Castilho, BA (reprint author), Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Rua Botucatu 862, Sao Paulo, SP, Brazil. EM bac@ecb.epm.br RI Castilho, Beatriz/C-2503-2012; Alves, Viviane/C-2776-2013; Pimenta, Daniel/B-4361-2008 OI Castilho, Beatriz/0000-0003-4509-5237; Pimenta, Daniel/0000-0003-2406-0860 NR 20 TC 19 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 30 PY 2004 VL 314 IS 1 BP 229 EP 234 DI 10.1016/j.bbrc.2003.12.086 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 765CU UT WOS:000188250200034 PM 14715270 ER PT J AU Prabakaran, P Mao, XD Dimitrov, DS AF Prabakaran, P Mao, XD Dimitrov, DS TI A model of the ACE2 structure and function as a SARS-CoV receptor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ACE2; structure prediction; SARS-CoV; S-glycoprotein; receptor; binding ID ANGIOTENSIN-CONVERTING ENZYME-2; HOMOLOGOUS PROTEINS; CRYSTAL-STRUCTURE; CARBOXYPEPTIDASE; GLYCOPROTEIN; CORONAVIRUS; LISINOPRIL; EXPRESSION; CAPTOPRIL; SEQUENCE AB The angiotensin-converting enzyme 2 (ACE2) is an important regulator of the renin-angiotensin system and was very recently identified as a functional receptor for the SARS virus. The ACE2 sequence is similar (sequence identities 43% and 35%, and similarities 61% and 55%, respectively) to those of the testis-specific form of ACE (tACE) and the Drosophila homolog of ACE (AnCE). The high level of sequence similarity allowed us to build a robust homology model of the ACE2 structure with a root-mean-square deviation from the aligned crystal structures of tACE and AnCE less than 0.5Angstrom. A prominent feature of the model is a deep channel on the top of the molecule that contains the catalytic site. Negatively charged ridges surrounding the channel may provide a possible binding site for the positively charged receptor-binding domain (RBD) of the S-glycoprotein, which we recently identified [Biochem. Biophys. Res. Commun. 312 (2003) 1159]. Several distinct patches of hydrophobic residues at the ACE2 surface were noted at close proximity to the charged ridges that could contribute to binding. These results suggest a possible binding region for the SARS-CoV S-glycoprotein on ACE2 and could help in the design of experiments to further elucidate the structure and function of ACE2. (C) 2003 Elsevier Inc. All rights reserved. C1 NCI, Lab Expt & Computat Biol, CCR, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, Lab Expt & Computat Biol, CCR, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov RI Ponraj, Prabakaran/D-6325-2011 NR 20 TC 50 Z9 57 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 30 PY 2004 VL 314 IS 1 BP 235 EP 241 DI 10.1016/j.bbrc.2003.12.081 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 765CU UT WOS:000188250200035 PM 14715271 ER PT J AU Nukaya, M Takahashi, Y Gonzalez, FJ Kamataki, T AF Nukaya, M Takahashi, Y Gonzalez, FJ Kamataki, T TI Aryl hydrocarbon receptor-mediated suppression of GH receptor and Janus kinase 2 expression in mice SO FEBS LETTERS LA English DT Article DE aryl hydrocarbon receptor; growth hormone receptor; 3-methylcholanthrene; Janus kinase 2; major urinary protein; signal transducer and activator of transcription 5; wasting syndrome ID PHEROMONE-BINDING-PROTEINS; LIVER-SPECIFIC PROMOTER; MAJOR URINARY PROTEINS; OSTEOBLASTS IN-VITRO; AH RECEPTOR; SEXUAL-DIMORPHISM; GENE-EXPRESSION; MAMMARY-GLAND; MOUSE-LIVER; GROWTH AB Differential mRNA display revealed that a cDNA encoding the major urinary protein 2 (MUP2) that belongs to the lipocalin superfamily was absent in livers of mice treated with 3-methylcholanthrene (MC). The expression of MUP2 is known to be stimulated by growth hormone (GH), through the GH receptor (GUR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) signal transduction pathway. Since MC is an aryl hydrocarbon receptor (AhR) ligand, the effects of MC treatment on the expression of GHR, JAK2 or STAT5 in the livers of wild-type or AhR-null mice were examined. The result indicated that the expression of GHR and JAK2 mRNA was greatly decreased by MC in wildtype mice but not in AhR-null mice. In addition, the binding activity of STAT5 bound to STAT5-binding element was reduced after MC treatment in wild-type mice but not in AhR-null mice. Based on these results, we conclude that the suppression of MUP2 mRNA expression by MC is caused by the AhR-mediated disruption of the GH signaling pathway. Possible mechanism(s) by which exposure to aromatic hydrocarbons causes a decrease in the body weight of mice, which has been referred to as wasting syndrome, will also be discussed. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Hokkaido Univ, Grad Sch Pharmaceut Sci, Div Pharmacobio Dynam, Lab Drug Metab,Kita Ku, Sapporo, Hokkaido 0600812, Japan. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Kamataki, T (reprint author), Hokkaido Univ, Grad Sch Pharmaceut Sci, Div Pharmacobio Dynam, Lab Drug Metab,Kita Ku, N12W6, Sapporo, Hokkaido 0600812, Japan. EM kamataki@pharm.hokudai.ac.jp NR 43 TC 16 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 30 PY 2004 VL 558 IS 1-3 BP 96 EP 100 DI 10.1016/S0014-5793(03)01528-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 772AJ UT WOS:000188817900019 PM 14759523 ER PT J AU Jeong, W Yoon, HW Lee, SR Rhee, SG AF Jeong, W Yoon, HW Lee, SR Rhee, SG TI Identification and characterization of TRP14, a thioredoxin-related protein of 14 kDa - New insights into the specificity of thioredoxin function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ESCHERICHIA-COLI THIOREDOXIN; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; MAMMALIAN PEROXIREDOXIN; MOLECULAR-CLONING; HYDROGEN-PEROXIDE; REDOX REGULATION; REDUCED FORM; REDUCTASE AB We have identified and characterized a 14-kDa human thioredoxin (Trx)-related protein designated TRP14. This cytosolic protein was expressed in all tissues and cell types examined, generally in smaller amounts than Trx1. Although TRP14 contains five cysteines, only the two Cys residues in its WCPDC motif were exposed and redox sensitive. Unlike Trx1, which was an equally good substrate for both Trx reductase 1 (TrxR1) and TrxR2, oxidized TRP14 was reduced by TrxR1 but not by TrxR2. Biochemical characterization of TRP14 suggested that, like Trx1, TRP14 is a disulfide reductase; its active site cysteine is sufficiently nucleophilic with the pK(a) value of 6.1; and its redox potential (-257 mV) is similar to those of other cellular thiol reductants. However, although TRP14 reduced small disulfide-containing peptides, it did not reduce the disulfides of known Trx1 substrates, ribonucleotide reductase, peroxiredoxin, and methionine sulfoxide reductase. These results suggest that TRP14 and Trx1 might act on distinct substrate proteins. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. RP Rhee, SG (reprint author), Bldg 50,Room 3523,South Dr,MSC 8015, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 52 TC 59 Z9 63 U1 1 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 JAN 30 PY 2004 VL 279 IS 5 BP 3142 EP 3150 DI 10.1074/jbc.M307932200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600003 PM 14607844 ER PT J AU Jeong, W Chang, TS Boja, ES Fales, HM Rhee, SG AF Jeong, W Chang, TS Boja, ES Fales, HM Rhee, SG TI Roles of TRP14, a thioredoxin-related protein in tumor necrosis factor-alpha signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; SUPEROXIDE-DISMUTASE GENE; STRESS-INDUCED APOPTOSIS; OXIDATIVE STRESS; CELL-DEATH; TRANSCRIPTION FACTOR; HYDROGEN-PEROXIDE; PROTECTIVE ACTIVITY; REDOX REGULATION; TNF RECEPTOR-1 AB The possible roles of a 14-kDa human thioredoxin (Trx)-related protein (TRP14) in TNF-alpha signaling were studied in comparison with those of Trx1 by RNA interference in HeLa cells. Depletion of TRP14 augmented the TNF-alpha-induced phosphorylation and degradation of IkappaBalpha as well as the consequent activation of NF-kappaB to a greater extent than did Trx1 depletion. Deficiency of TRP14 or Trx1 enhanced TNF-alpha-induced activation of caspases and subsequent apoptosis by a similar extent. The TNF-alpha-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs), however, was promoted by depletion of TRP14 but not by that of Trx1. Unlike Trx1, TRP14 neither associated with nor inhibited the kinase activity of apoptosis signal-regulating kinase-1 (ASK1), an upstream activator of JNK and p38. In combination with the results in the accompanying paper that TRP14 did not reduce the known substrates of Trx1, these results suggest that TRP14 modulates TNF-alpha signaling pathways, provably by interacting with proteins distinct from the targets of Trx1. In an effort to identify target proteins of TRP14, a mutant of TRP14, in which the active site cysteine (Cys46) was substituted with serine, was shown to form a disulfide-linked complex with LC8 cytoplasmic dynein light chain. The complex was detected in HeLa cells treated with H2O2 or TNF-alpha but not in untreated cells, suggesting that LC8 cytoplasmic dynein light chain is a possible substrate of TRP14. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), Bldg 50,Room 3523,South Dr,MSC 8015, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 66 TC 41 Z9 46 U1 1 U2 4 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 JAN 30 PY 2004 VL 279 IS 5 BP 3151 EP 3159 DI 10.1074/jbc.M307959200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600004 PM 14607843 ER PT J AU Kennett, SB Roberts, JD Olden, K AF Kennett, SB Roberts, JD Olden, K TI Requirement of protein kinase C mu activation and calpain-mediated proteolysis for arachidonic acid-stimulated adhesion of MDA-MB-435 human mammary carcinoma cells to collagen type IV SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT NEUTRAL PROTEASE; BREAST-CANCER; PKC-MU; PHOSPHORYLATION SITES; HUMAN-NEUTROPHILS; DOWN-REGULATION; PHORBOL ESTERS; LOOP SER(744); LINOLEIC-ACID; DNA-SYNTHESIS AB Arachidonic acid (AA) stimulation of adhesion of human metastatic breast carcinoma cells to collagen type IV depends on the protein kinase C (PKC) pathway(s) and is associated with the translocation of PKCmu from the cytoplasm to the membrane. In the present study, we have further explored the role of PKCmu in AA-stimulated adhesion. PKCmu activation site serines 738/742 and autophosphorylation site serine 910 are rapidly phosphorylated, and in vitro PKCmu kinase activity is enhanced in response to AA treatment. Inhibition of PKCmu activation blocks AA-stimulated adhesion. A phosphorylated, truncated species of PKCmu was detected in AA-treated cells. This 77-kDa protein contains the kinase domain but lacks a significant portion of the regulatory domains. Inhibition of calpain protease activity blocks generation of the truncated protein, promotes accumulation of the activated, full-length protein in the membrane, and blocks the AA-mediated increase in adhesion. p38 MAPK activity is also required for AA-stimulated adhesion. Activation of PKCmu and p38 are independent events. However, inhibition of p38 activity reduces calpain-mediated proteolysis of PKCmu and in vivo calpain activity, suggesting a role for p38 in regulation of calpain activity and a point for cross-talk between the PKC and MAPK pathways. These results support the hypothesis that AA stimulates activation of PKCmu, which is cleaved by calpain at the cell membrane. The resulting truncated kinase, as well as the full-length kinase, may be required for increased cell adhesion to collagen type IV. Additionally, these studies present the first evidence for calpain cleavage of a non-structural protein leading to the promotion of tumor cell adhesion. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Roberts, JD (reprint author), POB 12233,Mail Drop C2-14, Res Triangle Pk, NC 27709 USA. EM roberts1@niehs.nih.gov NR 60 TC 31 Z9 32 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 JAN 30 PY 2004 VL 279 IS 5 BP 3300 EP 3307 DI 10.1074/jbc.M305734200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600021 PM 14607845 ER PT J AU Kagansky, A Freeman, L Lukyanov, D Strunnikov, A AF Kagansky, A Freeman, L Lukyanov, D Strunnikov, A TI Histone tail-independent chromatin binding activity of recombinant cohesin holocomplex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CHROMOSOME CONDENSATION; SISTER CHROMATIDS; DNA-REPLICATION; FISSION YEAST; SMC PROTEINS; S-PHASE; COMPLEX; NUCLEOSOME AB Cohesin, an SMC (structural maintenance of chromosomes) protein-containing complex, governs several important aspects of chromatin dynamics, including the essential chromosomal process of sister chromatid cohesion. The exact mechanism by which cohesin achieves the bridging of sister chromatids is not known. To elucidate this mechanism, we reconstituted a recombinant cohesin complex and investigated its binding to DNA fragments corresponding to natural chromosomal sites with high and low cohesin occupancy in vivo. Cohesin displayed uniform but nonspecific binding activity with all DNA fragments tested. Interestingly, DNA fragments with high occupancy by cohesin in vivo showed strong nucleosome positioning in vitro. We therefore utilized a defined model chromatin fragment (purified reconstituted dinucleosome) as a substrate to analyze cohesin interaction with chromatin. The four-subunit cohesin holocomplex showed a distinct chromatin binding activity in vitro, whereas the Smc1p-Smc3p dimer was unable to bind chromatin. Histone tails and ATP are dispensable for cohesin binding to chromatin in this reaction. A model for cohesin association with chromatin is proposed. C1 NICHD, LGRD, NIH, Bethesda, MD 20892 USA. RP Strunnikov, A (reprint author), NICHD, LGRD, NIH, 18T Lib Dr,Rm 106, Bethesda, MD 20892 USA. EM strunnik@box-s.nih.gov RI Kagansky, Alexander/B-3137-2011; OI Kagansky, Alexander/0000-0002-6219-6892; Strunnikov, Alexander/0000-0002-9058-2256 FU Intramural NIH HHS [Z01 HD001903-11, Z99 AI999999] NR 59 TC 13 Z9 15 U1 1 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 JAN 30 PY 2004 VL 279 IS 5 BP 3382 EP 3388 DI 10.1074/jbc.M306078200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600031 PM 14613943 ER PT J AU Pendrak, ML Chao, MP Yan, SS Roberts, DD AF Pendrak, ML Chao, MP Yan, SS Roberts, DD TI Heme oxygenase in Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to alpha-biliverdin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; IRON SOURCES; IX-ALPHA; YEAST; EXPRESSION; GENE; BINDING; FIBRONECTIN; PROTEINS; IDENTIFICATION AB Candida albicans is an opportunistic pathogen that has adapted uniquely to life in mammalian hosts. One of the host factors recognized by this yeast is hemoglobin, which binds to a specific cell surface receptor. In addition to its regulating the expression of adhesion receptors on the yeast, we have found that hemoglobin induces the expression of a C. albicans heme oxygenase (CaHmx1p). Hemoglobin transcriptionally induces the CaHMX1 gene independent of the presence of inorganic iron in the medium. A Renilla luciferase reporter driven by the CaHMX1 promoter demonstrated rapid activation of transcription by hemoglobin and (cobalt protoporphyrin IX) globin but not by apoglobin or other proteins. In contrast, iron deficiency or exogenous hemin did not activate the reporter until after 3 h, suggesting that induction of the promoter by hemoglobin is mediated by receptor signaling rather than heme or iron flux into the cell. As observed following disruption of the Saccharomyces cerevisiae ortholog, HMX1, a CaHMX1 null mutant was unable to grow under iron restriction. This suggests a role for CaHmx1p in inorganic iron acquisition. CaHMX1 encodes a functional heme oxygenase. Exogenous heme or hemoglobin is exclusively metabolized to alpha-biliverdin. CaHMX1 is required for utilization of these exogenous substrates, indicating that C. albicans heme oxygenase confers a nutritional advantage for growth in mammalian hosts. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP NCI, Pathol Lab, NIH, Bldg 10 Rm 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM mxc107@po.cwru.edu; syan@cvm.fda.gov; droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 50 TC 58 Z9 61 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 30 PY 2004 VL 279 IS 5 BP 3426 EP 3433 DI 10.1074/jbc.M311550200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600037 PM 14615478 ER PT J AU Andreola, F Hayhurst, GP Luo, G Ferguson, SS Gonzalez, FJ Goldstein, JA De Luca, LM AF Andreola, F Hayhurst, GP Luo, G Ferguson, SS Gonzalez, FJ Goldstein, JA De Luca, LM TI Mouse liver CYP2C39 is a novel retinoic acid 4-hydroxylase - Its down-regulation offers a molecular basis for liver retinoid accumulation and fibrosis in aryl hydrocarbon receptor-null mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AH-RECEPTOR; DEFICIENT MICE; CYTOCHROME-P450; METABOLISM; INVOLVEMENT; EXPRESSION; LACKING; CLONING; GROWTH; ALLELE AB Livers of aryl hydrocarbon receptor (AHR)-null mice have high levels of retinoic acid (RA), retinol, and retinyl palmitate. Hepatic accumulation of RA in these mice may be responsible in part for the hepatic phenotype characterized by small liver size and fibrosis. The increased levels of hepatic RA may be due to decreased metabolism of RA to 4-hydroxyretinoic acid. To identify the P450 isoform(s) involved in RA metabolism, liver microsomes from AHR-null and wild-type mice were subjected to Western blotting and probed with antibodies to rat P450s that cross-react with murine forms. Signal intensity in Western blots probed with anti-rat CYP2C6 antibodies correlated with levels of RA 4-hydroxylation. Furthermore, this anti-rat CYP2C6 antibody inhibited RA 4-hydroxylase activity of wild-type mouse liver microsomes to the levels of AHR-null mouse liver. When used to screen a mouse liver cDNA expression library, this antibody exclusively recognized the murine P450 CYP2C39. Catalytic assays of five recombinant mouse CYP2Cs expressed in Escherichia coli revealed that only CYP2C39 was competent for RA 4-hydroxylation (K-m=812.3 nM and V-max 47.85 (fmol/min/pmol P450)). Real time reverse transcriptase-PCR used to assess the Cyp2C39 mRNA expression showed decreased levels (30%) of this transcript in AHR-null compared with wild-type liver, consistent with decreased protein levels observed by Western blot analysis using an antibody to a CYP2C39-specific peptide. These data show that CYP2C39 catalyzes RA catabolism and thus possibly controls RA levels in mouse liver. Down-regulation of Cyp2C39 is hypothesized to be responsible for the liver phenotype in the AHR-null mouse. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP De Luca, LM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Rm 4054C,37 Convent Dr, Bethesda, MD 20892 USA. EM luigi_de_luca@nih.gov RI Goldstein, Joyce/A-6681-2012 NR 23 TC 40 Z9 42 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 JAN 30 PY 2004 VL 279 IS 5 BP 3434 EP 3438 DI 10.1074/jbc.M305832200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600038 PM 14623888 ER PT J AU Angeloni, D Danilkovitch-Miagkova, A Miagkov, A Leonard, EJ Lerman, MI AF Angeloni, D Danilkovitch-Miagkova, A Miagkov, A Leonard, EJ Lerman, MI TI The soluble sema domain of the RON receptor inhibits macrophage-stimulating protein-induced receptor activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE-ACTIVITY; LEUKOCYTE SEMAPHORIN; INVASIVE GROWTH; CELL-LINES; BETA-CHAIN; GENE; MET; MSP; BINDING AB RON is a receptor tyrosine kinase of the MET family that is involved in cell proliferation, cell survival, and cell motility in both normal and disease states. Macrophage-stimulating protein (MSP) is the RON ligand whose binding to RON causes receptor activation. RON is a trans-membrane heterodimer comprised of one alpha- and one beta-chain originating from a single-chain precursor and held together by several disulfide bonds. The intracellular part of RON contains the kinase domain and regulatory elements. The extracellular region is characterized by the presence of a sema domain (a stretch of similar to500 amino acids with several highly conserved cysteine residues), a PSI ((p) under bar lexin, (s) under bar emaphorins, (i) under bar ntegrins) domain, and four immunoglobulin-like folds. Here we show that a soluble, secreted molecule representing the sema domain of RON (referred to as ron-sema) has a dominant negative effect on the ligand-induced receptor activation and is capable of inhibiting RON-dependent signaling pathways and cellular responses. Results suggest that the sema domain of RON participates in ligand binding by the full-length receptor. The ability of ron-sema to suppress growth of MSP-responsive cells in culture, including cancer cells, points to a potential therapeutic use of this molecule, and forced expression of it could potentially be used as a gene therapy tool for treating MSP-dependent types of cancer. C1 NCI, Immunobiol Lab, NIH, Frederick, MD 21702 USA. RP Lerman, MI (reprint author), NCI, Immunobiol Lab, NIH, Bldg 560,Rm 12-68, Frederick, MD 21702 USA. EM lerman@ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 46 TC 31 Z9 32 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 JAN 30 PY 2004 VL 279 IS 5 BP 3726 EP 3732 DI 10.1074/jbc.M309342200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766MF UT WOS:000188379600073 PM 14597639 ER PT J AU Scholl, D Kieleczawa, J Kemp, P Rush, J Richardson, CC Merril, C Adhya, S Molineux, IJ AF Scholl, D Kieleczawa, J Kemp, P Rush, J Richardson, CC Merril, C Adhya, S Molineux, IJ TI Genomic analysis of bacteriophages SP6 and K1-5, an estranged subgroup of the T7 supergroup SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE T7 supergroup; Salmonella typhimurium SP6; Escherichia coli K1-5; genomic analysis; comparative genomics ID COMPLETE NUCLEOTIDE-SEQUENCE; SP6-SPECIFIC RNA-POLYMERASE; PSEUDOMONAS-PUTIDA KT2440; ESCHERICHIA-COLI; ENDO-N; TAIL-FIBER; CAPSULAR POLYSACCHARIDE; RESTRICTION ENZYMES; BASE-PAIRS; START SITE AB We have determined the genome sequences of two closely related lytic bacteriophages, SP6 and K1-5, which infect Salmonella typhimurium LT2 and Escherichia coli serotypes K1 and K5, respectively. The genome organization of these phages is almost identical with the notable exception of the tail fiber genes that confer the different host specificities. The two phages have diverged extensively at the nucleotide level but they are still more closely related to each other than either is to any other phage currently characterized. The SP6 and K1-5 genomes contain, respectively, 43,769 bp and 44,385 bp, with 174 bp and 234 bp direct terminal repeats. About half of the 105 putative open reading frames in the two genomes combined show no significant similarity to database proteins with a known or predicted function that is obviously beneficial for growth of a bacteriophage. The overall genome organization of SP6 and K1-5 is comparable to that of the T7 group of phages, although the specific order of genes coding for DNA metabolism functions has not been conserved. Low levels of nucleotide similarity between genomes in the T7 and SP6 groups suggest that they diverged a long time ago but, on the basis of this conservation of genome organization, they are expected to have retained similar developmental strategies. (C) 2003 Elsevier Ltd. All rights reserved. C1 NIMH, Sect Biochem Genet, NIH, Bethesda, MD 20895 USA. Wyeth Genet Inst, Cambridge, MA 02140 USA. Univ Texas, Austin, TX 78712 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NCI, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. Univ Texas, Inst Cell & Mol Biol, Austin, TX 78712 USA. RP NIMH, Sect Biochem Genet, NIH, 9000 Rockville Pike, Bethesda, MD 20895 USA. EM dscholl@usa.net FU NIAID NIH HHS [AI-06045]; NIGMS NIH HHS [GM32095] NR 91 TC 59 Z9 68 U1 2 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 30 PY 2004 VL 335 IS 5 BP 1151 EP 1171 DI 10.1016/j.jmb.2003.11.035 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 767YK UT WOS:000188501300002 PM 14729334 ER PT J AU Ding, KY Louis, JM Gronenborn, AM AF Ding, KY Louis, JM Gronenborn, AM TI Insights into conformation and dynamics of protein GB1 during folding and unfolding by NMR SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE NMR; protein folding; melting hot spots; folding intermediates; residual dipolar coupling ID MACROMOLECULAR STRUCTURE DETERMINATION; IMMUNOGLOBULIN BINDING DOMAIN; POLYACRYLAMIDE GELS; MOLECULAR ALIGNMENT; DIPOLAR COUPLINGS; CORE; MOTIONS; PHASE AB Understanding protein stability requires characterization of structural determinants of the folded and unfolded states. Many proteins are capable of populating partially folded states under specific solution conditions. Occasionally, coexistence of the folded and an unfolded state under non- or mildly denaturing conditions can be observed by NMR, allowing us to structurally probe these states under identical conditions. Here we report on a destabilized mutant of the B1 domain of protein G (GB1) whose equilibrium unfolding was systematically investigated. Backbone amide residual dipolar couplings (RDCs), the tryptophan NE-H resonance and the amide nitrogen transverse relaxation rates (R(2)s) for varying pH values and different temperatures were measured. The backbone amide RDCs; indicate that prior to complete unfolding, two melting hot spots are formed at the turn around T11, L12 and K13 and the N terminus of the helix at A24 and T25. The RDCs for the low pH, thermally unfolded state of GB1 are very small and do not indicate the presence of any native-like structure. Amide nitrogen transverse relaxation rates for GB1 in the folded state at different temperatures exhibit large contributions from exchange processes and the associated dynamics display considerable heterogeneity. Our data provide clear evidence for intermediate conformations and multi-state equilibrium un/folding for this GB1 variant. Published by Elsevier Ltd. C1 NIDDKD, Phys Chem Lab, NIH, NIDDK, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, Phys Chem Lab, NIH, NIDDK, Bldg 5 Room 130, Bethesda, MD 20892 USA. EM gronenborn@nih.gov OI Gronenborn, Angela M/0000-0001-9072-3525 NR 33 TC 57 Z9 57 U1 1 U2 14 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 JAN 30 PY 2004 VL 335 IS 5 BP 1299 EP 1307 DI 10.1016/j.jmb.2003.11.042 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 767YK UT WOS:000188501300013 PM 14729345 ER PT J AU Moody, TW Dudek, J Zakowicz, H Walters, J Jensen, RT Petricoin, E Couldrey, C Green, JE AF Moody, TW Dudek, J Zakowicz, H Walters, J Jensen, RT Petricoin, E Couldrey, C Green, JE TI VIP receptor antagonists inhibit mammary carcinogenesis in C3(1)SV40T antigen mice SO LIFE SCIENCES LA English DT Article DE VIP receptor antagonist; mammary carcinogenesis; transgenic mice; chemoprevention; proteomics ID VASOACTIVE INTESTINAL POLYPEPTIDE; BREAST-CANCER-CELLS; FUNCTIONAL EXPRESSION; PEPTIDE RECEPTORS; TRANSGENIC MICE; PACAP RECEPTOR; HUMAN TUMORS; LUNG-CANCER; GROWTH; IDENTIFICATION AB The effects of a vasoactive intestinal peptide (VIP) receptor antagonist on mammary carcinogenesis were investigated using the C3(1)SV40T antigen (ag) mice. Ten mug/day VIPhybrid (VIPhyb) administered daily subcutaneously increased significantly the survival of C3(1)SV40Tag mice. At 5.2 months, VIPhyb significantly reduced the mammary tumor burden in C3(1)SV40Tag mice relative to control animals. I-125-VIP bound with high affinity to mouse mammary tumor homogenate. Because (Lys(15), Arg(16), Leu(27))VIP(1-7)GRF(8-27) (VPAC(1) selective) but not Ro25-1553 (VPAC(2) selective) inhibited specific I-125-VIP binding to mammary tumor membranes with high affinity, VPAC(1) receptors predominate. By RT-PCR, VPAC(1) receptor mRNA was detected in mammary tumors. By Western blot, a major 60 Kdalton band was detected in mammary tumor extracts using VPAC(1) receptor antisera. By immunocytochemistry, VPAC(1)-R immunostaining was detected in the cytosol and plasma membrane but not the nucleus of fixed mammary tumor tissue. Using laser capture microdissected tumor cells and surface enhanced laser desorption/ionization (SELDI) techniques on mammary tumor cells, the proteomic profile was altered in mice treated with VIPhyb. Because VPAC(1) receptor antagonists increase the survival and reduce the tumor burden in C3(1)SV40Tag mice, they may function as chemopreventive agents in mammary cancer. (C) 2003 Elsevier Inc. All rights reserved. C1 NCI, Dept Hlth & Human Serv, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. George Washington Univ, Genet Program, Washington, DC 20037 USA. NIDDK, Digest Dis Branch, Bethesda, MD USA. CBER FDA, Div Cytokine Biol, Bethesda, MD USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Dept Hlth & Human Serv, Ctr Canc Res, NIH, Bldg 31,Rm 3A34,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 37 TC 17 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 30 PY 2004 VL 74 IS 11 BP 1345 EP 1357 DI 10.1016/j.lfs.2003.07.043 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 763NJ UT WOS:000188092000004 PM 14706566 ER PT J AU Yusufzai, TM Tagami, H Nakatani, Y Felsenfeld, G AF Yusufzai, TM Tagami, H Nakatani, Y Felsenfeld, G TI CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species SO MOLECULAR CELL LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; HISTONE ACETYLATION; IN-VIVO; PROTEIN CTCF; METHYLATION; DNA; LOCALIZATION; PROTECTION; BOUNDARIES; COMPLEX AB Insulators can block an enhancer of one gene from activating a promoter on another nearby gene. Almost all described vertebrate insulators require binding of the regulatory protein CTCF for their activity. We show that CTCF copurifies with the nucleolar protein nucleophosmin and both are present at insulator sites in vivo. Furthermore, exogenous insulator sequences are tethered to the nucleolus in a CTCF-dependent manner. These interactions, quite different from those of the gypsy insulator element in Drosophila, may generate similar loop structures, suggesting a common theme and model for enhancer-blocking insulator action. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov NR 23 TC 298 Z9 310 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 30 PY 2004 VL 13 IS 2 BP 291 EP 298 DI 10.1016/S1097-2765(04)00029-2 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 771QN UT WOS:000188797700012 PM 14759373 ER PT J AU Verdel, A Jia, ST Gerber, S Sugiyama, T Gygi, S Grewal, SIS Moazed, D AF Verdel, A Jia, ST Gerber, S Sugiyama, T Gygi, S Grewal, SIS Moazed, D TI RNAi-mediated targeting of heterochromatin by the RITS complex SO SCIENCE LA English DT Article ID H3 LYSINE-9 METHYLATION; FISSION YEAST; HISTONE H3; EPIGENETIC CONTROL; GENE; DNA; DOMAIN; TRANSCRIPTION; INTERFERENCE; TETRAHYMENA AB RNA interference (RNAi) is a widespread silencing mechanism that acts at both the posttranscriptional and transcriptional levels. Here, we describe the purification of an RNAi effector complex termed RITS (RNA-induced initiation of transcriptional gene silencing) that is required for heterochromatin assembly in fission yeast. The RITS complex contains Ago1 ( the fission yeast Argonaute homolog), Chp1 ( a heterochromatin-associated chromodomain protein), and Tas3 ( a novel protein). In addition, the complex contains small RNAs that require the Dicer ribonuclease for their production. These small RNAs are homologous to centromeric repeats and are required for the localization of RITS to heterochromatic domains. The results suggest a mechanism for the role of the RNAi machinery and small RNAs in targeting of heterochromatin complexes and epigenetic gene silencing at specific chromosomal loci. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Taplin Biol Mass Spectrometry Facil, Boston, MA 02115 USA. RP Moazed, D (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov; danesh@hms.harvard.edu RI Verdel, Andre/M-5201-2013; OI Sugiyama, Tomoyasu/0000-0001-5704-6606; Gerber, Scott/0000-0002-2964-5051 FU Howard Hughes Medical Institute; NIGMS NIH HHS [R01 GM072805, R01 GM072805-01] NR 25 TC 737 Z9 779 U1 5 U2 31 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 JAN 30 PY 2004 VL 303 IS 5658 BP 672 EP 676 DI 10.1126/science.1093686 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768EN UT WOS:000188530800041 PM 14704433 ER PT J AU Roberts, BT Moriyama, H Wickner, RB AF Roberts, BT Moriyama, H Wickner, RB TI [URE3] prion propagation is abolished by a mutation of the primary cytosolic Hsp70 of budding yeast SO YEAST LA English DT Article DE prion; Hsp70; chaperone; genetics; yeast ID SACCHAROMYCES-CEREVISIAE; IN-VITRO; ANTAGONISTIC INTERACTIONS; SUBSTRATE-SPECIFICITY; BINDING DOMAIN; DNAK CHAPERONE; SUP35 PROTEIN; PSI(+); HSP104; PSI+ AB [URE3] and [PSI+] are infectious protein forms of the Saccharomyces cerevisiae Ure2p and Sup35p, respectively. We isolated an allelle of SSA2, the primary cytosolic Hsp70, in a screen for mutants unable to maintain [URE3]. Designated ssa2-10, the mutation results in a leucine substitution for proline 395, a conserved residue of the peptide-binding domain. This allele also unexpectedly destabilizes [URE3] in newly formed heterozygotes: [URE3] is either absent in heterozygotes formed by crossing wildtype [URE3] cells with ssa2-10 mutants, or present and fully stable. SSA2 deletion mutants are weakly capable of maintaining [URE3]. The ssa2-10 allele is compatible with propagation of [PSI+]. However, in combination with a deletion of SSA1, ssa2-10 eliminates the nonsense-suppression phenotype of [PSI+] cells. Copyright (C) 2003 John Wiley Sons, Ltd. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI MORIYAMA, Hiromitsu/F-9256-2013 NR 48 TC 41 Z9 41 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0749-503X EI 1097-0061 J9 YEAST JI Yeast PD JAN 30 PY 2004 VL 21 IS 2 BP 107 EP 117 DI 10.1002/yea.1062 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA 774KA UT WOS:000188977600002 PM 14755636 ER PT J AU Tamamura, H Sigano, DM Lewin, NE Blumberg, PM Marquez, VE AF Tamamura, H Sigano, DM Lewin, NE Blumberg, PM Marquez, VE TI Conformationally constrained analogues of diacylglycerol. 20. The search for an elusive binding site on protein kinase C through relocation of the carbonyl pharmacophore along the sn-1 side chain of 1,2-diacylglycerol lactones SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; GREEN FLUORESCENT PROTEIN; TUMOR-PROMOTING ACTIVITY; CYSTEINE-RICH DOMAINS; PHORBOL ESTER; LIVING CELLS; DAG-LACTONES; MOUSE SKIN; PK-C; ACTIVATION AB Previous studies with 1,2-diacylglycerol (DAG) lactones, which behave as high-affinity ligands for protein kinase C (PK-C), have established the importance of maintaining intact the pharmacophore triad of two carbonyl moieties (sn-1 and sn-2) and the primary alcohol. In addition, docking studies of DAG-lactones into an empty C1b receptor of PK-Cdelta (as it appears in complex with phorbol 13-O-acetate) have revealed that in either of the two possible binding alternatives (sn-1 or sn-2) only one carbonyl group of the DAG-lactone is involved in binding. Therefore, the unknown receptor for the orphaned carbonyl appears to lie outside the boundaries of this binary complex, possibly residing at the membrane or near the membrane-protein interface. A strategy to locate the optimal location of the unengaged carbonyl was conceived by utilizing a small group of DAG-lactones (1-4) with a highly branched chain adjacent to the sn-2 carbonyl such that sn-2 binding is favored. With these compounds, various locations of the sn-1 carbonyl along the side chain were tested for their binding affinity for PK-C. The results indicate that the location of the side chain sn-1 carbonyl in a DAG-lactone must have perfect mimicry to the sn-1 carbonyl of the parent DAG for it to display high binding affinity. A proposed model from this work is that the missing pharmacophore in the ternary complex, which includes the membrane, is close to the membrane-protein interface. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov RI Sigano, Dina/M-6144-2014 OI Sigano, Dina/0000-0001-7489-9555 NR 34 TC 11 Z9 11 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 29 PY 2004 VL 47 IS 3 BP 644 EP 655 DI 10.1021/jm030454h PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 766GP UT WOS:000188367800014 PM 14736244 ER PT J AU Yang, CY Nikolovska-Coleska, Z Li, P Roller, P Wang, SM AF Yang, CY Nikolovska-Coleska, Z Li, P Roller, P Wang, SM TI Solution conformations of wild-type and mutated Bak BH3 peptides via dynamical conformational sampling and implication to their binding to antiapoptotic Bcl-2 proteins SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; AQUEOUS-SOLUTION; FREE-ENERGY; SIMULATION; COMPLEX; APOPTOSIS; RECOGNITION; SYSTEMS AB The BH3 (Bcl-2 homology 3) domain of the Bcl-2 family of proteins plays a critical role in the regulation of programmed cell death, or apoptosis. A 16-residue peptide derived from the BH3 domain of the proapoptotic protein Bak potently binds to the antiapoptotic proteins Bcl-2 and Bcl-xL. While this Bak BH3 peptide adopts a well-defined helical conformation in the experimental NMR solution structure in complex with Bcl-xL, it does not adopt a stable helical conformation in water. Experimental structural determination of peptides without a stable and well-defined solution conformation remains a difficult task. In this paper, we investigated the solution conformations of this Bak BH3 peptide through extensive molecular dynamics (MD) simulations in water using a recently developed self-guided MD simulation (SGMD) method. Our simulations showed that the Bak peptide exhibits a partially formed helical structure with a fairly stable 6-residue helical segment at the N terminus and a less stable approximately 4-residue helical segment at the C terminus. Additionally, we also performed extensive SGMD simulations of two mutated Bak peptides, in which the arginine residue at position 5 is mutated to either an alanine or a glycine residue (R5A or R5G mutant) to investigate the influence of mutation on the solution conformations of the Bak peptide. We found that the R5G mutation greatly affects the solution conformations of the peptide, and the overall helix ratio decreases by a factor of 2 as compared to the wild-type Bak peptide. In contrast, the R5A mutation does not affect significantly the peptide solution conformations observed in the wild type. By use of a fluorescence-polarization-based binding assay, we quantitatively determined the binding affinities of these three Bak BH3 peptides to Bcl-xL protein. We found that the R5G and R5A mutants are 24 and 6 times less potent than the wild-type Bak peptide, respectively, suggesting that the helical ratio of the peptides is an important but not the only factor for their binding to Bcl-xL. Analysis of representative conformations of the R5A mutant suggested that the relatively stable helical segment close to the N terminus may greatly facilitate its binding to Bcl-xL. C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. FCRDC, Med Chem Lab, NIH, Frederick, MD 21702 USA. RP Wang, SM (reprint author), Univ Michigan, Dept Internal Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM shaomeng@med.umich.edu NR 34 TC 6 Z9 6 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 29 PY 2004 VL 108 IS 4 BP 1467 EP 1477 DI 10.1021/jp036009f PG 11 WC Chemistry, Physical SC Chemistry GA 768GR UT WOS:000188535700040 ER PT J AU Harries, D Ben-Shaul, A Szleifeo, I AF Harries, D Ben-Shaul, A Szleifeo, I TI Enveloping of charged proteins by lipid bilayers SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID COMPLEXES; STABILITY; MEMBRANES; CURVATURE; DELIVERY; CELLS; SALT AB The ability of a mixed lipid bilayer composed of neutral and charged lipids to encapsulate an oppositely charged protein is studied with use of a simple theoretical model. The free energy of the bilayer-enveloped protein complex is expressed as a sum of electrostatic and curvature elasticity contributions, and compared to that of a protein adsorbed on a mixed planar bilayer. The electrostatic adsorption energy on the planar bilayer is calculated by using an extended Poisson-Boltzmann approach, which allows for local lipid charge modulation in the adsorption zone. We find that the electrostatic interactions favor the wrapped state, while the bending energy prefers the planar bilayer. To enable the transition from the adsorbed to enveloped protein geometry, there is a minimal necessary protein charge. This "crossover" charge depends on the bending rigidity of the lipid membrane and the (composition dependent) spontaneous curvature of its constituent monolayers. The values for the crossover charge predicted by the theory are in line with the charge necessary for peptide shuttles to penetrate cell membranes. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Dept Phys Chem, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Fritz Haber Res Ctr, IL-91904 Jerusalem, Israel. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. RP Harries, D (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RI Harries, Daniel/F-7016-2012 OI Harries, Daniel/0000-0002-3057-9485 NR 20 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 29 PY 2004 VL 108 IS 4 BP 1491 EP 1496 DI 10.1021/jp036501z PG 6 WC Chemistry, Physical SC Chemistry GA 768GR UT WOS:000188535700043 ER PT J AU Poremba, A Malloy, M Saunders, RC Carson, RE Herscovitch, P Mishkin, M AF Poremba, A Malloy, M Saunders, RC Carson, RE Herscovitch, P Mishkin, M TI Species-specific calls evoke asymmetric activity in the monkey's temporal poles SO NATURE LA English DT Article ID AUDITORY-CORTEX; RHESUS-MONKEYS; VOCALIZATIONS; REPRESENTATION; PERCEPTION; MACAQUES; MARMOSET; BRAIN AB It has often been proposed that the vocal calls of monkeys are precursors of human speech, in part because they provide critical information to other members of the species who rely on them for survival and social interactions(1,2). Both behavioural and lesion studies suggest that monkeys, like humans, use the auditory system of the left hemisphere preferentially to process vocalizations(3,4). To investigate the pattern of neural activity that might underlie this particular form of functional asymmetry in monkeys, we measured local cerebral metabolic activity while the animals listened passively to species-specific calls compared with a variety of other classes of sound. Within the superior temporal gyrus, significantly greater metabolic activity occurred on the left side than on the right, only in the region of the temporal pole and only in response to monkey calls. This functional asymmetry was absent when these regions were separated by forebrain commissurotomy, suggesting that the perception of vocalizations elicits concurrent interhemispheric interactions that focus the auditory processing within a specialized area of one hemisphere. C1 Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Poremba, A (reprint author), Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. EM amy-poremba@uiowa.edu RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 24 TC 181 Z9 183 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 29 PY 2004 VL 427 IS 6973 BP 448 EP 451 DI 10.1038/nature02268 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 767UF UT WOS:000188470500045 PM 14749833 ER PT J AU Kauraniemi, P Hautaniemi, S Autio, R Astola, J Monni, O Elkahloun, A Kallioniemi, A AF Kauraniemi, P Hautaniemi, S Autio, R Astola, J Monni, O Elkahloun, A Kallioniemi, A TI Effects of Herceptin treatment on global gene expression patterns in HER2-amplified and nonamplified breast cancer cell lines SO ONCOGENE LA English DT Article DE HER2; herceptin; amplification; breast cancer; cDNA microarray ID MONOCLONAL-ANTIBODY; METASTATIC BREAST; C-FOS; MUTATIONS; THERAPY; KIT; CHEMOTHERAPY; TRASTUZUMAB; ACTIVATION; ESTROGEN AB Herceptin is a humanized monoclonal antibody targeted against the extracellular domain of the HER2 oncogene, which is amplified and overexpressed in 10-34% of breast cancers. Herceptin therapy provides effective treatment in HER2-positive metastatic breast cancer, although a favorable treatment response is not achieved in all cases. Here, we show that Herceptin treatment induces a dose-dependent growth reduction in breast cancer cell lines with HER2 amplification, whereas nonamplified cell lines are practically resistant. Time-course analysis of global gene expression patterns in amplified and nonamplified cell tines indicated a major change in transcript levels between 24 and 48 h of Herceptin treatment. A step-wise gene selection algorithm revealed a set of 439 genes whose temporal expression profiles differed most between the amplified and nonamplified cell lines. The discriminatory power of these genes was confirmed by both hierarchical clustering and self-organizing map analyses. In the amplified cell lines, the Herceptin treatment induced the expression of several genes involved in RNA processing and DNA repair, while cell adhesion mediators and known oncogenes, such as e-FOS and c-KIT, were downregulated. These results provide additional clues to the downstream effects of blocking the HER2 pathway in breast cancer and may provide new targets for more effective treatment. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33520 Tampere, Finland. Tampere Univ Hosp, FIN-33520 Tampere, Finland. Tampere Univ Technol, Inst Signal Proc, FIN-33101 Tampere, Finland. Univ Helsinki, Biomedicum Helsinki, Biomedicum Biochip Ctr, FIN-00290 Helsinki, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Kallioniemi, A (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33520 Tampere, Finland. EM anne.kallioniemi@uta.fi RI Hautaniemi, Sampsa/A-3122-2009; Autio, Reija/D-2037-2014; Astola, Jaakko/G-4297-2014; OI Hautaniemi, Sampsa/0000-0002-7749-2694; Astola, Jaakko/0000-0002-2750-5311 NR 27 TC 47 Z9 49 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 JAN 29 PY 2004 VL 23 IS 4 BP 1010 EP 1013 DI 10.1038/sj.onc.1207200 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 767UV UT WOS:000188486600018 PM 14647448 ER PT J AU Meyron-Holtz, EG Ghosh, MC Iwai, K LaVaute, T Brazzolotto, X Berger, UV Land, W Ollivierre-Wilson, H Grinberg, A Love, P Rouault, TA AF Meyron-Holtz, EG Ghosh, MC Iwai, K LaVaute, T Brazzolotto, X Berger, UV Land, W Ollivierre-Wilson, H Grinberg, A Love, P Rouault, TA TI Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis SO EMBO JOURNAL LA English DT Article DE cytosolic aconitase; iron metabolism; iron regulatory protein 1 (IRP1); iron-responsive element (IRE) ID ELEMENT-BINDING-PROTEIN; RNA-BINDING; CYTOSOLIC ACONITASE; FERRITIN SYNTHESIS; OXIDATIVE STRESS; CAENORHABDITIS-ELEGANS; ESCHERICHIA-COLI; SULFUR CLUSTERS; ADIPOSE-TISSUE; NITRIC-OXIDE AB The two iron regulatory proteins IRP1 and IRP2 bind to transcripts of ferritin, transferrin receptor and other target genes to control the expression of iron metabolism proteins at the post-transcriptional level. Here we compare the effects of genetic ablation of IRP1 to IRP2 in mice. IRP1 -/- mice misregulate iron metabolism only in the kidney and brown fat, two tissues in which the endogenous expression level of IRP1 greatly exceeds that of IRP2, whereas IRP2 -/- mice misregulate the expression of target proteins in all tissues. Surprisingly, the RNA-binding activity of IRP1 does not increase in animals on a low-iron diet that is sufficient to activate IRP2. In animal tissues, most of the bifunctional IRP1 is in the form of cytosolic aconitase rather than an RNA-binding protein. Our findings indicate that the small RNA-binding fraction of IRP1, which is insensitive to cellular iron status, contributes to basal mammalian iron homeostasis, whereas IRP2 is sensitive to iron status and can compensate for the loss of IRP1 by increasing its binding activity. Thus, IRP2 dominates post-transcriptional regulation of iron metabolism in mammals. C1 NICHD, Sect Human Iron Metab, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Gene Regulat & Dev, Bethesda, MD 20892 USA. UB In Situ, Natick, MA USA. RP Rouault, TA (reprint author), NICHD, Sect Human Iron Metab, NIH, Cell Biol & Metab Branch, Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM trou@helix.nih.gov RI Meyron-Holtz, Esther/B-5991-2013 NR 51 TC 217 Z9 224 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 28 PY 2004 VL 23 IS 2 BP 386 EP 395 DI 10.1038/sj.emboj.7600041 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 773JY UT WOS:000188921700014 PM 14726953 ER PT J AU Hisa, T Spence, SE Rachel, RA Fujita, M Nakamura, T Ward, JM Devor-Henneman, DE Saiki, Y Kutsuna, H Tessarollo, L Jenkins, NA Copeland, NG AF Hisa, T Spence, SE Rachel, RA Fujita, M Nakamura, T Ward, JM Devor-Henneman, DE Saiki, Y Kutsuna, H Tessarollo, L Jenkins, NA Copeland, NG TI Hematopoietic, angiogenic and eye defects in Meis1 mutant animals SO EMBO JOURNAL LA English DT Article DE angiogenesis; eye development; hematopoiesis; Meis1 ID ACUTE MYELOID-LEUKEMIA; FETAL LIVER HEMATOPOIESIS; DNA-BINDING PARTNERS; HOMEOBOX GENES; HOMEODOMAIN PROTEINS; NUCLEAR-LOCALIZATION; STEM-CELLS; DEFINITIVE HEMATOPOIESIS; TRANSCRIPTION FACTOR; PROTOONCOGENE PBX1 AB Meis1 and Hoxa9 expression is upregulated by retroviral integration in murine myeloid leukemias and in human leukemias carrying MLL translocations. Both genes also cooperate to induce leukemia in a mouse leukemia acceleration assay, which can be explained, in part, by their physical interaction with each other as well as the PBX family of homeodomain proteins. Here we show that Meis1-deficient embryos have partially duplicated retinas and smaller lenses than normal. They also fail to produce megakaryocytes, display extensive hemorrhaging, and die by embryonic day 14.5. In addition, Meis1-deficient embryos lack well-formed capillaries, although larger blood vessels are normal. Definitive myeloerythroid lineages are present in the mutant embryos, but the total numbers of colony-forming cells are dramatically reduced. Mutant fetal liver cells also fail to radioprotect lethally irradiated animals and they compete poorly in repopulation assays even though they can repopulate all hematopoietic lineages. These and other studies showing that Meis1 is expressed at high levels in hematopoietic stem cells (HSCs) suggest that Meis1 may also be required for the proliferation/self-renewal of the HSC. C1 NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. Japanese Fdn Canc Res, Inst Canc, Tokyo 170, Japan. NCI, Ctr Canc Res, Vet & Tumor Pathol Sect, Frederick, MD 21701 USA. Osaka City Univ, Sch Med, Dept Hematol, Osaka 545, Japan. RP Copeland, NG (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. EM copeland@ncifcrf.gov NR 56 TC 172 Z9 173 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 28 PY 2004 VL 23 IS 2 BP 450 EP 459 DI 10.1038/sj.emboj.7600038 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 773JY UT WOS:000188921700020 PM 14713950 ER PT J AU Bondy, CA Bakalov, VK AF Bondy, CA Bakalov, VK TI Genetic vs hormonal factors in lipid metabolism in women - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 JAN 28 PY 2004 VL 291 IS 4 BP 425 EP 425 DI 10.1001/jama.291.4.425-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 767EF UT WOS:000188426700023 ER PT J AU Kruit, MC van Buchem, MA Hofman, PAM Bakkers, JTN Terwindt, GM Ferrari, MD Launer, LJ AF Kruit, MC van Buchem, MA Hofman, PAM Bakkers, JTN Terwindt, GM Ferrari, MD Launer, LJ TI Migraine as a risk factor for subclinical brain lesions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FAMILIAL HEMIPLEGIC MIGRAINE; WHITE-MATTER; CARDIOVASCULAR HEALTH; ARTERIAL TERRITORIES; CLINICAL-FEATURES; ISCHEMIC STROKE; ELDERLY-PEOPLE; YOUNG-WOMEN; PREVALENCE; INFARCTS AB Context Clinical series have suggested an increased prevalence of cerebral infarction and white matter lesions (WMLs) in migraine patients. It is not known whether these lesions are prevalent in the general migraine population. Objectives To compare the prevalence of brain infarcts and WMLs in migraine cases and controls from the general population and to identify migraine characteristics associated with these lesions. Design Cross-sectional, prevalence study of population-based sample of Dutch adults aged 30 to 60 years. Participants Randomly selected patients with migraine with aura (n=161), patients with migraine without aura (n=134), and controls (n=140), who were frequency matched to cases for age, sex, and place of residence. Nearly 50% of the cases had not been previously diagnosed by a physician. Main Outcome Measures Brain magnetic resonance images were evaluated for infarcts, by location and vascular supply territory, and for periventricular WMLs (PVWMLs) and deep WMLs (DWMLs). The odds ratios (ORs) and 95% confidence intervals (CIs) of these brain lesions compared with controls were examined by migraine subtype (with or without aura) and monthly attack frequency (<1 attack, &GE;1 attack), controlling for cardiovascular risk factors and use of vasoconstrictor migraine agents. All participants underwent a standard neurological examination. Results No participants reported a history of stroke or transient ischemic attack or had relevant abnormalities at standard neurological examination. We found no significant difference between patients with migraine and controls in overall infarct prevalence (8.1% vs 5.0%). However, in the cerebellar region of the posterior circulation territory, patients with migraine had a higher prevalence of infarct than controls (5.4% vs 0.7%; P=.02; adjusted OR, 7.1; 95% CI, 0.9-55). The adjusted OR for posterior infarct varied by migraine subtype and attack frequency. The adjusted OR was 13.7 (95% CI, 1.7-112) for patients with migraine with aura compared with controls. In patients with migraine with a frequency of attacks of 1 or more per month, the adjusted OR was 9.3 (95% CI, 1.1-76). The highest risk was in patients with migraine with aura with 1 attack or more per month (OR, 15.8; 95% CI, 1.8-140). Among women, the risk for high DWML load (top 20th percentile of the distribution of DWML load vs lower 80th percentile) was increased in patients with migraine compared with controls (OR, 2.1; 95% Cl, 1.0-4.1); this risk increased with attack frequency (highest in those with &GE;1 attack per month: OR, 2.6; 95% CI, 1.2-5.7) but was similar in patients with migraine with or without aura. In men, controls and patients with migraine did not differ in the prevalence of DWMLs. There was no association between severity of PVWMLs and migraine, irrespective of sex or migraine frequency or subtype. Conclusions. These population-based findings suggest that some patients with migraine with and without aura are at increased risk for subclinical lesions in certain brain areas. C1 Leiden Univ, Med Ctr, Dept Radiol, NL-2333 ZA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Neurol, NL-2333 ZA Leiden, Netherlands. Acad Hosp Maastricht, Dept Radiol, Maastricht, Netherlands. Slingeland Hosp, Dept Radiol, Doetinchem, Netherlands. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Kruit, MC (reprint author), Leiden Univ, Med Ctr, Dept Radiol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. EM m.c.kruit@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X NR 47 TC 507 Z9 524 U1 3 U2 18 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 JAN 28 PY 2004 VL 291 IS 4 BP 427 EP 434 DI 10.1001/jama.291.4.427 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 767EF UT WOS:000188426700027 PM 14747499 ER PT J AU Miglioretti, DL Rutter, CM Geller, BM Cutter, G Barlow, WE Rosenberg, R Weaver, DL Taplin, SH Ballard-Barbash, R Carney, PA Yankaskas, BC Kerlikowske, K AF Miglioretti, DL Rutter, CM Geller, BM Cutter, G Barlow, WE Rosenberg, R Weaver, DL Taplin, SH Ballard-Barbash, R Carney, PA Yankaskas, BC Kerlikowske, K TI Effect of breast augmentation on the accuracy of mammography and cancer characteristics SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SCREENING MAMMOGRAPHY; UNITED-STATES; IMPLANTS; WOMEN; MAMMAPLASTY; DIAGNOSIS; SURVIVAL; PERFORMANCE; PROGNOSIS; DENSITY AB Context Breast augmentation is not associated with an increased risk of breast cancer; however, implants may interfere with the detection of breast cancer thereby delaying cancer diagnosis in women with augmentation. Objective To determine whether mammography accuracy and tumor characteristics are different for women with and without augmentation. Design, Setting, and Participants A prospective cohort of 137 women with augmentation and 685 women without augmentation diagnosed with breast cancer between January 1, 1995, and October 15, 2002, matched (1:5) by age, race/ethnicity, previous mammography screening, and mammography registry, and 10533 women with augmentation and 974915 women without augmentation and without breast cancer among 7 mammography registries in Denver, Colo; Lebanon, NH; Albuquerque, NM; Chapel Hill, NC; San Francisco, Calif; Seattle, Wash; and Burlington, Vt. Main Outcome Measures Comparison between women with and without augmentation of mammography performance measures and cancer characteristics, including invasive carcinoma or ductal carcinoma in situ, tumor stage, nodal status, size, grade, and estrogen-receptor status. Results Among asymptomatic women, the sensitivity of screening mammography based on the final assessment was lower in women with breast augmentation vs women without (45.0% [95% confidence interval {CI}, 29.3%-61.5%] vs 66.8% [95% CI, 60.4%-72.8%]; P=.008), and specificity was slightly higher in women with augmentation (97.7% [95% CI, 97.4%-98.0%] vs 96.7% [95% CI, 96.6%-96.7%]; P<.001). Among symptomatic women, both sensitivity and specificity were lower for women with augmentation compared with women without but these differences were not significant. Tumors were of similar stage, size, estrogen-receptor status, and nodal status but tended to be lower grade (P=.052) for women with breast augmentation vs without. Conclusions Breast augmentation decreases the sensitivity of screening mammography among asymptomatic women but does not increase the false-positive rate. Despite the lower accuracy of mammography in women with augmentation, the prognostic characteristics of tumors are not influenced by augmentation. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Canc Res & Biostat, Seattle, WA USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Nevada, Sch Med, Ctr Res Design & Stat Methods, Appl Res Facil, Reno, NV 89557 USA. Univ New Mexico, Hlth Sci Ctr, Dept Radiol, Albuquerque, NM 87131 USA. NCI, Appl Res Program, Dept Canc Control & Populat Sci, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Univ Calif San Francisco, Dept Vet Affairs, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med & Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Miglioretti, DL (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM miglioretti.d@ghc.org FU NCI NIH HHS [U01CA63731, U01CA63736, U01CA63740, U01CA69976, U01CA70013, U01CA70040, U01CA86076, U01CA86082] NR 37 TC 72 Z9 74 U1 2 U2 7 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 JAN 28 PY 2004 VL 291 IS 4 BP 442 EP 450 DI 10.1001/jama.291.4.442 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 767EF UT WOS:000188426700029 PM 14747501 ER PT J AU Shah, S Whittle, A Wilfond, B Gensler, G Wendler, D AF Shah, S Whittle, A Wilfond, B Gensler, G Wendler, D TI How do institutional review boards apply the federal risk and benefit standards for pediatric research? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHILDREN AB Context Federal regulations allow children in the United States to be enrolled in clinical research only when the institutional review board (IRB) determines that the risks are minimal or a minor increase over minimal, or that the research offers a prospect of direct benefit. Despite this reliance on IRBs, no data exist on how IRBs apply the risk and benefit categories for pediatric research. Objective To determine how IRB chairpersons apply the federal risk and benefit categories for pediatric research. Design, Setting, and Participants Telephone survey, conducted between May and August 2002 of 188 randomly selected chairpersons of IRBs in the Unites States. The survey consisted of 21 questions to assess the application of federal risk standards to research procedures, whether certain interventions offer a prospect of direct benefit to participating children, and the extent to which IRBs use the federal definition of minimal risk when categorizing the risks of research procedures in children. Main Outcome Measures Responses regarding categorization of the risk level and direct benefits of pediatric research procedures. Results A single blood draw was the only procedure categorized as minimal risk by a majority (152 or 81%) of the 188 respondents. An electromyogram was categorized as minimal or a minor increase over minimal risk by 100 (53%) and as more than a minor increase over minimal risk by 77 (41%). Allergy skin testing was categorized as minimal risk by 43 IRB chairpersons (23%), a minor increase over minimal risk by 81 (43%), and more than a minor increase over minimal risk by 51 (27%). Regarding benefits, 113 chairpersons (60%) considered added psychological counseling to be a direct benefit, while participant payment was considered a direct benefit by 10% (n = 19). Conclusions Application of the federal risk and benefit categories for pediatric research by IRB chairpersons is variable and sometimes contradicted by the available data on risks and the regulations themselves. To protect children from excessive risks while allowing appropriate research, IRB chairpersons need guidance on applying the federal risk and benefit categories and also need data on the risks children face in daily life and during routine physical or psychological tests. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. NIH, Human Genome Res Inst, Bethesda, MD 20892 USA. Emmes Corp, Bethesda, MD USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118,10 Ctr Dr, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 19 TC 151 Z9 153 U1 0 U2 3 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 JAN 28 PY 2004 VL 291 IS 4 BP 476 EP 482 DI 10.1001/jama.291.4.476 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 767EF UT WOS:000188426700033 PM 14747505 ER PT J AU Kerr, JND Plenz, D AF Kerr, JND Plenz, D TI Action potential timing determines dendritic calcium during striatal up-states SO JOURNAL OF NEUROSCIENCE LA English DT Article DE action potential backpropagation; spike timing; calcium; NMDA; plasticity; fura-2; organotypic culture; spiny projection neuron; dendritic processing; up-state; down-state; cortex; striatum; substantia nigra; electrophysiology; imaging ID SPINY PROJECTION NEURONS; NEOCORTICAL PYRAMIDAL NEURONS; PROPAGATING ACTION-POTENTIALS; TERM SYNAPTIC DEPRESSION; RAT NEOSTRIATAL NEURONS; MONKEY CAUDATE NEURONS; IN-VIVO; FUNCTIONAL-PROPERTIES; HIPPOCAMPAL-NEURONS; INTRACELLULAR MG2+ AB Up-states represent a key feature of synaptic integration in cortex and striatum that involves activation of many synaptic inputs. In the striatum, the sparse firing and tight control of action potential timing is in contrast to the large intracellular membrane potential depolarizations observed during the up-state. One hallmark of striatal spiny projection neurons is the delay to action potential generation in both up-states and suprathreshold depolarization by somatic current injection. By studying somatic and dendritic intracellular calcium ([Ca2+](i)) transients during spontaneous up-states in cortex-striatum-substantia nigra organotypic cultures, we show that the delay between up-state onset and action potential generation determines dendritic peak [Ca2+](i). Peak [Ca2+](i) from single action potentials reached maximum values when action potentials were close to up-state onset and sharply decayed to near subthreshold up-state [Ca2+] levels as a function of time (tau = 47 +/- 26 msec for tertiary dendrite). Similarly, a precisely timed action potential elicited during subthreshold up-states through somatic current injection established that the delay between up-state onset and action potential generation is the critical variable that controls peak [Ca2+](i). Blocking NMDA channels internally with high intracellular Mg2+ ([Mg2+](i)) (10 mM) abolished the dependency of peak [Ca2+](i) on action potential timing during spontaneous up-states. Finally, high [Mg2+](i) specifically blocked [Ca2+](i) transients that resulted from local NMDA application in conjunction with backpropagating action potentials. We conclude that precisely timed, single action potentials during striatal up-states control peak dendritic calcium levels. We suggest that this mechanism might play an important role in synaptic plasticity of the corticostriatal pathway. C1 NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Plenz, D (reprint author), NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Bldg 36,Room 2D-26,9000 Rockville Pike, Bethesda, MD 20892 USA. EM plenzd@intra.nimh.nih.gov NR 55 TC 45 Z9 45 U1 0 U2 6 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 JAN 28 PY 2004 VL 24 IS 4 BP 877 EP 885 DI 10.1523/JNEUROSCI.4475-03.2004 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 768DJ UT WOS:000188512700012 PM 14749432 ER PT J AU Zanuy, D Casanovas, J Aleman, C AF Zanuy, D Casanovas, J Aleman, C TI Thermal stability of the secondary structure of poly(alpha,L-glutamate) in self-assembled complexes as studied by molecular dynamics in chloroform solution SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ALPHA-HELIX; SOLID-STATE; SURFACTANT; CONFORMATION; ACID C1 NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Univ Lleida, Escola Politecn Super, Dept Quim, E-25001 Lleida, Spain. Univ Politecn Catalunya, ETSEIB, Dept Engn Quim, E-08028 Barcelona, Spain. RP Zanuy, D (reprint author), NCI, Lab Expt & Computat Biol, Bldg 469,Room 151, Frederick, MD 21702 USA. EM zanuyd@ncifcrf.gov; carlos.aleman@upc.es RI Casanovas, Jordi/B-5435-2013; Zanuy, David/G-3930-2014 OI Casanovas, Jordi/0000-0002-4914-9194; Zanuy, David/0000-0001-7704-2178 NR 12 TC 13 Z9 13 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 28 PY 2004 VL 126 IS 3 BP 704 EP 705 DI 10.1021/ja036803e PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 765YH UT WOS:000188318300005 PM 14733530 ER PT J AU O'Hare, AM Glidden, DV Fox, CS Hsu, CY AF O'Hare, AM Glidden, DV Fox, CS Hsu, CY TI High prevalence of peripheral arterial disease in persons with renal insufficiency - Results from the National Health and Nutrition Examination Survey 1999-2000 SO CIRCULATION LA English DT Article DE peripheral vascular disease; kidney; creatinine ID CARDIOVASCULAR-DISEASE; MORTALITY; RISK; OUTCOMES; ISSUES; INDEX; HEART AB Background - Although renal insufficiency is a recognized risk factor for coronary artery disease, little is known about the epidemiology of lower-extremity peripheral arterial disease ( PAD) in persons with renal insufficiency. Methods and Results - We examined the cross-sectional association of PAD, defined as an ankle-brachial index (ABI) < 0.9, and renal insufficiency, defined as an estimated creatinine clearance (CRCL) < 60 mL . min(-1) . 1.73 m(-2), among 2229 eligible participants in the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000. An estimated 1.2 +/- 0.3 million persons greater than or equal to40 years old with CRCL <60 mL &BULL; min(-1) &BULL; 1.73 m(-2) (24%) have PAD defined as an ABI <0.9 (versus 3.7% of persons with CRCL greater than or equal to 60 mL . min(-1) . 1.73 m(-2)). The association of ABI <0.9 with renal insufficiency was independent of potential confounders such as age, diabetes, hypertension, coronary artery disease, stroke history, and hypercholesterolemia (OR 2.5, 95% CI 1.2 to 5.1, P = 0.011, referent category ABI 1.0 to 1.3). Conclusions - Clinicians should be aware of the remarkably high prevalence of PAD among patients with renal insufficiency. In the clinical setting, accurate identification of patients with renal insufficiency combined with routine ABI measurement in this group would greatly enhance efforts to detect subclinical PAD. C1 Vet Affairs Med Ctr San Francisco, Div Nephrol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP O'Hare, AM (reprint author), Vet Affairs Med Ctr San Francisco, Div Nephrol, Box 111J Nephrol,4150 Clement St, San Francisco, CA 94121 USA. EM Ann.O'Hare@med.va.gov FU NIDDK NIH HHS [DK 61520] NR 20 TC 180 Z9 183 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 27 PY 2004 VL 109 IS 3 BP 320 EP 323 DI 10.1161/01.CIR.0000114519.75433.DD PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 767KP UT WOS:000188439000007 PM 14732743 ER PT J AU Goldstein, DS Holmes, C AF Goldstein, DS Holmes, C TI Vasodilation during systemic tyramine administration SO CIRCULATION LA English DT Letter ID ASSAY C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU NCRR NIH HHS [RR00095]; NHLBI NIH HHS [HL67232, HL56693] NR 4 TC 3 Z9 3 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 JAN 27 PY 2004 VL 109 IS 3 BP E17 EP E17 DI 10.1161/01.CIR.0000113705.87604.A9 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 767KP UT WOS:000188439000030 PM 14744961 ER PT J AU Moffat, SD Zonderman, AB Metter, EJ Kawas, C Blackman, MR Harman, SM Resnick, SM AF Moffat, SD Zonderman, AB Metter, EJ Kawas, C Blackman, MR Harman, SM Resnick, SM TI Free testosterone and risk for Alzheimer disease in older men SO NEUROLOGY LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; HORMONE-REPLACEMENT; SPATIAL COGNITION; VERBAL MEMORY; ELDERLY WOMEN; SERUM; DEMENTIA; AGE; IMPAIRMENT; PREVALENCE AB Objective: To investigate the relationships between age-associated decreases in endogenous serum total testosterone (T) and a free T index (FTI) in men and the subsequent development of Alzheimer disease (AD). Method: The authors used a prospective, longitudinal design with follow-up in men since 1958. Participants were from the Baltimore Longitudinal Study of Aging, a community-dwelling volunteer sample with baseline ages of 32 to 87 years. All subjects were free of AD at baseline T assessment. Five hundred seventy-four men assessed at multiple time points were followed for a mean of 19.1 years (range, 4 to 37 years). Diagnoses of AD were based on biennial physical, neurologic, and neuropsychological evaluations. Results: Diagnosis of AD was associated inversely with FTI by itself and after adjustments for age, education, smoking status, body mass index, diabetes, any cancer diagnoses, and hormone supplements. In separate analyses, total T and sex hormone binding globulin were not significant predictors after adjustment with covariates. Increases in the FTI were associated with decreased risk of AD (hazard ratio=0.74; 95% CI=0.57 to 0.96), a 26% decrease for each 10-nmol/nmol FTI increase. Conclusions: Calculated free testosterone concentrations were lower in men who developed Alzheimer disease, and this difference occurred before diagnosis. Future research may determine whether higher endogenous free testosterone levels offer protection against a diagnosis of Alzheimer disease in older men. C1 NIA, Lab Personal & Cognit, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. NIH, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Kronos Longev Res Inst, Phoenix, AZ USA. RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM resnick@lpc.grc.nia.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU NCRR NIH HHS [M01 RR02719]; NIA NIH HHS [AG05146, AG08325] NR 41 TC 184 Z9 193 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 27 PY 2004 VL 62 IS 2 BP 188 EP 193 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 767KT UT WOS:000188439300008 PM 14745052 ER PT J AU Kalmijn, S van Boxtel, MPJ Ocke, M Verschuren, WMM Kromhout, D Launer, LJ AF Kalmijn, S van Boxtel, MPJ Ocke, M Verschuren, WMM Kromhout, D Launer, LJ TI Dietary intake of fatty acids and fish in relation to cognitive performance at middle age SO NEUROLOGY LA English DT Article ID INCIDENT ALZHEIMER-DISEASE; ELDERLY PEOPLE; CHOLESTEROL DETERMINATION; RISK; DEMENTIA; CONSUMPTION; ROTTERDAM; ANTIOXIDANTS; INFLAMMATION; MULTICENTER AB Objective: To examine the associations of fatty acid and fish intake with cognitive function. Methods: Data are from a cross-sectional population-based study among 1,613 subjects ranging from 45 to 70 years old. From 1995 until 2000, an extensive cognitive battery was administered and compound scores were constructed for memory, psychomotor speed, cognitive flexibility (i.e., higher order information processing), and overall cognition. A self-administered food-frequency questionnaire was used to assess habitual food consumption. The risk of impaired cognitive function (lowest 10% of the compound score) according to the energy adjusted intake of fatty acids was assessed with logistic regression, adjusting for age, sex, education, smoking, alcohol consumption, and energy intake. Results: Marine omega-3 polyunsaturated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid) were inversely related to the risk of impaired overall cognitive function and speed (per SD increase: OR=0.81, 95% CI 0.66 to 1.00 and OR=0.72, 95% CI 0.57 to 0.90). Results for fatty fish consumption were similarly inverse. Higher dietary cholesterol intake was significantly associated with an increased risk of impaired memory and flexibility (per SD increase: OR=1.27, 95% CI 1.02 to 1.57 and OR=1.26, 95% CI 1.01 to 1.57). Per SD increase in saturated fat intake, the risk of impaired memory, speed, and flexibility was also increased, although not significantly. Conclusions: Fatty fish and marine omega-3 PUFA consumption was associated with a reduced risk and intake of cholesterol and saturated fat with an increased risk of impaired cognitive function in this middle-aged population. C1 Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. Univ Maastricht, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. Natl Inst Publ Hlth & Environm, Ctr Prevent & Hlth Care Res, NL-3720 BA Bilthoven, Netherlands. Natl Inst Publ Hlth & Environm, Div Nutr & Consumer Safety, NL-3720 BA Bilthoven, Netherlands. NIA, LEDB, NIH, Bethesda, MD 20892 USA. RP Kalmijn, S (reprint author), Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, D01-335,POB 85500, NL-3508 GA Utrecht, Netherlands. EM s.kalmijn@jc.azu.nl RI Kromhout, Daan/A-8566-2014 NR 42 TC 268 Z9 287 U1 5 U2 38 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 27 PY 2004 VL 62 IS 2 BP 275 EP 280 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 767KT UT WOS:000188439300023 PM 14745067 ER PT J AU Crawford, GE Holt, IE Mullikin, JC Tai, D Green, ED Wolfsberg, TG Collins, FS AF Crawford, GE Holt, IE Mullikin, JC Tai, D Green, ED Wolfsberg, TG Collins, FS CA Natl Inst Hlth Intra Seque Ctr TI Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMATIN; SEQUENCES; BINDING; SENSITIVITY; EXPRESSION; REGIONS AB Analysis of the human genome sequence has identified approximate to25,000-30,000 protein-coding genes, but little is known about how most of these are regulated. Mapping DNase I hypersensitive (HS) sites has traditionally represented the gold-standard experimental method for identifying regulatory elements, but the labor-intensive nature of this technique has limited its application to only a small number of human genes. We have developed a protocol to generate a genome-wide library of gene regulatory sequences by cloning DNase HS sites. We generated a library of DNase HS sites from quiescent primary human CD4(+) T cells and analyzed approximate to5,600 of the resulting clones. Compared to sequences from randomly generated in silico libraries, sequences from these clones were found to map more frequently to regions of the genome known to contain regulatory elements, such as regions upstream of genes, within CpG islands, and in sequences that align between mouse and human. These cloned sites also tend to map near genes that have detectable transcripts in CD4(+) T cells, demonstrating that transcriptionally active regions of the genome are being selected. Validation of putative regulatory elements was achieved by repeated recovery of the same sequence and real-time PCR. This cloning strategy, which can be scaled up and applied to any cell line or tissue, will be useful in identifying regulatory elements controlling global expression differences that delineate tissue types, stages of development, and disease susceptibility. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM francisc@exchange.nih.gov NR 22 TC 104 Z9 107 U1 2 U2 5 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 JAN 27 PY 2004 VL 101 IS 4 BP 992 EP 997 DI 10.1073/pnas.0307540100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768FU UT WOS:000188533600018 PM 14732688 ER PT J AU Schindler, CW Karcz-Kubicha, M Thorndike, EB Muller, CE Tella, SR Goldberg, SR Ferre, S AF Schindler, CW Karcz-Kubicha, M Thorndike, EB Muller, CE Tella, SR Goldberg, SR Ferre, S TI Lack of adenosine A(1) and dopamine D2 receptor-mediated modulation of the cardiovascular effects of the adenosine A(2A) receptor agonist CGS 21680 SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE adenosine A(2A) receptor; adenosine A(1) receptor; dopamine D-2 receptor; cardiovascular; motor activity ID VAGAL AFFERENT NEURONS; CENTRAL-NERVOUS-SYSTEM; ANTAGONIST IN-VIVO; NORMOTENSIVE RATS; CGS 21680; PHARMACOLOGY; STIMULATION; RESPONSES; PATTERNS; SUBTYPES AB Some behavioral and biochemical effects of the systemically administered adenosine A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5' -N-ethylcarboxamidoadenosine (CGS 21680) in rats are potentiated by adenosine A, receptor agonists and counteracted by dopamine D2 receptor agonists. In the present study we compared potentiating and antagonistic interactions between CGS 21680 and adenosine A, and dopamine D2 receptor agonists on motor activity and on cardiovascular responses (arterial blood pressure and heart rate). The motor-depressant effects produced by CGS 21680 (0.5 mg/kg, i.p.) were potentiated by the adenosine A, receptor agonist N-6-cyclopentyladenosine (CPA, 0.3 mg/kg, i.p.) and counteracted by the dopamine D2 receptor agonist quinpirole (0.5 mg/kg, i.p.). In contrast, neither CPA nor quinpirole significantly modified the decrease in arterial pressure or the increase in heart rate induced by CGS 21680. However, the adenosine A(2A) receptor antagonist 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3, 3 mg/kg, i.p.) counteracted both the motor-depressant and cardiovascular effects of CGS 21680. Therefore, the effects of the systemically administered adenosine A(2A) receptor agonist CGS 21680 on cardiovascular function, in contrast to its effects on motor behavior, appear to be independent of the effects of adenosine A(1) and dopamine D2 receptor activity. (C) 2003 Elsevier B.V. All rights reserved. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,IRP, Baltimore, MD 21224 USA. Univ Bonn, Inst Pharmaceut, D-53115 Bonn, Germany. Drug Enforcement Adm, Drug & Chem Evaluat Sect, Off Divers Control, Washington, DC 20537 USA. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM cschindl@helix.nih.gov RI Ferre, Sergi/K-6115-2014; Muller, Christa/C-7748-2014 OI Ferre, Sergi/0000-0002-1747-1779; Muller, Christa/0000-0002-0013-6624 NR 37 TC 11 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 26 PY 2004 VL 484 IS 2-3 BP 269 EP 275 DI 10.1016/j.ejphar.2003.11.010 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 769DH UT WOS:000188610800019 PM 14744613 ER PT J AU Nacsa, J Radaelli, A Edghill-Smith, Y Venzon, D Tsai, WP Morghen, CD Panicali, D Tartaglia, J Franchini, G AF Nacsa, J Radaelli, A Edghill-Smith, Y Venzon, D Tsai, WP Morghen, CD Panicali, D Tartaglia, J Franchini, G TI Avipox-based simian immunodeficiency virus (SIV) vaccines elicit a high frequency of SIV-specific CD4+ and CD8+ T-cell responses in vaccinia-experienced SIVmac251-infected macaques SO VACCINE LA English DT Article DE poxvirus; immunotherapy; SIVmac251 infection ID COMBINATION ANTIRETROVIRAL THERAPY; RHESUS-MONKEYS; PROTEASE INHIBITORS; BODY-COMPOSITION; ALVAC-SIV; INFECTION; HIV; LYMPHOCYTES; INDIVIDUALS; CHALLENGE AB The ability of ALVAC- or fowlpox-based simian immunodeficiency virus (SIV) vaccines to boost SIV-specific CD4+ and CD8+ T-cell responses was tested in 10 vaccinia-experienced macaques infected with SIVmac251. The CD8+ T-cell response to the dominant Gag(181-189) CM9 was quantitated in seven Mamu-A*01-positive macaques by tetramer staining, by ex vivo cytotoxic T-lymphocyte (CTL) activity, and by intracellular cytokine staining (ICS) with the specific Gag(181-189) CM9 peptide. The overall CD8+ T-cell response to Gag was assessed using a peptide pool encompassing the entire Gag protein followed by measurement of TNF-alpha production in ICS assay. Similarly, virus-specific CD4+ T-cell responses were measured by ICS for TNF-alpha following stimulation with the Gag-overlapping peptide and by proliferative response following stimulation with purified p27 Gag. The two vaccine modalities effectively boosted both CD4+ and CD8+ SIV-specific T-cell response despite prior exposure to the vaccinia-derivative NYVAC vector, suggesting that sequential boosting with either avipox-based vector vaccine candidate is a realistic approach in immune therapy of human immunodeficiency virus type I (HIV-1)-infected individuals. Published by Elsevier Ltd. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. CNR, Dept Pharmacol Sci, Med Pharmacol & Cellular & Mol Pharmacol Sect, I-20129 Milan, Italy. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Therion Biol Corp, Cambridge, MA USA. Aventis Pasteur, Toronto, ON M2R 3T4, Canada. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. EM jn97w@nih.gov; antonia.radaelli@unimi.it; ye7x@nih.gov; dv4m@nih.gov; wt37u@nih.gov; carlo.degiulimorghen@unimi.it; dpanicali@therionbio.com; jim.tartaglia@aventis.com; gf7u@nih.gov RI Venzon, David/B-3078-2008; OI Radaelli, Antonia/0000-0002-5683-6216 NR 38 TC 18 Z9 19 U1 0 U2 1 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 JAN 26 PY 2004 VL 22 IS 5-6 BP 597 EP 606 DI 10.1016/j.vaccine.2003.08.028 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 775YB UT WOS:000189087300010 PM 14741150 ER PT J AU Shibusawa, Y Fujiwara, T Shindo, H Ito, Y AF Shibusawa, Y Fujiwara, T Shindo, H Ito, Y TI Purification of alcohol dehydrogenase from bovine liver crude extract by dye-ligand affinity counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE purification; dye-ligand affinity counter-current chromatography; alcohol dehydrogenase ID COIL PLANET CENTRIFUGE; STATIONARY-PHASE; SEPARATION; RETENTION; PROTEINS; SYSTEMS; DESIGN AB Alcohol dehydrogenase (ADH) was extracted from a crude bovine liver homogenate by dye-ligand affinity counter-current chromatography (CCC) using a cross-axis coil planet centrifuge (x-axis CPC). The purification was performed using two types of polymer phase systems composed of 4.4% polyethylene glycol (PEG) 8000-7.0% dextran T500-0.1 M potassium phosphate buffers and 16% PEG 1000-12.5% potassium phosphate buffers, both containing a procion red dye as an affinity ligand at various pH values. The best purification was achieved using the PEG 1000-potassium phosphate system at pH 7.3 containing 0.05% procion red as a ligand. The upper PEG-rich phase containing procion red was used as the stationary phase and a crude bovine liver homogenate was eluted with the potassium phosphate-rich lower phase at 0.5 mi/min. After elution of bovine liver proteins in the homogenate, ADH still retained in the stationary phase was collected from the column by eluting with the PEG 1000-rich upper phase. Collected fractions were analyzed by ADH enzymatic activity and by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) to detect contaminant proteins in the ADH fractions. The ADH was purified directly from crude bovine liver extract within 6 h with minimum loss of its enzymatic activity. (C) 2003 Elsevier B.V. All rights reserved. C1 Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, Hachioji, Tokyo 1920392, Japan. Natl Heart Lung & Blood Inst, Lab Biophys Chem, NIH, Bethesda, MD 20892 USA. RP Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. NR 14 TC 7 Z9 13 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 25 PY 2004 VL 799 IS 2 BP 239 EP 244 DI 10.1016/j.jchromb.2003.10.039 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 758VB UT WOS:000187670500007 PM 14670742 ER PT J AU Moaddel, R Bullock, PL Wainer, IW AF Moaddel, R Bullock, PL Wainer, IW TI Development and characterization of an open tubular column containing immobilized P-glycoprotein for rapid on-line screening for P-glycoprotein substrates SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE substrates; ABC transporters; screening; P-glycoprotein ID BINDING; PURIFICATION; CANCER AB Cellular membranes from a cell line expressing P-glycoprotein (Pgp(+)) and from a cell line that does not express Pgp (Pgp(-)) were immobilized on the surface of glass capillaries (25 cm x 100 mum i.d.) by non-covalent interactions using the avidin-biotin coupling system to create two open tubular columns, Pgp(+)-OT and Pgp(-)-OT. Frontal displacement chromatography on the Pgp(+)-OT demonstrated that the immobilized Pgp retained its ability to specifically bind the known Pgp substrates vinblastin and ketoconazole. The calculated affinities, expressed as K-d, for vinblastin and ketoconazole were 97 nM and 12.1 muM, which were comparable with previously reported Kd values of 37 nM and 8.6 muM, respectively. The results confirm that the Pgp(+)-OT can be used to quantitatively estimate binding affinities for the Pgp. Frontal displacement chromatography on the Pgp(-)-OT demonstrated that the immobilized membranes retained the ability to bind some Pgp substrates, but that the binding was not due to specific binding to Pgp. A cohort of compounds containing high affinity Pgp substrates (vinblastin, prazosin) and moderate-low affinity Pgp substrates (doxorubicin, verapamil, ketoconazole) and a non-substrate (nicotine) were chromatographed on the Pgp(+)-OT and Pgp(-)-OT using fast frontal analysis and mass spectrometric detection. The results demonstrated that when the retention on the Pgp(+)-OT was corrected by subtraction of the retention on the Pgp(-)-OT, the test compounds could be accurately sorted into high, moderate-low and non-substrate categories. The data from the study indicates that a single 30-min parallel chromatographic experiment can be used to rank a compound based upon its relative affinity for the immobilized Pgp. (C) 2003 Elsevier B.V. All rights reserved. C1 NIA, Bioanalyt & Drug Discovery Unit, Intramural Res Program, Lab Clin Investigat,Gerontol Res Ctr, Baltimore, MD 21224 USA. Purdue Pharma LP, Discovery Support, Ardsley, NY USA. RP Wainer, IW (reprint author), NIA, Bioanalyt & Drug Discovery Unit, Intramural Res Program, Lab Clin Investigat,Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 16 TC 41 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 25 PY 2004 VL 799 IS 2 BP 255 EP 263 DI 10.1016/j.jchromb.2003.10.054 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 758VB UT WOS:000187670500009 PM 14670744 ER PT J AU Massad, LS Springer, G Jacobson, L Watts, H Anastos, K Korn, A Cejtin, H Stek, A Young, M Schmidt, J Minkofp, H AF Massad, LS Springer, G Jacobson, L Watts, H Anastos, K Korn, A Cejtin, H Stek, A Young, M Schmidt, J Minkofp, H TI Pregnancy rates and predictors of conception, miscarriage and abortion in US women with HIV SO AIDS LA English DT Article DE HIV; AIDS; pregnancy outcome; HAART ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; INTERAGENCY HIV; INFECTED WOMEN; HIV-1-INFECTED WOMEN; SEROPOSITIVE WOMEN; DRUG-USE; KNOWLEDGE; SEROSTATUS; DIAGNOSIS AB Objective: To determine frequency and outcomes of pregnancy in US women with HIV before and after introduction of highly active antiretroviral therapy (HAART). Design: Prospective cohort study at six US centers. Methods: HIV seropositive and at-risk seronegative women reported pregnancy outcomes at 6-month intervals during the period 1 October 1994 to 31 March 2002. Outcomes were tabulated and pregnancy rates calculated. Logistic regression defined outcome correlates. Results: Pregnancy rates were 7.4 and 15.2 per 100 person-years in seropositive and seronegative women, respectively (P<0.0001). Among seropositives, 119 (36%) pregnancies ended in live birth, six (2%) in stillbirth, 126 (36%) in abortion, 83 (24%) in miscarriage, 16 (5%) in ectopic pregnancy, and two (1%) in other outcomes (P= nonsignificant versus seronegatives). Independent baseline correlates of conception in seropositives included younger age [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.16-1.23], prior abortion (OR, 1.79; 95% Cl, 1.25-2.63), lower HIV RNA levels (OR, 1.30; 95% Cl, 1.10-1.54 for each log decrease), and being unmarried (OR, 1.59; 95% Cl, 1.02-2.44). Baseline antiretroviral use at baseline was linked to lower conception risk (OR, 0.34; 95% Cl, 0.49-0.98 for mono- or combination therapy; OR, 0.34; 95% Cl, 0.03-4.28 for HAART). Abortion was less likely during the HAART era, (OR, 0.68; 95% Cl, 0.35-1.33 during the early HAART era; OR, 0.46; 95% Cl, 0.23-0.90 during the later HAART era, compared with before HAART). Conclusions: Women with HIV were less likely to conceive than at-risk uninfected women, but pregnancy outcomes were similar. Abortion became less common after the introduction of HAART. (C) 2004 Lippincott Williams & Wilkins. C1 So Illinois Univ, Sch Med, Dept Obstet & Gynecol, Springfield, IL 62794 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. NICHHD, Bethesda, MD USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Lincoln Med & Mental Hlth Ctr, Bronx, NY 10451 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Univ So Calif, Los Angeles, CA USA. Georgetown Univ, Washington, DC USA. Maimonides Hosp, Brooklyn, NY 11219 USA. RP Massad, LS (reprint author), So Illinois Univ, Sch Med, Dept Obstet & Gynecol, POB 19640, Springfield, IL 62794 USA. NR 22 TC 68 Z9 71 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 23 PY 2004 VL 18 IS 2 BP 281 EP 286 DI 10.1097/01.aids.ooooiO4376.21567.24 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 774FB UT WOS:000188968100018 PM 15075546 ER PT J AU Lagunas, L Bradbury, CM Laszlo, A Hunt, CR Gius, D AF Lagunas, L Bradbury, CM Laszlo, A Hunt, CR Gius, D TI Indomethacin and ibuprofen induce Hsc70 nuclear localization and activation of the heat shock response in HeLa cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE indomethacin; ibuprofen; Hsc70; nuclear localization ID NF-KAPPA-B; RADIATION-INDUCED ACTIVATION; COLON-CANCER CELLS; IONIZING-RADIATION; FACTOR-I; INDUCED RADIOSENSITIZATION; MOLECULAR CHAPERONES; INDUCED APOPTOSIS; PROTEIN-KINASES; MAP KINASE AB It has been established that non-steroidal anti-inflammatory drugs (NSAIDs), such as sodium salicylate, sulindac, ibuprofen, and indomethacin, induce anti-inflammatory and anti-proliferative effects independent of cyclooxygenase. These cyclooxygenase-independent pharmacodynamic effects appear to regulate several signaling pathways involving proliferation, apoptosis, and heat shock response. However, the mechanisms of these actions remain an area of ongoing investigation. Hsc70 is a cytoplasmic chaperone protein involved in folding and trafficking of client proteins to different subcellular compartments, plays roles in signal transduction and apoptosis processes, and translocates to the nucleus following exposure to heat shock. Since NSAIDs induce some aspects of the heat shock response, we hypothesized that they may also induce Hsc70 nuclear translocation. Western immunoblotting and indirect cellular immunofluorescence showed that indomethacin and ibuprofen induce Hsc70 nuclear translocation at concentrations previously shown to induce HSF DNA-binding activity. Chemical inhibition of both p38(MAPK) and Erk42/44 had no effect on localization patterns. In addition, while indomethacin has been shown to behave as an oxidative stressor, the radical scavenging agent, N-acetyl cysteine, did not inhibit nuclear translocation. These results indicate that induction of the heat shock response by NSAIDs occurs at concentrations fivefold greater than those required to inhibit cyclooxygenase activity, suggesting a cyclooxygenase-independent mechanism, and in the presence or absence of kinase inhibitors and a free radical scavenger, suggesting independence of Erk42/44 or p38(MAPK) activities and intracellular oxidoreductive state. Published by Elsevier Inc. C1 NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiat Oncol,Div Radiat & Canc Biol, St Louis, MO USA. RP NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, Ctr Canc Res,NIH, Bldg 10, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov NR 41 TC 14 Z9 17 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 23 PY 2004 VL 313 IS 4 BP 863 EP 870 DI 10.1016/j.bbrc.2003.12.018 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 762TF UT WOS:000187997700007 PM 14706622 ER PT J AU Bonifacino, JS Glick, BS AF Bonifacino, JS Glick, BS TI The mechanisms of vesicle budding and fusion SO CELL LA English DT Review ID TO-GOLGI TRANSPORT; INTRACELLULAR PROTEIN-TRANSPORT; PLASMA-MEMBRANE ATPASE; COPII-COATED VESICLES; AMINO-TERMINAL DOMAIN; ENDOPLASMIC-RETICULUM; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE; VESICULAR TRANSPORT; SNARE PROTEINS AB Genetic and biochemical analyses of the secretory pathway have produced a detailed picture of the molecular mechanisms involved in selective cargo transport between organelles. This transport occurs by means of vesicular intermediates that bud from a donor compartment and fuse with an acceptor compartment. Vesicle budding and cargo selection are mediated by protein coats, while vesicle targeting and fusion depend on a machinery that includes the SNARE proteins. Precise regulation of these two aspects of vesicular transport ensures efficient cargo transfer while preserving organelle identity. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 NR 128 TC 849 Z9 879 U1 11 U2 163 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 23 PY 2004 VL 116 IS 2 BP 153 EP 166 DI 10.1016/S0092-8674(03)01079-1 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 768KG UT WOS:000188541700007 PM 14744428 ER PT J AU Wang, F Thirumurugan, K Stafford, WF Hammer, JA Knight, PJ Sellers, JR AF Wang, F Thirumurugan, K Stafford, WF Hammer, JA Knight, PJ Sellers, JR TI Regulated conformation of myosin V SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; F-ACTIN; BOUNDARY ANALYSIS; SCALLOP MYOSIN; MOTOR-ACTIVITY; LIGHT-CHAINS; TAIL DOMAIN; BINDING; CALCIUM; LOCALIZATION AB We have found that myosin V, an important actin-based vesicle transporter, has a folded conformation that is coupled to inhibition of its enzymatic activity in the absence of cargo and Ca2+. In the absence of Ca2+ where the actin-activated MgATPase activity is low, purified brain myosin V sediments in the analytical ultracentrifuge at 14 S as opposed to 11 S in the presence of Ca2+ where the activity is high. At high ionic strength it sediments at 10 S independent of Ca2+, and its regulation is poor. These data are consistent with myosin V having a compact, inactive conformation in the absence of Ca2+ and an extended conformation in the presence of Ca2+ or high ionic strength. Electron microscopy reveals that in the absence of Ca2+ the heads and tail are both folded to give a triangular shape, very different from the extended appearance of myosin V at high ionic strength. A recombinant myosin V heavy meromyosin fragment that is missing the distal portion of the tail domain is not regulated by calcium and has only a small change in sedimentation coefficient, which is in the opposite direction to that seen with intact myosin V. Electron microscopy shows that its heads are extended even in the absence of calcium. These data suggest that interaction between the motor and cargo binding domains may be a general mechanism for shutting down motor protein activity and thereby regulating the active movement of vesicles in cells. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England. Boston Biomed Res Inst, Watertown, MA 02472 USA. RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov OI Hammer, John/0000-0002-2496-5179; Thirumurugan, Kavitha/0000-0002-4673-4099 NR 37 TC 103 Z9 103 U1 2 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 JAN 23 PY 2004 VL 279 IS 4 BP 2333 EP 2336 DI 10.1074/jbc.C300488200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764MU UT WOS:000188211300002 PM 14634000 ER PT J AU Inoue, Y Yu, AM Inoue, J Gonzalez, FJ AF Inoue, Y Yu, AM Inoue, J Gonzalez, FJ TI Hepatocyte nuclear factor 4 alpha is a central regulator of bile acid conjugation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACYL-COA SYNTHETASE; N-ACYLTRANSFERASE; MOLECULAR-CLONING; SALT TRANSPORTERS; GENE-EXPRESSION; HNF4-ALPHA; PROMOTER; LIGASE AB Hepatocyte nuclear factor 4alpha (HNF4alpha) has an important role in regulating the expression of liver-specific genes. Because bile acids are produced from cholesterol in liver and many enzymes involved in their biosynthesis are preferentially expressed in liver, the role of HNF4alpha in the regulation of bile acid production was examined. In mice, unconjugated bile acids are conjugated with taurine by the liver-specific enzymes, bile acid-CoA ligase and bile acid-CoA: amino acid N-acyl-transferase ( BAT). Mice lacking hepatic HNF4alpha expression exhibited markedly decreased expression of the very long chain acyl-CoA synthase-related gene ( VLACSR), a mouse candidate for bile acid-CoA ligase, and BAT. This was associated with markedly elevated levels of unconjugated and glycine-conjugated bile acids in gallbladder. HNF4alpha was found to bind directly to the mouse VLACSR and BAT gene promoters, and the promoter activities were dependent on HNF4alpha-binding sites and HNF4alpha expression. In conclusion, HNF4alpha plays a central role in bile acid conjugation by direct regulation of VLACSR and BAT in vivo. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Rm 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 26 TC 55 Z9 55 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 JAN 23 PY 2004 VL 279 IS 4 BP 2480 EP 2489 DI 10.1074/jbc.M311015200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764MU UT WOS:000188211300019 PM 14583614 ER PT J AU Kang, SW Chang, TS Lee, TH Kim, ES Yu, DY Rhee, SG AF Kang, SW Chang, TS Lee, TH Kim, ES Yu, DY Rhee, SG TI Cytosolic peroxiredoxin attenuates the activation of JNK and p38 but potentiates that of ERK in HeLa cells stimulated with tumor necrosis factor-alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; NF-KAPPA-B; CYSTEINE-SULFINIC ACID; PROTEIN-KINASE KINASE; SIGNAL-TRANSDUCTION; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; MAMMALIAN PEROXIREDOXIN; TERMINAL KINASE; CELLULAR-RESPONSE AB Tumor necrosis factor-alpha (TNF-alpha) induces the activation of all three types of mitogen-activated protein kinase (MAPK): c-Jun NH2-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). This cytokine also induces the production of several types of reactive oxygen species, including H2O2. With the use both of HeLa cells expressing wild-type or dominant negative forms of the cytosolic peroxidase peroxiredoxin II and of mouse embryonic fibroblasts deficient in this protein, we evaluated the roles of H2O2 in the activation of MAPKs by TNF-alpha. In vitro kinase assays as well as immunoblot analysis with antibodies specific for activated MAPKs indicated that H2O2 produced in response to TNF-alpha potentiates the activation of JNK and p38 induced by this cytokine but inhibits that of ERK. Our results also suggest that cytosolic peroxiredoxins are important regulators of TNF signaling pathways. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Div Mol Life Sci, Seoul 120750, South Korea. Korea Res Inst Biosci & Biotechnol, Funct Prote Lab, Lab Dev & Differentiat, Taejon 305333, South Korea. RP Rhee, SG (reprint author), Bldg 50,Rm 3523,South Dr,MSC 8015, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 56 TC 59 Z9 62 U1 2 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 JAN 23 PY 2004 VL 279 IS 4 BP 2535 EP 2543 DI 10.1074/jbc.M307698200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764MU UT WOS:000188211300026 PM 14597634 ER PT J AU Lee, HJ Lee, JK Miyake, S Kim, SJ AF Lee, HJ Lee, JK Miyake, S Kim, SJ TI A novel E1A-like inhibitor of differentiation (EID) family member, EID-2, suppresses transforming growth factor (TGF)-beta signaling by blocking TGF-beta-induced formation of Smad3-Smad4 complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMAD PROTEINS; TRANSCRIPTIONAL ACTIVATION; DNA-BINDING; COACTIVATORS; SEQUENCE; CBP/P300; DOMAIN AB Smad proteins play key roles in intracellular signaling of the transforming growth factor-beta (TGF-beta) superfamily. E1A, an adenoviral oncoprotein, is known to inhibit TGF-beta-induced transactivation through binding to Smad proteins. Recently, an EID-1 (E1A-like inhibitor of differentiation-1) and EID-2 (EID-1-like inhibitor of differentiation-2) were identified. In this study, we examined the effect of EID-2 on Smad-mediated TGF-beta signaling. Here, we show that EID-2 inhibits TGF-beta/Smad transcriptional responses. EID-2 interacts constitutively with Smad proteins, and most strongly with Smad3. Stable expression of EID-2 in the TGF-beta1-responsive cell line inhibits endogenous Smad3-Smad4 complex formation and TGF-beta1-induced expression of p21 and p15. These results suggest that EID-2 may function as an endogenous suppressor of TGF-beta signaling. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Tohoku Univ, Grad Sch Med, Dept Dev Genet, Ctr Translat & Adv Anim Res Human Dis, Sendai, Miyagi 9808575, Japan. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. EM kims@mail.nih.gov NR 28 TC 17 Z9 20 U1 1 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 JAN 23 PY 2004 VL 279 IS 4 BP 2666 EP 2672 DI 10.1074/jbc.M310591200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764MU UT WOS:000188211300042 PM 14612439 ER PT J AU Golomb, E Ma, XF Jana, SS Preston, YA Kawamoto, S Shoham, NG Goldin, E Conti, MA Sellers, JR Adelstein, RS AF Golomb, E Ma, XF Jana, SS Preston, YA Kawamoto, S Shoham, NG Goldin, E Conti, MA Sellers, JR Adelstein, RS TI Identification and characterization of nonmuscle myosin II-C, a new member of the myosin II family SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA EXPRESSION; HEAVY-CHAIN ISOFORMS; IN-VITRO; MUSCLE-CONTRACTION; NEURITE OUTGROWTH; MOUSE HEART; LOCALIZATION; GENE; CLONING; CELLS AB A previously unrecognized nonmuscle myosin II heavy chain (NMHC II), which constitutes a distinct branch of the nonmuscle/ smooth muscle myosin II family, has recently been revealed in genome data bases. We characterized the biochemical properties and expression patterns of this myosin. Using nucleotide probes and affinity-purified antibodies, we found that the distribution of NMHC II-C mRNA and protein (MYH14) is widespread in human and mouse organs but is quantitatively and qualitatively distinct from NMHC II-A and II-B. In contrast to NMHC II-A and II-B, the mRNA level in human fetal tissues is substantially lower than in adult tissues. Immunofluorescence microscopy showed distinct patterns of expression for all three NMHC isoforms. NMHC II-C contains an alternatively spliced exon of 24 nucleotides in loop I at a location analogous to where a spliced exon appears in NMHC II-B and in the smooth muscle myosin heavy chain. However, unlike neuron-specific expression of the NMHC II-B insert, the NMHC II-C inserted isoform has widespread tissue distribution. Baculovirus expression of noninserted and inserted NMHC II-C heavy meromyosin (HMMII-C/HMM II-C1) resulted in significant quantities of expressed protein (mg of protein) for HMM II-C1 but not for HMM II-C. Functional characterization of HMM II-C1 by actin-activated MgATPase activity demonstrated a V-max of 0.55 + 0.18 s(-1), which was half-maximally activated at an actin concentration of 16.5 + 7.2 muM. HMM II-C1 translocated actin filaments at a rate of 0.05 + 0.011 mum/s in the absence of tropomyosin and at 0.072 + 0.019 mum/s in the presence of tropomyosin in an in vitro motility assay. C1 Shaare Zedek Med Ctr, Dept Pathol, IL-91031 Jerusalem, Israel. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NIAMS, Genet & Gen Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Golomb, E (reprint author), Shaare Zedek Med Ctr, Dept Pathol, IL-91031 Jerusalem, Israel. EM golomb@szmc.org.il OI Adelstein, Robert/0000-0002-8683-2144 NR 46 TC 194 Z9 208 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 JAN 23 PY 2004 VL 279 IS 4 BP 2800 EP 2808 DI 10.1074/jbc.M309981200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764MU UT WOS:000188211300058 PM 14594953 ER PT J AU Remmert, K Olszewski, TE Bowers, MB Dimitrova, M Ginsburg, A Hammer, JA AF Remmert, K Olszewski, TE Bowers, MB Dimitrova, M Ginsburg, A Hammer, JA TI CARMIL is a Bona fide capping protein interactant SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN POLYMERIZATION; ACANTHAMOEBA-CASTELLANII; ESCHERICHIA-COLI; SH3 DOMAIN; MYOSIN-I; BINDING; IDENTIFICATION; ACAN125; LOCALIZATION; PEPTIDE AB CARMIL, also known as Acan 125, is a multidomain protein that was originally identified on the basis of its interaction with the Src homology 3 (SH3) domain of type I myosins from Acanthamoeba. In a subsequent study of CARMIL from Dictyostelium, pull-down assays indicated that the protein also bound capping protein and the Arp2/3 complex. Here we present biochemical evidence that Acanthamoeba CARMIL interacts tightly with capping protein. In biochemical preparations, CARMIL copurified extensively with two polypeptides that were shown by microsequencing to be the alpha- and beta-subunits of Acanthamoeba capping protein. The complex between CARMIL and capping protein, which is readily demonstratable by chemical cross-linking, can be completely dissociated by size exclusion chromatography at pH 5.4. Analytical ultracentrifugation, surface plasmon resonance and SH3 domain pull-down assays indicate that the dissociation constant of capping protein for CARMIL is similar to0.4 muM or lower. Using CARMIL fusion proteins, the binding site for capping protein was shown to reside within the carboxyl-terminal, similar to200 residue, proline-rich domain of CARMIL. Finally, chemical cross-linking, analytical ultracentrifugation, and rotary shadowed electron microscopy revealed that CARMIL is asymmetric and that it exists in a monomer 7 dimer equilibrium with an association constant of 1.0 x 10(6) M-1. Together, these results indicate that CARMIL self-associates and interacts with capping protein with affinities that, given the cellular concentrations of the proteins (similar to1 and 2 muM for capping protein and CARMIL, respectively), indicate that both activities should be physiologically relevant. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2523,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov OI Hammer, John/0000-0002-2496-5179 NR 24 TC 20 Z9 21 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 JAN 23 PY 2004 VL 279 IS 4 BP 3068 EP 3077 DI 10.1074/jbc.M308829200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 764MU UT WOS:000188211300088 PM 14594951 ER PT J AU Mima, T Oga, T Rothwell, J Satow, T Yamamoto, J Toma, K Fukuyama, H Shibasaki, H Nagamine, T AF Mima, T Oga, T Rothwell, J Satow, T Yamamoto, J Toma, K Fukuyama, H Shibasaki, H Nagamine, T TI Short-term high-frequency iranscutaneous electrical nerve stimulation decreases human motor cortex excitability SO NEUROSCIENCE LETTERS LA English DT Article DE transcutaenous electrical nerve stimulation; transcranial magnetic stimulation; sensorimotor cortex; plasticity; sensory threshold; motor excitability ID SOMATOSENSORY INPUT; EVOKED-POTENTIALS; PAIN THRESHOLD; PLASTICITY; TENS; HAND AB Several pervious studies have shown that periods of changed sensory input can have after effects on the excitability of the corticospinal system. Here we test whether the parameters of peripheral stimulation conventionally used to treat pain with transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have modulatory effects on the motor system. We measured the amplitude of motor evoked potentials (MEPs) elicited by the focal transcranial magnetic stimulation in the right abductor pollicis brevis and first dorsal interosseous muscles before and after 30 min TENS over the right thenar eminence. In addition, we evaluated tactile and 2-point discrimination thresholds at the same site. TENS transiently reduced MEPs and increascd sensory thresholds. This suggests that short-term TENS might have an inhibitory effect on both the sensory and motor systems. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Kyoto Univ, Grad sch Med, Human & Brain Res Ctr, Dept Neurosurg, Kyoto 6068507, Japan. Inst Neurol, Sobell Dept Neurophysiol, London WC1N 3BG, England. Inst BIomed Res & Innovat, Kobe, Hyogo 6500047, Japan. NINDS, NIH, Bethesda, MD 20892 USA. RP Kyoto Univ, Grad sch Med, Human & Brain Res Ctr, Dept Neurosurg, Kyoto 6068507, Japan. EM mima@kuhp.kyoto-u.ac.jp OI Mima, Tatsuya/0000-0001-7787-4855; Rothwell, John/0000-0003-1367-6467 NR 19 TC 43 Z9 45 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 23 PY 2004 VL 355 IS 1-2 BP 85 EP 88 DI 10.1016/j.neulet.2003.10.045 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 766VN UT WOS:000188396300022 PM 14729241 ER PT J AU Zhou, DP Cantu, C Sagiv, Y Schrantz, N Kulkarni, AB Qi, XY Mahuran, DJ Morales, CR Grabowski, GA Benlagha, K Savage, P Bendelac, A Teyton, L AF Zhou, DP Cantu, C Sagiv, Y Schrantz, N Kulkarni, AB Qi, XY Mahuran, DJ Morales, CR Grabowski, GA Benlagha, K Savage, P Bendelac, A Teyton, L TI Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins SO SCIENCE LA English DT Article ID ACTIVATOR PROTEIN; CYTOPLASMIC TAIL; T-CELLS; INTRACELLULAR TRAFFICKING; ALPHA-GALACTOSIDASE; NKT CELLS; MOLECULES; MOUSE; CD1B; SPECIFICITY AB It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated antigen presentation and lack Valpha14 NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from CD1, thereby promoting the loading as well as the editing of lipids on CD1. Transient complexes between CD1, lipid, and LTP suggested a "tug-of-war" model in which lipid exchange between CD1 and LTP is on the basis of their respective affinities for lipids. LTPs constitute a previously unknown link between lipid metabolism and immunity and are likely to exert a profound influence on the repertoire of self, tumor, and microbial lipid antigens. C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Toronto, Dept Med & Pathobiol, Toronto, ON M5G 1X8, Canada. McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada. Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. RP Bendelac, A (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM abendela@bsd.uchicago.edu; lteyton@scripps.edu RI Morales, Carlos/H-1055-2011; Zhou, Dapeng/D-3059-2014; Benlagha, Kamel/I-5035-2016 OI Zhou, Dapeng/0000-0003-1347-3811; FU Canadian Institutes of Health Research [10435]; NIAID NIH HHS [R01 AI038339, AI38339, AI50867, P01 AI053725, P01 AI53725, R01 AI050867] NR 33 TC 235 Z9 239 U1 2 U2 9 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 JAN 23 PY 2004 VL 303 IS 5657 BP 523 EP 527 DI 10.1126/science.1092009 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765XM UT WOS:000188316400038 PM 14684827 ER PT J AU Matloubian, M Lo, CG Cinamon, G Lesneski, MJ Xu, Y Brinkmann, V Allende, ML Proia, RL Cyster, JG AF Matloubian, M Lo, CG Cinamon, G Lesneski, MJ Xu, Y Brinkmann, V Allende, ML Proia, RL Cyster, JG TI Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1 SO NATURE LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTORS; THYMOCYTE EMIGRATION; SPHINGOSINE-1-PHOSPHATE; MATURATION; FTY720; IMMUNOSUPPRESSANT; RESPONSIVENESS; KINASE AB Adaptive immunity depends on T- cell exit from the thymus and T and B cells travelling between secondary lymphoid organs to survey for antigens. After activation in lymphoid organs, T cells must again return to circulation to reach sites of infection; however, the mechanisms regulating lymphoid organ exit are unknown. An immunosuppressant drug, FTY720, inhibits lymphocyte emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate ( S1P) receptors(1-4). However, the role of S1P receptors in normal immune cell trafficking is unclear. Here we show that in mice whose haematopoietic cells lack a single S1P receptor ( S1P(1); also known as Edg1) there are no T cells in the periphery because mature T cells are unable to exit the thymus. Although B cells are present in peripheral lymphoid organs, they are severely deficient in blood and lymph. Adoptive cell transfer experiments establish an intrinsic requirement for S1P(1) in T and B cells for lymphoid organ egress. Furthermore, S1P(1)- dependent chemotactic responsiveness is strongly upregulated in T- cell development before exit from the thymus, whereas S1P(1) is downregulated during peripheral lymphocyte activation, and this is associated with retention in lymphoid organs. We find that FTY720 treatment downregulates S1P(1), creating a temporary pharmacological S1P(1)- null state in lymphocytes, providing an explanation for the mechanism of FTY720- induced lymphocyte sequestration. These findings establish that S1P(1) is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs. C1 Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Immunol Microbiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Cyster, JG (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM cyster@itsa.ucsf.edu RI Proia, Richard/A-7908-2012 NR 24 TC 1293 Z9 1337 U1 8 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 22 PY 2004 VL 427 IS 6972 BP 355 EP 360 DI 10.1038/nature02284 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765KE UT WOS:000188266200042 PM 14737169 ER PT J AU Tanaka, T Serneo, FF Tseng, HC Kulkarni, AB Tsai, LH Gleeson, JG AF Tanaka, T Serneo, FF Tseng, HC Kulkarni, AB Tsai, LH Gleeson, JG TI Cdk5 phosphorylation of doublecortin ser297 regulates its effect on neuronal migration SO NEURON LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; MICROTUBULE-ASSOCIATED PROTEIN; DYNEIN HEAVY-CHAIN; NERVOUS-SYSTEM; DEVELOPMENTAL-CHANGES; TAU-PHOSPHORYLATION; CYTOPLASMIC DYNEIN; BINDING DOMAIN; C-ELEGANS; LOCALIZATION AB Mutations in the doublecortin (DCX) gene in human or targeted disruption of the cdk5 gene in mouse lead to similar cortical lamination defects in the developing brain. Here we show that Dcx is phosphorylated by Cdk5. Dcx phosphorylation is developmentally regulated and corresponds to the timing of expression of p35, the major activating subunit for Cdk5. Mass spectrometry and Western blot analysis indicate phosphorylation at Dcx residue Ser297. Phosphorylation of Dcx lowers its affinity to microtubules in vitro, reduces its effect on polymerization, and displaces it from microtubules in cultured neurons. Mutation of Ser297 blocks the effect of Dcx on migration in a fashion similar to pharmacological inhibition of Cdk5 activity. These results suggest that Dcx phosphorylation by Cdk5 regulates its actions on migration through an effect on microtubules. C1 Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. RP Gleeson, JG (reprint author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. EM jogleeson@ucsd.edu FU NINDS NIH HHS [R01 NS041537]; PHS HHS [N5047101] NR 63 TC 155 Z9 163 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 22 PY 2004 VL 41 IS 2 BP 215 EP 227 DI 10.1016/S0896-6273(03)00852-3 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 821JZ UT WOS:000221457800008 PM 14741103 ER PT J AU Nakahara, H Itoh, H Kawagoe, R Takikawa, Y Hikosaka, O AF Nakahara, H Itoh, H Kawagoe, R Takikawa, Y Hikosaka, O TI Dopamine neurons can represent context-dependent prediction error SO NEURON LA English DT Article ID SUPPLEMENTARY EYE FIELD; MONKEY CAUDATE-NUCLEUS; PREFRONTAL CORTEX; BASAL GANGLIA; ANTERIOR CINGULATE; REWARD EXPECTANCY; NEURAL CORRELATE; MOTOR AREA; RESPONSES; MOVEMENTS AB Midbrain dopamine (DA) neurons are thought to encode reward prediction error. Reward prediction can be improved if any relevant context is taken into account. We found that monkey DA neurons can encode a context-dependent prediction error. In the first noncontextual task, a light stimulus was randomly followed by reward, with a fixed equal probability. The response of DA neurons was positively correlated with the number of preceding unrewarded trials and could be simulated by a conventional temporal difference (TD) model. In the second contextual task, a reward-indicating light stimulus was presented with the probability that, while fixed overall, was incremented as a function of the number of preceding unrewarded trials. The DA neuronal response then was negatively correlated with this number. This history effect corresponded to the prediction error based on the conditional probability of reward and could be simulated only by implementing the relevant context into the TD model. C1 RIKEN, Brain Sci Inst, Lab Math Neurosci, Wako, Saitama 3510198, Japan. Tokyo Inst Technol, Interdisciplinary Grad Sch Sci & Engn, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 2268502, Japan. Juntendo Univ, Sch Med, Dept Physiol, Tokyo 1138421, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Nakahara, H (reprint author), RIKEN, Brain Sci Inst, Lab Math Neurosci, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM hiro@brain.riken.go.jp RI Nakahara, Hiroyuki/N-5411-2015; OI Nakahara, Hiroyuki/0000-0001-6891-1175; Itoh, Hideaki/0000-0001-8623-2408 NR 57 TC 148 Z9 149 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 22 PY 2004 VL 41 IS 2 BP 269 EP 280 DI 10.1016/S0896-6273(03)00869-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 821JZ UT WOS:000221457800012 PM 14741107 ER PT J AU Whiteside, MA Chen, DT Desmond, RA Abdulkadir, SA Johanning, GL AF Whiteside, MA Chen, DT Desmond, RA Abdulkadir, SA Johanning, GL TI A novel time-course cDNA microarray analysis method identifies genes associated with the development of cisplatin resistance SO ONCOGENE LA English DT Article DE lung cancer; drug resistance; gene expression profiling; mechanisms of drug action ID CANCER CELL-LINES; PLASMINOGEN-ACTIVATOR; EXPRESSION PROFILES; LUNG-CANCER; DNA-REPAIR; STROMELYSIN-3; CHEMOSENSITIVITY; RADIATION; BRCA1; OVEREXPRESSION AB In recent years, most cDNA microarray studies of chemotherapeutic drug resistance have not considered the temporal pattern of gene expression. The objective of this study was to examine systematically changes in gene expression of NCI-H226 and NCI-H2170 lung cancer cells treated weekly with IC10 doses of cisplatin. NCI-H226 lung cancer cells were treated weekly with an IC10 dose of cisplatin. Candidate genes with a fold change of 2.0 or more were identified from this study. A second experiment was conducted by exposing NCI-H2170 cells to cisplatin doses that were increased in week 4 and decreased in week 5. Overall, 44 genes were differentially expressed in both the NCI-H226 and NCI-H2170 cell lines. In the NCI-H2170 cell line, 24 genes had a twofold gene expression change from weeks 3 to 4. Real-time PCR found a significant correlation of the gene expression changes for seven genes of interest. This small time-ordered series identified novel genes associated with cisplatin resistance. This kind of analysis should be viewed as a first step towards building gene-regulatory networks. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Univ Alabama, Biostat & Bioinformat Unit, Birmingham, AL USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Johanning, GL (reprint author), Univ Alabama, Dept Nutr Sci, Rm 404 Webb Bldg,1675 Univ Blvd, Birmingham, AL 35294 USA. EM garyj@uab.edu NR 34 TC 25 Z9 28 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 JAN 22 PY 2004 VL 23 IS 3 BP 744 EP 752 DI 10.1038/sj.onc.1207164 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 765VK UT WOS:000188304900013 PM 14737109 ER PT J AU Zhao, H Dupont, J Yakar, S Karas, M LeRoith, D AF Zhao, H Dupont, J Yakar, S Karas, M LeRoith, D TI PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells SO ONCOGENE LA English DT Article DE PTEN; IGF-IR; prostate cancer; protein synthesis; apoptosis ID ADENOVIRAL-MEDIATED EXPRESSION; ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; INSULIN; RECEPTOR; ACTIVATION; PHOSPHORYLATION; DEGRADATION; METASTASIS; BREAST AB PTEN is a tumor suppressor gene that is frequently mutated in human tumors. It functions primarily as a lipid phosphatase and plays a key role in the regulation of phosphatidylinositol-3'-kinase. PTEN appears to play a crucial role in modulating apoptosis by reducing the levels of PtdIns(3,4,5) P3, a phospholipid that activates AKT, a central regulator of apoptosis. To understand the role of PTEN in regulating cell proliferation and apoptosis, we stably overexpressed PTEN in PC3 cells, which are prostate cancer cells that lack PTEN. Overexpression of PTEN in two different clones inhibited cell proliferation and increased serum starvation-induced apoptosis, as compared to control cells. Interestingly, PTEN overexpression resulted in a 44 - 60% reduction in total insulin-like growth factor-I receptor (IGF-IR) protein levels and a 49 - 64% reduction in cell surface IGF-IR expression. [S-35] methionine pulse experiments in PC3 cells overexpressing PTEN demonstrated that these cells synthesize significantly lower levels of the IGF-IR precursor, whereas PTEN overexpression had no effect on IGF-IR degradation. Taken together, our results show that PTEN can regulate cell proliferation and apoptosis through inhibition of IGF-IR synthesis. These results have important implications for understanding the roles of PTEN and the IGF-IR in prostate cancer cell tumorigenesis. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Diabet Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 37 TC 91 Z9 98 U1 1 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 JAN 22 PY 2004 VL 23 IS 3 BP 786 EP 794 DI 10.1038/sj.onc.1207162 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 765VK UT WOS:000188304900017 PM 14737113 ER PT J AU Hu, N Wang, CY Han, XY He, LJ Tang, ZZ Giffen, C Emmert-Buck, MR Goldstein, AM Taylor, PR AF Hu, N Wang, CY Han, XY He, LJ Tang, ZZ Giffen, C Emmert-Buck, MR Goldstein, AM Taylor, PR TI Evaluation of BRCA2 in the genetic susceptibility of familial esophageal cancer SO ONCOGENE LA English DT Article DE familial; mutation; LOH; high risk; DNA sequencing ID SQUAMOUS-CELL CARCINOMA; ALLELIC LOSS; SHANXI-PROVINCE; CHINA; BREAST; POPULATION; MUTATION AB Previous studies of esophageal squamous cell carcinoma (ESCC) have shown a high frequency of allelic loss on chromosome 13q, infrequent somatic mutations in BRCA2, and a suggested association between a positive family history (FH+) of upper gastrointestinal cancer and germline BRCA2 mutations. In all, 70 ESCC patients ( 44 FH+ and 26 FH-) were examined by direct full sequencing of germline DNA for BRCA2 mutations. In addition, 28 family members of three of these patients and 232 unrelated healthy blood bank donor controls were examined for the mutations identified in the 70 ESCC patients. Five BRCA2 germline mutations, including three not previously reported (N1600del, A2054P, and V2109I), were identified in six of 44 FH+ patients, but none of 26 FH- patients ( 14 vs 0%, P = 0.078), consistent with our previous findings (3/34 or 9% FH+ vs 0/22 or 0% FH-, P = 0.27). The cumulative frequency of BRCA2 germline mutations in ESCC patients in this and our previous study combined is 12%, with all mutations found in FH+ as opposed to FH- cases (9/78 or 12% FH+ vs 0/48 or 0% FH-, P = 0.013). We conclude that germline mutations in BRCA2 in ESCC patients from this high-risk area of China are more frequent in FH+ than FH- cases, suggesting that BRCA2 may play a role in genetic susceptibility to familial ESCC. C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China. Yangcheng Canc Hosp, Yangcheng 048100, Shanxi, Peoples R China. Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Taylor, PR (reprint author), NCI, Canc Prevent Studies Branch, 6116 Execut Plaza,Suite 705, Bethesda, MD 20892 USA. EM ptaylor@mail.nih.gov NR 22 TC 20 Z9 20 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 JAN 22 PY 2004 VL 23 IS 3 BP 852 EP 858 DI 10.1038/sj.onc.1207150 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 765VK UT WOS:000188304900025 PM 14647438 ER PT J AU Saydah, SH Fradkin, J Cowie, CC AF Saydah, SH Fradkin, J Cowie, CC TI Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; MICROVASCULAR COMPLICATIONS; EDUCATION-PROGRAM; GLYCEMIC CONTROL; UNITED-STATES; US ADULTS; PREVALENCE; CARE; HYPERTENSION AB Context Control of blood glucose levels, blood pressure, and cholesterol levels is proven to reduce the risk of vascular disease among individuals with diabetes mellitus; however, the current state of control of these risk factors among individuals in the United States is uncertain. Objectives To examine 1999-2000 national data on control of risk factors for vascular disease among adults with previously diagnosed diabetes and to assess trends during the past decade. Design, Setting,and Participants Review of data from the Third National Health and Nutrition Examination Survey (NHANES III, conducted 1988-1994) and NHANES 1999-2000, cross-sectional surveys of a nationally representative sample of the non-institutionalized civilian US population. Participants were adults aged 20 years and older with previously diagnosed diabetes who participated in both the interview and examination in either NHANES III (n=1265) or NHANES 1999-2000 (n=441). Main Outcome Measures Levels of glycosylated hemoglobin (HbA(1c)), blood pressure, and total serum cholesterol in reference to target goals. Results Compared with NHANES III, participants with previously diagnosed diabetes in NHANES 1999-2000 were similar by age and sex, were less likely to be non-Hispanic white, were diagnosed at,an earlier age, had a higher body mass index, and were more likely to use insulin in combination with oral agents. In NHANES 19992000, only 37.0% of participants achieved the target goal of HbA(1c) level less than 7.0% and 37.2% of participants were above the recommended "take action" HbA(1c) level of greater than 8.0%; these percentages did not change significantly from NHANES III (P=.11 and P=.87, respectively). Only 35.8% of participants achieved the target of systolic blood pressure (SBP) less than 130 mm Hg and diastolic blood pressure (DBP) less than 80 mm Hg, and 40.4% had hypertensive blood pressure levels (SBP 140 or DBP 90 mm Hg). These percentages did not change significantly from NHANES III (P=.10 and P=.56, respectively). Over half (51.8%) of the participants in NHANES 1999-2000 had total cholesterol levels of 200 mg/dL or greater (vs 66.1% in NHANES III; P<.001). In total, only 7.3% (95% confidence interval, 2.8%-11.9%) of adults with diabetes in NHANES 1999-2000 attained recommended goals of HbA(1c) level less than 7%, blood pressure less than 130/80 mm Hg, and total cholesterol level less than 200 mg/dL (5.18 mmol/L). Conclusion Further public health efforts are needed to control risk factors for vascular disease among individuals with diagnosed diabetes. C1 NIDDKD, Diabet Epidemiol Program, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Cowie, CC (reprint author), NIDDKD, Diabet Epidemiol Program, 6707 Democracy Blvd,Room 691,MSC 5460, Bethesda, MD 20892 USA. EM cowiec@extra.niddk.nih.gov FU NIDDK NIH HHS [N01-DK-1-2478] NR 52 TC 817 Z9 844 U1 1 U2 23 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 JAN 21 PY 2004 VL 291 IS 3 BP 335 EP 342 DI 10.1001/jama.291.3.335 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 764ZZ UT WOS:000188243100033 PM 14734596 ER PT J AU Vineis, P Alavanja, M Buffler, P Fontham, E Franceschi, S Gao, YT Gupta, PC Hackshaw, A Matos, E Samet, J Sitas, F Smith, J Stayner, L Straif, K Thun, MJ Wichmann, HE Wu, AH Zaridze, D Peto, R Doll, R AF Vineis, P Alavanja, M Buffler, P Fontham, E Franceschi, S Gao, YT Gupta, PC Hackshaw, A Matos, E Samet, J Sitas, F Smith, J Stayner, L Straif, K Thun, MJ Wichmann, HE Wu, AH Zaridze, D Peto, R Doll, R TI Tobacco and cancer: Recent epidemiological evidence SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID UNITED-STATES VETERANS; LOW-RISK POPULATION; LUNG-CANCER; CIGARETTE-SMOKING; PASSIVE SMOKING; HEPATOCELLULAR-CARCINOMA; NONSMOKING WOMEN; STOMACH-CANCER; DNA-ADDUCTS; FOLLOW-UP C1 Univ Turin, Canc Epidemiol Unit, I-10126 Turin, Italy. ISI Fdn, Turin, Italy. NCI, Div Canc Epidemiol, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Louisiana State Univ, Dept Publ Hlth & Prevent Med, New Orleans, LA 70112 USA. Int Agcy Res Canc, F-69372 Lyon, France. Shaghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. Tata Inst Fundamental Res, Bombay, Maharashtra, India. UCL, Canc Trials Ctr, London, England. Univ Buenos Aires, Inst Oncol, Buenos Aires, DF, Argentina. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. UIC, Sch Publ Hlth, Chicago, IL USA. Natl Hlth Lab Serv, Johannesburg, South Africa. Amer Canc Soc, Atlanta, GA 30329 USA. GSF, Inst Epidemiol, Neuherberg, Germany. Univ So Calif, Los Angeles, CA USA. Russian Acad Med Sci, Inst Carcinogenesis, Moscow, Russia. Univ Oxford, Clin Trial Serv Unit, Oxford, England. Univ Oxford, Epidemiol Studies Unit, Oxford, England. RP Vineis, P (reprint author), Univ Turin, Canc Epidemiol Unit, Via Santena 7, I-10126 Turin, Italy. EM paolo.vineis@unito.it OI Sitas, Freddy/0000-0001-9679-1481 NR 83 TC 355 Z9 371 U1 1 U2 23 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JAN 21 PY 2004 VL 96 IS 2 BP 99 EP 106 DI 10.1093/jnci/djh014 PG 8 WC Oncology SC Oncology GA 765EE UT WOS:000188253500007 PM 14734699 ER PT J AU Neumeister, A Bain, E Nugent, AC Carson, RE Bonne, O Luckenbaugh, DA Eckelman, W Herscovitch, P Charney, DS Drevets, WC AF Neumeister, A Bain, E Nugent, AC Carson, RE Bonne, O Luckenbaugh, DA Eckelman, W Herscovitch, P Charney, DS Drevets, WC TI Reduced serotonin type 1(A) receptor binding in panic disorder SO JOURNAL OF NEUROSCIENCE LA English DT Article DE anxiety; imaging; neuron; neurotransmitter; positron emission tomography; serotonin ID DEPRESSION; HIPPOCAMPUS; ANXIETY; SCALE AB Recent animal models suggest that disturbances in serotonin type-1A receptor (5-HT1AR) function may contribute to chronic anxiety, although it is not clear at all whether such models constitute relevant models for panic disorder (PD) in humans. The selective 5-HT1AR radioligand [18F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (FCWAY) permits in vivo assessment of central 5-HT1AR binding using positron emission tomography (PET). We studied 16 unmedicated symptomatic outpatients with PD and 15 matched healthy controls. Seven patients had an additional diagnosis of a current major depressive episode, however PD was the primary diagnosis. A 120 min PET study of 5-HT1AR binding was acquired using a GE Advance scanner in three-dimensional mode. Using quantitative PET image analysis, regional values were obtained for[18F]-FCWAY volume of distribution (DV), corrected for plasma protein binding, and K1, the delivery rate of [18F]-FCWAY from plasma to tissue. MRI scanning was performed using a GE Signa Scanner (3.0 Tesla) to provide an anatomical framework for image analysis and partial volume correction of PET data. PD patients showed lower DV in the anterior cingulate (t = 4.3; p < 0.001), posterior cingulate (t = 4.1; p < 0.001), and raphe (t = 3.1; p = 0.004). Comparing patients with PD, patients with PD and comorbid depression, and healthy controls revealed that DVs did not differ between PD patients and PD patients with comorbid depression, whereas both patient groups differed significantly from controls. These results provide for the first time in vivo evidence for the involvement of 5-HT(1A)Rs in the pathophysiology of PD. C1 NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIH, Sect Expt Therapeut, Bethesda, MD 20892 USA. NIH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Imaging Ctr, Bethesda, MD 20892 USA. RP Neumeister, A (reprint author), NIMH, NIH, Mood & Anxiety Disorders Program, North Dr,Bldg 15K,Room 200, Bethesda, MD 20892 USA. EM neumeisa@intra.nimh.nih.gov RI Carson, Richard/H-3250-2011; OI Carson, Richard/0000-0002-9338-7966; Nugent, Allison/0000-0003-2569-2480 NR 14 TC 240 Z9 246 U1 0 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 JAN 21 PY 2004 VL 24 IS 3 BP 589 EP 591 DI 10.1523/JNEUROSCI.4921-03.2004 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 765UK UT WOS:000188302000002 PM 14736842 ER PT J AU Marquez, VE Ben-Kasus, T Barchi, JJ Green, KM Nicklaus, MC Agbaria, R AF Marquez, VE Ben-Kasus, T Barchi, JJ Green, KM Nicklaus, MC Agbaria, R TI Experimental and structural evidence that herpes 1 kinase and cellular DNA polymerase(s) discriminate on the basis of sugar pucker SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SIMPLEX-VIRUS TYPE-1; ADENOSINE RECEPTOR AGONISTS; THYMIDINE KINASE; CARBOCYCLIC THYMIDINE; BICYCLO<3.1.0>HEXANE TEMPLATE; N-METHANOCARBATHYMIDINE; CONFORMATIONAL-ANALYSIS; BIOLOGICAL-ACTIVITY; CRYSTAL-STRUCTURE; NEPLANOCIN-C AB Two isomers of methanocarba. (MC) thymidine (T), one an effective antiherpes agent with the pseudosugar moiety locked in the North (N) hemisphere of the pseudorotational cycle (1a, N-MCT) and the other an inactive isomer locked in the antipodean South (S) conformation (1b, S-MCT) were used to determine whether kinases and polymerases discriminate between their substrates on the basis of sugar conformation. A combined solid-state and solution conformational analysis of both compounds, coupled with the direct measurement of mono-, di-, and triphosphate levels in control cells, cells infected with the Herpes simplexvirus, or cells transfected with the corresponding viral kinase gene (HSV-tk), suggests that kinases prefer substrates that adopt the S sugar conformation. On the other hand, the cellular DNA polymerase(s) of a murine tumor cell line transfected with HSV-tk incorporated almost exclusively the triphosphate of the locked N conformer (N-MCTTP), notwithstanding the presence of higher triphosphate levels of the S-conformer (S-MCTTP). C1 NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Canc Res Ctr, 376 Boyles St, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov RI Nicklaus, Marc/N-4183-2014; Barchi Jr., Joseph/N-3784-2014; OI Nicklaus, Marc/0000-0002-4775-7030 NR 32 TC 76 Z9 79 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 21 PY 2004 VL 126 IS 2 BP 543 EP 549 DI 10.1021/ja037929e PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 764FY UT WOS:000188197800046 PM 14719951 ER PT J AU Scuteri, A Manolio, TA Marino, EK Arnold, AM Lakatta, EG AF Scuteri, A Manolio, TA Marino, EK Arnold, AM Lakatta, EG TI Prevalence of specific variant carotid geometric patterns and incidence of cardiovascular events in older persons - The cardiovascular health study (CHS E-131) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; WALL THICKNESS; ARTERIAL; HYPERTENSION; DISEASE; ADULTS; ATHEROSCLEROSIS; RISK; HYPERTROPHY; PREDICTORS AB OBJECTIVES We hypothesized that variant geometric patterns of the common carotid artery (CCA) predict the incidence of cardiovascular disease (CVD), after accounting for CCA intima-medial thickness (IMT). BACKGROUND Common carotid artery intima-media thickness has been associated with the incidence of cardiovascular disease. METHODS Noninvasive measurements of IMT were made with high-resolution ultrasonography in 5,640 subjects 65 years of age or older participating in the Cardiovascular Health Study. New coronary and/or cerebrovascular events served as outcome variables over a median 10.2-year follow-up. To characterize different carotid structural geometric patterns (CGP), vascular mass (VM) was combined with the wall-to-lumen ratio (W/L). Normal values for W/L and VM were defined as age-adjusted, gender-specific 75th percentiles of the 1,899 normotensive subjects free of CVD at baseline. Four CGPs were defined: CGP1 = normal W/L ratio and VM; CGP2 = arterial remodeling (i.e., increased W/L ratio with normal VM); CGP3 = arterial hypertrophy (i.e., increased W/L ratio with increased VM); and CGP4 = arterial hypertrophy with dilation (i.e., normal W/L ratio and increased VM). RESULTS Coronary or cerebrovascular events (adjusted for age, gender, traditional risk factors, and IMT) were associated with CGP in subjects free of CVD at baseline. Specifically, the hazard ratio (Cox proportional-hazards analyses) for CGP3 (arterial hypertrophy) was 1.25 (95% confidence interval [Cl] 1.03 to 1.53), and for CGP4 (arterial hypertrophy with dilation) was 1.43 (95% Cl 1.16 to 1.75) compared with CGP1 (normal). CONCLUSIONS Arterial hypertrophy defined by variant CGP patterns is associated with the development of new CVD, independent of age, traditional risk factors, and CCA IMT. (C) 2004 by the American College of Cardiology Foundation. C1 NIA, Cardiovasc Res Lab, NIH, Baltimore, MD 21224 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Dept Biostat, Seattle, WA 98195 USA. RP Scuteri, A (reprint author), NIA, Cardiovasc Res Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM scuteria@grc.nia.nih.gov FU NHLBI NIH HHS [N01 HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85086] NR 25 TC 20 Z9 21 U1 0 U2 2 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 JAN 21 PY 2004 VL 43 IS 2 BP 187 EP 193 DI 10.1016/j.jacc.2003.08.035 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 765CD UT WOS:000188248800007 PM 14736436 ER PT J AU Leischow, SJ Djordjevic, MV AF Leischow, SJ Djordjevic, MV TI Smoking reduction and tobacco-related cancers: The more things change, the more they stay the same SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID NICOTINE C1 NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. RP Leischow, SJ (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. EM SL83P@nih.gov NR 16 TC 3 Z9 3 U1 0 U2 0 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 JAN 21 PY 2004 VL 96 IS 2 BP 86 EP 87 DI 10.1093/jnci/djh030 PG 2 WC Oncology SC Oncology GA 765EE UT WOS:000188253500001 PM 14734690 ER PT J AU Sidorov, IA Gee, D Dimitrov, DS AF Sidorov, IA Gee, D Dimitrov, DS TI A kinetic model of telomere shortening in infants and adults SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE telomere dynamics; aging; kinetic model ID PEPTIDE NUCLEIC-ACIDS; HUMAN FIBROBLASTS; T-LYMPHOCYTES; CELL TURNOVER; INHIBITION; LENGTH; HIV; IDENTIFICATION; DYNAMICS; AGE AB We have previously demonstrated that telomeres shorten more rapidly in peripheral mononuclear cells (PBMC) of infants than in adults (Zeichner et al., Blood 93 (1999) 2824). Here we describe a mathematical model that allows quantification of telomere dynamics both in infants and in adults. In this model the dependence of the telomere dynamics on age is accounted by assuming proportionality between the body growth, as approximated by the Gompertz equation, and the increase in the number of PBMCs. The model also assumes the existence of two subpopulations of PBMC with significantly different rates of division. This assumption is based on the results from a previous analysis of in vitro data for telomere dynamics in presence of telomerase inhibitors and our recent data obtained by measurements of BrdU incorporation in T lymphocytes in humans (Kovacs et al., J. Exp. Med. 194 (2001) 173 1). The average telomere length of PBMC was calculated as the average length of these two subpopulations. The model fitted our experimental data well and allowed to derive a characteristic time of conversion of the rapidly proliferating cells to slowly proliferating cells on the order of 20 days. The half-life of the slowly proliferating cells was estimated to be about 6 months, which is in good agreement with data obtained by independent methodologies. Comparison of the one-population and two-subpopulations models demonstrated that one population model cannot explain the observed parameters of the terminal restriction fragment (TRF) dynamics while two-subpopulations model does. These results suggest that the rapid telomere shortening in infants is largely determined by the faster PBMC turnover compared to adults. This may have major implications for elucidation of the HIV pathogenesis in infants. One can speculate that the more rapid course of the HIV disease in infants is due to the existence of rapidly dividing cells, which are susceptible to HIV infection. In addition, these results could have implications for understanding of mechanisms of aging. (C) 2003 Elsevier Ltd. All rights reserved. C1 NCI, NIH, Frederick, MD 21702 USA. RP Sidorov, IA (reprint author), NCI, NIH, Bldg 469,Rm 110,POB B, Frederick, MD 21702 USA. OI Sidorov, Igor/0000-0001-6519-4983 NR 27 TC 11 Z9 12 U1 1 U2 2 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 JAN 21 PY 2004 VL 226 IS 2 BP 169 EP 175 DI 10.1016/j.jtbi.2003.08.009 PG 7 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 752WK UT WOS:000187199000004 PM 14643186 ER PT J AU Sergeev, YV Hejtmancik, JF Wingfield, PT AF Sergeev, YV Hejtmancik, JF Wingfield, PT TI Energetics of domain-domain interactions and entropy driven association of beta-crystallins SO BIOCHEMISTRY LA English DT Article ID C-TERMINAL EXTENSIONS; MONOMER-DIMER EQUILIBRIUM; X-RAY-ANALYSIS; EYE-LENS; GAMMA-CRYSTALLIN; CATARACT; PROTEINS; CLEAVAGE; GENE; EVOLUTION AB beta-Crystallins are major protein constituents of the mammalian lens, where their stability and association into higher order complexes are critical for lens clarity and refraction. They undergo modification as the lens ages, including cleavage of their terminal extensions. The energetics of betaA3- and betaB2-crystallin association was studied using site-directed mutagenesis and analytical ultracentrifugation. Recombinant (r) murine wild type betaA3- and betaB2-crystallins were modified by removal of either the N-terminal extension of betaA3 (rbetaA3Ntr) or betaB32 (rbeta2Ntr), or both the N- and C-terminal extensions of betaB2 (rbetaB2NCtr). The proteins were expressed in Sf9 insect cells or Escherichia coli and purified by gel-filtration and ion-exchange chromatography. All beta-crystallins studied demonstrated fast reversible monomer-dimer equilibria over the temperature range studied (5-35 degreesC) with a tendency to form tighter dimers at higher temperatures. The N-terminal deletion of rbetaA3 (rbetaA3Ntr) significantly increases the enthalpy (+10.9 kcal/mol) and entropy (+40.7 cal/deg mol) of binding relative to unmodified protein. Removal of both N- and C-terminal extensions of rbetaB2 also increases these parameters but to a lesser degree. Deletion of the betaB2-crystallin N-terminal extension alone (rbetaB2Ntr) gave almost no change relative to rbetaB2. The resultant net negative changes in the binding energy suggest that betaA3- and betaB2-crystallin association is entropically driven. The thermodynamic consequences of the loss of betaA3-crystallin terminal extensions by in vivo proteolytic processing could increase their tendency to associate and so promote the formation of higher order associates in the aging and cataractous lens. C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP NEI, OGVFB, NIH, 10-10B 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sergeev@helix.nih.gov NR 59 TC 18 Z9 19 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 20 PY 2004 VL 43 IS 2 BP 415 EP 424 DI 10.1021/bi034617f PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763RH UT WOS:000188113900014 PM 14717595 ER PT J AU Keller, JE Cai, F Neale, EA AF Keller, JE Cai, F Neale, EA TI Uptake of botulinum neurotoxin into cultured neurons SO BIOCHEMISTRY LA English DT Article ID SYNAPTIC PROTEIN SNAP-25; E DERIVATIVE TOXIN; SPINAL-CORD CELLS; CLOSTRIDIAL NEUROTOXINS; NEUROMUSCULAR-JUNCTION; TYROSINE PHOSPHORYLATION; LIPID BILAYERS; ION CHANNELS; HEAVY-CHAIN; SEROTYPE-A AB Botulinum neurotoxins (BoNTs) act within the synaptic terminal to block neurotransmitter release. The toxin enters the neuron by binding to neuronal membrane receptor(s), being taken up into an endosome-like compartment, and penetrating the endosome membrane via a pH-dependent translocation process. Once within the synaptic cytoplasm, BoNT serotypes A and E cleave separate sites on the C-terminus of the neuronal protein SNAP-25, one of the SNARE proteins required for synaptic vesicle fusion. In this study, we measured the effect of brief toxin exposure on SNAP-25 proteolysis in neuronal cell cultures as an indicator of toxin translocation. The results indicate that (1) uptake of both BoNT-A and -E is enhanced with synaptic activity induced by K+ depolarization in the presence of Ca2+ and (2) translocation of BoNT-A from the acidic endosomal compartment is slow relative to that of BoNT-E. Polyclonal antisera against each toxin protect cells when applied with the toxin during stimulation but has no effect when added immediately after toxin exposure, indicating that toxin endocytosis occurs with synaptic activity. Both serotypes cleave SNAP-25 at concentrations between 50 pM and 4 nM. IC50 values for SNAP-25 cleavage are approximately 0.5 nM for both serotypes. Inhibition of the pH-dependent translocation process by pretreating cultures with concanamycin A (Con A) prevents cleavage of SNAP-25 with IC50 values of similar to25 nM. Addition of Con A at times up to 15 min after toxin exposure abrogated BoNT-A action; however, addition of Con A after 40 min was no longer protective. In contrast, Con A inhibited, but did not prevent, translocation of BoNT-E even when added immediately after toxin exposure, indicating that pH-dependent translocation of BoNT-E is rapid relative to that of BoNT-A. This study demonstrates that uptake of both BoNT-A and -E is enhanced with synaptic activity and that translocation of the toxin catalytic moiety into the cytosol occurs at different rates for these two serotypes. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. EM kellerj@cber.fda.gov NR 50 TC 101 Z9 106 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 20 PY 2004 VL 43 IS 2 BP 526 EP 532 DI 10.1021/bi0356698 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763RH UT WOS:000188113900027 PM 14717608 ER PT J AU Monsonego, J Bosch, FX Coursaget, P Cox, JT Franco, E Frazer, I Sankaranarayanan, R Schiller, J Singer, A Wright, T Kinney, W Meijer, C Linder, J AF Monsonego, J Bosch, FX Coursaget, P Cox, JT Franco, E Frazer, I Sankaranarayanan, R Schiller, J Singer, A Wright, T Kinney, W Meijer, C Linder, J TI Cervical cancer control, priorities and new directions SO INTERNATIONAL JOURNAL OF CANCER LA English DT Review DE cervical neoplasia; human papillomavirus; screening; colposcopy; HPV vaccine ID HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS INTRAEPITHELIAL LESIONS; UNDETERMINED SIGNIFICANCE; MANAGEMENT STRATEGIES; VISUAL INSPECTION; PARTICLE VACCINE; ADULT VOLUNTEERS; ACETIC-ACID; COSTA-RICA; WOMEN AB Cervical cancer is caused by infection with a range of high risk "oncogenic" human papillomavirus (HPV) types, and it is now accepted that >99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than I in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, Screening for persistent HPV infection is effective in reducing the incidence of cervical cancer. Infection can be detected by molecular techniques or by cytological examination of exfoliated cervical cells. Persistent infection is the single best predictor of risk of cervical cancer.(1) The latest findings of HPV and cervical cancer research need to be widely disseminated to the scientific and medical societies that are updating screening and management protocols, public health professionals, and to women and clinicians. This report reviews current evidence, clinical implications and directions for further research in the prevention, control and management of cervical cancer. We report the conclusions of the Experts' Meeting at the EUROGIN 2003 conference. (C) 2003 Wiley-Liss, Inc. C1 EUROGIN, F-75017 Paris, France. Catalan Inst Oncol, Epidemiol & Canc Registrat Unit, Barcelona, Spain. Fac Pharm, Lab Immunol Malad Infect, Tours, France. Univ Calif Santa Barbara, Hlth Serv, Santa Barbara, CA 93106 USA. McGill Univ, Div Canc Epidemiol, Montreal, PQ, Canada. Princess Alexandra Hosp, CICR, Woolloongabba, Qld 4102, Australia. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Whittington & Royal No Hosp, Dept Obstet & Gynaecol, London, England. Columbia Univ, Coll Phys & Surg, New York, NY USA. Permanente Med Grp Inc, Sacramento, CA USA. Vrije Univ Amsterdam, Acad Ziekenhuis, Amsterdam, Netherlands. Cytyc Corp, Boxboro, MA USA. RP Monsonego, J (reprint author), EUROGIN, 174 Rue Courcelles, F-75017 Paris, France. RI BOSCH JOSE, FRANCESC XAVIER/J-6339-2012; OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Frazer, Ian/0000-0002-8002-4680; Franco, Eduardo/0000-0002-4409-8084 NR 39 TC 64 Z9 68 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 20 PY 2004 VL 108 IS 3 BP 329 EP 333 DI 10.1002/ijc.11530 PG 5 WC Oncology SC Oncology GA 754BK UT WOS:000187282700001 PM 14648697 ER PT J AU Mukhopadhyay, P Zheng, M Bedzyk, LA LaRossa, RA Storz, G AF Mukhopadhyay, P Zheng, M Bedzyk, LA LaRossa, RA Storz, G TI Prominent roles of the NorR and Fur regulators in the Escherichia coli transcriptional response to reactive nitrogen species SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NITRIC-OXIDE REDUCTION; NITROSATIVE STRESS; GENE-EXPRESSION; SALMONELLA-TYPHIMURIUM; FLAVOHEMOGLOBIN GENE; OXIDATIVE-STRESS; OXYR; ACTIVATION; K-12; IRON AB We examined the genomewide transcriptional responses of Escherichia coli treated with nitrosylated glutathione or the nitric oxide (NO)-generator acidified sodium nitrite (NaNO2) during aerobic growth. These assays showed that NorR, a homolog of NO-responsive transcription factors in Ralstonia eutrophus, and Fur, the global repressor of ferric ion uptake, are major regulators of the response to reactive nitrogen species. In contrast, SoxR and OxyR, regulators of the E. coli defenses against superoxide-generating compounds and hydrogen peroxide, respectively, have minor roles. Moreover, additional regulators of the E. coli response to reactive nitrogen species remain to be identified because several of the induced genes were regulated normally in norR, fur, soxRS, and oxyR mutant strains. We propose that the E. coli transcriptional response to reactive nitrogen species is a composite response mediated by the modification of multiple transcription factors containing iron or redox-active cysteines, some specifically designed to sense NO and its derivatives and others that are collaterally activated by the reactive nitrogen species. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. DuPont Co Inc, Cent Res & Dev, Wilmington, DE 19880 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM storz@helix.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Storz, Gisela/0000-0001-6698-1241 NR 51 TC 154 Z9 155 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 20 PY 2004 VL 101 IS 3 BP 745 EP 750 DI 10.1073/pnas.0307741100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768VH UT WOS:000188555400012 PM 14718666 ER PT J AU Lee, MK Nikoderm, VM AF Lee, MK Nikoderm, VM TI Differential role of ERK in cAMP-induced Nurr1 expression in N2A and C6 cells SO NEUROREPORT LA English DT Article DE CREB; forskolin; glioma; H89; MAPK; neuroblastoma; PD98059 ID ELEMENT-BINDING PROTEIN; ORPHAN RECEPTOR NURR1; TRANSCRIPTION FACTOR; KINASE-A; NEURONS; MICE; GENE; ACTIVATION; SIGNALS; CALCIUM AB We investigated the signal pathway related to induction of Nurr1, transcription factor, by cAMP in neuroblastoma N2A and C6 glioma cell lines. Nurr1 expression was induced by forskolin, an adenylate cyclase activator, via activation of CREB in both N2A and C6 cells. The effect of forskolin on ERK, however, was cell specific. ERK phosphorylation was stimulated by forskolin in N2A cells whereas it was inhibited in C6 cells. Pretreatment with H89, a PKA inhibitor, blocked the forskolin-induced Nurr1 expression in both N2A and C6 cells. Interestingly, pretreatment with PD98059, an MEK inhibitor, showed differential effects. Pretreatment with PD98059 inhibited the forskolin-induced Nurr1 expression in N2A cells, however, in C6 cells, Nurr1 expression was further increased. Our results suggest that ERK pathway plays a differential role in cAMP-induced Nurr1 expression in N2A and C6 cells. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Nikoderm, VM (reprint author), NIDDKD, NIH, Bldg 10,Rm 9D06,9000 Rockville Pike, Bethesda, MD 20892 USA. EM VeraN@intra.niddk.nih.gov NR 20 TC 17 Z9 17 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 19 PY 2004 VL 15 IS 1 BP 99 EP 102 DI 10.1097/01.wnr.0000102265.71579.b7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 871NG UT WOS:000225139800020 PM 15106839 ER PT J AU Williams, JL Kashfi, K Ouyang, N del Soldato, P Kopelovich, L Rigas, B AF Williams, JL Kashfi, K Ouyang, N del Soldato, P Kopelovich, L Rigas, B TI NO-donating aspirin inhibits intestinal carcinogenesis in Min (APC(MInl)) mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE nitric oxide-releasing aspirin; aspirin; nitric oxide; colon cancer; chemoprevention; proliferation; Min mice ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER CHEMOPREVENTION; COLORECTAL-CANCER; NSAIDS; CELLS; GROWTH AB The chemopreventive effect of nitric oxide-releasing aspirin (NO-ASA) against gastrointestinal tumorigenesis was evaluated in Min (APC(Min/+)) mice. NO-ASA consists of a traditional ASA that bears covalently attached to it an NO-releasing moiety. Four groups (N = 10) of six-week-old female C57BL/6J APC(Min/+) and the corresponding C57BL/6J(+/+) wild type mice were treated either with vehicle or NO-ASA 100 mg/kg/day intrarectally for 21 days. There were no signs of overt toxicity including gastrointestinal toxicity from NO-ASA. Vehicle treated Min mice had 24.7 +/- 3.8 tumors (mean +/- SEM) and NO-ASA treated Min mice had 10.1 +/- 1.4 tumors (59% reduction; P < 0.001). Wild type mice showed no tumors. NO-ASA did not affect cell proliferation in small intestinal mucosa, determined by immunohistochemical staining for PCNA. Our findings establish the strong inhibitory effect of NO-ASA in intestinal carcinogenesis in the Min mouse and suggest that this agent merits further evaluation as a chemopreventive agent against colon cancer. (C) 2003 Elsevier Inc. All rights reserved. C1 Amer Hlth Fdn, Ctr Canc, Inst Canc Prevent, Valhalla, NY USA. CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10031 USA. New York Med Coll, Valhalla, NY 10595 USA. NCI, Chemoprevent Branch, NIH, Bethesda, MD 20892 USA. RP Rigas, B (reprint author), Amer Hlth Fdn, Ctr Canc, Inst Canc Prevent, Valhalla, NY USA. EM brigas@ifcp.us FU NCI NIH HHS [CA92423] NR 16 TC 69 Z9 72 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 JAN 16 PY 2004 VL 313 IS 3 BP 784 EP 788 DI 10.1016/j.bbrc.2003.12.015 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 761HA UT WOS:000187894400051 PM 14697260 ER PT J AU Krajcikova, D Hartley, RW AF Krajcikova, D Hartley, RW TI A new member of the bacterial ribonuclease inhibitor family from Saccharopolyspora erythraea SO FEBS LETTERS LA English DT Article DE barstar; barnase; ribonuclease; ribonuclease inhibitor; phage display; mRNA secondary structure ID RNA SECONDARY STRUCTURE; ESCHERICHIA-COLI; BARSTAR; EXPRESSION; GENE; STREPTOMYCES; PROTEINS; TRANSLATION; BARNASE; CLONING AB We have identified Sti, the gene of a ribonuclease inhibitor from Saccharopolyspora erythraea, by using a T7 phage display system. A specific phage has been isolated from a genome library by a biopanning procedure, using RNase SO, a ribonuclease from Streptomyces aureofaciens, as bait. Sti, a protein of 121 amino acid residues, with molecular mass 13059 Da, is a homolog of barstar and other microbial ribonuclease inhibitors. To overexpress its gene in Escherichia coli, we optimized the secondary structure of its mRNA by introducing a series of silent mutations. Soluble protein was isolated and purified to homogeneity. Inhibition constants of complex of Sti and RNase Sa3 or barnase were determined at pH 7 as 5 X 10(-12) or 7 X 10(-7), respectively. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hartley, RW (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM hartleyr@helix.nih.gov OI Krajcikova, Daniela/0000-0002-4024-2384 NR 25 TC 3 Z9 4 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 JAN 16 PY 2004 VL 557 IS 1-3 BP 164 EP 168 DI 10.1016/S0014-5793(03)01468-6 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 769JZ UT WOS:000188648100030 PM 14741361 ER PT J AU Quinto, I Puca, A Greenhouse, J Silvera, P Yalley-Ogunro, J Lewis, MG Palmieri, C Trimboli, F Byrum, R Adelsberger, J Venzon, D Chen, XN Scala, G AF Quinto, I Puca, A Greenhouse, J Silvera, P Yalley-Ogunro, J Lewis, MG Palmieri, C Trimboli, F Byrum, R Adelsberger, J Venzon, D Chen, XN Scala, G TI High attenuation and immunogenicity of a simian immunodeficiency virus expressing a proteolysis-resistant inhibitor of NF-kappa B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; LONG TERMINAL REPEAT; RHESUS MACAQUES; IN-VITRO; NEF GENE; LIVE; REPLICATION; TAT; PROTECTION; CHALLENGE AB NF-kappaB/IkappaB proteins play a major role in the transcriptional regulation of human immunodeficiency virus, type-1 (HIV-1). In the case of simian immunodeficiency virus (SIV) the cellular factors required for the viral transcriptional activation and replication in vivo remain undefined. Here, we demonstrate that the p50/p65 NF-kappaB transcription factors enhanced the Tat-mediated transcriptional activation of SIVmac239. In addition, IkappaB-alphaS32/36A, a proteolysis-resistant inhibitor of NF-kappaB, strongly inhibited the Tat-mediated transactivation of SIVmac239. Based on this evidence, we have generated a self-regulatory virus by endowing the genome of SIVmac239 with IkappaB-alphaS32/36A; the resulting virus, SIVIkappaBalphaS32/36A, was nef-deleted and expressed the NF-kappaB inhibitor. We show that SIVIkappaB-alphaS32/36A was highly and stably attenuated both in cell cultures and in vivo in rhesus macaque as compared with a nef-deleted control virus. Moreover, the high attenuation was associated with a robust immune response as measured by SIV-specific antibody production, tetramer, and intracellular IFN-gamma staining of SIV gag-specific T cells. These results underscore the crucial role of NF-kappaB/IkappaB proteins in the regulation of SIV replication both in cell cultures and in monkeys. Thus, inhibitors of NF-kappaB could efficiently counteract the SIV/HIV replication in vivo and may assist in developing novel approaches for AIDS vaccine and therapy. C1 Univ Catanzaro, Sch Med, Dept Clin & Expt Med, I-88100 Catanzaro, Italy. Univ Naples Federico II, Sch Med, Dept Biochem & Biomed Technol, I-80131 Naples, Italy. So Res Inst, Frederick, MD 21701 USA. Bioqual, Rockville, MD 20850 USA. NCI, Sci Applicat Int Corp, Frederick Inc, Frederick, MD 21702 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Quinto, I (reprint author), Univ Catanzaro, Sch Med, Dept Clin & Expt Med, I-88100 Catanzaro, Italy. EM quinto@dbbm.unina.it RI Venzon, David/B-3078-2008; Palmieri, Camillo/A-3195-2009; SCALA, GIUSEPPE/A-3280-2009 OI Palmieri, Camillo/0000-0001-6707-4723; NR 38 TC 5 Z9 5 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 JAN 16 PY 2004 VL 279 IS 3 BP 1720 EP 1728 DI 10.1074/jbc.M309375200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 762WT UT WOS:000188005700021 PM 14593121 ER PT J AU Wolfe, MD Ahmed, F Lacourciere, GM Lauhon, CT Stadtman, TC Larson, TJ AF Wolfe, MD Ahmed, F Lacourciere, GM Lauhon, CT Stadtman, TC Larson, TJ TI Functional diversity of the rhodanese homology domain - The Escherichia coli ybbB gene encodes a selenophosphate-dependent tRNA 2-selenouridine synthase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 4-THIOURIDINE BIOSYNTHESIS; PERSULFIDE INTERMEDIATE; SALMONELLA-TYPHIMURIUM; CRYSTAL-STRUCTURE; 1ST POSITION; IN-VIVO; SELENIUM; SYNTHETASE; ENZYME; ISCS AB Escherichia coli has eight genes predicted to encode sulfurtransferases having the active site consensus sequence Cys-Xaa-Xaa-Gly. One of these genes, ybbB, is frequently found within bacterial operons that contain selD, the selenophosphate synthetase gene, suggesting a role in selenium metabolism. We show that ybbB is required in vivo for the specific substitution of selenium for sulfur in 2-thiouridine residues in E. coli tRNA. This modified tRNA nucleoside, 5-methylaminomethyl-2-selenouridine (mnm(5)se(2)U), is located at the wobble position of the anticodons of tRNALys, tRNAGlu, and tRNA(1)(Gln). Nucleoside analysis of tRNAs from wild-type and ybbB mutant strains revealed that production of mnm(5)se(2)U is lost in the ybbB mutant but that 5-methylaminomethyl-2- thiouridine, the mnm(5)se(2)U precursor, is unaffected by deletion of ybbB. Thus, ybbB is not required for the initial sulfurtransferase reaction but rather encodes a 2-selenouridine synthase that replaces a sulfur atom in 2-thiouridine in tRNA with selenium. Purified 2-selenouridine synthase containing a C-terminal His(6) tag exhibited spectral properties consistent with tRNA bound to the enzyme. In vitro mnm(5)se(2)U synthesis is shown to be dependent on 2-selenouridine synthase, SePO3, and tRNA. Finally, we demonstrate that the conserved Cys(97) ( but not Cys(96)) in the rhodanese sequence motif Cys(96)-Cys(97)-Xaa-Xaa-Gly is required for 2-selenouridine synthase in vivo activity. These data are consistent with the ybbB gene encoding a tRNA 2-selenouridine synthase and identifies a new role for the rhodanese homology domain in enzymes. C1 Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. RP Larson, TJ (reprint author), Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA. EM tilarson@vt.edu NR 51 TC 54 Z9 57 U1 1 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 JAN 16 PY 2004 VL 279 IS 3 BP 1801 EP 1809 DI 10.1074/jbc.M310442200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 762WT UT WOS:000188005700030 PM 14594807 ER PT J AU Aerbajinai, W Lee, YT Wojda, U Barr, VA Miller, JL AF Aerbajinai, W Lee, YT Wojda, U Barr, VA Miller, JL TI Cloning and characterization of a gene expressed during terminal differentiation that encodes a novel inhibitor of growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELLS; ERYTHROPOIESIS; DOMAIN; APOPTOSIS; PROTEINS; TISSUES AB We report here the cloning and initial characterization of a novel growth-related gene (EEG-1) that is located on the short arm of chromosome 12. Two spliced transcripts were cloned from human bone marrow and human erythroid progenitor cells: EEG-1L containing a 4350-nucleotide open reading frame encoding a putative protein of 1077 amino acids including a C1q-like globular domain, and an alternatively spliced transcript lacking exon 5 (EEG-1S) encodes a significantly smaller coding region and no C1q-like domain. Quantitative PCR revealed expression of both EEG-1 transcripts in all analyzed tissues. Plasmids encoding green fluorescent protein-tagged genes (GFP-EEG-1) were transfected into Chinese hamster ovary cells for localization and functional assays. In contrast to the diffuse cellular localization of the GFP control, GFP-EEG-1L was detected throughout the cytoplasm and excluded from the nucleus, and GFP-EEG-1S co-localized with aggregated mitochondria. Transfection of both isoforms was associated with significantly increased levels of apoptosis. Stable transfection assays additionally demonstrated decreased growth in those cells expressing EEG-1 at higher levels. Quantitative PCR analyses of mRNA obtained from differentiating erythroid cells from blood donors were performed to determine the transcriptional pattern of EEG-1 during erythropoiesis. EEG-1 expression was highly regulated with increased expression at the stage of differentiation associated with the onset of global nuclear condensation and reduced cell proliferation. We propose that the regulated expression of EEG-1 is involved in the orchestrated regulation of growth that occurs as erythroblasts shift from a highly proliferative state toward their terminal phase of differentiation. C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDK, Biol Chem Lab, NIH, Bldg 10,Rm 9B17, Bethesda, MD 20892 USA. EM jm7f@nih.gov RI Wojda, Urszula/M-6079-2015 OI Wojda, Urszula/0000-0002-4525-2004 NR 22 TC 26 Z9 27 U1 2 U2 4 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 JAN 16 PY 2004 VL 279 IS 3 BP 1916 EP 1921 DI 10.1074/jbc.M305634200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 762WT UT WOS:000188005700045 PM 14593112 ER PT J AU Kilav, R Bell, O Le, SY Silver, J Naveh-Many, T AF Kilav, R Bell, O Le, SY Silver, J Naveh-Many, T TI The parathyroid hormone mRNA 3 '-untranslated region AU-rich element is an unstructured functional element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SECONDARY STRUCTURES; TERMINATION SIGNAL; GENE-EXPRESSION; PROTEIN; BINDING; STABILITY; PHOSPHATE; SEQUENCE; CALCIUM; DEGRADATION AB Parathyroid hormone (PTH) gene expression is regulated post-transcriptionally by hypocalcemia and hypophosphatemia. This regulation is dependent upon binding of protective trans-acting factors to a specific element in the PTH mRNA 3'-untranslated region (UTR). We have previously demonstrated that a 63-nucleotide (nt) AU-rich PTH mRNA element is sufficient to confer regulation of RNA stability by calcium and phosphate in an in vitro degradation assay (IVDA). The 63-nt element consists of a core 26-nt minimal binding sequence and flanking regions. We have now studied the functionality of this element in HEK293 cells using reporter genes and showed that it destabilizes mRNAs for green fluorescent protein (GFP) and growth hormone, similar to its effect in the IVDA. To understand how the cis-element functions as an instability element, we have analyzed its structure by RNase H, primer extension, and computer modeling. The results indicate that the PTH mRNA 3'-UTR and in particular the region of the cis-element are dominated by significant open regions with little folded base pairing. Mutation analysis of the 26-nt core element demonstrated the importance of defined nucleotides for protein-RNA binding. In the GFP reporter system, the same mutations that prevented binding were also ineffective in destabilizing GFP mRNA in HEK293 cells. This is the first study of an AU-rich element that relates function to structure. The PTH mRNA 3'-UTR cis-acting element is an open region that utilizes the distinct sequence pattern to determine mRNA stability by its interaction with trans-acting factors. C1 Hebrew Univ Jerusalem, Sch Med, Hadassah Hosp, Minerva Ctr Calcium & Bone Metab,Nephrol Serv, IL-91120 Jerusalem, Israel. NCI, Lab Expt & Computat Biol, Frederick Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Naveh-Many, T (reprint author), Hebrew Univ Jerusalem, Sch Med, Hadassah Hosp, Minerva Ctr Calcium & Bone Metab,Nephrol Serv, POB 12000, IL-91120 Jerusalem, Israel. EM tally@huji.ac.il NR 27 TC 20 Z9 20 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 JAN 16 PY 2004 VL 279 IS 3 BP 2109 EP 2116 DI 10.1074/jbc.M305302200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 762WT UT WOS:000188005700067 PM 14585848 ER PT J AU Ma, XF Tu, PF Chen, YJ Zhang, TY Wei, Y Ito, YC AF Ma, XF Tu, PF Chen, YJ Zhang, TY Wei, Y Ito, YC TI Preparative isolation and purification of isoflavan and pterocarpan glycosides from Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; preparative chromatography; Astragalus membranaceus; plant materials; pharmaceutical analysis; isoflavan; pterocarpan; glycosides ID SEPARATION; FLAVONOIDS AB (3R)-(-)-7.2'-Dihydroxy-3',4'-dimethyl isoflavan-7-O-beta-D-glucopyranoside and (6aR, 11aR) 9,10-di-methoxypterocarpan-3-O-beta-D-glucopyranoside, were separated from the ethyl acetate extract of the root of Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao by high-speed counter-current chromatography (HSCCC). A two-phase system composed of ethyl acetate-ethanol-acetic acid-water (4:1:0.25:5, v/v) was selected by analytical HSCCC. Preparative HSCCC yielded, from 100 mg of the partially purified extract, 50 mg of isoflavan glycoside and 10 mg of pterocarpan glycoside each at over 95% purity by high-performance liquid chromatography (HPLC) analysis. Their structures were identified by MS, H-1 NMR and C-13 NMR. (C) 2003 Elsevier B.V. All rights reserved. C1 Acad Sinica, Grad Sch, Dept Biol, Beijing 100039, Peoples R China. Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tu, PF (reprint author), Acad Sinica, Grad Sch, Dept Biol, POB 3908, Beijing 100039, Peoples R China. EM itoy@nhlbi.nih.gov NR 14 TC 29 Z9 36 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 16 PY 2004 VL 1023 IS 2 BP 311 EP 315 DI 10.1016/j.chroma.2003.10.014 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 759CE UT WOS:000187720100017 PM 14753698 ER PT J AU Kanno, T Kanno, Y Siegel, RM Jang, MK Lenardo, MJ Ozato, K AF Kanno, T Kanno, Y Siegel, RM Jang, MK Lenardo, MJ Ozato, K TI Selective recognition of acetylated histones by bromodomain proteins visualized in living cells SO MOLECULAR CELL LA English DT Article ID MITOTIC CHROMOSOMES; STRUCTURAL BASIS; RAPID EXCHANGE; CHROMATIN; ACETYLTRANSFERASES; H3; H4; MITOSIS; ASSOCIATION; INHIBITION AB Acetylation and other modifications on histories comprise histone codes that govern transcriptional regulatory processes in chromatin. Yet little is known how different histone codes are translated and put into action. Using fluorescence resonance energy transfer, we show that bromodomain-containing proteins recognize different patterns of acetylated histories in intact nuclei of living cells. The bromodomain protein Brd2 selectively interacted with acetylated lysine 12 on histone H4, whereas TAF(II)250 and PCAF recognized H3 and other acetylated histones, indicating fine specificity of histone recognition by different bromodo-mains. This hierarchy of interactions was also seen in direct peptide binding assays. Interaction with acetylated histone was essential for Brd2 to amplify transcription. Moreover association of Brd2, but not other bromodomain proteins, with acetylated chromatin persisted on chromosomes during mitosis. Thus the recognition of histone acetylation code by bromodo-mains is selective, is involved in transcription, and potentially conveys transcriptional memory across cell divisions. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Tohoku Univ, Sch Med, Dept Microbiol & Immunol, Sendai, Miyagi 9808575, Japan. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. EM ozatok@nih.gov RI Siegel, Richard/C-7592-2009; Kanno, Yuka/B-5802-2013; OI Siegel, Richard/0000-0001-5953-9893; Kanno, Yuka/0000-0001-5668-9319 NR 41 TC 196 Z9 200 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 16 PY 2004 VL 13 IS 1 BP 33 EP 43 DI 10.1016/S1097-2765(03)00482-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 802MU UT WOS:000220168400006 PM 14731392 ER PT J AU Dave, UP Jenkins, NA Copeland, NG AF Dave, UP Jenkins, NA Copeland, NG TI Gene therapy insertional mutagenesis insights SO SCIENCE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; LEUKEMIA C1 NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. NR 7 TC 173 Z9 182 U1 1 U2 3 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 JAN 16 PY 2004 VL 303 IS 5656 BP 333 EP 333 DI 10.1126/science.1091667 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763QK UT WOS:000188111800032 PM 14726584 ER PT J AU Mizuguchi, G Shen, XT Landry, J Wu, WH Sen, S Wu, C AF Mizuguchi, G Shen, XT Landry, J Wu, WH Sen, S Wu, C TI ATP-Driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex SO SCIENCE LA English DT Article ID ACTIN-RELATED PROTEINS; NUCLEOSOME CORE PARTICLE; SACCHAROMYCES-CEREVISIAE; NUCLEAR ACTIN; DNA TRANSLOCATION; TRANSCRIPTION; CHROMOSOME; PROMOTER; RSC AB The conserved histone variant H2AZ has an important role in the regulation of gene expression and the establishment of a buffer to the spread of silent heterochromatin. How histone variants such as H2AZ are incorporated into nucleosomes has been obscure. We have found that Swr1, a Swi2/Snf2-related adenosine triphosphatase, is the catalytic core of a multisubunit, histone-variant exchanger that efficiently replaces conventional histone H2A with histone H2AZ in nucleosome arrays. Swr1 is required for the deposition of histone H2AZ at specific chromosome locations in vivo, and Swr1 and H2AZ commonly regulate a subset of yeast genes. These findings de. ne a previously unknown role for the adenosine triphosphate - dependent chromatin remodeling machinery. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Room 6068, Bethesda, MD 20892 USA. RI Sen, Subhojit/I-9033-2012 OI Sen, Subhojit/0000-0001-8457-915X NR 39 TC 710 Z9 743 U1 1 U2 29 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 JAN 16 PY 2004 VL 303 IS 5656 BP 343 EP 348 DI 10.1126/science.1090701 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763QK UT WOS:000188111800035 PM 14645854 ER PT J AU Bhargava, R Levin, IW AF Bhargava, R Levin, IW TI Probing structure and dynamics in liquid crystalline microdomains by infrared spectroscopy SO VIBRATIONAL SPECTROSCOPY LA English DT Article DE microdomains; probing structure; dynamics ID INDUCED PHASE-SEPARATION; FT-IR; POLYMERIC SYSTEMS; REFRACTIVE-INDEX; MIXTURES; DIAGRAMS; MORPHOLOGY; BEHAVIOR; DROPLETS; BLENDS AB While infrared spectroscopy is employed generally to characterize various physical phenomena, spectroscopic applications to macromolecular-liquid crystal (LC) composites have been limited to obtaining LC phase transitions and orientation information. We employ both Fourier transform infrared (FTIR) spectroscopy and FTIR spectroscopic imaging to delineate quantitatively the formation, microstructure and molecular dynamics within a flexible polymer-LC composite. Specifically, phase diagrams, molecular orientational and conformational order and transient molecular reorganizations of the LC upon application of an electric field are determined. The flexible and electrically unresponsive macromolecular component is found to be a dynamic entity during the nematic phase organization and reorientation processes demonstrating the necessity of including polymer segmental contributions to both phase separation and LC dynamics studies. Published by Elsevier B.V. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bhargava, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. OI Bhargava, Rohit/0000-0001-7360-994X NR 40 TC 6 Z9 7 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-2031 J9 VIB SPECTROSC JI Vib. Spectrosc. PD JAN 16 PY 2004 VL 34 IS 1 BP 13 EP 24 DI 10.1016/j.vibspec.2003.09.010 PG 12 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 765TJ UT WOS:000188299400003 ER PT J AU Rame, JE Ramilo, M Spencer, N Blewett, C Mehta, SK Dries, DL Drazner, MH AF Rame, JE Ramilo, M Spencer, N Blewett, C Mehta, SK Dries, DL Drazner, MH TI Development of a depressed left ventricular ejection fraction in patients with left ventricular hypertrophy and a normal election fraction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PRESSURE-OVERLOAD HYPERTROPHY; CONGESTIVE-HEART-FAILURE; NATURAL-HISTORY; HYPERTENSION; DYSFUNCTION; PATHOGENESIS; PROGRESSION AB The progression from concentric left ventricular (LV) hypertrophy to heart failure has not been well defined. Of 159 predominantly hypertensive African-American patients with LV hypertrophy and a normal ejection fraction (EF), 28 (18%) developed a reduced EF after a median follow-up of approximately 4 years. Risk factors for this outcome included a history of coronary artery disease, pulmonary edema seen on a chest x-ray, or a subsequent myocardial infarction. (C) 2004 by Excerpta Medica, Inc. C1 Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Heart Failure Res Unit, Div Cardiol,Donald W Reynolds Cardiovasc Clin Res, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75230 USA. RP Drazner, MH (reprint author), Univ Texas, SW Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Mark.Drazner@utsouthwestern.edu NR 15 TC 46 Z9 51 U1 0 U2 0 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 JAN 15 PY 2004 VL 93 IS 2 BP 234 EP 237 DI 10.1016/j.amjcard.2003.09.050 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 764MR UT WOS:000188211100024 PM 14715358 ER PT J AU Baird, DD AF Baird, DD TI Invited commentary: Uterine leiomyomata - We know so little but could learn so much SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID REPRODUCTIVE FACTORS; RISK-FACTORS; PREMENOPAUSAL WOMEN; UNITED-STATES; BIRTH-WEIGHT; FIBROIDS; AGE; MENARCHE; HYSTERECTOMY; SAMPLE C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,111 TW Alexander Dr,Bldg 101,Room, Res Triangle Pk, NC 27709 USA. EM baird@niehs.nih.gov OI Baird, Donna/0000-0002-5544-2653 NR 30 TC 20 Z9 20 U1 0 U2 3 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 JAN 15 PY 2004 VL 159 IS 2 BP 124 EP 126 DI 10.1093/aje/kwh017 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 764DY UT WOS:000188189100003 PM 14718212 ER PT J AU Zhang, YW Holford, TR Leaderer, B Boyle, P Zahm, SH Flynn, S Tallini, G Owens, PH Zheng, TZ AF Zhang, YW Holford, TR Leaderer, B Boyle, P Zahm, SH Flynn, S Tallini, G Owens, PH Zheng, TZ TI Hair-coloring product use and risk of non-Hodgkin's lymphoma: A population-based case-control study in Connecticut SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; Connecticut; hair dyes; lymphoma, non-Hodgkin; risk factors; women ID DYE USE; BREAST-CANCER; MULTIPLE-MYELOMA; LEUKEMIA AB A population-based case-control study was conducted in Connecticut in 1996-2002 to test the hypothesis that lifetime hair-coloring product use increases non-Hodgkin's lymphoma risk. A total of 601 histologically confirmed incident female cases and 717 population-based controls were included in the study. An increased risk of non-Hodgkin's lymphoma was observed among women who reported use of hair-coloring products before 1980 (odds ratio = 1.3, 95% confidence interval (CI): 1.0, 1.8). The odds ratios were 2.1 (95% CI: 1.0, 4.0) for those using darker permanent hair-coloring products for more than 25 years and 1.7 (95% CI: 1.0, 2.8) for those who had more than 200 applications. Follicular type, B-cell, and low-grade lymphoma generally showed an increased risk. On the other hand, the authors found no increased risk of non-Hodgkin's lymphoma overall and by subtype of exposure and disease among women who started using hair-coloring products in 1980 or later. It is currently unknown why an increased risk of non-Hodgkin's lymphoma was found only among women who started using hair-coloring products before 1980. Further studies are warranted to show whether the observed association reflects the change in hair dye formula contents during the past two decades or indicates that recent users are still in their induction and latent periods. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Europe Inst Oncol, Dept Epidemiol & Biostat, Milan, Italy. Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT USA. RP Zheng, TZ (reprint author), 129 Church St,Suite 700, New Haven, CT 06510 USA. EM tongzhang.zheng@yale.edu RI Boyle, Peter/A-4380-2014; Zahm, Shelia/B-5025-2015; OI Boyle, Peter/0000-0001-6251-0610; Tallini, Giovanni/0000-0003-0113-6682 FU NCI NIH HHS [CA62006] NR 24 TC 71 Z9 73 U1 0 U2 6 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 JAN 15 PY 2004 VL 159 IS 2 BP 148 EP 154 DI 10.1093/aje/kwh033 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 764DY UT WOS:000188189100007 PM 14718216 ER PT J AU Lambe, M Bjornadal, L Neregard, P Nyren, O Cooper, GS AF Lambe, M Bjornadal, L Neregard, P Nyren, O Cooper, GS TI Childbearing and the risk of scleroderma: A population-based study in Sweden SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE maternal-fetal exchange; parity; pregnancy; scleroderma, systemic ID SYSTEMIC-SCLEROSIS; AUTOIMMUNE-DISEASE; PREGNANCY; WOMEN; MICROCHIMERISM; EXPOSURE; ONSET AB This study examined associations between childbearing and risk of scleroderma by using national population-based registry data from Sweden. Women with a discharge diagnosis of scleroderma from 1964 to 1999 (n = 2,149) were identified in the Swedish Inpatient Register. These cases were matched by year and month of birth and region of residence to as many as five controls obtained from the Multi-Generation Register. Pregnancy history (number of births, age at each birth) was restricted to births before the first scleroderma-related hospitalization for cases and the corresponding age for their matched controls. Risk estimates, measured by the odds ratio and 95% confidence interval, were obtained by using conditional logistic regression. Nulliparity was associated with an increased risk of scleroderma (odds ratio = 1.37, 95% confidence interval: 1.22, 1.55). Risk decreased with increasing number of births. Similar results were found when analyses were limited to births up to 2 years or up to 5 years before hospitalization. Among parous women, younger age at first birth was associated with an increased risk of scleroderma. The association between lower parity and increased risk of scleroderma could reflect subfecundity caused by scleroderma before disease became clinically evident, possible common causes of infertility and scleroderma, or a protective effect of pregnancy through an unknown mechanism. C1 Karolinska Inst, Dept Epidemiol, Stockholm, Sweden. Karolinska Hosp, Dept Rheumatol, S-10401 Stockholm, Sweden. NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Durham, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. EM cooper1@niehs.nih.gov OI Lambe, Mats/0000-0002-4624-3767 NR 21 TC 20 Z9 22 U1 1 U2 2 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 JAN 15 PY 2004 VL 159 IS 2 BP 162 EP 166 DI 10.1093/aje/kwh027 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 764DY UT WOS:000188189100009 PM 14718218 ER PT J AU Kozma, C Slavotinek, AM Meck, JM AF Kozma, C Slavotinek, AM Meck, JM TI Seoregation of a t(1;3) translocation in multiple affected family members with both types of adjacent-1 segregants SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE partial trisomy 1q; partial trisomy 3p; partial monosomy 1q; partial monosomy 3p; congenital heart defects; chromosome abnormalities; adjacent-1 segregants ID KARYOTYPE-PHENOTYPE CORRELATION; SHORT ARM; PARTIAL MONOSOMY-3P; TERMINAL DELETION; CHROMOSOME-3; DUPLICATION; 1Q; HYBRIDIZATION; 3P-SYNDROME; DELINEATION AB the terminal regions of 1q and 3p was identified in a large family by high-resolution karyotype analysis and confirmed by fluorescence in situ hybridization (FISH) analysis. In this family, segregation of a balanced t(l:3)(q42.3;p25) chromosome translocation. led to two types of viable unbalanced complements. The proband inherited the derivative chromosome 3, resulting in partial trisomy of 1q and partial monosomy of 3p. A paternal uncle and cousin had the reciprocal rearrangement with a derivative of chromosome 1, resulting in partial monosomy for 1q and partial trisomy for 3p. While profound mental and physical retardation and congenital heart defects were characteristics for both rearrangements, facial dysmorphism was quite distinct for each imbalance. Individuals who had the derivative chromosome 3 had a long face, wide. eyebrows, small palpebral fissures, hypertelorism, prominent glabella, a large tip of the nose, long philtrum with thin upper lip, and low set-ears. In contrast, family members with the derivative of chromosome 1 had a tall forehead with bifrontal narrowing, full and large cheeks, and large simple ears. Since the translocated segments are small and approximately equal in size in this family, it is not surprising that viability was seen in individuals with both types of adjacent-1 segregation. In this kindred, the ratio of normal to abnormal individuals born to balanced carriers is believed to be about 1:1.5. This suggests that the recurrence risk for carriers is 50%. (C) 2003 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. NIH, NHGRI, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. RP Kozma, C (reprint author), Georgetown Univ Hosp, Dept Pediat, Ctr Child & Human Dev, 2PHC,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM kozmac@georgetown.edu NR 26 TC 9 Z9 9 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 A JI Am. J. Med. Genet. A PD JAN 15 PY 2004 VL 124A IS 2 BP 118 EP 128 DI 10.1002/ajmg.a.20332 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 761GL UT WOS:000187893100002 PM 14699608 ER PT J AU Shugart, YY Mundorff, J Kilshaw, J Doheny, K Doan, B Wanyee, J Green, ED Drayna, D AF Shugart, YY Mundorff, J Kilshaw, J Doheny, K Doan, B Wanyee, J Green, ED Drayna, D TI Results of a genome-wide linkage scan for stuttering SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE stuttering; linkage; speech disorder; non-parametric analysis AB We performed a linkage study of stuttering using 392 markers distributed across the genome in a series of 68 families identified in the general outbred population of North America and Europe. Standardized diagnosis was performed using recorded samples of both conversation and reading, in which stuttering dysfluencies were scored as percentage of dysfluent words and syllables. Analysis was first performed using nonparametric methods implemented in GENE-HUNTER, where we obtained maximum statistical support for markers of chromosome 18, with a maximum NPL (S-all) of 1.51 at D18S976. The single largest pedigree within our sample (pedigree 0006) alone gave an NPL of 4.72 at D18S976. For fine mapping, we analyzed 18 markers on chromosome 18 across all families using ALLEGRO. Overall NPL (Srobdo.) scores >5 were obtained with markers on 18p, and Z(1r), scores greater than or equal to2.5 on 18p and proximal 18q. Furthermore, pedigree 0006 alone gave an NPL (S-robdom) of 5.35. Overall our results suggest chromosome 18 may harbor a predisposing locus for this disorder, and additional genes may exist. Published 2003 Wiley-Liss, Inc.(dagger) C1 NIDCD, NIH, Rockville, MD 20850 USA. Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. Hollins Commun Res Inst, Roanoke, VA USA. NIDCD, NIH, Rockville, MD USA. Stuttering Fdn Amer, Memphis, TN USA. RP Drayna, D (reprint author), NIDCD, NIH, 5 Res Court,Room 2B-46, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov FU NHGRI NIH HHS [N01-HG-65403]; PHS HHS [Z01 00046-03] NR 9 TC 38 Z9 40 U1 0 U2 6 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 A JI Am. J. Med. Genet. A PD JAN 15 PY 2004 VL 124A IS 2 BP 133 EP 135 DI 10.1002/ajmg.a.20347 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 761GL UT WOS:000187893100004 PM 14699610 ER PT J AU Baker, SD Zhao, M He, P Carducci, MA Verweij, J Sparreboom, A AF Baker, SD Zhao, M He, P Carducci, MA Verweij, J Sparreboom, A TI Simultaneous analysis of docetaxel and the formulation vehicle polysorbate 80 in human plasma by liquid chromatography/tandem mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE docetaxel; polysorbate 80 (Tween 80); LC/MS/MS; pharmacokinetics ID SOLID-PHASE EXTRACTION; PHARMACOKINETICS; PACLITAXEL; TAXOTERE; CANCER; MICE; METABOLITES; VALIDATION; TAXANES; ASSAY AB An analytical procedure for the simultaneous determination of the anticancer agent docetaxel (Taxotere) and its formulation vehicle polysorbate 80 (Tween 80) in human plasma samples is described. Sample pretreatment involved a double liquid-liquid extraction step with a mixture of acetonitrile/n-butyl chloride (1/4, v/v). Separation of the compounds of interest, including the internal standard paclitaxel, was achieved on a reversed-phase Waters X-Terra mass spectrometry (MS) column (50 x 2.1 mm internal diameter) packed with a 3.5-mum octadecyl stationary phase, using isocratic elution. Detection of docetaxel and polysorbate 80 was performed using tandem MS detection with electrospray ionization. Validation results indicated that the method is accurate and precise and has lower limits of quantitation of 0.500 nM (similar to0.4 ng/ml) and 1.00 mug/ml for docetaxel and polysorbate 80, respectively. The method was subsequently used to measure concentrations of docetaxel and polysorbate 80 in plasma samples in support of a project to assess the influence of polysorbate 80 concentrations on the disposition and toxicity profile of docetaxel in cancer patients receiving Taxotere. (C) 2003 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Dr Daniel Den Hoed Canc Ctr, Erasmus Med Ctr, NL-3008 AE Rotterdam, Netherlands. NCI, Bethesda, MD 20892 USA. RP Baker, SD (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. RI Sparreboom, Alex/B-3247-2008 NR 24 TC 56 Z9 57 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 15 PY 2004 VL 324 IS 2 BP 276 EP 284 DI 10.1016/j.ab.2003.09.038 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 759JF UT WOS:000187734000014 PM 14690692 ER PT J AU Shears, SB AF Shears, SB TI How versatile are inositol phosphate kinases? SO BIOCHEMICAL JOURNAL LA English DT Review DE diphosphoinositol polyphosphate; inositol phosphate kinase; InsP(6) kinase; inositol phosphate multikinase (Ipmk); trisphosphate; tetrakisphosphate ID DIPHOSPHOINOSITOL POLYPHOSPHATE PHOSPHOHYDROLASE; ACTIVATED CHLORIDE CONDUCTANCE; DEPENDENT PROTEIN-KINASE; MESSENGER-RNA EXPORT; SACCHAROMYCES-CEREVISIAE; 1,3,4-TRISPHOSPHATE 5/6-KINASE; COP9 SIGNALOSOME; RAT-LIVER; ARGININE METABOLISM; IN-VIVO AB This review assesses the extent and the significance of catalytic versatility shown by several inositol phosphate kinases: the inositol phosphate multikinase, the reversible Ins(1,3,4)P-3/ Ins(3,4,5,6)P-4 kinase, and the kinases that synthesize diphosphoinositol polyphosphates. Particular emphasis is placed upon data that are relevant to the situation in vivo. It will be shown that catalytic promiscuity towards different inositol phosphates is not typically an evolutionary compromise, but instead is sometimes exploited to facilitate tight regulation of physiological processes. This multifunctionality can add to the complexity with which inositol signalling pathways interact. This review also assesses some proposed additional functions for the catalytic domains, including transcriptional regulation, protein kinase activity and control by molecular 'switching', all in the context of growing interest in 'moonlighting' (gene-sharing) proteins. C1 NIEHS, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), NIEHS, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov NR 154 TC 120 Z9 125 U1 2 U2 8 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2004 VL 377 BP 265 EP 280 DI 10.1042/BJ20031428 PN 2 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 769EA UT WOS:000188612400001 PM 14567754 ER PT J AU Bong, YS Park, YH Lee, HS Mood, K Ishimura, A Daar, IO AF Bong, YS Park, YH Lee, HS Mood, K Ishimura, A Daar, IO TI Tyr-298 in ephrinB1 is critical for an interaction with the Grb4 adaptor protein SO BIOCHEMICAL JOURNAL LA English DT Article DE ephrinB1; Grb4 (growth-factor-receptor-bound protein 4); tyrosine phosphorylation; Xenopus ID RECEPTOR TYROSINE KINASES; EPH RECEPTORS; XENOPUS-LAEVIS; TRANSMEMBRANE LIGANDS; CYTOPLASMIC DOMAIN; SIGNALING PATHWAYS; FAMILY; PHOSPHORYLATION; BINDING; EMBRYOS AB The Eph family of receptor tyrosine kinases and their membrane-bound ligands. the ephrins, are thought to play a role in the regulation of cell adhesion and migration during development by mediating cell-to-cell signalling events. The transmembrane ephrinB protein is a bidirectional signalling molecule that sends a forward signal through the activation of its cognate receptor tyrosine kinase residing on another cell. The reverse signal is transduced into the ephrinB-expressing cell via tyrosine phosphorylation of its conserved C-terminal cytoplasmic domain. Previous work from our laboratory has implicated the activated FGFR1 (fibroblast growth factor receptor 1) as a regulator of a deadhesion signal that results from overexpression of ephrinB1. In the present study, we report the isolation of Xenopus Grb4 (growth-factor-receptor- bound protein 4), an ephrinB1-interacting protein. and we show that when expressed in Xenopus oocytes, ephrmB1 interacts with Grb4 in the presence of an activated FGFR L Amino acid substitutions were generated in Grb4, and the resulting mutants were expressed along with ephrinB1 and an activated FGFR in Xenopus oocytes. Co-immunoprecipitation analysis shows that the FLVR motif within the Src homology 2 domain of Xenopus Grb4 is vital for this phosphorylation-dependent interaction with ephrinB1. More importantly, using deletion and substitution analysis we identify the tyrosine residue at position 298 of ephrinB1 as being required for the physical interaction with Grb4, whereas Tyr-305 and Tyr-310 are dispensable. Moreover, we show that the region between amino acids 301 and 304 of ephrinB1 is also required for this critical tyrosine-phosphorylation-dependent event. C1 NCI, Regulat Cell Growth Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Daar, IO (reprint author), NCI, Regulat Cell Growth Lab, Canc Res Ctr, Frederick, MD 21702 USA. EM daar@ncifcrf.gov RI Lee, Hyun-Shik/G-3555-2011; OI Daar, Ira/0000-0003-2657-526X NR 45 TC 21 Z9 21 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2004 VL 377 BP 499 EP 507 DI 10.1042/BJ20031449 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 769EA UT WOS:000188612400024 PM 14535844 ER PT J AU Luo, XG Klempan, TA Lappalainen, J Rosenheck, RA Charney, DS Erdos, J van Kammen, DP Kranzler, HR Kennedy, JL Gelernter, J AF Luo, XG Klempan, TA Lappalainen, J Rosenheck, RA Charney, DS Erdos, J van Kammen, DP Kranzler, HR Kennedy, JL Gelernter, J TI NOTCH4 gene haplotype is associated with schizophrenia in African Americans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; NOTCH4; haplotype; allele; African American population ID CHROMOSOME 6P; LOCUS; SUSCEPTIBILITY; POLYMORPHISM; CLOZAPINE; LINKAGE; DISEASE; DISEQUILIBRIUM; PROTOONCOGENE; FAMILIES AB Background: The goal of this study was to investigate the relationship between the NOTCH4 gene and schizophrenia in African American (A-A) and European American (EA) subjects. Methods: Two single nucleotide polymorphisms (SNPS) at the NOTCH4 locus were genotyped in 123 AA schizophrenia patients, 223 EA schizophrenia patients, 85 AA healty control subjects, and 211 EA healthy control subjects. The specific markers studied were -1725T/G and -25T/C. Comparisons of allele and haplotype frequencies between patients and control subjects were performed with the chi-square test, the Fisher's Exact Test, and CLUMP software. Linkage disequilibrium (LD) between these two SNPs was calculated with the 3LOCUS program, Results: The haplotype-1725G/-257-associates to schizophrenia in AA subjects (p = .0008), but not in EA subjects. Alleles -1725G and allele -25T are in positive LD both in AAs and EAs. Allele and haplotype frequencies differ significantly between AAs and EAs. Conclusions: The haplotype -1725G/-25T at tbe NOTCH4 locus, which results from SNPs of NOTCH4 that are in LD. may increase susceptibility to schizophrenia in AAs. Any effect of this locus on risk for schizophrenia is population-specific. C1 VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Toronto, Dept Psychiat, Neurogenet Sect, Ctr Addict & Mental Hlth, Toronto, ON, Canada. NIMH, Bethesda, MD 20892 USA. Aventis Pharmaceut, Bridgewater, MA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Connecticut, Sch Med, Dept Psychiat, Farmington, CT USA. RP Gelernter, J (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,Psychiat 116A2, West Haven, CT 06516 USA. FU NCRR NIH HHS [M01-RR06192]; NIAAA NIH HHS [K24-AA13736]; NIDA NIH HHS [DA12690, DA12849]; NIMH NIH HHS [K02-MH01387] NR 33 TC 23 Z9 24 U1 2 U2 3 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 JAN 15 PY 2004 VL 55 IS 2 BP 112 EP 117 DI 10.1016/S0006-3223(03)00588-2 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 764GX UT WOS:000188200100002 PM 14732589 ER PT J AU Lee, JW Kang, SU Lim, JO Choi, HK Jin, MK Toth, A Pearce, LV Tran, R Wang, Y Szabo, T Blumberg, PM AF Lee, JW Kang, SU Lim, JO Choi, HK Jin, MK Toth, A Pearce, LV Tran, R Wang, Y Szabo, T Blumberg, PM TI N-[4-(methylsulfonylamino)benzyl]thiourea analogues as vanilloid receptor antagonists: analysis of structure-activity relationships for the 'C-Region' SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE vanilloid receptor 1; antagonist ID HIGH-AFFINITY ANTAGONISTS; ROOT GANGLION NEURONS; CAPSAICIN-RECEPTOR; COMPETITIVE ANTAGONIST; IODO-RESINIFERATOXIN; ANALGESIC PROPERTIES; CAPSAZEPINE; RAT; POTENT; PAIN AB We recently reported that N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl] thiourea (2) was a high affinity antagonist of the vanilloid receptor with a binding affinity of K-i = 63 nM and an antagonism of K-i = 53.9 nM in rat VR1 heterologously expressed in Chinese hamster ovary (CHO) cells (Mol. Pharmacol. 2002, 62, 947-956). In an effort to further improve binding affinity and antagonistic potency, we have modified the C-region of the lead 4-t-butylbenzyl group with diverse surrogates, such as araalkyl, alkyl, 4-alkynylbenzyl, indanyl, 3,3-diarylpropyl, 4-alkoxybenzyl, 4-substituted piperazine and piperidine. The lipophilic surrogates, arylalkyl and alkyl, conferred modest decreases in binding affinities and antagonistic potencies; the groups having heteroatoms resulted in dramatic decreases. Our findings indicate that 4-t-butylbenzyl is one of the most favorable groups for high receptor binding and potent antagonism to VR1 in this structural series. (C) 2003 Elsevier Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. NCI, Ctr Canc Res, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. RP Lee, JW (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Shinlim Dong, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 NR 36 TC 22 Z9 24 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 15 PY 2004 VL 12 IS 2 BP 371 EP 385 DI 10.1016/j.bmc.2003.10.047 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 766UV UT WOS:000188394700006 PM 14723956 ER PT J AU Klion, AD Robyn, J Akin, C Noel, P Brown, M Law, M Metcalfe, DD Dunbar, C Nutman, TB AF Klion, AD Robyn, J Akin, C Noel, P Brown, M Law, M Metcalfe, DD Dunbar, C Nutman, TB TI Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome SO BLOOD LA English DT Article ID HUMAN EOSINOPHILS; FUSION; LEUKEMIA; TRYPTASE; KINASE; CELLS; A(2) AB We recently described a subset of patients with a myeloproliferative variant of hypereosinophilic syndrome (MHES) characterized by elevated serum tryptase levels, increased atypical mast cells in the bone marrow, tissue fibrosis, and the presence of the fusion tyrosine kinase, FIP1L1-PDGFRalpha, which is a therapeutic target of imatinib mesylate. Seven patients with MHES were treated with imatinib mesylate (300-400 mg daily). Clinical improvement and resolution of eosinophilia was observed in all patients, although cardiac dysfunction, when present, was not altered by therapy. Reversal of bone marrow pathology, including increased cellularity, the presence of spindle-shaped mast cells, and myelofibrosis, was evident in all patients at 4 to 8 weeks following initiation of therapy. This was accompanied by a decrease in activated eosinophils and mast cells in the peripheral blood and bone marrow, respectively. Serum tryptase levels declined rapidly to normal levels in all patients and remained in the normal range throughout therapy. Molecular remission, with disappearance of detectable FIP1L1/PDGFRA (F/P) transcripts, was achieved in 5 of 6 patients tested. The lack of reversal of cardiac abnormalities and persistence of the F/P mutation in some patients suggests that early intervention with higher doses of imatinib mesylate may be desirable in the treatment of patients with MHES. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm 126, Bethesda, MD 20892 USA. EM aklion@nih.gov OI Klion, Amy/0000-0002-4986-5326; Akin, Cem/0000-0001-6301-4520 NR 26 TC 162 Z9 171 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 JAN 15 PY 2004 VL 103 IS 2 BP 473 EP 478 DI 10.1182/blood-2003-08-2798 PG 6 WC Hematology SC Hematology GA 762CY UT WOS:000187954000025 PM 14504092 ER PT J AU Shin, MG Kajigaya, S McCoy, JP Levin, BC Young, NS AF Shin, MG Kajigaya, S McCoy, JP Levin, BC Young, NS TI Marked mitochondrial DNA sequence heterogeneity in single CD34(+) cell clones from normal adult bone marrow SO BLOOD LA English DT Article ID CONTROL REGION; MYELODYSPLASTIC SYNDROMES; MUTATIONS; VARIANT; HETEROPLASMY; GENOME; FREQUENCY; REVEALS; TISSUES; DISEASE AB Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in postmitotic tissues but have been postulated to be diluted and lost in continually proliferating tissues such as bone marrow (BM). Having observed marked sequence variation among healthy adult individuals' total BM cell mtDNA, we undertook analysis of the mtDNA control region in a total of 611 individual CD34(+) clones from 6 adult BM donors and comparison of these results with the sequences from 580 CD34(+) clones from 5 umbilical cord blood (CB) samples. On average, 25% (range, 11% to 50%) of individual CD34(+) clones from adult BM showed mtDNA heterogeneity, or sequence differences from the aggregate mtDNA sequence of total BM cells of the same individual. In contrast, only 1.6% of single CD34(+) clones from CB showed mtDNA sequence variation from the aggregate pattern. Thus, age-dependent accumulation of mtDNA mutations appears relatively common in a mitotically active human tissue and may provide a method to approximate the mutation rate in mammalian cells, to assess the contribution of reactive oxygen species to genomic instability, and for natural "marking" of hematopoietic stem cells; our data also have important implications for the aging process, forensic identifications, and anthropologic conclusions dependent on the mtDNA sequence. C1 NHLBI, Hematol Branch, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Div Biotechnol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, Flow Cytometry Core Facil, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM youngn@nhlbi.nih.gov NR 34 TC 29 Z9 30 U1 1 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 JAN 15 PY 2004 VL 103 IS 2 BP 553 EP 561 DI 10.1182/blood-2003-05-1724 PG 9 WC Hematology SC Hematology GA 762CY UT WOS:000187954000037 PM 14504082 ER PT J AU Konno, A Wada, T Schurman, SH Garabedian, EK Kirby, M Anderson, SM Candotti, F AF Konno, A Wada, T Schurman, SH Garabedian, EK Kirby, M Anderson, SM Candotti, F TI Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T- and B-cell lineages SO BLOOD LA English DT Article ID IN-VIVO REVERSION; ADENOSINE-DEAMINASE DEFICIENCY; SOMATIC MOSAICISM; INHERITED MUTATION; PATIENT; TRANSPLANTATION; LYMPHOCYTES; ACTIVATION AB Somatic mosaicism because of in vivo reversion has been recently reported in a small number of patients affected with Wiskott-Aldrich syndrome (WAS). Flow cytometry analysis of WAS protein (WASP) expression has shown that these patients carried revertant cells only among T lymphocytes. Here, we have used high-resolution capillary electrophoresis to analyze genomic DNA from highly purified cells of one of these patients and detected revertant sequences also within the B-cell fraction. The demonstration of revertant cells among both T and B lymphocytes in this patient is consistent with the reversion event having occurred in a common lymphoid progenitor. However, although WASP-expressing T cells showed selective advantage and were readily detectable in the periphery of the mosaic patient, revertant B lymphocytes remained below the detection threshold of flow cytometry. These findings suggest that, contrary to T cells, differentiation and survival of B lymphocytes is minimally dependent on WASP. C1 NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,49-3A20, Bethesda, MD 20892 USA. EM fabio@mail.nih.gov OI Schurman, Shepherd/0000-0002-9133-7906 NR 12 TC 32 Z9 33 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 JAN 15 PY 2004 VL 103 IS 2 BP 676 EP 678 DI 10.1182/blood-2003-05-1739 PG 3 WC Hematology SC Hematology GA 762CY UT WOS:000187954000055 PM 14504083 ER PT J AU West, KA Linnoila, IR Belinsky, SA Harris, CC Dennis, PA AF West, KA Linnoila, IR Belinsky, SA Harris, CC Dennis, PA TI Tobacco carcinogen-induced cellular transformation increases activation of the phosphatidylinositol 3 '-Kinase/Akt pathway in vitro and in vivo SO CANCER RESEARCH LA English DT Article ID BRONCHIAL EPITHELIAL-CELLS; FORKHEAD TRANSCRIPTION FACTOR; 3-KINASE/AKT PATHWAY; AKT; SURVIVAL; CANCER; PHOSPHORYLATION; EXPRESSION; APOPTOSIS AB The role of the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway during tobacco carcinogen-induced transformation is unknown. To address this question, we evaluated this pathway in isogenic immortalized or tumorigenic human bronchial epithelial cells in vitro, as well as in progressive murine lung lesions induced by a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Compared with immortalized cells, tumorigenic cells had greater activation of the PI3K/Akt pathway, enhanced survival, and increased apoptosis in response to inhibition of the pathway. In vivo, increased activation of Akt and mammalian target of rapamycin was observed with increased phenotypic progression. Collectively, these results support the hypothesis that maintenance of Akt activity is necessary for survival of preneoplastic as well as transformed lung epithelial cells and suggest that inhibition of the PI3K/Akt pathway might be a useful approach to arrest lung tumorigenesis. C1 NCI, Canc Res Ctr, Canc Therapeut Branch, NIH, Bethesda, MD USA. NCI, Canc Res Ctr, Cell & Canc Biol Branch, NIH, Bethesda, MD USA. NCI, Canc Res Ctr, Human Carcinogenesis Lab, NIH, Bethesda, MD USA. Lovelace Resp Res Inst, Albuquerque, NM USA. RP Dennis, PA (reprint author), USN, Naval Med Oncol, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 24 TC 83 Z9 85 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2004 VL 64 IS 2 BP 446 EP 451 DI 10.1158/0008-5472.CAN-03-3241 PG 6 WC Oncology SC Oncology GA 766WX UT WOS:000188399300003 PM 14744754 ER PT J AU Lin, DP Wang, YX Scherer, SJ Clark, AB Yang, K Avdievich, E Jin, B Werling, U Parris, T Kurihara, N Umar, A Kucherlapati, R Lipkin, M Kunkel, TA Edelmann, W AF Lin, DP Wang, YX Scherer, SJ Clark, AB Yang, K Avdievich, E Jin, B Werling, U Parris, T Kurihara, N Umar, A Kucherlapati, R Lipkin, M Kunkel, TA Edelmann, W TI An Msh2 point mutation uncouples DNA mismatch repair and apoptosis SO CANCER RESEARCH LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; CELL-LINE; SACCHAROMYCES-CEREVISIAE; MSH2-DEFICIENT MICE; ESCHERICHIA-COLI; APC MUTATIONS; RESISTANCE; CISPLATIN; BINDING; HMSH2 AB Mutations in the human DNA mismatch repair gene MSH2 are associated with hereditary nonpolyposis colorectal cancer as well as a significant proportion of sporadic colorectal cancer. The inactivation of MSH2 results in the accumulation of somatic mutations in the genome of tumor cells and resistance to the genotoxic effects of a variety of chemotherapeutic agents. Here we show that the DNA repair and DNA damage-induced apoptosis functions of Msh2 can be uncoupled using mice that carry the G674A missense mutation in the conserved ATPase domain. As a consequence, although Msh2(G674A) homozygous mutant mice are highly tumor prone, the onset of tumorigenesis is delayed as compared with Msh2-null mice. In addition, tumors that carry the mutant allele remain responsive to treatment with a chemotherapeutic agent Our results indicate that Msh2-mediated apoptosis is an important component of tumor suppression and that certain MSH2 missense mutations can cause mismatch repair deficiency while retaining the signaling functions that confer sensitivity to chemotherapeutic agents. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. NIEHS, Mol Genet Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Rockefeller Univ, Strang Canc Res Lab, New York, NY 10021 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. RP Edelmann, W (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM edelmann@aecom.yu.edu FU NCI NIH HHS [CA76329, CA84301, CA93484, CN05117, CA13330]; NIEHS NIH HHS [ES11040] NR 52 TC 122 Z9 124 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2004 VL 64 IS 2 BP 517 EP 522 DI 10.1158/0008-5472.CAN-03-2957 PG 6 WC Oncology SC Oncology GA 766WX UT WOS:000188399300013 PM 14744764 ER PT J AU Felix, K Polack, A Pretsch, W Jackson, SH Feigenbaum, L Bornkamm, GW Janz, S AF Felix, K Polack, A Pretsch, W Jackson, SH Feigenbaum, L Bornkamm, GW Janz, S TI Moderate hypermutability of a transgenic lacZ reporter gene in Myc-dependent inflammation-induced plasma cell tumors in mice SO CANCER RESEARCH LA English DT Article ID STRAND BREAK REPAIR; IN-VIVO MUTATIONS; ELEVATED MUTANT FREQUENCIES; UNCOUPLES DNA-REPLICATION; C-MYC; REACTIVE OXYGEN; TRANSCRIPTIONAL ACTIVATION; INDUCED LYMPHOMAGENESIS; MOUSE PLASMACYTOMAS; MULTIPLE MUTATIONS AB Mutator phenotypes, a common and largely unexplained attribute of human cancer, might be better understood in mouse tumors containing reporter genes for accurate mutation enumeration and analysis. Previous work on peritoneal plasmacytomas (PCTs) in mice suggested that PCTs have a mutator phenotype caused by Myc-deregulating chromosomal translocations and/or phagocyte-induced mutagenesis due to chronic inflammation. To investigate this hypothesis, we generated PCTs that harbored the transgenic shuttle vector, pUR288, with a lacZ reporter gene for the assessment of mutations in vivo. PCTs exhibited a 5.5 times higher mutant frequency in lacZ (40.3 +/- 5.1 x 10(-5)) than in normal B cells (7.36 +/- 0.77 x 10(-5)), demonstrating that the tumors exhibit the phenotype of increased mutability. Studies on lacZ mutant frequency in serially transplanted PCTs and phagocyte-induced lacZ mutations in B cells in vitro indicated that mutant levels in tumors are not determined by exogenous damage inflicted by inflammatory cells. In vitro studies with a newly developed transgenic model of inducible Myc expression (Tet-off/MYC) showed that deregulated Myc sensitizes B cells to chemically induced mutations, but does not cause, on its own, mutations in lacZ. These findings suggested that the hypermutability of PCT is governed mainly by intrinsic features of tumor cells, not by deregulated Myc or chronic inflammation. C1 NCI, Genet Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Inst Mol Biol & Tumor Genet, Munich, Germany. Inst Mammalian Genet, Neuherberg, Germany. Sci Applicat Int Corp, NCI, Frederick, MD USA. RP Janz, S (reprint author), NCI, Genet Lab, Canc Res Ctr, Bldg 37,Room 3140A, Bethesda, MD 20892 USA. EM sj4s@nih.gov NR 71 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2004 VL 64 IS 2 BP 530 EP 537 DI 10.1158/0008-5472.CAN-03-2602 PG 8 WC Oncology SC Oncology GA 766WX UT WOS:000188399300015 PM 14744766 ER PT J AU Schaeffer, AJ Nguyen, M Liem, A Lee, D Montagna, C Lambert, PF Ried, T Difilippantonio, MJ AF Schaeffer, AJ Nguyen, M Liem, A Lee, D Montagna, C Lambert, PF Ried, T Difilippantonio, MJ TI E6 and E7 oncoproteins induce distinct patterns of chromosomal aneuploidy in skin tumors from transgenic mice SO CANCER RESEARCH LA English DT Article ID PAPILLOMAVIRUS TYPE-16 E6; GENOMIC HYBRIDIZATION REVEALS; CENTROSOME AMPLIFICATION; CERVICAL DYSPLASIA; GENETIC CHANGES; CHEMICAL CARCINOGENS; RECURRENT PATTERN; CELL-DIVISION; RAS ONCOGENE; IN-SITU AB Inactivation of the tumor suppressor genes p53 and Rb are two of the most common genetic alterations in cancer cells. We use a mouse model to dissect the consequences of compromising the function of either of these genes on the maintenance of genomic stability. Thirteen cell lines established from skin tumors of mice expressing either the E6 or E7 oncoprotein of the human papillomavirus (HPV) type 16 under control of the keratin 14 promoter were analyzed by comparative genomic hybridization, spectral karyotyping and fluorescence in situ hybridization, reverse transcription-PCR, and mutation analysis. Deducing from the wealth of molecular cytogenetic data available from human cancers, we hypothesized that the more benign tumors in mice expressing E7 would be distinct from the more aggressive lesions in E6 transgenic mice. Tumorigenesis in E6-expressing mice required specifically the selection and maintenance of cells with extra copies of chromosome 6. Aneuploidy of chromosome 6 was independent of activating mutations in H-ras on chromosome 7. Expression of either E6 or E7 resulted in centrosome aberrations, indicating that each viral oncoprotein interferes independently with the centrosome cycle. Although centrosome aberrations are consistent with development of aneuploidy, no direct correlation was evident between the degree of aneuploidy and the percentage of cells with aberrant centrosomes. Our results show that although aneuploidy and centrosome aberrations are present in tumor cells from mice expressing either E6 or E7, tumorigenesis via E6 requires copy number increases of mouse chromosome 6, which is partially orthologous to human chromosome 3q, a region gained in HPV-associated carcinomas. C1 NCI, Sect Canc Genom, NIH, Genet Branch, Bethesda, MD 20892 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI USA. RP Difilippantonio, MJ (reprint author), NCI, Sect Canc Genom, NIH, Genet Branch, 50 South Dr,Room 1306, Bethesda, MD 20892 USA. EM difilipm@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 62 TC 33 Z9 35 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2004 VL 64 IS 2 BP 538 EP 546 DI 10.1158/0008-5472.CAN-03-0124 PG 9 WC Oncology SC Oncology GA 766WX UT WOS:000188399300016 PM 14744767 ER PT J AU Tester, AM Waltham, M Oh, SJ Bae, SN Bills, MM Walker, EC Kern, FG Stetler-Stevenson, WG Lippman, ME Thompson, EW AF Tester, AM Waltham, M Oh, SJ Bae, SN Bills, MM Walker, EC Kern, FG Stetler-Stevenson, WG Lippman, ME Thompson, EW TI Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice SO CANCER RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; BASEMENT-MEMBRANE; STROMAL CELLS; MESSENGER-RNA; GELATINASE-A; MESENCHYMAL TRANSITION; TUMOR PROGRESSION; BONE METASTASES; CARCINOMA CELLS; PROSTATE-CANCER AB The ability to activate pro-matrix metalloproteinase (pro-MMP)-2 via membrane type-MMP is a hallmark of human breast cancer cell lines that show increased invasiveness, suggesting that MMP-2 contributes to human breast cancer progression. To investigate this, we have stably transfected pro-MMP-2 into the human breast cancer cell line MDA-MB-231, which lacks MMP-2 expression but does express its cell surface activator, membrane type 1-MMP. Multiple clones were derived and shown to produce pro-MMP-2 and to activate it in response to concanavalin A. In vitro analysis showed that the pro-MMP-2-transfected clones exhibited an increased invasive potential in Boyden chamber and Matrigel outgrowth assays, compared with the parental cells or those transfected with vector only. When inoculated into the mammary fat pad of nude mice, each of the MMP-2-tranfected clones grew faster than each of the vector controls tested. After intracardiac inoculation into nude mice, pro-MMP-2-transfected clones showed a significant increase in the incidence of metastasis to brain, liver, bone, and kidney compared with the vector control clones but not lung. Increased tumor burden was seen in the primary site and in lung metastases, and a trend toward increased burden was seen in bone, however, no change was seen in brain, liver, or kidney. This data supports a role for MMP-2 in breast cancer progression, both in the growth of primary tumors and in their spread to distant organs. MMP-2 may be a useful target for breast cancer therapy when refinement of MMP inhibitors provides for MMP-specific agents. C1 Univ Melbourne, Dept Surg, Parkville, Vic 3052, Australia. St Vincent Hosp, Bernard O Brien Inst Microsurg, Melbourne, Vic, Australia. Catholic Univ Korea, Our Lady Mercy Hosp, Dept Surg, Inchon, South Korea. Catholic Univ, Korea Med Coll, Kangnam St Marys Hosp, Dept Obstet & Gynecol, Seoul, South Korea. Georgetown Univ, Ctr Med, Lombardi Canc Ctr, Washington, DC USA. NCI, Pathol Lab, Bethesda, MD USA. RP Thompson, EW (reprint author), Univ Melbourne, St Vincents Hosp, Dept Surg, Invas & Metastasis Unit, 29 Regent St, Fitzroy, Vic 3065, Australia. EM rik@medstv.unimelb.edu.au RI Waltham, Mark/A-1728-2009; Stetler-Stevenson, William/H-6956-2012; Thompson, Erik/A-1425-2009; OI Stetler-Stevenson, William/0000-0002-5500-5808; Thompson, Erik/0000-0002-9723-4924; Oh, Se Jeong/0000-0002-2583-4218 FU NCI NIH HHS [2P50-CA58185-04, 2P30-CA-51008] NR 61 TC 59 Z9 68 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2004 VL 64 IS 2 BP 652 EP 658 DI 10.1158/0008-5472.CAN-0384-2 PG 7 WC Oncology SC Oncology GA 766WX UT WOS:000188399300030 PM 14744781 ER PT J AU De Siervi, A Marinissen, M Diggs, J Wang, XF Pages, G Senderowicz, A AF De Siervi, A Marinissen, M Diggs, J Wang, XF Pages, G Senderowicz, A TI Transcriptional activation of p21(waf1)/(cip1) by alkylphospholipids: Role of the mitogen-activated protein kinase pathway in the transactivation of the human p21(waf1/cip1) promoter by Sp1 SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE CONTROL; INDUCED APOPTOSIS; CARCINOMA-CELLS; SIGNAL-TRANSDUCTION; DEPENDENT KINASES; CDK INHIBITORS; DNA-BINDING; EXPRESSION; DIFFERENTIATION; PHOSPHORYLATION AB Alkylphospholipids (ALKs) are a novel class of antitumor agents with an unknown mechanism of action. The first ALK tested in the clinic, miltefosine, has been approved recently in Europe for the local treatment of patients with cutaneous metastasis. Perifosine, the only available oral ALK, is being studied currently in human cancer clinical trials. We have shown previously that perifosine induces p21(waf1/cip1) in a p53-independent fashion and that induction of p21(waf1/cip1) is required for the perifosine-induced cell cycle arrest because cell lines lacking p21(waf1/cip1) are refractory to perifosine. In this report, we investigated the mechanism by which perifosine induces p21(waf1/cip1) protein expression. We observed that perifosine induces the accumulation of p21(waf1/cip1) mRNA without affecting p21(waf1/cip1) mRNA stability. Using several p21(waf1/cip1) promoter-driven luciferase reporter plasmids, we observed that perifosine activates the 2.4-kb full-length p21(waf1/cip1) promoter as well as a p21 promoter construct lacking p53-binding sites, suggesting that perifosine activates the p21(waf1/cip1) promoter independent of p53. The minimal p21 promoter region required for perifosine-induced p21 promoter activation contains four consensus Sp1-binding sites. Mutations in each particular Sp1 site block perifosine-induced p21(waf1/cip1) expression. Moreover, we showed that perifosine activates the mitogen-activated protein/extracellular signal-regulated kinase pathway, and this activation promotes the phosphorylation of Sp1 in known mitogen-activated protein kinase residues (threonine 453 and 739), thereby leading to increased Sp1 binding and enhanced p21(waf1/cip1) transcription. These results represent a novel mechanism by which alkylphospholipids modulate transcription, and may contribute to the discovery of new signal transduction pathways crucial for normal and neoplastic cell cycle control. C1 NICDR, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC USA. Ctr Antoine Lacassagne, Inst Signalling Dev Biol & Canc Res, F-06054 Nice, France. RP Senderowicz, A (reprint author), NICDR, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sendero@helix.nih.gov NR 69 TC 58 Z9 58 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2004 VL 64 IS 2 BP 743 EP 750 DI 10.1158/0008-5472.CAN-03-2505 PG 8 WC Oncology SC Oncology GA 766WX UT WOS:000188399300042 PM 14744793 ER PT J AU Walker, EB Haley, D Miller, W Floyd, K Wisner, KP Sanjuan, N Maecker, H Romero, P Hu, HM Alvord, WG Smith, JW Fox, BA Urba, WJ AF Walker, EB Haley, D Miller, W Floyd, K Wisner, KP Sanjuan, N Maecker, H Romero, P Hu, HM Alvord, WG Smith, JW Fox, BA Urba, WJ TI gp100(209-2M) peptide immunization of human lymphocyte antigen-A2(+) stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8(+) T cells SO CLINICAL CANCER RESEARCH LA English DT Article ID DENDRITIC CELLS; METASTATIC MELANOMA; SYNTHETIC PEPTIDES; CD8-T-CELL MEMORY; CD4-T-CELL HELP; VACCINE; RESPONSES; INDUCTION; VIRUS; ADJUVANT AB Thirty-five HLA-A2(+) patients with completely resected stage I-III melanoma were vaccinated multiple times over 6 months with a modified melanoma peptide, gp100(209-2M), emulsified in Montanide adjuvant. Direct ex vivo gp100(209-2M) tetramer analysis of pre- and postvaccine peripheral blood mononuclear cells (PBMCs) demonstrated significant increases in the frequency of tetramer(+) CD8(+) T cells after immunization for 33 of 35 evaluable patients (median, 0.36%; range, 0.05-8.9%). Ex vivo IFN-gamma cytokine flow cytometry analysis of postvaccine PBMCs after brief gp100(209-2M) in vitro activation showed that for all of the patients studied tetramer(+) CD8(+) T cells produced IFN-gamma; however, some patients had significant numbers of tetramer(+) IFN-gamma(-) CD8(+)T cells suggesting functional anergy. Additionally, 8 day gp100(209-2M) in vitro stimulation (IVS) of pre- and postvaccine PBMCs resulted in significant expansion of tetramer(+) CD8(+) T cells from postvaccine cells for 34 patients, and these IVS tetramer(+) CD8(+) T cells were functionally responsive by IFN-gamma cytokine flow cytometry analysis after restimulation with either native or modified gp100 peptide. However, correlated functional and phenotype analysis of IVS-expanded postvaccine CD8(+) T cells demonstrated the proliferation of functionally anergic gp100(209-2M)- tetramer(+) CD8(+) T cells in several patients and also indicated interpatient variability of gp100(209-2M) stimulated T-cell proliferation. Flow cytometry analysis of cryopreserved postvaccine PBMCs from representative patients showed that the majority of tetramer(+) CD8(+) T cells (78.1 +/- 4.2%) had either an "effector" (CD45 RA(+)/CCR7(-)) or an "effector-memory" phenotype (CD45 RA(-)/CCR7(-)). Notably, analysis of PBMCs collected 12-24 months after vaccine therapy demonstrated the durable presence of gp100(209-2M)-specific memory CD8(+) T cells with high proliferation potential. Overall, this report demonstrates that after vaccination with a MHC class I-restricted melanoma peptide, resected nonmetastatic melanoma patients can mount a significant antigen-specific CD8(+) T-cell immune response with a functionally intact memory component. The data further support the combined use of tetramer binding and functional assays in correlated ex vivo and IVS settings as a standard for immunomonitoring of cancer vaccine patients. C1 Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA. NCI, DMS, Frederick, MD 21701 USA. Ludwig Inst Canc Res, Div Oncol Immunol, Lausanne, Switzerland. Becton Dickinson Biosci, San Jose, CA USA. Oregon Hlth Sci Univ, Dept Mol & Microbiol & Immunol, Portland, OR 97201 USA. RP Walker, EB (reprint author), Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, 4805 NE Glisan,5F40, Portland, OR 97213 USA. EM edwin.walker@providence.org FU PHS HHS [1R21-CS82614-01] NR 36 TC 51 Z9 53 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2004 VL 10 IS 2 BP 668 EP 680 DI 10.1158/1078-0432.CCR-0095-03 PG 13 WC Oncology SC Oncology GA 771TA UT WOS:000188801100033 PM 14760090 ER PT J AU Pappas, PG Rex, JH Sobel, JD Filler, SG Dismukes, WE Walsh, TJ Edwards, JE AF Pappas, PG Rex, JH Sobel, JD Filler, SG Dismukes, WE Walsh, TJ Edwards, JE TI Guidelines for treatment of candidiasis SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; LIPOSOMAL AMPHOTERICIN-B; INVASIVE FUNGAL-INFECTIONS; ITRACONAZOLE ORAL SOLUTION; IN-VITRO ACTIVITIES; PLACEBO-CONTROLLED TRIAL; EMPIRICAL ANTIFUNGAL THERAPY; HOSPITAL-ACQUIRED CANDIDEMIA; LIVER-TRANSPLANT RECIPIENTS; VULVO-VAGINAL CANDIDIASIS AB Candida species are the most common cause of fungal infections. Candida species produce infections that range from non-life-threatening mucocutaneous illnesses to invasive processes that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. These guidelines summarize current knowledge about treatment of multiple forms of candidiasis for the Infectious Diseases Society of America (IDSA). Throughout this document, treatment recommendations are rated according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the supporting evidence and quality of the underlying data ( table 1). This document covers the following 4 major topical areas. C1 Univ Alabama, Div Infect Dis, Birmingham, AL 35294 USA. AstraZeneca Pharmaceut, Manchester, Lancs, England. Wayne State Univ, Sch Med, Detroit, MI USA. Harbor Univ Calif Los Angeles Med Ctr, Torrance, CA USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Pappas, PG (reprint author), Univ Alabama, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. RI Filler, Scott/A-2779-2009 NR 345 TC 766 Z9 851 U1 5 U2 36 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 JAN 15 PY 2004 VL 38 IS 2 BP 161 EP 189 DI 10.1086/380796 PG 29 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 757NN UT WOS:000187568500001 PM 14699449 ER PT J AU Bhattacharya, SK Jha, TK Sundar, S Thakur, CP Engel, J Sindermann, H Junge, K Karbwang, J Bryceson, ADM Berman, JD AF Bhattacharya, SK Jha, TK Sundar, S Thakur, CP Engel, J Sindermann, H Junge, K Karbwang, J Bryceson, ADM Berman, JD TI Efficacy and tolerability of miltefosine for childhood visceral leishmaniasis in India SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; DRUG-ADMINISTRATION APPROVAL; ORAL MILTEFOSINE; KALA-AZAR; HIV COINFECTION; DISEASE; BIHAR; TRIAL AB Miltefosine has previously been shown to cure 97% of cases of visceral leishmaniasis (VL) in Indian adults. Because approximately one-half of cases of VL occur in children, we evaluated use of the adult dosage of miltefosin (2.5 mg/kg per day for 28 days) in 80 Indian children (age, 2 - 11 years) with parasitologically confirmed infection in an open-label clinical trial. Clinical and parasitological parameters were reassessed at the end of treatment and 6 months later. One patient died of intercurrent pneumonia on day 6. The other 79 patients demonstrated no parasites after treatment, had marked clinical improvement, and were deemed initially cured. Three patients had relapse, and 1 patient was lost to follow-up. The final cure rate was 94% for all enrolled patients and 95% for evaluable patients. Side effects included mild-to-moderate vomiting or diarrhea (each in similar to25% of patients) and mild-to-moderate, transient elevations in the aspartate aminotransferase level during the early treatment phase (in 55%). This trial indicates that miltefosine is as effective and well tolerated in Indian children with VL as in adults and that it can be recommended as the first choice for treatment of childhood VL in India. C1 Rajendra Mem Res Inst Med Sci, Agamkuan, India. Balaji Utthan Sanastan, Patna, Bihar, India. Kalaazar Res Ctr, Muzaffarpur, India. Kalaazar Med Res Ctr, Muzaffarpur, India. Zentaris, Frankfurt, Germany. WHO, Special Program Res & Training Trop Dis, CH-1211 Geneva, Switzerland. London Sch Hyg & Trop Med, London WC1, England. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Bhattacharya, SK (reprint author), 6205 Poindexter Ln, Rockville, MD 20852 USA. NR 27 TC 86 Z9 89 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 15 PY 2004 VL 38 IS 2 BP 217 EP 221 DI 10.1086/380638 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 757NN UT WOS:000187568500005 PM 14699453 ER PT J AU Ahn, JI Lee, KH Shin, DM Shim, JW Lee, JS Chang, SY Lee, YS Brownstein, MJ Lee, SH Lee, YS AF Ahn, JI Lee, KH Shin, DM Shim, JW Lee, JS Chang, SY Lee, YS Brownstein, MJ Lee, SH Lee, YS TI Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons SO DEVELOPMENTAL BIOLOGY LA English DT Article DE ES cells; cDNA microarray; differentiation; neurogenesis ID WNT SIGNALING PATHWAY; PROGENITOR CELLS; GENE-EXPRESSION; DOPAMINERGIC-NEURONS; PRIMARY NEUROGENESIS; MICROARRAY ANALYSIS; LINEAGE SELECTION; SONIC HEDGEHOG; NEURAL STEM; IN-VITRO AB Neurogenesis is one of the most complex events in embryonic development. However, little information is available regarding the molecular events that occur during neurogenesis. To identify regulatory genes and underlying mechanisms involved in the differentiation of embryonic stem (ES) cells to neurons, gene expression profiling was performed using cDNA microarrays. In mouse ES cells, we compared the gene expression of each differentiated cell stage using a five-stage lineage selection method. Of 10,368 genes, 1633 (16%) known regulatory genes were differentially expressed at least 2-fold or greater at one or more stages. At stage 3, during which ES cells differentiate into neural stem cells, modulation of nearly 1000 genes was observed. Most of transcription factors (Otx2, Ebf-3, Ptx3, Sox4, 13, 18, engrailed, Irx2, Pax8, and Lim3), signaling molecules (Wnt, TGF, and Shh family members), and extracellular matrix/adhesion molecules (collagens, MAPs, and NCAM) were up-regulated. However, some genes which may play important roles in maintaining the pluripotency of ES cells (Kruppel-like factor 2, 4, 5, 9, myeloblast oncogene like2, ZFP 57, and Esg-1) were down-regulated. The many genes identified with this approach that are modulated during neurogenesis will facilitate studies of the mechanisms underlying ES cell differentiation, neural induction, and neurogenesis. (C) 2003 Elsevier Inc. All rights reserved. C1 Hanyang Univ, Coll Med, Dept Biochem, Seoul 133791, South Korea. Hanyang Univ, Grad Sch, Dept Environm Sci, Seoul 133791, South Korea. Hanyang Univ, Coll Med, Clin Invest Lab, Seoul 133791, South Korea. Hanyang Univ, Coll Sci & Technol, Dept Biochem & Mol Biol, Ansan 425791, South Korea. NIMH, Genet Lab, NIH, Cumberland, MD 21502 USA. RP Lee, YS (reprint author), Hanyang Univ, Coll Med, Dept Biochem, Seoul 133791, South Korea. EM yongsung@hanyang.ac.kr RI Lee, Jae-Seong/H-6013-2015 OI Lee, Jae-Seong/0000-0003-0944-5172 NR 50 TC 33 Z9 34 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2004 VL 265 IS 2 BP 491 EP 501 DI 10.1016/j.ydbio.2003.09.041 PG 11 WC Developmental Biology SC Developmental Biology GA 773NZ UT WOS:000188931000016 PM 14732407 ER PT J AU Sechi, S Oda, Y AF Sechi, S Oda, Y TI Quantitative proteomics using mass spectrometry SO DRUG DISCOVERY TODAY LA English DT Review ID CODED AFFINITY TAGS; 2-DIMENSIONAL GEL-ELECTROPHORESIS; RECEPTOR SIGNALING PATHWAYS; PROTEIN IDENTIFICATION; LIQUID-CHROMATOGRAPHY; ARRAY TECHNOLOGY; MESSENGER-RNA; GROWTH-FACTOR; PEPTIDES; EXPRESSION AB The use of stable isotopes as internal standards in mass spectrometry has opened a new era for quantitative proteomics. Depending on the point at which the label is introduced, most procedures can be classified as in vivo labeling, in vitro predigestion labeling or in vitro post-digestion labeling. In vivo labeling has been used for cells that can be grown in culture and has the advantage of being more accurate. The pre-digestion and post-digestion labeling procedures are suitable for all types of sample including human body fluids and biopsies. Several new mass spectrometric strategies mark significant achievements in determining relative protein concentrations and in quantifying post-translational modifications. However, further technology developments are needed for understanding the complexity of a dynamic system like the proteome. C1 NIDDKD, NIH, DHHS, Bethesda, MD 20892 USA. Eisai & Co Ltd, Lab Seeds Finding Technol, Tsukuba, Ibaraki 3002635, Japan. RP Sechi, S (reprint author), NIDDKD, NIH, DHHS, Bethesda, MD 20892 USA. EM Salvatore_Sechi@nih.gov NR 54 TC 3 Z9 3 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 JAN 15 PY 2004 VL 9 IS 2 SU S BP S41 EP S46 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 763JF UT WOS:000188081100006 PM 23573643 ER PT J AU Karginov, VA Robinson, TM Riemenschneider, J Golding, B Kennedy, M Shiloach, J Alibek, K AF Karginov, VA Robinson, TM Riemenschneider, J Golding, B Kennedy, M Shiloach, J Alibek, K TI Treatment of anthrax infection with combination of ciprofloxacin and antibodies to protective antigen of Bacillus anthracis SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE anthrax treatment; anti-protective antigen antibody; ciprofloxacin; mouse model ID DELIVERED POLYCLONAL ANTIBODIES; PSEUDOMONAS-AERUGINOSA; GUINEA-PIGS; IMMUNOGLOBULIN; PROPHYLAXIS; EFFICACY; SPORES; MICE AB Currently there is no effective treatment for inhalational anthrax beyond administration of antibiotics shortly after exposure. There is need for new, safe and effective treatments to supplement traditional antibiotic therapy. Our study was based on the premise that simultaneous inhibition of lethal toxin action with antibodies and blocking of bacterial growth by antibiotics will be beneficial for the treatment of anthrax. In this study, we tested the effects of a combination treatment using purified rabbit or sheep anti-protective antigen (PA) antibodies and the antibiotic ciprofloxacin in a rodent anthrax model. In mice infected with a dose of Bacillus anthracis Sterne strain corresponding to 10 LD50, antibiotic treatment with ciprofloxacin alone only cured 50% of infected animals. Administration of anti-PA IgG in combination with ciprofloxacin produced 90-100% survival. These data indicate that a combination of antibiotic/immunoglobulin therapy is more effective than antibiotic treatment alone in a rodent anthrax model. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Adv Biosyst Inc, Manassas, VA 20110 USA. CBER, FDA, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. George Mason Univ, Ctr Biodef, Manassas, VA USA. RP Karginov, VA (reprint author), Adv Biosyst Inc, 10900 Univ Blvd, Manassas, VA 20110 USA. EM vladimir.karginov@analex.com NR 14 TC 38 Z9 41 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD JAN 15 PY 2004 VL 40 IS 1 BP 71 EP 74 DI 10.1016/S0928-8244(03)00302-X PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 769FL UT WOS:000188615700009 PM 14734189 ER PT J AU Zhang, YQ Castellani, LW Sinal, CJ Gonzalez, FJ Edwards, PA AF Zhang, YQ Castellani, LW Sinal, CJ Gonzalez, FJ Edwards, PA TI Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR SO GENES & DEVELOPMENT LA English DT Article DE FXR; PGC-1 alpha; HNF4 alpha; PPAR gamma; triglyceride ID FARNESOID-X-RECEPTOR; FATTY-ACID SYNTHESIS; BILE-ACID; TRANSCRIPTIONAL COACTIVATOR; GENE-EXPRESSION; MITOCHONDRIAL BIOGENESIS; LIPID HOMEOSTASIS; ORPHAN RECEPTORS; PROTEIN GENE; TARGET GENES AB Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) has been shown to regulate adaptive thermogenesis and glucose metabolism. Here we show that PGC-1alpha regulates triglyceride metabolism through both farnesoid X receptor (FXR)-dependent and -independent pathways. PGC-1alpha increases FXR activity through two pathways: (1) it increases FXR mRNA levels by coactivation of PPARgamma and HNF4alpha to enhance FXR gene transcription; and (2) it interacts with the DNA-binding domain of FXR to enhance the transcription of FXR target genes. Ectopic expression of PGC-1alpha in murine primary hepatocytes reduces triglyceride secretion by a process that is dependent on the presence of FXR. Consistent with these in vitro studies, we demonstrate that fasting induces hepatic expression of PGC-1alpha and FXR and results in decreased plasma triglyceride levels in wild-type but not in FXR-null mice. Our data suggest that PGC-1alpha plays an important physiological role in maintaining energy homeostasis during fasting by decreasing triglyceride production/ secretion while it increases fatty acid beta-oxidation to meet energy needs. C1 Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 1X5, Canada. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Edwards, PA (reprint author), Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. EM pedwards@mednet.ucla.edu FU NHLBI NIH HHS [HL 30568, HL 68445, P01 HL030568, R01 HL068445] NR 49 TC 213 Z9 224 U1 2 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2004 VL 18 IS 2 BP 157 EP 169 DI 10.1101/gad.1138104 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 770GZ UT WOS:000188716000006 PM 14729567 ER PT J AU Maragakis, NJ Dietrich, J Wong, V Xue, HP Mayer-Proschel, M Rao, MS Rothstein, JD AF Maragakis, NJ Dietrich, J Wong, V Xue, HP Mayer-Proschel, M Rao, MS Rothstein, JD TI Glutamate transporter expression and function in human glial progenitors SO GLIA LA English DT Article DE astrocyte; transporter; development; human ID AMYOTROPHIC-LATERAL-SCLEROSIS; BONE MORPHOGENETIC PROTEINS; AMINO-ACID TRANSPORTER; HUMAN GLIOMA-CELLS; RAT-BRAIN; HUMAN CEREBELLUM; SYMPATHETIC NEURONS; PRECURSOR CELLS; NMDA RECEPTORS; NERVOUS-SYSTEM AB Glutamate is the major neurotransmitter of the brain, whose extracellular levels are tightly controlled by glutamate transporters. Five glutamate transporters in the human brain (EAAT1-5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: human glial restricted precursors (HGRP), human astrocyte precursors (HAPC), and early-differentiated astrocytes. EAAT 1, EAAT3, and EAAT4 are all expressed in GRPs with a subsequent upregulation of EAAT1 following differentiation of GRPs into GRP-derived astrocytes in the presence of bone morphogenic protein (BMP-4). This corresponds to a significant increase in the glutamate transport capacity of these cells. EAAT2, the transporter responsible for the bulk of glutamate transport in the adult brain, is not expressed as a full-length protein, nor does it appear to have functional significance (as determined by the EAAT2 inhibitor dihydrokainate) in these precursors. A splice variant of EAAT2, termed EAAT2b, does appear to be present in low levels, however. EAAT3 and EAAT4 expression is reduced as glial maturation progresses both in astrocyte precursors and early-differentiated astrocytes and is consistent with their role in adult tissues as primarily neuronal glutamate transporters. These human glial precursors offer several advantages as tools for understanding glial biology because they can be passaged extensively in the presence of mitogens, afford the potential to study the temporal changes in glutamate transporter expression in a tightly controlled fashion, and are cultured in the absence of neuronal coculture, allowing for the independent study of astroglial. biology. (C) 2003 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Dept Neurol & Neurosci, Baltimore, MD USA. Univ Rochester, Dept Biomed Genet, Rochester, NY USA. NIA, NIH, Baltimore, MD 21224 USA. RP Rothstein, JD (reprint author), Johns Hopkins Univ, Dept Neurol, Meyer 6-109,600 N Wolfe St, Baltimore, MD 21287 USA. EM jrothste@jhmi.edu RI rothstein, jeffrey/C-9470-2013 FU NINDS NIH HHS [NS 02131] NR 65 TC 47 Z9 48 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 0894-1491 J9 GLIA JI Glia PD JAN 15 PY 2004 VL 45 IS 2 BP 133 EP 143 DI 10.1002/glia.10310 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 770QL UT WOS:000188741700003 PM 14730707 ER PT J AU Jankowsky, JL Fadale, DJ Anderson, J Xu, GM Gonzales, V Jenkins, NA Copeland, NG Lee, MK Younkin, LH Wagner, SL Younkin, SG Borchelt, DR AF Jankowsky, JL Fadale, DJ Anderson, J Xu, GM Gonzales, V Jenkins, NA Copeland, NG Lee, MK Younkin, LH Wagner, SL Younkin, SG Borchelt, DR TI Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase SO HUMAN MOLECULAR GENETICS LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; COTTON WOOL PLAQUES; PRECURSOR-PROTEIN; TRANSGENIC MICE; A-BETA; CELL-SURFACE; TRANSMEMBRANE CLEAVAGE; SPASTIC PARAPARESIS; MISSENSE MUTATIONS; SENILE PLAQUES AB Amyloid precursor protein (APP) is endoproteolytically processed by BACE1 and gamma-secretase to release amyloid peptides (Abeta40 and 42) that aggregate to form senile plaques in the brains of patients with Alzheimer's disease (AD). The C-terminus of Abeta40/42 is generated by gamma-secretase, whose activity is dependent upon presenilin (PS 1 or 2). Missense mutations in PS1 (and PS2) occur in patients with early-onset familial AD (FAD), and previous studies in transgenic mice and cultured cell models demonstrated that FAD-PS1 variants shift the ratio of Abeta40 : 42 to favor Abeta42. One hypothesis to explain this outcome is that mutant PS alters the specificity of gamma-secretase to favor production of Abeta42 at the expense of Abeta40. To test this hypothesis in vivo, we studied Abeta40 and 42 levels in a series of transgenic mice that co-express the Swedish mutation of APP (APPswe) with two FAD-PS1 variants that differentially accelerate amyloid pathology in the brain. We demonstrate a direct correlation between the concentration of Abeta42 and the rate of amyloid deposition. We further show that the shift in Abeta42 : 40 ratios associated with the expression of FAD-PS1 variants is due to a specific elevation in the steady-state levels of Abeta42, while maintaining a constant level of Abeta40. These data suggest that PS1 variants do not simply alter the preferred cleavage site for gamma-secretase, but rather that they have more complex effects on the regulation of gamma-secretase and its access to substrates. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Merck Res Labs, La Jolla, CA 92037 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Neurogenet Inc, La Jolla, CA 92037 USA. RP Borchelt, DR (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 558 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM drbor@jhmi.edu RI Lee, Michael/D-9491-2013 OI Lee, Michael/0000-0001-5865-9682 FU NIA NIH HHS [1 P50 AG14248, 1 P01 AG-98-003]; NINDS NIH HHS [1 T32 NS07435] NR 80 TC 549 Z9 565 U1 2 U2 27 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2004 VL 13 IS 2 BP 159 EP 170 DI 10.1093/hmg/ddh019 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 762MM UT WOS:000187976200002 PM 14645205 ER PT J AU Anderson, WF Chu, KC Chang, S AF Anderson, WF Chu, KC Chang, S TI Inflammatory breast carcinoma: The sphinx of breast cancer research - In Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 NCI, Div Canc Prevent, Bethesda, MD USA. Ctr Canc Hlth Disparities, Bethesda, MD USA. Div Canc Prevent, Bethesda, MD USA. RP Anderson, WF (reprint author), NCI, Div Canc Prevent, Bethesda, MD USA. NR 6 TC 1 Z9 1 U1 0 U2 0 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 JAN 15 PY 2004 VL 22 IS 2 BP 383 EP 383 DI 10.1200/JCO.2004.99.183 PG 1 WC Oncology SC Oncology GA 764GT UT WOS:000188199700031 ER PT J AU Nakamura, K Kitani, A Fuss, I Pedersen, A Harada, N Nawata, H Strober, W AF Nakamura, K Kitani, A Fuss, I Pedersen, A Harada, N Nawata, H Strober, W TI TGF-beta 1 plays an important role in the mechanism of CD4(+)CD25(+) regulatory T cell activity in both humans and mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; IMMUNOLOGICAL SELF-TOLERANCE; LATENCY-ASSOCIATED PEPTIDE; AUTOIMMUNE-DISEASE; ANTIGEN 4; IN-VITRO; TGF-BETA; ACTIVATION; EXPRESSION; IMMUNOSUPPRESSION AB In previous studies, we have shown that murine CD4(+)CD25(+) regulatory T cells produce high levels of TGF-beta1 in a cell surface and/or secreted form, and blockade of such TGF-beta1 by anti-TGF-beta curtails the ability of these cells to suppress CD25(-) T cell proliferation and B cell Ig production in in vitro suppressor assays. In further support for the role of TGF-beta1 in suppression by CD4(+)CD25(+) T cells, we show in this study that another TGF-beta1-blocking molecule, recombinant latency-associated peptide of TGF-beta1 (rLAP), also reverses suppression by mouse CD4(+)CD25(+) T cells as well as their human counterparts, CD4(+)CD25(high) T cells. In addition, we show that CD25(-) T cells exposed to CD4(+)CD25(+) T cells in vitro manifest activation of Smad-2 and induction of CD103, the latter a TGF-beta-inducible surface integrin. In further studies, we show that while CD4(+)CD25(+) T cells from TGF-beta1 -deficient mice can suppress CD25(-) T cell proliferation in vitro, these cells do not protect recipient mice from colitis in the SCID transfer model in vivo, and, in addition, CD4(+)LAP(+), but not CD4(+)LAP(-) T cells from normal mice protect recipient mice from colitis in this model. Together, these studies demonstrate that TGF-beta1 produced by CD4(+)CD25(+) T cells is involved in the suppressor activity of these cells, particularly in their ability to regulate intestinal inflammation. C1 NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan. RP Strober, W (reprint author), NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bldg 10,Room 11N238,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 28 TC 466 Z9 508 U1 3 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2004 VL 172 IS 2 BP 834 EP 842 PG 9 WC Immunology SC Immunology GA 762WM UT WOS:000188005200012 PM 14707053 ER PT J AU Ortaldo, JR Young, HA Winkler-Pickett, RT Bere, EW Murphy, WJ Wiltrout, RH AF Ortaldo, JR Young, HA Winkler-Pickett, RT Bere, EW Murphy, WJ Wiltrout, RH TI Dissociation of NKT stimulation, cytokine induction, and NK activation in vivo by the use of distinct TCR-binding ceramides SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KILLER T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DEPENDENT DIABETES-MELLITUS; ALPHA-GALACTOSYLCERAMIDE; INTERFERON-GAMMA; NOD MICE; PREVENTS; EXPANSION; DEATH AB NKT and NK cells are important immune regulatory cells. The only efficient means to selectively stimulate NKT cells in vivo is alpha-galactosyleeramide (alphaGalCer). However, alphaGalCer effectively stimulates and then diminishes the number of detectable NKT cells. It also exhibits a potent, indirect ability to activate NK cells. We have now discovered another ceramide compound, beta-galactosylceramide (betaGalCer) (C12), that efficiently diminishes the number of detectable mouse NKT cells in vivo without inducing significant cytokine expression or activation of NK cells. Binding studies using CD1d tetramers loaded with betaGalCer (C12) demonstrated significant but lower intensity binding to NKT cells when compared with alphaGalCer, but both ceramides were equally efficient in reducing the number of NKT cells. However, betaGalCer (C12), in contrast to alphaGalCer, failed to increase NK cell size, number, and cytolytic activity. Also in contrast to alphaGalCer, betaGalCer (C12) is a poor inducer of IFN-gamma, TNF-alpha, GM-CSF, and IL-4 gene expression. These qualitative differences in NKT perturbation/NK activation have important implications for delineating the unique in vivo roles of NKT vs NK cells. Thus, aGalCer (which triggers NKT cells and activates NK cells) efficiently increases the resistance to allogeneic bone marrow transplantation while betaGalCer (C12) (which triggers NKT cells but does not activate NK cells) fails to enhance bone marrow graft rejection. Our results show betaGalCer (C12) can effectively discriminate between NKT-and NK-mediated responses in vivo. These results indicate the use of different TCR-binding ceramides can provide a unique approach for understanding the intricate immunoregulatory contributions of these two cell types. The Journal of Immunology, 2004, 172: 943-953. C1 NCI, Canc Res Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. RP Ortaldo, JR (reprint author), NCI, Canc Res Ctr, Expt Immunol Lab, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM ortaldo@mail.ncifcrf.gov RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 FU NCI NIH HHS [N01 CO 12400] NR 28 TC 76 Z9 79 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 JAN 15 PY 2004 VL 172 IS 2 BP 943 EP 953 PG 11 WC Immunology SC Immunology GA 762WM UT WOS:000188005200026 PM 14707067 ER PT J AU Kilmon, MA Shelburne, AE Chan-Li, Y Holmes, KL Conrad, DH AF Kilmon, MA Shelburne, AE Chan-Li, Y Holmes, KL Conrad, DH TI CD23 trimers are preassociated on the cell surface even in the absence of its ligand, IgE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LOW-AFFINITY RECEPTOR; FC-EPSILON-RII; ANTI-CD23 MONOCLONAL-ANTIBODIES; GREEN FLUORESCENT PROTEIN; RESONANCE ENERGY-TRANSFER; HOUSE-DUST MITE; B-CELLS; LYMPHOCYTES-B; CYSTEINE PROTEASE; BINDING AB Allergic disease is mediated by high levels of allergen-specific IgE. IgE binding to CD23, the low affinity receptor for IgE, results in a negative feedback signal leading to a decrease in IgE production. Previous studies have shown that CD23 associates as an oligomer and that cooperative binding of at least two lectin domains is required for high affinity IgE binding to CD23. We have previously shown that cooperative binding is required for regulation of IgE production. This study describes the production of several mAbs that bind the stalk region of murine CD23. One of the Abs, 19G5, inhibited the IgE/CD23 interaction at 37degreesC, but not at VC. Analysis of the binding properties of these Abs revealed that CD23 dissociates at high temperatures, such as 37degreesC; however, the N terminus is constitutively associated, indicating partial, rather than complete, dissociation. A novel finding was that the stalk region, previously thought to mediate trimer association, was not required for oligomerization. These data reveal important information about the structure of CD23 that may be useful in modulating IgE production. C1 Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA. NIAID, Flow Cytometry Sect, NIH, Bethesda, MD 20892 USA. RP Conrad, DH (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, Box 980678,MCV Stn, Richmond, VA 23298 USA. EM dconrad@hsc.vcu.edu FU NIAID NIH HHS [AI 07407, AI 18697, AI 44163] NR 50 TC 21 Z9 22 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 JAN 15 PY 2004 VL 172 IS 2 BP 1065 EP 1073 PG 9 WC Immunology SC Immunology GA 762WM UT WOS:000188005200039 PM 14707080 ER PT J AU Feng, CG Collazo-Custodio, CM Eckhaus, M Hieny, S Belkaid, Y Elkins, K Jankovic, D Taylor, GA Sher, A AF Feng, CG Collazo-Custodio, CM Eckhaus, M Hieny, S Belkaid, Y Elkins, K Jankovic, D Taylor, GA Sher, A TI Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; INDUCIBLY EXPRESSED GTPASE; INTERFERON-GAMMA; IFN-GAMMA; AVIUM INFECTION; TUBERCULOSIS INFECTION; T-CELLS; RESISTANCE; APOPTOSIS; IDENTIFICATION AB Although IFN-gamma is essential for host control of mycobacterial infection, the mechanisms by which the cytokine restricts pathogen growth are only partially understood. LRG-47 is an IFN-inducible GTP-binding protein previously shown to be required for IFN-gamma-dependent host resistance to acute Listeria monocytogenes and Toxoplasma gondii infections. To examine the role of LRG-47 in control of mycobacterial infection, LRG-47(-/-) and wild-type mice were infected with Mycobacterium avium, and host responses were analyzed. LRG-47 protein was strongly induced in livers of infected wild-type animals in an IFN-gamma-dependent manner. LRG-47(-/-) mice were unable to control bacterial replication, but survived the acute phase, succumbing 11-16 wk postinfection. IFN-gamma-primed, bone marrow-derived macrophages from LRG-47(-/-) and wild-type animals produced equivalent levels of TNF and NO upon M. avium infection in vitro and developed similar intracellular bacterial loads. In addition, priming for IFN-gamma production was observed in T cells isolated from infected LRG-47(-/-) mice. Importantly, however, mycobacterial granulomas in LRG-47(-/-) mice showed a marked lymphocyte deficiency. Further examination of these animals revealed a profound systemic lymphopenia and anemia triggered by infection. As LRG47(-/-) T lymphocytes were found to both survive and confer resistance to M. avium in recipient recombinase-activating gene-2(-/-) mice, the defect in cellular response and bacterial control in LRG-47(-/-) mice may also depend on a factor(s) expressed in a nonlymphocyte compartment. These findings establish a role for LRG-47 in host control of mycobacteria and demonstrate that in the context of the IFN-gamma response to persistent infection, LRG-47 can have downstream regulatory effects on lymphocyte survival. The Journal of Immunology, 2004, 172: 1163-1168. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Lab Mycobacterial Dis & Cellular Immun, Rockville, MD 20852 USA. Duke Univ, Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC 27710 USA. Duke Univ, Vet Affairs Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Duke Univ, Vet Affairs Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Vet Affairs Med Ctr, Dept Immunol, Durham, NC 27710 USA. RP Feng, CG (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, Room 6148,Bldg 50,50 S Dr, Bethesda, MD 20892 USA. EM cfeng@niaid.niti.gov NR 33 TC 83 Z9 90 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2004 VL 172 IS 2 BP 1163 EP 1168 PG 6 WC Immunology SC Immunology GA 762WM UT WOS:000188005200051 PM 14707092 ER PT J AU Smith, JD Miller, LH AF Smith, JD Miller, LH TI Infected erythrocyte binding to hyaluronic acid and malaria in pregnant women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID CHONDROITIN SULFATE-A; PLASMODIUM-FALCIPARUM; HUMAN PLACENTA; ADHESION; ANTIBODIES; RECEPTOR; GAMMA; CYTOADHERENCE; PROTEOGLYCANS; INTERFERON C1 Seattle Biomed Res Inst, Seattle, WA 98109 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD USA. RP Smith, JD (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA. EM joe.smith@sbri.org FU NIAID NIH HHS [AI47953] NR 40 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2004 VL 189 IS 2 BP 165 EP 168 DI 10.1086/380976 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 763QD UT WOS:000188097900001 PM 14722879 ER PT J AU Carroll, FI Zhang, L Mascarella, SW Navarro, HA Rothman, RB Cantrell, BE Zimmerman, DM Thomas, JB AF Carroll, FI Zhang, L Mascarella, SW Navarro, HA Rothman, RB Cantrell, BE Zimmerman, DM Thomas, JB TI Discovery of the first N-substituted 4 beta-methyl-5-(3-hydroxyphenyl) morphan to possess highly potent and selective opioid delta receptor antagonist activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID INVERSE AGONIST; G-PROTEIN; BINDING; CELLS; MICE; GROWTH AB A structurally novel opioid 6 receptor selective antagonist has been identified. This compound, (+)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]-non-7-yl-(1- phenyl-1-cyclopentane)carboxamide [(+)-KF4, (+)4], showed a K-e value of 0.15 nM in the [S-35]GTPgammaS functional assay. (+)-KF4 is also a 6 inverse agonist with an IC50 value of 1.8 nM. To our knowledge, this is the first potent and selective 6 opioid receptor antagonist from the 5-phenylmorphan class of opioids. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Clin Psychopharmacol Sect, IRP, NIH, Baltimore, MD 21224 USA. Eli Lilly & Co, Lilly Res Lab, Lilly Corp Ctr, Indianapolis, IN 46285 USA. RP Carroll, FI (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. EM fic@rti.org OI Mascarella, Wayne/0000-0003-0092-8178 FU NIDA NIH HHS [DA09045] NR 33 TC 11 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 15 PY 2004 VL 47 IS 2 BP 281 EP 284 DI 10.1021/jm030419a PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 761XW UT WOS:000187941600001 PM 14711299 ER PT J AU Lu, Q Yang, YT Chen, CS Davis, M Byrd, JC Etherton, MR Umar, A Chen, CS AF Lu, Q Yang, YT Chen, CS Davis, M Byrd, JC Etherton, MR Umar, A Chen, CS TI Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL CONTROL; CELL-DIFFERENTIATION; CYCLIC TETRAPEPTIDE; TRICHOSTATIN; CANCER; PROLIFERATION; TRAPOXIN; INDUCERS; ANALOGS; BUTYRATE AB Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition. C1 Ohio State Univ, Div Med Chem & Pharmacognosy, Coll Pharm, Columbus, OH 43210 USA. Ohio State Univ, Div Hematol Oncol, Arthur James Comprehens Canc Ctr, Columbus, OH 43210 USA. NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. RP Chen, CS (reprint author), Ohio State Univ, Div Med Chem & Pharmacognosy, Coll Pharm, Pks Hall,Rm 336,500 W 12th Ave, Columbus, OH 43210 USA. EM chen.844@osu.edu RI lu, qiang/C-7764-2009; Chen, Chang-Shi/B-9251-2009 FU NCI NIH HHS [CA94829] NR 28 TC 69 Z9 71 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 15 PY 2004 VL 47 IS 2 BP 467 EP 474 DI 10.1021/jm0303655 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 761XW UT WOS:000187941600018 PM 14711316 ER PT J AU Smith, A Wang, J Cheng, CM Zhou, J Weickert, CS Bondy, CA AF Smith, A Wang, J Cheng, CM Zhou, J Weickert, CS Bondy, CA TI High-level expression of Dok-1 in neurons of the primate prefrontal cortex and hippocampus SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE prefrontal cortex; neuron; IGF1 receptor; hippocampus; pyramidal neuron; rhesus monkey ID RASGAP-BINDING PROTEIN; GAP-ASSOCIATED PROTEIN; TYROSINE PHOSPHORYLATION; DOCKING PROTEIN; ACTIVATING PROTEIN; P62(DOK); RECEPTOR; KINASE; CELLS; P210(BCR-ABL) AB The docking protein p62Dok-1 (Dok-1) has a central role in cell signaling mediated by a wide range of protein tyrosine kinases, including intrinsic membrane kinases, such as the insulin-like growth factor-1 (IGF-1) receptor. To elucidate potential IGF signaling mechanisms, we used DNA array technology to investigate novel kinase targets expressed in the primate dorsolateral prefrontal cortex (DLPFC ). Dok-1 transcripts were among the most abundant found in this structure. Because Dok-1 expression has not been characterized in brain, we evaluated its expression pattern using immunoblotting, in situ hybridization, and immunohistochemistry in the rhesus monkey prefrontal cortex and hippocampal formation. Dok-1 antibodies identified a 62-kDa band in lysates from the DLPFC , consistent with the known size for Dok-1. In situ hybridization showed that Dok-1 mRNA was expressed in all layers of the DLPFC and in all neuronal subregions of the hippocampal formation. Immunohistochemical analysis showed Dok-1 immunoreactivity concentrated in pyramidal neurons of cortical layers IV-V and throughout Ammon's horn and in granule neurons of the dentate gyrus. Dok-1 expression was also identified in endothelial cells of cerebral blood vessels. These expression patterns are very similar to those of the IGF-1 receptor and suggest that Dok-1 could be among the downstream targets of IGF signaling in areas of the primate brain involved in learning and memory. Published 2003 Wiley-Liss, Inc.(+) C1 Natl Inst Child Hlth, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), Natl Inst Child Hlth, Dev Endocrinol Branch, NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011 NR 21 TC 10 Z9 10 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN 15 PY 2004 VL 75 IS 2 BP 218 EP 224 DI 10.1002/jnr.10842 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 761WU UT WOS:000187939100007 PM 14705142 ER PT J AU Kalra, A Hummer, G Garde, S AF Kalra, A Hummer, G Garde, S TI Methane partitioning and transport in hydrated carbon nanotubes SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SINGLE-FILE PORES; MOLECULAR-DYNAMICS; TEMPERATURE-DEPENDENCE; FLUID EXPERIMENTS; WATER TRANSPORT; LIQUID WATER; CHANNEL; PHASE; NANOCAPILLARITY; CAPILLARITY AB The well defined shape and size of carbon nanotubes (CNTs) makes them attractive candidates for theoretical and experimental studies of various nanoscopic phenomena such as protection and confinement of molecular species as well as transport of molecules through their interior pores. Here we investigate solute partitioning and transport using molecular dynamics simulations of CNTs in mixtures of hydrophobic solutes and water. The hydrophobic pores of CNTs provide a favorable environment for partitioning of hydrophobic solutes. We find that the transfer of a methane molecule from aqueous solution into the CNT interior is favored by about 16 kJ/mol of free energy. In 50 molecular dynamics simulations, we observe that methane molecules replace water molecules initially inside the nanotubes, and completely fill their interior channels over a nanosecond time scale. Once filled with methane molecules, the nanotubes are able to transport methane from one end to the other through successive methane uptake and release events at the tube ends. We estimate a net rate of transport of about 11 methane molecules per nanotube and nanosecond for a 1 mol/L methane concentration gradient. This concentration-corrected rate of methane transport even exceeds that of water through nanotubes (similar to1 per nanosecond at a 1 mol/L osmotic gradient). These results have implications for the design of molecule-selective CNT devices that may act through mechanisms similar to those of biological transmembrane channels. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Rensselaer Polytech Inst, Howard P Isermann Dept Chem & Biol Engn, Troy, NY 12180 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM hummer@helix.nih.gov; gardes@rpi.edu RI Garde, Shekhar/C-3060-2008; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 52 TC 39 Z9 40 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 15 PY 2004 VL 108 IS 2 BP 544 EP 549 DI 10.1021/jp035828x PG 6 WC Chemistry, Physical SC Chemistry GA 762CA UT WOS:000187951700007 ER PT J AU Comeau, DC Wilbur, WJ AF Comeau, DC Wilbur, WJ TI Non-word identification or spell checking without a dictionary SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY LA English DT Article ID TEXT AB MEDLINE(R) is a collection of more than 12 million references and abstracts covering recent life science literature. With its continued growth and cutting-edge terminology, spell-checking with a traditional lexicon based approach requires significant additional manual follow-up. In this work, an internal corpus based context quality rating a, frequency, and simple misspelling transformations are used to rank words from most likely to be misspellings to least likely. Eleven-point average precisions of 0.891 have been achieved within a class of 42,340 all alphabetic words having an a score less than 10. Our models predict that 16,274 or 38% of these words are misspellings. Based on test data, this result has a recall of 79% and a precision of 86%. In other words, spell checking can be done by statistics instead of with a dictionary. As an application we examine the time history of low a words in MEDLINE(R) titles and abstracts. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Comeau, DC (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,Room N611S,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 17 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1532-2882 J9 J AM SOC INF SCI TEC JI J. Am. Soc. Inf. Sci. Technol. PD JAN 15 PY 2004 VL 55 IS 2 BP 169 EP 177 DI 10.1002/asi.10354 PG 9 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 754UX UT WOS:000187351000007 ER PT J AU Leon-Sarmiento, FE Mendoza, E Torres-Hillera, M Pinto, N Prada, J Silva, CA Vera, SJ Castillo, E Valderrama, V Prada, DG Bayona-Prieto, J Garcia, I AF Leon-Sarmiento, FE Mendoza, E Torres-Hillera, M Pinto, N Prada, J Silva, CA Vera, SJ Castillo, E Valderrama, V Prada, DG Bayona-Prieto, J Garcia, I TI Trypanosoma cruzi-associated cerebrovascular disease: a case-control study in Eastern Colombia SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE cerebrovascular disease; Tryanosoma cruzi; Colombia; case-control studies; neurotrypanosomiasis; neuroepidemiology ID CHRONIC CHAGAS-DISEASE; NITRIC-OXIDE; STROKE; INFECTION AB Trypanosoma cruzi infection is a common cause of cardiopathy in South America leading it eventually to an established stroke; however, the association between T. cruzi infection itself and cerebrovascular disease is still unknown. We did a case-control study at Eastern Colombia and found that T. cruzi infection was more frequent and statistically significant in stroke cases (24.4%) than controls (1.9%), (Chi square: 21.72; OR: 16.13; 95% confidence interval (CI): 3.64-71.4; p < 0.00001). After removing the seropositive patients with cardiological abnormalities, the significance still remained by multivariate analysis (p < 0.05). This is the first case-control study that demonstrated a significant link between this infection and symptomatic cerebrovascular disease, mainly ischemic, regardless of cardiac abnormalities. Therefore, we recommend that patients with stroke must be screened for T. cruzi infection if they currently live or have lived in places where this parasite is considered endemic. (C) 2003 Elsevier B.V. All rights reserved. C1 Santander Univ, Sch Med, Bucaramanga, Colombia. Univ Pamplona, Pamplona, Colombia. Neuro Net Inst Colombiano Neurociencias Aplicades, Bucaramanga, Colombia. Univ Francisco Paula Santander, Cucuta, Colombia. Pontificia Univ Javeriana, Bogota, Colombia. Inst Nacl Salud, Bogota, Colombia. RP Leon-Sarmiento, FE (reprint author), NINDS, Med Neurol Branch, NIH, Bldg 10-5N 234,10 Ctr Dr, Bethesda, MD 20892 USA. EM leonf@ninds.nih.gov RI Prada-Arismendy, Jeanette/N-5696-2016 OI Prada-Arismendy, Jeanette/0000-0002-4779-1941 NR 21 TC 23 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JAN 15 PY 2004 VL 217 IS 1 BP 61 EP 64 DI 10.1016/j,jns.2003.08.015 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 764KN UT WOS:000188206200011 PM 14675611 ER PT J AU Hanada, K Yewdell, JW Yang, JC AF Hanada, K Yewdell, JW Yang, JC TI Immune recognition of a human renal cancer antigen through post-translational protein splicing SO NATURE LA English DT Article ID ENDOPLASMIC-RETICULUM; PROCESSING PATHWAY; CONCANAVALIN-A; LIGATION; CYTOSOL AB Cytotoxic T lymphocytes (CTLs) detect and destroy cells displaying class I molecules of the major histocompatibility complex (MHC) that present oligopeptides derived from aberrant self or foreign proteins. Most class I peptide ligands are created from proteins that are degraded by proteasomes and transported, by the transporter associated with antigen processing, from the cytosol into the endoplasmic reticulum, where peptides bind MHC class I molecules and are conveyed to the cell surface(1). C2 CTLs, cloned from human CTLs infiltrating a renal cell carcinoma, kill cancer cells overexpressing fibroblast growth factor-5 (FGF-5)(2). Here we show that C2 cells recognize human leukocyte antigen-A3 MHC class I molecules presenting a nine-residue FGF-5 peptide generated by protein splicing. This process, previously described strictly in plants(3) and unicellular organisms(4), entails post-translational excision of a polypeptide segment followed by ligation of the newly liberated carboxyterminal and amino-terminal residues. The occurrence of protein splicing in vertebrates has important implications for the complexity of the vertebrate proteome and for the immune recognition of self and foreign peptides. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hanada, K (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM khanada@nih.gov; jamesyang@mail.nih.gov RI Hanada, Ken-ichi/A-4642-2008; yewdell, jyewdell@nih.gov/A-1702-2012; Hanada, Ken-ichi/L-2481-2013 OI Hanada, Ken-ichi/0000-0003-2959-1257 NR 13 TC 140 Z9 146 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 15 PY 2004 VL 427 IS 6971 BP 252 EP 256 DI 10.1038/nature02240 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 763HE UT WOS:000188068100045 PM 14724640 ER PT J AU George, DT Rawlings, RR Williams, WA Phillips, MJ Fong, G Kerich, M Momenan, R Umhau, JC Hommer, D AF George, DT Rawlings, RR Williams, WA Phillips, MJ Fong, G Kerich, M Momenan, R Umhau, JC Hommer, D TI A select group of perpetrators of domestic violence: evidence of decreased metabolism in the right hypothalamus and reduced relationships between cortical/subcortical brain structures in position emission tomography SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE amygdala; fear-induced aggression; fight or flight; alcoholism ID ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; CEREBRAL GLUCOSE-METABOLISM; MIDBRAIN CENTRAL GRAY; ORBITOFRONTAL CORTEX; BASAL GANGLIA; AFFECTIVE DEFENSE; HUMAN AMYGDALA; CORTICAL PROJECTIONS; CONDITIONED FEAR AB In an earlier study, we reported that some perpetrators of domestic violence evidenced exaggerated fear-related responses to the panicogenic agent sodium lactate. In the current study, we employed positron emission tomography (PET) to investigate our hypothesis that there are differences in the neural structures and/or pathways that mediate and control the expression of fear-induced aggression in perpetrators of domestic violence. Regional cerebral glucose metabolism was measured in eight male perpetrators of domestic violence who fulfilled DSM-III-R criteria for alcohol dependence (DV-ALC), 11 male participants who fulfilled DSM-III-R criteria for alcohol dependence and had no history of interpersonal aggression (ALC) and 10 healthy male participants who did not fulfill criteria for any DSM-III-R axis I diagnosis and had no history of interpersonal aggression (M). DV-ALC had a significantly lower mean glucose uptake in the right hypothalamus compared to ALC and HCS. Correlations were performed between measures of glucose utilization in the brain structures involved in fear-induced aggression. The comparison of DV-ALC to HCS and to ALC differed in six and seven comparisons, respectively, involving various cortical and subcortical structures. HCS and ALC differed between the left thalamus and the left posterior orbitofrontal cortex. These PET findings show that some perpetrators of domestic violence differ from control participants in showing lower metabolism in the right hypothalamus and decreased correlations between cortical and subcortical brain structures. A possible psychological covariate of these changes in regional activity might be fear-induced aggression, but this hypothesis should be examined in larger study groups that undergo provocation during imaging. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NIAAA, DICBR, Clin Studies Lab, Bethesda, MD 20892 USA. RP George, DT (reprint author), NIAAA, DICBR, Clin Studies Lab, 10 Ctr Dr,MSC-1610,Bldg 10,Room 6S-240, Bethesda, MD 20892 USA. EM tedg@niaaa.nih.gov NR 84 TC 39 Z9 41 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JAN 15 PY 2004 VL 130 IS 1 BP 11 EP 25 DI 10.1016/S0925-4927(03)00105-7 PG 15 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 802AV UT WOS:000220137300002 PM 14972365 ER PT J AU Amundson, SA Bittner, M Fornace, AJ AF Amundson, SA Bittner, M Fornace, AJ TI Ionizing radiation as a model DNA-damaging agent: Global gene expression responses SO TOXICOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Toxicology-Society CY MAR 30-APR 02, 2003 CL EDINBURGH, SCOTLAND SP British Toxic Soc C1 NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 2 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 15 PY 2004 VL 194 IS 3 BP 200 EP 200 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 764WA UT WOS:000188227900007 ER PT J AU Negishi, M Moore, R Sueyoshi, T AF Negishi, M Moore, R Sueyoshi, T TI Transient humanization of nuclear receptor CAR in mouse liver SO TOXICOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Toxicology-Society CY MAR 30-APR 02, 2003 CL EDINBURGH, SCOTLAND SP British Toxic Soc C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 15 PY 2004 VL 194 IS 3 BP 217 EP 217 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 764WA UT WOS:000188227900030 ER PT J AU Toyoshiba, H Walker, NJ Bailer, AJ Portier, CJ AF Toyoshiba, H Walker, NJ Bailer, AJ Portier, CJ TI Evaluation of toxic equivalency factors for induction of cytochromes P450 CYP1A1 and CYP1A2 enzyme activity by dioxin-like compounds SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE TCDD; PCB; PeCDF; hill equations; Median Effective Doses (ED50) ID POLYCHLORINATED-BIPHENYLS PCBS; RISK-ASSESSMENT; RESPONSE RELATIONSHIPS; SUBCHRONIC EXPOSURE; FACTORS TEFS; POTENCY; DIBENZOFURANS; 2,3,7,8-TCDD; MIXTURES; PCDDS AB The toxic equivalency factor (TEF) method has been used to characterize the toxicity of human mixtures of dioxin-like compounds and is being considered for use with other classes of potentially toxic agents. TEFs are estimated by examining the relative potencies of the various congeners for a series of biological and toxicological effects. In this paper, we consider changes in activity for two enzymes, cytochrome P450 1A1 (CYP1A1)-associated 7-ethoxyresorufin-O-deethylase (EROD) and CYP1A2 -associated acetanilide-4-hydroxylase (A4H) activity, resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) or a mixture of these agents. The ratio of median effective dose (ED50) is one way to estimate the relative potencies, especially for gene expression and protein endpoints. ED50's were estimated with a nonlinear regression model in which dose-related changes in mean responses are described by a Hill function. ED50's along with other model parameters were estimated by fitting this model to a given data set. Significant differences in estimated model parameters were tested by likelihood ratio methods. The estimated parameters indicated that congener-specific dose-response shapes were significantly different, that additivity failed for these congeners, and that the ratios of ED50's did not predict the response seen for the mixture. These results indicate that for some biological responses, the use of a single relative potency factor (RPF) is not appropriate for the comparison of the dose response behavior of different dioxin-like congeners. Published by Elsevier Inc. C1 NIEHS, Lab Computat Biol, Res Triangle Pk, NC 27709 USA. Miami Univ, Dept Math & Stat, Ctr Environm Toxicol & Stat, Oxford, OH 45056 USA. RP Portier, CJ (reprint author), NIEHS, Lab Computat Biol, 111 TW Alexander Dr,Bldg 101,Room A-330, Res Triangle Pk, NC 27709 USA. EM portier@niehs.nih.gov RI Portier, Christopher/A-3160-2010; Walker, Nigel/D-6583-2012 OI Portier, Christopher/0000-0002-0954-0279; Walker, Nigel/0000-0002-9111-6855 NR 27 TC 52 Z9 52 U1 1 U2 5 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 JAN 15 PY 2004 VL 194 IS 2 BP 156 EP 168 DI 10.1016/j.taap.2003.09.015 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 777AV UT WOS:000189152600006 PM 14736496 ER PT J AU Rockett, JC Burczynski, ME Fornace, AJ Herrmann, PC Krawetz, SA Dix, DJ AF Rockett, JC Burczynski, ME Fornace, AJ Herrmann, PC Krawetz, SA Dix, DJ TI Surrogate tissue analysis: monitoring toxicant exposure and health status of inaccessible tissues through the analysis of accessible tissues and cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE disease states; genomics; hair follicles; ionizing radiation; proteomics; peripheral blood lymphocytes; peripheral blood mononuclear cells; renal cell carcinoma; sperm; STA, surrogate tissue analysis; toxicity ID GENE-EXPRESSION SIGNATURES; IONIZING-RADIATION; PREDICT SURVIVAL; STRESS GENES; PROFILES; CANCER; BLOOD; DISEASE; IDENTIFICATION; MICROARRAY AB Genomics and proteomics have made it possible to define molecular physiology in exquisite detail, when tissues are accessible for sampling. However, many tissues are not accessible for human diagnostic evaluations or experimental studies, creating the need for surrogates that afford insight into exposures and effects in such tissues. Surrogate tissue analysis (STA) incorporating contemporary genomic and proteomic technologies may be useful in determining toxicant exposure and effect, or disease state, in target tissues at the pre- or early clinical stage. We present here a discussion of STA based on presentations given at the Society of Toxicology's 2003 annual meeting's "Innovations in Applied Toxicology" symposium. Speakers at the symposium (Box 1) discussed various potential applications of STA, including the use of peripheral blood lymphocytes (PBLs) as a source of genetic biomarkers to monitor radiation exposure; the use of gene expression analysis of PBLs and hair follicles as a means to monitor the impact of toxicants on inaccessible organs; the characterization of disease-associated gene signatures in peripheral blood mononuclear cells (PBMCs) of renal cell carcinoma (RCC) patients; the use of sperm RNA to determine genetic and environmental effects on sperm development in the testis; and the use of serum protein profiles to monitor the development and progression of various cancers. Also discussed are some of the challenges that must be overcome if the utility of STA is to be proven, and thus permit researchers to move this concept from the laboratory to the clinical environment. Published by Elsevier Inc. C1 US EPA, Off Res & Dev, Natl Hlth & Environm Res Lab, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. Wyeth Ayerst Res, Discovery Med, Andover, MA 01810 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Wayne State Univ, Reprod Med Network, NICHD, Inst Comp Sci, Detroit, MI 48201 USA. RP Rockett, JC (reprint author), US EPA, Off Res & Dev, Natl Hlth & Environm Res Lab, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. EM rockett.john@epa.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NICHD NIH HHS [HD36512] NR 45 TC 48 Z9 51 U1 0 U2 4 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 JAN 15 PY 2004 VL 194 IS 2 BP 189 EP 199 DI 10.1016/j.taap.2003.09.005 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 777AV UT WOS:000189152600009 PM 14736499 ER PT J AU Mutskov, V Felsenfeld, G AF Mutskov, V Felsenfeld, G TI Silencing of transgene transcription precedes methylation of promoter DNA and histone H3 lysine 9 SO EMBO JOURNAL LA English DT Article DE chromatin; DNA methylation; histone acetylation; histone methylation; transgene silencing ID TUMOR-SUPPRESSOR GENE; HETEROCHROMATIN FORMATION; NEUROSPORA-CRASSA; CANCER-CELLS; ACTIVE GENES; GLOBIN GENE; METHYLTRANSFERASE; ACETYLATION; CHROMATIN; ELEMENT AB Transgenes stably integrated into cells or animals in many cases are silenced rapidly, probably under the influence of surrounding endogenous condensed chromatin. This gene silencing correlates with repressed chromatin structure marked by histone hypoacetylation, loss of methylation at H3 lysine 4, increase of histone H3 lysine 9 methylation as well as CpG DNA methylation at the promoter. However, the order and the timing of these modifications and their impact on transcription inactivation are less well understood. To determine the temporal order of these events, we examined a model system consisting of a transgenic cassette stably integrated in chicken erythroid cells. We found that histone H3 and H4 hypoacetylation and loss of methylation at H3 lysine 4 all occurred during the same window of time as transgene inactivation in both multicopy and low-copy-number lines. These results indicate that these histone modifications were the primary events in gene silencing. We show that the kinetics of silencing exclude histone H3 K9 and promoter DNA methylation as the primary causative events in our transgene system. C1 NIDDK, NIH, LMB, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDK, NIH, LMB, Bldg 5,Room 212,5 Ctr Dr,MSC 0540, Bethesda, MD 20892 USA. EM gary.felsendfeld@nih.gov NR 48 TC 198 Z9 208 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 14 PY 2004 VL 23 IS 1 BP 138 EP 149 DI 10.1038/sj.emboj.7600013 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 773JW UT WOS:000188921500014 PM 14685282 ER PT J AU Burstein, E Ganesh, L Dick, RD van de Sluis, B Wilkinson, JC Klomp, LWJ Wijmenga, C Brewer, GJ Nabel, GJ Duckett, CS AF Burstein, E Ganesh, L Dick, RD van de Sluis, B Wilkinson, JC Klomp, LWJ Wijmenga, C Brewer, GJ Nabel, GJ Duckett, CS TI A novel role for XIAP in copper homeostasis through regulation of MURR1 SO EMBO JOURNAL LA English DT Article DE copper; MURR1; ubiquitin; XIAP ID SERINE-PROTEASE OMI/HTRA2; ANTI-APOPTOTIC ACTIVITY; X-LINKED INHIBITOR; FACTOR-KAPPA-B; STRUCTURAL BASIS; CELL-DEATH; CASPASE INHIBITION; ENDOTHELIAL-CELLS; LIGASE ACTIVITY; CYTOCHROME-C AB XIAP is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases. Here we demonstrate a novel role for XIAP in the control of intracellular copper levels. XIAP was found to interact with MURR1, a factor recently implicated in copper homeostasis. XIAP binds to MURR1 in a manner that is distinct from that utilized by XIAP to bind caspases, and consistent with this, MURR1 did not affect the antiapoptotic properties of XIAP. However, cells and tissues derived from Xiap-deficient mice were found to contain reduced copper levels, while suppression of MURR1 resulted in increased intracellular copper in cultured cells. Consistent with these opposing effects, XIAP was observed to negatively regulate MURR1 protein levels by the formation of K48 polyubiquitin chains on MURR1 that promote its degradation. These findings represent the first described phenotypic alteration in Xiap-deficient mice and demonstrate that XIAP can function through MURR1 to regulate copper homeostasis. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Biomed Genet, Ann Arbor, MI USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Duckett, CS (reprint author), Univ Michigan, Sch Med, Dept Pathol, Room 5315,1301 Catherine Rd, Ann Arbor, MI 48109 USA. EM colind@umich.edu RI Wijmenga, Cisca/D-2173-2009; Burstein, Ezra/B-7247-2016; OI Burstein, Ezra/0000-0003-4341-6367; Wijmenga, Cisca/0000-0002-5635-1614 FU NCI NIH HHS [T32 CA009676, T32 CA09676]; NIDDK NIH HHS [5P30 DK34933-18, P30 DK034933] NR 48 TC 141 Z9 146 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 14 PY 2004 VL 23 IS 1 BP 244 EP 254 DI 10.1038/sj.emboj.7600031 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 773JW UT WOS:000188921500024 PM 14685266 ER PT J AU Ding, L Perkel, DJ AF Ding, L Perkel, DJ TI Long-term potentiation in an avian basal ganglia nucleus essential for vocal learning SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synaptic plasticity; song learning; songbird; basal ganglia; dopamine; glutamate ID ADULT ZEBRA FINCHES; SYNAPTIC-TRANSMISSION; AUDITORY-FEEDBACK; SPINY NEURONS; RECEPTOR ACTIVATION; FOREBRAIN NUCLEUS; RAT NEOSTRIATUM; NMDA RECEPTOR; IN-VITRO; SONG AB Vocal learning in songbirds provides an excellent model for sensorimotor learning in vertebrates, with an accessible, well-defined behavior and discrete neural substrate. The rich behavioral plasticity exhibited by songbirds, however, contrasts starkly with the scarcity of candidate cellular mechanisms. Here, we report for the first time on an activity-dependent form of synaptic plasticity in area X, a component of the song system required for song learning and song maintenance. In slice preparations of zebra finch area X, pairing of high-frequency presynaptic stimulation with postsynaptic depolarization induces Hebbian long-term potentiation (LTP) of the glutamatergic inputs to spiny neurons. This form of LTP requires activation of NMDA receptors and D1-like dopamine receptors. In addition, LTP is observed in birds as young as 47 d after hatching and also in adult birds but not in younger birds, providing evidence of developmental regulation of the onset of synaptic plasticity. These properties make this form of LTP the best known candidate mechanism for reinforcement-based vocal learning in juveniles and song maintenance in adult birds. C1 Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA. Univ Washington, Dept Biol, Seattle, WA 98195 USA. Univ Washington, Dept Otolaryngol, Seattle, WA 98195 USA. RP Ding, L (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. EM dingl@nei.nih.gov FU NIDCD NIH HHS [P30 DC04661]; NIMH NIH HHS [R01-MH56646, R01-MH0066128] NR 55 TC 52 Z9 56 U1 1 U2 5 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 JAN 14 PY 2004 VL 24 IS 2 BP 488 EP 494 DI 10.1523/JNEUROSCI.4358-03.2004 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 763QE UT WOS:000188098000020 PM 14724247 ER PT J AU O'Neil-Cabello, E Bryce, DL Nikonowicz, EP Bax, A AF O'Neil-Cabello, E Bryce, DL Nikonowicz, EP Bax, A TI Measurement of five dipolar couplings from a single 3D NMR multiplet applied to the study of RNA dynamics SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEINS; CONSTANTS; CONFORMATION; SPECTROSCOPY; INFORMATION; ASSIGNMENT C1 NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. EM bax@nih.gov RI Bryce, David/A-3534-2008 OI Bryce, David/0000-0001-9989-796X FU PHS HHS [08280] NR 19 TC 26 Z9 26 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 14 PY 2004 VL 126 IS 1 BP 66 EP 67 DI 10.1021/ja038314k PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 761ZM UT WOS:000187945400033 PM 14709062 ER PT J AU Pfeffer, B Becerra, S Borst, D Wong, P AF Pfeffer, B Becerra, S Borst, D Wong, P TI Expression of transthyretin and retinol binding protein mRNAs and secretion of transthyretin by cultured monkey retinal pigment epithelium SO MOLECULAR VISION LA English DT Article; Proceedings Paper CT 7th Annual Vision Research Conference CY 2003 CL FT LAUDERDALE, FLORIDA ID RAT EYE; VITAMIN-A; CHOROID-PLEXUS; SERUM-ALBUMIN; IN-VIVO; GENE; CELLS; AMYLOIDOSIS; RELEASE; PLASMA AB Purpose: To document the expression of mRNA for transthyretin (TTR) and retinol binding protein (RBP) in native and cultured Rhesus monkey retinal pigmented epithelium (RPE); to compare mRNA transcripts for these two proteins expressed in RPE with those found in whole monkey liver and brain; to demonstrate the secretion of TTR by RPE during short-term maintenance in a protein-free, defined medium, as a manifestation of the differentiated state of these cells in vitro. Methods: Total RNA was isolated from cultured RPE in first passage, after incubation for eight days in defined, protein-free medium. Conditioned medium was collected for western analysis at this time. Total RNA was also extracted from RPE/choroid freshly dissected from monkey eyes. Using cDNA probes for human TTR and RBP, northern analysis was performed on the total RNA from fresh and cultured RPE samples, together with poly(A+) mRNA purified from monkey liver and brain. Results: Conditioned medium from RPE yielded TTR protein of the expected monomer subunit molecular size. The TTR secreted de novo from the cultured cells was detectable in the absence of biosynthetic labeling. With the exception of some extremely low abundance transcripts expressed in cultured RPE, all samples contained a single 900 bp transcript for TTR. Based on relative amounts of actual message, RPE ranks higher than liver in abundance of TTR mRNA. In contrast, both native monkey RPE and cultured RPE cells expressed comparatively low levels of mRNA for RBP. All samples displayed a single RBP mRNA transcript at 1100 bp. Conclusions: Our results indicate that TTR is a significant gene product of the RPE, and may be considered as a marker for a differentiated phenotype for these cells in culture. There is increased recognition of various forms of ocular pathology associated with mutations or other malfunctions involving TTR and RBP, warranting a greater understanding of mechanisms of transcriptional and translational control for these two proteins. C1 Bausch & Lomb Inc, Res, Rochester, NY 14609 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. RP Pfeffer, B (reprint author), Bausch & Lomb Inc, Res, 1400 N Goodman St, Rochester, NY 14609 USA. EM Bruce_Pfeffer@bausch.com NR 56 TC 15 Z9 16 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JAN 14 PY 2004 VL 10 IS 3 BP 23 EP 30 PG 8 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 765KK UT WOS:000188278700001 PM 14737066 ER PT J AU Chen, J He, YZ Simons, S AF Chen, J He, YZ Simons, S TI Structure/activity relationships for GMEB-2: The second member of the glucocorticoid modulatory element-binding complex SO BIOCHEMISTRY LA English DT Article ID RECEPTOR TRANSACTIVATION; INDUCTION PROPERTIES; TRANSCRIPTION FACTOR; KDWK FAMILY; RESPONSE ELEMENT; AGONIST ACTIVITY; IN-VIVO; N-COR; PROTEIN; GENE AB The position of the dose-response curve of agonist complexes of glucocorticoid receptors (GRs), and the partial agonist activity of GR-antagonist complexes, can be modulated by two proteins (GMEB-1 and -2), which bind as oligomers to a DNA element that is called a glucocorticoid modulatory element, or GME. This element is active when located upstream of the glucocorticoid response element that controls the expression of a reporter gene. Here, we report the structure/activity relationships of GMEB-2 and compare them to our previous findings for GMEB-1. Most of the activities of GMEB-2, such as homo- and heterooligomerization, binding to GR and to CBP, DNA binding, and modulation of the above GR transcriptional properties, require large regions of the protein. Only the intrinsic transactivation activity could be localized to a small region of the protein. These studies shed light on the mechanism of action of GMEB-2 and further support our previous conclusion that the ability of factors to modulate the position of the dose-response curve, and the partial agonist activity, of GR complexes is unrelated to effects on the total levels of GR-induced gene expression. These studies also identify regions of GMEB-2 possessing yet unidentified properties that are critical for several activities. Finally, as the domain organization of GMEB-2 and -1 is extremely similar, we conclude that the quantitative differences in activities derive from variations in amino acid sequence rather than more global features of protein structure. C1 US Dept HHS, Steroid Hormones Sect, NIDDK, LMCB,NIH, Bethesda, MD USA. RP Simons, S (reprint author), US Dept HHS, Steroid Hormones Sect, NIDDK, LMCB,NIH, Bethesda, MD USA. NR 45 TC 6 Z9 7 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 JAN 13 PY 2004 VL 43 IS 1 BP 245 EP 255 DI 10.1021/bi035311b PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 761HE UT WOS:000187894800028 PM 14705952 ER PT J AU Bushara, KO Goldstein, SR Grimes, GJ Burstein, AH Hallett, M AF Bushara, KO Goldstein, SR Grimes, GJ Burstein, AH Hallett, M TI Pilot trial of 1-octanol in essential tremor SO NEUROLOGY LA English DT Article ID HARMALINE-INDUCED TREMOR AB 1-Octanol (an 8-C alcohol currently used as a food-flavoring agent) is known to inhibit tremor in essential tremor (ET) animal models at a much lower dose than ethyl alcohol. The authors conducted a randomized, placebo-controlled pilot trial of a single oral dose of 1 mg/kg of 1-octanol in 12 patients with ET. No significant side effects or signs of intoxication were observed. 1-Octanol significantly decreased tremor amplitude for up to 90 minutes. The results suggest 1-octanol as a well-tolerated and safe potential treatment for ET. Further trials are warranted. C1 Minneapolis Vet Affairs Med Ctr, Serv Neurol, Minneapolis, MN 55417 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Bushara, KO (reprint author), Minneapolis Vet Affairs Med Ctr, Neurol Serv 127, 1 Vet Dr, Minneapolis, MN 55417 USA. EM busha001@umn.edu NR 9 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 13 PY 2004 VL 62 IS 1 BP 122 EP 124 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 762XR UT WOS:000188010100032 PM 14718713 ER PT J AU Mentink-Kane, MM Cheever, AW Thompson, RW Hari, DM Kabatereine, NB Vennervald, BJ Ouma, JH Mwatha, JK Jones, FM Donaldson, DD Grusby, MJ Dunne, DW Wynn, TA AF Mentink-Kane, MM Cheever, AW Thompson, RW Hari, DM Kabatereine, NB Vennervald, BJ Ouma, JH Mwatha, JK Jones, FM Donaldson, DD Grusby, MJ Dunne, DW Wynn, TA TI IL-13 receptor alpha 2 down-modulates granulomatous inflammation and prolongs host survival in schistosomiasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MANSONI INFECTION; IL-13 RECEPTOR; MICE; INTERLEUKIN-13; PATHOLOGY; RESPONSES; FIBROSIS; DISTINCT; VACCINE; DISEASE AB An important feature of many chronic parasitic infections is the ability of the invading pathogen and host to establish a compromise, which ensures successful parasitism without killing the infected host. For many helminth infections, down-modulating the immune response is critical because persistent inflammation can become more damaging to the host than the invading pathogen itself. Such is the case with schistosomiasis mansoni, where chronic granulomatous inflammation in the liver causes portal hypertension, porto-pulmonary shunting, bleeding from collateral bypass vessels, and eventual death if not suppressed effectively. CD4(+) T helper type 2 cells (Th2) (secreting IL-4, IL-5, and IL-13) characterize the host response after Schistosoma mansoni infection, and recent studies have identified IL-13 as the principal mediator of hepatic fibrosis. Here, we show that the IL-13 receptor alpha 2 (IL-13Ralpha2) is a critical mediator of immune down-modulation, identifying the receptor as a life-sustaining off signal for chronic and pernicious inflammation in schistosomiasis. C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. Minist Hlth, Vector Control Div, Kampala, Uganda. Danish Bilharziasis Lab, DK-2920 Charlottenlund, Denmark. Minist Hlth, Div Vector Borne Infect Dis, Nairobi, Kenya. Kenya Govt Med Res Ctr, Nairobi, Kenya. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. Wyeth Res, Dept Resp Dis, Cambridge, MA 02140 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bldg 50,Room 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; OI Dunne, David/0000-0002-8940-9886 FU NIAID NIH HHS [AI4040171] NR 24 TC 90 Z9 96 U1 0 U2 7 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 JAN 13 PY 2004 VL 101 IS 2 BP 586 EP 590 DI 10.1073/pnas.0305064101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 764MJ UT WOS:000188210400032 PM 14699044 ER PT J AU Cho, JY Guo, CS Torello, M Lunstrum, GP Iwata, T Deng, CX Horton, WA AF Cho, JY Guo, CS Torello, M Lunstrum, GP Iwata, T Deng, CX Horton, WA TI Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; DOCKING-PROTEIN FRS2-ALPHA; THANATOPHORIC DYSPLASIA; TYROSINE KINASES; CHONDROCYTE PROLIFERATION; INTRACELLULAR-TRANSPORT; STAT ACTIVATION; DOWN-REGULATION; POINT MUTATION; FGF RECEPTORS AB Mutations of fibroblast growth factor receptor 3 (FGFR3) are responsible for achondroplasia (ACH) and related dwarfing conditions in humans. The pathogenesis involves constitutive activation of FGFR3, which inhibits proliferation and differentiation of growth plate chondrocytes. Here we report that activating mutations in FGFR3 increase the stability of the receptor. Our results suggest that the mutations disrupt c-Cbl-mediated ubiquitination that serves as a targeting signal for lysosomal degradation and termination of receptor signaling. The defect allows diversion of actively signaling receptors from lysosomes to a recycling pathway where their survival is prolonged, and, as a result, their signaling capacity is increased. The lysosomal targeting defect is additive to other mechanisms proposed to explain the pathogenesis of ACH. C1 Shriners Hosp Children, Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Horton, WA (reprint author), Shriners Hosp Children, Res Ctr, 3101 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM wah@shcc.org RI deng, chuxia/N-6713-2016 NR 51 TC 84 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 JAN 13 PY 2004 VL 101 IS 2 BP 609 EP 614 DI 10.1073/pnas.2237184100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 764MJ UT WOS:000188210400036 PM 14699054 ER PT J AU Dang, Q Chen, JB Unutmaz, D Coffin, JM Pathak, VK Powell, D KewalRamani, VN Maldarelli, F Hu, WS AF Dang, Q Chen, JB Unutmaz, D Coffin, JM Pathak, VK Powell, D KewalRamani, VN Maldarelli, F Hu, WS TI Nonrandom HIV-1 infection and double infection via direct and cell-mediated pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL SHUTTLE VECTOR; SINGLE REPLICATION CYCLE; ROUS SARCOMA VIRUS; IN-VIVO; GENETIC-RECOMBINATION; MUTATIONAL HOTSPOTS; TYPE-1 TRANSMISSION; DENDRITIC CELLS; BROAD-SPECTRUM AB Cells infected with two related retroviruses can generate heterozygous virions, which are the precursors of recombinant proviruses. Although many studies have focused on the frequencies and mechanisms of retroviral recombination, little is known about the dynamics of double infection. To examine this issue, viruses generated from two HIV-11 vectors containing different markers were mixed together, and were used to infect target cells. The numbers of cells expressing none, one, or both markers were measured and were used to calculate whether double infection occurred at frequencies expected from random infection events. We found that double infection occurred significantly more frequently than predicted from random distribution; increased rates of double infection were observed in both a T cell line and primary activated CD4(+) T cells. In addition to direct virus infection, we also examined the nature of cell-mediated HIV-1 double infection. Increased double infection was observed in all experiments regardless of whether a cell line or primary human dendritic cells were used for capture and transmission of HIV-1. Therefore, our results indicate that HIV-1 double infection occurs more frequently than it would at random in both direct and cell-mediated HIV-1 infections. To our knowledge, this is the first direct evidence of nonrandom double infection in HIV-1. Frequent double HIV-1 infections in infected individuals would allow the generation of recombinant viruses that could then affect their pathogenesis and evolution. C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. NCI, Data Management Serv, Ft Detrick, MD 21702 USA. W Virginia Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. Vanderbilt Univ, Dept Microbiol & Immunol, Nashville, TN USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 336, Ft Detrick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU NIAID NIH HHS [R01 AI049131, R01-AI49131] NR 36 TC 60 Z9 61 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 JAN 13 PY 2004 VL 101 IS 2 BP 632 EP 637 DI 10.1073/pnas.0307636100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 764MJ UT WOS:000188210400040 PM 14707263 ER PT J AU Lacey, JV Sherman, ME Hartge, P Schatzkin, A Schairer, C AF Lacey, JV Sherman, ME Hartge, P Schatzkin, A Schairer, C TI Medication use and risk of ovarian carcinoma: A prospective study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE acetaminophen; ovarian cancer; tranquilizers; diuretics; aspirin ID PROGESTIN REPLACEMENT THERAPY; CANCER RISK; UNITED-STATES; BREAST-CANCER; MENOPAUSAL ESTROGEN; ASPIRIN; WOMEN; ANTIDEPRESSANTS; PARACETAMOL; NSAIDS AB Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis. In a prospective study, we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed questionnaires through 1998 to update risk factor information and identify incident ovarian cancers. The 1992-95 questionnaire ascertained medication use, including duration and frequency of use for aspirin, acetaminophen, other nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine-receptor antagonists. A Poisson regression analysis generated rate ratios (RRs) and 95% confidence intervals (CIs) for the 31,364 women who were at risk of ovarian cancer and responded to the questionnaire that queried regular medication use. One hundred sixteen women developed ovarian cancer during follow-up. None of the anti-inflammatory medications was associated with ovarian cancer, but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5) and the RR for more than S years of regular "other NSAID" use was 2.0 (95% CI 0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6, 95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to increase risk. In our study, neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer. Potential associations with histamine-receptor antagonists may warrant further study. (C) 2003 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, DHHS,NIH, Rockville, MD 20852 USA. RP Lacey, JV (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, DHHS,NIH, 6120 Execut Blvd,MSC 7234, Rockville, MD 20852 USA. NR 30 TC 40 Z9 42 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 10 PY 2004 VL 108 IS 2 BP 281 EP 286 DI 10.1002/ijc.11538 PG 6 WC Oncology SC Oncology GA 753GX UT WOS:000187224600018 PM 14639616 ER PT J AU Mathew, A Peters, U Chatterjee, N Kulldorff, M Sinha, R AF Mathew, A Peters, U Chatterjee, N Kulldorff, M Sinha, R TI Fat, fiber, fruits, vegetables, and risk of colorectal adenomas SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colorectal adenoma; unsaturated fat; saturated fat; red meat fat; white meat fat; fiber; fruits and vegetables ID PARTIALLY HYDROGENATED OILS; DIETARY FIBER; COLON-CANCER; PROSPECTIVE COHORT; CONSUMPTION; POLYPS; MEAT; MEN; EPIDEMIOLOGY; WOMEN AB A case-control study was conducted at the National Naval Medical Center (Maryland, USA) from 1994 to 1996 to investigate the possible association between dietary factors and colorectal adenomas. Cases (n = 239) were subjects diagnosed with adenomas (146 new and 93 recurrent) by sigmoidoscopy or colonoscopy. Those with no evidence of adenomas found by sigmoidoscopy were recruited as controls (n = 228). Dietary variables, assessed by a 100-item food frequency questionnaire, were analyzed by the logistic regression model, which was adjusted for age, gender and total energy intake. Variables of fat intake were further adjusted for red meat intake. An increased risk of 7% [odds ratio (OR): 1.07; 95% confidence interval (95% Cl): 0.94-1.22] per 5% energy/day from total fat was observed. Every additional 5% unit of oleic acid intake/day significantly increased the adenoma risk by 115% (OR: 2.15; 95% CI: 1.05-4.39). Red meat fat increased the risk by 20% (OR: 1.20; 95% CI: 0.71-2.04), and white meat fat decreased the risk by 67% (OR: 0.33; 95% CI: 0.19-0.95) for every additional 5% unit of respective intake/day. Risk decreased by 41% (OR: 039; 95% CI: 0.41-0.86) for every additional 5% unit of fiber intake/day. Vegetable [OR per 100 g of vegetable intake/day: 0.83, 95% CI: 0.67-1.04] and fruit (OR per 100 g of fruit intake/day: 0.92, 95% CI: 0.82-1.03) intake showed an inverse association, and the results are suggestive of an association with the risk for adenomas. In conclusion, a strong positive association between oleic acid intake and colorectal adenoma risk was observed. This is likely to be an indicator of "unhealthy" food (meat, dairy, margarine, mayonnaise, sweet baked food) consumption in this population. Increased intake of dietary fiber was associated with a moderately decreased risk of adenomas. (C) 2003 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Connecticut, Sch Med, Div Epidemiol & Biostat, Farmington, CT USA. RP Mathew, A (reprint author), Reg Canc Ctr, Div Epidemiol & Clin Res, Trivandrum 695011, Kerala, India. RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kulldorff, Martin/0000-0002-5284-2993 NR 40 TC 46 Z9 48 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 10 PY 2004 VL 108 IS 2 BP 287 EP 292 DI 10.1002/ijc.10984 PG 6 WC Oncology SC Oncology GA 753GX UT WOS:000187224600019 PM 14639617 ER PT J AU Orchard, JA Ibbotson, RE Davis, Z Wiestner, A Rosenwald, A Thomas, PW Hamblin, TJ Staudt, LM Oscier, DG AF Orchard, JA Ibbotson, RE Davis, Z Wiestner, A Rosenwald, A Thomas, PW Hamblin, TJ Staudt, LM Oscier, DG TI ZAP-70 expression and prognosis in chronic lymphocytic leukaemia SO LANCET LA English DT Article ID VARIABLE-REGION MUTATIONS; PROTEIN-TYROSINE KINASE; CD38 EXPRESSION; GENE-EXPRESSION; B-CELLS; PHENOTYPE AB Background Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease; many patients never need treatment, whereas some have poor outcomes. New treatments, which can induce complete remissions, allow patients with poor outlook to be treated while they are still asymptomatic. Whether or not the IgVH gene is mutated is the best predictor of clinical outcome, but this assay is unsuited to the routine laboratory. The gene coding for ZAP-70, a tyrosine kinase protein normally expressed in T and NK cells, has been shown by gene-expression profiling to be differentially expressed between patients with mutated and unmutated IgVH genes. We assessed whether ZAP-70 could be used as a prognostic marker in CLL. Methods We developed a flow cytometry assay for ZAP-70 protein expression and investigated its concordance with ZAP-70 mRNA expression, IgVH gene mutational status, and clinical outcome in 167 patients with CLL. Findings We showed high concordance between ZAP-70 protein expression and IgVH gene mutations. 108 patients (65%) had mutated IgVH genes and were ZAP-70 negative; 46 (28%) had unmutated IgVH genes and were ZAP-70 positive. Findings were discordant in 13 patients: six (4%) had mutated IgVH genes but were ZAP-70 positive, and seven (4%) had unmutated IgVH genes and were ZAP-70 negative. Expression of mRNA showed 97% concordance with ZAP-70 protein. Median survival was 24.4 years (95% CI 15.1-33.8) in ZAP-70 negative patients and 9.3 years (7.0-11.5) in those who were ZAP-70 positive (hazard ratio 5.5, 2.8-10.8). Interpretation ZAP-70 protein, which can be measured by flow cytometry in the general laboratory, is a reliable prognostic marker in CLL, equivalent to that of IgVH gene mutational status. C1 Royal Bournemouth Hosp, Dept Haematol, Bournemouth BH7 7DW, Dorset, England. NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Poole Hosp, Dorset Res & Dev Support Unit, Poole, Dorset, England. RP Oscier, DG (reprint author), Royal Bournemouth Hosp, Dept Haematol, Bournemouth BH7 7DW, Dorset, England. OI Thomas, Peter/0000-0003-2478-4324 NR 30 TC 390 Z9 409 U1 1 U2 9 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 10 PY 2004 VL 363 IS 9403 BP 105 EP 111 DI 10.1016/S0140-6736(03)15260-9 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 761WV UT WOS:000187939200007 PM 14726163 ER PT J AU Murphy, E AF Murphy, E TI Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection SO CIRCULATION RESEARCH LA English DT Review DE apoptosis; cardioprotection; signaling pathways; preconditioning; mitochondria ID PROTEIN-KINASE-C; K-ATP CHANNELS; INDUCED DELAYED CARDIOPROTECTION; SENSITIVE POTASSIUM CHANNELS; MYOCARDIAL-ISCHEMIA-REPERFUSION; PERMEABILITY TRANSITION PORE; NITRIC-OXIDE SYNTHASE; RABBIT HEART; RAT-HEART; CARDIAC MITOCHONDRIA AB Cardioprotective mechanisms such as acute or early preconditioning activate several primary signaling pathways that seem to converge on mitochondrial targets, leading to altered cell metabolism and inhibition of apoptosis. Acute preconditioning leads to generation of agonists, which bind to G protein-coupled receptors, and initiates a signaling cascade that involves activation of phosphoinositide-3-kinase, endothelial NO synthase, protein kinase C, glycogen synthase kinase 3beta, mitogen-activated protein kinases, and other signaling pathways. Activation of these signaling pathways along with generation of reactive oxygen species leads to alterations in the activity of key mitochondrial proteins such as mitochondrial ATP-sensitive K+ channels, the mitochondrial permeability transition pore, and bcl-2 family members. Alterations in these mitochondrial proteins results in altered metabolism and inhibition of cell death, thus resulting in cardioprotection. C1 NIEHS, Lab Sirnal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Murphy, E (reprint author), Mail Drop F2-07,Box 12233, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov NR 118 TC 164 Z9 196 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JAN 9 PY 2004 VL 94 IS 1 BP 7 EP 16 DI 10.1161/01.RES.0000108082.76667.F4 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 761MC UT WOS:000187911700007 PM 14715531 ER PT J AU Colon, ML Qian, SY Vanderveer, D Bu, XR AF Colon, ML Qian, SY Vanderveer, D Bu, XR TI Chiral bimetallic complexes from chiral salen metal complexes and mercury (II) halides and acetates: the anionic groups interact with Cu(II) in apical position SO INORGANICA CHIMICA ACTA LA English DT Article DE chiral salen complexes; chiral bimetallic complexes; copper complexes; mercury complexes; EPR ID SCHIFF-BASE COMPLEXES; MOLECULAR-STRUCTURE; CRYSTAL-STRUCTURE; COPPER(II) COMPLEXES; EPOXIDATION; LIGANDS; SUBSTITUENTS; REACTIVITY; NICKEL(II); OXIDATION AB A series of chiral bimetallic complexes have been prepared containing both Cu(II) and Hg(11) metal centers. The complexes possess chiral salen ligands which host Cu(11) in the center of the cis-N2O2 chromophore and Hg(H) via two oxygen atoms of the chromophore. Halogen and acetate groups from mercury salts interact with the Cu(11) center. The X-ray crystallographic data of 11 reveals a short distance of (ClCu)-Cu-... (3.22-3.26 Angstrom). EPR study also discloses a strong interaction, in particular, of acetate group with Cu. (C) 2003 Published by Elsevier B.V. C1 Clark Atlanta Univ, Dept Chem, Atlanta, GA 30314 USA. NIEHS, Free Rad Metab Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA. RP Bu, XR (reprint author), Clark Atlanta Univ, Dept Chem, Atlanta, GA 30314 USA. EM xbu@cau.edu NR 41 TC 29 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0020-1693 J9 INORG CHIM ACTA JI Inorg. Chim. Acta PD JAN 9 PY 2004 VL 357 IS 1 BP 83 EP 88 DI 10.1016/S0020-1693(03)00426-2 PG 6 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 763BU UT WOS:000188050800011 ER PT J AU Qin, LY Liu, YX Wang, TG Wei, SJ Block, ML Wilson, B Liu, B Hong, JS AF Qin, LY Liu, YX Wang, TG Wei, SJ Block, ML Wilson, B Liu, B Hong, JS TI NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; NITRIC-OXIDE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; RESPIRATORY BURST; MESENCEPHALIC NEURONS; DOPAMINERGIC-NEURONS; SIGNAL-TRANSDUCTION; TETRAZOLIUM SALT; INTERFERON-GAMMA AB Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. We have previously reported that lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons is mediated by the release of proinflammatory factors from activated microglia. Here, we report the pivotal role of NADPH oxidase in inflammation-mediated neurotoxicity, where the LPS-induced loss of nigral dopaminergic neurons in vivo was significantly less pronounced in NADPH oxidase-deficient ( PHOX-/-) mice when compared with control (PHOX+/+) mice. Dopaminergic neurons in primary mensencephalic neuron-glia cultures from PHOX+/+ mice were significantly more sensitive to LPS- induced neurotoxicity in vitro when compared with PHOX-/- mice. Further, PHOX+/+ neuron-glia cultures chemically depleted of microglia failed to show dopaminergic neurotoxicity with the addition of LPS. Neuron-enriched cultures from both PHOX+/+ mice and PHOX-/- mice also failed to show any direct LPS- induced dopaminergic neurotoxicity. However, the addition of PHOX+/+ microglia to neuron-enriched cultures from either strain resulted in reinstatement of LPS- induced dopaminergic neurotoxicity, supporting the role of microglia as the primary source of NADPH oxidase-generated insult and neurotoxicity. Immunostaining for F4/80 in mensencephalic neuron-glia cultures revealed that PHOX-/- microglia failed to show activated morphology at 10 h, suggesting an important role of reactive oxygen species (ROS) generated from NADPH oxidase in the early activation of microglia. LPS also failed to elicit extracellular superoxide and produced low levels of intracellular ROS in microglia-enriched cultures from PHOX-/- mice. Gene expression and release of tumor necrosis factor alpha was much lower in PHOX-/- mice than in control PHOX-/- mice. Together, these results demonstrate the dual neurotoxic functions of microglial NADPH oxidase: 1) the production of extracellular ROS that is toxic to dopamine neurons and 2) the amplification of proinflammatory gene expression and associated neurotoxicity. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. RP Qin, LY (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. RI liu, Bin/A-7695-2009 NR 50 TC 347 Z9 364 U1 2 U2 20 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 JAN 9 PY 2004 VL 279 IS 2 BP 1415 EP 1421 DI 10.1074/jbc.M307657200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 759DJ UT WOS:000187722800071 PM 14578353 ER PT J AU Basu, NK Ciotti, M Hwang, MS Kole, L Mitra, PS Cho, JW Owens, IS AF Basu, NK Ciotti, M Hwang, MS Kole, L Mitra, PS Cho, JW Owens, IS TI Differential and special properties of the major human UGT1-encoded gastrointestinal UDP-glucuronosyltransferases enhance potential to control chemical uptake SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLON-CANCER; I PATIENT; BILIRUBIN; GLUCURONIDATION; EXPRESSION; CURCUMIN; PHENOL; LIVER; IDENTIFICATION; TRANSFERASE AB UDP- glucuronosyltransferase (UGT) isozymes detoxify metabolites, drugs, toxins, and environmental chemicals via conjugation to glucuronic acid. Based on the extended UGT1 locus combined with Northern blot analysis and in situ hybridization, we determined the distribution of UGT1A1 and UGT1A7 through UGT1A10 mRNAs and found them for the first time segmentally distributed in the mucosal epithelia layer of the gastrointestinal tract. Biochemically, recombinant isozymes exhibited pH optima of 5.5, 6.4, 7.6, 8.5, and/or a broad pH range, and activities were found to be unaffected or progressively inhibited by increasing substrate concentrations after attaining V-max for certain chemicals. Under different optimal conditions, all exhibited wide substrate selections for dietary and environmentally associated chemicals. Evidence also suggests tandem effects of isozymes in the time for completion of reactions when comparing short- and long-term incubations. Moreover, treatment of colon cells with certain diet-associated constituents, curcumin and nordihydroguaiaretic acid, reversibly targets UGTs causing inhibition without affecting protein levels; there is no direct inhibition of control UGT using curcumin as substrate in the in vitro assay. In summary, we demonstrate that UGTs are located in gastrointestinal mucosa, have vast overlapping activities under differential optimal conditions, and exhibit marked sensitivity to certain dietary substrates/constituents, representing a first comprehensive study of critical properties concerning glucuronidating isozymes in alimentary tissues. Additionally, the highly dynamic, complex, and variable properties necessarily impact absorption of ingested chemicals and therapeutic drugs. C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Owens, IS (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S-241, Bethesda, MD 20892 USA. NR 34 TC 61 Z9 65 U1 0 U2 9 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 JAN 9 PY 2004 VL 279 IS 2 BP 1429 EP 1441 DI 10.1074/jbc.M306439200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 759DJ UT WOS:000187722800073 PM 14557274 ER PT J AU Williams, DC Cai, ML Clore, GM AF Williams, DC Cai, ML Clore, GM TI Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1 center dot Sox2 center dot Hoxb1-DNA ternary transcription factor complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYL TRANSFER COMPLEX; LIQUID-CRYSTALLINE PHASE; NMR STRUCTURES; DIPOLAR COUPLINGS; BIOLOGICAL MACROMOLECULES; PROTEIN COMPLEXES; CROSS-VALIDATION; DNA COMPLEXES; MEAN FORCE; DOMAIN AB The Oct and Sox transcription factors control many different aspects of neural development and embryogenesis, often binding to adjacent sites on DNA, and interacting with one another through their DNA binding domains to regulate transcription synergistically. Oct proteins contain two DNA binding domains (POUS and POUHD) connected by a flexible linker, which interact with DNA in a bipartite manner. Residual dipolar coupling measurements on the binary Oct1.DNA complex reveal that the two domains are characterized by distinct alignment tensors in both phage pf1 and polyethylene glycol/hexanol liquid crystalline media. We show that this difference is due to a fast microscopic dissociation/association process involving alternative binding modes for the weaker binding POUS domain in the binary complex. Upon binding of Sox2 to an adjacent site in the Hoxb1 regulatory element, all components of the ternary Oct1.Sox2.DNA complex share a single alignment tensor. Thus ternary complex formation increases the site-specific affinity of Oct1 for DNA by effectively locking the POUS domain in a single orientation on the DNA. The solution NMR structure of the ternary 42 kDa Oct1.Sox2.Hoxb1.DNA complex, determined by novel procedures based on orientational restraints from dipolar couplings and conjoined rigid body/torsion angle dynamics, reveals that Sox2 and POUS interact through a predominantly hydrophobic interface, surrounded by a ring of electrostatic interactions. These observations suggest a mechanism of combinatorial control involving direct protein-protein interactions on the DNA whereby Oct1 in conjunction with a co-interacting transcription factor provide cell-specific transcription regulation. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm B1-301, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 50 TC 102 Z9 103 U1 1 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 JAN 9 PY 2004 VL 279 IS 2 BP 1449 EP 1457 DI 10.1074/jbc.M309790200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 759DJ UT WOS:000187722800075 PM 14559893 ER PT J AU Thompson, J Hess, S Pikis, A AF Thompson, J Hess, S Pikis, A TI Genes malh and pagl of Clostridium acetobutylicum ATCC 824 encode NAD(+)- and Mn2+-dependent phospho-alpha-glucosidase(s) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACID-SEQUENCE SIMILARITIES; ALPHA-GLUCOSIDASE AGLA; GLUCOSYL-D-FRUCTOSES; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; FUSOBACTERIUM-MORTIFERUM; KLEBSIELLA-PNEUMONIAE; GLYCOSYL HYDROLASES; FAMILY 4; PHOSPHOTRANSFERASE SYSTEM AB The genome of Clostridium acetobutylicum 824 contains two genes encoding NAD(+), Mn2+, and dithiothreitol-dependent phospho-alpha-glucosidases that can be assigned to family 4 of the glycosylhydrolase superfamily. The two genes, designated malh ((mal) under bar tose 6-phosphate (h) under bar ydrolase) and pagl ((p) under bar hospho-(α-gl) under bar ucosidase), respectively, reside in separate operons that also encode proteins of the phosphoenolpyruvate-dependent: sugar phosphotransferase system. C. acetobutylicum grows on a variety of alpha-linked glucosides, including maltose, methyl-alpha-D-glucoside, and the five isomers of sucrose. In the presence of the requisite cofactors, extracts of these cells readily hydrolyzed the chromogenic substrate p-nitrophenyl-alpha-D-glucopyranoside 6-phosphate, but whether hydrolysis reflected expression of enzymes encoded by the malh or pagl genes was not discernible by spectrophotometric analysis or polyacrylamide gel electrophoresis. Resolution of this question required the cloning of the malh and pagl genes, and subsequent high expression, purification, and characterization of maltose-6'-phosphate hydrolase (MalH) and phospho-alpha-glucosidase (PagL), respectively. MalH and PagL exhibit 50% residue identity, and in solution are tetramers comprising similar sized (similar to50 kDa) subunits. The two proteins cross-react with polyclonal rabbit antibody against phospho-alpha-glucosidase from Fusobacterium mortiferum. Purified MalH and PagL cleaved p-nitrophenyl-alpha-D-glucopyranoside 6-phosphate with comparable efficiency, but only MalH catalyzed the hydrolysis of disaccharide 6'-phosphates formed via the phosphoenolpyruvate-dependent: sugar phosphotransferase system. Importantly, analysis of the proteome of C. acetobutylicum 824 by electrospray ionization-mass spectrometry confirmed expression of MalH during growth on many alpha-glucosides tested. Site-directed changes C169S and D170N yielded full-length, but catalytically inactive MalH. Of the two putative operons, our findings suggest that only proteins encoded by the mal operon participate in the dissimilation of maltose and related O-alpha-linked glucosides by C. acetobutylicum 824. C1 NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Proteom & Mass Spectrometry Facil, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Thompson, J (reprint author), NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 528,Convent Dr,MSC-4350, Bethesda, MD 20892 USA. RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 NR 41 TC 21 Z9 24 U1 0 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 JAN 9 PY 2004 VL 279 IS 2 BP 1553 EP 1561 DI 10.1074/jbc.M310733200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 759DJ UT WOS:000187722800088 PM 14570887 ER PT J AU Contractor, RG Foran, CM Li, SF Willett, KL AF Contractor, RG Foran, CM Li, SF Willett, KL TI Evidence of gender- and tissue-specific promoter methylation and the potential for ethinylestradiol-induced changes in japanese medaka (Oryzias latipes) estrogen receptor and aromatase genes SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID MESSENGER-RNA EXPRESSION; SEWAGE-TREATMENT PLANT; ZEBRAFISH DANIO-RERIO; DNA METHYLATION; TELEOST FISH; HYPERGONADOTROPIC HYPOGONADISM; DEVELOPMENTAL EXPOSURE; MULTICYSTIC OVARIES; HERBICIDE ATRAZINE; BRAIN AB In order to explore the potential of DNA methylation to serve as a biomarker of toxicity, thus establishing a link between exposure to environmental contaminants and physiologically significant changes in gene expression, tissue- and gender-specific methylation patterns in the promoter regions of estrogen receptor (ER) and aromatase genes of Japanese medaka (Oryzias latipes) were determined. Adult male and female medaka were exposed to either 0 or 500 ng/L 17alpha-ethinylestradiol (EE) for 14d via a waterborne exposure. Livers, gonads, and brains were removed and genomic DNA was extracted. Samples of genomic DNA were then analyzed by bisulfite-mediated methylation-specific polymerase chain reaction (PCR) of an similar to300-bp region containing suspected methylation sites from the two genes, amplified, cloned, and sequenced. ER protein content in exposed medaka was significantly induced in all male and female tissues compared to controls. Aromatase activity in exposed medaka was significantly increased in the male brain, testes, and female brain as compared to controls. The methylation changes described by these studies indicate the potential for anthropogenic alteration of the mechanisms controlling gene expression, as well as gender- and tissue-specific sensitivity. While methylation differences were not paralleled by changes in protein expression in this study, changes in methylation have the potential to impact the regulation of normal gene expression and these changes could be transmitted to offspring. C1 Univ Mississippi, Dept Pharmacol, University, MS 38677 USA. Univ Mississippi, Pharmaceut Sci Res Inst, Environm Toxicol Res Program, University, MS 38677 USA. W Virginia Univ, Dept Biol, Morgantown, WV 26506 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Willett, KL (reprint author), Univ Mississippi, Dept Pharmacol, University, MS 38677 USA. EM kwillett@olemiss.edu NR 65 TC 50 Z9 55 U1 6 U2 31 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 JAN 9 PY 2004 VL 67 IS 1 BP 1 EP 22 DI 10.1080/15287390490253633 PG 22 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 763HJ UT WOS:000188078700001 PM 14668108 ER PT J AU Hummer, G AF Hummer, G TI From transition paths to transition states and rate coefficients SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ACTIVATED RATE-PROCESSES; RATE CONSTANTS; ISOMERIZATION DYNAMICS; KRAMERS PROBLEM; PATHWAYS; WATER AB Transition states are defined as points in configuration space with the highest probability that trajectories passing through them are reactive (i.e., form transition paths between reactants and products). In the high-friction (diffusive) limit of Langevin dynamics, the resulting ensemble of transition states is shown to coincide with the separatrix formed by points of equal commitment (or splitting) probabilities for reaching the product and reactant regions. Transition states according to the new criterion can be identified directly from equilibrium trajectories, or indirectly by calculating probability densities in the equilibrium and transition-path ensembles using umbrella and transition-path sampling, respectively. An algorithm is proposed to calculate rate coefficients from the transition-path and equilibrium ensembles by estimating the frequency of transitions between reactants and products. (C) 2004 American Institute of Physics. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 34 TC 177 Z9 177 U1 10 U2 48 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 8 PY 2004 VL 120 IS 2 BP 516 EP 523 DI 10.1063/1.1630572 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 759BN UT WOS:000187718200002 PM 15267886 ER PT J AU Lague, P Pastor, RW Brooks, BR AF Lague, P Pastor, RW Brooks, BR TI Pressure-based long-range correction for Lennard-Jones interactions in molecular dynamics simulations: Application to alkanes and interfaces SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; PARTICLE MESH EWALD; COMPUTER-SIMULATION; PHOSPHOLIPID MONOLAYER; LIPID-BILAYERS; WATER; FORCES; MOTION; GRAMICIDIN; DIFFUSION AB A straightforward method that accounts for the long-range Lennard-Jones (LJ) terms in constant pressure molecular dynamics simulations is presented. This long-range correction (LRC) consists of an additional applied pressure tensor which is periodically calculated from the difference of instantaneous pressures at the selected cutoff and a very long cutoff. It provides results that are nearly independent of the LJ cutoff distance at negligible additional calculation costs, and is particularly suited for anisotropic systems such as liquid/ liquid interfaces or heterogeneous macromolecules where approximations based on spherically symmetric radial distribution functions are expected to fail. The utility of the method is demonstrated for a series of alkanes and water, and for interfaces including a lipid bilayer. The LRC increases densities and decreases isothermal compressibilities, with the changes larger for alkanes than for water (where the long-range interactions are dominated by electrostatic interactions). While implementation of the LRC will not necessarily improve agreement with a particular experiment, it will provide a baseline for improvements in a parameter set that are consistent with the long-range Lennard-Jones interactions. C1 NIH, Struct Biol Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Brooks, BR (reprint author), NIH, Struct Biol Lab, Div Comp Res & Technol, Bldg 10, Bethesda, MD 20892 USA. NR 28 TC 69 Z9 72 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 8 PY 2004 VL 108 IS 1 BP 363 EP 368 DI 10.1021/jp030458y PG 6 WC Chemistry, Physical SC Chemistry GA 760MW UT WOS:000187838800049 ER PT J AU Pineda, VV Athos, JI Wang, HB Celver, J Ippolito, D Boulay, G Birnbaumer, L Storm, DR AF Pineda, VV Athos, JI Wang, HB Celver, J Ippolito, D Boulay, G Birnbaumer, L Storm, DR TI Removal of G(i alpha 1) constraints on adenylyl cyclase in the hippocampus enhances LTP and impairs memory formation SO NEURON LA English DT Article ID LONG-TERM POTENTIATION; MEDIATED GENE-EXPRESSION; KNOCK-OUT MICE; LATE-PHASE; MUSHROOM BODIES; PROTEIN-KINASE; MUTANT MICE; CA1 REGION; AREA CA1; CAMP AB Stimulation of adenylyl cyclase in the hippocampus is critical for memory formation. However, generation of cAMP signals within an optimal range for memory may require a balance between stimulatory and inhibitory mechanisms. The role of adenylyl cyclase inhibitory mechanisms for memory has not been addressed. One of the mechanisms for inhibition of adenylyl cyclase is through activation of G(i)-coupled receptors, a mechanism that could serve as a constraint on memory formation. Here we report that ablation of G(ialpha1) by gene disruption increases hippocampal adenylyl cyclase activity and enhances LTP in area CA1. Furthermore, gene ablation of G(ialpha1) or antisense oligonucleotide-mediated depletion of G(ialpha1) disrupted hippocampus-dependent memory. We conclude that G(ialpha1) provides a critical mechanism for tonic inhibition of adenylyl cyclase activity in the hippocampus. We hypothesize that loss of G(ialpha1) amplifies the responsiveness of CA1 postsynaptic neurons to stimuli that strengthen synaptic efficacy, thereby diminishing synapse-specific plasticity required for new memory formation. C1 Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Storm, DR (reprint author), Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. EM dstorm@u.washington.edu RI yu, yan/C-2322-2012 FU NIDCD NIH HHS [DC04156]; NIDDK NIH HHS [DK-19318]; NIGMS NIH HHS [32 GM07270]; NIMH NIH HHS [1F31MH064311]; NINDS NIH HHS [1F31NS042475, NS 20498] NR 47 TC 68 Z9 68 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 8 PY 2004 VL 41 IS 1 BP 153 EP 163 DI 10.1016/S0896-6273(03)00813-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 761YJ UT WOS:000187942800016 PM 14715142 ER PT J AU Dohoney, KM Guillerm, C Whiteford, C Elbi, C Lambert, PF Hager, GL Brady, JN AF Dohoney, KM Guillerm, C Whiteford, C Elbi, C Lambert, PF Hager, GL Brady, JN TI Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage SO ONCOGENE LA English DT Article DE p53; PP2A; phosphatase; DNA damage; serine 37 ID PROTEIN PHOSPHATASE 2A; CELL-CYCLE CHECKPOINT; CATALYTIC SUBUNIT; BINDING-SITE; OKADAIC ACID; T-ANTIGEN; MDM2; TRANSACTIVATION; INHIBITION; EXPRESSION AB The p53 tumor suppressor protein plays a critical role in mediating cellular response to stress. Upon DNA damage, post-translational modifications stabilize and activate this nuclear phosphoprotein. To determine the effect of phosphorylation site mutants in the context of the whole p53 protein, we performed reporter assays in p53 and MDM2 knockout mouse embryonic fibroblasts transfected with full-length p53 constructs. We show that mutation of S37 causes a decrease in p53 transcriptional activity compared to wild-type p53. Our data further suggest that the dephosphorylation of p53 at S37 is a regulated event involving protein phosphatase 2A (PP2A). Coimmunoprecipitation and immunofluorescence microscopy studies demonstrate that PP2A and p53 associate with one another in vivo following gamma-irradiation. Consistent with these observations, phosphorylated S37 accumulates in cell extracts prepared from gamma-irradiated Molt-4 cells in the presence of okadaic acid. Furthermore, in vitro phosphatase assays show that PP2A dephosphorylates p53 at S37. These results suggest that dephosphorylation of p53 at S37 plays a role in the transcriptional regulation of the p53 protein in response to DNA damage. C1 NCI, Basic Res Lab, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Ctr Canc Res, Gaithersburg, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Flinders Univ S Australia, Sch Med, Bedford Pk, SA 5042, Australia. RP Brady, JN (reprint author), NCI, Basic Res Lab, Virus Tumor Biol Sect, NIH, Bldg 41,Room B 201,41 Lib Dr MSC 5055, Bethesda, MD 20892 USA. EM bradyj@mail.nih.gov NR 47 TC 43 Z9 45 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 JAN 8 PY 2004 VL 23 IS 1 BP 49 EP 57 DI 10.1038/sj.onc.1207005 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 761HK UT WOS:000187895300006 PM 14712210 ER PT J AU Chikumi, H Barac, A Behbahani, B Gao, Y Teramoto, H Zheng, Y Gutkind, JS AF Chikumi, H Barac, A Behbahani, B Gao, Y Teramoto, H Zheng, Y Gutkind, JS TI Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential SO ONCOGENE LA English DT Article DE Rho; guanine-nucleotide exchange factor; transformation; GTPases; G proteins ID NUCLEOTIDE EXCHANGE FACTORS; VAV PROTOONCOGENE PRODUCT; HETEROTRIMERIC G-PROTEINS; LEUKEMIA-ASSOCIATED RHO; TYROSINE PHOSPHORYLATION; GUANOSINE TRIPHOSPHATASES; CELLULAR-TRANSFORMATION; DEPENDENT ACTIVATION; P115 RHOGEF; DBL FAMILY AB PDZ-RhoGEF, LARG, and p115RhoGEF are members of a newly identified family of Rho-guanine nucleotide exchange factors (GEFs) exhibiting a unique structural feature consisting of the presence of an area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a functional motif by which Galpha(12) and Galpha(13) can bind and regulate the activity of these RhoGEFs, thus providing a direct link from these heterotrimeric G proteins to Rho. PDZ-RhoGEF and LARG can also be phosphorylated by tyrosine kinases, including FAK, and associate with Plexin B, a semaphorin receptor, which controls axon guidance during development, through their PDZ domain, thereby stimulating Rho. Interestingly, while characterizing a PDZ-RhoGEF antiserum, we found that a transfected PDZ-RhoGEF construct associated with the endogenous PDZ-RhoGEF. Indeed, we observed that PDZ-RhoGEF and LARG can form homo- and hetero-oligomers, whereas p115RhoGEF can only homo-oligomerize, and that this intermolecular interaction was mediated by their unique C-terminal regions. Deletion of the C-terminal tail of PDZ-RhoGEF had no significant effect on the GEF catalytic activity towards Rho in vitro, but resulted in a drastic increase in the ability to stimulate a serum response element reporter and the accumulation of the GTP-bound Rho in vivo. Furthermore, removal of the C-termini of each of the three RGL-containing GEFs unleashed their full transforming potential. Together, these findings suggest the existence of a novel mechanism controlling the activity of PDZ-RhoGEF, LARG, and p115RhoGEF, which involves homo- and hetero-oligomerization through their inhibitory C-terminal region. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 9000 Rockville Pike,Bldg 30,Room 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Zheng, Yi/J-7235-2015; OI Zheng, Yi/0000-0001-7089-6074; Barac, Ana/0000-0002-9935-8904 NR 36 TC 74 Z9 74 U1 1 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 JAN 8 PY 2004 VL 23 IS 1 BP 233 EP 240 DI 10.1038/sj.onc.1207012 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 761HK UT WOS:000187895300024 PM 14712228 ER PT J AU Cencig, S Nanbru, C Le, SY Gueydan, C Huez, G Kruys, V AF Cencig, S Nanbru, C Le, SY Gueydan, C Huez, G Kruys, V TI Mapping and characterization of the minimal internal ribosome entry segment in the human c-myc mRNA 5 ' untranslated region SO ONCOGENE LA English DT Article DE translation; IRES; proto-oncogene; c-myc ID SITE-MEDIATED TRANSLATION; 5' UNTRANSLATED REGION; GROWTH-FACTOR; CELL-CYCLE; ALTERNATIVE TRANSLATION; PROTEIN-SYNTHESIS; INITIATION; TRANSCRIPTION; BINDING; IDENTIFICATION AB The human c-myc proto-oncogene is transcribed from four alternative promoters generating transcripts with 5' untranslated regions of various lengths. These transcripts encode two proteins, c-Myc1 and c-Myc2, from two initiation codons, CUG and AUG, respectively. We and others have previously demonstrated that the region of c-myc transcripts between nucleotides (nt) -363 and -94 upstream from the CUG start codon contained an internal ribosome entry site leading to the cap-independent translation of c-myc open reading frames (ORFs). Here, we mapped a 50-nt sequence (-143 -94), which is sufficient to promote internal translation initiation of c-myc ORFs. Interestingly, this 50-nt element can be further dissected into two segments of 14 nt, each capable of activating internal translation initiation. We also demonstrate that this 50-nt element acts as the ribosome landing site from which the preinitiation ribosomal complex scans the mRNA until the CUG or AUG start codons. C1 Free Univ Brussels, Inst Biol & Med Mol, Chim Biol Lab, B-6041 Gosselies, Belgium. NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Kruys, V (reprint author), Free Univ Brussels, Inst Biol & Med Mol, Chim Biol Lab, Rue Profs Jeener & Brachet 12, B-6041 Gosselies, Belgium. EM vkruys@ulb.ac.be OI Gueydan, Cyril/0000-0003-3097-7667 NR 48 TC 14 Z9 16 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 JAN 8 PY 2004 VL 23 IS 1 BP 267 EP 277 DI 10.1038/sj.onc.1207017 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 761HK UT WOS:000187895300028 PM 14712232 ER PT J AU Abashkin, YG Burt, SK AF Abashkin, YG Burt, SK TI (Salen)Mn-catalyzed epoxidation of alkenes: A two-zone process with different spin-state channels as suggested by DFT study SO ORGANIC LETTERS LA English DT Article ID JACOBSEN-KATSUKI EPOXIDATION; 2-STATE REACTIVITY; OXYGEN-TRANSFER; ENANTIOSELECTIVITY; ENERGY; DIASTEREOSELECTIVITY; APPROXIMATION; MECHANISMS; CHROMIUM; AGENTS AB A novel (two-zone process with different spin-state channels) mechanistic picture for the Jacobsen-Katsuki reaction is presented that provides insight into the still elusive understanding of the epoxidation mechanism. For the first time, we show that the salen moiety of the catalyst can be explicitly involved in the epoxidation process. C1 NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Abashkin, YG (reprint author), NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. EM abashkin@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 25 TC 42 Z9 42 U1 4 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JAN 8 PY 2004 VL 6 IS 1 BP 59 EP 62 DI 10.1021/ol036051t PG 4 WC Chemistry, Organic SC Chemistry GA 760BK UT WOS:000187790500016 PM 14703350 ER PT J AU Wu, T Han, C Shelhamer, JH AF Wu, T Han, C Shelhamer, JH TI Involvement of p38 and p42/44 MAP kinases and protein kinase C in the interferon-gamma and interleukin-1 alpha-induced phosphorylation of 85-kDa cytosolic phospholipase A(2) in primary human bronchial epithelial cells SO CYTOKINE LA English DT Article DE interferon-gamma; interleukin-1; phospholipase A(2); MAP kinase; protein kinase C ID ARACHIDONIC-ACID RELEASE; TUMOR-NECROSIS-FACTOR; CYSTIC-FIBROSIS; GENE-EXPRESSION; FACTOR-ALPHA; ASTHMA; ACTIVATION; CYTOKINES; CPLA(2); HYPERRESPONSIVENESS AB Interferon-gamma (IFN-gamma) and interleukin-1 (IL-1) play an important role in the modulation of acute and chronic airway inflammation. Both IFN-gamma and IL-1 are known to increase the release of arachidonic acid (AA) from airway epithelial cells, suggesting that AA metabolites may mediate the cytokine-induced inflammation. This study was designed to examine the direct effect of IFN-gamma and IL-alpha on the phosphorylation of 85-kDa cytosolic phospholipase A(2) (cPLA(2)) and AA release in primary normal human bronchial epithelial (NHBE) cells. Treatment with IFN-gamma and IL-1alpha for 15 min induced a rapid increase of AA release from NHBE cells, which was blocked by the cPLA(2) inhibitor MAFP (p<0.05) but not by the sPLA(2) inhibitor LY311727 or iPLA(2) inhibitor HELSS. Immunoprecipitation and Western blot analysis showed that both IFN-gamma and IL-1alpha induced a rapid phosphorylation of cPLA(2). The IFN-gamma and IL-1alpha-induced cPLA(2) phosphorylation and AA release in the NHBE cells were inhibited by the p38 MAP kinase (MAPK) inhibitor SB203580, p42/44 MAPK inhibitor PD98059 and protein kinase C (PKC) inhibitor bisindolylmaleimide I. These results demonstrate the involvement of p38 and p42/44 MAPKs as well as PKC in the IFN-gamma and IL-1alpha-induced cPLA(2) phosphorylation and AA release in human airway epithelial cells. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Presbyterian Univ Hosp, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Wu, T (reprint author), Univ Pittsburgh, Presbyterian Univ Hosp, Sch Med, Dept Pathol, C902,200 Lothrop St, Pittsburgh, PA 15213 USA. EM wut@msx.upmc.edu NR 49 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN 7 PY 2004 VL 25 IS 1 BP 11 EP 20 DI 10.1016/j.cyto.2003.08.013 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 765ZY UT WOS:000188322000002 PM 14687581 ER PT J AU Nagorsen, D Marincola, FM Panelli, MC AF Nagorsen, D Marincola, FM Panelli, MC TI Cytokine and chemokine expression profiles of maturing dendritic cells using multiprotein platform arrays SO CYTOKINE LA English DT Article DE dendritic cells; maturation; cytokine; chemokine ID CYTOTOXIC T-CELLS; MELANOMA PATIENTS; VACCINATION; MATURATION; REGRESSION; ACTIVATION; INJECTION; INDUCTION; KINETICS; HUMANS AB Understanding the whole process of dendritic cell (DC) activation might help in the development of more efficient immuno therapeutic strategies for tumor patients. Part of this process is cytokine secretion, which has important effects on innate and adaptive immune response. Here, we cultured circulating monocytes for five days with interleukin-4 and GM-CSF followed by two-day culture with or without CD40 ligand and LPS to create a mature DC (mDC) and an immature DC (iDC) phenotype, respectively, characterized by differential expression of co-stimulatory. molecules (CD80, CD83). We then compared the cytokine expression profile of the mDC and iDC using two protein platform arrays. Twelve supernatants from mDC paired with 12 from iDC were compared. The mDC protein expression profile showed significant increases in 16 out of 34 factors tested, including TNFalpha, IL-10, IL-12, IFNgamma, MIP1alpha, MIP1beta, IL-8, MDC, RANTES, and IL-6, which play a crucial role in the regulation of the innate immune response as well as the recruitment and activation of adaptive immune effectors. Interestingly, some of the cytokines expressed during maturation were also found in the gene expression profile identified in tumor metastases following IL-2 therapy using cDNA arrays. This finding suggests a possible role for resident DC maturation as a mediator of systemic IL-2 effects. Most important, the array of cytokines secreted during DC maturation may be considered an important component during adoptive transfer. Further characterization of the kinetics and persistence of their secretion should be undertaken in the future. Published by Elsevier Ltd. C1 Ctr Clin, Immunogenet Sect, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. RP Panelli, MC (reprint author), Ctr Clin, Immunogenet Sect, Dept Transfus Med, NIH, Bldg 10,Room IN226,10 Ctr Dr, Bethesda, MD 20892 USA. EM MPanelli@mail.cc.nih.gov NR 17 TC 31 Z9 33 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN 7 PY 2004 VL 25 IS 1 BP 31 EP 35 DI 10.1016/j.cyto.2003.08.012 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 765ZY UT WOS:000188322000004 PM 14687583 ER PT J AU Schernhammer, ES Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS AF Schernhammer, ES Kang, JH Chan, AT Michaud, DS Skinner, HG Giovannucci, E Colditz, GA Fuchs, CS TI A prospective study of aspirin use and the risk of pancreatic cancer in women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BREAST-CANCER; CELL-LINES; EXPRESSION; CYCLOOXYGENASE-2; CARCINOGENESIS; INHIBITION; WEIGHT AB Background: In vitro experiments and limited animal studies suggest that aspirin and nonsteroidal anti-inflammatory drugs may inhibit pancreatic carcinogenesis. Because few studies have examined the association between aspirin use and pancreatic cancer in humans and the results have been inconsistent, we examined the relationship between aspirin use and the development of pancreatic cancer in the Nurses' Health Study. Methods: Among 88 378 women without cancer at baseline, we documented 161 cases of pancreatic cancer during 18 years of follow-up. Aspirin use was first assessed at baseline in 1980 and updated biennially thereafter. All statistical tests were two-sided. Results: Participants were classified according to history of aspirin use. In a multivariable analysis, the risk of pancreatic cancer was not associated with current regular aspirin use (defined as two or more standard tablets per week; relative risk [RR] = 1.20, 95% confidence interval [CI] = 0.87 to 1.65), compared with use of fewer than two tablets per week. Increasing duration of regular aspirin use, compared with non-use, was associated with a statistically significant increase in risk: Women who reported more than 20 years of regular aspirin use had an increased risk of pancreatic cancer (RR = 1.58, 95% CI = 1.03 to 2.43; P-trend = .01). Among women who reported aspirin use on at least two of three consecutive biennial questionnaires compared with consistent non-users of aspirin, the risk increased with dose (one to three tablets per week: RR = 1.11, 95% CI = 0.70 to 1.76; four to six tablets per week: RR = 1.29, 95% CI = 0.70 to 2.40; seven to 13 tablets per week: RR = 1.41, 95% CI = 0.76 to 2.61; and 2:14 tablets per week: RR = 1.86, 95% CI = 1.03 to 3.35) (P-trend = .02). Conclusion: Extended periods of regular aspirin use appear to be associated with a statistically significantly increased risk of pancreatic cancer among women. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NCI, Nutr Epidemiol Branch, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schernhammer@channing.harvard.edu RI Skinner, Halcyon/A-1049-2009; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA55075, CA/ES62984, CA86102, CA87969, CA40356] NR 30 TC 88 Z9 94 U1 2 U2 5 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 JAN 7 PY 2004 VL 96 IS 1 BP 22 EP 28 DI 10.1093/jnci/djh001 PG 7 WC Oncology SC Oncology GA 765ED UT WOS:000188253400008 PM 14709735 ER PT J AU Beppu, K Jaboine, J Merchant, MS Mackall, CL Thiele, CJ AF Beppu, K Jaboine, J Merchant, MS Mackall, CL Thiele, CJ TI Effect of imatinib mesylate on neuroblastoma tumorigenesis and vascular endothelial growth factor expression SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID KINASE INHIBITOR STI571; ABL TYROSINE KINASE; STEM-CELL FACTOR; IN-VITRO; C-KIT; FACTOR RECEPTORS; TUMOR-GROWTH; APOPTOSIS; ANGIOGENESIS; LEUKEMIA AB Background: Alternative treatment options are needed for advanced neuroblastoma patients because their prognosis remains poor after intensive chemotherapy. Neuroblastoma cells express platelet-derived growth factor (PDGF), stem cell factor (SCF), and vascular endothelial growth factor (VEGF) and their respective receptors, PDGFR, c-Kit, and Flk-1. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the tyrosine kinase activities of c-Kit and PDGFR, on the growth of neuroblastoma cells in vivo and in vitro. Methods: We tested seven human neuroblastoma cell lines for their sensitivity to imatinib. Cell viability was assessed by trypan blue dye exclusion. Apoptosis was evaluated by nuclear staining, flow cytometry, and western blotting. Protein assays included immunoprecipitation, western blotting, enzyme-linked immunosorbent assays, and immunohistochemistry. mRNA expression was assessed by northern blotting. We used a xenograft model in SCID mice (10 mice per group) to evaluate the effects of imatinib oral therapy (50 or 100 mg/kg every 12 hours for 14 days) on neuroblastoma tumor growth. All statistical tests were two-sided. Results: All seven neuroblastoma cell lines treated with imatinib displayed concentration-dependent decreases in cell viability, which coincided with an induction of apoptosis, and with ligand-stimulated phosphorylation of c-Kit and PDGFR. The imatinib concentrations that caused 50% inhibition of growth and 50% inhibition of ligand-induced phosphorylation of these receptors were 9-13 muM and 0.1-0.5 muM, respectively. Expression of VEGF, but not phosphorylation of Flk-1, its receptor, was reduced in neuroblastoma cells treated with imatinib at 10 muM or higher. Mice treated with imatinib at 50 mg/kg or 100 mg/kg had statistically significantly smaller tumors than control mice treated with vehicle (mean tumor volume in mice treated with imatinib at 50 mg/kg = 1546 mm(3), in control mice = 2954 mm(3); difference = 1408 mm(3), 95% confidence interval [CI] = 657 to 2159 mm(3); P < .001; mean tumor volume in mice treated with imatinib at 100 mg/kg = 463 mm(3); difference = 2491 mm(3), 95% CI = 1740 to 3242 mm(3); P < .001). Conclusions: Imatinib inhibited the growth of neuroblastoma cells in vitro and in vivo. This inhibition was associated with suppression of PDGFR and c-Kit phosphorylation and inhibition of VEGF expression. C1 NCI, Ctr Canc Res, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Thiele, CJ (reprint author), NCI, Ctr Canc Res, Pediat Oncol Branch, NIH, 10 Ctr Dr,MSC 1298,Bldg 10-13N240, Bethesda, MD 20892 USA. EM ct47a@nih.gov NR 40 TC 112 Z9 113 U1 0 U2 3 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 JAN 7 PY 2004 VL 96 IS 1 BP 46 EP 55 DI 10.1093/jnci/djh004 PG 10 WC Oncology SC Oncology GA 765ED UT WOS:000188253400011 PM 14709738 ER PT J AU Curtis, RE Freedman, DM Sherman, ME Fraumeni, JF AF Curtis, RE Freedman, DM Sherman, ME Fraumeni, JF TI Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL-ADJUVANT-BREAST; ENDOMETRIAL CANCER; UTERINE SARCOMA; WOMEN AB Recent studies have indicated that the tamoxifen-related risk of uterine corpus cancer may be especially high or some uncommon cell types, although the magnitude of risk has not been quantified. We evaluated data from 39451 breast cancer patients diagnosed from 1980 through 2000 who were initially treated with tamoxifen and found that the overall risk of subsequent uterine corpus cancer was increased more than twofold (observed-to-expected ratio [O/E] = 2.17, 95% confidence interval [CI] = 1.95 to 2.41) relative to the general SEER population. The relative risk was substantially higher for malignant mixed mullerian tumors (MMMTs) (O/E = 4.62, O = 34, 95 % CI = 3.20 to 6.46) than for endometrial adenocarcinomas (O/E = 2.07, O = 306,95% CI = 1.85 to 2.32), although the excess absolute risk was smaller-an additional 1.4 versus 8.4 cancers per 10 000 women per year, respectively. Among those who survived for 5 years or longer, there was an eightfold relative risk for MMMTs and a 2.3-fold risk for endometrial adenocarcinomas, with patients developing MMMTs having a worse prognosis. These findings indicate that tamoxifen may have delayed effects, such as the increased risk of MMMTs, rare but aggressive tumors of unclear pathogenesis. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,HIH, Bethesda, MD 20892 USA. RP Curtis, RE (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,HIH, Execut Plaza S,Rm 7042, Bethesda, MD 20892 USA. EM rcurtis@mail.nih.gov NR 23 TC 62 Z9 64 U1 1 U2 1 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 JAN 7 PY 2004 VL 96 IS 1 BP 70 EP 74 DI 10.1093/jnci/djh007 PG 5 WC Oncology SC Oncology GA 765ED UT WOS:000188253400014 PM 14709741 ER PT J AU Muntner, P Hamm, LL Kusek, JW Chen, J Whelton, PK He, J AF Muntner, P Hamm, LL Kusek, JW Chen, J Whelton, PK He, J TI The prevalence of nontraditional risk factors for coronary heart disease in patients with chronic kidney disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CHRONIC-RENAL-FAILURE; GLOMERULAR-FILTRATION RATE; 3RD NATIONAL-HEALTH; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; SERUM CREATININE; ARTERY-DISEASE; UNITED-STATES; MYOCARDIAL-INFARCTION AB Background: Risk for coronary heart disease is high among patients with chronic kidney disease. Objective: To compare the prevalence of low apolipoprotein A1 levels and elevated apolipoprotein Ell, plasma fibrinogen, lipoprotein(a), homocysteine, and C-reactive protein levels by estimated glomerular filtration rate (GFR). Design: Cross-sectional study. Setting: Third National Health and Nutrition Examination survey. Participants: 12 547, 3180, and 744 persons with estimated GFRs of at least 90, 60 to 89, or less than 60 mL/min per 1.73 m(2), respectively, who were at least 18 years of age. Measurements: Chronic kidney disease was defined as an estimated GFR of less than 60 mL/min per 1.73 m(2) based on the abbreviated Modification of Diet in Renal Disease formula. Results: After standardization for age, race or ethnicity, and sex, lower estimated GFR (greater than or equal to90, 60 to 89, or <60 mL/min per 1.73 m 2) was associated with lower average levels of apolipoprotein A1 (1.44, 1.43, and 1.35 g/L) and higher levels of apolipoprotein B (1.03, 1.06, and 1.08 g/L), plasma fibrinogen (8.43, 8.44, and 9.53 mumol/L), homocysteine (8.5, 10.0, and 13.2 mumol/L), and C-reactive protein (3.0, 2.9, and 3.9 mg/L) (P < 0.05 for all values). The multivariate-adjusted odds ratios of an apolipoprotein A1 level of less than 1.2 g/L, a serum lipoprotein(a) level of at least 1.61 mumol/L (greater than or equal to45.3 mg/dL), a plasma fibrinogen level of at least 10.35 mumol/L, a serum homocysteine level of at least 15,mumol/L, and a C-reactive protein level of at least 10.0 mg/L for participants with chronic kidney disease compared with those with a GFR of at least 90 mL/min per 1.73 m(2) or greater were 1.92 (95% Cl, 1.02 to 3.63), 1.82 (Cl, 1.06 to 3.13), 1.74 (Cl, 1.35 to 2.24), 8.23 (Cl, 5.00 to 13.6), and 1.93 (Cl, 1.33 to 2.81), respectively. Conclusions: Levels of apolipoprotein A1 are decreased and levels of homocysteine, lipoprotein(a), fibrinogen, and C-reactive protein are increased among patients with chronic kidney disease. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave,SL18, New Orleans, LA 70118 USA. EM jhe@tulane.edu FU NCRR NIH HHS [P20 RR17659-01]; NIDDK NIH HHS [U01 DK60963] NR 48 TC 245 Z9 254 U1 0 U2 2 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 JAN 6 PY 2004 VL 140 IS 1 BP 9 EP 17 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 760VH UT WOS:000187855600002 PM 14706967 ER PT J AU Zhu, JH Katz, RJ Quyyumi, AA Canos, DA Rott, D Csako, G Zalles-Ganley, A Ogunmakinwa, J Wasserman, AG Epstein, SE AF Zhu, JH Katz, RJ Quyyumi, AA Canos, DA Rott, D Csako, G Zalles-Ganley, A Ogunmakinwa, J Wasserman, AG Epstein, SE TI Association of serum antibodies to heat-shock protein 65 with coronary calcification levels - Suggestion of pathogen-triggered autoimmunity in early atherosclerosis SO CIRCULATION LA English DT Article DE proteins; infection; calcification ID BEAM COMPUTED-TOMOGRAPHY; HEAT-SHOCK PROTEINS; HELICOBACTER-PYLORI STRAINS; ARTERY-DISEASE; CHLAMYDIA-PNEUMONIAE; RISK-FACTORS; ENDOTHELIAL CYTOTOXICITY; CAROTID ATHEROSCLEROSIS; IMMUNE-REACTIONS; INFECTION AB Background - Previous studies demonstrated an association between antibodies to mycobacterial heat-shock protein 65 (mHSP65) and carotid artery thickening. We examined whether mHSP65 antibodies are associated with levels of coronary calcification that appear to reflect preclinical coronary artery disease ( CAD). Methods and Results - Serum specimens from 201 healthy asymptomatic subjects (52% male; mean age, 56.6 years) undergoing electron-beam computed tomographic imaging were used to measure levels of mHSP65 and human HSP60 antibodies and antibodies to several infectious pathogens. We found that 84% of the study subjects had anti-mHSP65 IgG antibodies. Mean titers of mHSP65 antibodies were higher (1: 394 versus 1: 267, P = 0.012) in individuals with than in those without elevated levels of coronary calcium ( calcium score greater than or equal to 150). Increasing titers of mHSP65 antibodies were significantly associated, in a dose-response manner, with elevated levels of coronary calcification. Individuals with the highest titers of mHSP65 antibodies (greater than or equal to1: 800) had an adjusted odds ratio (OR) of 14.3 for having elevated coronary calcium (P = 0.004). Association of mHSP65 antibodies with elevated coronary calcification levels was independent of CAD risk factors after multivariate adjustment (P = 0.037). Interestingly, mHSP65 antibody titers were correlated with Helicobacter pylori infection (P = 0.004), which maintained significance after adjustment for CAD risk factors and seropositivities to other pathogens (adjusted OR, 3.1; 95% CI, 1.4 to 6.6). No association was found between antibodies to human HSP60 and levels of coronary calcification. Conclusions - Antibodies to mHSP65 are associated with elevated levels of coronary calcification and correlated with H pylori infection, suggesting that pathogen-triggered autoimmunity plays a role in early atherosclerosis. C1 Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. George Washington Univ, Washington, DC USA. Emory Univ Hosp, Atlanta, GA 30322 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Zhu, JH (reprint author), Washington Hosp Ctr, Cardiovasc Res Inst, 108 Irving St NW,GHRB Room 217, Washington, DC 20010 USA. NR 26 TC 53 Z9 58 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 JAN 6 PY 2004 VL 109 IS 1 BP 36 EP 41 DI 10.1161/01.CIR.0000105513.37677.B3 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 760BY UT WOS:000187791900010 PM 14662717 ER PT J AU Yanai, H Javitt, NB Higashi, Y Fuda, H Strott, CA AF Yanai, H Javitt, NB Higashi, Y Fuda, H Strott, CA TI Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets SO CIRCULATION LA English DT Article DE platelets; lipoproteins; apolipoproteins; cholesterol ID X-LINKED ICHTHYOSIS; BLOOD-PLATELETS; SULFATE; PLASMA; GENE; ISOFORMS AB Background - Cholesterol sulfate, the most important sterol sulfate in the human circulation, has emerged as a multifaceted molecule. Among its many demonstrated regulatory actions is its ability to influence blood clotting and fibrinolysis. Additionally, cholesterol sulfate is a constituent of human platelets, where it has been shown to support platelet aggregation. Methods and Results - We have documented the presence of the enzyme (SULT2B1b) that sulfonates cholesterol in human platelets and examined the influence of plasma lipoproteins on the expression and activity of this enzyme. SULT2B1b mRNA was detected by reverse transcription - polymerase chain reaction and found to be the only steroid/sterol sulfotransferase expressed in these discoid anucleate particles. Using real-time polymerase chain reaction for quantification, we found that the level of SULT2B1b mRNA in platelets was maintained at 4 degreesC but substantially diminished over a period of 4 hours at 37 degreesC. The loss of SULT2B1b mRNA, however, was markedly reduced in the presence of HDL but not LDL. The stabilizing influence of HDL was attributable specifically to its apolipoprotein (apo) A-I component, whereas apoA-II and apoE were without effect. Importantly, there was a direct correlation between platelet SULT2B1b mRNA and protein levels in the presence or absence of lipoprotein that was reflected in enzymatic activity and cholesterol sulfate production. Conclusions - Human platelets selectively express SULT2B1b, the physiological cholesterol sulfotransferase. Furthermore, the stability of SULT2B1b mRNA and protein in platelets maintained at 37 degreesC is subject to regulation by the apoA-I component of HDL. C1 NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Strott, CA (reprint author), NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36, Bethesda, MD 20892 USA. NR 28 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 6 PY 2004 VL 109 IS 1 BP 92 EP 96 DI 10.1161/01.CIR.0000108925.95658.8D PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 760BY UT WOS:000187791900019 PM 14676143 ER PT J AU Morales, M Wang, SD Diaz-Ruiz, O Jho, DHJ AF Morales, M Wang, SD Diaz-Ruiz, O Jho, DHJ TI Cannabinoid CB1 receptor and serotonin 3 receptor subunit a (5-HT3A) are co-expressed in GABA neurons in the rat telencephalon SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cortex; amygdala; CCK ID ADULT-MOUSE FOREBRAIN; NIGRA PARS RETICULATA; SHORT-TERM-MEMORY; GABAERGIC TRANSMISSION; SYNAPTIC-TRANSMISSION; HIPPOCAMPAL SLICES; CHOLECYSTOKININ RELEASE; FUNCTIONAL EXPRESSION; BASOLATERAL AMYGDALA; NUCLEUS-ACCUMBENS AB Among all described serotonin (5-HT) receptors in mammals, the type three (5-HT3) is the only ligand-gated ion channel receptor for serotonin. By using double in situ hybridization histochemistry, we found co-expression of the functional 5-HT3A subunit of the 5-HT3 receptor and the central CB1 cannabinoid receptor in neurons of the rat telencephalon. Double-labeled 5-HT3A/CB1 neurons were found in the anterior olfactory nucleus, superficial and deep layers of the cortex, hippocampal formation (hippocampus, dentate gyrus, subiculum, and entorhinal cortex) and amygdala. Analysis of the proportion of neurons co-expressing 5-HT3A and CB1 receptors in the cortex and amygdala showed that, depending on the brain region, 37-53% of all neurons expressing the 5-HT1A subunit also expressed CB1 transcripts; 16-72% of the total population of neurons expressing CB1 mRNA co-expressed the 5-HT3A subunit. By using a combination of double in situ hybridization and immunohistochemistry, we demonstrated that 5-HT3A/CB1-expressing neurons contained the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). These results imply that in distinct regions of the telencephalon, GABA neurons that react to cannabinoids may also be responsive to serotonin through 5-HT3 receptors. Cellular coexistence of 5-HT3A and CB1 transcripts in interneurons of the cortex, hippocampal formation, and amygdala suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission in brain areas involved in cognition, memory, and emotion. C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. Natl Def Med Ctr, Dept Biol & Anat, Taipei 114, Taiwan. RP Morales, M (reprint author), Natl Inst Drug Abuse, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mmorales@intra.nida.nih.gov RI Diaz-Ruiz, Oscar/F-3162-2010 NR 61 TC 31 Z9 31 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 6 PY 2004 VL 468 IS 2 BP 205 EP 216 DI 10.1002/cne.10968 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 750JW UT WOS:000186988400005 PM 14648680 ER PT J AU Zhang, JW Tang, QQ Vinson, C Lane, MD AF Zhang, JW Tang, QQ Vinson, C Lane, MD TI Dominant-negative C/EBP disrupts mitotic clonal expansion and differentiation of 3T3-L1 preadipocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 3T3-L1 adipocytes; nuclear localization; adipogenesis; obesity; cell cycle ID BINDING-PROTEIN-ALPHA; ADIPOCYTE DIFFERENTIATION; CELL-PROLIFERATION; HEPATOCYTE PROLIFERATION; TRANSCRIPTIONAL REGULATION; TRANSGENIC MICE; ADIPOSE-TISSUE; GENE PROMOTER; BETA; ADIPOGENESIS AB Hormonal induction of growth-arrested 3T3-L1 preadipocytes rapidly activates expression of CCAAT/enhancer-binding protein (C/EBP) beta. Acquisition of DNA-binding activity by C/EBPbeta, however, is delayed until the cells synchronously enter the S phase of mitotic clonal expansion (MCE). After MCE, C/EBPbeta activates expression of C/EBPalpha and peroxisome proliferator-activated receptor gamma, which then transcriptionally activate genes that give rise to the adipocyte phenotype. A-C/EBP, which possesses a leucine zipper but lacks functional DNA-binding and transactivation domains, forms stable inactive heterodimers with C/EBPbeta in vitro. Infection of 3T3-L1 preadipocytes with an adenovirus A-C/EBP expression vector interferes with C/EBPbeta function after induction of differentiation. A-C/EBP inhibited events associated with hormone-induced entry of S-phase of the cell cycle, including the turnover of p27/Kip1, a key cyclin-dependent kinase inhibitor, expression of cyclin A and cyclin-dependent kinase 2, DNA replication, MCE, and, subsequently, adipogenesis. Although A-C/EBP blocked cell proliferation associated with MCE, it did not inhibit normal proliferation of 3T3-L1 preadipocytes. Immunofluorescent staining of C/EBPbeta revealed that A-C/EBP prevented the normal punctate nuclear staining of centromeres, an indicator of C/EBPbeta binding to C/EBP regulatory elements in centromeric satellite DNA. The inhibitory effects of A-C/EBP appear to be due primarily to interference with nuclear import of C/EBPbeta caused by obscuring its nuclear localization signal. These findings show that both MCE and adipogenesis are dependent on C/EBPbeta. C1 Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Cellular & Mol Biol Grad Program, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Div Endocrinol, Baltimore, MD 21205 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Lane, MD (reprint author), Johns Hopkins Univ, Sch Med, Dept Biol Chem, Room 512,Wood Basic Sci Bldg, Baltimore, MD 21205 USA. EM dlane@jhmi.edu RI Zhang, Jiangwen/A-7654-2013 FU NIDDK NIH HHS [R01 DK038418, DK060787, DK38418, K01 DK061355, K01-DK61355, R01 DK060787] NR 37 TC 99 Z9 104 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2004 VL 101 IS 1 BP 43 EP 47 DI 10.1073/pnas.0307229101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200011 PM 14688407 ER PT J AU Kim, YO Park, SJ Balaban, RS Nirenberg, M Kim, Y AF Kim, YO Park, SJ Balaban, RS Nirenberg, M Kim, Y TI A functional genomic screen for cardiogenic genes using RNA interference in developing Drosophila embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CARDIAC DEVELOPMENT; HEART DEVELOPMENT; DORSAL VESSEL; PROTEIN; EXPRESSION; ELEGANS; DIFFERENTIATION; IDENTIFICATION; HYBRIDIZATION; MELANOGASTER AB Identifying genetic components is an essential step toward understanding complex developmental processes. The primitive heart of the fruit fly, the dorsal vessel, which is a hemolymph-pumping organ, has provided a unique model system to identify cardiogenic genes and to further our understanding of the molecular mechanisms of cardiogenesis. Using RNA interference in developing Drosophila embryos, we performed a genomewide search for cardiogenic genes. Through analyses of the >5,800 genes that cover approximate to40% of all predicted Drosophila genes, we identified a variety of genes encoding transcription factors and cell signaling proteins required for different steps during heart development. Analysis of mutant heart phenotypes and identified genes suggests that the Drosophila heart tube is segmentally patterned, like axial patterning, but assembled with regional modules. One of the identified genes, simjang, was further characterized. In the simjang mutant embryo, we found that within each segment a subset of cardial cells is missing. Interestingly, the simjang gene encodes a protein that is a component of the chromatin remodeling complex recruited by methyl-CpG-DNA binding proteins, suggesting that epigenetic information is crucial for specifying cardiac precursors. Together, these studies not only identify key regulators but also reveal mechanisms underlying heart development. C1 NHLBI, Off Director, Lab Res Program, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Nirenberg, M (reprint author), NHLBI, Off Director, Lab Res Program, NIH, Bldg 10,Room 7N204,10 Ctr Dr,MSC1762, Bethesda, MD 20892 USA. EM yongsok@helix.nih.gov RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 32 TC 59 Z9 67 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 JAN 6 PY 2004 VL 101 IS 1 BP 159 EP 164 DI 10.1073/pnas.0307205101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200031 PM 14684833 ER PT J AU Mooney, DM Zhang, L Basile, C Senatorov, VV Ngsee, J Omar, A Hu, B AF Mooney, DM Zhang, L Basile, C Senatorov, VV Ngsee, J Omar, A Hu, B TI Distinct forms of cholinergic modulation in parallel thalamic sensory pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MUSCARINIC TYPE-2 RECEPTORS; LATERAL GENICULATE-NUCLEUS; RAT AUDITORY THALAMUS; POTASSIUM CONDUCTANCE; SYNAPTIC TRANSMISSION; TEMPORAL CORTEX; GUINEA-PIG; IN-VITRO; NEURONS; BURST AB Mammalian thalamus is a critical site where early perception of sensorimotor signals is dynamically regulated by acetylcholine in a behavioral state-dependent manner. in this study, we examined how synaptic transmission is modulated by acetylcholine in auditory thalamus where sensory relay neurons form parallel lemniscal and nonlemniscal pathways. The former mediates tonotopic relay of acoustic signals, whereas the latter is involved in detecting and transmitting auditory cues of behavioral relevance. We report here that activation of cholinergic muscarinic receptors had opposite membrane effects on these parallel synaptic pathways. In lemniscal neurons, muscarine induced a sustained membrane depolarization and tonic firing by closing a linear K+ conductance. In contrast, in nonlemniscal neurons, muscarine evoked a membrane hyperpolarization by opening a voltage-independent K+ conductance. Depending on the level of membrane hyperpolarization and the strength of local synaptic input, nonlemniscal neurons were either suppressed or selectively engaged in detecting and transmitting synchronized synaptic input by firing a high-frequency spike burst. Immunohistochemical and Western blotting experiments showed that nonlemniscal neurons predominantly expressed M2 muscarinic receptors, whereas lemniscal cells had a significantly higher level of M1 receptors. Our data indicate that cholinergic modulation in the thalamus is pathway-specific. Enhanced cholinergic tone during behavioral arousal or attention may render synaptic transmission in nonlemniscal thalamus highly sensitive to the context of local synaptic activities. C1 Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Ottawa, ON K1Y 4E9, Canada. Univ Calgary, Fac Med, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada. NIMH, NIH, Bethesda, MD 20892 USA. RP Hu, B (reprint author), Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. EM hub@ucalgary.ca NR 51 TC 42 Z9 45 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2004 VL 101 IS 1 BP 320 EP 324 DI 10.1073/pnas.0304445101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200059 PM 14691260 ER PT J AU Yoshitake, T Wang, FH Kuteeva, E Holmberg, K Yamaguchi, M Crawley, JN Steiner, R Bartfai, T Ogren, SO Hokfelt, T Kehr, J AF Yoshitake, T Wang, FH Kuteeva, E Holmberg, K Yamaguchi, M Crawley, JN Steiner, R Bartfai, T Ogren, SO Hokfelt, T Kehr, J TI Enhanced hippocampal noradrenaline and serotonin release in galanin-overexpressing mice after repeated forced swimming test SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microdialysis; 5-hydroxytryptamine; transgenic mice; hippocampus; affective disorders ID PREPROGALANIN MESSENGER-RNA; CHRONIC RESTRAINT STRESS; LOCUS-COERULEUS NEURONS; TRANSGENIC MICE; NOREPINEPHRINE RELEASE; NEUROPEPTIDE-Y; FLUORESCENCE DETECTION; LIQUID-CHROMATOGRAPHY; RAT HIPPOCAMPUS; MICRODIALYSIS AB Basal and forced swimming (FS) stress-induced release of noradrenaline (NA) and serotonin (5-HT) were determined by in vivo microdialysis in the ventral hippocampus of mice overexpressing galanin under the platelet-derived growth factor B promoter (GaIOE/P) or under the dopamine beta-hydroxylase promoter (GaIOE/D) (only NA). WT mice served as controls. Intraventricular infusion of galanin significantly reduced basal extracellular NA in WT mice and in GaIOE/P mice (albeit less so). Microdialysis sampling during a 10-min FS showed that NA and 5-HT release were elevated to 213% and 156%, respectively, in the GaIOE/P group, whereas in the WT group the increases were only 127% and 119%, respectively. The second (repeated) 10-min FS (RFS) caused a marked enhancement of NA and 5-HT release in the GaIOE/P mice to 344% and 275%, respectively. However, the RFS caused only a 192% increase of extracellular NA levels in the GaIOE/D mice. Pretreatment with the putative peptidergic galanin receptor antagonist M35 almost completely blocked the elevation of NA and 5-HT levels in the GaIOE/P after RFS. These results suggest that the NA and 5-HT hippocampal afferents in GaIOE/P mice are hypersensitive to both conditioned and unconditioned stressful stimuli, such as FS, and that this effect is mediated by galanin receptors. The present findings support a role of galanin in the regulation of release of NA and 5-HT, two neurotransmitters involved in mood control. C1 Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Fukuoka Univ, Fac Pharmaceut Sci, Fukuoka 8140180, Japan. NIMH, Lab Behav Neurosci, Bethesda, MD 20815 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. Scripps Res Inst, La Jolla, CA 92037 USA. RP Kehr, J (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden. EM jan.kehr@neuro.ki.se OI Ogren, Sven Ove/0000-0003-2573-5276 NR 51 TC 49 Z9 53 U1 0 U2 5 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 JAN 6 PY 2004 VL 101 IS 1 BP 354 EP 359 DI 10.1073/pnas.0307042101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761VY UT WOS:000187937200065 PM 14701907 ER PT J AU Meffre, E Schaefer, A Wardemann, H Wilson, P Davis, E Nussenzweig, MC AF Meffre, E Schaefer, A Wardemann, H Wilson, P Davis, E Nussenzweig, MC TI Surrogate light chain expressing human peripheral B cells produce self-reactive antibodies SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE surrogate light chains; B lymphocytes; polyreactive; autoantibody ID SINGLE-STRANDED-DNA; EPSTEIN-BARR-VIRUS; NATURAL ANTIBODIES; POSITIVE SELECTION; IMMUNOGLOBULIN-M; MARGINAL ZONE; LYMPHOCYTES-B; AUTOANTIBODIES; RECEPTORS; DISEASE AB Human B cells that coexpress surrogate and conventional light chains (V-preB(+)L(+)) show an unusual heavy and light chain antibody repertoire that display evidence of receptor editing. However, it is unclear whether V-preB(+)L(+) B cells have been silenced by receptor editing or still express autoreactive antibodies. Here we report that 68% of the antibodies expressed by V-preB(+)L(+) B cells are autoreactive. A majority of these autoantibodies are true antinuclear antibodies (ANA), and 50% of the ANAs are also reactive with a diverse group of antigens that include dsDNA, ssDNA, immunoglobulin, insulin, and bacterial lipopolysaccharide. Such antibodies are rarely encountered among conventional B cells. We conclude that V-preB(+)L(+) B cells are a unique subset of normal circulating human B cells that escape central tolerance mechanisms and express self-reactive antibodies including potentially harmful ANAs. C1 Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY 10021 USA. NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Cornell Univ, Hosp Special Surg, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Meffre, E (reprint author), Hosp Surg, 535 E 70th St, New York, NY 10021 USA. EM meffree@hss.edu; nussen@mail.rockefeller.edu NR 30 TC 85 Z9 86 U1 0 U2 5 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 JAN 5 PY 2004 VL 199 IS 1 BP 145 EP 150 DI 10.1084/jem.20031550 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 763GC UT WOS:000188065700016 PM 14699083 ER PT J AU Wu, L Martin, TD Carrington, M KewalRamani, VN AF Wu, L Martin, TD Carrington, M KewalRamani, VN TI Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV transmission SO VIROLOGY LA English DT Article DE HIV-1; DC-SIGN; dendritic cells; Raji cells; THP-1 cells; transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELLS; DENDRITIC CELLS; TRANS-INFECTION; IMMUNOLOGICAL SYNAPSE; LYMPHOCYTES; RECEPTOR; LYMPHOMA; PROTEIN; BINDING AB A number of studies examining interactions of dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) with viral pathogens have relied on monocytic transfectants as models for primary DCs. Here we show that the presumed "THP-1" monocytic cells used in these studies are instead Raji B cells. Moreover, we demonstrate that true THP-1 cells do not support DC-SIGN-mediated HIV-1 transmission, whereas human B cell lines efficiently enhance this process. These data indicate that there are features common to B cells and DCs that facilitate transmission of HIV-1 and provide new insights toward the mechanism of DC-SIGN-mediated HIV-1 transmission. Published by Elsevier Inc. C1 NCI, Model Dev Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. RP KewalRamani, VN (reprint author), NCI, Model Dev Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. EM vineet@ncifcrf.gov RI Wu, Li/E-4330-2011 OI Wu, Li/0000-0002-5468-2487 FU NCI NIH HHS [N01-CO-12400] NR 28 TC 97 Z9 97 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2004 VL 318 IS 1 BP 17 EP 23 DI 10.1016/j.virol.2003.09.028 PG 7 WC Virology SC Virology GA 778LL UT WOS:000189243000003 PM 14972530 ER PT J AU Rawat, SS Eaton, J Gallo, SA Martin, TD Ablan, S Ratnayake, S Viard, M KewalRamani, VN Wang, JM Blumenthal, R Puri, A AF Rawat, SS Eaton, J Gallo, SA Martin, TD Ablan, S Ratnayake, S Viard, M KewalRamani, VN Wang, JM Blumenthal, R Puri, A TI Functional expression of CD4, CXCR4, and CCR5 in glycosphingolipid-deficient mouse melanoma GM95 cells and susceptibility to HIV-1 envelope glycoprotein-triggered membrane fusion SO VIROLOGY LA English DT Article DE HIV-1; membrane fusion; glycosphingolipid(s) ID HUMAN-IMMUNODEFICIENCY-VIRUS; GLUCOSYLCERAMIDE SYNTHASE; TYPE-1 ENVELOPE; IMPROVED INHIBITORS; MEDIATED FUSION; ENTRY; PROTEIN; MICRODOMAINS; GROWTH; LINES AB We had previously reported that glycosphingolipids (GSL) support human immunodeficiency virus type 1 (HIV-1) entry. In this study, we further examined this issue by expressing HIV-1 receptors in GSL-deficient GM95 cells. GM95 cells expressing low levels of CD4 and CXCR4 or CCR5 did not support HIV-1 Env-mediated fusion. However, higher expression of these receptors rendered GM95 cells highly susceptible to fusion with cells expressing appropriate HIV-1 envelope glycoproteins (HIV-1 Envs). The GM95 cells exhibited a different fusion phenotype when compared with GSL(+) NIH3T3 cells bearing similar receptor levels. Fusion of GM95 targets expressing higher levels of CD4 and coreceptors occurred at 25degreesC and was sensitive to cholesterol depletion or disruption of the cyloskeleton. In contrast, the fusion threshold of NIH3T3CD4X4/R5 targets was at greater than or equal to 28degreesC as previously reported and was insensitive to cholesterol depletion or cytoskeletal network disruption. On the basis of these observations, we propose that target membrane GSLs support HIV-1 Env-mediated fusion at low density of receptors by stabilizing receptor pools in natural targets. Published by Elsevier Inc. C1 NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NCI, HIV Drug Resistance Program, Canc Res Ctr, NIH, Frederick, MD 21701 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, Canc Res Ctr, NIH, Frederick, MD 21701 USA. RP Puri, A (reprint author), NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, POB B,Bldg 469,Room 211,Miller Dr, Frederick, MD 21702 USA. EM apuri@helix.nih.gov OI Gallo, Stephen/0000-0001-6043-2153 NR 42 TC 16 Z9 18 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 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2004 VL 318 IS 1 BP 55 EP 65 DI 10.1016/j.virol.2003.08.042 PG 11 WC Virology SC Virology GA 778LL UT WOS:000189243000008 PM 14972535 ER PT J AU Zhi, N Zadori, Z Brown, KE Tijssen, P AF Zhi, N Zadori, Z Brown, KE Tijssen, P TI Construction and sequencing of an infectious clone of the human parvovirus B19 SO VIROLOGY LA English DT Article DE parvovirus b19; complete sequence; infectious clone; erythrovirus; viral DNA replication; inverted terminal repeats ID ERYTHROCYTE-P-ANTIGEN; CELL-LINE; MINUTE VIRUS; FETAL LIVER; IDENTIFICATION; GENOME; DNA; REPLICATION; PROPAGATION; PROTEINS AB Human parvovirus B19 has a nonenveloped, icosahedral capsid packaging a linear single-stranded DNA genome of 5.6 kb with long inverted terminal repeats (ITR) at both the 5' and 3' end. Previous attempts to construct a full-length B19 clone were unsuccessful due to deletions in the ITR sequences. We cloned the complete parvovirus B19 genome with intact ITRs from an aplastic crisis patient. Sequence analysis of the complete viral genome indicated that both 5' and 3' ITRs have two sequence configurations and several base changes within the ITRs compared to previous published sequences. After transfection of the plasmid into permissive cells, spliced and non-spliced viral transcripts and viral capsid proteins could be detected. Southern blot analysis of the DNA purified from the plasmid-transfected cells confirmed parvovirus B19 DNA replication. Production of infectious virus by the B19 plasmid was shown by inoculation of cell lysate derived from transfected cells into fresh cells. Together, these results indicate the first successful production of an infectious clone for parvovirus B19 virus. Published by Elsevier Inc. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ, Canada. RP Zhi, N (reprint author), NIH, Room 7C218,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhin@nhlbi.nih.gov NR 37 TC 53 Z9 58 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2004 VL 318 IS 1 BP 142 EP 152 DI 10.1016/j.virol.2003.09.011 PG 11 WC Virology SC Virology GA 778LL UT WOS:000189243000016 PM 14972543 ER PT J AU Freidlin, B Korn, EL AF Freidlin, B Korn, EL TI Erythropoietin to treat anaemia in patients with head and neck cancer SO LANCET LA English DT Letter ID TRIAL C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NR 5 TC 7 Z9 7 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 3 PY 2004 VL 363 IS 9402 BP 81 EP 81 DI 10.1016/S0140-6736(03)15187-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 758YZ UT WOS:000187711300041 PM 14724012 ER PT J AU Mattapallil, JJ Letvin, NL Roederer, M AF Mattapallil, JJ Letvin, NL Roederer, M TI T-cell dynamics during acute SIV infection SO AIDS LA English DT Article DE naive; memory; SIV; acute infection; rhesus macaque; T and B cells; mucosal T cells; coreceptor ID SIMIAN IMMUNODEFICIENCY VIRUS; HIV-1 INFECTION; PERIPHERAL-BLOOD; RHESUS MACAQUES; ACTIVATION ANTIGENS; BETA(7) INTEGRINS; LYMPHOID-TISSUES; IN-VIVO; HLA-DR; MEMORY AB Objectives: To delineate T-cell dynamics during acute SIV infection, particularly of phenotypically defined memory T cell subsets. Design: T cells are a heterogeneous mix of naive and memory subsets delineated by simultaneously measuring CD4, CD8, CD45RA/RO, CD11a, CD28, and CD27. The effects of SIV infection on these subsets was measured to evaluate the impact of changes in functionally distinct cell types during pathogenesis. Methods: Peripheral blood was obtained from six SIV-infected macaques at multiple times before and after SIV infection and analyzed using 12-color flow cytometry. Results: Acute infection was characterized by an initial lymphopenia caused by a decline in B cells. Total T-cell counts remained steady during the early acute phase; however, CD4 cell counts declined while CD8 T cells increased. The decline in CD4 T cells was a result of a decline in both naive and memory cells. CCR5+ or CD103+ subsets of CD4 T cells were depleted but only partially accounted for the decline of CD4 memory T cells, suggesting that acute infection was associated with a rapid redistribution of T cells from the periphery. Naive CD8 cell counts declined while memory CD8 cell counts increased. The increase coincided with declines in plasma viremia and was made up initially of CD27-CD28- (effector) cells; subsequently, the predominant phenotype became CD27+CD28-, akin to central memory cells. Conclusions: A complete understanding of the T-cell dynamics during acute SIV or HIV infection requires the simultaneous evaluation of a broad spectrum of T-cell subsets. Changes in homeostasis and associated immunopathogenesis can no longer be accurately described simply by measuring naive and memory T-cell subsets. (C) 2004 Lippincott Williams Wilkins. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Roederer, M (reprint author), Room 5509,40 Convent Dr, Bethesda, MD 20895 USA. RI Roederer, Mario/G-1887-2011 NR 42 TC 51 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2004 VL 18 IS 1 BP 13 EP 23 DI 10.1097/01.aids.0000096899.73209.b6 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 776DN UT WOS:000189101600002 PM 15090825 ER PT J AU Ioannidis, JPA Tatsioni, A Abrams, EJ Bulterys, M Coombs, RW Goedert, JJ Korber, BT Mayaux, MJ Mofenson, LM Moye, J Newell, ML Shapiro, DE Teglas, JP Thompson, B Wiener, J AF Ioannidis, JPA Tatsioni, A Abrams, EJ Bulterys, M Coombs, RW Goedert, JJ Korber, BT Mayaux, MJ Mofenson, LM Moye, J Newell, ML Shapiro, DE Teglas, JP Thompson, B Wiener, J TI Maternal viral load and rate of disease progression among vertically HIV-1-infected children: an international meta-analysis SO AIDS LA English DT Article DE viral load; vertical transmission; meta-analysis; disease progression; AIDS ID IMMUNODEFICIENCY-VIRUS TYPE-1; PERINATAL TRANSMISSION; INFECTED CHILDREN; HIV-1 INFECTION; INFANTS; RISK; RNA; CCR5-DELTA-32; LIFE; ALLELES AB Objective: To evaluate whether maternal human immunodeficiency virus type 1 (HIV-1) RNA levels in the serum/plasma of mothers at or close to the time of delivery affects the rate of disease progression among vertically HIV-1-infected children and whether it correlates with other parameters affecting infant disease progression. Methods: International meta-analysis of eight studies with 574 HIV-1 infected infants with available maternal HIV-1 RNA measurements at or close to delivery and clinical follow-up. The primary outcome was disease progression (stage C disease or death, n=178). Cohort-stratified Cox models were used. Results: Higher maternal HIV-1 RNA level at or close to delivery significantly increased disease progression risk [hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.04-1.52 per 1 log(10) increase; P=0.02) with a borderline effect on mortality (HR, 1.26; 95% CI, 0.96-1.65; P=0.10]. The association with disease progression risk was strong in the first 6 months of life (HR, 1.77; 95% CI, 1.28-2.45; P=0.001), but not subsequently (HR, 1.03; 95% CI, 0.81-1.30). Maternal HIV-1 RNA, early infant HIV-1 RNA (at 30-200 days after birth) and infant CD4 were independent predictors of disease progression in the first 6 months. Maternal HIV-1 RNA at or close to delivery correlated with early infant HIV-1 RNA (r=0.26, P<0.001). Effects were independent of maternal and infant treatment. Conclusions: Higher maternal HIV-1 RNA at or close to delivery strongly predicts disease progression for HIV-1-infected infants, especially in their first 6 months of life and correlates with the early peak of viremia in the infected child. (C) 2004 Lippincott Williams & Wilkins. C1 Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece. Tufts New England Med Ctr, Div Clin Care Res, Boston, MA USA. Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA. Ctr Dis Control & Prevent, Mother Child Transmiss & Pediat & Adolescent Stud, Epidemiol Branch, Div HIV AIDS Prevent, Atlanta, GA USA. Univ Washington, Sch Med, Seattle, WA USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. INSERM, U569, F-94275 Le Kremlin Bicetre, France. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. Inst Child Hlth, European Collaborat Study Coordinating Ctr, Ctr Paediat Epidemiol & Biostat, London, England. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. EM jioannid@cc.uoi.gr RI Ioannidis, John/G-9836-2011; OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586; Newell, Marie-Louise/0000-0002-1074-7699; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [N01 AI 85339, U01 AI 34840, U01 AI 34841, U01 AI 34842, U01 AI 34856, U01 AI 34858]; NICHD NIH HHS [R01-1HD-25714, HD-8-2913] NR 33 TC 26 Z9 29 U1 0 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 JAN 2 PY 2004 VL 18 IS 1 BP 99 EP 108 DI 10.1097/01.aids.0000088200.77946.42 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 776DN UT WOS:000189101600012 PM 15090835 ER PT J AU Massad, LS Seaberg, EC Watts, DH Hessol, NA Melnick, S Bitterman, P Anastos, K Silver, S Levine, AM Minkoff, H AF Massad, LS Seaberg, EC Watts, DH Hessol, NA Melnick, S Bitterman, P Anastos, K Silver, S Levine, AM Minkoff, H TI Low incidence of invasive cervical cancer among HIV-infected US women in a prevention program SO AIDS LA English DT Article DE cervical cancer; cancer incidence; HIV in women; cancer screening; cancer registry ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SQUAMOUS INTRAEPITHELIAL LESIONS; SOUTH-AFRICA; SEROPOSITIVE WOMEN; INTERAGENCY HIV; RISK-FACTORS; NEOPLASIA; HPV; IMMUNOSUPPRESSION AB Objective: To measure the incidence of invasive cervical cancer (ICC) in US women infected with HIV. Design: Multicenter prospective cohort study, conducted between October 1994, and September 2001. Setting: HIV research centers operating as six urban consortia in the Women's Interagency HIV Study. Subjects: A total of 2131 women (462 HIV seronegative, 1661 HIV seropositive, and eight seroconverters). Women with a history of hysterectomy or of cervical cancer at baseline evaluation were excluded. Intervention: Cervical cytology obtained at 6-month intervals, with a colposcopy referral threshold of atypia, followed by individualized treatment. Main outcome measure: ICC diagnoses obtained from study databases and regional cancer registries and confirmed by a gynecologic pathologist. Results: No incident ICC were observed in HIV seronegative women during 2375 woman-years of observation. During 8260 woman-years of observation, eight putative incident cases of cervical cancer were identified in HIV seropositive women, but only one was confirmed, yielding an incidence rate of 1.2/10000 woman-years (95% confidence interval, 0.3-6.7/10000 woman-years). The difference in incidence between HIV seropositive and seronegative women was not significant (P=1.0). Conclusion: ICC is uncommon in HIV-infected US women participating in a regular prevention program. (C) 2004 Lippincott Williams Wilkins. C1 So Illinois Univ, Sch Med, Dept Obstet & Gynecol, Springfield, IL 62794 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, Bethesda, MD 20892 USA. Rush Med Coll, Chicago, IL 60612 USA. Monash Med Ctr, Bronx, NY USA. Lincoln Med & Mental Hlth Ctr, Bronx, NY 10451 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. SUNY, Maimonides Med Ctr, Brooklyn, NY USA. RP Massad, LS (reprint author), So Illinois Univ, Sch Med, Dept Obstet & Gynecol, POB 19640, Springfield, IL 62794 USA. FU NCRR NIH HHS [M01-RR-00079, M01-RR-00083]; NIAID NIH HHS [U01-AI-31834, U01-AI-34994, U01-AI-35004, U01-AI-42590, U01-AI-34993]; NICHD NIH HHS [U01-HD-32632] NR 33 TC 38 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2004 VL 18 IS 1 BP 109 EP 113 DI 10.1097/01.aids.0000104324.15729.10 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 776DN UT WOS:000189101600013 PM 15090836 ER PT J AU Fitch, RW Pei, XF Kaneko, Y Gupta, T Shi, D Federova, I Daly, JW AF Fitch, RW Pei, XF Kaneko, Y Gupta, T Shi, D Federova, I Daly, JW TI Homoepiboxidines: further potent agonists for nicotinic receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID NEUROBLASTOMA CLONAL LINE; EPIBATIDINE ANALOGS; ACETYLCHOLINE-RECEPTORS; PHARMACOLOGICAL-PROPERTIES; ANALGESIC ACTIVITY; LIGAND-BINDING; CELL-LINE; CHANNEL; RAT; EXPRESSION AB Homoepiboxidine (3) and the corresponding N-methyl (4) and N-benzyl (5) derivatives were prepared from a 6beta-carbomethoxynortropane (8). Affinities and functional activities at neuromuscular, central neuronal and ganglionic-type nicotinic receptors were compared to those of epibatidine 1, and epiboxidine 2. Homoepiboxidine had equivalent affinity/activity to epiboxidine at neuromuscular, neuronal alpha4beta2, and most alpha3-containing ganglionic-type nicotinic receptors. The N-substituted derivatives showed reduced affinity/activity at most receptor subtypes. Replacement of the methylisoxazole moiety of 3 and 4 with a methyloxadiazole moiety provided analogues 6 and 7, which had greatly reduced affinity/activity in virtually all assays at nicotinic receptors. Marked analgetic activity in mice occurred at the following ip doses: epibatidine 10 mug/kg; epiboxidine 25 mug/kg; homo-epiboxidine 100 mug/kg,- N-methylhomoepiboxidine 100 mug/kg; the methyloxadiazole (6) 100 pg/kg. The time course at such ip doses was significantly longer for homoepiboxidine 3 with marked analgesia still manifest at 30 min post-injection. Epiboxidine and the homoepiboxidines were less toxic than epibatidine. Published by Elsevier Ltd. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 46 TC 18 Z9 18 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 2 PY 2004 VL 12 IS 1 BP 179 EP 190 DI 10.1016/j.bmc.2003.10.015 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 763RC UT WOS:000188113400019 PM 14697783 ER PT J AU Greiner, E Folk, JE Jacobson, AE Rice, KC AF Greiner, E Folk, JE Jacobson, AE Rice, KC TI A novel and facile preparation of bremazocine enantiomers through optically pure N-norbremazocines SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID KAPPA-OPIOID RECEPTOR; EXPEDIENT SYNTHESIS; AGONIST; COCAINE AB In order to provide ready access to multigram quantities of the optically pure bremazocines [(-)- and (+)-9,9-dimethyl-5-ethyl-2-hydroxy-2-(1-hydroxy-cyclopropylmethyl)-6,7-benzomorphan)], we have developed an improved non-chromatographic synthesis, and determined the optical purity of their N-nor precursors using a rapid and relatively simple H-1 NMR method based on diastereomeric derivatization with optically pure 1-phenylethylisocyanate. This method of determining optical purity should be readily amenable to similar systems containing phenolic amino functionalities. Finally, a greatly simplified methodology for introduction of the N-(1-hydroxycyclopropylmethyl) substituent in bremazocine is described. The improved synthetic method-the overall yield was increased about 3-fold-combined with the practical methodology to determine optical purity will considerably facilitate the employment of these enantiomers as pharmacological tools for examination of the K-opioid receptor system, as well as their evaluation as drug abuse treatment agents. This synthesis will also enable the study of these enantiomers for other, non-classical applications (e.g., treatment agents for HIV). Published by Elsevier Ltd. C1 NIDDKD, Med Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, US Dept HHS, NIH, 8 Ctr Dr,MSC 0815, Bethesda, MD 20892 USA. EM kr21f@nih.gov NR 21 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 2 PY 2004 VL 12 IS 1 BP 233 EP 238 DI 10.1016/j.bmc.2003.10.029 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 763RC UT WOS:000188113400024 PM 14697788 ER PT J AU Heydorn, A Sondergaard, BP Hadrup, N Holst, B Haft, CR Schwartz, TW AF Heydorn, A Sondergaard, BP Hadrup, N Holst, B Haft, CR Schwartz, TW TI Distinct in vitro interaction pattern of dopamine receptor subtypes with adaptor proteins involved in post-endocytotic receptor targeting SO FEBS LETTERS LA English DT Article DE dopamine receptor; sorting nexin 1; ezrin-radixin-moesin-binding phosphoprotein 50; N-ethylmaleimide-sensitive factor; protein sorting ID BETA-2-ADRENERGIC RECEPTOR; D-3 RECEPTORS; BINDING; DESENSITIZATION; LOCALIZATION; ASSOCIATION; MODULATION; MECHANISMS; ARRESTINS; ABP-280 AB The mechanisms underlying targeted sorting of endocytosed receptors for recycling to the plasma membrane or degradation in lysosomes are poorly understood. In this report, the C-terminal tails of the five dopamine receptors (D1-D5) were expressed as glutathione S-transferase (GST) fusion proteins and studied for their interaction with ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) and N-ethylmaleimide-sensitive factor (NSF), which are known to be involved in post-endocytic recycling of receptors back to the plasma membrane, and with sorting nexin 1 (SNX1), known to be involved in targeting receptors to lysosomal degradation. EBP50 did not bind any of the dopamine receptor tails. NSF bound strongly to D1 and D5 and only weakly to D2, D3 and D4. However, SNX1 clearly distinguished between D1 and D5, as only D5 bound strongly to this protein. This report shows that there are distinct interaction patterns for NSF and SNX1 to the various dopamine receptor subtypes. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Univ Copenhagen, Panum Inst, Mol Pharmacol Lab, Dept Pharmacol, DK-2200 Copenhagen, Denmark. Univ Copenhagen, Panum Inst, Lab Cardiovasc Pharmacol, Dept Pharmacol, DK-2200 Copenhagen, Denmark. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schwartz, TW (reprint author), Univ Copenhagen, Panum Inst, Mol Pharmacol Lab, Dept Pharmacol, Bldg 18,6,Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM schwartz@molpharm.dk OI Hadrup, Niels/0000-0002-1188-445X NR 21 TC 26 Z9 27 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 JAN 2 PY 2004 VL 556 IS 1-3 BP 276 EP 280 DI 10.1016/S0014-5793(03)01431-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 763XK UT WOS:000188125600048 PM 14706863 ER PT J AU Shah, BH Farshori, MP Catt, KJ AF Shah, BH Farshori, MP Catt, KJ TI Neuropeptide-induced transactivation of a neuronal epidermal growth factor receptor is mediated by metalloprotease-dependent formation of heparin-binding epidermal growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; PROTEIN-COUPLED RECEPTORS; SMOOTH-MUSCLE-CELLS; KINASE-C-DELTA; ANGIOTENSIN-II; EGF RECEPTOR; MATRIX METALLOPROTEINASES; TYROSINE KINASES; NERVOUS-SYSTEM; ERK ACTIVATION AB Numerous external stimuli, including G protein-coupled receptor agonists, cytokines, growth factors, and steroids activate mitogen-activated protein kinases (MAPKs) through phosphorylation of the epidermal growth factor receptor (EGF-R). In immortalized hypothalamic neurons (GT1-7 cells), agonist binding to the gonadotropin-releasing hormone receptor (GnRH-R) causes phosphorylation of MAPKs that is mediated by protein kinase C (PKC)-dependent transactivation of the EGF-R. An analysis of the mechanisms involved in this process showed that GnRH stimulation of GT1-7 cells causes release/shedding of the soluble ligand, heparin binding epidermal growth factor (HB-EGF), as a consequence of metalloprotease activation. GnRH-induced phosphorylation of the EGF-R and, subsequently, of Shc, ERK1/2, and its dependent protein, p90(RSK-1) (p90 ribosomal S6 kinase 1 or RSK-1), was abolished by metalloprotease inhibition. Similarly, blockade of the effect of HB-EGF with the selective inhibitor CRM197 or a neutralizing antibody attenuated signals generated by GnRH and phorbol 12-myristate 13-acetate, but not those stimulated by EGF. In contrast, phosphorylation of the EGF-R, Shc, and ERK1/2 by EGF and HB-EGF was independent of PKC and metalloprotease activity. The signaling characteristics of HB-EGF closely resembled those of GnRH and EGF in terms of the phosphorylation of EGF-R, Shc, ERK1/2, and RSK-1 as well as the nuclear translocation of RSK-1. However, neither the selective Src kinase inhibitor PP2 nor the overexpression of negative regulatory Src kinase and dominant negative Pyk2 had any effect on HB-EGF-induced responses. In contrast to GT1-7 cells, human embryonic kidney 293 cells expressing the GnRH-R did not exhibit metalloprotease induction and EGF-R transactivation during GnRH stimulation. These data indicate that the GnRH-induced transactivation of the EGF-R and the subsequent ERK1/2 phosphorylation result from ectodomain shedding of HB-EGF through PKC-dependent activation of metalloprotease(s) in neuronal GT1-7 cells. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. NR 54 TC 34 Z9 35 U1 1 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 JAN 2 PY 2004 VL 279 IS 1 BP 414 EP 420 DI 10.1074/jbc.M309083200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757GU UT WOS:000187555300050 PM 14573593 ER PT J AU Nakamura, T Unda, F de-Vega, S Vilaxa, A Fukumoto, S Yamada, KM Yamada, Y AF Nakamura, T Unda, F de-Vega, S Vilaxa, A Fukumoto, S Yamada, KM Yamada, Y TI The Kruppel-like factor epiprofin is expressed by epithelium of developing teeth, hair follicles, and limb buds and promotes cell proliferation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR SP1; FACTOR FAMILY; TOOTH; GENE; DIFFERENTIATION; HYBRIDIZATION; PROTEINS; GROWTH; IDENTIFICATION; MORPHOGENESIS AB We identified a cDNA clone for epiprofin, which is preferentially expressed in teeth, by differential hybridization using DNA microarrays from an embryonic day 19.5 mouse molar cDNA library. Sequence analysis revealed that this cDNA encodes a member of the Kruppel-like factor family containing three characteristic C2H2-type zinc finger motifs. The full-length cDNA was obtained by the 5' Cap capture method. Except for its 5'-terminal sequence, the epiprofin mRNA sequence is almost identical to the predicted sequence of Kruppel-like factor 14/Sp6 ( specificity protein 6), which was previously identified in expressed sequence tag data bases and GenBank(TM) by an Sp1 zinc finger DNA-binding domain search (Scohy, S., Gabant, P., Van Reeth, T., Hertveldt, V., Dreze, P. L., Van Vooren, P., Riviere, M., Szpirer, J., and Szpirer, C. (2000) Genomics 70, 93 - 101). This sequence difference is due to differences in the assignment of the location of exon 1. In situ hybridization revealed that epiprofin mRNA is expressed by proliferating dental epithelium, differentiated odontoblast, and also hair follicle matrix epithelium. In addition, whole mount in situ hybridization showed transient expression of epiprofin mRNA in cells of the apical ectodermal ridge in developing limbs and the posterior neuropore. Transfection of an epiprofin expression vector revealed that this molecule is localized in the nucleus and promotes cell proliferation. Thus, epiprofin is a highly cell- and tissue-specific nuclear protein expressed primarily by proliferating epithelial cells of teeth, hair follicles, and limbs that may function in the development of these tissues by regulating cell growth. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Univ Basque Country, Fac Med & Dent, Dept Cell Biol & Histol, Leioa 48490, Spain. Univ Tarapaca, Dept Biol & Salud, Arica, Chile. RP Yamada, Y (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Rm 405,30 Convent Dr, Bethesda, MD 20892 USA. RI Nakamura, Takashi/P-7796-2016; SGIKER, Cienciometria/A-5759-2012; OI Nakamura, Takashi/0000-0001-9904-1037; Yamada, Kenneth/0000-0003-1512-6805 NR 33 TC 40 Z9 41 U1 3 U2 22 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 JAN 2 PY 2004 VL 279 IS 1 BP 626 EP 634 DI 10.1074/jbc.M307502200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757GU UT WOS:000187555300076 PM 14551215 ER PT J AU Fang, J Sullivan, M McCutchan, TF AF Fang, J Sullivan, M McCutchan, TF TI The effects of glucose concentration on the reciprocal regulation of rRNA promoters in Plasmodium falciparum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRINGENT CONTROL; ESCHERICHIA-COLI; MALARIA PARASITE; DNA; GENE; SEQUENCES; DISTINCT; YEAST; AMPLIFICATION; TRANSCRIPTION AB The developmental progression of Plasmodium falciparum is remarkably sensitive to glucose concentration. We have investigated the effects of glucose concentration on the parasite development cycle as reflected by changes of ribosomal RNA ( rRNA) transcription. We showed that glucose starvation differentially affects transcriptional control of the rRNA genes by sharply repressing transcription from those loci involved with asexual development of the parasite while up-regulating transcription at those loci involved with sexual development of the parasite. Temperature change also effects regulation of transcription. We found that the effects of temperature and glucose were synergistic. We identified and compared the upstream region of the transcription start sites of each gene. These putative promoter structures are considerably different from one another and contain structures remarkably similar to rRNA control elements in other organisms. C1 NIAID, Mol Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP McCutchan, TF (reprint author), NIAID, Mol Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NR 34 TC 24 Z9 24 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 JAN 2 PY 2004 VL 279 IS 1 BP 720 EP 725 DI 10.1074/jbc.M308284200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757GU UT WOS:000187555300086 PM 14570919 ER PT J AU Lee, JW Blanco, L Zhou, T Garcia-Diaz, M Bebenek, K Kunkel, TA Wang, ZG Povirk, LF AF Lee, JW Blanco, L Zhou, T Garcia-Diaz, M Bebenek, K Kunkel, TA Wang, ZG Povirk, LF TI Implication of DNA polymerase lambda in alignment-based gap filling for nonhomologous DNA end joining in human nuclear extracts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRAND BREAK; DEPENDENT PROTEIN-KINASE; CELL-FREE-EXTRACTS; MU POL-MU; IN-VITRO; LIGASE-IV; 3'-PHOSPHOGLYCOLATE TERMINI; MAMMALIAN CHROMOSOME; IONIZING-RADIATION; CATALYTIC SUBUNIT AB Accurate repair of free radical-mediated DNA double-strand breaks by the nonhomologous end joining pathway requires replacement of fragmented nucleotides in the aligned ends by a gap-filling DNA polymerase. Nuclear extracts of human HeLa cells, supplemented with recombinant XRCC4-DNA ligase IV complex (XRCC4/ligase IV), were capable of accurately rejoining model double-strand break substrates with a 1- or 2-base gap, and the gap-filling step was dependent on XRCC4/ligase IV. To determine what polymerase was responsible for gap filling, end joining was examined in the presence of polyclonal antibodies against each of two prime candidate enzymes, DNA polymerases mu and lambda, both of which were present in the extracts. For a DNA substrate with partially complementary 3' overhangs and a 2-base gap, antibodies to polymerase lambda completely eliminated both gap filling and accurate end joining, whereas antibodies to polymerase mu had little effect. Immunodepletion of polymerase lambda, but not polymerase mu, likewise blocked both gap filling and end joining, and both functions could be restored by addition of recombinant polymerase lambda. Recombinant polymerase mu, and a truncated polymerase lambda lacking the Brca1 C-terminal domain, were at least 10-fold less active in restoring gap filling to the immunodepleted extracts, and polymerase beta was completely inactive. The results suggest that polymerase lambda is the primary gap-filling polymerase for accurate nonhomologous end joining, and that the Brca1 C-terminal domain is required for this activity. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. NIEHS, Genet Mol Lab, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. RP Povirk, LF (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980230, Richmond, VA 23298 USA. RI Blanco, Luis/I-1848-2015 FU NCI NIH HHS [CA40615] NR 39 TC 149 Z9 154 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 JAN 2 PY 2004 VL 279 IS 1 BP 805 EP 811 DI 10.1074/jbc.M307913200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757GU UT WOS:000187555300096 PM 14561766 ER PT J AU Zhang, MY Shu, YU Rudolph, D Prabakaran, P Labrijn, AF Zwick, MB Lal, RB Dimitrov, DS AF Zhang, MY Shu, YU Rudolph, D Prabakaran, P Labrijn, AF Zwick, MB Lal, RB Dimitrov, DS TI Improved breadth and potency of an HIV-1-neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV; antibody; phage display; gp140; inhibitors ID IMMUNODEFICIENCY-VIRUS TYPE-1; CORECEPTOR USAGE; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; HIV-1; GP120; CD4; FUSION; INHIBITORS; PHENOTYPE AB Several human monoclonal antibodies can neutralize a range of human immunodeficiency virus type 1 (HIV-1) primary isolates but their potency and related ability to suppress generation of HIV-1 escape mutants is significantly lower than the activity of antiretroviral drugs currently in clinical use. Recently, a human Fab, X5, was identified and found to 2 neutralize primary isolates from different clades. Further improvement, of the potency and breadth of HIV-1 neutralization by this antibody, could be critical for its potential use in the treatment of HIV-1-infected patients. However, increasing potency of an antibody by selection from libraries may lead to a decrease in the breadth of neutralization. In an attempt to solve this problem, we subjected a random mutagenesis library of the scFv X5 to sequential rounds of selection on non-homologous HIV-1 envelope glycoproteins (Envs) dubbed sequential antigen panning (SAP). By using SAP, we identified two scFv antibodies, m6 and m9, that were tested with a panel of 33 diverse primary HIV-1 infectious isolates in an assay based on a reporter cell-line expressing high levels of CD4, CCR5 and CXCR4. The IC50 was less than 50 mug/ml for 21 (m6) and 19 (m9) out of 29 isolates from group M (subtypes A-C, F, G and CRF-01AE) and one isolate from group N; three isolates from group 0 were not significantly inhibited at 50 mug/ml. The average IC50 values for the two antibodies were significantly (p < 0.001, n = 29) lower compared to scFv X5. Their inhibitory activity does not appear to be related to the HIV-1 subtype, coreceptor usage or the disease stage. m9 inhibited infection of peripheral blood mononuclear cells by the primary isolates JRCSF, 89.6 and BR020 with IC90 of 4, 6 and 25 mug/ml, respectively; for a single-round infection by pseudovirus, the IC90 for JRSCF, 89.6, YU2 and HXBc2 was 15, 5, 15 and 5 mug/ml, respectively. In these two assays the IC90 for m9 was, on average, two- to threefold lower than for scFv X5. These results demonstrate that both the potency and the breadth of HIV-1 neutralization of one of the few known potent broadly cross-reactive human monoclonal antibodies, scFv X5, could be improved significantly. However, only experiments in animal models and clinical trials in humans will show whether these new scFvs and the approach for their identification have potential in the development of prophylactics and therapeutics for HIV-1 infections. (C) 2003 Elsevier Ltd. All rights reserved. C1 NCI, Human Immunovirol & Computat Biol Grp, LECB,CCR, NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, BRP, Frederick, MD 21702 USA. CDC, NCID, DASTLR, HIV Immunol & Diagnost Branch, Atlanta, GA 30333 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Dimitrov, DS (reprint author), NCI, Human Immunovirol & Computat Biol Grp, LECB,CCR, NIH, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov RI Ponraj, Prabakaran/D-6325-2011 FU PHS HHS [N01-C0-12400] NR 28 TC 48 Z9 50 U1 0 U2 4 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 JAN 2 PY 2004 VL 335 IS 1 BP 209 EP 219 DI 10.1016/j.jmb.2003.09.055 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 761BP UT WOS:000187879600016 PM 14659751 ER PT J AU Petkova, AT Buntkowsky, G Dyda, F Leapman, RD Yau, WM Tycko, R AF Petkova, AT Buntkowsky, G Dyda, F Leapman, RD Yau, WM Tycko, R TI Solid state NMR reveals a pH-dependent antiparallel beta-sheet registry in fibrils formed by a beta-amyloid peptide SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE amyloid fibrils; hydrogen bond registry; antiparallel beta-sheets; solid state NMR; Alzheimer's disease ID NUCLEAR-MAGNETIC-RESONANCE; SIDE-CHAIN INTERACTIONS; C-13 CHEMICAL-SHIFTS; X-RAY-DIFFRACTION; SUPRAMOLECULAR STRUCTURE; STRUCTURAL CONSTRAINTS; ROTATIONAL-ECHO; C-ALPHA; CONFORMATION; PARALLEL AB We report solid state nuclear magnetic resonance (NMR) measurements that probe the supramolecular organization of beta-sheets in the cross-beta motif of amyloid fibrils formed by residues 11-25 of the beta-amyloid peptide associated with Alzheimer's disease (Abeta(11-25)). Fibrils were prepared at pH 7.4 and pH 2.4. The solid state NMR data indicate that the central hydrophobic segment of Abeta(11-25) (sequence LVFFA) adopts a beta-strand conformation and participates in antiparallel beta-sheets at both pH values, but that the registry of intermolecular hydrogen bonds is pH-dependent. Moreover, both registries determined for Abeta(11-25) fibrils are different from the hydrogen bond registry in the antiparallel beta-sheets of Abeta(16-22) fibrils at pH 7.4 determined in earlier solid state NMR studies. In all three cases, the hydrogen bond registry is highly ordered, with no detectable "registry-shift" defects. These results suggest that the supramolecular organization of beta-sheets in amyloid fibrils is determined by a sensitive balance of multiple side-chain-side-chain interactions. Recent structural models for Abeta(11-25) fibrils based on X-ray fiber diffraction data are inconsistent with the solid state NMR data at both pH values. (C) 2003 Elsevier Ltd. All rights reserved. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Dept Chem, D-14195 Berlin, Germany. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM tycko@helix.nih.gov RI Buntkowsky, Gerd/B-3206-2010 OI Buntkowsky, Gerd/0000-0003-1304-9762 NR 49 TC 226 Z9 232 U1 5 U2 25 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 JAN 2 PY 2004 VL 335 IS 1 BP 247 EP 260 DI 10.1016/j.jmb.2003.10.044 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 761BP UT WOS:000187879600019 PM 14659754 ER PT J AU Li, HY Byeon, IJL Ju, Y Tsai, MD AF Li, HY Byeon, IJL Ju, Y Tsai, MD TI Structure of human Ki67 FHA domain and its binding to a phosphoprotein fragment from hNIFK reveal unique recognition sites and new views to the structural basis of FHA domain functions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE FHA; NMR; protein structure; binding surface; phosphoprotein ID FORKHEAD-ASSOCIATED DOMAIN; DEPENDENT PROLYL ISOMERIZATION; CELL-CYCLE; REGULATORY MECHANISM; PROTEIN PHOSPHATASE; ISOMERASE PIN1; ANTIBODY KI-67; YEAST RAD53; ANTIGEN; KINASE AB Recent studies by use of short phosphopepticles showed that forkhead-associated (FHA) domains recognize pTXX(D/I/L) motifs. Solution structures and crystal structures of several different FHA domains and their complexes with short phosphopeptides have been reported by several groups. We now report the solution structure of the FHA domain of human Ki67, a large nuclear protein associated with the cell-cycle. Using fragments of its binding partner hNIFK, we show that Ki67-hNIFK binding involves ca 44 residues without a pTXX(D/I/L) motif. The pThr site of hNIFK recognized by Ki67 FHA is pThr234-Pro235, a motif also recognized by the proline isomerase Pin1. Heteronuclear single quantum coherence (HSQC) NMR was then used to map out the binding surface, and structural analyses were used to identify key binding residues of Ki67 FHA. The results represent the first structural characterization of the complex of an FHA domain with a biologically relevant target protein fragment. Detailed analyses of the results led us to propose that three major factors control the interaction of FHA with its target protein: the pT residue, +1 to +3 residues, and an extended binding surface, and that variation in the three factors is the likely cause of the great diversity in the function and specificity of FHA domains from different sources. (C) 2003 Elsevier Ltd. All rights reserved. C1 Ohio State Univ, Dept Biochem, Campus Chem Instrument Ctr, Columbus, OH 43210 USA. Ohio State Univ, Dept Chem, Campus Chem Instrument Ctr, Columbus, OH 43210 USA. RP Byeon, IJL (reprint author), NIH, Bldg 5,Room B2-41, Bethesda, MD 20892 USA. EM in-jab@intra.niddk.nih.gov; tsai.7@osu.edu FU NCI NIH HHS [CA87031] NR 39 TC 29 Z9 33 U1 1 U2 4 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 JAN 2 PY 2004 VL 335 IS 1 BP 371 EP 381 DI 10.1016/j.jmb.2003.10.032 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 761BP UT WOS:000187879600029 PM 14659764 ER PT J AU Pifl, C Khorchide, M Kattinger, A Reither, H Hardy, J Hornykiewicz, O AF Pifl, C Khorchide, M Kattinger, A Reither, H Hardy, J Hornykiewicz, O TI alpha-Synuclein selectively increases manganese-induced viability loss in SK-N-MC neuroblastoma cells expressing the human dopamine transporter SO NEUROSCIENCE LETTERS LA English DT Article DE alpha-synuclein; manganese; dopamine; 1-methyl-4-phenylpyridinium; iron; neurodegeneration; Parkinson's disease ID ACID-PHOSPHATASE ASSAY; PARKINSONS-DISEASE; WILD-TYPE; IN-VITRO; SUSCEPTIBILITY; MUTATION; TOXICITY; MICE; AGGREGATION; BRAIN AB The established or potentially toxic agents implicated in the nigral cell death in Parkinson's disease, dopamine, 1-methyl-4-phenylpyridinium (MPP+), iron, and manganese, were examined as to their effects on the viability of cells overexpressing alpha-synuclein. SKN-MC neuroblastoma cells stably expressing the human dopamine transporter were transfected with human alpha-synuclein and cell clones with and without alpha-synuclein immunoreactivity were obtained. Cells were exposed for 24-72 h to 1-10 muM dopamine, 0.1-3 muM MPP+, 0.1-1 mM FeCl2 or 30-300 muM MnCl2 added to the culture medium. There was no difference between cells expressing alpha-synuclein and control cells after exposure to dopamine, MPP+ or FeCl2. However, MnCl2 resulted in a significantly stronger decreased viability of cells overexpressing alpha-synuclein after 72 h. These findings suggest that manganese may co-operate with alpha-synuclein in triggering neuronal cell death such as seen in manganese parkinsonism. The relevance of our observations for the pathoetiology of Parkinson's disease proper remains to be determined. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Univ Vienna, Inst Brain Res, A-1090 Vienna, Austria. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Pifl, C (reprint author), Univ Vienna, Inst Brain Res, Spitalgasse 4, A-1090 Vienna, Austria. EM christian.pifl@univie.ac.at RI Hardy, John/C-2451-2009 NR 26 TC 26 Z9 27 U1 0 U2 1 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 JAN 2 PY 2004 VL 354 IS 1 BP 34 EP 37 DI 10.1016/j.neulet.2003.09.064 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 765TA UT WOS:000188298500010 PM 14698476 ER PT B AU Xie, HC Li, G Ning, H Menard, C Coleman, CN Miller, RW AF Xie, HC Li, G Ning, H Menard, C Coleman, CN Miller, RW BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI 3D voxel fusion of multi-modality medical images in a clinical treatment planning system SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID RADIOTHERAPY AB We present a novel 3D voxel fusion approach to achieve multi-modality image fusion in our clinical treatment planning system. This approach shows its superior visual representation and straightforward operation in the image fusion process and in verification of the fusion result. With RGB color bands to represent each of the fusing imaging modalities (voxel volumes), the homogeneity of the color distribution in a given tissue or anatomic structure has demonstrated to be a good indicator for high quality fusion. With a pre-defined lookup table library for different imaging technologies and different body segments, tissue of interest can be selectively viewed and individually fused, especially for those served as fusion landmarks. With control of voxel transparency with its geometrical location, an "onion pealing" effect can be established for further examination of the interior of the voxel volumes. It will be shown that the 3D voxel fusion can resolve the ambiguity resulted from 3D pixel fusion, because the 3D voxel fusion can distinguish a systematic positioning error from the random error present in the fusion result. It will also be shown that the 3D voxel fusion is straight forward, in the form of real-time "virtual reality". It can be applied for setting initial fusion position, as well as fine-tuning final fusion result with an improved accuracy (single voxel, or sub mm). Its simplicity and accuracy has made this technique a practical tool for multi-modality image fusion and for quality assurance. Additional clinical applications can be developed based on this technique. C1 NCI, Radiat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Xie, HC (reprint author), NCI, Radiat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. OI Li, Guang/0000-0002-9022-2883 NR 6 TC 1 Z9 1 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 48 EP 53 DI 10.1109/CBMS.2004.1311690 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000010 ER PT B AU Seckman, CA Romano, C Rosenfeld, S AF Seckman, CA Romano, C Rosenfeld, S BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI Standard web-based clinical radiology images and reports at the point of care SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID PACS AB Web-based standard radiology images were successfully piloted and initially deployed to over 1300 users for onsight intranet access. User feedback from the pilot yielded positive reports for ease of,use convenience and acceptable format. Technical deployment of thin client technology was-found to be complex, time consuming and replaced with an alternate vendor strategy. One month implementation utilization data suggests moderate use of standard images. Recommendations yielded interest in pursuing web access to enhanced digital radiology images and off-sight access. C1 NIH, Bethesda, MD 20892 USA. RP Seckman, CA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 67 EP 71 DI 10.1109/CBMS.2004.1311693 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000013 ER PT B AU Cheung, H Fann, Y Wang, SA Upender, B Frazin, A Lingam, R Chintala, S Pecjak, F Wang, G Kellogg, M Martino, RL Johnson, C AF Cheung, H Fann, Y Wang, SA Upender, B Frazin, A Lingam, R Chintala, S Pecjak, F Wang, G Kellogg, M Martino, RL Johnson, C BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI A web-based protocol tracking management system for clinical research SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn AB Clinical research approval processes are complex since they involve human subject welfare as well as regulatory and ethical concerns. Typically, clinical research institutions have an elaborate established review process; the labor-intensive and time-consuming nature of this process can result in approval delays thus significantly impacting the biomedical research. This paper describes the development of a web-based information system designed to make the process of protocol approval more efficient, organized, and accurate. The system enables the principal investigators (PIs) to initiate, track and manage clinical studies, monitor review processes, view status changes, and quickly respond to requests for additional information. In addition, it allows the protocol coordinators (PCs) to manage the entire Institutional Review Board (IRB) approval process. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Cheung, H (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 2 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 72 EP 77 DI 10.1109/CBMS.2004.1311694 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000014 ER PT B AU Hauser, SE Demner-Fushman, D Ford, G Thoma, GR AF Hauser, SE Demner-Fushman, D Ford, G Thoma, GR BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI A testbed system for mobile point-of-care information delivery SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn AB PubMed on Tap is a testbed system that supports search of and retrieval from the National Library of Medicine's MEDLINE(R) database from a PDA. The goal of the PubMed on Tap project is to discover and implement design principles for point-of-care delivery of clinical support information. The project explores user interface issues, information content and organization, and system performance. Here we present our progress in these areas. C1 NIH, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med,Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Hauser, SE (reprint author), NIH, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med,Dept Hlth & Human Serv, Bethesda, MD 20894 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 147 EP 152 DI 10.1109/CBMS.2004.1311706 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000026 ER PT B AU Vahabzadeh, M Epstein, D Mezghanni, M Lin, JL Preston, K AF Vahabzadeh, M Epstein, D Mezghanni, M Lin, JL Preston, K BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI An electronic diary software for Ecological Momentary Assessment (EMA) in clinical trials SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID REAL-TIME; SMOKING; LAPSES AB Experience sampling is a research technique in which participants record their behaviors and moods in real time in their day-to-day environments. Ecological Momentary Assessment (EMA) is a refinement of experience sampling in which randomly timed assessments are combined with event-contingent assessments. EMA data are more reliable if obtained with handheld computers than with paper diaries. Robust EMA applications sufficiently flexible and easily adaptable for our various research efforts, including a study of polydrug use we are now undertaking at our outpatient treatment/research clinic, were not available. We developed Transactional Electronic Diary (TED), a highly configurable EMA program. TED provides investigators the capability to conduct close assessment and monitoring of symptoms and intensity of drug withdrawal in participants. Data collected via TED is subsequently incorporated into our Human Research Information System (HuRIS) for further analysis. C1 NIDA, DHHS, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Vahabzadeh, M (reprint author), NIDA, DHHS, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 7 TC 14 Z9 14 U1 1 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 167 EP 172 DI 10.1109/CBMS.2004.1311709 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000029 ER PT B AU Vahabzadeh, M Lin, JL Gupman, A Schmittner, J Preston, K AF Vahabzadeh, M Lin, JL Gupman, A Schmittner, J Preston, K BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI Automating variations in clinical research protocols workflow SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn AB Clinical research protocols follow rigorous methodologies requiring painstaking precision in every step of the process. A variety of factors determine the required steps an individual participant will take throughout the protocol timeline. Such steps could easily become more complicated and complex in a research setting aimed at new discoveries, which require various degrees of flexibility depending on the specific conditions at various points of the study. In this paper we describe our Protocol Workflow System (PWS), which is designed to accommodate all of the current and potential future protocols while simultaneously providing the capability for workflow adjustments during various phases of ongoing studies. Furthermore, it is robust enough to organize and handle participants who are enrolled concurrently in multiple protocols. This automated system not only collects information at an outpatient research center, but also automates the workflow and data collection points throughout the clinic. C1 NIDA, DHHS, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Vahabzadeh, M (reprint author), NIDA, DHHS, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 8 TC 3 Z9 3 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 248 EP 253 DI 10.1109/CBMS.2004.1311723 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000043 ER PT B AU Bai, O Nolte, G Zoltan, M Vorbach, S Hallett, M AF Bai, O Nolte, G Zoltan, M Vorbach, S Hallett, M BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI Visualization of spatiotemporal patterns of EEG rhythms during voluntary movements SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID COHERENCE; POTENTIALS AB The power change of electroencephalographic (EEG) rhythms is an indicator to investigate neuronal activation underlying EEG electrodes. We developed a software routine for analysis and visualization of spatiotemporal patterns of EEG oscillations: event-related desynchronization (ERD) and event-related synchronization (ERS). Further, the spatiotemporal representation of task-related coherence (TRC) was also proposed for investigation of interregional neuronal connectivity. As concurrent artifacts and volume conduction effect may result incorrect or spatially blurred estimation of EEG features, we have embedded data preprocessing functions to reduce these effects including: correcting eye movement-related artifact, changing reference methods and spatial filtering undesirable neuronal activity. These functions were subsequently applied to study EEG time-frequency patterns during self-paced movements in normal volunteers. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD USA. RP Bai, O (reprint author), NINDS, Human Motor Control Sect, NIH, Bethesda, MD USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 267 EP 272 DI 10.1109/CBMS.2004.1311726 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000046 ER PT B AU Alesci, S Su, YA Chrousos, GP AF Alesci, S Su, YA Chrousos, GP BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI hMiDas and hMitChip: New opportunities in mitochondrial Bioinformatics and genomic medicine SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID INFORMATION; DATABASE AB We developed a human mitochondria-focused gene database (hMiDas) and customized cDNA microarray chip (hMitChip) to help biomedical research in mitochondrial genomics. The current version of hMiDas contains 1,242 gene entries (including mtDAA genes, nuclear genes related to mitochondria structure and functions, predicted loci and experimental genes), organized in 15 categories and 24 subcategories. The database interface allows keyword-based searches as well as advanced field and/or case-sensitive searches. Each gene record includes 19 fields, mostly hyperlinked to the corresponding source. Moreover, for each gene, the user is given the option to run literature search using PubMed, and gene/protein homology search using BLAST and FASTA. The hMitChip was constructed using hMiDas as a reference. Currently, it contains a selection of 501 mitochondria-related nuclear genes and 192 control elements, all spotted in duplicate on glass slides. Slide quality was checked by microarray hybridization with 50 mug of Cy3-labeled sample cDNA and Cy5-labeled comparing cDNA, followed by array scan and image analysis. The hMitChip was tested in vitro using RNA extracted from cancer cell lines. Gene expression changes detected by hMitChip were confirmed by quantitative real-time RT-PCR analysis. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Alesci, S (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 329 EP 334 DI 10.1109/CBMS.2004.1311736 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000056 ER PT B AU Chen, WP Zha, W Cox, T Zhao, XJ Russell, P AF Chen, WP Zha, W Cox, T Zhao, XJ Russell, P BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI 3Si: A computer program for the optimal design of short interfering RNA (siRNA) for gene silencing SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID SECONDARY STRUCTURE; MAMMALIAN-CELLS; PREDICTION; EXPRESSION; DROSOPHILA; MICE AB siRNA is a powerful technique for gene silencing. However, it is still not clear how to accurately determine an effective gene targeting region for siRNA. It is also controversial if the targeted mRNA secondary structure would have a significant impact on the gene silencing by the siRNA. Understanding the relationship between the secondary structure and gene silencing by siRNA could help in high throughput function-based genetic screens and for development of therapeutic tools. Our hypothesis is that the selection of a single-stranded region as the target region should increase the efficiency of siRNA silencing. For the first time, a formula and a computer program were developed to select the single-stranded regions for siRNA silencing. We statistically analyzed quantitative relationships between gene silencing by the siRNA and ten parameters from published siRNA sequences. The four nonlinear significant parameters for designing siRNA are the RNA Single-Stranded Index (SSi), a new parameter that identifies the target position and its related secondary structures, the GC content, DeltaG free energy of the siRNA, and the 5'GC content of the first four bases of the antisense siRNA. The nonlinear complexity suggested that one should not use simple criteria such as a GC content of around 30 to 50% or the absence of the sequence pattern GGG for designing siRNA. Our results indicate that the targeted mRNA secondary structure is a statistically significant determinant in gene silencing and should be used to optimize RNAi technology. C1 NEI, Bethesda, MD 20892 USA. RP Chen, WP (reprint author), NEI, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 335 EP 342 DI 10.1109/CBMS.2004.1311737 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000057 ER PT B AU Chen, WP Wu, DY Zha, W Russell, P AF Chen, WP Wu, DY Zha, W Russell, P BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI Identification of highly significant sequence patterns in siRNAs for the optimal design of SiRNA SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID SMALL INTERFERING RNAS; GENE-FUNCTION AB siRNAs for gene silencing studies have a broad range of applications. Studies have addressed the design of siRNAs based on the target sequence patterns, such as the sequence AA around the ends of the siRNA or the avoidance of GGG in siRNA sequences. However, information from just these two patterns is not sufficient for effectively designing siRNA, Nine sequence patterns were identified as highly significantly correlated motifs in studies on oligonucleotides antisense activities. The correlation between the sequence patterns of the siRNA and the gene silencing ratio (GSR) by siRNA has not been described. Understanding this relationship may guide one to a systematic design of the most effective siRNAs. We designed a computer program to calculate the sequence patterns from our siRNA silencing database. Four statistical methods were used to identify the frequency and the distribution of the highly significant sequence patterns from the 1344 combinations for the three, four and five nucleotide sequences. For the first time, 52 sequence patterns were identified as the highly significant patterns by ANOVA and Pearson correlation analyses with the GSR. These 52 patterns were further clustered into 18 groups. Information from this study may help in the optimized design of siRNA. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Chen, WP (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 343 EP 350 DI 10.1109/CBMS.2004.1311738 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000058 ER PT B AU Srikanchana, R Thomasson, D Choyke, P Dwyer, A AF Srikanchana, R Thomasson, D Choyke, P Dwyer, A BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI A comparison of pharmacokinetic models of dynamic contrast enhanced MRI SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID PARAMETERS AB Dynamic Contrast Enhanced MRI (DCE-MRI) is often employed as an indicator of drug activity in clinical trials of angiogenic inhibitors. The data obtained with DCE-MRI is reported semi quantitatively using parameters derived from pharmacokinetic models. Most MPI kinetic models were developed from Nuclear Medicine quantitative studies but the limitations of MRI dictated specific modifications. A number of these MRI models are in current use. In this work, we review several pharmacokinetic models used in DCE-MRI in order to determine the most appropriate model to assess tumor angiogenesis. These models are compared with respect to their physiological appropriateness; compartmental analysis; initial and boundary conditions; and clinically relevant output parameters. C1 NCI, Bethesda, MD 20892 USA. RP Srikanchana, R (reprint author), NCI, Bethesda, MD 20892 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 361 EP 366 DI 10.1109/CBMS.2004.1311740 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000060 ER PT B AU Pfeffer, L Ide, D Stewart, C Plenz, D AF Pfeffer, L Ide, D Stewart, C Plenz, D BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI A life support system for stimulation of and recording from rodent neuron networks grown on multi-electrode arrays SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn AB One promising approach to studying how large numbers of neurons interact is the combination of neuronal cell cultures with multi-electrode arrays (MEAs) Together, these allow simultaneous recording from many neurons. A particular challenge has been the long-term growth of organotypic neuronal cultures on MEAs. These cultures need alternate exposure to air and a liquid growth medium. Continuous rotary motion (of suitable closed chambers) provides this, but greatly complicates recording of large numbers of low-level electrical signals. An alternative approach is to rock chambers incorporating MEAs cyclically through a limited angle, thus facilitating direct connections. A variable speed trajectory balances cycle frequency against the shear forces acting to dislodge the tissue. Different trajectories can be used to optimize culture health during different development periods. We discuss the design of a microprocessor based life-support system that implements such a limited-angle, variable-speed cycle to culture rat brain slices on MEAs, while maintaining direct electrical connections. We show some of the neurophysiological results thus made possible, and consider improvements for a subsequent life-support system for future research. C1 NIMH, Res Serv Branch, Bethesda, MD 20892 USA. RP Pfeffer, L (reprint author), NIMH, Res Serv Branch, Bethesda, MD 20892 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 473 EP 478 DI 10.1109/CBMS.2004.1311759 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000079 ER PT B AU Johann, DJ McGuigan, MD Tomov, S Blum, E Whiteley, GR Petricoin, EF Liotta, LA AF Johann, DJ McGuigan, MD Tomov, S Blum, E Whiteley, GR Petricoin, EF Liotta, LA BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI Toward a systems biology software toolkit SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID PROTEOMIC PATTERNS; PROSTATE-CANCER; SERUM AB Insight to complex problems may be revealed when domain data sets are viewed or structured in new and innovative ways. Systems approaches to biomedical problems fundamentally involve forecasting, and a deliberate integration of diverse data sources. Adding a clinical proteomic dimension to these developing efforts affirms the ultimate aims of enhanced diagnostic prediction, maximizing the possibility for a rational therapy individualized to a patient's pathologic process, and thus, improving patient outcomes. Consistent with these evolving goals, computer-aided diagnostic systems are rapidly approaching a new paradigm involving the integration of medical imaging with high throughput molecular medicine tests. As medical imaging systems become more sensitive in finding anatomic anomalies, their lack of specificity becomes much more of a clinical dilemma. Proteomic tests may be used to help resolve the lack of specificity of imaging findings. A synergistic test composed of a targeted imaging study correlated with a genomic or proteomic test(s), offers the potential of a tremendous medical advancement. Bioinformatic software toolkits are crucial components Of these systems. Open source software provides a mechanism for leveraging existing toolkits, sharing expertise, accelerating development, and furthering biomedical, software, and systems sciences in new and complex multi-disciplinary fields. Our evolving toolkit utilizes components from several existing open source projects. It will initially be customized for serum proteomic pattern diagnostics, which will be used in the upcoming NCI/CCR Clinical Trial involving the monitoring for ovarian cancer recurrence. C1 NIH, Bethesda, MD 20892 USA. RP Johann, DJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 500 EP 505 DI 10.1109/CBMS.2004.1311764 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000084 ER PT B AU Zhang, Z Ackerman, MJ Li, JX AF Zhang, Z Ackerman, MJ Li, JX BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI A prototype colon straightening system for polyp detection SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID VIRTUAL ENDOSCOPY AB Early detection and removal of polyps can reduce mortality due to colon cancers. The "fly-through" method in CT colonography has drawbacks. We are developing a prototype colon straightening system so as to provide a paradigm to inspect the colon wall in a "cut-open" fashion. The core component of the system is the straightening module, which models the colon straightening as a solid elastic deformation process with specially designated constraints and boundary conditions. It is demonstrated that the prototype system can retain consistency of surface points' spatial relationship and handle geometry with large-degree bendings. Future work is discussed. C1 NIH, OHPCC, Natl Lib Med, Bethesda, MD 20892 USA. RP Zhang, Z (reprint author), NIH, OHPCC, Natl Lib Med, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 548 EP 552 DI 10.1109/CBMS.2004.1311772 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000092 ER PT B AU Jeronimo, J Schiffman, M Long, LR Neve, L Antani, S AF Jeronimo, J Schiffman, M Long, LR Neve, L Antani, S BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI A tool for collection of region based data from uterine cervix images for correlation of visual and clinical variables related to cervical neoplasia SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn ID CANCER AB The National Cancer Institute (NCI) is collaborating with the National Library of Medicine (NLM) to create a database of digitized images of the uterine cervix for research, training, and education. The database of 100,000 images collected in NCI projects will be Web-accessible and will contain not only the digitized images, but also clinical, longitudinal data relevant to the detection of uterine cervix cancer. The database will also contain spatial data in the form of expert-marked boundary regions of anatomy and tissue regions of high interest. The collection of this spatial data is enabled by customized software, the Boundary Marking Tool (BMT). The BMT, its significance, and its use in preliminary research studies, are described in this paper. C1 NCI, Hormonal & Reprod Epidemiol Branch, DCEG, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Jeronimo, J (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, DCEG, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 8 TC 3 Z9 3 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 558 EP 562 DI 10.1109/CBMS.2004.1311774 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000094 ER PT B AU Bopf, M Coleman, T Long, LR Antani, S Thoma, GR Jeronimo, J Schiffman, M AF Bopf, M Coleman, T Long, LR Antani, S Thoma, GR Jeronimo, J Schiffman, M BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI An architecture for streamlining the implementation of biomedical text/image databases on the Web SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn AB To date the implementation of biomedical text/images databases on the Web has been hindered by the lack of software flexibility to enable new datasets to be "rolled in" to existing database systems without extensive programming modifications. An R&D division of the National Library of Medicine (NLM) is creating a new database system, the Multimedia Database Tool (MDT), built on an architecture that moves the required customization for a particular dataset from the programmer to the database administrator level, thereby reducing potentially high labor costs. The first database application to be supported will be uterine cervix data from the National Cancer Institute, including 100,000 digitized images, and NHANES 11 and III databases now hosted by the NLM Web-based Medical Information Retrieval System (WebMIRS). C1 NIH, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bopf, M (reprint author), NIH, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med,Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 2 TC 3 Z9 3 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 563 EP 568 DI 10.1109/CBMS.2004.1311775 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000095 ER PT B AU Wang, SHA Fann, Y Cheung, H Pecjak, F Upender, B Frazin, A Lingam, R Chintala, S Wang, G Kellogg, M Martino, RL Johnson, CA AF Wang, SHA Fann, Y Cheung, H Pecjak, F Upender, B Frazin, A Lingam, R Chintala, S Wang, G Kellogg, M Martino, RL Johnson, CA BE Long, R Antani, S Lee, DJ Nutter, B Zhang, M TI Performance of using oracle XMLDB in the evaluation of CDISC ODM for a clinical study informatics system SO 17TH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS LA English DT Proceedings Paper CT 17th IEEE Symposium on Computer-Based Medical Systems CY JUN 24-25, 2004 CL Bethesda, MD SP IEEEComp Soc, tccm, Texas Tech Univ Coll Engn AB This paper describes potential strategies for data modeling and implementation as part Of the general architecture of CSIS, a Clinical Study and Informatics System that has been developed for the National Institute of Neuroscience and Stroke (NINDS). We discuss the NINDS requirements and how they influenced the system design, with an emphasis on dynamic form creation. We also evaluate open standards such as "CDISC ODM" and several database technology choices, namely conventional relational "EAV" tables and the new "XMLDB" from Oracle. We describe performance test results, which show that it is feasible to implement CDISC ODM in Oracle XMLDB and the schema-based storage option for storing XML content is better than "CLOB"-based for applications that require high numbers of queries for XML fragments. For storage and retrieval of whole XML documents, CLOB storage is optimal. CSIS implements a hybrid approach of combining CLOB storage for storing XML documents with relational tables for storing metadata. Due to the complexity of the CDISC schema and related performance and implementation concerns, we have decided not to implement CDISC internal storage in our system. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Wang, SHA (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 4 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2104-5 PY 2004 BP 594 EP 599 DI 10.1109/CBMS.2004.1311780 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Radiology, Nuclear Medicine & Medical Imaging GA BAN73 UT WOS:000222998000100 ER PT S AU Riboldi, S Seidel, J Green, M Monaldo, J Kakareka, J Pohida, T AF Riboldi, S Seidel, J Green, M Monaldo, J Kakareka, J Pohida, T BE Metzler, SD TI Investigation of signal readout methods for the Hamamatsu R8500 flat panel PSPMT SO 2003 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-5 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2003 CL Portland, OR SP IEEE, Nucl & Plasma Sci Soc AB Pulse processing efficiency is among the most important parameters to maximize when designing effective systems for positron emission tomography (PET) applications. As the activity of the positron source increases, the attainable processing efficiency is often limited by the increased probability of pulse pileup. Various techniques have been proposed to read out position-sensitive multi-wire or multi-anode photomultiplier tubes (PSPMTs) that trade resistance to pulse-pileup against the simplicity (and cost) of the readout method. Light spreading onto the detector surface also affects the choice of readout method for multi-anode tubes. Four methods for readout of signals are compared for the H8500 Hamamatsu multi-anode PSPMT. The first combines signals from the entire device surface; the second scheme implements readout of signals from four separate quadrants. The third scheme, proposed by Majewska et al., is based on row and column readout. We propose a fourth, and new, readout scheme based on a geometrical arrangement of overlapping square sectors. We show that this solution reduces pulse pileup yet requires a relatively small number of output signal lines to determine the energy and position of each scintillation event. C1 NIH, Ctr Informat Technol, Div Computat Biosci,Signal Proc & Instrumentat Se, Computat Biosci & Engn Lab, Bethesda, MD 20892 USA. RP Riboldi, S (reprint author), NIH, Ctr Informat Technol, Div Computat Biosci,Signal Proc & Instrumentat Se, Computat Biosci & Engn Lab, Bldg 10, Bethesda, MD 20892 USA. RI Riboldi, Stefano/L-3502-2016 NR 1 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-8257-9 J9 IEEE NUCL SCI CONF R PY 2004 BP 2452 EP 2456 DI 10.1109/NSSMIC.2003.1352390 PG 5 WC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAS86 UT WOS:000223398000543 ER PT S AU Carson, RE Barker, WC Liow, JS Johnson, CA AF Carson, RE Barker, WC Liow, JS Johnson, CA BE Metzler, SD TI Design of a motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction for the HRRT SO 2003 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-5 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2003 CL Portland, OR SP IEEE, Nucl & Plasma Sci Soc DE \ ID IMAGE-RECONSTRUCTION; EMISSION-TOMOGRAPHY; 3D RECONSTRUCTION; PET DATA; IMPLEMENTATION AB The HRRT PET system has the potential to produce human brain images with resolution better than 3 mm. To achieve the best possible accuracy and precision, we have designed MOLAR, a Motion-compensation OSEM List-mode Algorithm for resolution-recovery Reconstruction on a computer cluster with the following features: direct use of list mode data with dynamic motion information (Polaris); exact reprojection of each line-of-response (LOR); system matrix computed from voxel-to-LOR distances (radial and axial); spatially varying resolution model implemented for each event by selection from precomputed line spread functions based on factors including detector obliqueness, crystal layer, and block detector position; distribution of events to processors and to subsets based on order of arrival; removal of voxels and events outside a reduced field-of-view defined by the attenuation map; no pre-corrections to Poisson data, i.e., all physical effects are defined in the model; randoms estimation from singles; model-based scatter simulation incorporated into the iterations; and component-based normalization. Preliminary computation estimates suggest than reconstruction of a single frame in one hour is achievable. Careful evaluation of this system will define which factors play an important role in producing high resolution, low-noise images with quantitative accuracy. C1 NIH, Warren Grant Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, Warren Grant Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 12 TC 6 Z9 6 U1 2 U2 8 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-8257-9 J9 IEEE NUCL SCI CONF R PY 2004 BP 3281 EP 3285 DI 10.1109/NSSMIC.2003.1352597 PG 5 WC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAS86 UT WOS:000223398000731 ER PT B AU Yao, JH Lee, JS Collins, MT Butman, JA AF Yao, JH Lee, JS Collins, MT Butman, JA GP IEEE TI Computer aided monitoring of fibrous dysplasia disease in craniofacial bones SO 2004 2ND IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1 and 2 LA English DT Proceedings Paper CT 2nd IEEE International Symposium on Biomedical Imaging CY APR 15-18, 2004 CL Arlington, VA SP IEEE DE computer aided monitoring; fibrous dysplasia; bone change quantification AB This paper presents a method to assist the monitoring of bone remodeling in annual CT scans of craniofacial bones performed in patients with polyostotic fibrous dysplasia. The method combines several advanced computer vision and graphics techniques, including image segmentation, surface reconstruction, image registration, and image fusion. The method is fully automatic and achieves sub-pixel accuracy. Several metrics were designed to quantitate the bone changes between two studies, and were compared to a visual assessment of bone involvement The quantitative analysis provides physicians a useful tool to evaluate the disease development and monitor the treatment progress. C1 NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. OI Butman, John/0000-0002-1547-9195 NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8388-5 PY 2004 BP 245 EP 248 PG 4 WC Acoustics; Neuroimaging; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BBT20 UT WOS:000227671300062 ER PT B AU Zhang, Z Li, JX Ackerman, MJ AF Zhang, Z Li, JX Ackerman, MJ GP IEEE TI Colon straightening based on an elastic mechanics model SO 2004 2ND IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1 and 2 LA English DT Proceedings Paper CT 2nd IEEE International Symposium on Biomedical Imaging CY APR 15-18, 2004 CL Arlington, VA SP IEEE ID VIRTUAL COLONOSCOPY; CT COLOGRAPHY; VISUALIZATION; ENDOSCOPY; POLYPS; IMAGES AB Early detection and removal of polyps can reduce mortality due to colon cancers. In CT colonography, colon straightening can facilitate visualization and detection of polyps. We presented a new method to straighten the colon based on an elastic deformation model with specially designated boundary conditions and centerline constraints. With a digitally generated phantom it was demonstrated that the elastic deformation model can straighten the colon in a consistent manner (i.e., to preserve the relative spatial relationships of points on the colon surface, such as left vs. right, up vs. down) and can handle large-angle bendings in colon geometry. It was observed that the proposed model may impose relatively small distortion effects on structures on the colon surface after straightening. Further research was mentioned. C1 NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20892 USA. RP Zhang, Z (reprint author), NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8388-5 PY 2004 BP 292 EP 295 PG 4 WC Acoustics; Neuroimaging; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BBT20 UT WOS:000227671300074 ER PT B AU Carson, RE AF Carson, RE GP IEEE TI Tracer kinetic parametric imaging in pet SO 2004 2ND IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1 and 2 LA English DT Proceedings Paper CT 2nd IEEE International Symposium on Biomedical Imaging CY APR 15-18, 2004 CL Arlington, VA SP IEEE ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; BRAIN TRANSFER CONSTANTS; REFERENCE TISSUE MODEL; TIME UPTAKE DATA; GRAPHICAL EVALUATION; AUTOMATED ALGORITHM; INPUT FUNCTION; RECONSTRUCTION; REGISTRATION AB Dynamic PET image acquisition is combined with tracer kinetic modeling techniques to produce quantitative estimates of physiological parameters on the regional or voxel level. Current and future challenges in this area are explored. As the resolution of PET scanners improves, correction for subject motion during the long acquisition periods must be applied. Direct measurement of an appropriate input function for the models is being replaced by image-based analyses. Development of improved. rapid parameter estimation algorithms is necessary to assure unbiased parametric images with low statistical noise. Finally, direct incorporation of the kinetic model into the reconstruction process is likely to be the ultimate path for production of tracer kinetic parametric images for PET. C1 NIH, PET Dept, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 40 TC 1 Z9 1 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8388-5 PY 2004 BP 611 EP 615 PG 5 WC Acoustics; Neuroimaging; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BBT20 UT WOS:000227671300154 ER PT B AU Rohde, GK Pajevic, S Pierpaoli, C AF Rohde, GK Pajevic, S Pierpaoli, C GP IEEE TI Multi-channel registration of diffusion tensor images using directional information SO 2004 2ND IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1 and 2 LA English DT Proceedings Paper CT 2nd IEEE International Symposium on Biomedical Imaging CY APR 15-18, 2004 CL Arlington, VA SP IEEE AB The problem of registering Diffusion Tensor (DT) images is considered. We describe a novel intensity based registration method capable of performing affine and nonlinear registration of multi-channel images such as DT images. We use this method to register 3 dimensional DT images of the human brain based on several channel configurations derived from the DT model. Specifically, we compare the use of channel configurations that include rotationally invariant scalar quantities derived from the DT model against channel configurations that include directional information, such as the elements of the diffusion tensor. Experiments performed with real and simulated data show that the use of the directional information present in the diffusion tensor elements can, in some instances, significantly improve the accuracy of the registration results when compared to methods that use rotationally invariant scalar information. C1 NICHD, STBB, LIMB, Bethesda, MD 20892 USA. RP Rohde, GK (reprint author), NICHD, STBB, LIMB, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8388-5 PY 2004 BP 712 EP 715 PG 4 WC Acoustics; Neuroimaging; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BBT20 UT WOS:000227671300179 ER PT B AU Saad, ZS Reynolds, RC Argall, B Japee, S Cox, RW AF Saad, ZS Reynolds, RC Argall, B Japee, S Cox, RW GP IEEE TI Suma: An interface for surface-based intra- and inter-subject analysis with AFNI SO 2004 2ND IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: MACRO TO NANO, VOLS 1 and 2 LA English DT Proceedings Paper CT 2nd IEEE International Symposium on Biomedical Imaging CY APR 15-18, 2004 CL Arlington, VA SP IEEE ID HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; COORDINATE SYSTEM; VISUALIZATION; SEGMENTATION AB Surface-based brain imaging analysis is increasingly being used for detailed analysis of the topology of brain activation patterns and changes in cerebral gray matter. Here we present SUMA, a new interface for visualizing and performing surface-based brain imaging analysis that is tightly coupled to AFNI - a volume-based brain imaging analysis suite. The interactive part of SUMA is used for rapid and interactive surface and data visualization, access and manipulations with direct link to the volumetric data rendered in AFNI. The batch-mode part of SUMA allows for surface based operations such as geometry and data smoothing [1, 2], surface to volume domain mapping in both directions and node-based statistical and computational tools. We also present methods for mapping low resolution functional data onto the cortical surface while preserving the topological information present in the volumetric data and detail an efficient procedure for performing cross-subject, surface-based analysis with minimal interpolation of the functional data. C1 NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Saad, ZS (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Argall, Brenna/G-2543-2011 NR 14 TC 6 Z9 6 U1 3 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8388-5 PY 2004 BP 1510 EP 1513 PG 4 WC Acoustics; Neuroimaging; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BBT20 UT WOS:000227671301118 ER PT B AU Le, SY Maizel, JV Zhang, KZ AF Le, SY Maizel, JV Zhang, KZ GP IEEE Comp Soc TI An algorithm for detecting homologues of known structured RNAs in genomes SO 2004 IEEE COMPUTATIONAL SYSTEMS BIOINFORMATICS CONFERENCE, PROCEEDINGS LA English DT Proceedings Paper CT IEEE Computational Systems Bioinformatics Conference (CSB 2004) CY AUG 16-19, 2004 CL Stanford, CA SP IEEE Comp Soc, Hewlett-Packard Co, Coop Platinum, BioMed Cent, Off Sci, US DOE ID SECONDARY STRUCTURE; TRANSLATIONAL REGULATION; COMPUTING SIMILARITY; NONCODING RNAS; MESSENGER-RNA; SEQUENCE; PROGRAM; GENES; ALIGNMENT; IDENTIFICATION AB Distinct RNA structures are frequently involved in a wide-range of functions in various biological mechanisms. The three dimensional RNA structures solved by X-ray crystallography and various well-established RNA phylogenetic structures indicate that functional RNAs have characteristic RNA structural motifs represented by specific combinations of base pairings and conserved nucleotides in the loop region. Discovery of well-ordered RNA structures and their homologues in genome-wide searches will enhance our ability to detect the RNA structural motifs and help us to highlight their association with functional and regulatory RNA elements. We present here a novel computer algorithm, HomoStRscan, that takes a single RNA sequence with its secondary structure to search for homologous RNAs in complete genomes. This novel algorithm completely differs from other currently used search algorithms of homologous structures or structural motifs. For an arbitrary segment (or window) given in the target sequence, that has similar size to the query sequence, HomoStRscan finds the most similar structure to the input query structure and computes the maximal similarity score (MSS) between the two structures. The homologous RNA structures are then statistically inferred from the MSS distribution computed in the target genome. The method provides a flexible, robust and fine search tool for any homologous structural RNAs. C1 NCI, Lab Expt & Computat Biol, NIH, Ft Detrick, MD 21702 USA. RP Le, SY (reprint author), NCI, Lab Expt & Computat Biol, NIH, Bldg 469,Room 151, Ft Detrick, MD 21702 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2194-0 PY 2004 BP 300 EP 310 PG 11 WC Biotechnology & Applied Microbiology; Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Genetics & Heredity SC Biotechnology & Applied Microbiology; Computer Science; Genetics & Heredity GA BAX76 UT WOS:000224127800030 ER PT B AU Smith, LH Nelson, DJ AF Smith, LH Nelson, DJ GP IEEE TI An estimate of physical scale from speech SO 2004 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOL I, PROCEEDINGS: SPEECH PROCESSING LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing CY MAY 17-21, 2004 CL Montreal, CANADA SP IEEE Signal Proc Soc, IEEE ID GENDER RECOGNITION; SPEAKER HEIGHT; CORRELATE; WEIGHT AB We present an algorithm, based on the EM algorithm, which simultaneously estimates both physical scale and vowel identities from a segment of speech. The validity of the algorithm depends on the scale hypothesis that the variation of the formant frequencies for a given vowel is mainly influenced by the physical size of the speaker. This is both a new application and a new confirmation of a hypothesis that is often accepted without proof. C1 NIH, Bethesda, MD 20892 USA. RP Smith, LH (reprint author), NIH, Bethesda, MD 20892 USA. NR 16 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8484-9 PY 2004 BP 561 EP 564 PG 4 WC Acoustics; Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Telecommunications SC Acoustics; Computer Science; Engineering; Telecommunications GA BAG99 UT WOS:000222173500141 ER PT S AU Chernomordik, V Gandjbakhche, AH AF Chernomordik, V Gandjbakhche, AH GP ieee TI Time-resolved quantitative spectroscopy of breast using random walk theory SO 2004 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2 SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 17th Annual Meeting of the IEEE-Lasers-and-Electro-Optics-Society CY NOV 07-11, 2004 CL Rio Grande, PR SP IEEE Lasers & Electro Opt Soc, IEEE AB Application of our methodology, based on the random walk model, to quantify the optical properties of the breast tumors is discussed. Time-resolved in vivo data for several patients, obtained at PTB (Berlin), are analyzed. C1 NIH, Bethesda, MD 20892 USA. RP Chernomordik, V (reprint author), NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 0-7803-8557-8 J9 IEEE LEOS ANN MTG PY 2004 BP 765 EP 766 PG 2 WC Optics SC Optics GA BBG19 UT WOS:000225390900380 ER PT S AU Gannot, I Goren, A Harrington, JA AF Gannot, I Goren, A Harrington, JA GP ieee TI Coherent, hollow-core waveguide bundles as a potential tool for transendocopic infrared imaging. SO 2004 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2 SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 17th Annual Meeting of the IEEE-Lasers-and-Electro-Optics-Society CY NOV 07-11, 2004 CL Rio Grande, PR SP IEEE Lasers & Electro Opt Soc, IEEE C1 NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Gannot, I (reprint author), NIH, Lab Integrat & Med Biophys, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 0-7803-8557-8 J9 IEEE LEOS ANN MTG PY 2004 BP 829 EP 830 PG 2 WC Optics SC Optics GA BBG19 UT WOS:000225390900413 ER PT S AU Gannot, I Chernomordik, V Gandjbachkhe, A AF Gannot, I Chernomordik, V Gandjbachkhe, A GP ieee TI Fluorescence imaging of lesions, deep beneath tissue surface. SO 2004 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2 SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 17th Annual Meeting of the IEEE-Lasers-and-Electro-Optics-Society CY NOV 07-11, 2004 CL Rio Grande, PR SP IEEE Lasers & Electro Opt Soc, IEEE C1 NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Gannot, I (reprint author), NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 0-7803-8557-8 J9 IEEE LEOS ANN MTG PY 2004 BP 898 EP 899 PG 2 WC Optics SC Optics GA BBG19 UT WOS:000225390900448 ER PT S AU Barker, WC Liow, JS Rodriguez, M Thada, S Iano-Fletcher, AR Lenox, M Michel, C Johnson, CA Carson, RE AF Barker, WC Liow, JS Rodriguez, M Thada, S Iano-Fletcher, AR Lenox, M Michel, C Johnson, CA Carson, RE BE Seibert, JA TI Randoms estimation for list-mode reconstruction for the ECAT HRRT SO 2004 IEEE Nuclear Science Symposium Conference Record, Vols 1-7 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT Nuclear Science Symposium/Medical Imaging Conference CY OCT 16-22, 2004 CL Rome, ITALY SP IEEE Commun Soc, Nucl & Plasma Sci Soc AB A randoms correction method has been implemented for list-mode image reconstruction of data from the ECAT HRRT (High Resolution Research Tomograph). The random coincidence rate for each list-mode event is estimated from the relevant block singles rates, the estimated coincidence timing window (7), and the fractional efficiency of the crystal within the block. From a decaying phantom study, tau ranged from 2.80-2.97 nsec, consistent with the expected value of 3 nsec, having only a slight variation with count rate. Because the fractional crystal efficiencies were also found to be count rate dependent with higher LYSO/LSO relative efficiency at higher count rates, we have determined that a count rate dependent correction is necessary. No photon energy/object size dependence was found for the efficiencies. C1 NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Barker, WC (reprint author), NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 5 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-8700-7 J9 IEEE NUCL SCI CONF R PY 2004 BP 3510 EP 3513 PG 4 WC Nuclear Science & Technology; Physics, Nuclear; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BCZ05 UT WOS:000232002105037 ER PT S AU Johnson, CA Thada, S Rodriguez, M Zhao, YS Iano-Fletcher, AR Liow, JS Barker, WC Martino, RL Carson, RE AF Johnson, CA Thada, S Rodriguez, M Zhao, YS Iano-Fletcher, AR Liow, JS Barker, WC Martino, RL Carson, RE BE Seibert, JA TI Software architecture of the MOLAR-HRRT reconstruction engine SO 2004 IEEE Nuclear Science Symposium Conference Record, Vols 1-7 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT Nuclear Science Symposium/Medical Imaging Conference CY OCT 16-22, 2004 CL Rome, ITALY SP IEEE Commun Soc, Nucl & Plasma Sci Soc ID IMAGE AB The Motion-compensation OSEM List-mode Algorithm for Resolution-recovery Reconstruction (MOLAR) is a complete system for managing and performing iterative PET reconstructions. Although it was designed for use with the ECAT HRRT, its pluggable component architecture is readily extendable to any PET scanner, list-mode or frame-mode. List-mode data are stored on a distributed set of linked lists of event packets. Each event packet stores all information needed for one coincidence event. The resolution model uses a distance-based approximation and assumes separability of the radial and axial factors. Since the complete computation of the global sensitivity image Q (the denominator outside the sum in the OSEM update equation) requires a back-projection of all 4.5x10(9) possible LORs in the HRRT at all time increments in the scan frame and is thus intractable, we have devised an approximation in which the back projection is performed on only a randomized sub-sampling of LOR space. To test the randomized approach we generated 10 realizations of the Q image at various count levels and measured the average coefficient of variation (COV) per slice at each count level. We characterize the dependence of image noise on error in Q. We also provide a result demonstrating that we have achieved image resolution of less than 3 mm, a critical design goal. C1 NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Johnson, CA (reprint author), NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 8 TC 4 Z9 4 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-8700-7 J9 IEEE NUCL SCI CONF R PY 2004 BP 3956 EP 3960 DI 10.1109/NSSMIC.2004.1466744 PG 5 WC Nuclear Science & Technology; Physics, Nuclear; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BCZ05 UT WOS:000232002105138 ER PT S AU Zhou, QF Shung, KK Huang, Y AF Zhou, QF Shung, KK Huang, Y BE Yuhas, MP TI Fabrication of Sol-gel modified piezoelectric thick films for high frequency ultrasonic applications SO 2004 IEEE Ultrasonics Symposium, Vols 1-3 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY AUG 23-27, 2004 CL Montreal, CANADA SP IEEE Ultrason Ferroelect & Frequency Control Soc DE thick films; PZT; ultrasound ID TRANSDUCERS; COMPOSITE AB In this work, a fabrication process of piezoelectric PZT thick films up to 60 gm deposited on silicon and aluminum substrates is reported. Crystalline spherical modified PZT powder about 0.3 mu m in diameter was used as filler. PZT polymeric precursor produced by Chemat Inc was used as the matrix material. Spinning films were annealed at 700 C in the furnace for half an hour in air. The thickness of the thick films was measured using a scanning electron microscope (SEM). Compared with previous piezoelectric PZT composite films, the modified piezoelectric thick films exhibit very good dielectric properties. The dielectric constant is over 780 and dielectric loss is 0.04 at 1 KHz. Using a PiezoCAD model, the high frequency transducer was designed and fabricated. It showed a bandwidth of 75% at 40 MHz. C1 Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA USA. RP Zhou, QF (reprint author), Univ So Calif, NIH, Transducer Resource Ctr, Los Angeles, CA USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-8413-X J9 ULTRASON PY 2004 BP 1958 EP 1961 PG 4 WC Acoustics; Physics, Applied SC Acoustics; Physics GA BCC37 UT WOS:000228557202097 ER PT B AU Silvestri, LS Taraporewala, ZF Tortorici, MA Patton, JT AF Silvestri, LS Taraporewala, ZF Tortorici, MA Patton, JT GP medimond TI Characterization of rotavirus genome replication using RNA interference SO 2ND EUROPEAN CONGRESS OF VIROLOGY, PROCEEDINGS LA English DT Proceedings Paper CT 2nd European Congress of Virology CY SEP 05-09, 2004 CL Madrid, SPAIN AB The segmented double-stranded (ds)RNA genome of rotavirus is synthesized by early assembly intermediates in cytoplasmic inclusion bodies (viroplasms). We have used short interfering RNAs (siRNAs) to study the contribution of viral (+)RNAs and their protein products on dsRNA synthesis and particle assembly. The results show that (+)RNAs which direct dsRNA synthesis in viroplasms are resistant to degradation by siRNA-induced RNase, and thus replication templates do not derive from the RNase-sensitive (+)RNAs that direct translation in the cytosol. Instead, BrUTP-labeling experiments indicate that replication templates are made in viroplasms. Protein knockdown experiments reveal the critical role that viroplasms play in all aspects of the viral life cycle, including dsRNA synthesis, RNA amplification, and particle assembly. C1 NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Silvestri, LS (reprint author), NIAID, Infect Dis Lab, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-076-4 PY 2004 BP 27 EP 31 PG 5 WC Virology SC Virology GA BBE79 UT WOS:000225160200006 ER PT B AU Rebmann, AJ Butman, JA AF Rebmann, AJ Butman, JA GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Heterogeneity of MR signal intensity mapped onto brain surface models SO 32ND APPLIED IMAGERY PATTERN RECOGNITION WORKSHOP, PROCEEDINGS LA English DT Proceedings Paper CT 32nd Applied Imagery Pattern Recognition Workshop CY OCT 15-17, 2003 CL Washington, DC SP IEEE Comp Soc, TC Pattern Anal & Machine Intelligence ID SOFTWARE; CORTEX AB Heterogeneity of gray matter signal intensity can be demonstrated on some MR sequences, particularly FLAIR. Quantifying this heterogeneity is of interest as it may distinguish among different cortical areas. Gray matter segmentation fails on FLAIR data due to overlap of gray and white matter signal intensity. This overlap also compromises region of interest based approaches. Although volume rendering can visualize some of these differences, it is non quantitative and averaging gray and white matter cannot be avoided. To overcome these obstacles we obtained T1 weighted data in addition to FLAIR data. T1 weighted data provides strong gray/white contrast, allowing a cortical surface to be extracted. Volume based registration of the FLAIR data set to the T1 data allows FLAIR signal intensity data to be mapped onto the surface generated from the T1 dataset. This allows regional FLAIR signal intensity differences to be visualized and to be compared across subjects. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Rebmann, AJ (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 2 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2029-4 PY 2004 BP 119 EP 124 PG 6 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BAA60 UT WOS:000221356000020 ER PT B AU Kim, J Le, DX Thoma, GR AF Kim, J Le, DX Thoma, GR BE Callaos, N Lesso, W Kurogi, S Tanaka, A Castillo, O TI Automated labeling from biomedical journals published in foreign languages SO 8TH WORLD MULTI-CONFERENCE ON SYSTEMICS, CYBERNETICS AND INFORMATICS, VOL V, PROCEEDINGS: COMPUTER SCIENCE AND ENGINEERING LA English DT Proceedings Paper CT 8th World Multi-Conference on Systemics, Cybernetics and Informatics CY JUL 18-21, 2004 CL Orlando, FL SP Int Inst Informat & System, Amer Soc Cybernet, Acad Non Linear Sci, Univ Las Palmas Gran Canaria, Telemat Engn Dept, Concurrency & Architecture Grp, CUST, Blaise Pascal Univ, Engn Sci Inst, Cybernet & Human Knowing, Int Federat Syst Res, Int Syst Inst, Int Soc Syst Sci, Italian Soc System, Univ Nacl San Luis, Lab Res Computac Intelligence, Dept Informat, Polish Syst Soc, Slovenian Artificial Intelligence Soc, Soc Appl Syst Res, Syst Soc Poland, Ctr Syst Studies, Tunisian Sci Soc, World Org System & Cybernet, IEEE Comp Soc, Venezuela Chapter, IEEE, Venezuela Chapter, Natl Res Council Canada, Steacie Inst Mol Sci DE labeling module; rule-based algorithm; foreign language journals; OCR; MARS ID DOCUMENT IMAGES AB An automated labeling (AL) module is developed to produce bibliographic records such as English title, vernacular title, author, affiliation, and English abstract from biomedical articles published in foreign language journals. Optical character recognition (OCR) output from scanned biomedical journals is used in this labeling process. Since frequently occurring words in a zone are important features, word lists are used as key features in the AL module. The AL module uses geometric and contextual features, and geometric relations between zones, as the basis for the rule-based labeling algorithms in the module. The algorithms uses 131 rules derived for foreign language journals. Experiments conducted with several medical journal articles show about 95% accuracy. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Kim, J (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU INT INST INFORMATICS & SYSTEMICS PI ORLANDO PA 14269 LORD BARCLAY DR, ORLANDO, FL 32837 USA BN 980-6560-13-2 PY 2004 BP 444 EP 449 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA BBT28 UT WOS:000227679300079 ER PT B AU Le, DX Thoma, GR AF Le, DX Thoma, GR BE Callaos, N Lesso, W Kurogi, S Tanaka, A Castillo, O TI Automated article links identification for web-based online medical journals SO 8TH WORLD MULTI-CONFERENCE ON SYSTEMICS, CYBERNETICS AND INFORMATICS, VOL V, PROCEEDINGS: COMPUTER SCIENCE AND ENGINEERING LA English DT Proceedings Paper CT 8th World Multi-Conference on Systemics, Cybernetics and Informatics CY JUL 18-21, 2004 CL Orlando, FL SP Int Inst Informat & System, Amer Soc Cybernet, Acad Non Linear Sci, Univ Las Palmas Gran Canaria, Telemat Engn Dept, Concurrency & Architecture Grp, CUST, Blaise Pascal Univ, Engn Sci Inst, Cybernet & Human Knowing, Int Federat Syst Res, Int Syst Inst, Int Soc Syst Sci, Italian Soc System, Univ Nacl San Luis, Lab Res Computac Intelligence, Dept Informat, Polish Syst Soc, Slovenian Artificial Intelligence Soc, Soc Appl Syst Res, Syst Soc Poland, Ctr Syst Studies, Tunisian Sci Soc, World Org System & Cybernet, IEEE Comp Soc, Venezuela Chapter, IEEE, Venezuela Chapter, Natl Res Council Canada, Steacie Inst Mol Sci DE instance-based learning algorithm; a nearest neighbor methodology AB As part of research into Web-based document analysis including Web page downloading and classification, an algorithm has been developed to automatically identify article links in Web-based online journals. This algorithm is based on feature vectors calculated from attributes and contents of links extracted from HTML files, and an instance-based learning algorithm using a nearest neighbor methodology to identify article links. The performance of the algorithm has been evaluated using a sample size of several thousand HTML links of Web-based medical journals. Evaluation shows that the algorithm is capable of identifying article links at an accuracy greater than 99%. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU INT INST INFORMATICS & SYSTEMICS PI ORLANDO PA 14269 LORD BARCLAY DR, ORLANDO, FL 32837 USA BN 980-6560-13-2 PY 2004 BP 462 EP 466 PG 5 WC Computer Science, Artificial Intelligence SC Computer Science GA BBT28 UT WOS:000227679300082 ER PT S AU Yakel, JL Shao, ZY AF Yakel, JL Shao, ZY BE Descarries, L Krnjevic, K Steriade, M TI Functional and molecular characterization of neuronal nicotinic ACh receptors in rat hippocampal interneurons SO ACETYLCHOLINE IN THE CEREBRAL CORTEX SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 24th International Symposium of the Centre-for-Research-in-Neurological-Sciences (CRSN) CY MAY 06-07, 2002 CL UNIV MONTREAL, MONTREAL, CANADA SP Ctr Res Neurol Sci HO UNIV MONTREAL ID CENTRAL-NERVOUS-SYSTEM; ACETYLCHOLINE-RECEPTORS; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; GANGLION NEURONS; ALPHA-7 SUBUNITS; HIGH-AFFINITY; CA1 NEURONS; BRAIN; SUBTYPES C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,F2-08,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov NR 56 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-51125-3 J9 PROG BRAIN RES PY 2004 VL 145 BP 95 EP 107 DI 10.1016/S0079-6123(03)45006-1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA BY28W UT WOS:000188788200006 PM 14650909 ER PT J AU Greig, NH Giordano, T Zhu, XX Yu, QS Perry, TA Holloway, HW Brossi, A Rogers, JT Sambamurti, K Lahiri, DK AF Greig, NH Giordano, T Zhu, XX Yu, QS Perry, TA Holloway, HW Brossi, A Rogers, JT Sambamurti, K Lahiri, DK TI Thalidomide-based TNF-alpha inhibitors for neurodegenerative diseases SO ACTA NEUROBIOLOGIAE EXPERIMENTALIS LA English DT Article DE thalidomide; thalidomide analogues; TNF-alpha inhibitors; Alzheimer's disease; amyloid precursor protein; amyloid-beta peptide; lipopolysacharide (LPS); peripheral blood mononuclear cells (PBMC); rheumatoid arthritis; erythema nodosum leprosum (ENL); amyotrophic lateral sclerosis (ALS); translational regulation ID AMYLOID PRECURSOR PROTEIN; NECROSIS-FACTOR-ALPHA; AU-RICH ELEMENTS; MESSENGER-RNA DEGRADATION; NF-KAPPA-B; ALZHEIMERS-DISEASE; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT; HUMAN BRAIN; INTERLEUKIN-1 AB Inflammatory processes associated with the over-production of cytokines, particularly of TNF-alpha, accompany numerous neurodegenerative diseases, such as Alzheimer's disease, in addition to numerous systemic conditions, exemplified by rheumatoid arthritis and erythema nodosum leprosum (ENL). TNF-alpha has been validated as a drug target with Remicade and Enbrel available as prescription medications. Both, however, are large macromolecules, require injection and have limited brain access. The classical drug, thalidomide is being increasingly used in the clinical management of a wide spectrum of diseases. As its clinical value in treating ENL derives from its TNF-alpha inhibitory activity, thalidomide was chosen for structural modification for the discovery of novel and more potent isosteric analogues with appropriate lipophilicity to insure high brain penetration. TNF-alpha inhibitory activity was evaluated against lipopolysacharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) in cell culture, whose viability was quantified to differentiate reductions in TNF-alpha secretion from that associated with cellular toxicity. Specific analogues potently inhibited TNF-alpha secretion, compared to thalidomide. This involved a post-transcriptional mechanism, as they decreased TNF-alpha rnRNA stability via its 3'-untranslated region (UTR), as determined by luciferase activity in stably transfected cells with and without the 3'-UTR of human TNF-alpha. C1 NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Prog,NIH, Baltimore, MD 21224 USA. Louisiana State Univ, Dept Mol Biol & Biochem, Shreveport, LA 71130 USA. Univ N Carolina, Sch Pharm, Dept Chem, Chapel Hill, NC 27599 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit,Dept Neurol, Charlestown, MA 02129 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Indiana Univ, Sch Med, Inst Psychiat Res, Indianapolis, IN 46202 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Prog,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM GreigN@vax.grc.nia.nih.gov NR 63 TC 30 Z9 34 U1 0 U2 0 PU NENCKI INST EXPERIMENTAL BIOLOGY PI WARSAW PA UL PASTEURA 3, 02-093 WARSAW, POLAND SN 0065-1400 J9 ACTA NEUROBIOL EXP JI Acta Neurobiol. Exp. PY 2004 VL 64 IS 1 BP 1 EP 9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 805KZ UT WOS:000220366500002 PM 15190675 ER PT J AU Markowska, A AF Markowska, A TI Kazimierz Zielinski (1929-2004) SO ACTA NEUROBIOLOGIAE EXPERIMENTALIS LA English DT Biographical-Item C1 NIH, Bethesda, MD 20892 USA. RP Markowska, A (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NENCKI INST EXPERIMENTAL BIOLOGY PI WARSAW PA UL PASTEURA 3, 02-093 WARSAW, POLAND SN 0065-1400 J9 ACTA NEUROBIOL EXP JI Acta Neurobiol. Exp. PY 2004 VL 64 IS 2 BP III EP IV PG 2 WC Neurosciences SC Neurosciences & Neurology GA 820BS UT WOS:000221362100020 ER PT J AU Moore, R Doherty, D Chamberlain, R Khuri, F AF Moore, R Doherty, D Chamberlain, R Khuri, F TI Sex differences in survival in non-small cell lung cancer patients 1974-1998 SO ACTA ONCOLOGICA LA English DT Article ID WOMEN; SMOKING; GENDER; RISK; CARCINOMA; RESECTION; MEN AB This study comprised a total of 7 553 patients with non-small cell lung cancer (2 660 women and 4 893 men) treated at a comprehensive cancer centre between 1974 and 1998. Significant differences in tumour histology were associated with gender (p < 0.001); adenocarcinoma was the most common diagnosis in both men (50.0%) and women (41.7%); squamous cell carcinoma was the second most prevalent diagnosis (21% and 31% in women and men, respectively); and bronchioalveolar tumours were more prevalent in men (3% compared with 7% in women). Frequency distributions with local, regional or distant disease at registration were similar between men and women (p = 0.906). In a multivariable Cox regression analysis the indications were that gender is an important risk factor for survival. Adjusting for age, stage, treatment received and ability to pay for care, a statistically significant interaction between gender and tumour histology (p = 0.043) was found, where, in relation to female sex and histologies other than squamous carcinoma, women who presented with squamous carcinoma had an increased risk of death (HR = 1.09, 95% CI 1.02-1.18) while men had an increased risk of death for all histologies (HR = 1.29, 95% CI 1.21-1.40, and HR = 1.15, 95% CI 1.07-1.24 for squamous and other histologies, respectively). This study confirms previous reports of strong gender-dependent differences in survival in patients with non-small cell lung cancer, including a histology-specific effect in women. C1 NINDS, Dept Epidemiol, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. NINDS, Dept Biostat, Bethesda, MD 20892 USA. NINDS, Dept Thorac Head & Neck Med Oncol, Bethesda, MD 20892 USA. RP Moore, R (reprint author), NINDS, Dept Epidemiol, Lab Funct & Mol Imaging, Bldg 10,Room B1D106,10 Ctr Dr,MSC 1065, Bethesda, MD 20892 USA. EM moorer@ninds.nih.gov FU NCI NIH HHS [3R25 CA5770-8S2.9] NR 32 TC 34 Z9 34 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD JAN PY 2004 VL 43 IS 1 BP 57 EP 64 DI 10.1080//02841860310017973 PG 8 WC Oncology SC Oncology GA 771BA UT WOS:000188764600011 PM 15068321 ER PT J AU Altshuler, LL Rasgon, NL Elman, S Bitran, J Labarca, R Saad, M Kupka, RW Nolen, WA Frye, MA Suppes, T McElroy, SL Keck, PE Leverich, GS Grunze, G Walden, J Post, RM Mintz, J AF Altshuler, LL Rasgon, NL Elman, S Bitran, J Labarca, R Saad, M Kupka, RW Nolen, WA Frye, MA Suppes, T McElroy, SL Keck, PE Leverich, GS Grunze, G Walden, J Post, RM Mintz, J TI Reproductive and metabolic hormone levels in bipolar women SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 94304 USA. Stanford Univ, Sch Med, Palo Alto, CA USA. Inst Neuropsiquiat Chile, Santiago, Chile. Altrech Inst Mental Hlth Care, Utrecht, Netherlands. Univ Groningen Hosp, Groningen, 75230, Netherlands. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Cincinnati, Coll Med, Cincinnati, OH 20892 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD USA. LMU Munich, D-7800 Munich, Germany. Univ Freiburg, D-4400 Freiburg, Germany. Univ Munster, Munster, Germany. RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 14 EP 15 PG 2 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100025 ER PT J AU Frye, MA Levander, E McElroy, SL Suppes, T Keck, PE Nolen, WA Leverich, GS Grunze, H Walden, J Kupka, RW Altshuler, L Mintz, J Post, RM AF Frye, MA Levander, E McElroy, SL Suppes, T Keck, PE Nolen, WA Leverich, GS Grunze, H Walden, J Kupka, RW Altshuler, L Mintz, J Post, RM TI Additional axis I comorbidity in patients with bipolar disorder and alcoholism SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Utrecht, Utrecht, Netherlands. NIMH, DHHS, NIH, Bethesda, MD 20892 USA. Univ Munich, Psychiat Klin, Munich, Germany. Univ Freiburg, Psychiat Klin, Freiburg, Germany. RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 19 EP 19 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100040 ER PT J AU Grunze, H Dittmann, S Nolen, WA Kupka, RW Schaerer, LO Bauer, M Frye, MA Altshuler, LL Keck, PE Leverich, GS McElroy, SL Suppes, T Post, RM AF Grunze, H Dittmann, S Nolen, WA Kupka, RW Schaerer, LO Bauer, M Frye, MA Altshuler, LL Keck, PE Leverich, GS McElroy, SL Suppes, T Post, RM TI Acamprosate as adjunctive treatment in rapid cycling bipolar disorder: an open pilot study SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Univ Utrecht, Utrecht, Netherlands. Univ Munich, Munich, Germany. Univ Freiburg, Freiburg, Germany. Univ Berlin, Berlin, Germany. Univ Calif Los Angeles, Ambulatory Clin Res Ctr, Los Angeles, CA 90024 USA. VA Med Ctr, Los Angeles, CA 90024 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NIMH, DHHS, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, Austin, TX 78712 USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 21 EP 21 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100046 ER PT J AU Keck, PE Hibbeln, J McElroy, SL Freeman, M Suppes, T Nolen, WA Kupka, RW Grunze, H Mintz, J Frye, MA Altshuler, L Denicoff, K Walden, J Leverich, GS Post, RM AF Keck, PE Hibbeln, J McElroy, SL Freeman, M Suppes, T Nolen, WA Kupka, RW Grunze, H Mintz, J Frye, MA Altshuler, L Denicoff, K Walden, J Leverich, GS Post, RM TI Omega-3 fatty acid blood concentrations and response in bipolar depression and rapid cycling bipolar disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. NIMH, Bethesda, MD 20892 USA. Univ Arizona, Sch Med, Tucson, AZ 85721 USA. Univ Texas, SW Med Sch, Dallas, TX USA. Univ Munich, Psychiat Klin, Munich, Germany. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Freiburg, Psychiat Klin, D-7800 Freiburg, Germany. RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 23 EP 23 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100052 ER PT J AU Suppes, T Kupka, RW McElroy, SL Altshuler, L Mintz, J Frye, MA Keck, PE Leverich, GS Grunze, H Nolen, WA Post, RM AF Suppes, T Kupka, RW McElroy, SL Altshuler, L Mintz, J Frye, MA Keck, PE Leverich, GS Grunze, H Nolen, WA Post, RM TI Increased incidence of mixed symptoms in hypomania in females SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Altrecht Ctr Mental Hlth Care, Utrecht, Netherlands. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NIMH, Bethesda, MD USA. Univ Munich, Munich, Germany. RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 24 EP 25 PG 2 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100057 ER PT J AU Kupka, RW Luckenbaugh, D Post, RM Altshuler, L Denicoff, KD Frye, MA Grunze, H Keck, PE Leverich, GS McElroy, SL Suppes, T Walden, J Nolen, WA AF Kupka, RW Luckenbaugh, D Post, RM Altshuler, L Denicoff, KD Frye, MA Grunze, H Keck, PE Leverich, GS McElroy, SL Suppes, T Walden, J Nolen, WA TI Rapid cycling bipolar disorder: a 5-year prospective follow-up SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA. Univ Cincinnati, Psychopharmacol Res Program, Cincinnati, OH USA. Univ Munich, Psychiat Klin, Munich, Germany. Univ Freiburg, Psychiat Klin, Freiburg, Germany. Univ Groningen, Dept Psychiat, Groningen, Netherlands. RI Nolen, Willem/E-9006-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 25 EP 25 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100058 ER PT J AU Leverich, GS Altshuler, LL Frye, MA Suppes, T McElroy, SL Keck, PE Kupka, RW Nolen, WA Grunze, H Martinez, MI Post, RM AF Leverich, GS Altshuler, LL Frye, MA Suppes, T McElroy, SL Keck, PE Kupka, RW Nolen, WA Grunze, H Martinez, MI Post, RM TI The range of hypo/manic severities on antidepressants by the daily LCM SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 NIMH, DHHS, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Cincinnati, Coll Med, Psychopharmacol Program, Cincinnati, OH USA. Altrecht Inst Mental Hlth Care, Altrecht, Netherlands. Univ Med Ctr, Altrecht, Netherlands. Univ Groningen, Dept Psychiat, NL-9700 AB Groningen, Netherlands. Univ Munich, Munich, Germany. RI Nolen, Willem/E-9006-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 25 EP 26 PG 2 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100060 ER PT J AU Post, RM Altshuler, LL Leverich, GS Frye, MA Nolen, WA Kupka, RW Suppes, T McElroy, SL Keck, PE Denicoff, KD Grunze, H Walden, J Kitchen, C AF Post, RM Altshuler, LL Leverich, GS Frye, MA Nolen, WA Kupka, RW Suppes, T McElroy, SL Keck, PE Denicoff, KD Grunze, H Walden, J Kitchen, C TI Switch rate on venlafaxine compared with bupropion and sertraline SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Meeting Abstract C1 NIMH, DHHS, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA. Univ Groningen, Dept Psychiat, Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Cincinnati, Coll Med, Psychopharmacol Res Program, Cincinnati, OH 45221 USA. Univ Munich, Psychiat Klin, Munich, Germany. Univ Freiburg, Psychiat Klin, Freiburg, Germany. Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PY 2004 VL 110 SU 423 BP 32 EP 32 PG 1 WC Psychiatry SC Psychiatry GA 859VX UT WOS:000224297100082 ER PT S AU Pine, DS AF Pine, DS BE Dahl, RE Spear, LP TI Integrating research on developmental psychopathology and neuroscience in the study of adolescence - Introduction to Part II SO ADOLESCENT BRAIN DEVELOPMENT: VULNERABILITIES AND OPPORTUNITIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Adolescent Brain Development - Vulnerabilities and Opportunities CY SEP 18-20, 2003 CL New York, NY SP New York Acad Sci, Univ Pittsburgh Sch Med, Ctr Continuing Educ DE neuroscience; psychopathology; adolescence; brain development ID ANXIETY; STRESS; GENE AB This chapter introduces three papers that summarize research findings in clinical and basic neuroscience. They integrate prior research on clinical aspects of developmental psychopathology, basic research on brain development in nonhuman primates, and neuroimaging research on both normal and abnormal human development. From the clinical perspective these papers call attention to the unique relationship between adolescence and psychopathology. From the basic science perspective they call attention to the sequence of events that culminates in a fully mature central nervous system. C1 NIMH, Sect Dev & Affect Neurosci, Intramural Res Program, NIH, Bethesda, MD 20817 USA. RP Pine, DS (reprint author), NIMH, Sect Dev & Affect Neurosci, Intramural Res Program, NIH, Bldg 15-K,Room 110,MSC-2670, Bethesda, MD 20817 USA. EM daniel.pine@nih.gov NR 5 TC 2 Z9 2 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-506-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1021 BP 61 EP 63 DI 10.1196/annals.1308.007 PG 3 WC Behavioral Sciences; Substance Abuse; Psychology, Developmental; Multidisciplinary Sciences; Neurosciences; Pediatrics; Psychology SC Behavioral Sciences; Substance Abuse; Psychology; Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BAN60 UT WOS:000222980100007 PM 15251875 ER PT S AU Giedd, JN AF Giedd, JN BE Dahl, RE Spear, LP TI Structural magnetic resonance imaging of the adolescent brain SO ADOLESCENT BRAIN DEVELOPMENT: VULNERABILITIES AND OPPORTUNITIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Adolescent Brain Development - Vulnerabilities and Opportunities CY SEP 18-20, 2003 CL New York, NY SP New York Acad Sci, Univ Pittsburgh Sch Med, Ctr Continuing Educ DE magnetic resonance imaging (MRI); adolescence; gray matter; white matter ID DEFICIT-HYPERACTIVITY DISORDER; CORPUS-CALLOSUM MORPHOLOGY; AGE-RELATED-CHANGES; TOURETTES-SYNDROME; MORPHOMETRIC ANALYSIS; CHRONIC-SCHIZOPHRENIA; BASAL GANGLIA; RHESUS-MONKEY; IN-VIVO; MRI AB Magnetic resonance imaging (MRI) provides accurate anatomical brain images without the use of ionizing radiation, allowing longitudinal studies of brain morphometry during adolescent development. Results from an ongoing brain imaging project being conducted at the Child Psychiatry Branch of the National Institute of Mental Health indicate dynamic changes in brain anatomy throughout adolescence. White matter increases in a roughly linear pattern, with minor differences in slope in the four major lobes (frontal, parietal, temporal, occipital). Cortical gray matter follows an inverted U-shape developmental course with greater regional variation than white matter. For instance, frontal gray matter volume peaks at about age 11.0 years in girls and 12.1 years in boys, whereas temporal gray matter volume peaks at about age at 16.7 years in girls and 16.2 years in boys. The dorsal lateral prefrontal cortex, important for controlling impulses, is among the latest brain regions to mature without reaching adult dimensions until the early 20s. The details of the relationships between anatomical changes and behavioral changes, and the forces that influence brain development, have not been well established and remain a prominent goal of ongoing investigations. C1 NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Room 4C110,10 Ctr Dr MSC 1367, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 57 TC 675 Z9 682 U1 5 U2 55 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-506-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1021 BP 77 EP 85 DI 10.1196/annals.1308.009 PG 9 WC Behavioral Sciences; Substance Abuse; Psychology, Developmental; Multidisciplinary Sciences; Neurosciences; Pediatrics; Psychology SC Behavioral Sciences; Substance Abuse; Psychology; Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BAN60 UT WOS:000222980100009 PM 15251877 ER PT S AU Merikangas, KR AF Merikangas, KR BE Dahl, RE Spear, LP TI The importance of adolescence in the development of nicotine dependence - Comments on Part V SO ADOLESCENT BRAIN DEVELOPMENT: VULNERABILITIES AND OPPORTUNITIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Adolescent Brain Development - Vulnerabilities and Opportunities CY SEP 18-20, 2003 CL New York, NY SP New York Acad Sci, Univ Pittsburgh Sch Med, Ctr Continuing Educ AB This conference has provided a unique opportunity for scientists engaged in disparate domains of function to address this central theme (nicotine dependence) from multiple perspectives of brain function and its communication with experience. The lack of knowledge on the role of development in exposure and progression of substance use is a particularly critical gap that impedes our ability to understand, treat, and prevent substance abuse. This section on the importance of adolescence in the emergence of tobacco use and the development of nicotine dependence includes two outstanding presentations that identified common developmental differences in drug exposure from the perspectives of animal research(1) and human community-based research.(2) C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), NIMH, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM merikank@intra.nimh.nih.gov NR 7 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-506-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1021 BP 198 EP 201 DI 10.1196/annals.1308.024 PG 4 WC Behavioral Sciences; Substance Abuse; Psychology, Developmental; Multidisciplinary Sciences; Neurosciences; Pediatrics; Psychology SC Behavioral Sciences; Substance Abuse; Psychology; Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BAN60 UT WOS:000222980100021 PM 15251889 ER PT S AU Barr, CS Schwandt, ML Newman, TK Higley, JD AF Barr, CS Schwandt, ML Newman, TK Higley, JD BE Dahl, RE Spear, LP TI The use of adolescent nonhuman primates to model human alcohol intake - Neurobiological, genetic, and psychological variables SO ADOLESCENT BRAIN DEVELOPMENT: VULNERABILITIES AND OPPORTUNITIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Adolescent Brain Development - Vulnerabilities and Opportunities CY SEP 18-20, 2003 CL New York, NY SP New York Acad Sci, Univ Pittsburgh Sch Med, Ctr Continuing Educ DE serotonin; primate; alcohol; stress; rearing; polymorphism; adolescent; GxE interaction ID SYSTEM SEROTONERGIC RESPONSIVITY; CHILDHOOD PARENTAL LOSS; ANXIETY-RELATED TRAITS; MONOAMINE-OXIDASE; RHESUS-MONKEYS; REGULATORY POLYMORPHISM; EARLY EXPERIENCE; VERVET MONKEYS; SOCIAL-GROUPS; LIFE STRESS AB Traits characteristic of type I and type II alcoholism are thought to relate to dysregulated central nervous system serotonin functioning. In this review, we discuss variables associated with high adolescent alcohol consumption and other risk-taking behaviors in a nonhuman primate model. Adolescent primates with low CSF concentrations of the serotonin metabolite 5-HIAA are more impulsive and exhibit increased levels of alcohol consumption. Both genetic and environmental factors contribute to alcohol-seeking behavior in adolescent macaques. Sequence variation within serotonin system genes, for example, a repeat polymorphism in the transcriptional control region of the monoamine oxidase gene (MAOA-LPR), increases the propensity for adolescent males to consume alcohol. Environmental factors, such as early life stress in the form of peer-rearing or early age of exposure to alcohol, are also associated with increased alcohol consumption. Peer-reared females, especially those exposed to alcohol during early adolescence, exhibit increased rates of alcohol consumption compared to those exposed to alcohol later in development. When genetic variables are also considered, there is an interaction between the low activity serotonin transporter gene promoters allele (rh5-HTTLPR) and rearing condition on alcohol preference in females but not males, suggesting that the interactions between genes and the environment may be sexually dichotomous. By learning more about the interactions between genes, early experience, and alcohol intake in the adolescent nonhuman primate, we may be able to identify factors that contribute to the susceptibility, pathogenesis, and progression of impulse control disorders, such as alcoholism. C1 NIAAA, Clin Studies Lab, Primate Unit, Div Intramural Clin & Biol Res, Poolesville, MD 20837 USA. EM cbaff@mail.nih.gov RI Schwandt, Melanie/L-9866-2016 NR 74 TC 55 Z9 56 U1 5 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-506-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1021 BP 221 EP 233 DI 10.1196/annals.1308.027 PG 13 WC Behavioral Sciences; Substance Abuse; Psychology, Developmental; Multidisciplinary Sciences; Neurosciences; Pediatrics; Psychology SC Behavioral Sciences; Substance Abuse; Psychology; Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BAN60 UT WOS:000222980100024 PM 15251892 ER PT S AU Blumberg, HP Kaufman, J Martin, A Charney, DS Krystal, JH Peterson, BS AF Blumberg, HP Kaufman, J Martin, A Charney, DS Krystal, JH Peterson, BS BE Dahl, RE Spear, LP TI Significance of adolescent neurodevelopment for the neural circuitry of bipolar disorder SO ADOLESCENT BRAIN DEVELOPMENT: VULNERABILITIES AND OPPORTUNITIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Adolescent Brain Development - Vulnerabilities and Opportunities CY SEP 18-20, 2003 CL New York, NY SP New York Acad Sci, Univ Pittsburgh Sch Med, Ctr Continuing Educ DE bipolar disorder; magnetic resonance imaging; child development ID PREFRONTAL CORTEX; BRAIN MORPHOLOGY; AGE; ABNORMALITIES; CHILDHOOD; AMYGDALA; MRI AB The deficits of executive control of emotions and impulses of adult BD implicate involvement of a ventral prefrontal cortex (VPFC) neural system that subserves these functions that include the VPFC, as well as its subcortical connection sites of amygdala, striatum, and thalamus. Differences in the timing of major developmental changes in the structures within this neural system suggest that abnormalities in particular components of this neural system may emerge during critical developmental epochs during the course of the illness. Our recent neuroimaging data suggest that abnormalities in the subcortical components of VPFC neural systems may be evident by early adolescence in BD, whereas VPFC deficits progress over the course of adolescence and may be difficult to detect prior to late adolescence or early adulthood. This potential neurodevelopmental model for BD) could have important implications for the recognition of early signs of the disorder and for age-specific treatment strategies. C1 Yale Univ, Sch Med, VA Depress Res Ctr, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. NIMH, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. Columbia Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Blumberg, HP (reprint author), Yale Univ, Sch Med, VA Depress Res Ctr, VA Connecticut Healthcare Syst, 950 Campbell Ave, West Haven, CT 06516 USA. EM hilary.blumberg@yale.edu FU NIAAA NIH HHS [KO2AA 00261-01]; NIMH NIH HHS [MH59139, MH01792, MH01232] NR 21 TC 69 Z9 69 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-506-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1021 BP 376 EP 383 DI 10.1196/annals.1308.048 PG 8 WC Behavioral Sciences; Substance Abuse; Psychology, Developmental; Multidisciplinary Sciences; Neurosciences; Pediatrics; Psychology SC Behavioral Sciences; Substance Abuse; Psychology; Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BAN60 UT WOS:000222980100045 PM 15251913 ER PT J AU Finch, PW Rubin, JS AF Finch, PW Rubin, JS TI Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair SO ADVANCES IN CANCER RESEARCH, VOL 91 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID INDUCED LUNG INJURY; FACTOR RECEPTOR 2; INFLAMMATORY-BOWEL-DISEASE; MESSENGER-RNA EXPRESSION; VERSUS-HOST-DISEASE; DELTA T-CELLS; FACTOR GENE-EXPRESSION; SURFACTANT PROTEIN-A; PLASMINOGEN-ACTIVATOR ACTIVITY; HEPARAN-SULFATE PROTEOGLYCANS AB Keratinocyte growth factor (KGF) is a paracrine-acting, epithelial mitogen produced by cells of mesenchymal origin. It is a member of the fibroblast growth factor (FGF) family, and acts exclusively through a subset of FGF receptor isoforms (FGFR2b) expressed predominantly by epithelial cells. The upregulation of KGF after epithelial injury suggested it had an important role in tissue repair. This hypothesis was reinforced by evidence that intestinal damage was worse and healing impaired in KGF null mice. Preclinical data from several animal models demonstrated that recombinant human KGF could enhance the regenerative capacity of epithelial tissues and protect them from a variety of toxic exposures. These beneficial effects are attributed to multiple mechanisms that collectively act to strengthen the integrity of the epithelial barrier, and include the stimulation of cell proliferation, migration, differentiation, survival, DNA repair, and induction of enzymes involved in the detoxification of reactive oxygen species. KGF is currently being evaluated in clinical trials to test its ability to ameliorate severe oral mucositis (OM) that results from cancer chemoradiotherapy. In a phase 3 trial involving patients who were treated with myeloablative chemoradiotherapy before autologous peripheral blood progenitor cell transplantation for hematologic malignancies, KGF significantly reduced both the incidence and duration of severe OM. Similar investigations are underway in patients being treated for solid tumors. On the basis of its success in ameliorating chemoradiotherapy-induced OM in humans and tissue damage in a variety of animal models, additional clinical applications of KGF are worthy of investigation. (C) 2004 Elsevier Inc. C1 NCI, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. NR 333 TC 127 Z9 138 U1 1 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 2004 VL 91 BP 69 EP + DI 10.1016/S0065-230X(04)91003-2 PG 71 WC Oncology SC Oncology GA BBI57 UT WOS:000225618000003 PM 15327889 ER PT J AU Bulavin, DV Fornace, AJ AF Bulavin, DV Fornace, AJ TI p38 MAP kinase's emerging role as a tumor suppressor SO ADVANCES IN CANCER RESEARCH, VOL 92 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID ACTIVATED PROTEIN-KINASE; CELL-CYCLE ARREST; NF-KAPPA-B; NEGATIVE FEEDBACK-REGULATION; PROLYL ISOMERASE PIN1; DNA-DAMAGE; TRANSCRIPTIONAL REPRESSOR; HUMAN P53; POSTTRANSLATIONAL MODIFICATIONS; P16(INK4A) EXPRESSION AB The p38 proteins are an evolutionally conserved family of mitogen-activated protein kinases (MAPK). Recent studies have led to progress in our understanding the roles of p38 MAPK in regulation of tumorigenesis through key cellular growth-control mechanisms. Along with the previously well-characterized proapoptotic functions, new data highlight the critical contributions of p38 MAPK in the negative regulation of cell cycle progression. This review will focus on the ability of p38 MAPK to positively regulate several tumor suppressor (p53- and Rb-dependent) pathways and to attenuate oncogenic (Cdc25A and Cdc25B phosphatases) signals. The concept of p38 MAPK as a potential tumor suppressor will be developed. (c) 2004 Elsevier Inc. C1 Inst Cellular & Mol Biol, Singapore 138673, Singapore. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bulavin, DV (reprint author), Inst Cellular & Mol Biol, Singapore 138673, Singapore. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 111 TC 158 Z9 165 U1 1 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 2004 VL 92 BP 95 EP 118 DI 10.1016/S0065-230X(04)92005-2 PG 24 WC Oncology SC Oncology GA BBT48 UT WOS:000227700500005 PM 15530558 ER PT S AU Shears, SB Yang, L Qian, X AF Shears, SB Yang, L Qian, X BE Weber, G TI Cell signaling by a physiologically reversible inositol phosphate kinase/phosphatase SO ADVANCES IN ENZYME REGULATION, VOL 44 SE ADVANCES IN ENZYME REGULATION LA English DT Article; Proceedings Paper CT 44th International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY SEP 22-23, 2003 CL Indiana Univ Sch Med, Indianapolis, IN HO Indiana Univ Sch Med ID ACTIVATED CHLORIDE CHANNELS; DEPENDENT PROTEIN-KINASE; MAMMARY-TUMOR CELLS; 1,3,4-TRISPHOSPHATE 5/6-KINASE; COP9 SIGNALOSOME; CL-CHANNELS; MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; 1,3,4,6-TETRAKISPHOSPHATE 5-KINASE; ACINAR-CELLS; RAT-LIVER C1 NIEHS, Lab Signal Transduct, Inositol Signaling Sect, NIH,DHSS, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), NIEHS, Lab Signal Transduct, Inositol Signaling Sect, NIH,DHSS, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov NR 56 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0065-2571 BN 0-08-044414-8 J9 ADV ENZYME REGUL PY 2004 VL 44 BP 265 EP 277 DI 10.1016/j.advenzreg.2004.02.002 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BBQ25 UT WOS:000227039000018 PM 15581495 ER PT S AU Hood, BL Veenstra, TD Conrads, TP AF Hood, BL Veenstra, TD Conrads, TP BE Daya, S Harrison, RF Kempers, RD TI Mass spectrometry-based proteomics SO ADVANCES IN FERTILITY AND REPRODUCTIVE MEDICINE SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 18th World Congress on Fertility and Sterility CY MAY 23-28, 2004 CL Montreal, CANADA SP Canadian Fertil & Androl Soc, Int Federat Fertils Soc DE proteomics; mass spectrometry; multidimensional separation; 2D PAGE; ICAT ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; CODED AFFINITY TAGS; QUANTITATIVE-ANALYSIS; TECHNOLOGY AB Advances in genomic analysis, including improvements in DNA sequencing, bioinformatics and the routine application of microarray technology to characterize gene expression profiles, have set the stage for understanding how genes are organized and regulated. However, the genetic blueprint cannot accurately predict which proteins are expressed, where they are localized in a cell, and in what quantity and form they are present. Proteomics is a field of study that addresses these important and varied issues. Rapid innovations in core technologies such as separations and mass spectrometry (MS) required to characterize proteins on a global scale are poised to bring about a comprehensive understanding of how changes in protein expression and function affect complex signaling and regulatory networks. These advances have significant implications for understanding how the myriad activities carried out in a cell are regulated in health and disease. This review discusses basic proteomics advances including specific examples that utilize such methodologies as two-dimensional polyacrylamide gel electrophoresis (2D PAGE), solution-based "shotgun" proteomics utilizing multidimensional separations of complex mixtures and the use of stable-isotope labeling for conducting global protein abundance profiles. (C) 2004 Published by Elsevier B.V. C1 SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, Mass Spectrometry Ctr, Frederick, MD 21702 USA. RP Conrads, TP (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, Mass Spectrometry Ctr, POB B, Frederick, MD 21702 USA. NR 16 TC 2 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51545-3 J9 INT CONGR SER PY 2004 VL 1266 BP 375 EP 380 DI 10.1016/j.ics.2004.02.087 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA BAP70 UT WOS:000223166200050 ER PT J AU Singer, A Bosselut, R AF Singer, A Bosselut, R TI CD4/CD8 coreceptors in thymocyte development, selection, and lineage commitment: Analysis of the CD4/CD8 lineage decision SO ADVANCES IN IMMUNOLOGY, VOL 83 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID T-CELL-RECEPTOR; PROTEIN-TYROSINE KINASE; IMMATURE CD4+CD8+ THYMOCYTES; MHC CLASS-II; AMINO-TERMINAL DOMAIN; TCR-ALPHA PROTEINS; MICE LACKING CD4; NF-KAPPA-B; POSITIVE SELECTION; ANTIGEN RECEPTOR C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 181 TC 68 Z9 70 U1 2 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2004 VL 83 BP 91 EP 131 PG 41 WC Immunology SC Immunology GA BAK35 UT WOS:000222633600003 PM 15135629 ER PT J AU Henkart, PA Catalfamo, M AF Henkart, PA Catalfamo, M TI CD8(+) effector cells SO ADVANCES IN IMMUNOLOGY, VOL 83 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; NATURAL-KILLER-CELLS; GRANULE-MEDIATED APOPTOSIS; ASSEMBLY PROTEIN SET; GRANZYME-B; TARGET-CELLS; IN-VIVO; CASPASE ACTIVATION; FAS LIGAND; FUNCTIONAL DIFFERENCES C1 NIH, Bethesda, MD 20892 USA. RP Henkart, PA (reprint author), NIH, Bethesda, MD 20892 USA. NR 86 TC 12 Z9 12 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2004 VL 83 BP 233 EP 252 PG 20 WC Immunology SC Immunology GA BAK35 UT WOS:000222633600007 PM 15135633 ER PT S AU Kopp, JJ Terrio, D AF Kopp, James J. Terrio, Dan BE Garten, ED TI INFORMATION PRIORITIES: REVISING OUR "WORLD-VIEW" OF SERVICE SO ADVANCES IN LIBRARY ADMINISTRATION AND ORGANIZATION, VOL 21 SE Advances in Library Administration and Organization LA English DT Article; Book Chapter C1 [Kopp, James J.] Lewis & Clark Coll, Aubrey R Watzek Lib, Portland, OR 97219 USA. [Kopp, James J.] Univ Portland, Portland, OR 97203 USA. [Kopp, James J.] Washington State Univ, Pullman, WA 99164 USA. [Kopp, James J.] Columbia Univ, New York, NY 10027 USA. [Kopp, James J.] Natl Lib Med, Bethesda, MD 20894 USA. [Terrio, Dan] Lewis Clark State Coll, Lewiston, ID USA. [Terrio, Dan] Miami Univ, Richard T Farmer Sch Business, Oxford, OH 45056 USA. [Terrio, Dan] Augsburg Coll, Acad Comp, Minneapolis, MN USA. RP Kopp, JJ (reprint author), Lewis & Clark Coll, Aubrey R Watzek Lib, Portland, OR 97219 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU EMERALD GROUP PUBLISHING LIMITED PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY, W YORKSHIRE BD16 1WA, ENGLAND SN 0732-0671 BN 978-0-7623-1121-7 J9 ADV LIBR ADM ORGAN PY 2004 VL 21 BP 193 EP 199 DI 10.1016/S0732-0671(04)21010-0 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA BLR35 UT WOS:000270857400010 ER PT J AU Hostetter, TH AF Hostetter, TH TI Research opportunities for reducing racial disparities in kidney disease SO ADVANCES IN RENAL REPLACEMENT THERAPY LA English DT Article DE chronic kidney disease; research; race; ethnicity; health services ID CONVERTING ENZYME-INHIBITORS; PLASMA-RENIN ACTIVITY; RENAL-DISEASE; DIABETIC NEPHROPATHY; INSURED POPULATION; AFRICAN-AMERICAN; BLOOD-PRESSURE; UNITED-STATES; BIRTH-WEIGHT; ANGIOTENSIN AB Several minority populations in the United States have higher risks for end-stage renal disease than does the white population. This article addresses some areas for research aimed at reducing the disproportionate risks. Four general areas are considered: health services, risk factors and causative agents, clinical trials, and awareness campaigns. (C) 2004 by the National Kidney Foundation, Inc. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hostetter, TH (reprint author), NIDDKD, NIH, 6707 Democracy Blvd,Room 625, Bethesda, MD 20892 USA. EM hostettert@extra.niddk.nih.gov NR 48 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1073-4449 J9 ADV RENAL REPLACE TH JI Adv. Renal Replace. Ther. PD JAN PY 2004 VL 11 IS 1 BP 59 EP 65 DI 10.1053/j.arrt.2003.10.009 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 770AF UT WOS:000188700100008 PM 14730539 ER PT J AU Mattson, MP AF Mattson, MP TI Infectious agents and age-related neurodegenerative disorders SO AGEING RESEARCH REVIEWS LA English DT Review DE neurodegenerative disorder; blood-brain barrier; Chlamydia pneumoniae ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROSTATE APOPTOSIS RESPONSE-4; ISCHEMIC BRAIN-INJURY; PERTURBED CALCIUM HOMEOSTASIS; AMYLOID PRECURSOR PROTEIN; SIMPLEX-VIRUS TYPE-1; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CHLAMYDIA-PNEUMONIAE; OXIDATIVE STRESS AB As with other organ systems, the vulnerability of the nervous system to infectious agents increases with aging. Several different infectious agents can cause neurodegenerative conditions, with prominent examples being human immunodeficiency virus (HIV-1) dementia and prion disorders. Such infections of the central nervous system (CNS) typically have a relatively long incubation period and a chronic progressive course, and are therefore increasing in frequency as more people live longer. Infectious agents may enter the central nervous system in infected migratory macrophages, by transcytosis across blood-brain barrier cells or by intraneuronal transfer from peripheral nerves. Synapses and lipid rafts are important sites at which infectious agents may enter neurons and/or exert their cytotoxic effects. Recent findings suggest the possibility that infectious agents may increase the risk of common age-related neurodegenerative disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and stroke. While scenarios can be envisioned whereby viruses such as Chlamydia pneumoniae, herpes simplex and influenza promote damage to neurons during aging, there is no conclusive evidence for a major role of these pathogens in neurodegenerative disorders. In the case of stroke, blood vessels may be adversely affected by bacteria or viruses resulting in atherosclerosis. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Div Neurosci, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Johns Hopkins Univ, Sch Med, Div Neurosci, 725 N Wolfe St, Baltimore, MD 21205 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 101 TC 43 Z9 45 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD JAN PY 2004 VL 3 IS 1 BP 105 EP 120 DI 10.1016/j.arr.2003.08.005 PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 802LV UT WOS:000220165900007 PM 15163105 ER PT J AU Stoff, DM AF Stoff, DM TI Mental health research in HIV/AIDS and aging: problems and prospects SO AIDS LA English DT Article; Proceedings Paper CT Workshop on Mental Health Research Issues in HIV Infection and Aging CY APR, 2002 CL WASHINGTON, DC SP Natl Inst Mental Hlth C1 NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. RP Stoff, DM (reprint author), NIMH, Ctr Mental Hlth Res AIDS, 6001 EXecut Blvd,Room 6210, Bethesda, MD 20892 USA. NR 17 TC 22 Z9 23 U1 2 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 JAN PY 2004 VL 18 SU 1 BP S3 EP S10 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 805OL UT WOS:000220375500002 PM 15075492 ER PT J AU Stoff, DM Khalsa, JH Monjan, A Portegies, P AF Stoff, DM Khalsa, JH Monjan, A Portegies, P TI HIV/AIDS and aging - Introduction SO AIDS LA English DT Editorial Material C1 NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NIDA, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. OLVG Hosp, Dept Neurol, Amsterdam, Netherlands. RP Stoff, DM (reprint author), NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NR 2 TC 32 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN PY 2004 VL 18 SU 1 BP S1 EP S2 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 805OL UT WOS:000220375500001 PM 15075491 ER PT J AU Stoff, DM Mitnick, L Kalichman, S AF Stoff, DM Mitnick, L Kalichman, S TI Research issues in the multiple diagnoses of HIV/AIDS, mental illness and substance abuse SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Editorial Material ID UNITED-STATES; INFECTED ADULTS; HIV; DISORDERS; SERVICES; HEALTH C1 NIMH, Div AIDS & Hlth & Behav Res, Bethesda, MD USA. Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. RP Stoff, DM (reprint author), NIH, Ctr Mental Hlth Res AIDS, Neuropsychiat HIV AIDS Program, 6001 Execut Blvd,Room 6210,MSC 9619, Bethesda, MD 20892 USA. EM dstoff@nih.gov NR 11 TC 17 Z9 17 U1 1 U2 2 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids/Hiv PY 2004 VL 16 SU 1 BP S1 EP S5 DI 10.1080/09540120412331315321 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 879QR UT WOS:000225732800001 PM 15739265 ER PT J AU Tsai, CC Emau, P Jiang, YH Agy, MB Shattock, RJ Schmidt, A Morton, WR Gustafson, KR Boyd, MR AF Tsai, CC Emau, P Jiang, YH Agy, MB Shattock, RJ Schmidt, A Morton, WR Gustafson, KR Boyd, MR TI Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RHESUS-MONKEYS; INACTIVATING PROTEIN; HIV TRANSMISSION; VIRAL LOAD; MACAQUES; VACCINES; DISEASE; PLASMA; TARGET AB The cyanobacterial protein cyanovirin-N (CV-N) potently inactivates diverse strains of HIV-1 and other lentiviruses due to irreversible binding of CV-N to the viral envelope glycoprotein gp120. In this study, we show that recombinant CV-N effectively blocks HIV-1(Ba-L) infection of human ectocervical explants. Furthermore, we demonstrate the in vivo efficacy of CV-N gel in a vaginal challenge model by exposing CV-N-treated female macaques ( Macaca fascicularis) to a pathogenic chimeric SIV/HIV-1 virus, SHIV89.6P. All of the placebo-treated and untreated control macaques ( 8 of 8) became infected. In contrast, 15 of 18 CV-N-treated macaques showed no evidence of SHIV infection. Further, CV-N produced no cytotoxic or clinical adverse effects in either the in vitro or in vivo model systems. Together these studies suggest that CV-N is a good candidate for testing in humans as an anti-HIV topical microbicide. C1 Univ Washington, Natl Primate Res Ctr, Seattle, WA 98195 USA. St George Hosp, Sch Med, Dept Infect Dis, London SW17 0RE, England. NCI, Mol Targets Dev Program, Ctr Canc Res, NIH, Frederick, MD USA. Univ S Alabama, Coll Med, USA Canc Res Inst, Mobile, AL 36688 USA. RP Tsai, CC (reprint author), Univ Washington, Natl Primate Res Ctr, Box 357330,1705 NE Pacific St, Seattle, WA 98195 USA. EM cctsai@bart.rprc.washington.edu FU NCRR NIH HHS [RR-00166]; NIAID NIH HHS [AI-15450, AI-51650, AI-65311] NR 30 TC 151 Z9 161 U1 0 U2 9 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2004 VL 20 IS 1 BP 11 EP 18 DI 10.1089/088922204322749459 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 772VD UT WOS:000188861700002 PM 15000694 ER PT J AU Touloumi, G Pantazis, N Karafoulidou, A Mandalaki, T Goedert, JJ Kostrikis, LG Hatzakis, A AF Touloumi, G Pantazis, N Karafoulidou, A Mandalaki, T Goedert, JJ Kostrikis, LG Hatzakis, A TI Changes in T cell receptor excision DNA circle (TREC) levels in HIV type 1-infected subjects pre- and post-highly active antiretroviral therapy SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECENT THYMIC EMIGRANTS; VIROLOGICAL TREATMENT FAILURE; IMMUNE RECONSTITUTION; HIV-1-INFECTED CHILDREN; INFECTED PATIENTS; IN-VIVO; AGE; OUTPUT; TRANSPLANTATION AB The T cell receptor excision DNA circle (TREC) level is an independent predictor of HIV-1 disease prognosis. We studied the temporal changes in TREC levels prior to and after highly active antiretroviral therapy ( HAART) in a cohort of 131 Greek men with hemophilia who were followed up for up to 20 years since seroconversion (SC). TREC levels were determined in all available cryopreserved samples of peripheral blood mononuclear cells ( PBMCs) using a multiplex real-time polymerase chain reaction (PCR) assay. Trends in log(10) TREC values were described using random effects models. Prior to HAART initiation TREC levels tended to decrease over time ( mean rate of drop 19% per year; 95% CI: 16 - 22%). Initial TREC values were higher with younger age at SC, but the subsequent rate of drop did not differ significantly by age at SC. There was a monotonic relationship between baseline HIV-RNA levels and TREC slopes with steeper slopes at higher levels of HIV-RNA. The TREC slopes differed significantly by clinical outcome being steeper in subjects who progressed to AIDS sooner. After HAART initiation, TREC values tended to increase on average by 35% per year ( 95% CI: 27 - 94%) but the increase was evident only in subjects with a pre-HAART CD4 count below 80 cells/mul. TREC values, which likely represent a simple indicator of naive T-lymphocyte reserve, may be a clinically useful marker for long-term prognosis of HIV-1 infection and for immune reconstitution after successful HAART. C1 Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens 11527, Greece. Laikon Gen Hosp, Hemophilia Ctr, Athens, Greece. Natl Canc Inst, Viral Epidemiol Branch, Rockville, MD 20857 USA. RP Hatzakis, A (reprint author), Univ Athens, Sch Med, Dept Hyg & Epidemiol, 75 Mikras Asias St, Athens 11527, Greece. EM ahatzak@cc.uoa.gr RI Kostrikis, Leondios/A-5330-2016 OI Kostrikis, Leondios/0000-0002-5340-7109 FU NCI NIH HHS [N01-CP-33002] NR 35 TC 10 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2004 VL 20 IS 1 BP 47 EP 54 DI 10.1089/088922204322749495 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 772VD UT WOS:000188861700006 PM 15000698 ER PT J AU Gerschenson, M Nguyen, V Ewings, EL Ceresa, A Shaw, JA St Claire, MC Nagashima, K Harbaugh, SW Harbaugh, JW Olivero, OA Divi, RL Albert, PS Poirier, MC AF Gerschenson, M Nguyen, V Ewings, EL Ceresa, A Shaw, JA St Claire, MC Nagashima, K Harbaugh, SW Harbaugh, JW Olivero, OA Divi, RL Albert, PS Poirier, MC TI Mitochondrial toxicity in fetal Erythrocebus patas monkeys exposed transplacentally to zidovudine plus lamivudine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-POLYMERASE-GAMMA; REVERSE-TRANSCRIPTASE; SKELETAL-MUSCLE; INTRACELLULAR PHOSPHORYLATION; ANTIRETROVIRAL THERAPY; NUCLEOSIDE ANALOGS; INFECTED PATIENTS; PREGNANT-WOMEN; TRANSMISSION AB This study was designed to investigate fetal mitochondrial toxicity in Erythrocebus patas monkeys exposed in utero to zidovudine (AZT) and lamivudine (3TC), and taken at term. Pregnant patas monkeys were given a daily dose of 40 mg AZT (86% of the human daily dose, based on body weight), for the last 10 weeks (50%) of gestation, and a daily dose of 24 mg 3TC (84% of the human daily dose, based on body weight) for the last 4 weeks of gestation. At term, AZT was found to be incorporated into fetal mitochondrial DNA from skeletal muscle, liver, kidney, and placenta. By transmission electron microscopy ( EM) drug-exposed fetal cardiac and skeletal muscle cells showed mitochondrial membrane compromise, mitochondrial proliferation, and damaged sarcomeres, while mitochondria in brain cerebrum and cerebellum were morphologically normal. Substantial depletion of oxidative phosphorylation (OXPHOS) Complex I specific activities was observed in heart (87% reduction in mean, p = 0.02) and skeletal muscle (98% reduction in mean, p = 0.002) from drug-exposed fetuses, compared to unexposed fetuses. In addition Complex IV activity was highly depleted (85% reduction in mean, p = 0.004) in skeletal muscle from the drug-exposed fetuses ( p 5 0.004). Brain cerebrum and cerebellum showed no statistically significant OXPHOS changes with drug exposure. Mitochondrial DNA quantity was substantially depleted (>50%) in heart, skeletal muscle, cerebellum, and cerebrum from drug-exposed fetuses compared to unexposed controls. Overall, the data indicate that significant mitochondrial damage was observed at birth in monkey fetuses exposed in utero to AZT plus 3TC in a human-equivalent dosing protocol. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. NCI, Image Anal Lab, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Poirier, MC (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bldg 37,Rm 4032,37 Covent Dr,MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov NR 49 TC 49 Z9 50 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2004 VL 20 IS 1 BP 91 EP 100 DI 10.1089/088922204322749530 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 772VD UT WOS:000188861700010 PM 15000702 ER PT J AU Hirsch, VM AF Hirsch, VM TI What can natural infection of African monkeys with simian immunodeficiency virus tell us about the pathogenesis of AIDS? SO AIDS REVIEWS LA English DT Review DE SIV; pathogenesis; animal models; long-term non-progressors ID CROSS-SPECIES TRANSMISSION; T-CELL TURNOVER; GREEN MONKEYS; MANDRILLUS-SPHINX; SOOTY MANGABEYS; SIV INFECTION; NONHUMAN-PRIMATES; TANTALUS MONKEYS; HIGHLY DIVERGENT; IN-VIVO AB The simian immunodeficiency viruses are a diverse group of viruses that naturally infect a wide range of African primates, including chimpanzees, African green monkeys (AGM) and sooty mangabey monkeys (SM). Although natural infection is widespread in feral populations of AGMs and SMs, this infection does not result in immunodeficiency. However, experimental inoculation of Asian macaque species results in an immunodeficiency syndrome that is remarkably similar in pathogenesis to human AIDS. Thus, SIVsm infection of macaques results in AIDS, and similarly experimental inoculation of pigtailed macaques with at least one SIVagm isolate, SIVIhoest or SIVsun, results in AIDS. The extent of plasma viremia in pathogenic infection is an excellent prognostic indicator of clinical course, with higher viral load being predictive of shorter survival and low viremia being predictive of longterm non-progression. Based upon this paradigm, one would have expected naturally infected animals to exhibit low levels of viremia. In reality, AGMs, SMs, mandrills and chimpanzees infected naturally with their own unique viruses display moderate to high levels of plasma viremia. A significant reduction in CD4+ T-cells in infected versus uninfected SMs suggests that the virus may be cytopathic to some degree. These infected animals still maintain adequate CD4+ T-cells over their entire life in captivity. A distinct characteristic of natural infection is the lack of immunopathology as demonstrated by normal lymph node morphology, lower expression of activation and proliferation markers on CD4+ T-cells, and a generally muted immune response to the virus. Naturally infected SMs and AGMs clearly mount antiviral cellular and humoral immune responses. Therefore, models suggesting immune tolerance to SIV are far too simplistic to explain the lack of disease in these animals. It is probable that a unique balance between T-cell renewal and proliferation and loss through activation-induced apoptosis, and virus-induced cell death has been achieved in SMs and AGMs. The study of the dynamics of T-cell production, proliferation and cell death in asymptomatic natural infection should, therefore, yield insights into the pathogenesis of AIDS. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, 12441 Pk Lawn Dr, Rockville, MD 20852 USA. EM vhirsch@nlaid.nih.gov NR 93 TC 62 Z9 63 U1 0 U2 2 PU PERMANYER PUBLICATIONS PI BARCELONA PA MALLORCA, 310, BARCELONA, SPAIN SN 1139-6121 J9 AIDS REV JI Aids Rev. PD JAN-MAR PY 2004 VL 6 IS 1 BP 40 EP 53 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 885MM UT WOS:000226161300006 PM 15168740 ER PT J AU Russo, D Purohit, V Foudin, L Salin, M AF Russo, D Purohit, V Foudin, L Salin, M TI Workshop on alcohol use and health disparities 2002: a call to arms SO ALCOHOL LA English DT Editorial Material DE health disparities; cirrhosis; cardiomyopathy; fetal alcohol spectrum disorders (FASD); esophageal cancer; ethanol ID INDUCED TISSUE-INJURY; BREAST-CANCER; METABOLISM; MORTALITY; RISK AB The National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) sponsored a "Workshop on Alcohol Use and Health Disparities 2002: A Call to Arms," on December 5, 2002, in Bethesda, Maryland, USA. This workshop was part of the NIAAA/NIH comprehensive strategic plan to reduce, and ultimately eliminate, health disparities. Eleven topics were addressed: (1) biomedical risk factors that may contribute to disparities in the toxic effects of alcohol; (2) alcohol and gene-environment interactions that affect the health of diverse groups; (3) alcohol pharmacogenetics in Mexican-Americans; (4) determinants of risk for alcoholism in minority populations; (5) consideration of population groups in linkage-disequilibrium studies to identify genes associated with alcohol dependence: (6) interaction between alcohol dependence and African-American ethnicity in disordered sleep, nocturnal cytokines, and immunity: (7) disparities of brain functional reserve capacity affecting brain morbidity related to substance abuse; (8) alcohol and pregnancy disparities; (9) role of alcohol in cancer risk disparities; (10) ethnic diversity in alcoholic cardiomyopathy; and (11) postmenopausal health disparities. On the basis of these presentations, seven conclusions emerged: (1) Genetic variations in alcohol-metabolizing enzymes exist in various populations. (2) These enzymes play a role in the variation in health effect outcomes seen in different populations, owing to alcohol consumption. (3) Differences between and among population groups can be critically important for the design and interpretation of studies in genetics. These include differences in expression of phenotype, in locus heterogeneity, in risk alleles, and in population structure. (4) Incidence rates for fetal alcohol syndrome and fetal alcohol spectrum disorders are greater in African-Americans and Native-Americans than in Caucasians. Genetic polymorphisms, nutrition, and other factors may account for these differences. (5) The highest mortality rate for cirrhosis has been found in white Hispanic men. (6) Mexican-Americans have a low frequency of the protective alleles ADH1B*2 and ALDH2*2 and a relatively high frequency of CYP2E1 c2, which is associated with early onset alcoholism. (7) The incidence rate for cancer is greater for African-Americans than for Caucasians, and part of the higher risk may be attributed to heavier drinking. (C) 2004 Elsevier Inc. All rights reserved. C1 NIAAA, Biomed Res Branch, Div Basic Res, NIH, Bethesda, MD 20892 USA. RP Russo, D (reprint author), NIAAA, Biomed Res Branch, Div Basic Res, NIH, 6000 Execut Blvd,Suite 402, Bethesda, MD 20892 USA. EM drusso@mail.nih.gov NR 14 TC 41 Z9 41 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD JAN PY 2004 VL 32 IS 1 BP 37 EP 43 DI 10.1016/j.alcohol.2004.01.003 PG 7 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 814DO UT WOS:000220955600005 PM 15066702 ER PT J AU Verlaan, M Te Morsche, RHM Roelofs, HMJ Laheij, RJF Jansen, JBMJ Peters, WHM Drenth, JPH AF Verlaan, M Te Morsche, RHM Roelofs, HMJ Laheij, RJF Jansen, JBMJ Peters, WHM Drenth, JPH TI Genetic polymorphisms in alcohol-metabolizing enzymes and chronic pancreatitis SO ALCOHOL AND ALCOHOLISM LA English DT Article ID SERINE-PROTEASE INHIBITOR; RSAI POLYMORPHISM; KAZAL TYPE-1; CYP2E1 GENE; HUMAN-LIVER; SUSCEPTIBILITY; PREDISPOSITION; MUTATIONS; GENOTYPES; CIRRHOSIS AB Aims: Alcohol misuse is now regarded as an important risk factor for development of chronic pancreatitis (CP). However, not every alcohol misuser develops CP and it therefore might be suggested that susceptibility could be further influenced by inter-individual variations in the activities of alcohol-metabolizing enzymes. Several genetic polymorphisms that may affect the activities of alcohol-metabolizing enzymes have been described. Therefore we determined whether polymorphisms in the genes for alcohol dehydrogenase 3 (ADH3) or cytochrome P450 2E1 (CYP2E1) predispose to the development of CP. Methods: DNA samples were obtained from 142 adult CP patients with hereditary (n = 21), alcoholic (n = 82) or idiopathic (n = 39) CP. DNA from 128 healthy controls and from 93 alcoholic controls was analysed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in ADH3 and CYP2E1 were determined by PCR, followed by restriction-fragment-length-polymorphism analyses in all subjects. Results: The frequencies of ADH3 and CYP2E1 c1c2 genotypes did not differ between CP patients and alcoholic and healthy controls. However, a trend for a higher frequency of the CYP2E1 intron 6 D allele was demonstrated in patients with alcohol-induced CP, compared to that of healthy controls (OR = 3.03, 95%CI = 1.0-9.1) or alcoholic controls (OR = 2.76, 95%CI = 0.9-8.7). Conclusions: These data suggest that the presence of the CYP2E1 intron 6 DD genotype might confer a higher risk of alcoholic CP. C1 Univ Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Verlaan, M (reprint author), Univ Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM m.verlaan@mdl.umcn.nl RI Drenth, J.P.H./H-8025-2014; Peters, W.H.M./L-4572-2015; te Morsche, Rene/P-9143-2015 NR 26 TC 29 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JAN-FEB PY 2004 VL 39 IS 1 BP 20 EP 24 DI 10.1093/alcalc/agh001 PG 5 WC Substance Abuse SC Substance Abuse GA 762MA UT WOS:000187975000004 PM 14691069 ER PT J AU Zhu, W Volkow, ND Ma, YM Fowler, JS Wang, GJ AF Zhu, W Volkow, ND Ma, YM Fowler, JS Wang, GJ TI Relationship between ethanol-induced changes in brain regional metabolism and its motor, behavioural and cognitive effects SO ALCOHOL AND ALCOHOLISM LA English DT Article ID CEREBRAL-BLOOD-FLOW; ACUTE ALCOHOL-INTOXICATION; ADENOSINERGIC MODULATION; CANONICAL CORRELATION; PERFORMANCE; RATS; INCOORDINATION; AGGRESSION; FRAMEWORK; EMOTION AB Aims and Methods: Acute alcohol administration induces marked decreases in glucose metabolism throughout the human brain. However, the relationship between alcohol's effects on brain metabolism and the behavioural changes that occur with intoxication are still unclear. Here we assessed this association using principal component analysis for dimension reduction and canonical correlations to gauge inter-class relationships. We also used canonical correlations in the polynomial space to assess for possible nonlinear relationships. Results: After normalizing the regional measures to account for the large whole brain decreases observed with intoxication we show that the largest decreases occurred in occipital cortex and that there were relative increases in basal ganglia. Principal component analysis of the changes in the normalized measures revealed that 60% of the variance was accounted for by two factors; one that contrasted cerebellum versus frontal and anterior cingulate metabolism, and another that contrasted basal ganglia and insula. The square of the first factor was significantly correlated with the deterioration in cognitive performance. The second factor showed a significant linear correlation with self-reports of intoxication and with deterioration in cognitive and motor performance. Conclusions: These findings suggest that the contrasting effects of alcohol in basal ganglia versus the insula are involved in the perception of 'feeling drunk' and that its contrasting effects in cerebellum versus those in frontal and parietal cortices are involved in its motor incoordinating effects. On the other hand alcohol's impact on cognitive performance implicates a more complex pattern of brain effects that includes linear as well as non-linear associations. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. NIDA, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. RP Zhu, W (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. EM zhu@ams.sunysb.edu FU NIAAA NIH HHS [AA 09481] NR 34 TC 27 Z9 28 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JAN-FEB PY 2004 VL 39 IS 1 BP 53 EP 58 DI 10.1093/alcalc/agh023 PG 6 WC Substance Abuse SC Substance Abuse GA 762MA UT WOS:000187975000010 PM 14691075 ER PT J AU Peterson, K AF Peterson, K TI Biomarkers for alcohol use and abuse - A summary SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE screening and diagnostic method for AOD (alcohol and other drug) use; pattern of AOD use; alcohol-related biological markers; alcohol-related biochemical makers; alcohol-related genetic markers ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; ACID ETHYL-ESTERS; ETHANOL INTAKE; MASS SPECTROMETRY; MARKERS; TEETOTALERS; GLUCURONIDE; METABOLITE; DOPAMINE; DRINKING AB Clinicians can use several biochemical measurements to objectively assess patients' current or past alcohol use. However, none of these currently available biomarkers-including measures of various liver enzymes and blood volume are ideal. Several more experimental markers hold promise for measuring acute alcohol consumption and relapse. These include certain alcohol byproducts, such as acetaldehyde, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEE), as well as two measures of sialic acid, a carbohydrate that appears to be altered in alcoholics. Some progress has been made in finding markers that predict people's genetic predisposition to alcoholism, such as genetic differences in several neurotransmitters, including beta-endorphin and gamma-aminobutryic acid (GABA). C1 NIAAA, Res Policy & Special Programs Branch, Off Sci Affairs, Bethesda, MD USA. RP Peterson, K (reprint author), NIAAA, Res Policy & Special Programs Branch, Off Sci Affairs, Bethesda, MD USA. RI Peterson, Karen/E-8084-2015 OI Peterson, Karen/0000-0001-6737-8698 NR 30 TC 37 Z9 38 U1 0 U2 3 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2004 VL 28 IS 1 BP 30 EP 37 PG 8 WC Substance Abuse SC Substance Abuse GA 988MY UT WOS:000233606500004 PM 19006989 ER PT J AU Chezem, JDL AF Chezem, JDL TI Legal barriers to alcohol screening in emergency departments and trauma centers SO ALCOHOL RESEARCH & HEALTH LA English DT Article C1 NIAAA, Bethesda, MD USA. Purdue Univ, Sch Agr, Dept Youth Dev & Agr Educ, W Lafayette, IN 47907 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. RP Chezem, JDL (reprint author), NIAAA, Bethesda, MD USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2004 VL 28 IS 2 BP 73 EP 77 PG 5 WC Substance Abuse SC Substance Abuse GA 988NA UT WOS:000233606700003 ER PT J AU Chen, CM Dufour, MC Yi, HY AF Chen, CM Dufour, MC Yi, HY TI Alcohol consumption among young adults ages 18-24 in the United States: Results from the 2001-2002 NESARC SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE young adult; undergraduate student; underage drinking; National Epidemiologic Survey on Alcohol and Related Conditions (NESARC); heavy drinking; binge drinking; AOD (alcohol and other drug) use pattern; AOD use frequency; amount of AOD Use; AOD intake per occasion; AOD use frequency; individual AOD consumption; aggregate AOD consumption; gender differences; ethnic differences; racial differences ID BINGE DRINKING; DEPENDENCE; ONSET; ABUSE AB The high prevalence of drinking in young adults is a serious public health concern. Alcohol use among young adults often is associated with a wide variety of risky behaviors and both immediate and long-term negative consequences. The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) presents a unique opportunity to examine young adult drinking because it has an excellent response rate, oversamples young adults ages 18-24, and includes college-related group housing. According to the NESARC data, in 2001-2002 over three-quarters of young adults ages 21-24 were current drinkers, as were nearly two-thirds of those ages 18-20, despite the fact that the legal drinking age is 21. More than half of young adult men exceeded the recommended daily drinking limit, as did two-fifths of young adult women. Although the prevalence of exceeding the daily limit is higher for those ages 21-24 than for those ages 18-20, it also is substantial for those ages 18-20. Because drinking more than the recommended per-occasion maximum is likely to impair mental and physical performance, the increase over the past decade in the prevalence among young adults of drinking five or more drinks 12 or more times per year may help explain the increased risk of injury and other acute negative consequences commonly observed among college students ages 18-24. C1 NIAAA, CSR Inc, Arlington, VA USA. RP Chen, CM (reprint author), NIAAA, CSR Inc, Arlington, VA USA. NR 18 TC 75 Z9 75 U1 3 U2 12 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2004 VL 28 IS 4 BP 269 EP 280 PG 12 WC Substance Abuse SC Substance Abuse GA 004BX UT WOS:000234728100014 ER PT J AU Neumark, YD Friedlander, Y Durst, R Leitersdorf, E Jaffe, D Ramchandani, VA O'Connor, S Carr, LG Li, TK AF Neumark, YD Friedlander, Y Durst, R Leitersdorf, E Jaffe, D Ramchandani, VA O'Connor, S Carr, LG Li, TK TI Alcohol dehydrogenase Polymorphisms influence alcohol-elimination rates in a male Jewish population SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; elimination; ADH; genetics; Jews ID ADH2-ASTERISK-2 ALLELE; GENETIC-POLYMORPHISM; RISK; MEN; DEPENDENCE; METABOLISM; VALIDATION; RESPONSES; GENOTYPES; EUROPEANS AB Background: Genetic variation in the alcohol dehydrogenase (ADH) enzyme is associated with an aversion to alcohol and a lower risk of alcoholism among Asians. There is growing evidence of a functional role of the ADH2*2 allele in alcohol-drinking patterns among Jews, who have traditionally exhibited low rates of alcoholism and alcohol-related problems. The mechanism by which this allelic effect is mediated is not yet clearly understood. This study examined the effect of ADH2*2 on alcohol-elimination rates (AER) under experimental conditions. Methods: Young adult male Jews (N = 109) received an intravenous alcohol infusion; metabolism was measured by using standard breath alcohol concentration tests. A clamping technique was used to achieve and maintain a target breath alcohol concentration of 50 mg/100 ml for a defined time period. The AER at steady state was calculated. The alcohol disappearance rate was also calculated from the descending limb slope. Polymerase chain reaction was used for allelic determination of the ADH2 and ADH3 loci. Results: The mean AER among ADH2*2 carriers was significantly higher (8.09 +/- 1.4 g/hr) than among ADH2*1 homozygotes (7.14 +/- 1.5 g/hr; p = 0.003). Significance was retained on adjustment for potential confounding covariates. The ADH2 allele explains 8.5% of the AER variance in this population. Little AER difference was observed across ADH3 genotype groups. The slope of the descending limb increased with increasing copies of the ADH2*2 allele. Conclusions: The rate of alcohol elimination is significantly associated with the ADH2 genotype of Jewish males. Evidence for variation in alcohol metabolism across ADH genotypic groups provides support for the role of physiologic protective factors in alcohol drinking and suggests that reduced drinking among Jews may be genetically as well as environmentally determined. We believe that application of the novel "Indiana clamp" enhances AER measurement accuracy, allowing for detection of hitherto undetectable differences. C1 Hebrew Univ Jerusalem Hadassah, Braun Sch Publ Hlth & Community Med, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Ctr Res Prevent & Treatment Atherosclerosis, IL-91120 Jerusalem, Israel. NIAAA, Bethesda, MD USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Neumark, YD (reprint author), Hebrew Univ Jerusalem Hadassah, Braun Sch Publ Hlth & Community Med, POB 12272, IL-91120 Jerusalem, Israel. EM yneumark@md2.huji.ac.il FU NIAAA NIH HHS [P50 AA07611, R37 AA02342] NR 23 TC 102 Z9 106 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2004 VL 28 IS 1 BP 10 EP 14 DI 10.1097/01.ALC.0000108667.79219.4D PG 5 WC Substance Abuse SC Substance Abuse GA 768XN UT WOS:000188596400003 PM 14745297 ER PT J AU Grune, B Fallon, M Howard, C Hudson, V Kulpa-Eddy, JA Larson, J Leary, S Roi, A van der Valk, J Wood, M Dorendahl, A Kohler-Hahn, D Box, R Spielmann, H AF Grune, B Fallon, M Howard, C Hudson, V Kulpa-Eddy, JA Larson, J Leary, S Roi, A van der Valk, J Wood, M Dorendahl, A Kohler-Hahn, D Box, R Spielmann, H TI Report and recommendations of the workshop "Retrieval approaches for information on alternative methods to animal experiments" SO ALTEX-ALTERNATIVEN ZU TIEREXPERIMENTEN LA English DT Article DE alternative methods; in vitro methods; database; information; publications; searching; retrieval; Internet; index terms; thesaurus; workshop; 3Rs concept; ZEBET; BfR AB In the member states of the EU and in the USA, scientists are obliged by animal welfare legislation not to conduct an animal experiment if another scientifically satisfactory method is reasonably and practicably available. To meet the regulatory obligation to use alternatives to animal experiments, scientists should consult literature and other relevant sources on alternatives prior to any experimental study on laboratory animals. It is the responsibility of the individual scientist to select the most appropriate database to obtain information on alternatives, which have been defined as methods that refine, reduce or replace animal experiments (the 3 Rs concept of Russell and Burch (1959)). Specialised information services provide support to scientists searching for publications on alternative methods. On occasion of a workshop in Berlin in November 2003, representatives of animal welfare information centres discussed currently available information sources on alternative methods, index terms for alternative methods, and search strategies based on index terms for alternative methods. ZEBET presented an investigation on the current status Of indexing systems on alternative methods in established literature databases. The project analysed how the results of a search for publications on alternatives was influenced by the indexing procedure. The results of the study were exemplified by a typical search result. The results of the study indicated that the current indexing systems do not provide the required information, since not all of the relevant information is indexed under "alternative methods". The workshop participants developed recommendations for ad hoc working groups and research projects, e.g. development of suitable search strategies on alternative methods for scientists. C1 BfR, ZEBET, Ctr Document & Evaluat Alternat Methods Anim Expt, D-12277 Berlin, Germany. Vet Affairs Med Ctr, Dept Vet Affairs, Atlanta, GA 30033 USA. Emory Univ, Decatur & Dept Lab Med, Atlanta, GA 30322 USA. John Hopkins Ctr Alternat Anim Testing, Baltimore, MD USA. Natl Lib Med, Specialized Informat Serv Div, Bethesda, MD USA. USDA, APHIS, Riverdale, MD USA. USDA, Anim Welfare Informat Ctr, Beltsville, MD 20705 USA. Alternat Res & Dev Fdn, Jenkintown, PA USA. Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM Sci Informat Serv, I-21020 Ispra, Italy. Univ Utrecht, Fac Vet Med, Dept Anim Sci & Soc, NCA, Utrecht, Netherlands. Univ Calif Davis, Sch Vet Med, Ctr Anim Alternat, Davis, CA 95616 USA. RP Grune, B (reprint author), BfR, ZEBET, Ctr Document & Evaluat Alternat Methods Anim Expt, Diederdorfer Weg 1, D-12277 Berlin, Germany. EM grune.zebet@bfr.bund.de RI van der Valk, Jan/A-8529-2008 NR 22 TC 6 Z9 8 U1 0 U2 1 PU SPEKTRUM AKAD VERLAG PI HEIDELBERG PA SLEVOGTSTRASSE 3-5, D-69126 HEIDELBERG, GERMANY SN 0946-7785 J9 ALTEX-ALTERN TIEREXP JI Altex Altern. Tierexp. PY 2004 VL 21 IS 3 BP 115 EP 127 PG 13 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 858GO UT WOS:000224180500003 PM 15329775 ER PT J AU Hutchings, CB Mann, NC Daya, M Jui, J Goldberg, R Cooper, L Goff, DC Cornell, C AF Hutchings, CB Mann, NC Daya, M Jui, J Goldberg, R Cooper, L Goff, DC Cornell, C CA REACT Study TI Patients with chest pain calling 9-1-1 or self-transporting to reach definitive care: Which mode is quicker? SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; EMERGENCY MEDICAL-SERVICES; CINCINNATI-HEART-PROJECT; RAPID EARLY ACTION; CORONARY TREATMENT; TIME DELAYS; SYSTEM; THROMBOLYSIS; MORTALITY; THERAPY AB Objective We examined differences in transport times for patients with chest pain who used private transportation compared with patients who used emergency medical services (EMS) to reach definitive medical care. Methods This was a retrospective cohort study with data used from the Rapid Early Action for Coronary Treatment (REACT) trial conducted in 20 US cities. Elapsed time to care was examined through the use of (1) decision to seek care to initial care (emergency department [ED] arrival versus EMS arrival on scene [n = 1209]); (2) decision to ED arrival (for both groups [n=2388]); (3) time to thrombolytic therapy once admitted to the ED (for both groups [n=309]); and (4) decision to seek care to thrombolytic therapy (n=276). Elapsed travel times were ranked within Zip Codes and submitted to a nested analysis of variance model to determine if elapsed times were different between modes of transport. Results Private transportation (35 minutes) resulted in faster ED arrival than using EMS (39 minutes, P = .0014). However, if one considers EMS treatment to be initial care, calling 9-1-1 (6 minutes) resulted in much quicker care than patients using private transportation to the ED (32 minutes, P < .001). Transport by EMS resulted in a shorter elapsed time to thrombolytic administration compared with patients using private transportation when considering ED "door-to-needle" time (32 vs 49 minutes, respectively [P < .001]) or time from decision to seek care until administration of thrombolytic therapy (75 vs 92 minutes, respectively, [P = .042]). Conclusions Although private transportation results in a faster trip to the ED, quicker care is obtained with the use of EMS. C1 Univ Utah, Sch Med, Intermt Injury Control Res Ctr, Salt Lake City, UT 84108 USA. Oregon Hlth Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. Univ Massachusetts, Sch Med, Dept Cardiol, Worcester, MA USA. NHLBI, Washington, DC USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Univ Alabama, Sch Med, Birmingham, AL USA. RP Mann, NC (reprint author), Univ Utah, Sch Med, Intermt Injury Control Res Ctr, 615 Arapeen Dr,Suite 202, Salt Lake City, UT 84108 USA. EM clay.mann@hsc.utah.edu FU NHLBI NIH HHS [U01-HL-53412, U01-HL-53135, U01-HL-53141, U01-HL-53149, U01-HL-53155, U01-HL-53211] NR 22 TC 46 Z9 52 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2004 VL 147 IS 1 BP 35 EP 41 DI 10.1016/S0002-8703(03)00510-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 803TQ UT WOS:000220253800006 PM 14691416 ER PT J AU Wei, WQ Abnet, CC Qiao, YL Dawsey, SM Dong, ZW Sun, XD Fan, JH Gunter, EW Taylor, PR Mark, SD AF Wei, WQ Abnet, CC Qiao, YL Dawsey, SM Dong, ZW Sun, XD Fan, JH Gunter, EW Taylor, PR Mark, SD TI Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE selenium; esophageal squamous cell carcinoma; gastric cardia cancer; stroke; heart disease; cohort ID NUTRITION INTERVENTION TRIALS; MYOCARDIAL-INFARCTION; PREVENTION TRIAL; SUPPLEMENTATION; LINXIAN; CHINA; MORTALITY; RISK; MECHANISMS; COHORT AB Background: We previously reported an inverse association between prediagnostic serum selenium concentrations and the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia cancer (GCC) but not gastric noncardia cancer (GNCC) in a nested study from the Nutrition Intervention Trial in Linxian, China. Objective: We examined the relation between baseline serum selenium and the subsequent risk of death from ESCC, GCC, GNCC, heart disease (HD), stroke, and total death over 15 y of follow-up (1986-2001). Design: We measured baseline serum selenium concentrations in 1103 subjects randomly selected from a larger trial cohort. We identified 516 deaths during the 15-y follow up, including 75 from ESCC, 36 from GCC, 146 from HD, and 167 from stroke. Relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards regression models. Reported RRs estimated the change in risk conferred by a 25% increase in serum selenium relative to the population distribution. All estimates were adjusted for sex, age, smoking, drinking, and serum cholesterol. Results: We found significant inverse associations between baseline serum selenium and death from ESCC (RR: 0.83; 95% Cl: 0.71, 0.98) and GCC (0.75; 0.59, 0.95). Trends toward inverse associations were noted for death from HD (0.89; 0.78, 1.01; P = 0.07), but no association was noted for total death (0.96; 0.90, 1.02) or stroke (0.99; 0.88, 1.11). Conclusion: Population-wide selenium supplementation in the region of China with low serum selenium and high incidences of ESCC and GCC merits serious consideration. C1 NCI, Canc Prevent Studies Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, Beijing 100037, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. Ctr Dis Control & Prevent, Natl Hlth & Nutr Examinat Survey Lab, Atlanta, GA USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Abnet, CC (reprint author), NCI, Canc Prevent Studies Branch, Canc Res Ctr, 6116 Execut Blvd,Room 705, Bethesda, MD 20892 USA. RI Qiao, You-Lin/B-4139-2012; OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 33 TC 113 Z9 117 U1 0 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2004 VL 79 IS 1 BP 80 EP 85 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 757NZ UT WOS:000187569500013 PM 14684401 ER PT J AU Brennan, P Lewis, S Hashibe, M Bell, DA Boffetta, P Bouchardy, C Caporaso, N Chen, C Coutelle, C Diehl, SR Hayes, RB Olshan, AF Schwartz, SM Sturgis, EM Wei, QY Zavras, AI Benhamou, S AF Brennan, P Lewis, S Hashibe, M Bell, DA Boffetta, P Bouchardy, C Caporaso, N Chen, C Coutelle, C Diehl, SR Hayes, RB Olshan, AF Schwartz, SM Sturgis, EM Wei, QY Zavras, AI Benhamou, S TI Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: A HuGE review SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE ADH1B; ADH1C; alcohol dehydrogenase; aldehyde dehydrogenase; ALDH2; epidemiology; genetics; head and neck neoplasms ID SQUAMOUS-CELL CARCINOMA; MITOCHONDRIAL ALDEHYDE DEHYDROGENASE; HUMAN-LIVER ALCOHOL; UPPER AERODIGESTIVE TRACT; ORAL-CAVITY CANCER; S-TRANSFERASE M1; ALCOHOL-DEHYDROGENASE-3 GENOTYPE; HUMAN-PAPILLOMAVIRUS; GENETIC-POLYMORPHISM; CYTOCHROME P-4502E1 AB Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field. C1 Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69008 Lyon, France. NIEHS, Environm Genom Sect, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Univ Geneva, Inst Social & Prevent Med, Geneva Canc Registry, Geneva, Switzerland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Bordeaux Univ, Dept Med Biochem & Mol Biol, Bordeaux, France. Univ Med & Dent New Jersey, New Jersey Dent Sch, Ctr Pharmacogenom & Complex Dis Res, Newark, NJ USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Harvard Univ, Sch Dent Med, Dept Hlth Policy & Epidemiol, Boston, MA 02115 USA. Natl Inst Hlth & Med Res, Evry, France. Evry Univ EMI 00 06, Evry, France. RP Brennan, P (reprint author), Int Agcy Res Canc, Unit Environm Canc Epidemiol, 150 Cours Albert Thomas, F-69008 Lyon, France. EM brennan@iarc.fr FU NIDCR NIH HHS [R01 DE012609] NR 86 TC 132 Z9 137 U1 1 U2 9 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 JAN 1 PY 2004 VL 159 IS 1 BP 1 EP 16 DI 10.1093/aje/kwh003 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762LY UT WOS:000187974800001 PM 14693654 ER PT J AU Parker, AS Cerhan, JR Lynch, CF Leibovich, BC Cantor, KP AF Parker, AS Cerhan, JR Lynch, CF Leibovich, BC Cantor, KP TI History of urinary tract infection and risk of renal cell carcinoma SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carcinoma; renal cell; case-control studies; smoking; urinary tract infections ID CANCER; EXPRESSION; BLADDER; CYCLOOXYGENASE-2; KIDNEY; IOWA AB Limited data exist regarding whether a history of urinary tract infection (UTI) increases risk of developing renal cell carcinoma (RCC). Furthermore, it is unclear whether any association of RCC with a history of UTIs is modified by known risk factors for RCC (i.e., smoking, obesity). The authors report data from a 1986-1989 population-based case-control study in Iowa. RCC cases (233 males, 139 females) were identified through the Iowa Cancer Registry; controls (1,497 males, 751 females) were randomly selected from the general population, frequency matched on age and sex. Subjects provided detailed information on demographic, anthropometric, lifestyle, dietary, and medical history risk factors. In age-adjusted analysis, risk increased for subjects who self-reported a history of physician-diagnosed kidney or bladder infection (odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.5, 2.5) compared with those reporting no such history. Both sex and smoking status modified the risk of RCC associated with a history of UTI, with the strongest risk reported for males (OR = 2.7, 95% CI: 1.9, 3.8) and current smokers (OR = 4.3, 95% CI: 2.7, 6.7). The strongest risk was reported for male current smokers with a history of UTI (OR = 9.7, 95% CI: 5.0, 18.1). Multivariate adjustment for anthropometric, lifestyle, and dietary factors did not alter these findings. Results suggest a positive association of UTI history with RCC development, with elevated risks most notable for males with a history of smoking. C1 Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Mayo Clin, Dept Urol, Rochester, MN USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Parker, AS (reprint author), Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM parker.alexander@mayo.edu OI Cerhan, James/0000-0002-7482-178X NR 26 TC 22 Z9 23 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 JAN 1 PY 2004 VL 159 IS 1 BP 42 EP 48 DI 10.1093/aje/kwh014 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762LY UT WOS:000187974800005 PM 14693658 ER PT J AU Vahratian, A Buekens, P Bennett, TA Meyer, RE Kogan, MD Yu, SM AF Vahratian, A Buekens, P Bennett, TA Meyer, RE Kogan, MD Yu, SM TI Preterm delivery rates in North Carolina: Are they really declining among non-Hispanic African Americans? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the Society-for-Pediatric-and-Perinatal-Epidemiologic-Research CY JUN 17-18, 2002 CL PALM DESERT, CALIFORNIA SP Soc Pediatr & Perinatal Epidemiol Res DE bias (epidemiology); birth certificates; blacks; classification; delivery; obstetric; gestational age; infant; premature ID BIRTH-WEIGHT; GESTATIONAL-AGE; UNITED-STATES; MORTALITY AB The preterm delivery rate in North Carolina is consistently higher than the national average. However, recent reports suggest that singleton preterm delivery rates for non-Hispanic Whites are increasing while those for non-Hispanic African Americans are decreasing. To study this pattern further, the authors examined data on singleton non-Hispanic White and non-Hispanic African-American births in 1989 and 1999 by using North Carolina vital statistics data. They found that the frequency of preterm delivery rose 1.1% (8.5% to 9.6%) among non-Hispanic Whites but declined 1.4% (17.9% to 16.5%) among non-Hispanic African Americans over the same time period. For both subgroups, a bimodal distribution of birth weights was apparent among preterm births at 28-31 weeks of gestation. The second peak with its cluster of normal-weight infants was more prominent among non-Hispanic African Americans in 1989 than in 1999. To reduce the potential for bias due to misclassification of infant gestational age, frequencies of preterm delivery of infants who weighed less than 2,500 g were calculated. Unlike the original analysis, this calculation showed that preterm delivery increased for both subgroups. A number of non-Hispanic African-American births classified as preterm were apparently term births mistakenly assigned short gestational ages. Such misclassification was more frequent in 1989 than in 1999, inflating 1989 preterm delivery rates. C1 Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA. N Carolina Div Hlth & Human Serv, State Ctr Hlth Stat, Div Publ Hlth, Raleigh, NC USA. Maternal & Child Hlth Bur, Off Data & Informat Management, Rockville, MD USA. RP Vahratian, A (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM vahratia@mail.nih.gov RI Vahratian, Anjel/A-1182-2011 NR 10 TC 24 Z9 25 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 JAN 1 PY 2004 VL 159 IS 1 BP 59 EP 63 DI 10.1093/aje/kwh011 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762LY UT WOS:000187974800007 PM 14693660 ER PT J AU DeChristoforo, R Penzak, SR AF DeChristoforo, R Penzak, SR TI Tenofovir: A nucleotide analogue reverse-transcriptase inhibitor for treatment of HIV infection SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID ANTIRETROVIRAL-EXPERIENCED PATIENTS; MONKEYS MACACA-MULATTA; IN-VITRO SELECTION; DISOPROXIL FUMARATE; HEPATITIS-B; THERAPY; SAFETY; PMPA; 9-<2-(R)-(PHOSPHONOMETHOXY)PROPYL>ADENINE; PHARMACOKINETICS C1 NIH, Dept Pharm, Bethesda, MD 20892 USA. NIH, Clin Pharmacokinet Res Lab, Clin Ctr Pharm Dept, Bethesda, MD 20892 USA. RP DeChristoforo, R (reprint author), NIH, Dept Pharm, Bldg 10,IN-257 MSC 1196,10 Ctr Dr, Bethesda, MD 20892 USA. NR 59 TC 5 Z9 10 U1 1 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JAN 1 PY 2004 VL 61 IS 1 BP 86 EP 98 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 759JY UT WOS:000187735600014 PM 14725126 ER PT J AU Zimprich, A Muller-Myhsok, B Farrer, M Leitner, P Sharma, M Hulihan, M Lockhart, P Strongosky, A Kachergus, J Calne, DB Stoessl, J Uitti, RJ Pfeiffer, RF Trenkwalder, C Homann, N Ott, E Wenzel, K Asmus, F Hardy, J Wszolek, Z Gasser, T AF Zimprich, A Muller-Myhsok, B Farrer, M Leitner, P Sharma, M Hulihan, M Lockhart, P Strongosky, A Kachergus, J Calne, DB Stoessl, J Uitti, RJ Pfeiffer, RF Trenkwalder, C Homann, N Ott, E Wenzel, K Asmus, F Hardy, J Wszolek, Z Gasser, T TI The PARK8 locus in autosomal dominant parkinsonism: Confirmation of linkage and further delineation of the disease-containing interval SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; ALPHA-SYNUCLEIN; LEWY BODIES; TAU-SYNUCLEIN; GENE; MUTATIONS; FAMILY; PROTEIN; BRAIN; ONSET AB Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission for linkage in this region. Criteria for inclusion were at least three affected individuals in more than one generation. A total of 29 markers were used to saturate the candidate region. One hundred sixty-seven family members were tested ( 84 affected and 83 unaffected). Under the assumption of heterogeneity and through use of an affecteds- only model, a maximum multipoint LOD score of 2.01 was achieved in the total sample, with an estimated proportion of families with linkage of 0.32. This LOD score is significant for linkage in a replication study and corresponds to a P value of .0047. Two families ( family A [ German Canadian] and family D [ from western Nebraska]) reached significant linkage on their own, with a combined maximum multipoint LOD score of 3.33, calculated with an affecteds- only model (family A: LOD score 1.67; P =.0028 family D: LOD score 1.67, P = .0028). When a penetrance-dependent model was calculated, the combined multipoint LOD score achieved was 3.92 (family A: LOD score 1.68, P = .0027; family D: LOD score 2.24, P =.0007). On the basis of the multipoint analysis for the combined families A and D, the 1-LOD support interval suggests that the most likely disease location is between a CA repeat polymorphism on genomic clone AC025253 (44.5 Mb) and marker D12S1701 (47.7 Mb). Our data provide evidence that the PARK8 locus is responsible for the disease in a subset of families of white ancestry with autosomal dominant parkinsonism, suggesting that it could be a more common locus. C1 Univ Tubingen, Dept Neurodegenerat Disorders, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany. Max Planck Inst Psychiat, D-80804 Munich, Germany. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. Univ Hosp, Pacific Parkinsons Res Ctr, Vancouver, BC, Canada. Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada. Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. Univ Goettingen, Dept Clin Neurophysiol, Gottingen, Germany. Karl Franzens Univ Graz, Univ Hosp Graz, Dept Neurol, Graz, Austria. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Gasser, T (reprint author), Univ Tubingen, Dept Neurodegenerat Disorders, Hertie Inst Clin Brain Res, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM Thomas.Gasser@med.uni-tuebingen.de RI Hardy, John/C-2451-2009; Muller-Myhsok, Bertram/A-3289-2013; Lockhart, Paul/E-7753-2011; Zimprich, Alexander/A-5232-2017 OI Lockhart, Paul/0000-0003-2531-8413; Zimprich, Alexander/0000-0002-1668-5177 FU NINDS NIH HHS [NS 40256, P01 NS040256, P50 NS040256] NR 42 TC 116 Z9 121 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2004 VL 74 IS 1 BP 11 EP 19 DI 10.1086/380647 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 759DR UT WOS:000187723500002 PM 14691730 ER PT J AU Abbott, KC Cruess, DF Agodoa, LYC Sawyers, ES Tveit, DP AF Abbott, KC Cruess, DF Agodoa, LYC Sawyers, ES Tveit, DP TI Early renal insufficiency and late venous thromboembolism after renal transplantation in the United States SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE pulmonary embolism (PE); deep venous thrombosis (DVT); venous thromboembolism (VTE); Medicare claim; renal transplant; polycystic kidney disease; Modification of Diet in Renal Disease (MDRD); glomerular filtration rate (GFR); end-stage renal disease (ESRD); United States Renal Data System (USRDS) ID CHRONIC DIALYSIS PATIENTS; PULMONARY-EMBOLISM; PERITONEAL-DIALYSIS; UREMIC PATIENTS; RISK-FACTORS; THROMBOSIS; DISEASE; COMPLICATIONS; HEMODIALYSIS; RECIPIENTS AB Background: Pulmonary embolism (PE) is the most common preventable cause of death in hospitalized patients. Patients with severe chronic kidney disease (CKD) may be at increased risk for PE in comparison to the general population. Whether severe CKD is associated with increased risk for late venous thromboembolism (VTE) in a population of renal transplant recipients has not been determined. Methods: Using the US Renal Data System database, we studied 28,924 patients receiving a kidney transplant from January 1, 1996, to July 31, 2000, with Medicare as primary payer, followed up until December 31, 2000. Cox proportional hazards regression models were used to calculate the association of transplant recipient estimated glomerular filtration rate (eGFR; by the Modification of Diet in Renal Disease formula) less than 30 mL/min/1.73 m(2) (versus >30 mL/min/1.73 m(2)) 1 year after renal transplantation with Medicare claims for VTE (either deep-venous thrombosis or PE/infarction) 1.5 to 3 years after renal transplantation. Results: The rate of VTE occurring 1.5 to 3 years after transplantation was 2.9 episodes/1,000 person-years. eGFR less than 30 mL/min/1.73 m(2) versus higher at the end of the first year after renal transplantation was associated with significantly increased risk for later VTE (adjusted hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.89). Conclusion: Patients with severe CKD after renal transplantation should be regarded as high risk for late VTE, which is a potentially preventable cause of death in this population. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Serv Nephrol, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 35 TC 27 Z9 30 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2004 VL 43 IS 1 BP 120 EP 130 DI 10.1053/j.ajkd.2003.08.047 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 761KG UT WOS:000187907500015 PM 14712435 ER PT J AU Myers, AJ Marshall, H Holmans, P Compton, D Crook, RJP Mander, AP Nowotny, P Smemo, S Dunstan, M Jehu, L Wang, JC Hamshere, M Morris, JC Norton, J Chakraventy, S Tunstall, N Lovestone, S Petersen, R O'Donovan, M Jones, L Williams, J Owen, MJ John, HY Goate, A AF Myers, AJ Marshall, H Holmans, P Compton, D Crook, RJP Mander, AP Nowotny, P Smemo, S Dunstan, M Jehu, L Wang, JC Hamshere, M Morris, JC Norton, J Chakraventy, S Tunstall, N Lovestone, S Petersen, R O'Donovan, M Jones, L Williams, J Owen, MJ John, HY Goate, A TI Variation in the urokinase-plasminogen activator gene does not explain the chromosome 10 linkage signal for late onset AD SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Alzheimer disease; candidate gene; association study; urokinase-plasminogen activator; PLAU ID FAMILIAL ALZHEIMERS-DISEASE; AMYLOID BETA-PROTEIN; TRANSGENIC MICE; IN-VIVO; POLYMORPHISMS; DEPOSITION; HAPLOTYPE; PLAQUES; BRAINS; REGION AB Linkage studies indicate that the same region of chromosome 10 contains a risk locus for late onset Alzheimer disease (LOAD) and a QTL for plasma Abeta42 levels suggesting that a single locus may influence risk for AD by elevating plasma Abeta42 [Ertekin-Taner et al., 2000; Myers et al., 2000]. A strong positional and biological candidate is the urokinase-plasminogen activator (PLAU) gene. Eight polymorphisms spanning the entire gene were examined using case control (CC) and family-based association methods. No association was observed by any method making it unlikely that variation in PLAU explains our linkage data. (C) 2003 Wiley-Liss, Inc. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Univ Forvie Site, Inst Publ Hlth, MRC, Biostat Unit, Cambridge, England. Mayo Clin Jacksonville, Neurogenet Lab, Jacksonville, FL 32224 USA. GSK, Clin Pharmacol Stat & Data Sci, Harlow, Essex, England. Univ Wales Coll Med, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales. Inst Psychiat, London, England. Mayo Clin, Dept Neurol, Alzheimers Dis Res Ctr, Rochester, MN USA. RP Myers, AJ (reprint author), NIA, Neurogenet Lab, NIH, 9000 Rockville Pike,MSC 0900,Bldg 9,Room 1S128, Bethesda, MD 20892 USA. EM myersa@mail.nih.gov RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; mander, adrian/E-5261-2010; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; Holmans, Peter/F-4518-2015; OI Myers, Amanda/0000-0002-3100-9396; mander, adrian/0000-0002-0742-9040; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379 FU NIA NIH HHS [AG5681, AG 06786, AG 16574, AG16208, U24 AG021886] NR 21 TC 20 Z9 22 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 B JI Am. J. Med. Genet. B PD JAN 1 PY 2004 VL 124B IS 1 BP 29 EP 37 DI 10.1002/ajmg.b.20036 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 777PE UT WOS:000189186100006 PM 14681909 ER PT J AU Simon, JF Swanson, SJ Agodoa, LYC Cruess, DF Bohen, EM Abbott, KC AF Simon, JF Swanson, SJ Agodoa, LYC Cruess, DF Bohen, EM Abbott, KC TI Induction sirolimus and delayed graft function after deceased donor kidney transplantation in the United States SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE sirolimus; delayed graft function; deceased donor kidney transplantation ID CADAVERIC RENAL-TRANSPLANTATION; EARLY CYCLOSPORINE WITHDRAWAL; LONG-TERM TRIAL; RANDOMIZED MULTICENTER; RECIPIENTS; TACROLIMUS; REJECTION; RECOVERY; IMMUNOSUPPRESSION; EFFICACY AB Background/Aims: Previous studies have reported a link between the use of induction sirolimus (INDSRL) and delayed graft function (DGF) after kidney transplantation. However, none have had sufficient power to adjust for all factors known to be associated with DGF. Methods: We conducted a retrospective cohort study of US deceased donor kidney transplantation recipients in the United States Renal Data System (USRDS) from January 1, 2000 to May 31, 2001. Logistic regression analysis was used to model adjusted odds ratios (AOR) for the development of DGF, adjusted for other factors previously reported to be associated with DGF. Results: Among 8,319 patients meeting inclusion criteria, 361 patients received INDSRL, of whom 98 (27.1%) had DGF, compared to 22.5% among patients who did not receive INDSRL. In multivariate analysis, INDSRL was associated with an increased risk of DGF, with an adjusted odds ratio of 1.42 (95% CI: 1.07-1.90). Other factors associated with DGF were similar to those previously reported. INDSRL was not significantly associated with graft loss at 1 year in Cox regression. Conclusions: INDSRL was independently associated with DGF in US deceased donor kidney transplantation recipients, adjusted for all other factors previously shown to be associated with DGF. Copyright (C) 2004 S. Karger AG, Basel. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. WRAMC, Organ Transplant Serv, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 23 TC 20 Z9 21 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2004 VL 24 IS 4 BP 393 EP 401 DI 10.1159/000079734 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 854IR UT WOS:000223896800003 PM 15256804 ER PT J AU Almasy, L Howard, BV Lee, ET Bost, L Welty, TK Devereux, R Fabsitz, RR Cole, S Laston, S Goring, HHH Diego, VP Dyke, B MacCluer, JW AF Almasy, L. Howard, B. V. Lee, E. T. Bost, L. Welty, T. K. Devereux, R. Fabsitz, R. R. Cole, S. Laston, S. Goring, H. H. H. Diego, V. P. Dyke, B. MacCluer, J. W. TI Quantitative trait linkage mapping in the Strong Heart Family Study of American Indians SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 [Almasy, L.; Cole, S.; Laston, S.; Goring, H. H. H.; Diego, V. P.; Dyke, B.; MacCluer, J. W.] SW Fdn Biomed Res, San Antonio, TX USA. [Lee, E. T.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Bost, L.; Welty, T. K.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. [Devereux, R.] Cornell Univ Med Coll, New York, NY USA. [Fabsitz, R. R.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2004 SU 38 BP 52 EP 52 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA V16BZ UT WOS:000207846400011 ER PT J AU Czarnecki, JM Friedlaender, JS Mgone, CS Stoner, GL AF Czarnecki, J. M. Friedlaender, J. S. Mgone, C. S. Stoner, G. L. TI JC Virus genotype distribution in Papua New Guinea SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 [Czarnecki, J. M.] Naval Med Res Ctr, Biol Def Res Directorate, Bethesda, MD USA. [Friedlaender, J. S.] Temple Univ, Dept Anthropol, Philadelphia, PA 19122 USA. [Stoner, G. L.] NINDS, Neurotoxicol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2004 SU 38 BP 81 EP 81 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA V16BZ UT WOS:000207846400122 ER PT J AU Dvoskin, RL Barr, CS Newman, TK Goldman, D Suomi, SJ Higley, JD AF Dvoskin, R. L. Barr, C. S. Newman, T. K. Goldman, D. Suomi, S. J. Higley, J. D. TI The rhesus macaque (Macaca mulatta) corticotropin-releasing hormone gene: Sequence analysis and variation. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 [Dvoskin, R. L.] NYU, New York Consortium Evolutionary Primatol, Dept Anthropol, New York, NY 10003 USA. [Dvoskin, R. L.; Barr, C. S.; Newman, T. K.; Goldman, D.; Higley, J. D.] NIAAA, NIH, Bethesda, MD USA. [Suomi, S. J.] NICHD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2004 SU 38 BP 91 EP 91 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA V16BZ UT WOS:000207846400158 ER PT J AU Newman, TK Gibson, N Babb, P Higley, JD Goldman, D AF Newman, T. K. Gibson, N. Babb, P. Higley, J. D. Goldman, D. TI Comparative sequence analysis of a repeat polymorphism in the monoamine oxidase A (MAOA) gene promoter region in primates: Evidence for selection? SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 [Newman, T. K.; Gibson, N.; Babb, P.; Higley, J. D.; Goldman, D.] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2004 SU 38 BP 152 EP 153 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA V16BZ UT WOS:000207846400400 ER PT J AU Sherry, ST AF Sherry, S. T. TI Haplotype resources in dbSNP: NCBI's database of genetic variation. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 [Sherry, S. T.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2004 SU 38 BP 180 EP 181 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA V16BZ UT WOS:000207846400507 ER PT J AU Fueger, PT Bracy, DP Malabanan, CM Pencek, RR Wasserman, DH AF Fueger, PT Bracy, DP Malabanan, CM Pencek, RR Wasserman, DH TI Distributed control of glucose uptake by working muscles of conscious mice: roles of transport and phosphorylation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE delivery; glucose transporter 4; hexokinase; exercise; 2-deoxyglucose ID RAT SKELETAL-MUSCLE; TRANSGENIC MICE; GLUT4 PROTEIN; HEXOKINASE-II; OVEREXPRESSING GLUT4; DYNAMIC EXERCISE; INSULIN; GLYCOGEN; HUMANS; HOMEOSTASIS AB Muscle glucose uptake (MGU) is determined by glucose delivery, transport, and phosphorylation. C57Bl/6J mice overexpressing GLUT4, hexokinase II (HK II), or both were used to determine the barriers to MGU. A carotid artery and jugular vein were catheterized for arterial blood sampling and venous infusions. Experiments were conducted in conscious mice similar to7 days after surgery. 2-Deoxy-[H-3] glucose was administered during rest or treadmill exercise to calculate glucose concentration-dependent (R-g) and - independent (K-g) indexes of MGU. Compared with wild-type controls, GLUT4-overexpressing mice had lowered fasting glycemia (165 +/- 6 vs. 115 +/- 6 mg/dl) and increased Rg by 230 and 166% in the gastrocnemius and superficial vastus lateralis (SVL) muscles under sedentary conditions. GLUT4 overexpression was not able to augment exercise-stimulated R-g or K-g. Whereas HK II overexpression had no effect on fasting glycemia ( 170 +/- 6 mg/dl) or sedentary R-g, it increased exercise-stimulated R-g by 82, 60, and 169% in soleus, gastrocnemius, and SVL muscles, respectively. Combined GLUT4 and HK II overexpression lowered fasting glycemia (106 +/- 6 mg/dl), increased nonesterified fatty acids, and increased sedentary R-g. Combined GLUT4 and HK II overexpression did not enhance exercise-stimulated R-g compared with HK II-overexpressing mice because of the reduced glucose concentration. GLUT4 combined with HK II overexpression resulted in a marked increase in exercise-stimulated K-g. In conclusion, control of MGU shifts from membrane transport at rest to phosphorylation during exercise. Glucose transport is not normally a significant barrier during exercise. However, when the phosphorylation barrier is lowered by HK II overexpression, glucose transport becomes a key site of control for regulating MGU during exercise. C1 Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. RP Fueger, PT (reprint author), Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, 221 Kirkland Hall, Nashville, TN 37232 USA. FU NIDDK NIH HHS [R01 DK 54902, U24 DK 59637] NR 44 TC 40 Z9 41 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN 1 PY 2004 VL 286 IS 1 BP E77 EP E84 DI 10.1152/ajpendo.00309.2003 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 751ND UT WOS:000187072700011 PM 13129858 ER PT J AU Campia, U Sullivan, G Bryant, MB Waclawiw, MA Quon, MJ Panza, JA AF Campia, U Sullivan, G Bryant, MB Waclawiw, MA Quon, MJ Panza, JA TI Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hyperinsulinemia; endothelial function; cholesterol; metabolic syndrome ID NITRIC-OXIDE; RESISTANCE; HYPERINSULINEMIA; CELLS; BLOOD; DYSFUNCTION; LIPOPROTEIN; DISEASE; HUMANS; TRIAL AB Insulin resistance is a risk factor for atherosclerosis and is associated with hyperinsulinemia, abnormal lipid profile, and hypertension. Whether hyperinsulinemia affects vascular function independent of insulin resistance or other metabolic risk factors is unknown. This investigation aimed to assess the effects of hyperinsulinemia on endothelial function in subjects with a spectrum of insulin sensitivity and lipid profile. Endothelium- dependent ( flow- mediated dilation, FMD) and - independent ( nitroglycerin) responses of the brachial artery were studied by high- resolution ultrasound before and during hyperinsulinemia ( euglycemic clamp) in 25 normoglycemic, normotensive subjects. Participants were divided into an insulin- sensitive and an insulin-resistant subgroup based on their sensitivity index values, with a cutoff of 8, and into a normal- cholesterol and a high- cholesterol subgroup based on their total cholesterol levels, with a cutoff of 5.2 mmol/ l ( 200 mg/ dl). In the whole population, FMD was lower during hyperinsulinemia compared with baseline ( 2.3 +/- 0.6% vs. 6 +/- 0.6%; P < 0.001). Resting FMD was lower in the insulin- resistant subgroup compared with the insulin- sensitive subgroup ( 4.2 +/- 0.9% vs. 7.4 +/- 0.8%; P = 0.014) and in the high- cholesterol subjects compared with the normal- cholesterol subjects ( 4.4 +/- 0.7% vs. 8 +/- 0.7%; P = 0.002). Hyperinsulinemia decreased FMD in both the insulin- sensitive ( from 7.4 +/- 0.8% to 3.6 +/- 0.4%; P < 0.001) and insulin- resistant ( from 4.2% to 1.22%; P = 0.012) subgroups and in both the normal- cholesterol ( from 8 +/- 0.7% to 3.9 +/- 0.4%; P < 0.001) and high- cholesterol ( from 4.4 +/- 0.7% to 1.1 +/- 0.8%; P = 0.01) participants. Acute hyperinsulinemia impairs conduit vessel endothelial function independent of insulin sensitivity and lipid profile. Insulin may trigger endothelial dysfunction and promote atherosclerosis. C1 NHLBI, Cardiol Branch, NIH, Rockville, MD 20852 USA. NHLBI, Off Biostat Res, NIH, Rockville, MD 20852 USA. RP Panza, JA (reprint author), Washington Hosp Ctr, 110 Irving St NW,Suite 2A 74, Washington, DC 20010 USA. RI Quon, Michael/B-1970-2008 NR 30 TC 31 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN 1 PY 2004 VL 286 IS 1 BP H76 EP H82 DI 10.1152/ajpheart.00539.2003 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 754UR UT WOS:000187350500011 PM 12946932 ER PT J AU Wise, RA AF Wise, RA TI Dopamine and food reward: back to the elements SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Editorial Material ID NUCLEUS-ACCUMBENS C1 NIDA, Intramural Res Program, NIH, US Dept HHS, Baltimore, MD 21224 USA. RP Wise, RA (reprint author), NIDA, Intramural Res Program, NIH, US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Wise, Roy/A-6465-2012 NR 9 TC 22 Z9 23 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN 1 PY 2004 VL 286 IS 1 BP R13 EP R13 DI 10.1152/ajpregu.00590.2003 PG 1 WC Physiology SC Physiology GA 751BX UT WOS:000187033900002 PM 14660469 ER PT J AU Cai, Q Ferraris, JD Burg, MB AF Cai, Q Ferraris, JD Burg, MB TI Greater tolerance of renal medullary cells for a slow increase in osmolality is associated with enhanced expression of HSP70 and other osmoprotective genes SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE osmotic stress; organic osmolyte; heat shock protein; mRNA abundance ID POLYMERASE CHAIN-REACTION; OSMOTIC-STRESS; HEAT-SHOCK; MDCK CELLS; ISOVOLUMETRIC REGULATION; ENDOPLASMIC-RETICULUM; MOLECULAR CHAPERONES; ORGANIC OSMOLYTES; HEME OXYGENASE-1; BINDING PROTEIN AB In tests of osmotic tolerance of renal inner medullary cells in tissue culture, osmolality has usually been increased in a single step, whereas in vivo the increase occurs gradually over several hours. We previously found that more passage 2 mouse inner medullary epithelial (p2mIME) cells survive a linear increase in NaCl and urea from 640 to 1,640 mosmol/kgH(2)O over 20 h (which is similar to the change that may occur in vivo) than they do a step increase. The present studies examine accompanying differences in gene expression. Among mRNAs of genes known to be protective, tonicity-responsive enhancer binding protein and aldose reductase increase with a linear but decrease with a step increase; betaine transporter BGT1 decreases with a step but not a linear increase; heat shock protein 70.1 (HSP70.1) and HSP70.3 increase more with a linear than a step increase; and osmotic stress protein 94 and heme oxygenase-1 increase with a linear but decrease with a step increase. mRNAs for known urea-responsive proteins, GADD153 and Egr-1, increase with both a step and linear increase. A step increase in urea alone reduces mRNAs, similar to the combination of NaCl and urea, but a step increase in NaCl alone does not. HSP70 protein increases substantially with a linear rise in osmolality but does not change significantly with a step rise. We speculate that poorer survival of p2mIME cells with a step than with linear increase in NaCl and urea is accounted for, at least in part, by urea-induced suppression of protective genes, particularly HSP70. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Cai, Q (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N319, Bethesda, MD 20892 USA. EM caiq@nhlbi.nih.gov NR 47 TC 25 Z9 25 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2004 VL 286 IS 1 BP F58 EP F67 DI 10.1152/ajprenal.00037.2003 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 749VB UT WOS:000186948600007 PM 13129850 ER PT J AU Hoffert, JD van Balkom, BWM Chou, CL Knepper, MA AF Hoffert, JD van Balkom, BWM Chou, CL Knepper, MA TI Application of difference gel electrophoresis to the identification of inner medullary collecting duct proteins SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE inner medullary collecting duct; kidney; two-dimensional electrophoresis; difference gel electrophoresis; proteomics ID RECEPTOR-MEDIATED ENDOCYTOSIS; RAT-KIDNEY; BINDING PROTEIN; ANGIOTENSIN-IV; ANION CHANNEL; TRANSGLUTAMINASE; LOCALIZATION; AQUAPORINS; PROTEOMICS; SYSTEM AB In this study, we present a standardized approach to purification of native inner medullary collecting duct (IMCD) cells from rat kidney for proteomic analysis and apply the approach to identification of abundant proteins utilizing two-dimensional difference gel electrophoresis (DIGE) coupled with matrix-assisted laser desorption-ionization-time of flight mass spectrometry. Fractionation of inner medullary cell suspensions by low-speed centrifugation gave a highly purified IMCD cell fraction in which aquaporin-2 was enriched 10-fold. When DIGE was initially applied to rat inner medullas fractionated into IMCD cells ( labeled with Cy3) and non-IMCD cells ( labeled with Cy5), we identified 50 highly abundant proteins expressed in the IMCD cells. These proteins, identifiable without subcellular fractionation, included chiefly enzymes, structural proteins, and signaling intermediates. An additional 35 proteins were found predominantly in the non-IMCD cell types. Proteins that were highly enriched in the IMCD fraction included cytokeratin 8, cytokeratin 18, transglutaminase II, aminopeptidase B, T-plastin, heat shock protein (HSP) 27, HSP70, and lactate dehydrogenase A. Semiquantitative immunoblotting and immunohistochemistry confirmed relative expression levels and distribution of selected proteins. An additional 40 IMCD proteins were identified in separate experiments aimed at further enrichment of proteins through optimization of sample loading. These studies document the applicability of a standardized approach to purification of IMCD cells for proteomic analysis of IMCD proteins and demonstrate the feasibility of large-scale identification of proteins in the native IMCD cell. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 35 TC 34 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2004 VL 286 IS 1 BP F170 EP F179 DI 10.1152/ajprenal.00223.2003 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 749VB UT WOS:000186948600020 PM 12965894 ER PT J AU Briss, P Rimer, B Reilley, B Coates, RC Lee, NC Mullen, P Corso, P Hutchinson, AB Hiatt, R Kerner, J George, P White, C Gandhi, N Saraiya, M Breslow, R Isham, G Teutsch, SM Hinman, AR Lawrence, R AF Briss, P Rimer, B Reilley, B Coates, RC Lee, NC Mullen, P Corso, P Hutchinson, AB Hiatt, R Kerner, J George, P White, C Gandhi, N Saraiya, M Breslow, R Isham, G Teutsch, SM Hinman, AR Lawrence, R CA Task Force on Community Preventive TI Promoting informed decisions about cancer screening in communities and healthcare systems SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HORMONE REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; PROSTATE-CANCER; PREVENTIVE-SERVICES; COLORECTAL-CANCER; PATIENTS PREFERENCES; MAKING INTERVENTION; AID; PARTICIPATION; CONSENT AB Individuals are increasingly involved in decisions about their health care. Shared decision making (SDM), an intervention in the clinical setting in which patients and providers collaborate in decision making, is an important approach for informing patients and involving them in their health care. However, SDM cannot bear the entire burden for informing and involving individuals. Population-oriented interventions to promote informed decision making (IDM) should also be explored. This review provides a conceptual background for population-oriented interventions to promote informed decisions (IDM interventions), followed by a systematic review of studies of IDM interventions to promote cancer screening. This review specifically asked whether IDM interventions (1) promote understanding of cancer screening, (2) facilitate participation in decision making about cancer screening at a level that is comfortable for individuals; or (3) encourage individuals to make cancer-screening decisions that are consistent with their preferences and values. Fifteen intervention arms met the intervention definition. They used small media, counseling, small-group education, provider-oriented strategies, or combinations of these to promote IDM. The interventions were generally consistent in improving individuals' knowledge about the disease, accuracy of risk perceptions, or knowledge and beliefs about the pros and cons of screening and treatment options. However, few studies evaluated whether these interventions resulted in individuals participating in decision making at a desirable level, or whether they led to decisions that were consistent with individuals' values and preferences. More research is needed on how best to promote and facilitate individuals' participation in health care. Work is especially needed on how to facilitate participation at a level desired by individuals, how to promote decisions by patients that are consistent with their preferences and values, how to per-form effective and cost-effective IDM interventions for healthcare systems and providers and in community settings (outside of clinical settings), and how to implement these interventions in diverse populations (such as populations that are older, nonwhite, or disadvantaged). Finally, work is needed on the presence and magnitude of barriers to and harms of IDM interventions and how they might be avoided. C1 Ctr Dis Control & Prevent, Epidemiol Program Off, Community Guide Branch, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Hlth Program Dev, Houston, TX USA. Calif Dept Hlth Serv, Sacramento, CA 95814 USA. Merck & Co Inc, W Point, PA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Task Force Child Survival & Dev, Atlanta, GA USA. HealthPartners, Minneapolis, MN USA. RP Briss, P (reprint author), Ctr Dis Control & Prevent, Epidemiol Program Off, Community Guide Branch, 4770 Buford Highway,MS-K73, Atlanta, GA 30341 USA. OI Kerner, Jon/0000-0002-8792-3830 NR 55 TC 188 Z9 188 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2004 VL 26 IS 1 BP 67 EP 80 DI 10.1016/j.amepre.2003.09.012 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 760DZ UT WOS:000187797500011 PM 14700715 ER PT J AU Charney, DS AF Charney, DS TI Discovering the neural basis of human social anxiety: A diagnostic and therapeutic imperative SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; NATIONAL COMORBIDITY SURVEY; CEREBRAL LATERALITY; PHOBIA; EPIDEMIOLOGY; HERITABILITY C1 NIMH, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RP Charney, DS (reprint author), NIMH, Mood & Anxiety Disorders Res Program, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 71 Z9 72 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2004 VL 161 IS 1 BP 1 EP 2 DI 10.1176/appi.ajp.161.1.1 PG 2 WC Psychiatry SC Psychiatry GA 818WR UT WOS:000221275700001 PM 14702241 ER PT J AU Gaser, C Nenadic, I Buchsbaum, BR Hazlett, EA Buchsbaum, MS AF Gaser, C Nenadic, I Buchsbaum, BR Hazlett, EA Buchsbaum, MS TI Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SCHIZOTYPAL PERSONALITY-DISORDER; MRI AB Objective: Enlargement of the lateral ventricles is among the most frequently reported macroscopic brain structural changes in schizophrenia, although variable in extent and localization. The authors investigated whether ventricular enlargement is related to regionally specific volume loss. Method. High-resolution magnetic resonance imaging scans from 39 patients with schizophrenia were analyzed with deformation-based morphometry, a voxel-wise whole brain morphometric technique. Results: Significant negative correlations with the ventricle-brain ratio were found for voxels in the left and right thalamus and posterior putamen and in the left superior temporal gyrus and insula. Conclusions: Thalamic shrinkage, especially of medial nuclei and the adjacent striatum and insular cortex, appear to be important contributors to ventricular enlargement in schizophrenia. C1 Univ Jena, Dept Psychiat, D-07743 Jena, Germany. Mt Sinai Sch Med, Dept Psychiat, Neurosci PET Lab, New York, NY USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Gaser, C (reprint author), Univ Jena, Dept Psychiat, Philosophenweg 3, D-07743 Jena, Germany. EM Christian.Gaser@uni-jena.de RI Gaser, Christian/F-5103-2010 OI Gaser, Christian/0000-0002-9940-099X FU NIMH NIH HHS [MH-40071, MH-60023, MH-56489] NR 13 TC 53 Z9 55 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2004 VL 161 IS 1 BP 154 EP 156 DI 10.1176/appi.ajp.161.1.154 PG 3 WC Psychiatry SC Psychiatry GA 818WR UT WOS:000221275700024 PM 14702264 ER PT J AU Zarate, CA Tohen, M AF Zarate, CA Tohen, M TI Double-blind comparison of the continued use of antipsychotic treatment versus its discontinuation in remitted manic patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 58th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CA SP Soc Biol Psychiat ID RATING-SCALE; DISORDER; LITHIUM AB Objective: The goal of this study was to determine the benefits of the continued use of a typical antipsychotic agent following remission from an acute manic episode. Method: Immediately following remission of a manic episode treated with the combination of a typical antipsychotic (perphenazine) and a mood stabilizer (lithium, carbamazepine, or valproate), 37 patients were randomly assigned to 6 months of double-blind treatment in which in addition to the mood stabilizer they received either continued perphenazine treatment or placebo. Results: Patients randomly assigned to continue perphenazine treatment, relative to those who discontinued it, were more likely to have a shorter time to depressive relapse, discontinue the study, and have increased rates of dysphoria, depressive symptoms, and extrapyramidal symptoms. Conclusions: There were no short-term benefits with the continued use of a typical antipsychotic after achieving remission from an episode of acute mania. In fact, its continued use was associated with detrimental effects. C1 Harvard Univ, McLean Hosp, Sch Med, Consolidated Dept Psychiat,Bipolar & Psychot Diso, Belmont, MA 02178 USA. RP Zarate, CA (reprint author), NIMH, Mood & Anxiety Disorders Program, 9000 Rockville Pike,Bldg 10,Unit 3W,Room 3s250, Bethesda, MD 20892 USA. EM zaratec@intra.nimh.nih.gov NR 14 TC 75 Z9 77 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2004 VL 161 IS 1 BP 169 EP 171 DI 10.1176/appi.ajp.161.1.169 PG 3 WC Psychiatry SC Psychiatry GA 818WR UT WOS:000221275700029 PM 14702269 ER PT J AU Zarate, CA Payne, JL Quiroz, J Sporn, J Denicoff, KK Luckenbaugh, D Charney, DS Manji, HK AF Zarate, CA Payne, JL Quiroz, J Sporn, J Denicoff, KK Luckenbaugh, D Charney, DS Manji, HK TI An open-label trial of riluzole in patients with treatment-resistant major depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEUROTROPHIC FACTOR; DOUBLE-BLIND; DRUGS; NMDA AB Objective: This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in patients with recurrent major depression. Method: After a 1-week drug-free period, subjects 18 years or older with a diagnosis of recurrent major depression and a Montgomery-Asberg Depression Rating Scale score greater than or equal to20 received riluzole monotherapy (100-200 mg/day) openly for 6 weeks. Results: Nineteen treatment-resistant depressed patients, 53% of whom were classified as having stage 2 treatment resistance or greater, received riluzole at a mean dose of 169 mg/day. Significant improvement occurred during weeks 3 through 6 for all patients and weeks 2 through 6 for completers. Conclusions: Although preliminary, these results indicate that riluzole may have antidepressant properties in some patients. C1 NIMH, Lab Mol Pathophysiol & Expt Therapeut, Mood & Anxiety Disorders Program, Dept Human & Hlth Serv,NIH, Bethesda, MD 20892 USA. NIMH, Pathophysiol Branch, Mood & Anxiety Disorders Program, Dept Human & Hlth Serv,NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), 9000 Rockville Pike,Bldg 10,Unit 3W,Rm 3s250, Bethesda, MD 20892 USA. EM zaratec@intra.nimh.nih.gov NR 17 TC 202 Z9 213 U1 0 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2004 VL 161 IS 1 BP 171 EP 174 DI 10.1176/appi.ajp.161.1.171 PG 4 WC Psychiatry SC Psychiatry GA 818WR UT WOS:000221275700030 PM 14702270 ER PT J AU Fee, E Brown, TM Laylor, J Gross, M Sember, R AF Fee, E Brown, TM Laylor, J Gross, M Sember, R TI On cultural competence and scientific rigor in transgender treatment - Response SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 Natl Lib Med, Hist Med Div, Bethesda, MD USA. Natl Lib Med, Off Director, Bethesda, MD USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM elizabeth_fee@nlm.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2004 VL 94 IS 1 BP 6 EP 7 DI 10.2105/AJPH.94.1.6-a PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762CL UT WOS:000187952700002 ER PT J AU Havas, S Roccella, EJ Lenfant, C AF Havas, S Roccella, EJ Lenfant, C TI Reducing the public health burden from elevated blood pressure levels in the United States by lowering intake of dietary sodium SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID EDUCATION-PROGRAM; PRIMARY PREVENTION; HYPERTENSION; RISK; POPULATION; PREVALENCE; DISEASE; TRIAL AB Elevated blood pressure levels are a major cause of heart disease and stroke. Healthy People 2010 established objectives to reduce mortality from these diseases by 20% and to reduce the major causal factors associated with these elevated levels, such as excess sodium intake. The American public consumes far more sodium than is needed, most of which is added by food manufacturers and restaurants. In November 2002, the American Public Health Association adopted a policy resolution calling for a 50% reduction in sodium in the nation's food supply over the next 10 years. Such a reduction would greatly enhance the chances of attaining the Healthy People 2010 objectives and would save at least 150000 lives annually. This issue warrants public health intervention. (Am J Public Health. 2004;94:19-22). C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. NHLBI, Bethesda, MD 20892 USA. RP Havas, S (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 660 W Redwood St, Baltimore, MD 21201 USA. EM shavas@epi.umaryland.edu NR 30 TC 60 Z9 62 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2004 VL 94 IS 1 BP 19 EP 22 DI 10.2105/AJPH.94.1.19 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762CL UT WOS:000187952700012 PM 14713688 ER PT J AU Bachrach, CA Abeles, RP AF Bachrach, CA Abeles, RP TI Social science and health research: Growth at the National Institutes of Health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BIRTH-WEIGHT; BLOOD-PRESSURE; COMMUNITY; CARE; SUPPLEMENTATION; INTERVENTION; EPIDEMIOLOGY; POPULATION; DIRECTIONS; BEHAVIOR AB Programs within the National Institutes of Health (NIH) have recently taken steps to enhance social science contributions to health research. A June 2000 conference convened by the NIH Office of Behavioral and Social Sciences Research highlighted the role of the social sciences in health research and developed an agenda for advancing such research. The conference and agenda underscored the importance of research on basic social scientific concepts and constructs, basic social science research on the etiology of health and illness, and the application of basic social science constructs in health services, treatment, and prevention research. Recent activities at NIH suggest a growing commitment to social science research and its integration into interdisciplinary multilevel studies of health. (Am J Public Health. 2004;94:22-28). C1 Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Bachrach, CA (reprint author), Natl Inst Child Hlth & Human Dev, 6100 Execut Blvd,Room 8B07,MSC 7510, Bethesda, MD 20892 USA. EM cbachrach@nih.gov NR 49 TC 26 Z9 26 U1 2 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2004 VL 94 IS 1 BP 22 EP 28 DI 10.2105/AJPH.94.1.22 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762CL UT WOS:000187952700013 PM 14713689 ER PT J AU Brown, TM Fee, E AF Brown, TM Fee, E TI Peace and feminism SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Univ Rochester, Dept Hist, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM theodore_brown@urmc.rochester.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2004 VL 94 IS 1 BP 34 EP 34 DI 10.2105/AJPH.94.1.34 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762CL UT WOS:000187952700016 PM 14713692 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI Dispelling the specter of nuclear holocaust SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID WAR C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM elizabeth_fee@nlm.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2004 VL 94 IS 1 BP 36 EP 36 DI 10.2105/AJPH.94.1.36 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762CL UT WOS:000187952700017 PM 14713693 ER PT J AU Summers, RM Dempsey, J Campbell, SR Yao, J Franaszek, M Brickman, D Dwyer, A Hara, A AF Summers, RM Dempsey, J Campbell, SR Yao, J Franaszek, M Brickman, D Dwyer, A Hara, A TI CT colonography with intravenous contrast enhancement: Computer-aided polyp and mass detection SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 NIH, Bethesda, MD 20892 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 75 EP 75 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100287 ER PT J AU Fidler, JL Christensen, JA Summers, RM Fletcher, JG Johnson, CD AF Fidler, JL Christensen, JA Summers, RM Fletcher, JG Johnson, CD TI Comparison of two automated mechanical CO2 insufflation devices for colonic distention in CT colonography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 Mayo Clin, Rochester, MN USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 76 EP 76 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100291 ER PT J AU Avila, NA Dwyer, AJ Rabel, A Moss, J AF Avila, NA Dwyer, AJ Rabel, A Moss, J TI Lymphangioleiomyomatosis (LAM): Spectrum and prevalence of radiologic features on body computed tomography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 86 EP 86 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100329 ER PT J AU Alexander, JO Bednarski, M Guccione, S Yao, J Menard, C Li, K Choyke, P AF Alexander, JO Bednarski, M Guccione, S Yao, J Menard, C Li, K Choyke, P TI Systemic prostate specific antigen (PSA) is a measure of vascular permeability: A study of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc C1 NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PY 2004 VL 182 IS 4 SU S BP 97 EP 97 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808UD UT WOS:000220593100383 ER PT J AU Hoffmann, S Jacobson, LM Muehrer, RJ Kirk, AD Knechtle, S Becker, BN AF Hoffmann, S Jacobson, LM Muehrer, RJ Kirk, AD Knechtle, S Becker, BN TI Distinct fibrosis patterns characterize Campath-1H plus rapamycin versus traditional therapy with calcineurin inhibition. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, Bethesda, MD USA. Univ Wisconsin, Madison, WI 53706 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1 BP 160 EP 160 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500002 ER PT J AU Zoghby, Z Thomas, W O'Bryan, T Salahudeen, A Rosenberg, M Hostetter, T Ibrahim, H AF Zoghby, Z Thomas, W O'Bryan, T Salahudeen, A Rosenberg, M Hostetter, T Ibrahim, H TI Comparison of three serum creatinine based formulas in estimating glomerular filtration rate in subjects with chronic allograft nephropathy. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Minnesota, Minneapolis, MN 55455 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 34 BP 168 EP 168 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500035 ER PT J AU Anam, K Black, A Hale, DA AF Anam, K Black, A Hale, DA TI Low dose busulfan (BU) facilitates induction of titratable macrochimerism in fully allogenic mice treated with T cell depletion (TCD), sirolimus (sir) and donor bone marrow (BM). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 105 BP 188 EP 188 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500106 ER PT J AU Akpinar, E Craighead, N Anam, K Smoot, D Hale, D AF Akpinar, E Craighead, N Anam, K Smoot, D Hale, D TI C-kit plus lin plus fraction of donor bone marrow (BM) possesses superior potency compared to whole BM in prolonging skin allograft survival in mice treated with antilymphocyte serum (ALS) and sirolimus. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 111 BP 189 EP 189 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500112 ER PT J AU Mannon, RB Post, D Kowalski, R Kirk, AD Hale, D Britz, J AF Mannon, RB Post, D Kowalski, R Kirk, AD Hale, D Britz, J TI Assessing immune reconsitution: Monitoring lymphocyte immune function following depletional therapy using the ImmunKnow (TM) assay. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Cylex Inc, Columbia, MO USA. NIDDK, NIH, DHHS, Transplantat Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 234 BP 222 EP 222 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500234 ER PT J AU Shaked, A Hulbert-Shearon, TE Everhart, J Merion, RM AF Shaked, A Hulbert-Shearon, TE Everhart, J Merion, RM CA A2ALL Study Grp TI Rejection is decreased among adult recipients of living vs. deceased donor liver allografts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 399 BP 268 EP 268 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500399 ER PT J AU Mannon, RB Cheng, OH Hoffmann, SC Kirk, AD Grottendorst, G AF Mannon, RB Cheng, OH Hoffmann, SC Kirk, AD Grottendorst, G TI Predicting the future: Connective tissue growth factor (CTGF), a surrogate for the development of chronic allograft nephropathy (CAN) in man. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, DHHS, Transplantat Branch, Bethesda, MD USA. Univ Miami, Miami, FL 33152 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 430 BP 276 EP 276 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500430 ER PT J AU Xu, H Zhang, XJ Mannon, RB Kirk, AD AF Xu, H Zhang, XJ Mannon, RB Kirk, AD TI A nuclear factor-kappa B inhibitor, BAY 11-7082, inhibits interactions between human endothelial cells, T-cells, and monocytes. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 467 BP 286 EP 286 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500467 ER PT J AU Pearl, JP Xu, H Christopher, KL Leopardi, F Preston, E Cendales, L Hale, D Kirk, AD AF Pearl, JP Xu, H Christopher, KL Leopardi, F Preston, E Cendales, L Hale, D Kirk, AD TI Aggressive lymphocyte depletion does not eliminate immune memory. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, DHHS, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 525 BP 302 EP 302 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500525 ER PT J AU Pearl, JP Parris, J McCoy, KL Hoffman, SC Christopher, KL Xu, H Mannon, RB Hale, D Swanson, SJ Kirk, AD AF Pearl, JP Parris, J McCoy, KL Hoffman, SC Christopher, KL Xu, H Mannon, RB Hale, D Swanson, SJ Kirk, AD TI Immunocompetent memory T-cells are the dominant cell type following antibody-mediated T-cell depletion and may be a barrier to achieving tolerance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, DHHS, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 527 BP 303 EP 303 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500527 ER PT J AU Mannon, RB Hoffman, SC Kampen, R Cheng, OH Hale, D Kirk, AD Kleiner, DE AF Mannon, RB Hoffman, SC Kampen, R Cheng, OH Hale, D Kirk, AD Kleiner, DE TI Death and destruction: The molecular and cellular events of polyomavirus nephropathy (PVN). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, DHHS, Transplantat Branch, Bethesda, MD USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 541 BP 307 EP 307 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500541 ER PT J AU Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA AF Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA TI Time-dependent changes in gene expression in a rat cardiac transplant model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 546 BP 308 EP 308 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500546 ER PT J AU Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA AF Deans, KJ Minneci, PC Hergen, AE Logun, C Sittler, KJ Barb, JJ Munson, PJ Danner, RL Solomon, MA TI Gene expression profiles in a rat heart transplant model of acute cellular rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 545 BP 308 EP 308 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500545 ER PT J AU Akpinar, E Park, J Hale, DA AF Akpinar, E Park, J Hale, DA TI Establishment of a bone marrow (BM) expansion system for ex vivo generation of cells with potent capacity to prolong skin graft survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 630 BP 329 EP 329 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500630 ER PT J AU Dhanireddy, KK Xu, H Preston, EH Pearl, JP Leopardi, FV Johnson, LB Kirk, AD AF Dhanireddy, KK Xu, H Preston, EH Pearl, JP Leopardi, FV Johnson, LB Kirk, AD TI Alloantibody develops coincident with rejection of skin and renal allografts in non-human primates treated with the anti CD-154 monoclonal antibody IDEC-131 combined with donor specific transfusion (DST) and sirolimus. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 640 BP 332 EP 332 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500640 ER PT J AU Hoffmann, SC Kampen, RL Pearl, JP Hale, DA Jacobson, LM Kleiner, DE Mannon, RB Muehrer, RJ Swanson, SJ Becker, BN Kirk, AD AF Hoffmann, SC Kampen, RL Pearl, JP Hale, DA Jacobson, LM Kleiner, DE Mannon, RB Muehrer, RJ Swanson, SJ Becker, BN Kirk, AD TI The new standard of care: Alemtuzumab induction with Tacrolimus and Sirolimus maintenance immunosuppression to limit acute and chronic allograft rejection. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, Bethesda, MD USA. Univ Wisconsin, Med Ctr, Madison, WI 53706 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 639 BP 332 EP 332 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500639 ER PT J AU Akpinar, E Keary, JM Kurlander, R Hale, DA AF Akpinar, E Keary, JM Kurlander, R Hale, DA TI Measurement of chimerism in cynomolgus monkeys using human specific short tandem repeat (STR) based assay. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. CC NIH, Hematol DLM, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 644 BP 333 EP 333 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500644 ER PT J AU Cendales, LC Kleiner, D Eckhaus, MA Kampen, R Kirk, AD AF Cendales, LC Kleiner, D Eckhaus, MA Kampen, R Kirk, AD TI Characterization of human and non-human primate composite tissue allograft rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 672 BP 341 EP 341 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500672 ER PT J AU Hering, BJ Close, NC Anand, R Eggerman, TL AF Hering, BJ Close, NC Anand, R Eggerman, TL TI Collaborative Islet Transplant Registry (CITR). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Minnesota, Diabet Inst Immunol & Transplantat, Minneapolis, MN 55455 USA. EMMES Corp, Rockville, MD USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 804 BP 377 EP 377 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500803 ER PT J AU Xu, H Zhang, XJ Kirk, AD AF Xu, H Zhang, XJ Kirk, AD TI Monocytes engulf endothelial membranes via a scavenger receptor, and scavenger receptor blockade prevents monocyte activation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 863 BP 393 EP 393 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500862 ER PT J AU Hoffmann, SC Pearl, JP Hale, DA Mannon, RB Swanson, SJ Kirk, AD AF Hoffmann, SC Pearl, JP Hale, DA Mannon, RB Swanson, SJ Kirk, AD TI Early allograft rejection is mediated by CD3+CD4+CD45RA-CD62L-memory cells following alemtuzumab depletion. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, Bethesda, MD USA. Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 934 BP 413 EP 413 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322500933 ER PT J AU Morgun, A Shulzhenko, N Perez-Diez, A Matzinger, P Gerbase-DeLima, M AF Morgun, A Shulzhenko, N Perez-Diez, A Matzinger, P Gerbase-DeLima, M TI Using gene chips to discriminate among rejection, non-rejection and Chagas' disease reactivation in heart transplants SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 UNIFESP, Dept Pediat, Sao Paulo, Brazil. NIAID, LCMI, NIH, Bethesda, MD 20892 USA. RI Gerbase-DeLima, Maria/K-2515-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1082 BP 454 EP 454 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501080 ER PT J AU Elster, EA Hale, D Cendales, LB Kleiner, D Ring, M Niles, B Swanson, SJ Mannon, RB Kirk, AD AF Elster, EA Hale, D Cendales, LB Kleiner, D Ring, M Niles, B Swanson, SJ Mannon, RB Kirk, AD TI Correlation of renal resistance index and biopsy proven chronic allograft nephropathy: A part of the general transplant physical exam SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Transplantat Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1196 BP 485 EP 485 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501193 ER PT J AU Cendales, LC Zhang, XJ Xu, H Bacher, J Kirk, AD AF Cendales, LC Zhang, XJ Xu, H Bacher, J Kirk, AD TI Composite tissue allotransplantation: Development of a non-human primate model SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Bethesda, MD USA. NIH, Div Vet Resources, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1276 BP 508 EP 508 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501272 ER PT J AU Cheng, OH Zhang, XJ Grottendorst, G Mannon, RB AF Cheng, OH Zhang, XJ Grottendorst, G Mannon, RB TI Modulating chronic graft injury: A new role for connective tissue growth factor (CTGF) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, Bethesda, MD USA. Univ Miami, Miami, FL 33152 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1336 BP 524 EP 524 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501332 ER PT J AU Akpinar, E Keary, JM Preston, E Xu, H Kurlander, R Hale, DA AF Akpinar, E Keary, JM Preston, E Xu, H Kurlander, R Hale, DA TI The trials and tribulations of translating a murine tolerance model to the nonhuman primate. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. NIH, Ctr Clin, Hematol DLM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1341 BP 526 EP 526 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501337 ER PT J AU Xu, H Dhanireddy, KK Kirk, AD AF Xu, H Dhanireddy, KK Kirk, AD TI Monocytes act as a bridge between T cells and allogeneic endothelial cells via IFN gamma-dependent processes. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1386 BP 538 EP 538 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501382 ER PT J AU Elster, EA Chamberlain, C Salaita, C Kirk, AD Hale, D Mannon, RB AF Elster, EA Chamberlain, C Salaita, C Kirk, AD Hale, D Mannon, RB TI Steroids have no calories: Weight gain post transplantation is not prevented by steroid avoidance. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, DHHS, Transplantat Branch, Bethesda, MD USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1411 BP 545 EP 545 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501407 ER PT J AU Shapiro, J Ricordi, C Hering, B DiMercurio, B Lindblad, R Cagliero, E Brendel, M Robertson, P Berney, T Secchi, A Brennan, D Ramos, E Viviano, L Ryan, E Close, N Lakey, J AF Shapiro, J Ricordi, C Hering, B DiMercurio, B Lindblad, R Cagliero, E Brendel, M Robertson, P Berney, T Secchi, A Brennan, D Ramos, E Viviano, L Ryan, E Close, N Lakey, J TI International multicenter trial of islet transplantation using the Edmonton Protocol in patients with Type 1 diabetes SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Alberta, Edmonton, AB T6G 2M7, Canada. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Miami, Miami, FL 33152 USA. NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Giessen, D-35390 Giessen, Germany. Pacific NW Res Inst, Seattle, WA USA. Univ Geneva, CH-1211 Geneva 4, Switzerland. Univ Milan, I-20122 Milan, Italy. Washington Univ, St Louis, MO 63130 USA. Immune Tolerance Network, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1434 BP 552 EP 552 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501430 ER PT J AU Tao, R Ye, QR Han, RX Love, PE Hancock, WW AF Tao, R Ye, QR Han, RX Love, PE Hancock, WW TI Exploiting tissue-specific homing to therapeutic effect: Targeting the TECK/CCR9 pathway prolongs small bowel allograft survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Univ Penn, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1462 BP 559 EP 559 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501458 ER PT J AU Chamberlain, CE Elster, E Hale, D Kirk, AD Daniels, CE Mannon, RB AF Chamberlain, CE Elster, E Hale, D Kirk, AD Daniels, CE Mannon, RB TI Weaker and weaker still: Steroid avoidance does not prevent bone loss following kidney transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIH, Ctr Clin, DHHS, Dept Pharm, Bethesda, MD 20892 USA. NIDDK, NIH, DHHS, Transplantat Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1485 BP 566 EP 566 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501481 ER PT J AU Xu, H Zhang, XJ Leopradi, F Mannon, RB Kirk, AD AF Xu, H Zhang, XJ Leopradi, F Mannon, RB Kirk, AD TI Human platelet-derived CD154 plays an important role in initiating allograft rejetion SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1542 BP 581 EP 581 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501538 ER PT J AU Zhang, XJ Cheng, OH Mannon, RB AF Zhang, XJ Cheng, OH Mannon, RB TI Connective tissue growth factor (CTGF): A potential effector of ischemia/reperfusion injury (IRI). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT American Transplant Congress CY MAY 14-19, 2004 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 NIDDK, NIH, DHHS, Transplantat Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2004 VL 4 SU 8 MA 1569 BP 589 EP 589 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 819NT UT WOS:000221322501565 ER PT J AU Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Bridge, P Mintz, J AF Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Bridge, P Mintz, J TI Cortical gray matter volumes are associated with subjective responses to cocaine infusion SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MAGNETIC-RESONANCE; BRAIN MORPHOLOGY; IN-VIVO; AGE; ABUSERS; LOBE; ADDICTS; MRI; ABNORMALITIES; HIPPOCAMPUS AB We analyzed the relationship between cocaine-induced euphoria and measures of frontal and temporal gray matter volumes in eleven cocaine-dependent (CD) patients who underwent magnetic resonance imaging (MRI). Self-reported ratings of the intensity of euphoric response to cocaine infusion were obtained from the CD subjects at 3, 10, and 30 minutes after cocaine infusion. Significant positive correlation between frontal and temporal cortical gray matter volume and the intensity of euphoria was observed at 10 minutes after IV cocaine. The data suggest that frontal and temporal lobe gray matter volume is associated with some of the reinforcing effects of cocaine. Given the well-established negative linear relationship between cortical gray matter volume and age, cortical gray matter volume may be a marker for the neurobiological substrate of the age-related reduction in addiction rates. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. NIDA, Medicat Dev Div, Rockville, MD USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Alzheimers Dis Ctr, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 NR 30 TC 13 Z9 16 U1 1 U2 3 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2004 VL 13 IS 1 BP 64 EP 73 DI 10.1080/10550490490265352 PG 10 WC Substance Abuse SC Substance Abuse GA 771EH UT WOS:000188772300006 PM 14766439 ER PT J AU Amass, L Ling, W Freese, TE Reiber, C Annon, JJ Cohen, AJ McCarty, D Reid, MS Brown, LS Clark, C Ziedonis, DM Krejci, J Stine, S Winhusen, T Brigham, G Babcock, D Muir, JA Buchan, BJ Horton, T AF Amass, L Ling, W Freese, TE Reiber, C Annon, JJ Cohen, AJ McCarty, D Reid, MS Brown, LS Clark, C Ziedonis, DM Krejci, J Stine, S Winhusen, T Brigham, G Babcock, D Muir, JA Buchan, BJ Horton, T TI Bringing buprenorphine-naloxone detoxification to community treatment providers: The NIDA Clinical Trials Network field experience SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID OPIOID-DEPENDENT HUMANS; RANDOMIZED CONTROLLED-TRIAL; METHADONE-MAINTENANCE; INTRAVENOUS BUPRENORPHINE; OPIATE ADDICTS; MAINTAINED VOLUNTEERS; HEROIN DEPENDENCE; DRUG-ABUSE; FOLLOW-UP; WITHDRAWAL AB In October 2002, the U.S. Food and Drug Administration approved buprenorphine naloxone (Suboxone(R)) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Dials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women mere randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence. C1 Friends Res Inst Inc, Pacific Reg Node, Los Angeles, CA 90025 USA. NIDA, Natl Drug Abuse Treatment Clin Trials Network, Lexington, KY USA. Univ Calif Los Angeles, Integrated Subst Abuse Programs, Pacific Reg Node, Los Angeles, CA USA. Aegis Med Syst Inc, Pacific Reg Node, Oxnard, CA USA. Oregon Hlth & Sci Univ, Sch Med, Oregon Node, Portland, OR 97201 USA. NYU, Sch Med, New York Node, New York, NY USA. Addict Res & Treatment Corp, New York Node, Brooklyn, NY USA. Treatment Res Inst, Delaware Valley Node, Philadelphia, PA USA. Robert Wood Johnson Med Sch, Delaware Valley Node, Piscataway, NJ USA. Mercer Trenton Addict Sci Ctr, Delaware Valley Node, Trenton, NJ USA. Wayne State Univ, Sch Med, Great Lakes Reg Node, Detroit, MI USA. Univ Cincinnati, Ohio Valley Node, Cincinnati, OH USA. Maryhaven, Ohio Valley Node, Columbus, OH USA. Midtown Community Mental Hlth Ctr, Ohio Valley Node, Indianapolis, IN USA. Univ Miami, Ctr Studies Family, Florida Node, Miami, FL 33152 USA. Operat PAR Inc, Florida Node, St Petersburg, FL USA. Phoenix House, Long Isl Reg Node, New York, NY USA. RP Amass, L (reprint author), Friends Res Inst Inc, Pacific Reg Node, 11075 Santa Monica Blvd,Suite 200, Los Angeles, CA 90025 USA. EM lamass@friendsresearch.org OI Stine, Susan/0000-0001-5426-4448; Brigham, Gregory/0000-0003-1150-4493; Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [U10 DA 13720, U10 DA 13035, U10 DA 13036, U10 DA 13043, U10 DA 13045, U10 DA 13046, U10 DA 13710, U10 DA 13732, U10 DA013035, U10 DA013036, U10 DA013043, U10 DA013045, U10 DA013046, U10 DA013710, U10 DA013720, U10 DA013732] NR 89 TC 81 Z9 83 U1 3 U2 7 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2004 VL 13 SU 1 BP S42 EP S66 DI 10.1080/10550490490440807 PG 25 WC Substance Abuse SC Substance Abuse GA 819ZM UT WOS:000221355300005 PM 15204675 ER PT J AU Fozard, JL Norman, DA Thomas, JC Barr, RA AF Fozard, JL Norman, DA Thomas, JC Barr, RA TI Nancy Collier Waugh (1930-2002) - Obituary SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 Florida Gerontol Res & Training Serv, Palm Harbor, FL 32137 USA. Northwestern Univ, Evanston, IL 60208 USA. IBM Res Hawthorne, Yorktown Hts, NY USA. NIA, Bethesda, MD 20892 USA. RP Fozard, JL (reprint author), Florida Gerontol Res & Training Serv, Palm Harbor, FL 32137 USA. RI Fozard, James Leonard/B-3660-2009 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD JAN PY 2004 VL 59 IS 1 BP 45 EP 45 DI 10.1037/0003-066X.59.1.45 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 765LP UT WOS:000188285300007 PM 14736321 ER PT J AU Keohavong, P Gao, WM Zheng, KC Mady, H Lan, Q Melhem, M Mumford, J AF Keohavong, P Gao, WM Zheng, KC Mady, H Lan, Q Melhem, M Mumford, J TI Detection of K-ras and p53 mutations in sputum samples of lung cancer patients using laser capture microdissection microscope and mutation analysis SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE lung cancer; sputum; laser capture microdissection; K-ras and p53 mutations ID BRONCHOALVEOLAR LAVAGE FLUID; TUMOR-SUPPRESSOR GENE; ONCOGENE MUTATIONS; EARLY DIAGNOSIS; CELL CARCINOMA; HIGH-FREQUENCY; ADENOCARCINOMA; TISSUES; DNA; AMPLIFICATION AB Mutations in the p53 tumor suppressor gene and the K-ras oncogene have been frequently found in, sputum and bronchoalveolar lavage (BAL) samples of lung cancer patients and other patients prior to presenting clinical symptoms of lung cancer, suggesting that they may provide useful biomarkers for early lung cancer diagnosis. However, the detection of these gene mutations in sputum and BAL samples has been complicated by the fact that they often occur in only a small fraction of epithelial cells among sputum cells and, in the case of p53 gene, at many codons. In this study, sputum cells were collected on a filter membrane by sputum cytocentrifugation and morphologically analyzed. Epithelial cells were selectively taken by using a laser capture microdissection microscope and analyzed by polymerase chain reaction (PCR) and single-stranded conformational polymorphism (SSCP) for p53 mutations and by PCR and denaturing gradient gel electrophoresis (DGGE) for K-ras mutations. This method was used to analyze sputum of 15 Chinese women with lung cancer from Xuan Wei County, China and detected mutations in sputum of 7 (46.7%) patients, including 5 patients with p53 mutations, 1 patient with a K-ras mutation, and 1 patient with K-ras and p53 mutations. For comparison, only two of the mutations were detected by conventional methods. Therefore, the laser capture/mutation analysis method is sensitive and facilitates the detection of low-fraction mutations occurring throughout the p53 and K-ras genes in sputum of lung cancer patients. This method may be applicable to the analysis of epithelial cells from clinically normal sputum or BAL samples from individuals with a high risk for developing lung cancer. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pathol, Sch Med, Pittsburgh, PA 15240 USA. Vet Adm Hlth Care Syst, Pittsburgh, PA 15240 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. US EPA, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA. RP Keohavong, P (reprint author), Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. OI Keohavong, Phouthone/0000-0001-7812-4925 NR 42 TC 21 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 2004 VL 324 IS 1 BP 92 EP 99 DI 10.1016/j.ab.2003.09.030 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 757MR UT WOS:000187566500013 PM 14654050 ER PT J AU Westergaard, GC Liv, C Rocca, AM Cleveland, A Suomi, SJ AF Westergaard, GC Liv, C Rocca, AM Cleveland, A Suomi, SJ TI Tufted capuchins (Cebus apella) attribute value to foods and tools during voluntary exchanges with humans SO ANIMAL COGNITION LA English DT Article DE Cebus apella; tool use; exchange; barter; food sharing ID MONKEYS; CAPUCINUS; PREDATION AB This research examined exchange and value attribution in tufted capuchin monkeys (Cebus apella). We presented subjects with opportunities to obtain various foods and a tool from an experimenter in exchange for the foods or tool in the subjects' possession. The times elapsed before the first chow biscuits were expelled and/or an exchange took place were recorded as the dependent measures. Laboratory chow biscuits, grapes, apples, and a metal bolt (a tool used to probe for syrup) were used as experimental stimuli. The subjects demonstrated the ability to recognize that exchanges could occur when an experimenter was present with a desirable food. Results indicate that subjects exhibited significant variation in their willingness to barter based upon the types of foods that were both in their possession and presented by the experimenter. Subjects more readily traded chow biscuits for fruit, and more readily traded apples for grapes than grapes for apples. During the exchange of tools and food, the subjects preferred the following in descending order when the probing apparatus was baited with sweet syrup: grapes, metal bolts, and chow biscuits. However when the apparatus was not baited, the values changed to the following in descending order: grapes, chow, and metal bolts. These results indicate that tufted capuchins recognize opportunities to exchange and engage in a simple barter system whereby low-valued foods are readily traded for more highly valued food. Furthermore, these capuchins demonstrate that their value for a tool changes depending upon its utility. C1 LABS Virginia Inc, Div Res & Dev, Yemassee, SC 29945 USA. NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Westergaard, GC (reprint author), LABS Virginia Inc, Div Res & Dev, 95 Castle Hall Rd,POB 557, Yemassee, SC 29945 USA. EM Gwprimaie@netscape.net NR 18 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER-VERLAG HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1435-9448 J9 ANIM COGN JI Anim. Cogn. PD JAN PY 2004 VL 7 IS 1 BP 19 EP 24 DI 10.1007/s10071-003-0181-z PG 6 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 776DF UT WOS:000189100900003 PM 12884078 ER PT J AU Ronckers, C Land, C Hayes, R Verduijn, P Van Leeuwen, F AF Ronckers, C Land, C Hayes, R Verduijn, P Van Leeuwen, F TI Factors impacting questionnaire response in a dutch retrospective cohort study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE questionnaires; epidemiologic methods; response rates; cohort studies ID NASOPHARYNGEAL RADIUM IRRADIATION; CANCER INCIDENCE; POSTAL QUESTIONNAIRES; MAILING STRATEGIES; RANDOMIZED TRIAL; RATES; POPULATION; LENGTH; INCENTIVES; MORTALITY AB PURPOSE: To study questionnaire length, type of consent, approach to recruitment, and subject characteristics on participation in epidemiologic studies. METHODS: As part of a health survey among Dutch subjects treated for ear, nose, and throat disorders in childhood, we conducted a pilot study of 200 individuals who were randomly assigned to one of four categories, defined by length of questionnaire (long vs. short) and type of consent form (basic vs. multi-option). In addition, among 8402 subjects eligible to be in the main study (average age 41 years in 1997), we examined the effect of approach to recruitment and subject characteristics on participation rates. RESULTS: The pilot study showed a non-significant 10% increase in participation rate using the shorter questionnaire, but no differences by type of consent form. In the full survey, the participation rate was 49% after the first mailing. Response increased by 15% after a written reminder and by 10% after a telephone survey. The total participation rate was 74%. Attained age, sex, exposure status, age at exposure, and response to an earlier survey were determinants of participation rates. Among male non-participants, outright refusal was less frequent than non-response. The refusal rate, unlike the non-response rate, was positively associated with older age at time of survey. CONCLUSION: Health survey participation is influenced by questionnaire length, frequency of contact, and subject characteristics. (C) 2003 Elsevier Inc. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Reinaert Klin, Maastricht, Netherlands. Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. RP Ronckers, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01CP330013] NR 31 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2004 VL 14 IS 1 BP 66 EP 72 DI 10.1016/S1047-2797(03)00123-6 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 755WR UT WOS:000187434900010 PM 14664782 ER PT J AU Klebanoff, MA Longnecker, MP AF Klebanoff, MA Longnecker, MP TI Regarding "An unexpected distribution of sodium concentration in serum specimens stored for more than 30 years" - Response SO ANNALS OF EPIDEMIOLOGY LA English DT Letter ID SPONTANEOUS-ABORTION; CAFFEINE INTAKE; PARAXANTHINE; PREGNANCY; RISK C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Klebanoff, MA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2004 VL 14 IS 1 BP 79 EP 80 DI 10.1016/S1047-2797(03)00247-3 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 755WR UT WOS:000187434900013 ER PT J AU Li, Z Gastwirth, JL AF Li, Z Gastwirth, JL TI On the power of affected relative pair designs for linkage studies SO ANNALS OF HUMAN GENETICS LA English DT Article ID GENETICALLY COMPLEX TRAITS; STRATEGIES AB Using the recurrence risk ratio (lambda), Risch (1990b) indicated that affected pairs of distant relatives are preferable to affected sib-pairs for linkage analysis when lambda is large and the mode of inheritance is additive. By using the optimum test for affected sib-pairs instead of the test used by Risch (1990b), the range of values of lambda for which the affected sib-pair design has larger or smaller power than other pairs is clarified. Risch's conclusion remains true when; lambda(O) > 2.5, however, sib-pairs have larger power for lower values. As affected sib-pairs occur smore frequently than other relative pairs, when ascertainment costs are non-negligible, they may be the most cost-effective relative pairs to use. C1 George Washington Univ, Dept Stat, Washington, DC 20052 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. RP Li, Z (reprint author), George Washington Univ, Dept Stat, 315 Funger Hall, Washington, DC 20052 USA. EM zli@gwu.edu FU NEI NIH HHS [EY14478] NR 10 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2004 VL 68 BP 65 EP 68 DI 10.1046/j.1529-8817.2003.00066.x PN 1 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 771JX UT WOS:000188782800006 PM 14748831 ER PT J AU Koulu, M Movafagh, S Tuohimaa, J Jaakkola, U Kallio, J Pesonen, U Geng, YX Karvonen, MK Vainio-Jylha, E Pollonen, M Kaipio-Salmi, K Seppala, H Lee, EW Higgins, RD Zukowska, Z AF Koulu, M Movafagh, S Tuohimaa, J Jaakkola, U Kallio, J Pesonen, U Geng, YX Karvonen, MK Vainio-Jylha, E Pollonen, M Kaipio-Salmi, K Seppala, H Lee, EW Higgins, RD Zukowska, Z TI Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization SO ANNALS OF MEDICINE LA English DT Article DE neuropeptide Y; retinopathy; Y2-receptor ID OXYGEN-INDUCED RETINOPATHY; ENDOTHELIAL GROWTH-FACTOR; PROLINE 7 POLYMORPHISM; PREPRONEUROPEPTIDE-Y; SIGNAL PEPTIDE; MOUSE MODEL; CAROTID ATHEROSCLEROSIS; ISCHEMIC ANGIOGENESIS; LEU7PRO POLYMORPHISM; ALCOHOL DEPENDENCE AB BACKGROUND: Neuropeptide Y is a sympathetic neurotransmitter, a potent endothelium-derived angiogenic factor and a vascular mitogen. We have studied the role of the functional leucine7 to proline7 polymorphism of the signal peptide region of preproneuropeptide Y (prepro-NPY) as a genetic susceptibility factor for diabetic retinopathy. In addition, we investigated the role of the NPY Y2-receptor as a putative mediator of angiogenic NPY signaling in the retina. METHODS: Frequencies of proline7 (Pro7) carriers in the prepro-NPY were determined in type 1 and type 2 diabetes patients having retinopathy, in type 2 diabetes patients without retinopathy and in healthy control subjects. The role of Y2-receptor in hyperoxemia-induced retinal neovascularization was investigated in Y2-receptor knockout mice (Y2(-/-)) and in rats administered Y2-receptor mRNA antisense oligonucleotide. RESULTS: The carriers having Pro? in the preproNPY are markedly over-represented among type 2 diabetes patients with retinopathy compared to type 2 diabetes patients without retinopathy and to the population control. Neonatal exposure to hyperoxia resulted in development of retinal neovascularization that was prevented in Y2(-/-)-mice, and significantly inhibited in rats treated with the Y2-receptor antisense oligonucleotide. CONCLUSIONS: NPY and Y2-receptor play important roles in diabetic retinopathy and retinal neovascularization and are thus potential new targets for drug molecules for treatment of retinopathy. C1 Univ Turku, Dept Pharmacol & Clin Pharmacol, Turku 20520, Finland. Georgetown Univ, Dept Physiol & Biophys, Med Ctr, Washington, DC 20057 USA. Turku Univ Hosp, Dept Ophthalmol, FIN-20520 Turku, Finland. Hormos Med Corp, Turku, Finland. Turku City Hosp, Dept Ophthalmol, Turku, Finland. NICHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD USA. RP Zukowska, Z (reprint author), Univ Turku, Dept Pharmacol & Clin Pharmacol, Itainen Pitkakatu 4B, Turku 20520, Finland. EM mkoulu@utu.fi; zzukow0l@georgetown.edu OI Lee, Edward/0000-0003-0418-1454 FU NHLBI NIH HHS [HL67357] NR 33 TC 44 Z9 45 U1 2 U2 4 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2004 VL 36 IS 3 BP 232 EP 240 DI 10.1080/07853890410031236 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 823HJ UT WOS:000221600900008 PM 15181979 ER PT J AU Goldstein, DS AF Goldstein, DS TI Spinal cord stimulation for chronic reflex sympathetic dystrophy SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID PAIN; MECHANISMS; SKIN; CRPS C1 Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 16 TC 3 Z9 3 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2004 VL 55 IS 1 BP 5 EP 6 DI 10.1002/ana.10857 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 762AW UT WOS:000187948500002 PM 14705105 ER PT J AU Chalela, JA Kang, DW Luby, M Ezzeddine, M Latour, LL Todd, JW Dunn, B Warach, S AF Chalela, JA Kang, DW Luby, M Ezzeddine, M Latour, LL Todd, JW Dunn, B Warach, S TI Early MRI findings in patients receiving tissue plasminogen activator predict outcome: Insights into the pathophysiology of acute stroke in the thrombolysis era SO ANNALS OF NEUROLOGY LA English DT Article ID PERFUSION-WEIGHTED MRI; ACUTE ISCHEMIC-STROKE; DIFFUSION; THERAPY; TPA; HEMORRHAGE; INJURY AB We measured ischemic brain changes with diffusion and perfusion MRI in 42 ischemic stroke patients before and 2 hours (range approximately 1.5 to 4.5 hours) after standard intravenous tissue plasminogen activator (tPA) therapy. The median time from stroke onset to tPA was 131 minutes. Clinical and MRI variables (change in perfusion and/or diffusion weighted lesion volume) were compared between those with excellent outcome defined as 3-month modified Rankin score (mRS) of 0 to 1 and those with incomplete recovery (mRS > 1). In multivariate logististic regression analysis, the most powerful independent predictor for excellent outcome was improved brain perfusion: hypoperfusion volume on mean transit time (MTT) map decrease >30% from baseline to 2-hour post tPA scan (p = 0.009; odds ratio [95% confidence interval], 20.7 [2.1-203.9]). Except for age <70 years, no other baseline clinical or imaging variable was an independent predictor of outcome. We propose MTT lesion volume decrease more than 30% 2 hours after tPA as an early marker of long-term clinical benefit of thrombolytic therapy. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Chalela, JA (reprint author), 10 Ctr Dr,Room B1D733,MSC 1063, Bethesda, MD 20892 USA. EM chalelaj@ninds.nih.gov NR 13 TC 67 Z9 71 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2004 VL 55 IS 1 BP 105 EP 112 DI 10.1002/ana.10781 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 762AW UT WOS:000187948500015 PM 14705118 ER PT J AU Evans, EW Hague, S Singleton, A AF Evans, EW Hague, S Singleton, A TI The R98Q variation in DJ-1 represents a rare polymorphism - Reply SO ANNALS OF NEUROLOGY LA English DT Letter ID PARKINSONS-DISEASE C1 NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Evans, EW (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 NR 3 TC 1 Z9 1 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2004 VL 55 IS 1 BP 145 EP 146 DI 10.1002/ana.10817 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 762AW UT WOS:000187948500025 ER PT J AU Dancey, J AF Dancey, Janet TI The Importance of Patient Selection in Trials of Molecularly Targeted Therapies SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Dancey, Janet] NCI, Div Canc Treatment, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 4 EP 4 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900011 ER PT J AU Di Blasio, B Ardizzoni, A Camisa, R Ceci, G Bisagni, G Boni, C Bruzzi, P Cocconi, G AF Di Blasio, Beatrice Ardizzoni, Andrea Camisa, Roberta Ceci, Guido Bisagni, Giancarlo Boni, Corrado Bruzzi, P. Cocconi, Giorgio TI PRIMARY CHEMOTHERAPY (PC) IN OPERABLE BREAST CARCINOMA COMPARING CMF WITH AN ANTHRACYCLINE-CONTAINING REGIMEN (CMFEV): RELATIONSHIP BETWEEN THE SHORT-TERM CLINICAL COMPLETE RESPONSE AND THE LONG-TERM OUTCOME SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Di Blasio, Beatrice; Ardizzoni, Andrea; Camisa, Roberta; Ceci, Guido; Cocconi, Giorgio] Univ Hosp, Med Oncol Unit, Parma, Italy. [Bisagni, Giancarlo; Boni, Corrado] Arcispedale S Maria Nuova, Med Oncol Unit, Reggio Emilia, Italy. [Bruzzi, P.] Natl Canc Inst, Epidemiol Unit, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 2 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA V14FR UT WOS:000207720800081 ER PT J AU Lee, FT Mountain, A Rigopolous, A Smyth, F Brechbiel, M Scott, A AF Lee, Fook T. Mountain, Angela Rigopolous, Angela Smyth, Fiona Brechbiel, Martin Scott, Andrew TI Epidermal growth factor receptor TK inhibitor AG1478 enhances radioimmunotherapy of A431 human epidermoid carcinoma xenografts SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 [Lee, Fook T.; Mountain, Angela; Rigopolous, Angela; Smyth, Fiona; Scott, Andrew] Ludwig Inst Canc Res, Tumor Targeting Program, Heidelberg, Vic, Australia. [Brechbiel, Martin] NIH, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 3 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA V14FS UT WOS:000207720900099 ER PT J AU Stevens, EV Posadas, EM Davidson, B Kohn, EC AF Stevens, EV Posadas, EM Davidson, B Kohn, EC TI Proteomics in cancer SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 29th Congress of the European-Society-for-Medical-Oncology (ESMO) CY OCT 29-NOV 02, 2004 CL Vienna, AUSTRIA SP European Soc Med Oncol ID LASER-DESORPTION/IONIZATION-TIME; FLIGHT-MASS-SPECTROMETRY; OVARIAN-CANCER; PROSTATE-CANCER; CLINICAL PROTEOMICS; CELL LINES; SERUM; IDENTIFICATION; PATTERNS; BIOMARKERS C1 NCI, Mol Signaling Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Stevens, EV (reprint author), NCI, Mol Signaling Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NR 36 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 4 BP 167 EP 171 DI 10.1093/annonc/mdh922 PG 5 WC Oncology SC Oncology GA 873QK UT WOS:000225295600024 ER PT J AU Dancey, JE AF Dancey, JE TI Molecular targeting: P13 kinase pathway SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 29th Congress of the European-Society-for-Medical-Oncology (ESMO) CY OCT 29-NOV 02, 2004 CL Vienna, AUSTRIA SP European Soc Med Oncol ID BREAST-CANCER CELLS; ETHER LIPID ANALOGS; IN-VITRO; PROTEIN-KINASE; INDUCED APOPTOSIS; UCN-01 7-HYDROXYSTAUROSPORINE; ALKYL-LYSOPHOSPHOLIPIDS; CLINICAL-PHARMACOLOGY; PRECLINICAL MODELS; ANTITUMOR-ACTIVITY C1 Natl Canc Inst, Investigat Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. RP Dancey, JE (reprint author), Natl Canc Inst, Investigat Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. NR 73 TC 34 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2004 VL 15 SU 4 BP 233 EP 239 DI 10.1093/annonc/mdh932 PG 7 WC Oncology SC Oncology GA 873QK UT WOS:000225295600034 ER PT J AU Weissberg, RP O'Brien, MU AF Weissberg, RP O'Brien, MU TI What works in school-based social and emotional learning programs for positive youth development SO ANNALS OF THE AMERICAN ACADEMY OF POLITICAL AND SOCIAL SCIENCE LA English DT Article; Proceedings Paper CT Conference on Positive Development - Realizing the Potential of Youth CY 2003 CL UNIV PENN, PHILADELPHIA, PENNSYLVANIA SP Annenberg Fdn Trust Sunnylands HO UNIV PENN DE social and emotional learning; school; children; prevention ID ADOLESCENT HEALTH; PREVENTION; CHILDREN; COMPETENCE; BEHAVIORS AB Two challenges for researchers of school-based action are to identify effective approaches to prevent problem behaviors and promote positive youth development and to support the widespread implementation and sustainability of evidence-based preschool through high school practice. In this article, the authors describe integrated social, emotional, and academic education as a useful framework for conceptualizing school-based positive youth development programming. We then review findings from selected exemplary studies and research syntheses to support this perspective. We conclude with guidelines for implementing integrated social, emotional, and academic learning programs. C1 Univ Illinois, CASEL, NIMH, Chicago, IL 60680 USA. RP Weissberg, RP (reprint author), Univ Illinois, CASEL, NIMH, Chicago, IL 60680 USA. NR 37 TC 38 Z9 38 U1 2 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7162 J9 ANN AM ACAD POLIT SS JI Ann. Am. Acad. Polit. Soc. Sci. PD JAN PY 2004 VL 591 BP 86 EP 97 DI 10.1177/0002716203260093 PG 12 WC Political Science; Social Sciences, Interdisciplinary SC Government & Law; Social Sciences - Other Topics GA 753FU UT WOS:000187222100007 ER PT J AU Parks, CG Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS Pandey, JP AF Parks, CG Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS Pandey, JP TI Systemic lupus erythematosus and genetic variation in the interleukin 1 gene cluster: a population based study in the southeastern United States SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID IL-1 RECEPTOR ANTAGONIST; MONONUCLEAR-CELLS; CHINESE PATIENTS; PLASMA-LEVELS; POLYMORPHISM; ASSOCIATION; IL-1-BETA; IL1A AB Background: Interleukin (IL)1alpha and IL1beta, and their endogenous receptor antagonist (IL1Ra), have been related to the pathology of systemic lupus erythematosus (SLE), but the role of IL1 polymorphisms in the aetiology of SLE is unknown. Objective: To examine polymorphisms at IL1alpha -889(C-->T), IL1alpha +4845(C-->T), IL1beta -511(C-->T), IL1beta +3953(G-->T), and IL1Ra (86 bp VNTR) in a population based study of SLE in North Carolina and South Carolina. Methods: Genotypes from 230 cases who met ACR classification criteria, and from 275 controls matched for age, sex, and state, were analysed separately for African Americans and whites. Odds ratios (ORs) were estimated by logistic regression models for each locus alone and also after adjusting for polymorphisms at adjacent loci. Results: An increased risk of SLE for the IL1alpha -889C/C genotype compared with carriage of the -889T allele was found in both African Americans (OR = 3.1, p = 0.001) and whites ( OR = 2.9, p = 0.005). In African Americans, carriage of the IL1beta -511T allele was associated with a higher risk of SLE than carriage of the -511C/C genotype (OR = 2.4, p = 0.017), independent of variation at IL1alpha -889. Conclusions: The observed associations support the hypothesis that genetic variation in IL1 is involved in the aetiology of SLE and merit further investigation. C1 NIEHS, Epidemiol Branch, NIH, DHHS, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Greenville, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, NIH, DHHS, A3-05,POB 12233, Durham, NC USA. OI Parks, Christine/0000-0002-5734-3456 NR 16 TC 58 Z9 64 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2004 VL 63 IS 1 BP 91 EP 94 DI 10.1136/ard.2003.007336 PG 4 WC Rheumatology SC Rheumatology GA 760JR UT WOS:000187808300020 PM 14672899 ER PT J AU Subramaniam, S Milne, JLS AF Subramaniam, S Milne, JLS TI Three-dimensional electron microscopy at molecular resolution SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE three-dimensional imaging; three-dimensional reconstruction; electron tomography; cryo-electron microscopy; automation ID 7.5 ANGSTROM RESOLUTION; S-RIBOSOMAL SUBUNITS; CRYOELECTRON MICROSCOPY; ESCHERICHIA-COLI; TILT SERIES; ATOMIC-RESOLUTION; MACROMOLECULAR COMPLEXES; BIOLOGICAL STRUCTURES; RELATIONAL DATABASE; 3D RECONSTRUCTION AB Emerging methods in cryo-electron microscopy allow determination of the three-dimensional architectures of objects ranging in size from small proteins to large eukaryotic cells, spanning a size range of more than 12 orders of magnitude. Advances in determining structures by "single particle" microscopy and by "electron tomography" provide exciting opportunities to describe the structures of subcellular assemblies that are either too large or too heterogeneous to be investigated by conventional crystallographic methods. Here, we review selected aspects of progress in structure determination by cryo-electron microscopy at molecular resolution, with a particular emphasis on topics at the interface of single particle and tomographic approaches. The rapid pace of development in this field suggests that comprehensive descriptions of the structures of whole cells and organelles in terms of the spatial arrangements of their molecular components may soon become routine. C1 NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. EM ss1@nih.gov; jmilne@nih.gov NR 110 TC 55 Z9 58 U1 1 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 2004 VL 33 BP 141 EP 155 DI 10.1146/annurev.biophys.33.110502.140339 PG 19 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 833LV UT WOS:000222339700009 PM 15139808 ER PT J AU Lipsitz, RS Tjandra, N AF Lipsitz, RS Tjandra, N TI Residual dipolar couplings in NMR structure analysis SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE nuclear magnetic resonance; RDCs; structure determination; domain orientation ID LIQUID-CRYSTALLINE PHASE; PROTEIN-STRUCTURE DETERMINATION; ORIENTED PHOSPHOLIPID MICELLES; MALTODEXTRIN-BINDING-PROTEIN; DIRECT STRUCTURE REFINEMENT; DE-NOVO DETERMINATION; RELATIVE ORIENTATION; INDUCED ALIGNMENT; BIOLOGICAL MACROMOLECULES; DOMAIN ORIENTATION AB Residual dipolar couplings (RDCs) have recently emerged as a new tool in nuclear magnetic resonance (NMR) with which to study macromolecular structure and function in a solution environment. RDCs are complementary to the more conventional use of NOES to provide structural information. While NOES are local-distance restraints, RDCs provide long-range orientational information. RDCs are now widely utilized in structure calculations. Increasingly, they are being used in novel applications to address complex issues in structural biology such as the accurate determination of the global structure of oligonucleotides and the relative orientation of protein domains. This review briefly describes the theory and methods for obtaining RDCs and then describes the range of biological applications where RDCs have been used. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Lipsitz, RS (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM nico@helix.nih.gov; lipsitzr@nhlbi.nih.gov NR 76 TC 114 Z9 115 U1 3 U2 22 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 2004 VL 33 BP 387 EP 413 DI 10.1146/annurev.biophys.33.110502.140306 PG 29 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 833LV UT WOS:000222339700020 PM 15139819 ER PT J AU Wei, CJ Xu, X Lo, CW AF Wei, CJ Xu, X Lo, CW TI Connexins and cell signaling in development and disease SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE gap junction; knockout mice; motility; mutations; protein interaction ID GAP-JUNCTIONAL COMMUNICATION; ADULT-RAT CARDIOMYOCYTES; PROTEIN-KINASE-C; NEURAL CREST CELLS; ZONULAR PULVERULENT CATARACTS; IMPLANTATION MOUSE EMBRYO; MICE LACKING CONNEXIN43; MARIE-TOOTH DISEASE; N-CADHERIN; INTERCELLULAR COMMUNICATION AB Gap junctions contain hydrophilic membrane channels that allow direct communication between neighboring cells through the diffusion of ions, metabolites, and small cell signaling molecules. They are made up of a hexameric array of polypeptides encoded by the connexin multi-gene family. Cell-cell communication mediated by connexins is crucial to various cellular functions, including the regulation of cell growth, differentiation, and development. Mutations in connexin genes have been linked to a variety of human diseases, including cardiovascular anomalies, peripheral neuropathy, deafness, skin disorders, and cataracts. In addition to their coupling function, recent studies suggest that connexin proteins may also mediate signaling. This could involve interactions with other protein partners that may play a role not only in connexin assembly, trafficking, gating and turnover, but also in the coordinate regulation of cell-cell communication with cell adhesion and cell motility. The integration of these cell functions is likely to be important in the role of gap junctions in development and disease. C1 NHLBI, Dev Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Wei, CJ (reprint author), NHLBI, Dev Biol Lab, NIH, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM weic@nhlbi.nih.gov; xux@nhlbi.nih.gov; loc@nhlbi.nih.gov FU NHLBI NIH HHS [Z01 HL 005701] NR 183 TC 258 Z9 276 U1 1 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2004 VL 20 BP 811 EP 838 DI 10.1146/annurev.cellbio.19.111301.144309 PG 28 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 873YQ UT WOS:000225318200030 PM 15473861 ER PT J AU Steingrimsson, E Copeland, NG Jenkins, NA AF Steingrimsson, E Copeland, NG Jenkins, NA TI Melanocytes and the Microphthalmia transcription factor network SO ANNUAL REVIEW OF GENETICS LA English DT Review DE microphthalmia transcription factor; bHLH-Zip proteins; melanocytes; transcription factor networks ID CULTURED MAST-CELLS; WAARDENBURG-SYNDROME TYPE-2; RETINAL-PIGMENT EPITHELIUM; RECEPTOR TYROSINE KINASE; NEURAL CREST DEVELOPMENT; WNT SIGNALING PATHWAY; ENDOTHELIN-B RECEPTOR; ACID-PHOSPHATASE GENE; DUPLICATE MITF GENES; LOOP-HELIX PROTEIN AB The first mouse microphthalmia transcription factor (Mitf) mutation was discovered over 60 years ago, and since then over 24 spontaneous and induced mutations have been identified at the locus. Mitf encodes a member of the Myc supergene family of basic helix-loop-helix zipper (bHLH-Zip) transcription factors. Like Myc, Mitf regulates gene expression by binding to DNA as a homodimer or as a heterodimer with another related family member, in the case of Mitf the Tfe3, Tfeb, and Tfec proteins. The study of Mitf has provided many insights into the biology of melanocytes and helped to explain how melanocyte-specific gene expression and signaling is regulated. The human homologue of MITF is mutated in patients with the pigmentary and deafness disorder Waardenburg Syndrome Type 2A (WS2A). The mouse Mitf mutations therefore serve as a model for the study of this human disease. Mutations and/or aberrant expression of several MITF family member genes have also been reported in human cancer, including melanoma (MITT), papillary renal cell carcinoma (TFE3, TFEB), and alveolar soft part sarcoma (TFE3). Genes in the MITF/TFE pathway may therefore also represent valuable therapeutic targets for the treatment of human cancer. Here we review recent developments in the analysis of Mitf function in vivo and in vitro and show how traditional genetics, modem forward genetics and in vitro biochemical analyses have combined to produce an intriguing story on the role and actions of a gene family in a living organism. C1 Univ Iceland, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland. NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Steingrimsson, E (reprint author), Univ Iceland, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland. EM eirikurs@hi.is; copeland@ncifcrf.gov; jenkins@ncifcrf.gov NR 232 TC 329 Z9 356 U1 7 U2 37 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 EI 1545-2948 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2004 VL 38 BP 365 EP 411 DI 10.1146/annurev.genet.38.072902.092717 PG 51 WC Genetics & Heredity SC Genetics & Heredity GA 886QY UT WOS:000226244600012 PM 15568981 ER PT J AU Wickner, RB Edskes, HK Ross, ED Pierce, MM Baxa, U Brachmann, A Shewmaker, F AF Wickner, RB Edskes, HK Ross, ED Pierce, MM Baxa, U Brachmann, A Shewmaker, F TI Prion genetics: New rules for a new kind of gene SO ANNUAL REVIEW OF GENETICS LA English DT Review DE amyloid; [URE3]; [PSI]; [Het-s]; [PIN]; PrP ID YEAST SACCHAROMYCES-CEREVISIAE; FUNGUS PODOSPORA-ANSERINA; UREIDOSUCCINIC ACID UPTAKE; CHAPERONE PROTEIN HSP104; CHAIN RELEASE FACTOR; DE-NOVO APPEARANCE; SOLID-STATE NMR; SCRAPIE PRION; IN-VITRO; GUANIDINE-HYDROCHLORIDE AB Just as nucleic acids can carry out enzymatic reactions, proteins can be genes. These heritable infectious proteins (prions) follow unique genetic rules that enable their identification: reversible curing, inducible "spontaneous generation," and phenotype surprises. Most prions are based on self-propagating amyloids, depend heavily on chaperones, show strain phenomena and, like other infectious elements, show species barriers to transmission. A recently identified prion is based on obligatory self-activation of an enzyme in trans. Although prions can be detrimental, they may also be beneficial to their hosts. C1 NIDDKD, NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov; edskes@helix.nih.gov; ericr@intra.niddk.nih.gov; michaelp@intra.niddk.nih.gov; Ulrich_Baxa@nih.gov; andreasb@intra.niddk.nih.gov; franksh@niddk.nih.gov RI Brachmann, Andreas/I-2241-2013; OI Brachmann, Andreas/0000-0001-7980-8173; Ross, Eric/0000-0002-6473-9977 NR 143 TC 60 Z9 65 U1 0 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2004 VL 38 BP 681 EP 707 DI 10.1146/annurev.genet.38.072902.092200 PG 31 WC Genetics & Heredity SC Genetics & Heredity GA 886QY UT WOS:000226244600021 PM 15355224 ER PT J AU Yang, D Biragyn, A Hoover, DM Lubkowski, J Oppenheim, JJ AF Yang, D Biragyn, A Hoover, DM Lubkowski, J Oppenheim, JJ TI Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE antimicrobial; chemotaxis; dendritic cells; GPCR; immune response ID ANTIBACTERIAL PEPTIDE LL-37; HUMAN INTESTINAL DEFENSIN; IMMATURE DENDRITIC CELLS; HUMAN BETA-DEFENSINS; ACUTE INFLAMMATORY RESPONSE; HUMAN NEUTROPHIL DEFENSINS; AIRWAY EPITHELIAL-CELLS; HUMAN PERIPHERAL-BLOOD; INNATE IMMUNITY; HUMAN BETA-DEFENSIN-1 AB Mammals generate a diverse array of antimicrobial proteins, largely represented by defensins or cathelicidins. The direct in vitro microbicidal activity of antimicrobial proteins has long been considered an important innate immune defense, although the in vivo relevance has only very recently been established for certain defensins and cathelicidins. Mammalian defensins and cathelicidins have also been shown to have multiple receptor-mediated effects on immune cells. Beta-defensins interact with CCR6; murine beta-defensin-2 in addition activates TLR4. Cathelicidins act on FPRL1 -expressing cells. Furthermore, several defensins have considerable immunoenhancing activity. Thus, it appears that mammalian antimicrobial proteins contribute to both innate and adaptive antimicrobial immunity. C1 NCI, Basic Res Program, Frederick, MD 21702 USA. NCI, Macromol Crystallog Lab, SAIC, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. NIA, Immunol Lab, Gerontol Res Ctr, Bethesda, MD 20892 USA. RP Yang, D (reprint author), NCI, Basic Res Program, Frederick, MD 21702 USA. EM oppenhei@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 227 TC 352 Z9 386 U1 5 U2 26 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2004 VL 22 BP 181 EP 215 DI 10.1146/annurev.immunol.22.012703.104603 PG 37 WC Immunology SC Immunology GA 823HP UT WOS:000221601500007 PM 15032578 ER PT J AU Sitkovsky, MV Lukashev, D Apasov, S Kojima, H Koshiba, M Caldwell, C Ohta, A Thiel, M AF Sitkovsky, MV Lukashev, D Apasov, S Kojima, H Koshiba, M Caldwell, C Ohta, A Thiel, M TI Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A(2A) receptors SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE hypoxia; adenosine receptors; immunity; inflammation ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; TUMOR-NECROSIS-FACTOR; TRIGGERED RESPIRATORY BURST; ACTIVATED PROTEIN-KINASE; DEFICIENT MICE REVEALS; HUMAN-NEUTROPHILS; EXTRACELLULAR ADENOSINE; CYCLIC-AMP; IN-VIVO; LYMPHOCYTE DEVELOPMENT AB Immune cell-mediated destruction of pathogens may result in excessive collateral damage to normal tissues, and the failure to control activated immune cells may cause inummopathologies. The search for physiological mechanisms that down-regulate activated immune cells has revealed a critical role for extracellular adenosine and for immuno suppressive A(2A) adenosine receptors in protecting tissue from inflammatory damage. Tissue damage-associated deep hypoxia, hypoxia-inducible factors, and hypoxia-induced accumulation of adenosine may represent one of the most fundamental and immediate tissue-protecting mechanisms, with adenosine A(2A) receptors triggering "OFF" signals in activated immune cells. In these regulatory mechanisms, oxygen deprivation and extracellular adenosine accumulation serve as "reporters," while A(2A) adenosine receptors serve as "sensors" of excessive tissue damage. The A(2A) receptor-triggered generation of intracellular cAMP then inhibits activated immune cells in a delayed negative feedback manner to prevent additional tissue damage. Targeting A(2A) adenosine receptors may have important clinical applications. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N256, Bethesda, MD 20892 USA. EM msitkov@helix.nih.gov RI Lukashev, Dmitriy/F-8133-2010; OI Caldwell, Charles/0000-0003-1692-4550 NR 120 TC 403 Z9 416 U1 2 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2004 VL 22 BP 657 EP 682 DI 10.1146/annurev.immunol.22.012703.104731 PG 26 WC Immunology SC Immunology GA 823HP UT WOS:000221601500022 PM 15032592 ER PT J AU Austin, CP AF Austin, CP TI The impact of the completed human genome sequence on the development of novel therapeutics for human disease SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE translational research; chemical genomics; drug development; Human Genome Project ID B-CELL LYMPHOMA; GENE-EXPRESSION; DRUG DEVELOPMENT; BREAST-CANCER; UROTENSIN-II; DOUBLE HELIX; MEDICINE; PHARMACOGENETICS; INNOVATION; DISCOVERY AB With the official completion of the Human Genome Project in April 2003, we have both the opportunity and the imperative to translate this unprecedented scientific accomplishment into tangible improvements in human health. Medical benefits from the genome will come in stages and can be conceptualized as occurring in three areas: improved understanding of disease causation at the molecular level, improved diagnosis and disease classification based on genetic profiles, and new therapeutics based on targets identified in the genome. These improvements will require increased physician understanding of genetic principles applied to common diseases. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Austin, CP (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM austinc@mail.nih.gov NR 51 TC 46 Z9 48 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 1 EP 13 DI 10.1146/annurev.med.55.091902.104426 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000001 PM 14746506 ER PT J AU Hardy, J AF Hardy, J TI Toward Alzheimer therapies based on genetic knowledge SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE animal models; cholesterol; anti-inflammatory; immunotherapy; amyloid ID AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; GAMMA-SECRETASE ACTIVITY; ALPHA-SYNUCLEIN; BETA-PEPTIDE; IN-VIVO; PARKINSONS-DISEASE; LEWY BODY; MICE; PATHOLOGY AB Genetic analysis has allowed the dissection of the pathogenic pathway that leads to Alzheimer's disease. It has also been integral to the development of earlier and more accurate diagnostic practices. This analysis has identified many potential therapeutic targets, and clinical trials aimed at these targets are now under way. If these approaches are successful, it will be a spectacular validation of genetic-knowledge-based treatment strategies; if they are not, researchers will need to re-evaluate this approach toward understanding and developing strategies for treating complex diseases. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009 NR 63 TC 22 Z9 25 U1 1 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 15 EP 25 DI 10.1146/annurev.med.55.091902.103607 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000002 PM 14746507 ER PT J AU Spiegel, AM Weinstein, LS AF Spiegel, AM Weinstein, LS TI Inherited diseases involving G proteins and G protein-coupled receptors SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE signal transduction; gain- and loss-of-function mutations; hormone resistance ID MCCUNE-ALBRIGHT SYNDROME; PSEUDOHYPOPARATHYROIDISM TYPE IB; STIMULATORY G-PROTEIN; FIBROUS DYSPLASIA; ACTIVATING MUTATIONS; ALPHA MUTATION; GENE; GNAS1; BONE; RESISTANCE AB Heterotrimeric G proteins couple seven-transmembrane receptors for diverse extracellular signals to effectors that generate intracellular signals altering cell function. Mutations in the gene encoding the a subunit of the G protein-coupling receptors to stimulation of adenylyl cyclase cause developmental abnormalities of bone, as well as hormone resistance (pseudohypoparathyroidism caused by loss-of-function mutations) and hormone hypersecretion (McCune-Albright syndrome caused by gain-of-function mutations). Loss- and gain-of-function mutations in genes encoding G protein-coupled receptors (GPCRs) have been identified as the cause of an increasing number of retinal, endocrine, metabolic, and developmental disorders. GPCRs comprise an evolutionarily conserved gene superfamily (1). By coupling to heterotrimeric G proteins, GPCRs transduce a wide variety of extracellular signals including monoamine, amino acid, and nucleoside neurotransmitters, as well as photons, chemical odorants, divalent cations, hormones, lipids, peptides and proteins. Following a brief overview of G protein-coupled signal transduction, we review the growing body of evidence that mutations in genes encoding GPCRs and G proteins are an important cause of human disease. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM spiegela@extra.niddk.nih.gov OI Weinstein, Lee/0000-0002-1899-5152 NR 50 TC 147 Z9 153 U1 0 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 27 EP 39 DI 10.1146/annurev.med.55.091902.103843 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000003 PM 14746508 ER PT J AU Rosenblatt, KP Bryant-Greenwood, P Killian, JK Mehta, A Geho, D Espina, V Petricoin, EE Liotta, LA AF Rosenblatt, KP Bryant-Greenwood, P Killian, JK Mehta, A Geho, D Espina, V Petricoin, EE Liotta, LA TI Serum proteomics in cancer diagnosis and management SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE proteomics; mass spectrometry; SELDI; protein profiling ID FLIGHT-MASS-SPECTROMETRY; OVARIAN-CANCER; PROSTATE-CANCER; IDENTIFICATION; BIOMARKERS; DISCOVERY; PATTERNS; CHALLENGES; INTERFACE; TIME AB Mass spectrometry-based diagnostics has the potential to revolutionize molecular medicine. Using modem mass-spectrometer technologies, clinical tests can be developed that are practical, robust, accurate, and inexpensive. Serum proteomic pattern profiling couples mass spectrometry with adaptive artificial-intelligence-based bioinformatics, which can now be employed to detect pathological states reflected in the serum proteome. With this approach, rapid and cost-effective tests with exquisite clinical sensitivity and specificity are emerging. These tools may dramatically change how disease is detected, monitored, and managed. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Hawaii, John A Burns Sch Med, Dept Pathol, Honolulu, HI 96822 USA. NCI, Food & Drug Adm, Clin Prote Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Rosenblatt, KP (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM rosenblk@nihexchange2.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 46 TC 101 Z9 109 U1 2 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 97 EP 112 DI 10.1146/annurev.med.55.091902.105237 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000006 PM 14746511 ER PT J AU Berman, JD Straus, SE AF Berman, JD Straus, SE TI Implementing a research agenda for complementary and alternative medicine SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE complementary medicine; alternative medicine; research ID ST-JOHNS-WORT; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIAL; VITAMIN-C; ECHINACEA-PURPUREA; HERBAL MEDICINES; UNITED-STATES; DOUBLE-BLIND; COMMON COLD; EFFICACY AB Complementary and alternative medicine (CAM) consists of diverse clinical interventions that are practiced because of their popularity rather than the prior demonstration of safety and efficacy required for conventional agents. CAM therapies can be grouped into five categories: biologically based therapies, manipulative and body-based interventions, mind-body interventions, "energy" therapies, and alternative medical systems. The present evidence that individual CAM interventions are efficacious is largely anecdotal, but hundreds of small trials have yielded positive results. For a few modalities, existing data are either very encouraging or else sufficient to conclude that they are ineffective. CAM interventions are presumed to be safe, yet they may not be, particularly in the case of botanical agents with inherent toxicities, significant drug interactions, or potent adulterants. The public health questions regarding CAM can only be addressed through a research agenda that defines which interventions have favorable therapeutic indices. Implementation of this agenda involves adequate characterization and standardization of the product or practice, with rigorous investigation to demonstrate its safety, mechanism of action, and efficacy. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Berman, JD (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. EM Bermanjo@mail.nih.gov NR 49 TC 32 Z9 35 U1 2 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 239 EP 254 DI 10.1146/annurev.med.55.091902.103657 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000015 PM 14746520 ER PT J AU Akin, C Metcalfe, DD AF Akin, C Metcalfe, DD TI Systemic mastocytosis SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE mast cells; urticaria pigmentosa; c-kit; bone marrow ID MAST-CELL DISEASE; KINASE INHIBITOR STI571; BONE-MARROW PATHOLOGY; PROTOONCOGENE C-KIT; TYROSINE KINASE; TRYPTASE LEVELS; WILD-TYPE; SMOLDERING MASTOCYTOSIS; PEDIATRIC MASTOCYTOSIS; URTICARIA PIGMENTOSA AB Systemic mastocytosis is a clonal disorder of the mast cell and its progenitor. The symptoms of systemic mastocytosis are due to the pathologic accumulation and activation of mast cells in various tissues such as bone marrow, skin, gastrointestinal tract, liver, and spleen. Recent studies revealed striking differences between the molecular and cellular biology of mast cells in patients with mastocytosis and those of healthy individuals. These findings are being used in formulating diagnostic criteria as well as designing novel treatment approaches to the disease. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Akin, C (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM cakin@niaid.nih.gov; dmetcalfe@niaid.nih.gov OI Akin, Cem/0000-0001-6301-4520 NR 56 TC 136 Z9 136 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 419 EP 432 DI 10.1146/annurev.med.55.091902.103822 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000024 PM 14746529 ER PT J AU Childs, RW Barrett, J AF Childs, RW Barrett, J TI Nonmyeloablative allogeneic immunotherapy for solid tumors SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE allogeneic stem cell transplantation; nonmyeloablative transplant; graft-versus-tumor; graft-versus-leukemia; renal cell carcinoma ID RENAL-CELL CARCINOMA; BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; T-CELLS; HOST-DISEASE; ADOPTIVE IMMUNOTHERAPY; BREAST-CANCER; MYELOABLATIVE THERAPY AB Over the past decade, considerable advances have been made in the field of allogeneic hematopoietic stem cell transplantation. Recognition that transplanted donor immune cells can cure patients with leukemia has led to the development of nonmyeloablative or "low-intensity" conditioning regimens, which have expanded the application of allogeneic transplantation to a growing number of hematological malignancies. The improved safety and preliminary success of this transplant approach have justified applying allogeneic immunotherapy to patients with treatment-refractory solid tumors. C1 NHLBI, Allogene Hematopoiet Cell Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, Allogene Hematopoiet Cell Transplant Unit, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM childsr@nih.gov; barrettj@nih.gov NR 77 TC 20 Z9 22 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2004 VL 55 BP 459 EP 475 DI 10.1146/annurev.med.55.091902.104511 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 827RL UT WOS:000221918000026 PM 14746531 ER PT J AU Gottesman, S AF Gottesman, S TI The small RNA regulators of Escherichia coli: Roles and mechanisms SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE Hfq; DsrA; OxyS; RyhB; Spot 42 ID SM-LIKE PROTEIN; SMALL RIBONUCLEIC-ACIDS; MESSENGER-RNA; GENE-EXPRESSION; ANTISENSE-RNA; RPOS TRANSLATION; DSRA-RNA; 2-COMPONENT SYSTEM; NONCODING RNAS; HFQ PROTEIN AB Small noncoding RNAs have been found in all organisms, primarily as regulators of translation and message stability. The most exhaustive searches have taken place in E. coli, resulting in identification of more than 50 small RNAs, or 1%-2% of the number of protein-coding genes. One large class of these small RNAs uses the RNA chaperone Hfq; members of this class act by pairing to target messenger RNAs. Among the members of this class are DsrA and RprA, which positively regulate rpoS translation, OxyS, which negatively regulates rpoS translation and fhlA translation, RyhB, which reapportions iron use in the cell by downregulating translation of many genes that encode Fe-containing proteins, and Spot 42, which changes the polarity of translation in the gal operon. The promoters of these small RNAs are tightly regulated, frequently as part of well-understood regulons. Lessons learned from the study of small RNAs in E. coli can be applied to finding these important regulators in other organisms. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 120 TC 377 Z9 395 U1 3 U2 50 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2004 VL 58 BP 303 EP 328 DI 10.1146/annurev.micro.58.030603.123841 PG 28 WC Microbiology SC Microbiology GA 873YT UT WOS:000225318500014 PM 15487940 ER PT J AU Insel, TR Fernald, RD AF Insel, TR Fernald, RD TI How the brain processes social information: Searching for the social brain SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE imprinting; vomeronasal; oxytocin; parental care; affiliation ID QUANTITATIVE BEHAVIORAL OBSERVATIONS; GONADOTROPIN-RELEASING-HORMONE; VOLES MICROTUS-OCHROGASTER; ACCESSORY OLFACTORY-BULB; MEDIAL PREOPTIC AREA; PAIR-BOND FORMATION; DARK-REARED CHICKS; MATERNAL-BEHAVIOR; LACTATING RATS; PRAIRIE VOLE AB Because information about gender, kin, and social status are essential for reproduction and survival, it seems likely that specialized neural mechanisms have evolved to process social information. This review describes recent studies of four aspects of social information processing: (a) perception of social signals via the vomeronasal system, (b) formation of social memory via long-term filial imprinting and short-term recognition, (c) motivation for parental behavior and pair bonding, and (d) the neural consequences of social experience. Results from these studies and some recent functional imaging studies in human subjects begin to define the circuitry of a "social brain." Such neurodevelopmental disorders as autism and schizophrenia are characterized by abnormal social cognition and corresponding deficits in social behavior; thus social neuroscience offers an important opportunity for translational research with an impact on public health. C1 NIMH, Bethesda, MD 20892 USA. Stanford Univ, Program Neurosci, Stanford, CA 94305 USA. RP Insel, TR (reprint author), NIMH, Bethesda, MD 20892 USA. EM insel@mail.nih.gov; russ@psych.stanford.edu FU NEI NIH HHS [EY-05051]; NINDS NIH HHS [NS 34950] NR 140 TC 245 Z9 248 U1 10 U2 66 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2004 VL 27 BP 697 EP 722 DI 10.1146/annurev.neuro.27.070203.144148 PG 26 WC Neurosciences SC Neurosciences & Neurology GA 845MH UT WOS:000223246300025 PM 15217348 ER PT J AU Chen, AM Rogan, WJ AF Chen, AM Rogan, WJ TI Isoflavones in soy infant formula: A review of evidence for endocrine and other activity in infants SO ANNUAL REVIEW OF NUTRITION LA English DT Review DE genistein; soybeans; milk; estrogens; immunity ID ESTROGEN-RECEPTOR-BETA; SPRAGUE-DAWLEY RATS; PHYTOESTROGEN GENISTEIN; ENVIRONMENTAL ESTROGENS; PHYTO-ESTROGENS; PROTEIN INTAKE; IMMUNE STATUS; COWS MILK; ER-BETA; EXPOSURE AB Soy infant formulas are widely used, but few studies have evaluated long-term safety or examined specific forms of toxicity, such as to the endocrine or immune systems. This review focuses on newer experimental studies of the effects on estrogen activity, immune function, and thyroid economy of genistein and daidzein, two isoflavones in soy infant formula, and existing human studies of soy formula use. In order to judge the likelihood that an endpoint seen in laboratory studies might occur in soy-fed infants, we examined the doses and the resulting serum or plasma concentrations from the laboratory studies and compared them with doses and concentrations seen in soy-fed infants. We also summarized the estimates of the potency of the isoflavone compounds relative to estradiol. Given the scarcity and inconsistency of existing human data and the substantial laboratory evidence of hormonal and other activity at doses relevant to the soy-fed infant, we conclude that more clinical and epidemiological study is warranted. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Chen, AM (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. EM chen17@niehs.nih.gov; rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 83 TC 86 Z9 91 U1 1 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2004 VL 24 BP 33 EP 54 DI 10.1146/annurev.nutr.24.101603.064950 PG 22 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 839EM UT WOS:000222766200003 PM 15189112 ER PT J AU Forman, MR Hursting, SD Umar, A Barrett, JC AF Forman, MR Hursting, SD Umar, A Barrett, JC TI Nutrition and cancer prevention: A multidisciplinary perspective on human trials SO ANNUAL REVIEW OF NUTRITION LA English DT Review DE diet; carcinogenesis; molecular targets; epidemiology; carotenoids; retinoids ID UPPER AERODIGESTIVE TRACT; BETA-CAROTENE SUPPLEMENTS; BASE-LINE CHARACTERISTICS; SQUAMOUS-CELL CARCINOMA; LOW-DOSE ISOTRETINOIN; 2ND PRIMARY TUMORS; HIGH-FIBER DIET; TERM FOLLOW-UP; LUNG-CANCER; COLORECTAL ADENOMAS AB More than one million Americans were expected to be diagnosed with cancer in 2003 (7a). Compelling experimental, epidemiological, and clinical evidence indicates that many cancers are preventable, especially because diet and nutrition are key factors in the modulation of cancer risk. The road to nutritional intervention in cancer prevention has led to successful trials as well as trials that did not reach their intended endpoints. This chapter reviews four case studies of trials, with two ending in success and two ending in null findings or adverse effects. The goal is to identify lessons learned from all four case studies and from the investigations of the complexities inherent to nutritional intervention trials. Additional insights are presented by the research addressing potential mechanisms underlying the endpoints of human trials. Future progress in nutrition and cancer prevention will require expertise from multidisciplinary teams to develop new knowledge about specific nutrients and dietary modifications within a framework of interaction between animal and human research. C1 NCI, Ctr Canc Res, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Lab Biosyst & Canc, Rockville, MD 20852 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Forman, MR (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Bethesda, MD 20892 USA. EM mf63p@nih.gov; sh63v@nih.gov; Asad.Umar@nih.gov; barrett@mail.nih.gov NR 106 TC 26 Z9 31 U1 0 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2004 VL 24 BP 223 EP 254 DI 10.1146/annurev.nutr.24.012003.132315 PG 32 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 839EM UT WOS:000222766200011 PM 15189120 ER PT J AU Gladyshev, VN Kryukov, GV Fomenko, DE Hatfield, DL AF Gladyshev, VN Kryukov, GV Fomenko, DE Hatfield, DL TI Identification of trace element - Containing proteins in genomic databases SO ANNUAL REVIEW OF NUTRITION LA English DT Review DE bioinformatics; metal-containing proteins; selenium; selenoprotein; selenoproteome ID SELENOCYSTEINE-CONTAINING PROTEINS; INSERTION-SEQUENCE SECIS; RNA STRUCTURAL MOTIF; ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; CHLAMYDOMONAS-REINHARDTII; MAMMALIAN SELENOPROTEIN; THIOREDOXIN REDUCTASES; SELENIUM METABOLISM; INCREASED COVERAGE AB Development of bioinformatics tools provided researchers with the ability to identify full sets of trace element-containing proteins in organisms for which complete genomic sequences are available. Recently, independent bioinformatics methods were used to identify all, or almost all, genes encoding selenocysteine-containing proteins in human, mouse, and Drosophila genomes, characterizing entire selenoproteomes in these organisms. It also should be possible to search for entire sets of other trace element-associated proteins, such as metal-containing proteins, although methods for their identification are still in development. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Canc Res Ctr, Lab Canc Prevent, Sect Mol Biol Selenium,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu; hatfield@dc37a.nci.nih.gov RI Kryukov, Gregory/A-9592-2008; Gladyshev, Vadim/A-9894-2013; OI Kryukov, Gregory/0000-0002-6131-9483 FU NIGMS NIH HHS [GM061603] NR 74 TC 35 Z9 40 U1 0 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2004 VL 24 BP 579 EP 596 DI 10.1146/annurev.nutr.24.012003.132241 PG 20 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 839EM UT WOS:000222766200024 PM 15189132 ER PT J AU Wess, J AF Wess, J TI Muscarinic acetylcholine receptor knockout mice: Novel phenotypes and clinical implications SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE gene targeting; muscarinic agonist; muscarinic antagonist; parasympathetic nervous system; signal transduction ID CEREBRAL BLOOD-FLOW; SUBTYPE-SPECIFIC ANTIBODIES; CENTRAL-NERVOUS-SYSTEM; ISOLATED RAT SKIN; SMOOTH-MUSCLE; ALZHEIMERS-DISEASE; DOPAMINE RELEASE; NEUROTRANSMITTER RELEASE; CHOLINERGIC STIMULATION; SEIZURE ACTIVITY AB Muscarinic acetylcholine receptors (mAChRs; M-1-M-5) play key roles in regulating the activity of many important functions of the central and peripheral nervous system. Because of the lack of ligands endowed with a high degree of receptor subtype selectivity and the fact that most tissues or cell types express two or more mAChR subtypes, identification of the physiological and pathophysiological roles of the individual mAChR subtypes has proven a difficult task. To circumvent these difficulties, several laboratories recently employed gene-targeting techniques to generate mutant mouse strains deficient in each of the five mAChR subtypes. Phenotyping studies showed that each mutant mouse line displayed characteristic physiological, pharmacological, behavioral, biochemical, or neurochemical deficits. The novel in-sights gained from these studies should prove instrumental for the development of novel classes of muscarinic drugs. C1 NIDDKD, Mol Signalling Sect, Bioorgan Chem Lab, DHHS, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDKD, Mol Signalling Sect, Bioorgan Chem Lab, DHHS, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov NR 110 TC 225 Z9 236 U1 1 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2004 VL 44 BP 423 EP 450 DI 10.1146/annurev.pharmtox.44.101802.121622 PG 28 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 780BJ UT WOS:000189351000018 PM 14744253 ER PT J AU Mayer, ML Armstrong, N AF Mayer, ML Armstrong, N TI Structure and function of glutamate receptor ion channels SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE AMPA; kainate; NMDA; crystallography; channels; structure ID LIGAND-BINDING DOMAIN; D-ASPARTATE RECEPTOR; AMPA RECEPTOR; CRYSTAL-STRUCTURE; POTASSIUM CHANNEL; KAINATE RECEPTORS; MOLECULAR-ORGANIZATION; ESCHERICHIA-COLI; N-GLYCOSYLATION; NMDA RECEPTORS AB Avast number of proteins are involved in synaptic function. Many have been cloned and their functional role defined with varying degrees of success, but their number and complexity currently defy any molecular understanding of the physiology of synapses. A beacon of success in this medieval era of synaptic biology is an emerging understanding of the mechanisms underlying the activity of the neurotransmitter receptors for glutamate. Largely as a result of structural studies performed in the past three years we now have a mechanistic explanation for the activation of channel gating by agonists and partial agonists; the process of desensitization, and its block by allosteric modulators, is also mostly explained; and the basis of receptor subtype selectivity is emerging with clarity as more and more structures are solved. In the space of months we have gone from cartoons of postulated mechanisms to hard fact. It is anticipated that this level of understanding will emerge for other synaptic proteins in the coming decade. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, DHHS, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, DHHS, Bldg 36,Room 2B28, Bethesda, MD 20892 USA. EM mlm@helix.nih.gov; naa15@columbia.edu RI Mayer, Mark/H-5500-2013 NR 78 TC 245 Z9 259 U1 4 U2 18 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2004 VL 66 BP 161 EP 181 DI 10.1146/annurev.physiol.66.050802.084104 PG 27 WC Physiology SC Physiology GA 812GK UT WOS:000220827800008 PM 14977400 ER PT J AU Alavanja, MCR Hoppin, JA Kamel, F AF Alavanja, MCR Hoppin, JA Kamel, F TI Health effects of chronic pesticide exposure: Cancer and neurotoxicity SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE pesticides; epidemiology; exposure assessment; chronic disease; adult health ID NON-HODGKINS-LYMPHOMA; OCCUPATIONAL RISK-FACTORS; SOFT-TISSUE SARCOMA; AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON-DISEASE; PRIMARY LIVER-CANCER; LONG-TERM EXPOSURE; CHRONIC NEUROLOGICAL SEQUELAE; POSTMENOPAUSAL BREAST-CANCER; HORMONE REPLACEMENT THERAPY AB Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20892 USA. EM alavanjm@mail.nih.gov OI Kamel, Freya/0000-0001-5052-6615 NR 314 TC 227 Z9 248 U1 9 U2 84 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2004 VL 25 BP 155 EP 197 DI 10.1146/annurev.publhealth.25.101802.123020 PG 43 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 816SW UT WOS:000221130600010 PM 15015917 ER PT J AU Randolph, W Viswanath, K AF Randolph, W Viswanath, K TI Lessons learned from public health mass media campaigns: Marketing health in a crowded media world SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Article DE health behavior; interventions; messages; counteradvertising; public service announcements ID VIETNAMESE-AMERICAN CHILDREN; HEPATITIS-B VACCINATIONS; FRAMED MESSAGES; PROMOTION; BEHAVIOR; SMOKING; PROGRAM; TRUTH; ADOLESCENTS; TELEVISION AB Every year, new public health mass media campaigns are launched attempting to change health behavior and improve health outcomes. These campaigns enter a crowded media environment filled with messages from competing sources. Public health practitioners have to capture not only the attention of the public amid such competition, but also motivate them to change health behaviors that are often entrenched or to initiate habits that may be new or difficult. In what ways are public health mass media campaigns now attempting to succeed in a world crowded with media messages from a myriad of sources? What are the conditions that are necessary for a media campaign to successfully alter health behaviors and alter outcomes in the long term? To what extent can the successes and failures of previous campaigns be useful in teaching important lessons to those planning campaigns in the future? In this chapter we attempt to answer these questions, drawing from recent literature on public health mass media campaigns. C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Randolph, W (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM randolwh@mail.nih.gov; Viswanav@mail.nih.gov NR 67 TC 158 Z9 158 U1 8 U2 52 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2004 VL 25 BP 419 EP 437 DI 10.1146/annurev.publhealth.25.101802.123046 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 816SW UT WOS:000221130600021 PM 15015928 ER PT J AU Hazra, R Balis, FM Tullio, AN DeCarlo, E Worrell, CJ Steinberg, SM Flaherty, JF Yale, K Poblenz, M Kearney, BP Zhong, LJ Coakley, DF Blanche, S Bresson, JL Zuckerman, JA Zeichner, SL AF Hazra, R Balis, FM Tullio, AN DeCarlo, E Worrell, CJ Steinberg, SM Flaherty, JF Yale, K Poblenz, M Kearney, BP Zhong, LJ Coakley, DF Blanche, S Bresson, JL Zuckerman, JA Zeichner, SL TI Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIRETROVIRAL-EXPERIENCED PATIENTS; PHASE I/II; SAFETY; THERAPY; PREVENTION; MACAQUES; TRIAL; DF AB Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m(2); the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) was 2,150 ng . h/ml and the geometric mean maximum concentration (C-max) was 266 ng/ml. Subsequently, other antiretrovirals were added,to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng . h/ml and was significantly higher than the AUC(0-infinity) after the first dose (P = 0.0004). The geometric mean C-max at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, similar to3,000 ng . h/ml; C-max, similar to300 ng/ml) treated with tenofovir DF at 300 mg. C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Gilead Sci Inc, Foster City, CA 94404 USA. Hop Necker Enfants Malad, Paris, France. RP Zeichner, SL (reprint author), Bldg 10,Room 10S255,MSC 1868, Bethesda, MD 20892 USA. NR 15 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2004 VL 48 IS 1 BP 124 EP 129 DI 10.1128/AAC.48.1.1240129.2004 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 759FW UT WOS:000187728500018 PM 14693529 ER PT S AU Kapetanovic, IM Umar, A Khan, J AF Kapetanovic, IM Umar, A Khan, J BE Umar, A Kapetanovic, I Khan, J TI Proceedings: The applications of bioinformatics in cancer detection workshop SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE bioinformatics; data mining; cancer; early detection; risk assessment; genomics; proteomics; drug discovery ID ARTIFICIAL NEURAL NETWORKS; PROSTATE-CANCER; MICROARRAY DATA; COMPUTATION; PREDICTION; PATTERNS AB The Division of Cancer Prevention of the National Cancer Institute sponsored and organized the Applications of Bioinformatics in Cancer Detection Workshop on August 6-7, 2002. The goal of the workshop was to evaluate the state of the science of bioinformatics and determine how it may be used to assist early cancer detection, risk identification, risk assessment, and risk reduction. This paper summarizes the proceedings of this conference and points out future directions for research. C1 NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA. NCI, Oncogenom Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. EM kapetani@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 16 TC 1 Z9 2 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 1 EP 9 DI 10.1196/annals.1310.002 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400001 PM 15208178 ER PT S AU Kapetanovic, IM Rosenfeld, S Izmirlian, G AF Kapetanovic, IM Rosenfeld, S Izmirlian, G BE Umar, A Kapetanovic, I Khan, J TI Overview of commonly used bioinformatics methods and their applications SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE bioinformatics; data mining; cancer; early detection; risk assessment; hierarchical clustering; neural networks; support vector machines; fuzzy logic; genomics; proteomics; drug discovery ID ARTIFICIAL NEURAL NETWORKS; BREAST-CANCER DIAGNOSIS; GENE-EXPRESSION DATA; FUZZY-LOGIC; PROSTATE-CANCER; MEDICAL APPLICATIONS; PATTERNS; CLASSIFICATION; PROFILES; SERUM AB Bioinformatics, in its broad sense, involves application of computer processes to solve biological problems. A wide range of computational tools are needed to effectively and efficiently process large amounts of data being generated as a result of recent technological innovations in biology and medicine. A number of computational tools have been developed or adapted to deal with the experimental riches of complex and multivariate data and transition from data collection to information or knowledge. These include a wide variety of clustering and classification algorithms, including self-organized maps (SOM), artificial neural networks (ANN), support vector machines (SVM), fuzzy logic, and even hyphenated techniques as neuro-jazzy networks. These bioinformatics tools are being evaluated and applied in various medical areas including early detection, risk assessment, classification, and prognosis of cancer. The goal of these efforts is to develop and identify bioinformatics methods with optimal sensitivity, specificity, and predictive capabilities. C1 NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. EM kapetani@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 52 TC 37 Z9 41 U1 0 U2 12 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-511-7; 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 10 EP 21 DI 10.1196/annals.1310.003 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400002 PM 15208179 ER PT S AU Rosenfeld, S AF Rosenfeld, S BE Umar, A Kapetanovic, I Khan, J TI New developments in cancer-related computational statistics SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE Bayesian Networks; expression profiles; microarray; multiple testing; Hidden Markov Chain; support vector machines; optimization ID MICROARRAY GENE-EXPRESSION; FALSE DISCOVERY RATE; CLASSIFICATION; DYNAMICS AB A brief overview is presented of recently developed and currently emerging statistical and computational techniques that have been proved to be highly helpful in handling the avalanche of the new type of data generated by modern high-throughput technologies in experimental biology. The review, in no way comprehensive, focuses attention on Bayesian Networks, Hidden Markov Chain, and methods of chaotic dynamics for time-course genomic data; innovative methods in optimization and clustering; and multiple testing in the context of identification of differentially expressed genes. C1 NCI, Biometry Res Grp, Div Canc Prevent, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Rosenfeld, S (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, Dept Hlth & Human Serv,NIH, EPN 3136,6130 Execut Blvd, Bethesda, MD 20892 USA. EM sr2l2a@nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 25 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-511-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 22 EP 31 DI 10.1196/annals.1310.004 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400003 PM 15208180 ER PT S AU Greer, BT Khan, J AF Greer, BT Khan, J BE Umar, A Kapetanovic, I Khan, J TI Diagnostic classification of cancer using DNA microarrays and artificial intelligence SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE artificial neural networks; support vector machines; artificial intelligence; microarray ID GENE-EXPRESSION PROFILES; BREAST-CANCER; NEURAL NETWORKS; PREDICTION AB The application of artificial intelligence (AI) to microarray data has been receiving much attention in recent years because of the possibility of automated diagnosis in the near future. Studies have been published predicting tumor type, estrogen receptor status, and prognosis using a variety of AI algorithms. The performance of intelligent computing decisions based on gene expression signatures is in some cases comparable to or better than the current clinical decision schemas. The goal of these tools is not to make clinicians obsolete, but rather to give clinicians one more tool in their armamentarium to accurately diagnose and hence better treat cancer patients. Several such applications are summarized in this chapter, and some of the common pitfalls are noted. C1 NCI, Ctr Adv Technol, NIH, Gaithersburg, MD 20877 USA. RP Khan, J (reprint author), NCI, Ctr Adv Technol, NIH, Room 134E,8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM khanjav@mail.nih.gov; khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 17 TC 23 Z9 25 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 49 EP 66 DI 10.1196/annals.1310.007 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400006 PM 15208183 ER PT S AU Yang, HH Lee, MP AF Yang, HH Lee, MP BE Umar, A Kapetanovic, I Khan, J TI Application of bioinformatics in cancer epigenetics SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE genomics; bioinformatics; cancer; epigenetics; genomic imprinting ID BECKWITH-WIEDEMANN-SYNDROME; 11P15 IMPRINTED DOMAIN; GENE-EXPRESSION; ALLELIC VARIATION; HUMAN GENOME; CPG ISLAND; REGION; SEQUENCE; IDENTIFICATION; CHROMOSOME AB With the completion of the human genome sequence and the advent of high-throughput genomics-based technologies, it is now possible to study the entire human genome and epigenome. The challenge in the next decade of biomedical research is to functionally annotate the genome, epigenome, transcriptome, and proteome. High-throughput genome technology has already produced massive amounts of data including genome sequences, single nucleotide polymorphisms, and microarray gene expression. Our ability to manage and analyze data needs to match the speed of data acquisition. We will summarize our studies of allele-specific gene expression using genomic and computational approaches and identification of sequence motifs that are signature of imprinted genes. We will also discuss about how bioinformatics can facilitate epigenetic researches. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Lee, MP (reprint author), NCI, Lab Populat Genet, 41 Lib Dr D702C, Bethesda, MD 20892 USA. EM leemax@mail.nih.gov NR 28 TC 4 Z9 5 U1 1 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 67 EP 76 DI 10.1196/annals.1310.008 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400007 PM 15208184 ER PT S AU Schaefer, CF AF Schaefer, CF BE Umar, A Kapetanovic, I Khan, J TI Pathway databases SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE bioinformatics; pathway; database ID PROTEIN-PROTEIN INTERACTIONS; BIOLOGICAL PATHWAYS; INTEGRATED-SYSTEM; NETWORK DATABASE; INFORMATION; TOOL; KEGG AB Network representations of biological pathways offer a functional view of molecular biology that is different from and complementary to sequence, expression, and structure databases. There is currently available a wide range of digital collections of pathway data, differing in organisms included, functional area covered (e.g., metabolism vs. signaling), detail of modeling, and support for dynamic pathway construction. While it is currently impossible for these databases to communicate with each other, there are several efforts at standardizing a data exchange language for pathway data. Databases that represent pathway data at the level of individual interactions make it possible to combine data from different predefined pathways and to query by network connectivity. Computable representations of pathways provide a basis for various analyses, including detection of broad network patterns, comparison with mRNA or protein abundance, and simulation. C1 NCI, Ctr Bioinformat, Rockville, MD 20852 USA. RP Schaefer, CF (reprint author), NCI, Ctr Bioinformat, 6116 Execut Blvd,Suite 403, Rockville, MD 20852 USA. EM schaefec@mail.nih.gov NR 33 TC 17 Z9 17 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 77 EP 91 DI 10.1196/annals.1310.009 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400008 PM 15208185 ER PT S AU Kawasaki, ES AF Kawasaki, ES BE Umar, A Kapetanovic, I Khan, J TI Microarrays and the gene expression profile of a single cell SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE single cell; microarray; expression profile; laser capture; cancer cell ID LASER CAPTURE MICRODISSECTION; MESSENGER-RNA AMPLIFICATION; DENSITY OLIGONUCLEOTIDE ARRAYS; LINEAR AMPLIFICATION; CDNA MICROARRAY; AMPLIFIED RNA; STEM-CELLS; HYBRIDIZATION; CANCER; FIDELITY AB With completion of the human genome sequence, it is now possible to study the expression of the entire human gene complement of similar to30,000-35,000 genes. To accomplish this goal, microarrays have become the leading methodology for the analysis of global gene expression. Improvements in technology have increased the sensitivity of microarrays to the point where it is feasible to study gene expression in a small number of cells and even at the single cell level. A summary of developments in the area of expression profiling in single cells will be described, and the rationale for these types of studies will be presented. In addition, from a biologist's point of view, some bioinformatic challenges of expression analysis of single cells will be discussed. C1 NCI, Ctr Adv Technol, NIH, Bethesda, MD 20892 USA. RP Kawasaki, ES (reprint author), NCI, Ctr Adv Technol, NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM kawasake@mail.nih.gov NR 65 TC 22 Z9 25 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 92 EP 100 DI 10.1193/annals.1310.010 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400009 PM 15208186 ER PT S AU Clifford, RJ Edmonson, MN Nguyen, C Scherpbier, T Hu, Y Buetow, KH AF Clifford, RJ Edmonson, MN Nguyen, C Scherpbier, T Hu, Y Buetow, KH BE Umar, A Kapetanovic, I Khan, J TI Bioinformatics tools for single nucleotide polymorphism discovery and analysis SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE bioinformatics; single nucleotide polymorphisms; SNPs ID HUMAN GENOME; MAP; COLLECTION; DATABASE; CANCER; FUTURE AB Single nucleotide polymorphisms (SNPs) are a valuable resource for investigating the genetic basis of disease. These variants can serve as markers for fine-scale genetic mapping experiments and genome-wide association studies. Certain of these nucleotide polymorphisms may predispose individuals to illnesses such as diabetes, hypertension, or cancer, or affect disease progression. Bioinformatics techniques can play an important role in SNP discovery and analysis. We use computational methods to identify SNPs and to predict whether they are likely to be neutral or deleterious. We also use informatics to annotate genes that contain SNPs. To make this information available to the research community, we provide a variety of Internet-accessible tools for data access and display. These tools allow researchers to retrieve data about SNPs based on gene of interest, genetic or physical map location, or expression pattern. C1 NCI, Ctr Canc Res, Lab Populat Genet, Bethesda, MD 20892 USA. RP Clifford, RJ (reprint author), NCI, Ctr Canc Res, Lab Populat Genet, MSC8302,8424 Helgerman Court, Bethesda, MD 20892 USA. EM clifforr@mail.nih.gov NR 19 TC 21 Z9 23 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 101 EP 109 DI 10.1196/annals.1310.011 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400010 PM 15208187 ER PT S AU Rosenfeld, S Wang, T Kim, Y Milner, J AF Rosenfeld, S Wang, T Kim, Y Milner, J BE Umar, A Kapetanovic, I Khan, J TI Numerical deconvolution of cDNA microarray signal - Simulation study SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE microarray data analysis; numerical simulation; polymerase chain reaction (PCR); replicated experiment ID GENE-EXPRESSION; PCR; PATTERNS; DISPLAY; SINGLE; GENOME AB A computational model for simulation of the cDNA microarray experiments has been created. The simulation allows one to foresee the statistical properties of replicated experiments without actually performing them. We introduce a new concept, the so-called bio-weight, which allows for reconciliation between conflicting meanings of biological and statistical significance in microarray experiments. It is shown that, for a small sample size, the bio-weight is a more powerful criterion of the presence of a signal in microarray data as compared to the standard approach based on t test. Joint simulation of microarray and quantitative PCR data shows that the genes recovered by using the bio-weight have better chances to be confirmed by PCR than those obtained by the t test technique. We also employ extreme value considerations to derive plausible cutoff levels for hypothesis testing. C1 NCI, Biometry Res Grp, Div Canc Prevent, Dept Hlth & Human Serv,NIH, Rockville, MD 20892 USA. USDA, Phytonutrients Lab, Beltsville, MD 20705 USA. NCI, Div Canc Prevent, Nutr Sci Res Grp, Dept Hlth & Human Serv,NIH, Rockville, MD 20892 USA. RP Rosenfeld, S (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, Dept Hlth & Human Serv,NIH, EPN 3136,6130 Execut Blvd, Rockville, MD 20892 USA. EM sr212a@nih.gov NR 19 TC 4 Z9 5 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-511-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 110 EP 123 DI 10.1196/annals.1310.012 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400011 PM 15208188 ER PT S AU Izmirlian, G AF Izmirlian, G BE Umar, A Kapetanovic, I Khan, J TI Application of the random forest classification algorithm to a SELDI-TOF proteomics study in the setting of a cancer prevention trial SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE random forest (RF) algorithm; SELDI-TOF; cancer; classifier; classification tree (CT); detection; prevention; MDM; statistic ID OVARIAN-CANCER; PATTERNS; SERUM AB A thorough discussion of the random forest (RF) algorithm as it relates to a SELDI-TOF proteomics study is presented, with special emphasis on its application for cancer prevention: specifically, what makes it an efficient, yet reliable classifier, and what makes it optimal among the many available approaches. The main body of the paper treats the particulars of how to successfully apply the RF algorithm in a proteomics profiling study to construct a classifier and discover peak intensities most likely responsible for the separation between the classes. C1 NCI, DHHS, Div Canc Prevent, Biometry Res Grp, Rockville, MD 20852 USA. RP Izmirlian, G (reprint author), NCI, DHHS, Div Canc Prevent, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Rockville, MD 20852 USA. EM izmirlian@nih.gov NR 21 TC 53 Z9 55 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 154 EP 174 DI 10.1196/annals.1310.015 PG 21 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400014 PM 15208191 ER PT S AU Umar, A AF Umar, A BE Umar, A Kapetanovic, I Khan, J TI Applications of Bioinformatics in cancer detection: A lexicon of bio-informatics terms SO APPLICATIONS OF BIOINFORMATICS IN CANCER DETECTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Applications of Bioinformatics in Cancer Detection Workshop CY AUG 06-07, 2002 CL Bethesda, MD SP NCI, Div Canc Prevent DE bioinformatics; cancer; detection; prevention; technique ID ARTIFICIAL NEURAL-NETWORKS; META-ANALYSIS; FUZZY-SETS AB This paper compiles a list of numerous bioinformatics terms for the Applications of Bioinformatics in Cancer Detection conference. It should be helpful as a lexicon for the volume as a whole. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Umar, A (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM asad.umar@nih.gov; asad.umar@nih.gov NR 24 TC 0 Z9 0 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-510-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1020 BP 263 EP 276 DI 10.1196/annals.1310.021 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Oncology; Computer Science, Interdisciplinary Applications; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Oncology; Computer Science; Science & Technology - Other Topics GA BAH03 UT WOS:000222177400020 PM 15208197 ER PT J AU Gogtay, N Sporn, A Clasen, LS Nugent, TF Greenstein, D Nicolson, R Giedd, JN Lenane, M Gochman, P Evans, A Rapoport, JL AF Gogtay, N Sporn, A Clasen, LS Nugent, TF Greenstein, D Nicolson, R Giedd, JN Lenane, M Gochman, P Evans, A Rapoport, JL TI Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BRAIN-DEVELOPMENT; 1ST-EPISODE PSYCHOSIS; ANTIPSYCHOTIC-DRUGS; LONGITUDINAL MRI; MOOD DISORDERS; VOLUME CHANGES; ADOLESCENCE; CLOZAPINE; FEATURES; CHILDREN AB Background: Recent anatomical brain magnetic resonance imaging (MRI) studies show a striking postpsychotic progressive loss of cortical gray matter (GM) in patients with childhood-onset schizophrenia (COS), which appears greater than that seen for adult patients. However, the diagnostic specificity and the relationship of these changes to drug treatment and cognitive functioning remain unclear. We performed a comparative prospective brain MRI study in patients with COS and pediatric patients with transient psychosis with behavior problems (psychosis not otherwise specified) provisionally considered multidimensionally impaired (MDI). We hypothesized that cortical GM loss would occur in patients with COS but not in adolescents with atypical psychoses. Methods: Anatomical brain MRI was performed at baseline and follow-up in 19 patients in the MDl group (mean [SD] age of 13.3 [3.1] years); in 23 patients with COS matched for age, sex, IQ score, and drug treatment (mean [SDI age of 13.9 [2.5] years); and 38 healthy control subjects matched for age and sex (mean [SD] age of 13.3 [3.1] years). The mean (SD) follow-up was 2.5 (0.8) years. Volumes of the cerebrum and total and regional GM were obtained by using automated analysis, and percent change in volume across time was calculated. One-way analyses. of variance with post hoc Tukey Honestly Significantly Different comparisons were performed to examine group differences in the percent change in GM across follow-up. Results: The COS group had significantly greater total, frontal, temporal, and parietal GM loss than did the MDI or healthy control groups; analysis of variance post hoc P values ranged from .03 to .001. The MDI and control groups did not differ significantly from each other. Conclusions: The cortical GM volume loss in COS appears diagnostically specific; it was not seen in children and adolescents with atypical psychosis. Because both patient groups had similar early developmental patterns, cognitive functioning, medications, and hospitalizations, this progressive loss appears to be intrinsic to COS. An ongoing neurodevelopmental process and/or brain response specific to the illness could account for these changes. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N 202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. EM nitin@codon.nih.gov RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 36 TC 92 Z9 92 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2004 VL 61 IS 1 BP 17 EP 22 DI 10.1001/archpsyc.61.1.17 PG 6 WC Psychiatry SC Psychiatry GA 761GW UT WOS:000187894000002 PM 14706940 ER PT J AU London, ED Simon, SL Berman, SM Mandelkern, MA Lichtman, AM Bramen, J Shinn, AK Miotto, K Learn, J Dong, Y Matochik, JA Kurian, V Newton, T Woods, R Rawson, R Ling, W AF London, ED Simon, SL Berman, SM Mandelkern, MA Lichtman, AM Bramen, J Shinn, AK Miotto, K Learn, J Dong, Y Matochik, JA Kurian, V Newton, T Woods, R Rawson, R Ling, W TI Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 08-12, 2002 CL SAN JUAN, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID POSITRON-EMISSION-TOMOGRAPHY; TYROSINE-HYDROXYLASE ACTIVITY; HUMAN BRAIN; BLOOD-FLOW; DOPAMINE TRANSPORTER; GLUCOSE-UTILIZATION; PREFRONTAL CORTEX; ANTERIOR CINGULATE; RAT-BRAIN; COCAINE AB Background: Mood disturbances in methamphetamine (MA) abusers likely influence drug use, but the neurobiological bases for these problems are poorly understood. Objective: To assess regional brain function and its possible relationships with negative affect in newly abstinent MA abusers. Design: Two groups were compared by measures of mood and cerebral glucose metabolism ( [F-18]fluorodeoxyglucose positron emission tomography) during performance of a vigilance task. Setting: Participants were recruited from the general community to a research center. Participants: Seventeen abstaining (4-7 days) MA abusers (6 women) were compared with 18 control subjects (8 women). Main Outcome Measures: Self-reports of depressive symptoms and anxiety were measured, as were global and relative glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and insular cortices and the amygdala, striatum, and cerebellum. Results: Abusers of MA provided higher self-ratings of depression and anxiety than control subjects. and differed significantly in relative regional glucose metabolism: lower in the anterior cingulate and insula and higher in the lateral orbitofrontal area, middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA abusers, self-reports of depressive symptoms covaried positively with relative glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and amygdala) and ratings of state and trait anxiety covaried negatively with relative activity in the anterior cingulate cortex and left insula. Trait anxiety also covaried negatively with relative activity in the orbitoftontal cortex and positively with amygdala activity. Conclusions: Abusers of MA have abnormalities in brain regions' implicated in mood disorders. Relationships between relative glucose metabolism in limbic and paralimbic regions and self-reports of depression and anxiety in MA abusers suggest that these regions are involved in affective dysregulation and may be an important target of intervention for MA dependence. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Neuropsychiat, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP London, ED (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,POB 175919, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu OI newton, thomas/0000-0002-3198-5901 FU NCRR NIH HHS [M01 RR 00865]; NIDA NIH HHS [1Y01 DA 50038, T32 DA 07272] NR 72 TC 217 Z9 228 U1 7 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2004 VL 61 IS 1 BP 73 EP 84 DI 10.1001/archpsyc.61.1.73 PG 12 WC Psychiatry SC Psychiatry GA 761GW UT WOS:000187894000008 PM 14706946 ER PT J AU Canino, G Shrout, PE Rubio-Stipec, M Bird, HR Bravo, M Ramirez, R Chavez, L Alegria, M Bauermeister, JJ Hohmann, A Ribera, J Garcia, P Martinez-Taboas, A AF Canino, G Shrout, PE Rubio-Stipec, M Bird, HR Bravo, M Ramirez, R Chavez, L Alegria, M Bauermeister, JJ Hohmann, A Ribera, J Garcia, P Martinez-Taboas, A TI The DSM-IV rates of child and adolescent disorders in Puerto Rico - Prevalence, correlates, service use, and the effects of impairment SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; PSYCHIATRIC-ASSESSMENT CAPA; TEST-RETEST RELIABILITY; GREAT SMOKY MOUNTAINS; UNITED-STATES; CLINICAL-SIGNIFICANCE; MENTAL-DISORDERS; WHITE YOUTH; PSYCHOPATHOLOGY; COMMUNITY AB Background: Few prevalence studies in which DSM-IV criteria were used in children in representative community samples have been reported. We present prevalence data for the child and adolescent population of Puerto Rico and examine the relation of DSM-IV diagnoses to global impairment, demographic correlates, and service use in an island-wide representative sample. Methods: We sampled 1886 child-caretaker dyads in Puerto Rico by using a multistage sampling design. Children were aged 4 to 17 years. Response rate was 90.1%. Face-to-face interviews of children and their primary caretakers were performed by trained laypersons who administered the Diagnostic Interview Schedule for Children, version IV (DISC-IV) in Spanish. Global impairment was measured by using the Children's Global Assessment Scale scored by the interviewer of the parent. Reports of service use were obtained by using the Service Assessment for Children and Adolescents. Results: Although 19.8% of the sample met DSM-IV criteria without considering impairment, 16.4% of the population had I or more of the DSM-IV disorders when a measure of impairment specific to each diagnosis- was considered. The overall prevalence was further reduced to 6.9% when a measure of global impairment was added to that definition. The most prevalent disorders were attention-deficit/hyperactivity disorder (8.0%) and oppositional defiant disorder (5.5%). Children in urban settings had higher rates than those in rural regions. Older age was related to higher rates of major depression and social phobia, and younger age was related to higher rates of attention-deficit/hyperactivity disorder. Both overall rates and rates of specific DSM-IWDISC-IV disorders were related to service use. Children with impairment without diagnosis were more likely to use school services, whereas children with impairment with diagnosis were more likely to use the specialty mental health sector. Of those with both a diagnosis and global impairment, only half received services from any source. Conclusions: Because we used the DISC-IV to apply DSM-IV criteria, the study yielded prevalence rates that are generally comparable with those found in previous surveys. The inclusion of diagnosis-specific impairment criteria reduced rates slightly. When global impairment criteria were imposed, the rates were reduced by approximately half. C1 Carlos Albizu Univ, Dept Psychol, San Juan, PR USA. San Juan Vet Adm Hosp, Dept Psychol, San Juan, PR USA. NIMH, Bethesda, MD 20892 USA. Cambridge Hlth Alliance, Ctr Multicultural Res, Cambridge, MA USA. Harvard Univ, Dept Psychiat, Cambridge, MA 02138 USA. Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. Amer Psychiat Inst Res & Educ, Washington, DC USA. NYU, Dept Psychol, New York, NY 10003 USA. Univ Puerto Rico, Dept Psychol, Rio Piedras, PR 00931 USA. Univ Puerto Rico, Dept Pediat, Rio Piedras, PR 00931 USA. Behav Sci Res Inst, San Juan, PR 00936 USA. RP Canino, G (reprint author), Behav Sci Res Inst, Med Sci Campus,POB 365067, San Juan, PR 00936 USA. EM gcanino@rcm.upr.edu OI ramirez, rafael/0000-0002-9504-7260 FU NIMH NIH HHS [P01 MH 59876, U01 MH 54827] NR 57 TC 247 Z9 255 U1 7 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2004 VL 61 IS 1 BP 85 EP 93 DI 10.1001/archpsyc.61.1.85 PG 9 WC Psychiatry SC Psychiatry GA 761GW UT WOS:000187894000009 PM 14706947 ER PT J AU Bartali, B Turrini, A Salvini, S Lauretani, F Russo, CR Corsi, AM Bandinelli, S D'Amicis, A Palli, D Guralnik, JM Ferrucci, L AF Bartali, B Turrini, A Salvini, S Lauretani, F Russo, CR Corsi, AM Bandinelli, S D'Amicis, A Palli, D Guralnik, JM Ferrucci, L TI Dietary intallke estimated using different methods in two Italian older populations SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE dietary intake; dietary assessment; food frequency questionnaire ID ELDERLY-PEOPLE AB Most of the tools used to assess nutritional intake in large epidemiological studies were originally developed to be used in young and middle-aged subjects and, therefore, their validity and reliability when employed in older subjects remain uncertain. We conducted this study to verify whether the questionnaire developed in the context of the European Prospective Investigation into Cancer and nutrition (EPIC) could be used to assess dietary intake in the participants of InCHIANTI, an epidemiological study of risk factors for disability in late life, performed in 633 men (78% aged, greater than or equal to65 years) and 802 women (81% aged, greater than or equal to65 years) randomly sampled from the general population. In particular, the aim of this project was to collect preliminary information that could support a future study of concurrent validity. Data on food consumption assessed using the EPIC questionnaire from the InCHIANTI participants were compared with those collected using a 7-day diary in the National Nutritional Investigation into Dietary Behavior (INN-CA), a study conducted in 15 Italian centres aimed at assessing Italian households' and individuals' dietary intake. In spite of different populations and different methods used in data collection, the distributions of dietary intake from the two studies were remarkably similar for most macro- and micro-nutrients, both in men and women and according to age groups. At a population level, a food frequency questionnaire and a costly and time-consuming objective method provided similar estimates of dietary intake. Future study should attempt to generalize these findings at an individual level by collecting data with both instruments in the same subjects. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH,Harbor Hosp Ctr, Baltimore, MD 21225 USA. Natl INRCA, Lab Clin Epidemiol, Dept Geriatr, I-50125 Florence, Italy. INRAN, Natl Inst Res Food & Nutr, I-00178 Rome, Italy. Sci Inst Tuscany, CSPO, Canc Study & Prevent Ctr, Mol & Nutrit Epidemiol Unit, I-50135 Florence, Italy. NIA, Lab Epidemiol, Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIH,Harbor Hosp Ctr, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA. RI Turrini, Aida/K-5353-2016 OI Turrini, Aida/0000-0002-2188-9406 FU NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13] NR 14 TC 26 Z9 27 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD JAN-FEB PY 2004 VL 38 IS 1 BP 51 EP 60 DI 10.1016/S0167-4943(03)00084-0 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 759MJ UT WOS:000187741200006 PM 14599704 ER PT J AU Blackburn, MB Loeb, MJ Clark, E Jaffe, H AF Blackburn, MB Loeb, MJ Clark, E Jaffe, H TI Stimulation of midgut stem cell proliferation by Manduca sexta alpha-arylphorin SO ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY LA English DT Article ID IN-VITRO; ARTHROPOD HEMOCYANINS; DIFFERENTIATION; PROTEIN; EPITHELIUM; EVOLUTION; HEMOLYMPH; LARVAL AB Extracts of the green-colored perivisceral fat body of newly ecdysed Manduca sexta pupae stimulate mitosis in midgut stem cells of Heliothis virescens cultured in vitro. Using a combination of cation- and anion-exchange chromatography, we have isolated a protein from these fat body extracts that accounts for the observed stem cell proliferation. SDS-PAGE analysis of the protein results in a single band of 77 kDa. Sequences of tryptic peptides from this protein are identical to internal sequences of the storage hexamer alpha-arylphorin. The alpha-arylphorin isolated by our procedure represents a small fraction of the total arylphorin present in the fat body extract. However, it alone seems responsible for the stimulation of mitotic activity in H. virescens midgut stem cells. C1 ARS, USDA, PSI, IBL, Beltsville, MD 20705 USA. Natl Inst Neurol Disorders & Stroke, Prot Peptide Sequencing Facil, NIH, Bethesda, MD USA. RP Blackburn, MB (reprint author), ARS, USDA, PSI, IBL, Bldg 011A,Rm 214,BARC W, Beltsville, MD 20705 USA. NR 22 TC 22 Z9 25 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0739-4462 J9 ARCH INSECT BIOCHEM JI Arch. Insect Biochem. Physiol. PD JAN PY 2004 VL 55 IS 1 BP 26 EP 32 DI 10.1002/arch.10119 PG 7 WC Biochemistry & Molecular Biology; Entomology; Physiology SC Biochemistry & Molecular Biology; Entomology; Physiology GA 760HQ UT WOS:000187805900002 PM 14691960 ER PT J AU Gwinn-Hardy, K AF Gwinn-Hardy, K TI When is ataxia not ataxia? SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID DOPA-RESPONSIVE PARKINSONISM; MACHADO-JOSEPH-DISEASE; TYPE-2; EXPANSION; PHENOTYPE; FAMILY; REPEAT; SCA2 C1 NINDS, Neurogenet Lab, Parkinsons Unit, NIH, Bethesda, MD 20892 USA. RP Gwinn-Hardy, K (reprint author), NINDS, Neurogenet Lab, Parkinsons Unit, NIH, Bethesda, MD 20892 USA. EM gwinnk@ninds.nih.gov RI Gwinn, Katrina/C-2508-2009 NR 17 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2004 VL 61 IS 1 BP 25 EP 26 DI 10.1001/archneur.61.1.25 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 763BV UT WOS:000188050900002 PM 14732614 ER PT J AU Longstreth, WT Katz, R Olson, J Bernick, C Carr, JJ Malinow, MR Hess, DL Cushman, M Schwartz, SM AF Longstreth, WT Katz, R Olson, J Bernick, C Carr, JJ Malinow, MR Hess, DL Cushman, M Schwartz, SM TI Plasma total homocysteine levels and cranial magnetic resonance imaging findings in elderly persons - The Cardiovascular Health Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID BRAIN INFARCTS; RISK FACTOR; DISEASE; PEOPLE; STROKE; MICROANGIOPATHY; RATIONALE; DESIGN; TRIAL AB Background: An elevated plasma total homocysteine (tHcy) level is associated with an increased risk of vascular disease. Some studies have shown associations between tHcy level and small-vessel disease of the brain on magnetic resonance imaging (MRI). Design: In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke had results for tHcy level and cranial MRI. We sought associations between tHcy level and MRI findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We controlled for other factors, including levels of creatinine, folate, and vitamins 136 and B,, and methylenetetrahydrofolate reductase genotype. Results: After controlling for age and sex, tHcy level was not associated with the individual MRI findings. Further adjustments for other factors and other blood tests had little effect on these findings. The only significant finding was a linear trend across quintiles of tHcy level and a pattern of MRI findings combining infarcts and high white matter grade. The linear trend remained significant after controlling for other risk factors and atherosclerotic markers (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96-11.20; P=.04 for linear trend) but was slightly diminished after further controlling for creatinine, folate, and vitamins B-6 and B-12 (odds ratio, 3.2; 95% confidence interval, 0.81-13. 10; P =.07 for linear trend). Conclusion: We were unable to confirm the results of previous studies with respect to tHcy level and individual MRI findings, although an association was seen for an MRI pattern combining infarcts and high white matter grade. C1 Univ Washington, Harborview Med Ctr, Dept Neurol, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98104 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Nevada, Div Neurol, Las Vegas, NV USA. Wake Forest Univ, Dept Radiol, Winston Salem, NC 27109 USA. Oregon Hlth Sci Univ, Div Pathobiol & Immunol, Portland, OR USA. Oregon Hlth Sci Univ, Div Reprod Sci, Portland, OR USA. Oregon Hlth Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR USA. Univ Vermont, Dept Med, Colchester, Essex, England. Univ Vermont, Dept Pathol, Colchester, Essex, England. RP Longstreth, WT (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurol, 325 9Th Ave, Seattle, WA 98104 USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 FU NHLBI NIH HHS [N01 HC 35129, N01 HC 15103, N01 HC 85079, N01 HC 85086, R01 HL 5471, R01 HL054711, R01 HL054711-03] NR 18 TC 35 Z9 36 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2004 VL 61 IS 1 BP 67 EP 72 DI 10.1001/archneur.61.1.67 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 763BV UT WOS:000188050900011 PM 14732622 ER PT J AU Lissau, I Overpeck, MD Ruan, WJ Due, P Holstein, BE Hediger, ML AF Lissau, I Overpeck, MD Ruan, WJ Due, P Holstein, BE Hediger, ML CA Hlth Behaviour Sch-aged Children Obes TI Body mass index and overweight in adolescents in 13 European countries, Israel, and the United States SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID CHILDHOOD OBESITY; FOLLOW-UP; CHILDREN; WEIGHT; PREVALENCE; MORTALITY; TRENDS; ASSOCIATION; MORBIDITY; VALIDITY AB Objective: To compare the body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) and the prevalence of BMI at or above the 85th centile and 95th centile (overweight) in adolescents. Design: Cross-sectional, nationally representative school based surveys in 1997-1998 by means of identical data collection methods. Setting: Austria, Czech Republic, Denmark, Flemish Belgium, Finland, France, Germany, Greece, Lithuania, Ireland, Israel, Portugal, Slovakia, Sweden, and the United States. Participants: A total of 29 242 boys and girls, aged 13 and 15 years. Main Outcome Measures: The BMI, BMI at or above the 85th centile, and BMI at or above the 95th centile (overweight) from self-reported height and weight. Results: The highest prevalence of overweight was found in the United States and the lowest in Lithuania. On the basis of the study reference standard, the prevalence of overweight (percentage) in the United States was 12.6% in 13-year-old boys, 10.8% in 13-year-old girls, 13.9% in 15-year-old boys, and 15.1% in 15-year-old girls, all significantly increased. Prevalence of overweight in Lithuania was significantly below the expected 5%, with 1.8% in 13-year-old boys, 2.6% in 13-year-old girls, 0.8% in 15-year-old boys, and 2.1% in 15-year-old girls. Relative rankings among countries were similar for BMI at or above the 85th centile, although there were less dramatic differences at this level. Conclusions: The highest prevalences of overweight were found in the United States, Ireland, Greece, and Portugal. C1 US Dept HHS, US Hlth Resources & Serv Adm, Maternal & Child Hlth Bur, Rockville, MD USA. Allied Technol Grp Inc, Rockville, MD USA. Univ Copenhagen, Dept Social Med, Copenhagen, Denmark. NICHHD, Div Epidemiol Stat & Prevent Res, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Lissau, I (reprint author), 18 Almindingen, DK-2870 Dyssegaard, Denmark. EM Ingeandhenning@mobilixnet.dk RI Gaspar de Matos, Margarida/H-3824-2012; OI Gaspar de Matos, Margarida/0000-0003-2114-2350; Lissau, Inge/0000-0002-2225-9975 NR 39 TC 218 Z9 227 U1 3 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JAN PY 2004 VL 158 IS 1 BP 27 EP 33 DI 10.1001/archpedi.158.1.27 PG 7 WC Pediatrics SC Pediatrics GA 760UK UT WOS:000187853400006 PM 14706954 ER PT J AU Burger, H Marincek, C Jaeger, RJ AF Burger, H Marincek, C Jaeger, RJ TI Prosthetic device provision to landmine survivors in Bosnia and Herzegovina: Outcomes in 3 ethnic groups SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE amputees; artificial limbs; prosthesis fitting; rehabilitation; war ID LOWER-LIMB AMPUTATION; LOCOMOTOR DISABILITY; MINE INJURIES; WAR AMPUTEES; VIETNAM-WAR; FOLLOW-UP; AFGHANISTAN; EXPERIENCE; REHABILITATION; MOZAMBIQUE AB Objective: To determine differences in prosthetic provision, use, and effectiveness among unilateral lower-extremity amputees from 3 ethnic groups in Bosnia and Herzegovina. Design: Case series with a consecutive sample of patients seen in field clinics. Setting: Multiple field clinics in Bosnia and Herzegovina from October 1998 to May 2002. Participants: A total of 671 patients were examined, and information about their prosthetic history was recorded from observation or verbal responses. The majority of the amputations resulted from injuries inflicted by landmines. Interventions: Not applicable. Main Outcome Measures: Self-reported walking distance per day, prosthesis functionality (functional or nonfunctional as assessed by a physician and a prothetist), prosthesis status (broken or nonbroken as assessed by a physician and a prothetist), and employment status. Results: Ethnic groups differed significantly in types of prostheses provided, functional status of the prostheses, and use of the prostheses for community ambulation. Conclusion: Prosthetic devices and delivery of rehabilitation services for unilateral lower-extremity amputees differed between ethnic groups. Despite these differences, functional prosthetic devices increased mobility. Persons in all 3 ethnic groups with functional prostheses were more mobile than persons with nonfunctional prostheses. The employment rate was higher for people with functional prostheses. C1 Inst Rehabil, Ljubljana 1112, Slovenia. US Dept HHS, Phys Disabilities Branch, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD USA. RP Burger, H (reprint author), Inst Rehabil, Linhartova 51, Ljubljana 1112, Slovenia. EM helena.burger@mail.ir-rs.si NR 46 TC 4 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2004 VL 85 IS 1 BP 19 EP 28 DI 10.1016/j.apmr.2003.07.010 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 761GH UT WOS:000187892800004 PM 14970963 ER PT J AU Moratz, C Harrison, K Kehri, JH AF Moratz, C Harrison, K Kehri, JH TI Role of RGS proteins in regulating the migration of B lymphocytes SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE RGS proteins; chemokine; lymphoid tissue; germinal centers; G protein ID GTPASE-ACTIVATING PROTEINS; HETEROTRIMERIC G-PROTEINS; CELL-MIGRATION; ANTIBODY-RESPONSES; LYMPHOID-TISSUES; TRANSITION-STATE; FAMILY-MEMBERS; ALPHA-SUBUNITS; IN-VIVO; CHEMOKINE AB The migration of B lymphocytes into distinct microenvironments in secondary lymphoid tissues and maintenance of cells in these micro-domains is strictly structured and likely supports the proper regulation of immune responses to both foreign and self-antigens. Chemokines' and other chemoattactants' signals serve as signposts to direct cell migration. They signal cells through heptahelical receptors, which couple to heterotrimeric G proteins (G protein-coupled receptors or GPCRs). The regulation of the signals transduced through these receptors ultimately determines the positioning of cells in lymphoid tissues. A variety of mechanisms regulate GPCR signaling including a family of approximately 25 proteins termed regulators of G protein signaling (RGS). These proteins act as GTPase activating proteins for Galpha subunits and can also function as effector antagonists of specific Got subunits, thereby attenuating signaling through GPCRs such as chemokine receptors. RGS proteins possess some degree of receptor and Galpha subunit specificity. Thus, the particular spectrum of RGS proteins and their expression levels within a cell will determine the duration and magnitude of G protein signaling initiated by chemokines. In this review we illustrate the role RGS proteins have in regulating B cell signaling responses to chemoattractant stimuli during homeostasis as well as during an immune response. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20891 USA. RP Kehri, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bld 10,Rm 11B13,10 Ctr Dr,MSC 1876, Bethesda, MD 20891 USA. EM jkehri@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 70 TC 9 Z9 10 U1 0 U2 1 PU INST IMMUNOLOGY & EXPERIMENTAL THERAPY PI WROCLAW PA POLISH ACADEMY OF SCIENCES CZERSKA 12, 53-114 WROCLAW, POLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PD JAN-FEB PY 2004 VL 52 IS 1 BP 27 EP 35 PG 9 WC Immunology SC Immunology GA 801AI UT WOS:000220068400004 PM 15053230 ER PT J AU Bolzani, VD Cragg, GM AF Bolzani, VD Cragg, GM TI Professor Otto Richard Gottlieb - A tribute SO ARKIVOC LA English DT Biographical-Item C1 UNESP, Inst Quim, Sao Paulo, Brazil. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Nat Prod Branch, Bethesda, MD 20892 USA. RP Bolzani, VD (reprint author), UNESP, Inst Quim, Sao Paulo, Brazil. NR 2 TC 1 Z9 1 U1 0 U2 2 PU ARKAT USA INC PI GAINESVILLE PA C/O ALAN R KATRITZKY, UNIV FLORIDA, DEPT CHEMISTRY, PO BOX 117200, GAINESVILLE, FL 32611 USA J9 ARKIVOC JI Arkivoc PY 2004 BP 1 EP 4 PN 6 PG 4 WC Chemistry, Organic SC Chemistry GA 857XN UT WOS:000224153100001 ER PT J AU Grammer, AC Fischer, R Lee, O Zhang, X Lipsky, PE AF Grammer, AC Fischer, R Lee, O Zhang, X Lipsky, PE TI Flow cytometric assessment of the signaling status of human B lymphocytes from normal and autoimmune individuals SO ARTHRITIS RESEARCH & THERAPY LA English DT Review DE B lymphocytes; flow cytometry; human; IkB; intracellular staining; MAPK; SLE ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELL SUBSETS; TYROSINE PHOSPHORYLATION; CD154-CD40 INTERACTIONS; SUSCEPTIBILITY GENES; GERMINAL-CENTERS; GENOME SCAN; KINASE; DIFFERENTIATION; TRANSDUCTION AB Abnormalities in lymphocyte signaling cascades are thought to play an important role in the development of autoimmune disease. However, the large amount of cellular material needed for standard biochemical assessment of signaling status has made it difficult to evaluate putative abnormalities completely using primary lymphocytes. The development of technology to employ intracellular staining and flow cytometry to assess the signaling status of individual cells has now made it possible to delineate the perturbations that are present in lymphocytes from patients with autoimmune disease. As an example, human B cells from the Ramos B cell line and the periphery of systemic lupus erythematosus (SLE) patients or normal nonautoimmune controls were assessed for activation of the NF-kB and mitogen activated protein kinase (MAPK) signaling cascades by intracellular multiparameter flow cytometric analysis and biochemical Western blotting. In combination with fluorochrome conjugated antibodies specific for surface proteins that define B cell subsets, antibodies that recognize activated, or phosphorylated inhibitors of kB (IkB) as well as the extracellular regulated kinase (ERK), jun N-terminal kinase (JNK) or p38 MAPKs were used to stain fixed and permeabilized human B cells and analyze them flow cytometrically. Examination of the known signaling pathways following engagement of CD40 on human B cells confirmed that intracellular flow cytometry and Western blotting equivalently assay CD154-induced phosphorylation and degradation of IkB proteins as well as phosphorylation of the MAPKs ERK, JNK and p38. In addition, B cells from the periphery of SLE patients had a more activated status immediately ex vivo as assessed by intracellular flow cytometric analysis of phosphorylated ERK, JNK and p38 when compared with B cells from the periphery of normal, nonautoimmune individuals. Together, these results indicate that multiparameter intracellular flow cytometric analysis of signaling pathways, such as the NF-kB and MAPK cascades, can be used routinely to assess the activation status of a small number of cells and thus delineate abnormalities in signaling molecules expressed in primary lymphocytes from patients with autoimmune disease. C1 NIAMS, Intramural Res Prog, Autoimmun Branch, Bethesda, MD 20892 USA. NIAMS, B Cell Biol Grp, Bethesda, MD 20892 USA. RP Grammer, AC (reprint author), NIAMS, Intramural Res Prog, Autoimmun Branch, 9000 Rockville Pike,Bldg 10,Rm 6D47A, Bethesda, MD 20892 USA. EM grammera@mail.nih.gov NR 37 TC 30 Z9 30 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2004 VL 6 IS 1 BP 28 EP 38 DI 10.1086/ar1155 PG 11 WC Rheumatology SC Rheumatology GA 750WM UT WOS:000187021500018 ER PT J AU Waldmann, TA AF Waldmann, TA TI Targeting the interleukin-15/interleukin-15 receptor system in inflammatory autoimmune diseases SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE autoimmune disease; interleukin-15; memory T cells; rheumatoid arthritis ID RHEUMATOID-ARTHRITIS; BETA-CHAIN; T-CELLS; INTERLEUKIN-2 RECEPTOR; IL-15 RECEPTOR; IN-VIVO; CYTOKINES; HOMEOSTASIS; MODEL; DEATH AB Interleukin (IL)-15 is a dangerous inflammatory cytokine that induces tumor-necrosis factor-alpha, IL-1beta and inflammatory chemokines. It inhibits self-tolerance mediated by IL-2 mediated activation-induced cell death and facilitates maintenance of CD8(+) memory T-cell survival including that of self-directed memory cells. Disordered IL-15 expression has been reported in patients with an array of inflammatory autoimmune diseases. A series of therapeutic agents that inhibit IL-15 action have been introduced, including the soluble IL-15 receptor (IL-15R) alpha chain, mutant IL-15, and antibodies directed against the IL-15 cytokine and against the IL-2R/IL-15R beta subunit used by IL-2 and IL-15. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov NR 21 TC 38 Z9 39 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2004 VL 6 IS 4 BP 174 EP 177 DI 10.1186/ar1202 PG 4 WC Rheumatology SC Rheumatology GA 841LL UT WOS:000222931200007 PM 15225362 ER PT J AU Mittleman, BB AF Mittleman, BB TI Biomarkers for systemic lupus erythematosus: has the right time finally arrived? SO ARTHRITIS RESEARCH & THERAPY LA English DT Editorial Material ID KNOWLEDGE C1 NIAMSD, Sci & Technol Branch, Sci Interchange Sect, NIH,US Dept Hlth Human Serv, Bethesda, MD 20892 USA. RP Mittleman, BB (reprint author), NIAMSD, Sci & Technol Branch, Sci Interchange Sect, NIH,US Dept Hlth Human Serv, Bethesda, MD 20892 USA. EM mittlemb@mail.nih.gov NR 4 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2004 VL 6 IS 5 BP 223 EP 224 DI 10.1186/ar1186 PG 2 WC Rheumatology SC Rheumatology GA 855RU UT WOS:000223992200005 PM 15380037 ER PT J AU Carrick, DM Lai, WS Blackshear, PJ AF Carrick, DM Lai, WS Blackshear, PJ TI The tandem CCCH zinc finger protein tristetraprolin and its relevance to cytokine mRNA turnover and arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Review DE AU-rich elements; deadenylation; granulocyte-macrophage colony-stimulating factor; mRNA turnover; rheumatoid arthritis; tumor necrosis factor ID AU-RICH ELEMENT; TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; TNF-ALPHA; TRANSCRIPTION FACTOR; DEFICIENCY SYNDROME; SWISS-MODEL; SEQUENCE; BINDING; EXPRESSION AB Tristetraprolin (TTP) is the best-studied member of a small family of three proteins in humans that is characterized by a tandem CCCH zinc finger (TZF) domain with highly conserved sequences and spacing. Although initially discovered as a gene that could be induced rapidly and transiently by the stimulation of fibroblasts with growth factors and mitogens, it is now known that TTP can bind to AU-rich elements in mRNA, leading to the removal of the poly(A) tail from that mRNA and increased rates of mRNA turnover. This activity was discovered after TTP-deficient mice were created and found to have a systemic inflammatory syndrome with severe polyarticular arthritis and autoimmunity, as well as medullary and extramedullary myeloid hyperplasia. The syndrome seemed to be due predominantly to excess circulating tumor necrosis factor-alpha (TNF-alpha), resulting from the increased stability of the TNF-alpha mRNA and subsequent higher rates of secretion of the cytokine. The myeloid hyperplasia might be due in part to increased stability of granulocyte-macrophage colony-stimulating factor (GM-CSF). This review highlights briefly the characteristics of the TTP-deficiency syndrome in mice and its possible genetic modifiers, as well as recent data on the characteristics of the TTP-binding site in the TNF-alpha and GM-CSF mRNAs. Recent structural data on the characteristics of the complex between RNA and one of the TTP-related proteins are reviewed, and used to model the TTP-RNA binding complex. We review the current knowledge of TTP sequence variants in humans and discuss the possible contributions of the TTP-related proteins in mouse physiology and in human monocytes. The TTP pathway of TNF-alpha and GM-CSF mRNA degradation is a possible novel target for anti-TNF-alpha therapies for rheumatoid arthritis, and also for other conditions proven to respond to anti-TNF-alpha therapy. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, POB 12233, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov NR 59 TC 116 Z9 120 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2004 VL 6 IS 6 BP 248 EP 264 DI 10.1186/ar1441 PG 17 WC Rheumatology SC Rheumatology GA 871US UT WOS:000225160100003 PM 15535838 ER PT J AU Witter, J Dionne, RA AF Witter, J Dionne, RA TI What can chronic arthritis pain teach about developing new analgesic drugs? SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE analgesics; chronic pain; drug development; individual responses; pain mechanisms AB Chronic pain remains an important public health need with greater impact on the US economy than most other chronic conditions. Current pain management is largely limited to opioids and non-steroidal anti-inflammatory drugs, indicating a gap in the translation of new knowledge to the development of improved pain treatments. Strategies suggested include the re-evaluation of current drug screening methods, a recognition that molecular-genetic events occurring acutely contribute to the development of pain chronicity, the validation of analgesic targets in the intended patient population, consideration of the unique genetic profile that varies between individuals, and the introduction of individual response measures to improve the capture of outcomes in clinical trials. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM raymond.dionne@nih.gov NR 6 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2004 VL 6 IS 6 BP 279 EP 281 DI 10.1186/ar1450 PG 3 WC Rheumatology SC Rheumatology GA 871US UT WOS:000225160100005 PM 15535840 ER PT J AU Depner, TA Greene, T Daugirdas, JT Cheung, AK Gotch, FA Leypoldt, JK AF Depner, TA Greene, T Daugirdas, JT Cheung, AK Gotch, FA Leypoldt, JK TI Dialyzer performance in the HEMO study: In vivo K(0)A and true blood flow determined from a model of cross-dialyzer urea extraction SO ASAIO JOURNAL LA English DT Article ID TRANSFER-AREA COEFFICIENTS; HEMODIALYSIS HEMO; DIALYSIS; INCREASES; CLEARANCE; KT/V; FLUX AB Inlet and outlet blood urea concentrations (C-in and C-out) can be used to directly measure dialyzer performance if simultaneous blood flow measurements (Q(b)) are available. Dialyzer clearance, for example, is the product of the urea extraction ratio [ER = (C-in - C-out)/C-in] and Q(b). Urea concentrations are measured routinely in all hemodialysis clinics, but Q(b) is usually reported as the product of the pump rotational speed and pump segment stroke volume, which can be inaccurate at high flow rates. Dialyzer urea extraction is also a function of Q(b), dialysate flow (Q(d)), and the membrane permeability-area coefficient (K(0)A) for urea. To determine true in vivo values for Q(b) and K(0)A in the absence of direct flow measurements, we developed a model based on an existing mathematical equation for hemodialyzer ER under conditions of countercurrent flow. Q(b), K(0)A, and other variables were adjusted to fit the modeled ER to ER measured in 1,285 patients treated with Q(b) that ranged from 200 to 450 ml/min during the HEMO Study. Fitting was performed by least squares nonlinear regression using parametric and nonparametric methods for estimating true flow. As Q(b) rose above 250 ml/min, both methods for estimating actual Q(b) showed increasing deviations from the flow reported by the blood pump meter. Modeled values for K(0)A differed significantly among dialyzer models, ranging from 71% to 96% of the in vitro values. The previously described 14% increase in K(0)A, as Q(d) increased in vitro from 500 to 800 ml/min, was much less in vivo, averaging only 5.5 +/- 1.5% higher. Dialyzer reprocessing was associated with a 6.3 +/- 1.0% reduction in K(0)A and an approximate 2% fall in urea clearance per 10 reuses (p < 0.001). Multiple regression analysis showed a small but significant dialysis center effect on ER but no independent effects of other variables, including the ultrafiltration rate, diabetic status, race, ethnicity, sex, method of reuse, treatment time, access recirculation, and use of central venous accesses. The new algorithm allowed a more accurate determination of true Q(b) and in vivo K(0)A in the absence of direct flow measurements in a large population treated with a wide range of blood flow rates. Application of this technique for more than 1000 patients in the HEMO Study confirmed that in vitro measurements using simple crystalloid solutions cannot readily substitute for in vivo measurements of dialyzer function, and permitted a more accurate calculation of each patient's prescribed dialysis dose and urea volume. C1 NIH, Hemodialysis HEMO Study Grp, Bethesda, MD 20892 USA. RP Depner, TA (reprint author), Univ Calif Davis, Div Nephrol, 4150 V St,Suite 3500, Sacramento, CA 95817 USA. EM tadepner@ucdavis.edu NR 21 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 2004 VL 50 IS 1 BP 85 EP 93 DI 10.1097/01.MAT.0000104824.55517.6C PG 9 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 766TW UT WOS:000188392500015 PM 14763497 ER PT J AU Sharrett, AR Coady, SA Folsom, AR Couper, DJ Heiss, G AF Sharrett, AR Coady, SA Folsom, AR Couper, DJ Heiss, G TI Smoking and diabetes differ in their associations with subclinical atherosclerosis and coronary heart disease - the ARIC Study SO ATHEROSCLEROSIS LA English DT Article DE atherosclerosis; coronary disease; carotid artery disease; diabetes mellitus; smoking ID CARDIOVASCULAR RISK-FACTORS; CAROTID ATHEROSCLEROSIS; VASCULAR-DISEASE; ARTERY-DISEASE; COMMUNITIES; WOMEN; MEN; LESIONS; PLAQUE; YOUTH AB Atherosclerosis, nearly universally present in major arteries of Western adults, is characterized in all affected arteries by cholesterol-laden plaques and consistently associated with blood cholesterol levels. Other risk factors are reported to have relatively stronger or weaker associations with different atherosclerotic manifestations, but such differences have never previously been quantified. Measuring them may offer fresh clues to atherogenic processes and their prevention. The Atherosclerosis Risk in Communities Stud (ARIC) ascertained incident coronary heart disease (CHD) and measured subclinical atherosclerosis as carotid artery intimal medial thickness using ultrasound and as lower extremity arterial disease (LEAD) using ankle-brachial blood pressure index. Blood cholesterol was associated with all endpoints. When standardized against LDL cholesterol associations, diabetes and smoking showed substantially different strengths of associations with different endpoints. Relative to associations with LDL cholesterol: (1) smoking, but not diabetes, increased in its strength of association with the severity of the underlying arterial disease; (2) the diabetes and smoking associations with CHD were much stronger in women than men, a phenomenon which. the standardization pattern suggests, is due to a gender difference in CHD pathogenesis, possibly attributable to arteriolar differences. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. NHLBI, Epidemiol & Biomet Program, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Sharrett, AR (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E6518, Baltimore, MD 21218 USA. EM rsharret@jhsph.edu NR 28 TC 27 Z9 29 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2004 VL 172 IS 1 BP 143 EP 149 DI 10.1016/j.atherosclerosis.2003.09.015 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 765NJ UT WOS:000188289600019 ER PT J AU Cui, RZ Iso, H Pi, JB Kumagai, Y Yamagishi, K Tanigawa, T Shimojo, N Shimamoto, T AF Cui, RZ Iso, H Pi, JB Kumagai, Y Yamagishi, K Tanigawa, T Shimojo, N Shimamoto, T TI Urinary cyclic GMP excretion and blood pressure levels in a general population SO ATHEROSCLEROSIS LA English DT Article DE cyclic GMP; nitric oxide; hypertension; cross-sectional studies ID DEPENDENT VASCULAR RELAXATION; NITRIC-OXIDE SYNTHESIS; ESSENTIAL-HYPERTENSION; RELAXING FACTOR; L-ARGININE; SMOOTH-MUSCLE; JAPANESE MEN; ENDOTHELIUM; DISEASE; RELEASE AB Dysfunction of the nitric oxide (NO) system is potentially involved in the development of hypertension, but only limited data are currently available from experimental or clinical studies. We investigated cross-sectionally the relation between urinary excretion of cyclic guanosine 3'.5'-monophosphate (cyclic GMP), a second messenger of NO, and hypertension in a general population sample of Japanese men and women. The samples comprised 1541 subjects (788 men and 753 women) aged 40-79 years who participated in cardiovascular risk surveys between 1997 and 2002 and underwent a 24 h urine collection. Urinary excretion of cyclic GMP was measured using a I-125-labeled cyclic GMP radioimmunoassay, and was adjusted for urinary creatinine, excretion (nmol/mmol creatinine). Urinary cyclic GMP excretion was 66.0 +/- 62.0 nmol/mmol creatinine (mean +/- S.D.). Compared with normal blood pressure individuals, the multivariate-adjusted mean value of urinary cyclic GMP excretion was significantly higher in people with moderate hypertension, but not higher in severe hypertension. Among subjects with hypertensive end-organ damage, we observed reduced urinary cyclic GMP excretion in severe hypertension and no increased excretion in moderate hypertension, compared with normal blood pressure. Although we had the limited number of subjects with severe hypertension (n = 15), our data suggest that NO bioactivity may be increase in the early stage of hypertension but decreased in severe hypertension with end-organ damage. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Univ Tsukuba, Inst Community Med, Dept Publ Hlth Med, Tsukuba, Ibaraki 3058575, Japan. Univ Tsukuba, Inst Community Med, Dept Environm Med, Tsukuba, Ibaraki 3058575, Japan. NIEHS, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, NCI,NIH, Res Triangle Pk, NC 27709 USA. Osaka Med Ctr Hlth Sci & Promot, Higashinari Ku, Osaka 5370025, Japan. RP Iso, H (reprint author), Univ Tsukuba, Inst Community Med, Dept Publ Hlth Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM fygh5640@mb.infoweb.ne.jp OI Iso, Hiroyasu /0000-0002-9241-7289; yamagishi, kazumasa/0000-0003-3301-5519 NR 27 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2004 VL 172 IS 1 BP 161 EP 166 DI 10.1016/j.atherosclerosis.2003.09.018 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 765NJ UT WOS:000188289600022 PM 14709371 ER PT J AU Chandler, RK Peters, RH Field, G Juliano-Bult, D AF Chandler, RK Peters, RH Field, G Juliano-Bult, D TI Challenges in implementing evidence-based treatment practices for co-occurring disorders in the criminal justice system SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID SUBSTANCE-ABUSE TREATMENT; PRISON-BASED TREATMENT; SEVERE MENTAL-ILLNESS; DRUG-TREATMENT; PSYCHIATRIC-DISORDERS; JAIL DETAINEES; INCARCERATED WOMEN; TREATMENT PROGRAM; DUAL DISORDERS; PAROLE SERVICE AB The presence of adults with mental health and substance abuse disorders within the criminal justice system has become increasingly evident over the past decade. Interventions and treatment services have been designed and research conducted in an effort to establish evidence-based practices that effectively address the complex needs of this population. However, adopting and implementing these evidence-based interventions and practices within the real-world setting of criminal justice environments is challenging. This article reviews the research literature related to evidence-based treatment practices for offenders with co-occurring mental health and substance abuse disorders and explores the inherent challenges of fitting these interventions and services within criminal justice settings. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NIDA, NIH, Bethesda, MD USA. Univ S Florida, Florida Mental Hlth Inst, Dept Mental Hlth Law & Policy, Tampa, FL 33620 USA. RP Chandler, RK (reprint author), NIDA, NIH, 6001 Execut Blvd,Room 4222,MSC 9565, Bethesda, MD USA. EM rchandle@nida.nih.gov NR 92 TC 27 Z9 27 U1 3 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PY 2004 VL 22 IS 4 BP 431 EP 448 DI 10.1002/bsl.598 PG 18 WC Psychology, Applied; Law SC Psychology; Government & Law GA 845TW UT WOS:000223269200002 PM 15282833 ER PT S AU Rose, AB Merke, DP Clasen, LS Rosenthal, MA Wallace, GL Vaituzis, AC Fields, JD Giedd, JN AF Rose, AB Merke, DP Clasen, LS Rosenthal, MA Wallace, GL Vaituzis, AC Fields, JD Giedd, JN BE Yehuda, R McEwen, B TI Effects of hormones and sex chromosomes on stress-influenced regions of the developing pediatric brain SO BIOBEHAVIORAL STRESS RESPONSE: PROTECTIVE AND DAMAGING EFFECTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protective and Damaging Effects of the Biobehavioral Stress Response CY SEP 07-09, 2003 CL New York, NY SP Glaxosmithkline, Janssen Pharmaceut, Pfizer Inc, Solvay, Bristol Myers Squibb, Novartis Pharmaceut, Astrazeneca, Eli Lilly & Co, Johnson & Johnson, Merck, Ortho McNeil Pharmaceut Inc DE hormones; sex chromosomes; stress; pediatric brain ID AMYGDALA AB Recently discovered sexual dimorphism within developing brain structures such as the amygdala and hippocampus suggests that biological factors may account for many of the sex differences in stress reactivity. In this study, we have relied on studies of naturally occurring anomalous processes, such as congenital adrenal hyperplasia (CAH) and Klinefelter's syndrome (XXY), to observe the effects of hormones and sex chromosomes on brain structures thought to influence an individual's vulnerability to stress. Brain magnetic resonance imaging (MRI) scans were obtained both from 16 boys with classic CAH and 34 age- and sex-matched controls and from 20 XXY children and 40 age-matched controls. Smaller amygdala volumes were observed in boys with CAH than in matched controls, and in XXY patients than in matched controls. XXY patients were also found to have smaller hippocampus volumes when compared with matched controls. Acknowledging that hormone and sex chromosome effects upon the developing human brain are widespread and complex, it is difficult to conclude, with any certainty, the etiology of the differences found in this study. Future studies that examine longitudinal data and/or other diagnostic groups, however, may help to better elucidate specific hormone and sex chromosome effects upon stress-related structures in the brain. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, NIH, Bldg 10,Rm 4C110,10 Ctr Dr, Bethesda, MD 20892 USA. EM jgiedd@mail.nih.gov RI Giedd, Jay/A-3080-2008; Wallace, Gregory/A-4789-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace, Gregory/0000-0003-0329-5054 NR 3 TC 20 Z9 20 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-518-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1032 BP 231 EP 233 DI 10.1196/annals.1314.027 PG 3 WC Behavioral Sciences; Endocrinology & Metabolism; Multidisciplinary Sciences; Physiology; Psychology SC Behavioral Sciences; Endocrinology & Metabolism; Science & Technology - Other Topics; Physiology; Psychology GA BBW44 UT WOS:000228129700028 PM 15677417 ER PT J AU Liu, QR Zhang, PW Lin, ZC Li, QF Woods, AS Troncoso, J Uhl, GR AF Liu, QR Zhang, PW Lin, ZC Li, QF Woods, AS Troncoso, J Uhl, GR TI GBPI, a novel gastrointestinal- and brain-specific PP1-inhibitory protein, is activated by PKC and inactivated by PKA SO BIOCHEMICAL JOURNAL LA English DT Article DE cell signalling; inhibitor; PKA (protein kinase A); PKC (protein kinase C); PP1 (protein phosphatase 1) ID INTEGRIN-LINKED KINASE; CAMP-REGULATED PHOSPHOPROTEIN; SITE-DIRECTED MUTAGENESIS; MYOSIN PHOSPHATASE; SMOOTH-MUSCLE; CATALYTIC SUBUNIT; NUCLEOPHOSMIN B23; CRYSTAL-STRUCTURE; IN-VIVO; PHOSPHORYLATION AB The activities of PP1 (protein phosphatase 1), a principal cellular phosphatase that reverses serine/threonine protein phosphorylation, can be altered by inhibitors whose activities are themselves regulated by phosphorylation. We now describe a novel PKC (protein kinase C)-dependent PP1 inhibitor, namely GBPI (gut and brain phosphatase inhibitor). The shorter mRNA that encodes this protein, GBPI-1, is expressed in brain, stomach, small intestine, colon and kidney, whereas a longer GBPI-2 splice variant mRNA is found in testis. Human GBPI-1 mRNA encodes a 145-amino-acid, 16.5 kDa protein with pI 7.92. GBPI contains a consensus PP1-binding motif at residues 21-25 and consensus sites for phosphorylation by enzymes, including PKC, PKA (protein kinase A or cAMP-dependent protein kinase) and casein kinase II. Recombinant GBPI-1-fusion protein inhibits PP1 activity with IC50 = 3 nM after phosphorylation by PKC. Phospho-GBPI can even enhance PP2A activity by > 50% at submicromolar concentrations. Non-phosphorylated GBPI-1 is inactive in both assays. Each of the mutations in amino acids located in potential PP1-binding sequences, K21E + K22E and W25A, decrease the ability of GBPI-1 to inhibit PP1. Mutations in the potential PKC phosphoacceptor site T58E also dramatically decrease the ability of GBPI-1 to inhibit PP1. Interestingly, when PKC-phosphorylated GBPI-1 is further phosphorylated by PKA, it no longer inhibits PP1. Thus, GBPI-1 is well positioned to integrate PKC and PKA modulation of PP1 to regulate differentially protein phosphorylation patterns in brain and gut. GBPI, its closest family member CPI (PKC-potentiated PP1 inhibitor) and two other family members, kinase-enhanced phosphatase inhibitor and phosphatase holoenzyme inhibitor, probably modulate integrated control of protein phosphorylation states in these and other tissues. C1 NIDA, IRP, Mol Neurobiol Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Xiamen Univ, Lab Cell Biol & Tumor Cell Engn, Xiamen 361005, Peoples R China. NIDA, IRP, Chem & Drug Metab Sect, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA. RP Uhl, GR (reprint author), NIDA, IRP, Mol Neurobiol Branch, NIH,Dept Hlth & Human Serv, POB 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Li, QF/G-4604-2010; Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 NR 43 TC 20 Z9 28 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2004 VL 377 BP 171 EP 181 DI 10.1042/BJ20030128 PN 1 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 762DH UT WOS:000187955200018 PM 12974676 ER PT J AU Youle, RJ AF Youle, RJ TI Mitochondrial morphogenesis and apoptosis SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 13th European Bioenergetics Conference (EBEC 2004) CY AUG 21-26, 2004 CL Pisa, ITALY C1 NINDS, Biochem Sect, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2004 VL 1658 SU S BP 81 EP 81 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 848XE UT WOS:000223500600093 ER PT J AU Hopper, RK Carroll, S Balaban, RS AF Hopper, RK Carroll, S Balaban, RS TI Proteomic analysis of calcium-induced phosphorylation events in porcine heart mitochondria SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 13th European Bioenergetics Conference (EBEC 2004) CY AUG 21-26, 2004 CL Pisa, ITALY C1 NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. EM hopperr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2004 VL 1658 SU S BP 178 EP 178 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 848XE UT WOS:000223500600235 ER PT J AU Karbowski, M Jeong, SY Youle, R AF Karbowski, M Jeong, SY Youle, R TI Quantification of mitochondrial fusion SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 13th European Bioenergetics Conference (EBEC 2004) CY AUG 21-26, 2004 CL Pisa, ITALY C1 NINDS, Biochem Sect, NIH, Bethesda, MD 20815 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2004 VL 1658 SU S BP 179 EP 179 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 848XE UT WOS:000223500600238 ER PT J AU Rostovtseva, T Antonsson, B Suzuki, M Youle, R Colombini, M Bezrukov, S AF Rostovtseva, T Antonsson, B Suzuki, M Youle, R Colombini, M Bezrukov, S TI Effect of proapoptotic proteins on VDAC channels SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 13th European Bioenergetics Conference (EBEC 2004) CY AUG 21-26, 2004 CL Pisa, ITALY C1 NICHD, Bethesda, MD USA. Serono Pharmaceut Res Inst, Geneva, Switzerland. NINDS, NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. RI Colombini, Marco/A-1540-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2004 VL 1658 SU S BP 261 EP 261 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 848XE UT WOS:000223500600360 ER PT J AU Divi, R Leonard, S Kuo, M Nagashima, K St Claire, M Wade, N Walker, V Poirier, M AF Divi, R Leonard, S Kuo, M Nagashima, K St Claire, M Wade, N Walker, V Poirier, M TI In utero exposure to anti-HIV drugs causes mitochondrial damage and mtDNA depletion in umbilical cord tissue from human infants and fetal Erythrocebus Patas monkeys SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 6th European Meeting on Mitochondrial Pathology CY JUL 01-04, 2004 CL Univ Med Ctr Nijmegen, Nijmegen, NETHERLANDS HO Univ Med Ctr Nijmegen C1 NCI, CDI LCCTP, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD USA. NCI, SAIC, Frederick, MD 21701 USA. Albany Med Ctr, Albany, NY USA. LRRI, Albuquerque, NM USA. EM divir@exchange.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2004 VL 1657 SU 1 BP 97 EP 98 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 836WX UT WOS:000222588000250 ER PT J AU Dean, J AF Dean, J TI Reassessing the molecular biology of sperm-egg recognition with mouse genetics SO BIOESSAYS LA English DT Review ID ZONA-PELLUCIDA GLYCOPROTEINS; O-LINKED OLIGOSACCHARIDES; FURIN CLEAVAGE-SITE; ACROSOME REACTION; RECEPTOR ACTIVITY; XENOPUS-LAEVIS; COORDINATE EXPRESSION; TRANSGENIC MICE; KNOCKOUT MICE; PIG OOCYTE AB The zona pellucida is an extracellular coat that surrounds mammalian eggs and early embryos. This insoluble matrix separates germ from somatic cells during folliculogenesis and plays critical roles during fertilization and early development. The mouse and human zona pellucida contain three glycoproteins (ZP1 or ZPB, ZP2, ZP3), the primary structures of which have been deduced by molecular cloning. Targeted mutagenesis of endogenous mouse genes and transgenesis with human homologues provide models to investigate the roles of individual zona components. Collectively, the genetic data indicate that no single mouse zona pellucida protein is obligatory for taxon-specific sperm binding and that two human proteins are not sufficient to support human sperm binding. An observed post-fertilization persistence of mouse sperm binding to "humanized" zona pellucida correlates with uncleaved ZP2. These observations are consistent with a model for sperm binding in which the supramolecular structure of the zona pellucida necessary for sperm binding is modulated by the cleavage status of ZP2. Published 2003 Wiley Periodicals, Inc.(dagger) C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3134,50 South Dr, Bethesda, MD 20892 USA. EM jurrien@helix.nih.gov NR 76 TC 58 Z9 60 U1 0 U2 10 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2004 VL 26 IS 1 BP 29 EP 38 DI 10.1002/bies.10412 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 760YF UT WOS:000187862300005 PM 14696038 ER PT J AU Sommers, CL Samelson, LE Love, PE AF Sommers, CL Samelson, LE Love, PE TI LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways SO BIOESSAYS LA English DT Review ID CELL DEVELOPMENT; TYROSINE RESIDUES; KNOCKOUT MICE; KINASE-C; PRE-TCR; ACTIVATION; TRANSDUCTION; RAS; DIFFERENTIATION; MUTATION AB Adapter molecules in a variety of signal transduction systems link receptors to a limited number of commonly used downstream signaling pathways. During T-cell development and mature T-cell effector function, a multi-chain receptor (the pre-T-cell antigen receptor or the T-cell antigen receptor) activates several protein tyrosine kinases. Receptor and kinase activation is linked to distal signaling pathways (PLC-gamma1 activation, Ca2+ influx, PKC activation and Ras/Erk activation) via the adapter protein LAT (Linker for Activation of T cells). Structure/function studies of LAT including expression of selected LAT point mutations in vivo reveals that these multiple pathways are integrated at the level of the LAT adapter. These studies suggest that similar levels of control may be found in other systems where adapter molecules are known to have important functions. Published 2003 Wiley Periodicals, Inc(dagger). C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Sommers, CL (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM connies@helix.nih.gov NR 47 TC 49 Z9 56 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2004 VL 26 IS 1 BP 61 EP 67 DI 10.1002/bies.10384 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 760YF UT WOS:000187862300008 PM 14696041 ER PT J AU Ridnour, LA Thomas, DD Mancardi, D Espey, MG Miranda, KM Paolocci, N Feelisch, M Fukuto, J Wink, DA AF Ridnour, LA Thomas, DD Mancardi, D Espey, MG Miranda, KM Paolocci, N Feelisch, M Fukuto, J Wink, DA TI The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations SO BIOLOGICAL CHEMISTRY LA English DT Review DE N-nitrosamines; nitration; nitrosative stress; NO2; N2O3; S-nitrosothiols ID WOODCHUCK HEPATITIS-VIRUS; ENDOTHELIAL-CELLS; RELAXING FACTOR; GUANYLATE-CYCLASE; HYDROGEN-PEROXIDE; CHEMICAL BIOLOGY; S-NITROSOTHIOLS; DONOR COMPOUNDS; SERUM-ALBUMIN; MARMOTA-MONAX AB This review addresses many of the chemical aspects of nitrosative stress mediated by N2O3. From a cellular perspective, N2O3 and the resulting reactive nitrogen oxide species target specific motifs such as thiols, lysine active sites, and zinc fingers and is dependant upon both the rates of production as well as consumption of NO and must be taken into account in order to access the nitrosative environment. Since production and consumption are integral parts of N2O3 generation, we predict that nitrosative stress occurs under specific conditions, such as chronic inflammation. In contrast to conditions of stress, nitrosative chemistry may also provide cellular protection through the regulation of critical signaling pathways. Therefore, a careful evaluation of the chemistry of nitrosation based upon specific experimental conditions may provide a better understanding of how the subtle balance between oxidative and nitrosative stress may be involved in the etiology and control of various disease processes. C1 NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Wink, DA (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM wink@mail.nih.gov RI Miranda, Katrina/B-7823-2009; Feelisch, Martin/C-3042-2008; OI Feelisch, Martin/0000-0003-2320-1158; MANCARDI, Daniele/0000-0003-3809-6047 NR 87 TC 140 Z9 149 U1 2 U2 17 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD JAN PY 2004 VL 385 IS 1 BP 1 EP 10 DI 10.1515/BC.2004.001 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 773JK UT WOS:000188919500001 PM 14977040 ER PT J AU Dickstein, DP Treland, JE Snow, J McClure, EB Mehta, MS Towbin, KE Pine, DS Leibenluft, E AF Dickstein, DP Treland, JE Snow, J McClure, EB Mehta, MS Towbin, KE Pine, DS Leibenluft, E TI Neuropsychological performance in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; child; psychological tests; neuropsychology ID DEFICIT HYPERACTIVITY DISORDER; PREFRONTAL CORTEX; ATTENTION-DEFICIT; EUTHYMIC PATIENTS; UNIPOLAR DEPRESSION; INHIBITORY CONTROL; WORKING-MEMORY; MOOD DISORDERS; RATING-SCALE; I DISORDER AB Background: Growing awareness of childhood bipolar disorder necessitates further cognitive neuroscience research to determine unique developmental differences between pediatric and adult onset bipolar disorder. We sought to examine whether neuropsychological function in children with bipolar disorder resembles that in adults with the illness and to extend our knowledge about cognitive function in pediatric bipolar disorder. Methods. We administered a computerized neuropsychological test battery known as the Cambridge Neuropsychological Test Automated Battery to a sample of 21 children and adolescents with bipolar disorder and compared them with 21 age- and gender-matcbed controls. Results: In comparison to controls, children with bipolar disorder were impaired on measures of attentional set-shifting and visuospatial memory. Post hoc analyses in pediatric bipolar disorder subjects did not show significant associations between neuropsychological performance and manic symptomatology or attention-deficit/hyperactivity disorder comorbidity. Conclusions. Cambridge Neuropsychological Test Automated Battery data presented here in pediatric bipolar disorder fit well within the broader framework of known neurocognitive deficits in adult bipolar disorder. Our pediatric bipolar disorder subjects demonstrated selective deficiencies in attentional set-shifting and visuospatial memory. Our work suggests altered ventrolateral prefrontal cortex function, especially when linked to other lesion and neuroimaging studies. (C) 2004 Society of Biological Psychiatry. C1 NIMH, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Dickstein, DP (reprint author), NIMH, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv, NIH, 10 Ctr Dr MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 NR 51 TC 117 Z9 125 U1 3 U2 10 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 JAN 1 PY 2004 VL 55 IS 1 BP 32 EP 39 DI 10.1016/S0006-3223(03)00701-7 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 759NH UT WOS:000187743400004 PM 14706422 ER PT J AU Horiuchi, Y Nakayama, J Ishiguro, H Ohtsuki, T Detera-Wadleigh, SD Toyota, T Yamada, K Nankai, M Shibuya, H Yoshikawa, T Arinami, T AF Horiuchi, Y Nakayama, J Ishiguro, H Ohtsuki, T Detera-Wadleigh, SD Toyota, T Yamada, K Nankai, M Shibuya, H Yoshikawa, T Arinami, T TI Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE mood disorder; association; transmission disequilibrium test; GABRA1; genetics ID PEDIGREES; DEPRESSION; EPILEPSY; LINKAGE AB Background: The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of mood disorders. The GABRA1 gene encodes one of the subunits of GABA-A receptor and is located on human chromosome 5q34-q35, which is a region reportedly linked to mood disorders. We examined the GABRA1 gene as a candidate for mood disorders. Methods: We performed mutation screening of GABRA1 in 24 Japanese bipolar patients and evaluated associations in Japanese case-control subjects consisting of 125 patients with bipolar disorder, 147 patients with depressive disorders, and 191 healthy control subjects. Associations were confirmed in the National Institute of Mental Health (NIMH) initiative Bipolar Pedigrees, which consists Of 88 multiplex pedigrees with 480 informative persons. Results: We identified 13 polymorphisms in the GABRA1 gene. Nonsynonymous mutations were not found. Association of a specific haplotype with affective disorders was suggested in the Japanese case-control population (corrected p = .0008). This haplotype association was confirmed in the NIMH pedigrees (p = .007). Conclusions. These results indicate that the GABRA1 gene may play a role in the etiology of bipolar disorders. (C) 2004 Society of Biological Psychiatry. C1 Univ Tsukuba, Dept Med Genet, Inst Basic Med Sci, Tsukuba, Ibaraki 3058575, Japan. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama 35101, Japan. Tokyo Metropolitan Police Hosp, Dept Neuropsychiat, Tokyo, Japan. Natl Sanat Minami Hanamaki Hosp, Hanamaki, Iwate, Japan. RP Arinami, T (reprint author), Univ Tsukuba, Dept Med Genet, Inst Basic Med Sci, Tsukuba, Ibaraki 3058575, Japan. FU NIMH NIH HHS [U01 MH46274, U01 MH46280, U01 MH46282] NR 19 TC 30 Z9 32 U1 0 U2 1 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 JAN 1 PY 2004 VL 55 IS 1 BP 40 EP 45 DI 10.1016/S0006-3223(03)00689-9 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 759NH UT WOS:000187743400005 PM 14706423 ER PT J AU Welniak, LA Karas, M Yakar, S Anver, MR Murphy, WF LeRoith, D AF Welniak, LA Karas, M Yakar, S Anver, MR Murphy, WF LeRoith, D TI Effects of organ-specific loss of insulin-like growth factor-I production on murine hematopoiesis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE myelopoiesis; growth hormone; mobilization; progenitors ID IGF-I; MYELOID PROGENITORS; HORMONE; CELLS; MICE; EXPRESSION; VIVO; RECONSTITUTION; ENGRAFTMENT; INTEGRINS AB To determine whether circulating insulin-like growth factor (IGF)-I has a role in hematopoiesis, we examined hematologic parameters in mice with markedly reduced serum levels resulting from a liver-specific inactivation of the IGF-I gene. These mice have normal postnatal growth and development, suggesting that local production of IGF-I can maintain anabolic effects. Liver-specific IGF-I-deficient (LID) mice were compared with control littermates with regard to hematopoietic parameters. Spleen cellularity was decreased in the LID mice compared with control mice. Spleen myeloid progenitors, as determined by colony-forming units-granulocyte/monocyte (CFU-GM) and colony-forming units-high proliferative potential (CFU-HPP), were significantly decreased in the LID mice. Immune parameters, as indicated by the absolute number of B and T cells, did not significantly differ between the knockout and control mice. In contrast to the decreased cellularity and myelopoiesis in the spleen, bone marrow cellularity was not different between the 2 groups, but the total femoral content of CFU-GM and CFU-HPP was significantly increased in the LID mice. The decrease in splenic myelopoiesis was not due to the inability of progenitors to exit the bone marrow, because CFU-GM and burst-forming units-erythroid were significantly increased in the blood of LID mice compared with normal littermates. Administration of exogenous IGF-I to the LID mice for 4 days partially restored myelopoietic parameters in the spleen. Liver production of IGF-I and, therefore, normal serum levels of this hormone, although not necessary for general organ growth and development, seems necessary for survival or transition of myeloid progenitors into the spleen. (C) 2004 American Society for Blood and Marrow Transplantation. C1 Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. SAIC, Pathol Histotechnol Lab, Frederick, MD USA. RP Murphy, WF (reprint author), Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. EM wmurphy@unr.edu FU NCI NIH HHS [N01-CO-12400] NR 28 TC 15 Z9 15 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2004 VL 10 IS 1 BP 32 EP 39 DI 10.1016/j.bbmt.2003.09.008 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 767JF UT WOS:000188435900003 PM 14752777 ER PT J AU Nakamura, R Battiwalla, M Solomon, S Follmann, D Chakrabarti, S Cortez, K Hensel, N Childs, R Barrett, AJ AF Nakamura, R Battiwalla, M Solomon, S Follmann, D Chakrabarti, S Cortez, K Hensel, N Childs, R Barrett, AJ TI Persisting posttransplantation cytomegalovirus antigenemia correlates with poor lymphocyte proliferation to cytomegalovirus antigen and predicts for increased late relapse and treatment failure SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE cytomegalovirus; CMV antigenemia; allogeneic stem cell transplantation; immune reconstitution ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HEMATOLOGICAL MALIGNANCIES; IDENTIFY PATIENTS; IMMUNE-RESPONSE; RISK-FACTORS; CMV DISEASE; ACUTE GVHD; GANCICLOVIR; INFECTION AB Numerous clinical studies link cytomegalovirus (CMV) infection with incomplete posttransplantation T-cell recovery. We hypothesized that the inability of transplant recipients to handle CMV reactivation might correlate with a defective graft-versus-leukemia response and increased posttransplantation morbidity. Between May 1995 and August 2001, 82 patients who were CMV seropositive and survived the first 100 days after transplantation were identified for a day 100 landmark analysis of the effect of CMV reactivation patterns on eventual transplantation outcome. All patients underwent a myeloablative HLA-identical sibling donor T cell- depleted stem cell transplantation with scheduled donor T-cell add-back on day 45. Median follow-up was 1032 days. Forty-two patients who had either no reactivation or only I positive test with quick clearance were designated as a CMV immune competent group. Forty patients designated as CMV immune deficient (ID) had at least 2 positive tests. Apart from younger age (3 3 versus 3 8 years; P = .05) in the ID group, the 2 groups were balanced for clinical characteristics. In multivariate analysis, ID patients had a significantly higher incidence of leukemia relapse (58% versus 21%; P = .03) and worse disease-free survival (31% versus 66%; P = .04). There was no significant difference in week 1 to 14 posttransplantation lymphocyte counts between the 2 groups. In 67 patients tested 3 to 6 months after transplantation, a proliferative response to CMV antigen (stimulation index greater than or equal to2) occurred in 27 of 36 immune competent patients compared with 15 of 31 ID patients (P = .006). These results show that recurrent CMV reactivation in the first 100 days after transplantation predicts for reduced disease-free survival and increased leukemic relapse beyond 100 days and correlates with inferior proliferative responses to CMV. The higher relapse rate may reflect poor immune reconstitution in ID patients or an adverse effect of prolonged antiviral treatment. (C) 2004 American Society for Blood and Marrow Transplantation. C1 NHLBI, Stem Cell Allogene Transplantat Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allogene Transplantat Unit, Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 7C103, Bethesda, MD 20892 USA. EM barrettj@nih.gov NR 32 TC 44 Z9 45 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2004 VL 10 IS 1 BP 49 EP 57 DI 10.1016/j.bbmt.2003.08.011 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 767JF UT WOS:000188435900005 PM 14752779 ER PT J AU Kim, YS Nakanishi, G Oudes, AJ Kim, KH Wang, H Kilpatrick, DL Jetten, AM AF Kim, YS Nakanishi, G Oudes, AJ Kim, KH Wang, H Kilpatrick, DL Jetten, AM TI Tsp57: A novel gene induced during a specific stage of spermatogenesis SO BIOLOGY OF REPRODUCTION LA English DT Article DE gamete biology; male reproductive tract; spermatid; spermatogenesis; testis ID CELL NUCLEAR FACTOR; TESTIS-ASSOCIATED RECEPTOR; EXPRESSION; DIFFERENTIATION; SUPERFAMILY; CLONING; MEMBER; CREM AB Recently, we described the identification of a novel protein, nuclear receptor-associated protein 80 (RAP80), which is highly expressed in spermatocytes and appears to have a role in regulating gene expression. To identify proteins interacting with this protein, we performed yeast two-hybrid screening using full-length RAP80 as bait. This screen identified one in-frame clone encoding a novel testis-specific protein (Tsp), referred to as Tsp57. Tsp57 encodes a basic protein with a mass of 56.8 kDa. The amino acid sequence of Tsp57 is highly conserved (87%) between mouse and human. The mouse and human Tsp57 genes map to chromosomes 9A1 and 11921, respectively. Northern blot analysis showed that the expression of Tsp57 mRNA was highly restricted to the testis and temporally regulated during testicular development. Tsp57 mRNA was greatly induced between Day 21 and Day 25 of postnatal testicular development. In situ hybridization analysis demonstrated that the hybridization signal for Tsp57 mRNA was strongest in sections of seminiferous tubules at stages VI-VI I I of spermatogenesis, consistent with the conclusion that Tsp57 is most highly expressed in round spermatids. Study of Tsp57 expression in several purified subpopulations of spermatogenic cells confirmed maximum levels of expression in round spermatids. Consistently, Tsp57 expression was absent in testes from vitamin A-deficient mice, which do not have any round spermatids, and was reduced in RARalpha null mice, which have lowered numbers of round spermatids in their testes. These results indicate the possibility that Tsp57 protein plays a role in the postmeiotic phase of germ cell differentiation. Tsp57 contains two putative nuclear localization signals: NLS1 and NLS2. Examination of the cellular localization showed that the green fluorescent protein-Tsp57 fusion protein localized to both cytoplasm and nucleus. After deletion of NLS1 but not NLS2, Tsp57 localized solely to the cytoplasm, indicating a role for NLS1 in the nuclear localization of Tsp57. The localization suggests a nuclear function for Tsp57. Pull-down analysis demonstrated that Tsp57 and RAP80 form a complex in intact cells. C1 NIEHS, Cell Biol Sect, Div Intramural Res, DHHS,NIH, Res Triangle Pk, NC 27709 USA. Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, DHHS,NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 22 TC 5 Z9 8 U1 1 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2004 VL 70 IS 1 BP 106 EP 113 DI 10.1095/biolreprod.103.018465 PG 8 WC Reproductive Biology SC Reproductive Biology GA 757QG UT WOS:000187572500015 PM 12954732 ER PT J AU Keelan, JA Yang, J Romero, RJ Chaiworapongsa, T Marvin, KW Sato, TA Mitchell, MD AF Keelan, JA Yang, J Romero, RJ Chaiworapongsa, T Marvin, KW Sato, TA Mitchell, MD TI Epithelial cell-derived neutrophil-activating peptide-78 is present in fetal membranes and amniotic fluid at increased concentrations with intra-amniotic infection and preterm delivery SO BIOLOGY OF REPRODUCTION LA English DT Article DE cytokines; decidua; parturition; placenta; pregnancy ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; LABOR-ASSOCIATED CHANGES; CXC-CHEMOKINES; GRO-ALPHA; BACTERIAL LIPOPOLYSACCHARIDE; HISTOLOGIC CHORIOAMNIONITIS; DIFFERENTIAL EXPRESSION; GESTATIONAL MEMBRANES; MICROBIAL INVASION; ENDOTHELIAL-CELLS AB Intra-amniotic secretion and abundance of epithelial cell-derived neutrophil-activating peptide (ENA)-78, a potent chemoattractant and activator of neutrophils, was studied in the context of term and preterm parturition. Staining of ENA-78 immunoperoxidase was localized predominantly to chorionic trophoblasts and amniotic epithelium in term and preterm gestational membranes, with weaker and less consistent staining in decidual cells. The abundance of ENA-78 in membrane tissue homogenates was significantly increased (similar to4-fold) with term labor in amnion (n = 15), and with preterm labor (similar to30-fold) in amnion and choriodecidua (n = 31). In amnion tissue homogenate extracts, ENA-78 levels were positively correlated with the degree of leukocyte infiltration (r(2) = 0.481). In amniotic fluids, median ENA-78 levels from pregnancies with preterm labor without intra-amniotic infection were significantly lower (P < 0.01 by ANOVA) than those from pregnancies with preterm deliveries with infection. levels in samples derived from term pregnancies were similar before and after labor. Production of ENA-78 by amnion monolayers was stimulated in a concentration-dependent fashion by both interleukin-1beta and tumor necrosis factor et. Production of ENA-78 by choriodecidual explants was increased modestly after 2-4 h of exposure to lipopolysaccharide (5 mug/ml). An immunoreactive doublet (similar to8 kDa) was detected in choriodecidual explant-conditioned media by immunoblotting. We conclude that ENA-78, derived from the gestational membranes, is present in increased abundance in the amniotic cavity in response to intrauterine infection and, hence, may play a role in the mechanism of infection-driven preterm birth and rupture of membranes secondary to leukocyte recruitment and activation. C1 Univ Auckland, Liggins Inst, Auckland, New Zealand. Univ Auckland, Dept Pharmacol & Clin Pharmacol, Auckland, New Zealand. Univ Auckland, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, Auckland, New Zealand. Hutzel Hosp, NICHD, Perinatal Res Branch, Detroit, MI 48201 USA. RP Keelan, JA (reprint author), Univ Auckland, Liggins Inst, 2-6 Pk Ave, Auckland, New Zealand. RI Mitchell, Murray/A-8639-2010; Keelan, Jeffrey/G-2170-2011 OI Mitchell, Murray/0000-0002-6167-7176; Keelan, Jeffrey/0000-0002-5403-6266 NR 46 TC 36 Z9 37 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2004 VL 70 IS 1 BP 253 EP 259 DI 10.1095/biolreprod.103.016204 PG 7 WC Reproductive Biology SC Reproductive Biology GA 757QG UT WOS:000187572500034 PM 13679321 ER PT J AU Kelty, MF AF Kelty, MF TI Ethics of biological research: Ethical aspects of the collection, attribution, and sharing of data. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA TF1 BP 81 EP 81 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400010 ER PT J AU Eddy, EM AF Eddy, EM TI Post-meiotic differentiation: Novel genes for novel needs. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA MS32 BP 88 EP 89 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400045 ER PT J AU Turner, JMA Aprelikova, O Xu, XL Wang, RH Burgoyne, P Deng, CX AF Turner, JMA Aprelikova, O Xu, XL Wang, RH Burgoyne, P Deng, CX TI Silencing the spermatogenic X chromosome. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Natl Inst Med Res, London NW7 1AA, England. NCI, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA MS33 BP 89 EP 89 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400046 ER PT J AU Mantena, SR Cheon, YP Kannan, A Johnson, P Bagchi, MK Bagchi, IC AF Mantena, SR Cheon, YP Kannan, A Johnson, P Bagchi, MK Bagchi, IC TI Estrogen receptor-mediated induction of CCAAT/Enhancer Binding Protein (C/EBP) beta is essentlal for uterine decidualization. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 3 BP 93 EP 93 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400063 ER PT J AU Wu, JM Mattison, JA Lawson, MS Takahashi, DL Pau, F Ingram, DK Roth, GS Lane, MA Ottinger, MA Zelinski-Wooten, MB AF Wu, JM Mattison, JA Lawson, MS Takahashi, DL Pau, F Ingram, DK Roth, GS Lane, MA Ottinger, MA Zelinski-Wooten, MB TI Dynamic changes in follicle-stimulating hormone and inhibin B during peri-menopause in rhesus monkeys. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod Sci, Beaverton, OR USA. Merck & Co Inc, Merck Res Labs, Rahway, NJ 07065 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 33 BP 100 EP 100 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400093 ER PT J AU Hoodbhoy, T Rankin, T Boja, ES Epifano, O Fales, HM Dean, J AF Hoodbhoy, T Rankin, T Boja, ES Epifano, O Fales, HM Dean, J TI Structural determinants for sperm binding to the mammalian zona pellucida. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 53 BP 105 EP 105 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400113 ER PT J AU Rosewell, KL Nuttall, R Edwards, D Davis, BJ Curry, TE AF Rosewell, KL Nuttall, R Edwards, D Davis, BJ Curry, TE TI A survey of the matrix metalloproteinase family in the periovulatory mouse ovary: A real-time PCR study. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Univ Kentucky, Coll Med, Dept Obstet & Gynecol, Lexington, KY 40506 USA. Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 187 BP 135 EP 136 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400247 ER PT J AU Hewitt, SC Collins, J Grissom, S Deroo, B Korach, KS AF Hewitt, SC Collins, J Grissom, S Deroo, B Korach, KS TI Global uterine genomics in vivo calls for re-evaluation of the estrogen receptor alpha-growth factor cross talk hypothesis. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 NIEHS, LRDT, Res Triangle Pk, NC 27709 USA. NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 310 BP 164 EP 164 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400370 ER PT J AU Jayes, FL Davis, BJ AF Jayes, FL Davis, BJ TI Granulosa cell function is impaired by environmentally relevant levels of mono-(2-ethylhexyl) phthalate (MEHP). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 318 BP 166 EP 166 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400378 ER PT J AU Jefferson, WN Pepling, M Padilla-Banks, E Newbold, RR AF Jefferson, WN Pepling, M Padilla-Banks, E Newbold, RR TI The phytoestrogen genistein alters ovarian differentiation and subsequent fertility SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 NIEHS, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Raleigh, NC 27695 USA. Syracuse Univ, Syracuse, NY 13244 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 447 BP 195 EP 195 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400506 ER PT J AU Beres, BJ Howard, S Hahn, KL Wilson-Rawls, J AF Beres, BJ Howard, S Hahn, KL Wilson-Rawls, J TI Differential expression of Numb isoforms in the prepubertal and mature testis SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. Arizona State Univ, Biol Grad Program, Tempe, AZ 85287 USA. Arizona State Univ, NIH Minor Access Res Careers, Tempe, AZ 85287 USA. Arizona State Univ, Mol & Cellular Biol Grad Program, Tempe, AZ 85287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 595 BP 229 EP 230 PG 2 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400654 ER PT J AU Hahn, K Howard, S Beres, BJ Wilson-Rawls, J AF Hahn, K Howard, S Beres, BJ Wilson-Rawls, J TI Lunatic fringe null mice have a testis defect SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. Arizona State Univ, Mol & Cellular Biol Grad Program, Tempe, AZ 85287 USA. Arizona State Univ, NIH Minor Access Res Carers, Tempe, AZ 85287 USA. Arizona State Univ, Biol Grad Program, Tempe, AZ 85287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 753 BP 265 EP 265 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400812 ER PT J AU Emmen, JMA Couse, JF Yates, MM Kissling, GE Korach, KS AF Emmen, JMA Couse, JF Yates, MM Kissling, GE Korach, KS TI Role of estrogen receptors alpha and beta in growth, rupture, and luteinization of murine ovarian follicles in vitro. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2004 SI SI MA 782 BP 272 EP 272 PG 1 WC Reproductive Biology SC Reproductive Biology GA 840HJ UT WOS:000222848400841 ER PT J AU Horkay, F Basser, PJ AF Horkay, F Basser, PJ TI Osmotic observations on chemically cross-linked DNA gels in physiological salt solutions SO BIOMACROMOLECULES LA English DT Article ID POLYELECTROLYTE SOLUTIONS; CONDENSATION; HYDROGELS; PRESSURE AB Neutralized DNA gels exhibit a reversible volume transition when CaCl2 is added to the surrounding aqueous NaCl solution. In this paper, a systematic study of the osmotic and mechanical properties of Na-DNA gels is presented to determine, qualitatively and quantitatively, the effect of Ca-Na exchange on the volume transition. It is found that in the absence of CaCl2 the DNA gels exhibit osmotic behavior similar to that of DNA solutions with reduced DNA concentration. At low CaCl2 concentration, the gel volume gradually decreases as the CaCl2 concentration increases. Below the volume transition, the concentration dependence of the osmotic pressure can be satisfactorily described by a Flory-Huggins-type equation. The Ca2+ ions primarily affect the third-order interaction term, which strongly increases upon the introduction of Ca2+ ions. The second-order interaction term only slightly depends on the CaCl2 concentration. It is demonstrated that DNA gels cross-linked in solutions containing CaCl2 exhibit reduced osmotic mixing pressure. The concentration dependence of the shear modulus of DNA gels can be described by a single power law. The scaling exponent is practically independent of the NaCl concentration and increases with increasing CaCl2 content. C1 NIH, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Horkay, F (reprint author), NIH, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Bldg 10, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 27 TC 47 Z9 47 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD JAN-FEB PY 2004 VL 5 IS 1 BP 232 EP 237 DI 10.1021/bm034372m PG 6 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 777MY UT WOS:000189183200032 PM 14715031 ER PT S AU Mager, DE Merritt, MM Kasturi, J Witkin, LR Urdiqui-Macdonald, M Sollers, JJ Evans, MK Zonderman, AB Abernethy, DR Thayer, JF AF Mager, DE Merritt, MM Kasturi, J Witkin, LR Urdiqui-Macdonald, M Sollers, JJ Evans, MK Zonderman, AB Abernethy, DR Thayer, JF GP ISA TI Kullback-Leibler clustering of continuous wavelet transform measures of heart rate variability SO BIOMEDICAL SCIENCES INSTRUMENTATION, VOL 40 SE TECHNICAL PAPERS OF ISA LA English DT Proceedings Paper CT 41st Annual Rocky Mountain Bioengineering Symposium/41st International ISA Biomedical Sciences Instrumentation Symposium CY APR 23-25, 2004 CL Ft Collins, CO SP Instrumentat Syst & Automat Soc DE heart rate variability; African-Americans; continuous wavelet transform; self-organizing maps AB Power spectral analysis of beat-to-boat heart rate variability (HRV) has provided a useful means of understanding the interplay between autonomic and cardiovascular functionality. Despite their utility, commonly employed frequency-domain techniques are limited in their prerequisite for stationary signals and their inability to account for temporal changes in the power spectral and/or frequency properties of signals. The purpose of this study is to develop an algorithm that utilizes continuous wavelet transform (CWT) parameters as inputs to a Kohonen self-organizing map (SOM), providing a method of clustering subjects with similar wavelet transform signatures. Continuous interbeat-intervals were recorded (Portapres monitor at 200Hz) during a perception of affect test in 79 African-American volunteers (ages 21-83), where after a 5-min baseline, participants evaluated emotional expressions in sentences and pictures of faces, followed by a 5-min recovery. Individual HRV biosignals from each session were pre-processed (artifact replacement and signal resampling at 2Hz) and a CWT was applied (db9 wavelet basis function over 32 scales). Standard deviations of resulting wavelet coefficients at each scale were calculated, normalized, and used as inputs into a SOM with Kullback-Leibler divergence as the dissimilarity. measure used for clustering. Differences in subject demographics between two final clusters were assessed via two-independent-groups t-tests or chi-square or Fishet's exact tests of contingency tables. Significant differences were found for age, initial systolic blood pressure, smoking status., and mean A. of coefficients in the high frequency hand (0.15-0.4Hz). These findings may have clinical significance and the developed algorithm provides an alternative means of analyzing HRV data originating from populations with complex covariates. C1 NIA, Baltimore, MD 21224 USA. RP Mager, DE (reprint author), NIA, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 10 TC 2 Z9 2 U1 0 U2 0 PU INSTRUMENT SOC AMER PI RESEARCH TRIANGLE PARK PA 67 ALEXANDER DR, PO BOX 12277, RESEARCH TRIANGLE PARK, NC 27709 USA SN 1054-0032 J9 TECH PAPERS ISA PY 2004 VL 449 BP 337 EP 342 PG 6 WC Engineering, Biomedical; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA BAE76 UT WOS:000221906600056 ER PT S AU Schlucker, S Huffman, SW Levin, IW AF Schlucker, S Huffman, SW Levin, IW BE MahadevanJansen, A Sowa, MG Puppels, GJ Gryczynski, Z VoDinh, T Lakowicz, JR TI Vibrational microspectroscopic imaging: Spatial resolution enhancement SO BIOMEDICAL VIBRATIONAL SPECTROSCOPY AND BIOHAZARD DETECTION TECHNOLOGIES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biomedical Vibrational Spectroscopy and Biohazard Detection Technologies CY JAN 25-27, 2004 CL San Jose, CA SP SPIE, USAF Off Sci Res DE vibrational microspectroscopic imaging; Raman and infrared spectroscopy; spatial resolution; spatial oversampling; deconvolution techniques ID TOOL AB We propose a methodology for enhancing the diffraction limited spatial resolution attained in Raman and Fourier transform infrared microspectroscopic imaging techniques. Near-field scanning optical microscopy (SNOM) and spectroscopy employ apertureless and aperture approaches to provide ultra-high spatially resolved images at the nanometer level. In contrast, we employ conventional spectral acquisition schemes modified by spatial oversampling with the subsequent application of deconvolution techniques. As an example, this methodology is applied to flat samples using point illumination. Simulated data, assuming idealized sample concentration profiles, are presented together with experimental Raman microspectroscopic data from chemically and morphologically well-defined test samples. Intensity profiles determined using conventional mapping and imaging techniques are compared to those obtained by the probe/deconvolution methodology. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5229-7 J9 P SOC PHOTO-OPT INS PY 2004 VL 5321 BP 157 EP 163 DI 10.1117/12.528652 PG 7 WC Engineering, Biomedical; Instruments & Instrumentation; Spectroscopy SC Engineering; Instruments & Instrumentation; Spectroscopy GA BAO14 UT WOS:000223057100020 ER PT J AU Gunasekaran, K Ma, BY Tsai, CJ Nussinov, R AF Gunasekaran, K Ma, BY Tsai, CJ Nussinov, R TI Functional dynamics: Conserved mechanisms across different folds, sequences and functions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc ID ENZYME FUNCTION C1 NCI Frederick, SA IC, Frederick, MD USA. Tel Aviv Univ, SA IC, NCI Frederick, Frederick, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 1A EP 1A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200004 ER PT J AU Veigel, C Molloy, JE Schmitz, S Sellers, JR Kendrick-Jones, J AF Veigel, C Molloy, JE Schmitz, S Sellers, JR Kendrick-Jones, J TI Load dependent kinetics of force production by myosin motors, measured using optical tweezers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIMR, London, England. NIH, Bethesda, MD 20892 USA. LMB, Cambridge, England. NR 0 TC 0 Z9 0 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 3A EP 3A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200014 ER PT J AU Mizuuchi, K Greene, EC AF Mizuuchi, K Greene, EC TI DNA transposition immunity: Visualizing ATP-dependent redistribution of MuB protein along single DNA molecules SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, NIDDK, LMB, Bethesda, MD USA. NIH, NIDDK, LMB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 4A EP 5A PN 2 PG 2 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200021 ER PT J AU Cruceanu, M Urbaneja, M Branciforte, D Gorelick, RJ Casas-Finet, JR Martin, SL Williams, MC AF Cruceanu, M Urbaneja, M Branciforte, D Gorelick, RJ Casas-Finet, JR Martin, SL Williams, MC TI Single molecule DNA stretching studies of nucleic acid chaperone proteins with and without zinc fingers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Northeastern Univ, Dept Phys, Boston, MA 02115 USA. NCI Frederick, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD USA. Univ Colorado, Sch Med, Dept Cellular & Struct Biol, Denver, CO USA. Univ Colorado, Sch Med, Program Mol Biol, Denver, CO USA. Medimmune Inc, Gaithersburg, MD 20878 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 6A EP 7A PN 2 PG 2 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200031 ER PT J AU Horning, MS Mayer, ML AF Horning, MS Mayer, ML TI Regulation of AMPA receptor gating by ligand binding core dimers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 8A EP 8A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200039 ER PT J AU Swartz, KJ Lee, HC Lee, JM AF Swartz, KJ Lee, HC Lee, JM TI Interaction between extracellular hanatoxin and the resting conformation of the voltage-sensor paddle in Kv 2.1 channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 8A EP 8A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200041 ER PT J AU Baumgart, T Farkas, E Hess, S Hammond, A Holowka, D Baird, B Webb, W AF Baumgart, T Farkas, E Hess, S Hammond, A Holowka, D Baird, B Webb, W TI Experimental and theoretical analysis of fluid/fluid domain coexistence, interphase tension and curvature in giant unilamellar vesicles (GUVs) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Cornell Univ, Ithaca, NY USA. NIH, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 18A EP 18A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200087 ER PT J AU Svitel, J Schuck, P AF Svitel, J Schuck, P TI Combined affinity and rate constant distributions of ligand populations from experimental surface-binding kinetics and equilibria SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, Div Bioengn & Phys Sci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 22A EP 22A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200106 ER PT J AU Whittington, KC Moaddel, R Wainer, IW AF Whittington, KC Moaddel, R Wainer, IW TI A comparison of nicotinic ligand affinities for the neuronal nicotinic receptor subtypes alpha 3 beta 2, alpha 3 beta 4, alpha 4 beta 2, and alpha 4 beta 4 using novel liquid chromatography stationary phases SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, Gerontol Res Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 22A EP 22A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200108 ER PT J AU Tong, Q Chu, X Cheung, JY Barber, DL Birnbaumer, L Miller, BA AF Tong, Q Chu, X Cheung, JY Barber, DL Birnbaumer, L Miller, BA TI Erythropoietin-modulated calcium influx through Trpc2 is mediated by phospholipase C and Ip3r SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Geisinger Med Ctr, Weis Ctr Res, Danville, PA USA. Ontario Canc Inst, Toronto, ON, Canada. NIH, NIEHS, Res Triangle Pk, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 25A EP 25A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200125 ER PT J AU Leapman, R Kocsis, E Zhang, GF Talbot, T Laquerriere, P AF Leapman, R Kocsis, E Zhang, GF Talbot, T Laquerriere, P TI Three-dimensional distributions of elements in biological structures by energy-filtered electron tomography SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD 20892 USA. RI Laquerriere, Patrice/P-1025-2016 OI Laquerriere, Patrice/0000-0001-7637-9094 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 27A EP 27A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200134 ER PT J AU Zhang, PJ Juliani, J Lefman, J Land, W Smith, S Lee, S Leapman, R Kessel, M Rouault, T Subramaniam, S AF Zhang, PJ Juliani, J Lefman, J Land, W Smith, S Lee, S Leapman, R Kessel, M Rouault, T Subramaniam, S TI Altered ferritin distribution detected by 3D electron microscopy suggests impaired normal axonal ferritin transport in IRP2-/- mice SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, OD, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 27A EP 27A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200133 ER PT J AU Ishikawa, T Cheng, NQ Liu, X Korn, ED Steven, AC AF Ishikawa, T Cheng, NQ Liu, X Korn, ED Steven, AC TI Subdomain organization of the AMIC myosin I tail by cryo-electron microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NHLBI, Lcb, NIH, Bethesda, MD 20892 USA. NIAMS, Lsbr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 29A EP 30A PN 2 PG 2 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200145 ER PT J AU Liu, X Shu, S Korn, ED AF Liu, X Shu, S Korn, ED TI Changes in HCM loop effect biochemical and biological properties of Dictyostelium myosin II SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 29A EP 29A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200143 ER PT J AU Wei, QZ Takeda, K Singh, AK Liu, CY Yu, ZX Adelstein, RS AF Wei, QZ Takeda, K Singh, AK Liu, CY Yu, ZX Adelstein, RS TI Brain and cardiac abnormalities in tissue-specific nonmuscle myosin heavy chain II-B ablated mice SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, Pathol Core Facil, Bethesda, MD 20892 USA. NIH, Transgen Mouse Core Facil, Bethesda, MD 20892 USA. NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 29A EP 29A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200142 ER PT J AU Gaede, HC Gawrisch, K AF Gaede, HC Gawrisch, K TI Lateral diffusion in multilamellar liposomes measured by pulsed field gradient magic angle spinning (PFG-MAS) NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. RI Gaede, Holly/B-7392-2015 OI Gaede, Holly/0000-0003-4444-4394 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 30A EP 30A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200149 ER PT J AU Sakamoto, T Yildiz, A Selvin, PR Sellers, JR AF Sakamoto, T Yildiz, A Selvin, PR Sellers, JR TI Myosin V moves by a hand-over-hand lever arm mechanism SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Univ Illinois, Ctr Biophys, Urbana, IL 61801 USA. Univ Illinois, Dept Phys, Urbana, IL 61801 USA. NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 30A EP 30A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200146 ER PT J AU Parsegian, VA Podgornik, R AF Parsegian, VA Podgornik, R TI Van der Waals forces across multilayers: polarization anisotropy and discreteness of layers. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 38A EP 38A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200190 ER PT J AU Leikina, E Kim, CS Epand, RF Epand, RM Shin, YK Chernomordik, LV AF Leikina, E Kim, CS Epand, RF Epand, RM Shin, YK Chernomordik, LV TI Fusion mediated by ectodomain of HA2 subunit of influenza virus hemagglutinin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, Bethesda, MD USA. Iowa State Univ, Dept Biochem & Biophys, Ames, IA USA. McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 43A EP 43A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200218 ER PT J AU Zaitseva, E Leikina, E Mittal, A Chernomordik, LV AF Zaitseva, E Leikina, E Mittal, A Chernomordik, LV TI Structurally diverse Sindbis virus E1 protein and influenza virus hemagglutinin drive cell fusion through similar membrane intermediates. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, Mol Cell Biophys Lab, Sect Membrane Biol, Bethesda, MD USA. RI Mittal, Aditya/E-3087-2010 OI Mittal, Aditya/0000-0002-4030-0951 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 43A EP 43A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200217 ER PT J AU Mittal, A Chernomordik, LV Podbilewicz, B AF Mittal, A Chernomordik, LV Podbilewicz, B TI Characterizing kinetics of cell fusion in developing C-elegans embryos SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, Lab Cellular & Mol Biophys, Sect Membrane Biol, Bethesda, MD USA. Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. RI Mittal, Aditya/E-3087-2010; Podbilewicz, Benjamin/N-4825-2014 OI Mittal, Aditya/0000-0002-4030-0951; NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 45A EP 45A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200231 ER PT J AU Tocchetti, CG Katori, T Zaccolo, M Mancardi, D Belardi, DF Takimoto, E Wink, DA Kass, DA Paolocci, N AF Tocchetti, CG Katori, T Zaccolo, M Mancardi, D Belardi, DF Takimoto, E Wink, DA Kass, DA Paolocci, N TI The HNO/NO- donor Angeli's salt enhances cardiomyocyte contractility in a PKA-dependent manner SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD USA. NCI, NIH, Bethesda, MD USA. RI Zaccolo, Manuela/B-3802-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 47A EP 47A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200240 ER PT J AU Schmitz, S Wang, F Sakamoto, T Molloy, JE Sellers, JR Veigel, C AF Schmitz, S Wang, F Sakamoto, T Molloy, JE Sellers, JR Veigel, C TI Single molecule mechanics of myosin V constructs SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, NHLB, Bethesda, MD 20892 USA. NIMR, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 53A EP 53A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200272 ER PT J AU Forgacs, E Cartwright, S Conyers, B Wang, F Sellers, J White, H AF Forgacs, E Cartwright, S Conyers, B Wang, F Sellers, J White, H TI Kinetics of hydrolysis to and phosphate dissociation from acto-myosinV-S1-ADP-Pi SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 55A EP 55A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200282 ER PT J AU Gafurov, B Chen, YD Chalovich, JM AF Gafurov, B Chen, YD Chalovich, JM TI Effects of FHC causing mutations of troponin T and changes in ionic strength and Ca++ on S1-ADP binding to regulated actin: Support for an allosteric model of regulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 E Carolina Univ, Sch Med, Greenville, NC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 56A EP 56A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200287 ER PT J AU Gutierrez-Cruz, G Lewis, MK Wang, K AF Gutierrez-Cruz, G Lewis, MK Wang, K TI Nebulin Regulation of the Actin-Myosin Interaction investigated with in vitro motility assays and single molecule fluorescence microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIAMS, NIH, DHHS, Lab Muscle Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 56A EP 56A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200289 ER PT J AU Nahirney, PC Gutierrez-Cruz, G Lewis, MK Wang, K AF Nahirney, PC Gutierrez-Cruz, G Lewis, MK Wang, K TI Endo- and exo-sarcomeric lattice ultrastructure in sonic muscle fibers of the type I male midshipman fish SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIAMS, Muscle Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 60A EP 61A PN 2 PG 2 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200312 ER PT J AU Xie, L Wang, K AF Xie, L Wang, K TI Profiling nebulin interaction with proteins of the thin and thick filament assemblies in the striated muscle sarcomere SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, Niams, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 67A EP 67A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200346 ER PT J AU Carroll, S Lu, SJ Herrera, AH Horowits, R AF Carroll, S Lu, SJ Herrera, AH Horowits, R TI N-RAP scaffolds I-Z-I cardiomyocytes assembly during myofibrillogenesis in cultured chick cardiomyocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 48th Annual Meeting of the Biophysical Society CY FEB 14-18, 2004 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2004 VL 86 IS 1 SU S BP 70A EP 70A PN 2 PG 1 WC Biophysics SC Biophysics GA 762KQ UT WOS:000187971200362 ER EF