FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Petrella, JR Grossman, RI McGowan, JC Campbell, G Cohen, JA AF Petrella, JR Grossman, RI McGowan, JC Campbell, G Cohen, JA TI Multiple sclerosis lesions: Relationship between MR enhancement pattern and magnetization transfer effect SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE sclerosis, multiple; magnetic resonance, magnetization transfer; magnetic resonance, contrast enhancement AB PURPOSE: To investigate the relationship between the enhancement pattern of a multiple sclerosis lesion and its magnetization transfer effect. METHODS: Fifty-four lesions were chosen from 29 patients with multiple sclerosis on the basis of enhancement pattern on contrast-enhanced T1-weighted MR images. They included 14 homogeneously enhancing lesions, 26 nonenhancing lesions, and 14 ring-enhancing lesions. Magnetization transfer ratios of the homogeneously enhancing lesions, nonenhancing lesions, and central portion of the ring-enhancing lesions were measured. Means were calculated and compared. RESULTS: The magnetization transfer ratios for homogeneously enhancing lesions were higher (mean, 32.2%; SD, 3.4%) than those for nonenhancing lesions (mean, 29.4; SD, 4.3%) and for the central portion of ring-enhancing lesions (mean, 24.5%; SD, 4.0%). Significant differences were found between the ring-enhancing lesions and the homogeneously enhancing lesions and between the ring-enhancing lesions and the nonenhancing lesions. CONCLUSION: We found a relationship between decreased magnetization transfer ratios and those enhancement patterns in which myelin is known to be decreased histopathologically, Thus, use of the magnetization transfer technique may increase the specificity of MR imaging in assessing the extent of residual myelination in multiple sclerosis lesions. C1 HOSP UNIV PENN,DEPT RADIOL,NEURORADIOL SECT,PHILADELPHIA,PA 19104. HOSP UNIV PENN,DEPT NEUROL,PHILADELPHIA,PA 19104. NINCDS,LAB DIAGNOST RADIOL RES,NIH,BETHESDA,MD 20892. FU NINDS NIH HHS [R01 NS29029-01A1] NR 16 TC 84 Z9 86 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 1996 VL 17 IS 6 BP 1041 EP 1049 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UQ749 UT WOS:A1996UQ74900008 PM 8791914 ER PT J AU Mercer, BM Goldenberg, RL Das, A Moawad, AH Iams, JD Meis, PJ Copper, RL Johnson, F Thom, E McNellis, D Miodovnik, M Menard, MK Caritis, SN Thurnau, GR Bottoms, SF Roberts, J AF Mercer, BM Goldenberg, RL Das, A Moawad, AH Iams, JD Meis, PJ Copper, RL Johnson, F Thom, E McNellis, D Miodovnik, M Menard, MK Caritis, SN Thurnau, GR Bottoms, SF Roberts, J TI The preterm prediction study: A clinical risk assessment system SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the Central-Association-of-Obstetricians-and-Gynecologists CY OCT 19-21, 1995 CL PALM DESERT, CA SP Cent Assoc Obstetricians & Gynecologists DE preterm birth; prematurity prediction; preterm delivery ID BACTERIAL VAGINOSIS; BIRTH PREVENTION; DELIVERY; PREGNANCY; INFECTION; LABOR AB OBJECTIVE: Our aims were to develop a risk assessment system for the prediction of spontaneous preterm delivery using clinical information available at 23 to 24 weeks' gestation and to determine the predictive value of such a system. STUDY DESIGN: A total of 2929 women were evaluated between 23 and 24 weeks' gestation at 10 centers. Demographic factors, socioeconomic status, home and work environment, drug and alcohol use, and medical history were evaluated. Information regarding symptoms, cultures, and treatments in the current pregnancy were ascertained. Anthropomorphic and cervical examinations were performed. Univariate analysis and multivariate logistic regression were performed in a random selection, constituting 85% of the study population. The derived risk assessment system was applied to the remaining 15% of the population to evaluate its validity. RESULTS: A total of 10.4% of women were delivered of preterm infants. The multivariate models for spontaneous preterm delivery were highly associated with spontaneous preterm delivery (p < 0.0001). A low body mass index ( < 19.8) and increasing Bishop scores were significantly associated with spontaneous preterm delivery in nulliparous and multiparous women. Black race, poor social environment, and work during pregnancy were associated with increased risk for nulliparous women. Prior obstetric outcome overshadowed socioeconomic risk factors in multiparous women with a twofold increase in the odds of spontaneous preterm delivery for each prior spontaneous preterm delivery. Current pregnancy symptoms, including vaginal bleeding, symptomatic contractions within 2 weeks, and acute or chronic lung disease were variably associated with spontaneous preterm delivery in nulliparous and multiparous women. When the system was applied to the remainder of the population, women defined to be at high risk for spontaneous preterm delivery ( greater than or equal to 20% risk) carried a 3.8-fold (nulliparous women) and 3.3-fold (multiparous women) higher risk of spontaneous preterm delivery than those predicted to be at low risk. However, the risk assessment system identified a minority of women who had spontaneous preterm deliveries. The sensitivities were 24.2% and 18.2% and positive predictive values were 28.6% and 33.3%, respectively, for nulliparous and multiparous women. CONCLUSIONS: Although it is possible to develop a graded risk assessment system that includes factors that are highly associated with spontaneous preterm delivery in nulliparous and multiparous women, such a system does not identify most women who subsequently have a spontaneous preterm delivery. This system has investigational value as the basis for evaluating new technologies designed to identify at-risk subpopulations. C1 NICHHD,MATERNAL FETAL MED UNITS NETWORK,BETHESDA,MD 20892. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [U10-HD-27917, U10-HD-21410, U10-HD-27915] NR 19 TC 190 Z9 194 U1 2 U2 10 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 1996 VL 174 IS 6 BP 1885 EP 1893 DI 10.1016/S0002-9378(96)70225-9 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UU993 UT WOS:A1996UU99300082 PM 8678155 ER PT J AU Li, ZH Aaltonen, LA Shu, QP Srivastava, S Grizzle, WE Shibata, D AF Li, ZH Aaltonen, LA Shu, QP Srivastava, S Grizzle, WE Shibata, D TI Effects of mutation and growth rates on patterns of microsatellite instability SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COLORECTAL-CANCER; HISTORY; CELLS AB The detection of somatic microsatellite (MS) alterations in tumors is often interpreted as a sign of underlying genomic instability, However, it is unclear why the proportions of altered MS loci vary between different mutator phenotype tumors, We present a simple mathematical analysis that can account for some of these differences, recognizing that the mutations accumulated in a tumor reflect both its mutation rate and number of cell divisions. Only a small proportion of mutated MS loci are expected in tumors with normal or low mutation rates. In contrast, tumors with high mutation rates may or may not acquire mutations depending on the numbers of divisions that proceed the onset of the mutator phenotype. The majority of MS loci should accumulate mutations if high mutation rates are acquired early in tumor progression. Somatic MS mutations provide clues to both the mode and tempo of tumorigenesis. C1 UNIV SO CALIF,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90033. HELSINKI UNIV,HAARTMAN INST,HELSINKI,FINLAND. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. RI Aaltonen, Lauri/A-5375-2010 OI Aaltonen, Lauri/0000-0001-6839-4286 FU NCI NIH HHS [CA58704, CN-45547-63, P30 CA14089] NR 24 TC 10 Z9 11 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1996 VL 148 IS 6 BP 1757 EP 1761 PG 5 WC Pathology SC Pathology GA UN468 UT WOS:A1996UN46800006 PM 8669462 ER PT J AU Cribbs, DH Chen, LS Bende, SM LaFerla, FM AF Cribbs, DH Chen, LS Bende, SM LaFerla, FM TI Widespread neuronal expression of the presenilin-1 early-onset Alzheimer's disease gene in the murine brain SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PRECURSOR PROTEIN GENE; INSITU HYBRIDIZATION; APOLIPOPROTEIN-E; MUTATION; TISSUE AB Mutations in the presenilin-1 (S182) gene have been genetically linked to early-onset Alzheimer's disease. To clarify the underlying molecular mechanism through which presenilin-1 is involved in the pathogenesis of this neurodegenerative disorder, the regional and cellular transcription profile of this gene was characterized in primary cells isolated from the murine brain by Northern blot hybridization and in tissue sections by in situ hybridization using digoxigenin-labeled riboprobes. Our results indicate that presenilin-1 mRNA transcripts are widely distributed throughout the adult mouse brain. furthermore, immunohistochemical labeling of hybridized sections indicates that expression was predominantly localized to neuronal cells. Neurons in the hippocampus and cerebral cortex, which are severely compromised in Alzheimer's disease, showed prominent expression of presenilin-1. In contrast, white matter areas and endothelial cells do not appear to express presenilin-1 to detectable levels, presenilin-1 transcripts, however, are also present less frequently in certain nonneuronal cell populations such as ependymal cells in the choroid plexus. Analysis of primary cells isolated from murine brain supported the results obtained by in situ hybridization and showed that cultured primary neurons and astrocytes express presenilin-1. Overall, it appears that the pattern of presenilin-1 gene expression parallels that previously described for the amyloid precursor protein. C1 UNIV CALIF IRVINE,DEPT PSYCHOBIOL,IRVINE,CA 92717. UNIV CALIF IRVINE,DEPT NEUROL,IRVINE,CA 92717. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. FU NIA NIH HHS [P50-AG01542] NR 35 TC 60 Z9 60 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1996 VL 148 IS 6 BP 1797 EP 1806 PG 10 WC Pathology SC Pathology GA UN468 UT WOS:A1996UN46800011 PM 8669467 ER PT J AU Liu, ZH Striker, GE StetlerStevenson, M Fukushima, P Patel, A Striker, LJ AF Liu, ZH Striker, GE StetlerStevenson, M Fukushima, P Patel, A Striker, LJ TI TNF-alpha and IL-1 alpha induce mannose receptors and apoptosis in glomerular mesangial but not endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE mouse; endocytosis; cytokine; fluorescence-activated cell sorter analysis ID TUMOR-NECROSIS-FACTOR; DEATH APOPTOSIS; FLOW-CYTOMETRY; MACROPHAGES; THYMOCYTES; MONOCYTES; GROWTH AB The macrophage mannose receptor, a carbohydrate-binding membrane protein, mediates endocytosis and phagocytosis. This study was undertaken to determine whether mannose receptors were expressed in resting glomerular mesangial and endothelial cells and whether their level was affected by cytokines. Neither mannose receptor mRNA nor proteins were found in resting mesangial or endothelial cells. Mannose receptor mRNA was induced in a dose- and time-dependent manner in mesangial cells by interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF-alpha) but not by platelet-derived growth factor-B or IL-6. Cell surface receptors were found by fluorescence-activated cell sorter analysis. Binding to stimulated mesangial cells was saturable and inhibited by excess mannose-bovine serum albumin (BSA) but not by galactose-BSA. TNF-alpha and IL-1 alpha also induced apoptosis in mesangial cells. Mannose receptor expression was not restricted to apoptotic stimulated mesangial cells. Neither agonist induced mannose receptor expression or apoptosis in endothelial cells. Because immunoglobulin A, M, and G contain mannose residues, immune aggregates may be removed from the mesangium through cytokine-induced mannose receptors. C1 NIDDK, NIH, METAB DIS BRANCH, RENAL CELL BIOL SECT, BETHESDA, MD 20892 USA. NCI, NIH, PATHOL LAB, FLOW CYTOMETRY UNIT, BETHESDA, MD 20982 USA. NR 30 TC 36 Z9 38 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 1996 VL 270 IS 6 BP C1595 EP C1601 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UU611 UT WOS:A1996UU61100004 ER PT J AU Miller, DS Fricker, G Schramm, U Henson, JH Hager, DN Nundy, S Ballatori, N Boyer, JL AF Miller, DS Fricker, G Schramm, U Henson, JH Hager, DN Nundy, S Ballatori, N Boyer, JL TI Active microtubule-dependent secretion of a fluorescent bile salt derivative in skate hepatocyte clusters SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE bile canaliculus; elasmobranch; fluorescence microscopy; hepatic transport; little skate; liver; nocodazole; taurocholate ID RAT HEPATOCYTE; BILIARY-SECRETION; RAJA-ERINACEA; TRANSPORT; SYSTEM; LIVER; EXPRESSION; COUPLETS; TUBULES AB Fluorescence microscopy and video image analysis were used to study the transport of a fluorescent bile acid derivative {N-[7-(4-nitrobenzo-2-oxa-1,3-diazol)]-7 beta-amino-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oyl-2-aminoethanesulfonate (NBD-TC)} in isolated clusters of hepatocytes from the little skate Raja erinacea. Analysis of images of hepatocyte clusters that were incubated in medium with 0.5-1 mu M NBD-TC showed that the fluorescent derivative accumulated in the cells and that the clusters retained a patent canalicular lumen as well as the ability to actively transport the bile acid derivative from the cells into the lumen; i.e., the lumen-to-cell fluorescence ratio greatly exceeded unity. NBD-TC uptake by hepatocytes was inhibited by several organic anions, of which taurocholate was the most effective. Uptake was also blocked by metabolic inhibitors and by incubation in the cold. Neither Na replacement nor increased medium K, which depolarizes the membrane electrical potential [potential difference (PD)], affected NBD-TC accumulation by hepatocytes. Transport of NBD-TC into the canalicular lumen was inhibited by incubation in the cold and was substantially reduced by high-K medium; these blocks were removed by warming and transfer to normal-K medium, respectively. Treatment of hepatocytes with 20-40 mu M nocodazole, a drug that reversibly depolymerizes microtubules, reduced cellular NBD-TC accumulation and blocked its secretion into the canalicular lumen; nocodazole effects were reversed by washing the hepatocyte clusters in drug-free medium. Thus uptake of NBD-TC by skate hepatocytes is active and carrier mediated but not dependent on the PD or Na gradient. NBD-TC secretion from cell to canalicular lumen also appears to be active and carrier mediated. Canalicular secretion appears to be driven at least in part by the PD and is highly dependent on an intact microtubular system in this marine species. C1 SANDOZ PHARMA LTD, CH-4002 BASEL, SWITZERLAND. DICKINSON COLL, DEPT BIOL, CARLISLE, PA 17013 USA. YALE UNIV, SCH MED, DEPT MED, NEW HAVEN, CT 06510 USA. YALE UNIV, SCH MED, CTR LIVER, NEW HAVEN, CT 06510 USA. UNIV ROCHESTER, SCH MED, DEPT ENVIRONM MED, ROCHESTER, NY 14642 USA. MT DESERT ISL BIOL LAB, SALSBURY COVE, ME 04672 USA. RP Miller, DS (reprint author), NIEHS, CELLULAR & MOLEC PHARMACOL LAB, NIH, POB 12233, RES TRIANGLE PK, NC 27709 USA. FU NIDDK NIH HHS [DK-34989, DK-25636]; NIEHS NIH HHS [ES-03828] NR 31 TC 11 Z9 11 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 1996 VL 270 IS 6 BP G887 EP G896 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA UU990 UT WOS:A1996UU99000001 PM 8764193 ER PT J AU Kriketos, AD Pan, DA Lillioja, S Cooney, GJ Baur, LA Milner, MR Sutton, JR Jenkins, AB Bogardus, C Storlien, LH AF Kriketos, AD Pan, DA Lillioja, S Cooney, GJ Baur, LA Milner, MR Sutton, JR Jenkins, AB Bogardus, C Storlien, LH TI Interrelationships between muscle morphology, insulin action, and adiposity SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE skeletal muscle; fiber type; humans; oxidative capacity; fatty acid composition; NIH image; obesity; capillary density ID FATTY-ACID COMPOSITION; SKELETAL-MUSCLE; CAPILLARY DENSITY; DIETARY-FAT; WEIGHT-GAIN; FIBER TYPES; RESISTANCE; RATS; OBESITY; DISEASE AB There is evidence that insulin resistance and obesity are associated with relative increases in the proportion of glycolytic type IIb muscle fibers and decreases in the proportion of oxidative type I fibers. Futhermore, insulin resistance and obesity are associated with the fatty acid (FA) profile of structural membrane lipids. The present study was undertaken to define interrelationships between muscle fiber type and oxidative capacity, muscle membrane FA composition, and insulin action and obesity. Muscle morphology, insulin action, and body fat-content were measured in 48 male nondiabetic Pima Indians. Percent body fat (pFAT, determined by hydrodensitometry) correlated negatively with percentage of type I fibers (r = -0.44, P = 0.002) and positively with percentage of type IIb fibers (r = 0.40, P = 0.005). Consistent with this finding, pFAT was also significantly related to oxidative capacity of muscle, as assessed by NADH staining (r = -0.47, P = 0.0007) and citrate synthase (CS) activity (r = -0.43, P = 0.008). Insulin action was correlated with oxidative capacity (CS; r = 0.41, P = 0.01) and weekly correlated with percentage of type IIb fibers (r = -0.29, P = 0.05). In addition, relationships were shown between muscle fiber type and FA composition (e.g., percentage of type I fibers related to n-3 FA; r = 0.37, P = 0.01). Thus leaness and insulin sensitivity are associated with increased oxidative capacity and unsaturation of membranes in skeletal muscle. Present studies support the hypothesis that muscle oxidative capacity and fiber type may play a genetically determined or an environmentally modified role in development of obesity and insulin resistance. C1 ROYAL PRINCE ALFRED HOSP, DEPT ENDOCRINOL, SYDNEY, NSW 2050, AUSTRALIA. UNIV WOLLONGONG, DEPT BIOMED SCI, WOLLONGONG, NSW 2522, AUSTRALIA. NIDDK, CLIN DIABET & NUTR SECT, NIH, PHOENIX, AZ 85016 USA. RP Kriketos, AD (reprint author), UNIV SYDNEY, DEPT MED ENDOCRINOL, SYDNEY, NSW 2006, AUSTRALIA. RI Lillioja, Stephen/A-8185-2012; Jenkins, Arthur/D-4533-2012 NR 37 TC 83 Z9 85 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUN PY 1996 VL 270 IS 6 BP R1332 EP R1339 PG 8 WC Physiology SC Physiology GA UU589 UT WOS:A1996UU58900022 ER PT J AU Baird, DD Weinberg, CR Voigt, LF Daling, JR AF Baird, DD Weinberg, CR Voigt, LF Daling, JR TI Vaginal douching and reduced fertility SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PELVIC INFLAMMATORY DISEASE; CHLAMYDIA-TRACHOMATIS INFECTION; CIGARETTE-SMOKING; ECTOPIC PREGNANCY; UNITED-STATES; RISK FACTOR; DELAYED CONCEPTION; TUBAL INFERTILITY; WOMEN; ASSOCIATION AB Objectives. This study investigated douching and reduced fertility. Methods. The monthly probability of conception for douchers and nondouchers was compared in a sample of 840 married, parous women in King County, Washington. Data on the number of months required to conceive were analyzed. Results. In comparison with nondouchers, women who douched were 30% less likely to become pregnant each month they attempted pregnancy. This relationship remained after adjustment for covariates, and it could not be explained by women douching for medical reasons. The reduction was not related to the type of douching preparation used. Young women who douched had significantly greater reductions in monthly fertility than older women (50% reduction for women 18 to 24 years old, 29% reduction for women 25 to 29 years old, and 6% reduction for women 30 to 39 years old). Conclusions. Douching was associated with reduced fertility. Further research is needed to determine whether the relationship is causal and, if so, to what extent it is mediated by pelvic infection. In the meantime, women should be informed that douching may have adverse effects. C1 UNIV WASHINGTON, SCH PUBL HLTH & COMMUNITY MED, DEPT EPIDEMIOL, SEATTLE, WA 98195 USA. RP Baird, DD (reprint author), NIEHS, EPIDEMIOL BRANCH, DIV INTRAMURAL RES, MD A3-05, POB 12233, RES TRIANGLE PK, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 FU NICHD NIH HHS [1NO1 HD 02821] NR 47 TC 48 Z9 48 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1996 VL 86 IS 6 BP 844 EP 850 DI 10.2105/AJPH.86.6.844 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UQ530 UT WOS:A1996UQ53000018 PM 8659660 ER PT J AU Gladen, BC Rogan, WJ AF Gladen, BC Rogan, WJ TI DDE and insufficient breast milk - Response SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 NIEHS,OFF SCI DIRECTOR,RES TRIANGLE PK,NC 27709. RP Gladen, BC (reprint author), NIEHS,STAT & BIOMATH BRANCH,MAIL DROP A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1996 VL 86 IS 6 BP 887 EP 888 DI 10.2105/AJPH.86.6.887-a PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UQ530 UT WOS:A1996UQ53000031 ER PT J AU Scheidt, PC Harel, Y Trumble, AC Jones, DH Overpeck, MD Bijur, PE AF Scheidt, PC Harel, Y Trumble, AC Jones, DH Overpeck, MD Bijur, PE TI Nonfatal injuries among US children - Response SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 NICHHD,NIH,BETHESDA,MD 20892. BAR ILAN UNIV,DEPT SOCIOL,RAMAT GAN,ISRAEL. CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30341. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1996 VL 86 IS 6 BP 892 EP 893 DI 10.2105/AJPH.86.6.892-b PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UQ530 UT WOS:A1996UQ53000040 ER PT J AU Gerwin, BI AF Gerwin, BI TI Cytokine signaling in mesothelial cells: Receptor expression closes the autocrine loop SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID IL-6; INDUCTION; INVITRO; FAMILY; LINES RP Gerwin, BI (reprint author), NCI,HUMAN CARCINOGENESIS LAB,NIH,BLDG 37,ROOM 2C08,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 1996 VL 14 IS 6 BP 505 EP 507 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA UR399 UT WOS:A1996UR39900001 PM 8652178 ER PT J AU Kumar, S Kingma, DW Weiss, WB Raffeld, M Jaffe, ES AF Kumar, S Kingma, DW Weiss, WB Raffeld, M Jaffe, ES TI Primary cutaneous Hodgkin's disease with evolution to systemic disease - Association with the Epstein-Barr virus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE primary cutaneous Hodgkin's disease; Epstein Barr virus ID REED-STERNBERG CELLS; LYMPHOMATOID PAPULOSIS; INVOLVEMENT; EXPRESSION; ABSENCE AB Hodgkin's disease rarely involves the skin and when it does is an indication of advanced stage disease. Primary cutaneous Hodgkin's disease is exceedingly rare, and only a few cases are reported. We describe a patient who developed multiple cutaneous lesions of Hodgkin's disease 2 years before manifesting nodal disease of mixed cellularity subtype. Reed-Sternberg cells in the skin as well as lymph nodes and bone marrow were positive for Epstein-Barr viral transcripts and expressed viral latent membrane protein. Epstein-Barr virus has not previously been demonstrated in primary cutaneous Hodgkin's disease, and its presence in lesions at all sites in this case supports a diagnosis of primary cutaneous disease with subsequent evolution into systemic disease. C1 NCI, HEMATOPATHOL SECT, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NR 24 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 1996 VL 20 IS 6 BP 754 EP 759 DI 10.1097/00000478-199606000-00014 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA UL347 UT WOS:A1996UL34700014 PM 8651356 ER PT J AU Darwish, MA Faris, R Clemens, JD Rao, MR Edelman, R AF Darwish, MA Faris, R Clemens, JD Rao, MR Edelman, R TI High seroprevalence of hepatitis A, B, C, and E viruses in residents in an Egyptian village in Nile Delta: A pilot study SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID BLOOD-DONORS; SCHISTOSOMA-MANSONI; FAST-ELISA; INFECTION; EPIDEMIOLOGY; ANTIBODY; CHILDREN; PREVALENCE AB Hepatitis C virus (HCV) infection is hyperendemic in Egypt, with seroprevalence rates of 10-20% among volunteer blood donors, and even higher rates reported among segments of the general population. We attempted to confirm the high seroprevalence of HCV and to compare it with the age-specific seroprevalence rates for hepatitis A, hepatitis B, and hepatitis E among 155 nonrandomly selected residents of a semiurban village in the Nile River delta. Of the two orally transmitted viruses (HAV and HEV), all 1-3-year-old children had been infected by HAN and the seroprevalence rate of 100% persisted until age 67. In contrast, HEV infections were not detected until children were 4-9-years old, and the 57% seroprevalence rate in this age group did not increase appreciably in older age groups. Of the two parenterally transmitted viruses, HBV was first detected in 1-3-year-olds, whereas HCV was first detected later, in 10-19-year-olds. The seroprevalence rates of both viruses increased progressively with age, peaking in the 40-67-year-old group at 66% for HBV and at 51% For HCV. The number of persons who had only one infection, or no infection at all, was too small to allow meaningful statistical analysis of serologically pure groups infected only by HBV, HCV, or HEV. The results of this pilot study revealed extraordinarily high seroprevalence rates of HBV, HCV, and KEV in this village, and distinctive age-specific seroprevalence rates suggesting different patterns of transmission. C1 UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. AIN SHAMS UNIV,FAC MED,DEPT MICROBIOL,CAIRO,EGYPT. AIN SHAMS UNIV,FAC MED,DEPT COMMUNITY & PREVENT MED,CAIRO,EGYPT. NICHHD,EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MED,DIV GEOG MED,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. NR 27 TC 69 Z9 73 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1996 VL 54 IS 6 BP 554 EP 558 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA UX379 UT WOS:A1996UX37900002 PM 8686770 ER PT J AU Corbin, DOC Mora, CA Garriques, S RodgersJohnson, P Gibbs, CJ AF Corbin, DOC Mora, CA Garriques, S RodgersJohnson, P Gibbs, CJ TI Anterior horn cell degeneration in polymyositis associated with human T lymphotropic virus type-1 in patients from Barbados SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID I-ASSOCIATED MYELOPATHY; TROPICAL SPASTIC PARAPARESIS; INFECTION; HTLV-1 AB Anterior horn cell degeneration has only occasionally been noted in patients with tropical spastic paraparesis associated with human T lymphotropic virus type-1 (HTLV-1) infection. We report on three adult patients with HTLV-1-associated polymyositis who had clinical evidence of anterior horn cell degeneration. One patient had moderate proximal weakness and muscle wasting in all four limbs, while two had mild upper limb weakness with more profound proximal weakness and wasting in the lower limbs. In all three patients, electromyographic findings were compatible with motor unit loss and muscle biopsies showed mononuclear inflammatory cell infiltration; muscle biopsies in two patients showed features of denervation. Immunoglobulin G (IgG) antibodies to HTLV-1 were detected by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western immunoblot in serum and cerebrospinal fluid in all three patients. In two, cell cultures were established from peripheral blood lymphocytes and HTLV-1 antigen was identified by immunofluorescence and the ELISA antigen-capture technique using an anti-p19 HTLV-1 mouse monoclonal antibody. The three cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. In some cases of HTLV-1-associated polymyositis, anterior horn cell degeneration may make a significant contribution to the muscle atrophy observed. C1 QUEEN ELIZABETH HOSP,DEPT PATHOL,BRIDGETOWN,BARBADOS. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD. UNIV W INDIES,MONA,JAMAICA. RP Corbin, DOC (reprint author), QUEEN ELIZABETH HOSP,DEPT MED,BRIDGETOWN,BARBADOS. NR 23 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1996 VL 54 IS 6 BP 625 EP 628 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA UX379 UT WOS:A1996UX37900014 PM 8686782 ER PT J AU Bouare, M Sangare, D Bagayoko, M Toure, A Toure, YT Vernick, KD AF Bouare, M Sangare, D Bagayoko, M Toure, A Toure, YT Vernick, KD TI Short report: Simultaneous detection by polymerase chain reaction of mosquito species and Plasmodium falciparum infection in Anopheles gambiae sensu lato SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID RIBOSOMAL-RNA; GENES AB Total RNA purified from Anopheles gambiae mosquitoes can be used for detection of both 1) infection by Plasmodium falciparum using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay specific for P. falciparum ribosomal RNA (rRNA) of sporogonic stage parasites, and 2) mosquito species using a PCR assay that distinguishes members of the Anopheles gambiae complex. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RP Bouare, M (reprint author), ECOLE NATL MED & PHARM,DEPT EPIDEMIOL AFFECTAT PARASITAIRES,BP 1805,BAMAKO,MALI. NR 7 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1996 VL 54 IS 6 BP 629 EP 631 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA UX379 UT WOS:A1996UX37900015 PM 8686783 ER PT J AU Klotz, FW Cohen, SJ Szarfman, A Aikawa, M Howard, RJ AF Klotz, FW Cohen, SJ Szarfman, A Aikawa, M Howard, RJ TI Cross-reactive epitope among proteins in Plasmodium falciparum Maurer's clefts and primate leukocytes and platelets SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INFECTED ERYTHROCYTES; THAI PATIENTS; LIVER STAGES; MALARIA; MEMBRANE; ANTIBODY; CELLS; AUTOANTIBODIES; MEROZOITE; VESICLES AB Erythrocytes infected with malaria parasites often contain membranous vesicles that are presumed to facilitate macromolecule traffic between the parasite and erythrocyte membranes. One such vesicle network, called Maurer's clefts, is expressed in Plasmodium falciparum-infected erythrocytes and contains a 50-kD polypeptide. Using a monoclonal antibody reactive with this polypeptide, we show that hepatic stages of P. falciparum express an epitope common to this blood-stage antigen. In addition, this epitope is cross-reactive with antigens expressed by primate leukocytes and platelets. Such epitopes may induce autoantibodies commonly seen in patients with malaria. C1 WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, DEPT IMMUNOL, WASHINGTON, DC 20307 USA. NIH, PARASIT DIS LAB, MALARIA SECT, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, DEPT MICROBIOL & IMMUNOL, WASHINGTON, DC USA. USN, MED RES INST, BETHESDA, MD USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. CASE WESTERN RESERVE UNIV, INST PATHOL, CLEVELAND, OH 44106 USA. AFFYMAX RES INST, PALO ALTO, CA USA. FU NIAID NIH HHS [AI-10645] NR 31 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1996 VL 54 IS 6 BP 655 EP 659 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA UX379 UT WOS:A1996UX37900020 PM 8686788 ER PT J AU Muegge, K AF Muegge, K TI Third Annual Conference of the International Cytokine Society - Harrogate, UK, September 12-15, 1995 SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Editorial Material DE cytokine; signal transduction; transgenic RP Muegge, K (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE, ENGLAND LA6 2LA SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD JUN PY 1996 VL 3 IS 2 BP 140 EP 143 DI 10.3109/13506129609014367 PG 4 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA UX216 UT WOS:A1996UX21600009 ER PT J AU Balaban, RS Mootha, VK Arai, A AF Balaban, RS Mootha, VK Arai, A TI Spectroscopic determination of cytochrome c oxidase content in tissues containing myoglobin or hemoglobin SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID RAT-HEART; MITOCHONDRIA; CAPACITY AB A simple spectroscopic method for determining the cytochrome c oxidase, cytochrome a, a(3), content in tissue and mitochondria samples independent of myoglobin or blood contamination is described. Using tissue homogenates solubilized in Triton X-100, this assay relies on the selective reduction of mitochondrial cytochromes by the action of potassium cyanide. Monitoring the optical absorbance of these samples at 605 nm provided a quantitative determination of cytochrome c oxidase content in the presence of myoglobin or blood. The cytochrome c oxidase content of porcine heart mitochondria and whole tissue was determined to be 0.85 nmol/mg protein and 30.5 nmol/g wet wt, respectively. (C) 1996 Academic Press, Inc. RP Balaban, RS (reprint author), NHLBI,CARDIAC ENERGET LAB,NIH,BLDG 10,ROOM B1D-161,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 15 TC 59 Z9 59 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN 1 PY 1996 VL 237 IS 2 BP 274 EP 278 DI 10.1006/abio.1996.0239 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UP625 UT WOS:A1996UP62500016 PM 8660576 ER PT J AU Schaeberle, MD Kalasinsky, VF Luke, JL Lewis, EN Levin, IW Treado, PJ AF Schaeberle, MD Kalasinsky, VF Luke, JL Lewis, EN Levin, IW Treado, PJ TI Raman chemical imaging: Histopathology of inclusions in human breast tissue SO ANALYTICAL CHEMISTRY LA English DT Article ID SPECTROSCOPY; MICROPROBE; MICROSCOPY; EXCITATION; SPECIMENS; FILTER AB High-definition Raman chemical imaging microscopy is applied to the histopathological characterization of biopsied human breast tissue containing foreign polymer inclusions. The polymer material is found in a patient with a history of silicone implant breast reconstructive surgery. Silicone implants are, on occasion, anchored to the soft tissues of the chest with polyester patches. In the case studied here, the polyester anchors were incorporated into the patient's fibrous tissue surrounding the implant. High-definition Raman chemical imaging provides molecular-specific image contrast in the complex breast tissue matrix without the use of stains or dyes. This is the first example in which Raman spectroscopic imaging microscopy has been applied to pathology. A goal of this and future studies is to complement traditional histopathologic diagnoses of disease states utilizing vibrational spectroscopic imaging techniques. C1 UNIV PITTSBURGH,DEPT CHEM,PITTSBURGH,PA 15260. ARMED FORCES INST PATHOL,DEPT ENVIRONM & TOXICOL PATHOL,WASHINGTON,DC 20306. NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 37 TC 62 Z9 63 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 1 PY 1996 VL 68 IS 11 BP 1829 EP 1833 DI 10.1021/ac951245a PG 5 WC Chemistry, Analytical SC Chemistry GA UN470 UT WOS:A1996UN47000009 PM 8686910 ER PT J AU Slavkin, HC Diekwisch, T AF Slavkin, HC Diekwisch, T TI Evolution in tooth developmental biology: Of morphology and molecules SO ANATOMICAL RECORD LA English DT Review DE agnathans; gnathostomes; tooth development; heterochrony; enamelin; amelogenin; homeobox genes; growth factors and cognate receptors; enamel biomineralization; calcium hydroxyapatite crystals ID EPITHELIAL-MESENCHYMAL INTERACTIONS; MOUSE MANDIBULAR MORPHOGENESIS; CREST CELL-MIGRATION; DENTAL HARD TISSUES; NEURAL CREST; SQUALUS-ACANTHIAS; IMMUNOHISTOCHEMICAL LOCALIZATION; SECRETORY AMELOGENESIS; EXTRACELLULAR-MATRIX; ENAMEL PROTEINS RP Slavkin, HC (reprint author), NIAMSD, CRANIOFACIAL DEV SECT,NIH,6 CTR DR,MSC 2745, BLDG 6, RM 324, BETHESDA, MD 20892 USA. FU NIDCR NIH HHS [DE-09165, DE-06425, DE-02848] NR 164 TC 46 Z9 47 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0003-276X J9 ANAT RECORD JI Anat. Rec. PD JUN PY 1996 VL 245 IS 2 BP 131 EP 150 PG 20 WC Anatomy & Morphology SC Anatomy & Morphology GA UN849 UT WOS:A1996UN84900003 PM 8769659 ER PT J AU Voskuhl, RR PitchekianHalabi, H MacKenzieGraham, A McFarland, HF Raine, CS AF Voskuhl, RR PitchekianHalabi, H MacKenzieGraham, A McFarland, HF Raine, CS TI Gender differences in autoimmune demyelination in the mouse: Implications for multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ADOPTIVE TRANSFER; IMMUNE-RESPONSES; FINE-SPECIFICITY; T-CELLS; MICE; SEX; SUPPRESSION; PREGNANCY AB Gender-related differences in experimental allergic encephalomyelitis (EAE) were examined in the SJL mouse with the purpose of characterizing an animal model ideal for the study of gender-related differences in multiple sclerosis (MS), For the model to allow for study of the induction and the effector phase of disease, the adoptive EAE model was characterized. First, the SJL strain was shown to be nonresponsive with regard to the development of antisyngeneic HY-specific responses in females, thereby permitting intergender adoptive transfers of T lymphocytes during EAE induction, Then, when myelin basic protein (MBP)-specific T cells derived from females were adoptively transferred into female and male recipients, female recipients demonstrated a more rapid onset of disease (p = 0.01), greater maximal acute-phase clinical scores (p < 0.0001) and greater mean clinical scores (p = 0.0001) compared with male recipients. When MBP-specific T cells derived from males were adoptively transferred, female recipients again tended to be more severely affected. Histopathologic analysis revealed quantitative differences between genders that paralleled clinical expression. These results document a clear gender-related difference in adoptive EAE in the SJL, with clinical and histopathologic disease greater in females compared with males. This model will be a useful tool for addressing autoimmune mechanisms underlying gender-related differences in MS. C1 NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,DEPT PATHOL NEUROPATHOL NEUROL & NEUROSCI,BRONX,NY 10467. RP Voskuhl, RR (reprint author), UNIV CALIF LOS ANGELES,DEPT NEUROL,REED NEUROL RES CTR,ROOM A-145,10833 LE CONTE,LOS ANGELES,CA 90024, USA. OI MacKenzie-Graham, Allan/0000-0001-9966-2335 FU NINDS NIH HHS [NS08952, NS07098, NS11920] NR 39 TC 89 Z9 93 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1996 VL 39 IS 6 BP 724 EP 733 DI 10.1002/ana.410390608 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UQ881 UT WOS:A1996UQ88100007 PM 8651644 ER PT J AU Voskuhl, RR Goldstein, AM Simonis, T Davey, RJ McFarland, HF AF Voskuhl, RR Goldstein, AM Simonis, T Davey, RJ McFarland, HF TI DR2/DQwl inheritance and haplotype sharing in affected siblings from multiple sclerosis families SO ANNALS OF NEUROLOGY LA English DT Article ID DETERMINANTS; ASSOCIATION AB Although the human leukocyte antigen DR2/DQw1 allele has been associated with multiple sclerosis, studies of DR2/DQw1 inheritance in multiple sclerosis multiplex families have yielded conflicting results. We examined this question in ''high-incidence'' families, defined as families with more than 50% of siblings affected. DR2/DQw1 allele frequencies were significantly increased, particularly in mothers and affected siblings (p < 0.0001). The transmission of DR2/DQw1 from both parents was more frequent in affected offspring (p = 0.005). While evidence for segregation of disease with a particular parental allele was lacking in most families, the frequency of haplotype sharing was higher in affected sib pairs (p < 0.01). C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NATL CANC INST,BETHESDA,MD. NIH,DEPT TRANSFUS MED,BETHESDA,MD. NR 16 TC 15 Z9 15 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1996 VL 39 IS 6 BP 804 EP 807 DI 10.1002/ana.410390618 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UQ881 UT WOS:A1996UQ88100017 PM 8651654 ER PT J AU Pass, HI Mew, DJY Kranda, KC Temeck, BK Donington, JS Rosenberg, SA AF Pass, HI Mew, DJY Kranda, KC Temeck, BK Donington, JS Rosenberg, SA TI Isolated lung perfusion with tumor necrosis factor for pulmonary metastases SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 09-11, 1993 CL SAN ANTONIO, TX SP So Thoracic Surg Assoc ID INTERFERON-GAMMA; FACTOR-ALPHA; HYPERTHERMIA; MECHANISMS; TOXICITY; CELLS; EDEMA AB Background. A phase I trial was initiated to define the feasibility and safety of single-lung isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and moderate hyperthermia for patients with unresectable pulmonary metastases. Methods. Twenty patients with lung metastases (Ewing's, 2; sarcoma, 8; melanoma, 6; other, 4) were considered for single-lung isolation perfusion with 0.3 to 6.0 mg of tumor necrosis factor-alpha and 0.2 mg interferon-gamma delivered through an oxygenated pump circuit. Sixteen perfusions were performed in 15 patients (bilateral in 1). Metastases were completely resected (no single-lung isolation perfusion) in 3 patients, 1 patient had extrapulmonary disease, and one single-lung isolation perfusion was aborted for mechanical reasons. Results. There were no significant changes in systemic arterial blood pressure or cardiac output during perfusion. Systolic pulmonary artery pressure increased with isolation, but returned to pre-single-lung isolation perfusion levels after clamp release. The maximum systemic tumor necrosis factor-alpha level was 8 ng/mL, whereas pump-circuit levels ranged from 200 to 10,976 ng/mL. There were no deaths, and the mean hospitalization period was 9 days (range, 5 to 34 days). A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients (melanoma in 1, adenoid cystic carcinoma in 1, renal cell carcinoma in 1). Conclusions. Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function. RP Pass, HI (reprint author), NCI,THORAC ONCOL SECT,SURG BRANCH,NIH,BLDG 10,RM 2B07,BETHESDA,MD 20892, USA. NR 20 TC 64 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1996 VL 61 IS 6 BP 1609 EP 1617 DI 10.1016/0003-4975(96)00166-X PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UN412 UT WOS:A1996UN41200004 PM 8651757 ER PT J AU Jacobson, JM Davidian, M Rainey, PM Hafner, R Raasch, RH Luft, BJ AF Jacobson, JM Davidian, M Rainey, PM Hafner, R Raasch, RH Luft, BJ TI Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ENCEPHALITIS; AIDS; SULFADIAZINE; COMBINATION; SULFADOXINE; EFFICACY; THERAPY; SERUM AB Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102), Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose, Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 mu g . h/ml; half-life, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection, Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients. C1 MT SINAI SCH MED,NEW YORK,NY. SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT LAB MED,NEW HAVEN,CT 06510. NIAID,DIV AIDS,WASHINGTON,DC. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC. RP Jacobson, JM (reprint author), BRONX VET AFFAIRS MED CTR,DEPT MED,DIV INFECT DIS,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. OI Luft, Benjamin/0000-0001-9008-7004 NR 25 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1996 VL 40 IS 6 BP 1360 EP 1365 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UP107 UT WOS:A1996UP10700007 PM 8726001 ER PT J AU deJonge, BLM Chang, YS Xu, N Gage, D AF deJonge, BLM Chang, YS Xu, N Gage, D TI Effect of exogenous glycine on peptidoglycan composition and resistance in a methicillin-resistant Staphylococcus aureus strain SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PENICILLIN-BINDING PROTEIN-2A; HETEROGENEOUS STRAINS; EXPRESSION; BIOSYNTHESIS AB A highly homogeneously methicillin-resistant Staphylococcus aureus strain was grown in the presence of various concentrations of exogenous glycine. Increasing concentrations of glycine in the medium resulted in a decrease in methicillin resistance and the appearance of a heterogeneous resistance phenotype. Parallel to the gradual changes in resistance was an alteration in the muropeptide composition of peptidoglycan. Increasing concentrations of glycine in the medium resulted in peptidoglycan in which muropeptides with a D-alanyl-D-alanine terminus were replaced with D-alanyl-glycine-terminating muropeptides. The disappearance of D-alanyl-D-alanine-terminating muropeptides in peptidoglycan and the concomitant decrease in resistance indicate a central role for D-alanyl-D-alanine-terminating precursors in methicillin resistance. C1 HANYANG UNIV,DEPT CHEM,ANSAN,SOUTH KOREA. MICHIGAN STATE UNIV,DEPT BIOCHEM,MASS SPECTROMETRY FACIL,NIH,E LANSING,MI 48824. RP deJonge, BLM (reprint author), ROCKEFELLER UNIV,MICROBIOL LAB,BOX 152,NEW YORK,NY 10021, USA. FU NCRR NIH HHS [RR00480] NR 26 TC 17 Z9 18 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1996 VL 40 IS 6 BP 1498 EP 1503 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UP107 UT WOS:A1996UP10700032 PM 8726026 ER PT J AU Patterson, RM He, CY Selkirk, JK Merrick, BA AF Patterson, RM He, CY Selkirk, JK Merrick, BA TI Human p53 expressed in baculovirus-infected Sf9 cells displays a two-dimensional isoform pattern identical to wild-type p53 from human cells SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE baculovirus; protein expression; p53 protein; electrophoresis; two-dimensional PAGE; phosphorylation ID TUMOR SUPPRESSOR PROTEIN; GROWTH ARREST; ELECTROPHORESIS; P53-PROTEIN; SECRETION; INVITRO; BINDING AB Baculovirus expression of human p53 protein, a nuclear cell cycle regulator, was examined in Sf9 cells and compared to native p53 synthesized in primary human cells, Maximum expression of the recombinant p53 protein occurred 48 h postinfection. De novo synthesis of the protein was evident for only 2 days postinfection; however, in pulse-chase studies, 30% of the synthesized protein remained stable up to 5 days. Seventy-seven percent of immunoprecipitated, [S-35]-methionine-labeled, recombinant p53 protein resided in the cytoplasm of Sf9 cells, while 15% localized to the nucleus and 8% was released extracellularly. Separation of modified p53 protein, by charge and molecular weight, was accomplished by two-dimensional PAGE, and the electrophoretic pattern of the recombinant protein was identical to the wild-type protein from primary human mammary epithelial cells, indicating that the posttranslational modifications of the recombinant protein in this system are similar to those in primary human cells. Eleven isoforms focused between pI 5.75 and pI 6.5. The recombinant p53 isoforms were phosphorylated by P-32-labeling, Phosphatase digestion of immunoprecipitated p53 effectively removed phosphorous groups from the recombinant protein, reducing the number of isoforms from 11 to 2, demonstrating that phosphorylation is the major posttranslational event in the recombinant protein. (C) 1996 Academic Press, Inc. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 50 TC 14 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 1996 VL 330 IS 1 BP 71 EP 79 DI 10.1006/abbi.1996.0227 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UP131 UT WOS:A1996UP13100010 PM 8651706 ER PT J AU Zeldin, DC Moomaw, CR Jesse, N Tomer, KB Beetham, J Hammock, BD Wu, S AF Zeldin, DC Moomaw, CR Jesse, N Tomer, KB Beetham, J Hammock, BD Wu, S TI Biochemical characterization of the human liver cytochrome P450 arachidonic acid epoxygenase pathway SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE eicosanoid; epoxyeicosatrienoic acid; dihydroxyeicosatrienoic acid; cytosolic epoxide hydrolase; microsomal epoxide hydrolase ID CYTOSOLIC EPOXIDE HYDROLASE; ENDOGENOUS EPOXYEICOSATRIENOIC ACIDS; MICROSOMAL CYTOCHROME-P-450; RAT-KIDNEY; ENANTIOFACIAL SELECTIVITY; CHROMOSOMAL LOCALIZATION; RENAL CORTEX; METABOLITES; PURIFICATION; EXPRESSION AB Human liver microsomal fractions metabolized arachidonic acid in the presence of NADPH yielding epoxyeicosatrienoic acids and their hydration products, dihydroxyeicosatrienoic acids, as the principal reaction products. Inhibition studies using polyclonal antibodies prepared against recombinant CYP2C8, an abundant human liver cytochrome P450 epoxygenase, demonstrated 85-90% inhibition of arachidonic acid epoxide formation, Both epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids were detected in large amounts in human liver using gas chromatography/mass spectrometry, Chiral analysis of the endogenous liver epoxides demonstrated a preference for the 14(R),15(S)-, 11(R),12(S)-, and 8(S),9(R)-epoxyeicosatrienoic acid enantiomers, Importantly, the chirality of liver epoxyeicosatrienoic acids matched that previously reported for recombinant CYP2C8 (Zeldin et al, (1995) Arch, Biochem, Biophys, 322, 76-86), Incubations of both human liver cytosolic and microsomal fractions with synthetic epoxyeicosatrienoic acids revealed a 10-fold higher rate of dihydroxyeicosatrienoic acid formation with cytosolic relative to microsomal fractions, Recombinant human liver cytosolic epoxide hydrolase rapidly and regioselectively hydrated epoxyeicosatrienoic acids, We conclude, based on these data, that CYP2C8 is one of the primary, constitutive hepatic arachidonic acid epoxygenases responsible for formation of epoxyeicosatrienoic acids and that cytosolic epoxide hydrolase is the principal liver enzyme which forms the dihydroxyeicosatrienoic acids. We speculate that these biologically active eicosanoids may be important in maintaining homeostasis in the liver. (C) 1996 Academic Press, Inc. C1 NIEHS, NIH, LAB MOLEC BIOPHYS, RES TRIANGLE PK, NC 27709 USA. UNIV CALIF DAVIS, DEPT ENTOMOL, DAVIS, CA 95616 USA. UNIV CALIF DAVIS, DEPT ENVIRONM TOXICOL, DAVIS, CA 95616 USA. RP NIEHS, NIH, PULM PATHOBIOL LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 FU NIEHS NIH HHS [ES 02710]; PHS HHS [N0K 38226] NR 71 TC 105 Z9 105 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 1996 VL 330 IS 1 BP 87 EP 96 DI 10.1006/abbi.1996.0229 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UP131 UT WOS:A1996UP13100012 PM 8651708 ER PT J AU Simon, M Kind, P Kaudewitz, P Graf, A Schirren, CG Raffeld, M Sander, CA AF Simon, M Kind, P Kaudewitz, P Graf, A Schirren, CG Raffeld, M Sander, CA TI Detection of herpesvirus-like DNA in HIV-associated and classical Kaposi's sarcoma SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE Kaposi's sarcoma; herpesvirus-like DNA; HIV; PCR analysis ID VIRUS; INFECTION C1 UNIV MUNICH,DEPT DERMATOL,D-80337 MUNICH,GERMANY. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 16 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD JUN PY 1996 VL 288 IS 7 BP 402 EP 404 PG 3 WC Dermatology SC Dermatology GA UV791 UT WOS:A1996UV79100010 PM 8818189 ER PT J AU DiGiovanna, JJ Sollitto, RB Steinberg, SM Reynolds, JC AF DiGiovanna, JJ Sollitto, RB Steinberg, SM Reynolds, JC TI Osteoporosis and long-term etretinate therapy - Reply SO ARCHIVES OF DERMATOLOGY LA English DT Letter RP DiGiovanna, JJ (reprint author), NIAMSD,DERMATOL CLIN RES UNIT,NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 1996 VL 132 IS 6 BP 714 EP 714 PG 1 WC Dermatology SC Dermatology GA UQ751 UT WOS:A1996UQ75100024 ER PT J AU Virkkunen, M Eggert, M Rawlings, R Linnoila, M AF Virkkunen, M Eggert, M Rawlings, R Linnoila, M TI A prospective follow-up study of alcoholic violent offenders and fire setters SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FLUID 5-HYDROXYINDOLEACETIC ACID; CEREBROSPINAL-FLUID; SERUM-CHOLESTEROL; AUTONOMIC MEASURES; HOMOVANILLIC-ACID; BEHAVIOR; 3-METHOXY-4-HYDROXYPHENYLGLYCOL; METABOLITES; PREDICTION; RECIDIVISM AB Background: This study investigated biochemical and family variables and predictors of recidivism among forensic psychiatric patients who had committed violent offenses or set fires. Methods: One hundred fourteen male alcoholic violent offenders and fire setters were followed up for an average of 4.5 years after release from prison. At the beginning of their incarceration, the first half of the offenders were administered clinical diagnostic interviews, whereas the latter half received the Structured Clinical Interview for DSM-III (SCID) that was blind rated. A structured family history questionnaire was administered to all available first-degree relatives of offenders. The offenders also received lumbar punctures for monoamine metabolites, an oral glucose tolerance test, and a measurement of fasting plasma cholesterol level. At the end of the follow-up, the Finnish criminal registry was searched for recidivist crimes. Results: Among all offenders, low cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (S-HIAA) and homovanillic acid (HVA) concentrations were associated with a family history positive for paternal alcoholism with violence. Low plasma cholesterol concentration was associated with a family history positive for paternal alcoholism without violence. The recidivists, who committed violent offenses or set fires during the follow-up period, had low CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations compared with those in nonrecidivists. Early family environments of the recidivists, compared with those of the nonrecidivists, were characterized by common paternal absence from and presence of brothers at home. Conclusion: Among male alcoholic violent offenders and fire setters, low CSF S-HIAA and HVA concentrations are strongly associated with a family history positive for paternal violence and alcoholism, while low fasting plasma cholesterol concentration is associated with a family history positive for paternal alcoholism. Recidivist violent offenders and fire setters are predicted by low CSF 5-HIAA and MHPG concentrations and a developmental history positive for early paternal absence from and presence of brothers in the family of origin. C1 NIAAA,CLIN STUDIES LAB,DICBR,BETHESDA,MD 20892. UNIV HELSINKI,DEPT PSYCHIAT,SF-00180 HELSINKI,FINLAND. RI McCarthy, Jodie/B-5760-2012 NR 45 TC 99 Z9 99 U1 3 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1996 VL 53 IS 6 BP 523 EP 529 PG 7 WC Psychiatry SC Psychiatry GA UP723 UT WOS:A1996UP72300006 PM 8639035 ER PT J AU Higley, JD Mehlman, PT Higley, SB Fernald, B Vickers, J Lindell, SG Taub, DM Suomi, SJ Linnoila, M AF Higley, JD Mehlman, PT Higley, SB Fernald, B Vickers, J Lindell, SG Taub, DM Suomi, SJ Linnoila, M TI Excessive mortality in young free-ranging male nonhuman primates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MONKEYS MACACA-MULATTA; RHESUS-MONKEYS; METABOLITES; MONOAMINE; BEHAVIOR AB Background: The purpose of this study was to assess the impact of central serotonin turnover rate on survival to adulthood among nonhuman primates living in a large, free-ranging colony. Methods: The rate of mortality was ascertained over a 4-year period after obtaining blood and cisternal cerebrospinal fluid (CSF) samples from 49 free-ranging, 2-year-old prepubertal male rhesus monkeys. Cerebrospinal fluid was assayed for 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, 3-methoxy-4-hydroxyphenylgycol, and homovanillic acid. Blood plasma was assayed for adrenocorticotropic hormone, cortisol, and testosterone. Following the sampling of body fluids, records of scars and wounds and aggressive encounters were used to rank the subjects from low to high in aggressiveness. Direct observations of aggressive behavior were collected from 27 of the subjects over a 3-month period. Results: Four years later, 6 of the 49 subjects were known to be dead and an additional 5 had been missing for more than 2 years and were presumed dead. The CSF 5-HIAA concentrations were predictive of which subjects died, with 46% of the subjects with low CSF 5-HIAA concentrations dead or presumed dead. None of the subjects from the highest CSF 5-HIAA concentration quartile were dead or missing. Indeed, 91% of the dead subjects came from the 2 lowest quartiles of CSF 5-HIAA concentrations. Direct observations of aggressive behavior showed that dead or missing subjects had initiated escalated aggression, a measure of unrestrained aggression that has a high probability of trauma or injury, at a higher rate than subjects that were known to be alive. The cause of death could be ascertained for 6 of the 11 missing subjects. The 4 subjects that were known to die as a consequence of aggressive encounters came from the lowest quartile of CSF 5-HIAA concentrations and had been rated as more aggressive during their initial capture. Subjects captured more than once possessed lower CSF 5-HIAA concentrations, were rated as more aggressive, and were more likely to suffer early death than those captured only once. Conclusion: These findings suggest that low CSF 5-HIAA concentrations quantified early in life is a powerful biological predictor of future excessive aggression, risk taking, and premature death among nonhuman primate males. C1 NIAAA,SECT NEUROCHEM & NEUROENDOCRINOL,CLIN STUDIES LAB,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20205. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. LAB ANIM BREEDERS & SERV INC,YEMASSEE,SC. FU PHS HHS [223-89-1101] NR 25 TC 138 Z9 138 U1 1 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1996 VL 53 IS 6 BP 537 EP 543 PG 7 WC Psychiatry SC Psychiatry GA UP723 UT WOS:A1996UP72300008 PM 8639037 ER PT J AU Podgor, MJ Remaley, NA Chew, E AF Podgor, MJ Remaley, NA Chew, E TI Associations between siblings for esotropia and exotropia SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CORRELATED BINARY REGRESSION; FAMILIAL AGGREGATION; MODELS AB Objective: To quantify familial aggregation of esotropia and exotropia in children examined in a large multicenter study. Methods: Pregnant women and their children were examined in the Collaborative Perinatal Project of the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Strabismus was evaluated in the children during follow-up examinations up to the age of 7 years. The second-order generalized estimating equations approach to logistic regression was used to estimate familial aggregation of esotropia and exotropia. Results: For any pair of siblings, the odds for one sibling having esotropia more than doubled when the other sibling had esotropia. For exotropia, there were differences in sibling associations based on birth relationships. In particular, there was no statistically significant association be tween siblings from separate single births. On the other hand, for the pairs of siblings from multiple births (ie, twins, triplets, and quadruplets), the odds for exotropia in one sibling were increased by at least a factor of 17 when the other sibling from that birth also had exotropia. For both esotropia and exotropia, adjustment for previously identified risk factors only somewhat reduced the magnitudes of the observed associations. Limited data on zygosity showed a stronger association between monozygotic twins than between dizygotic twins. Conclusions: There is a significant familial component in the cause of strabismus. Furthermore, there are important contributions to this familial aggregation beyond those associated with known risk factors for strabismus. RP Podgor, MJ (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,NIH,BLDG 31,ROOM 6A52,31 CTR DR MSC 2510,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z99 EY999999] NR 21 TC 23 Z9 24 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1996 VL 114 IS 6 BP 739 EP 744 PG 6 WC Ophthalmology SC Ophthalmology GA UP245 UT WOS:A1996UP24500017 PM 8639089 ER PT J AU McIntosh, K Comeau, AM Wara, D Diaz, C Landesman, S Pitt, J Rich, K Lew, J Moye, J Kalish, LA AF McIntosh, K Comeau, AM Wara, D Diaz, C Landesman, S Pitt, J Rich, K Lew, J Moye, J Kalish, LA TI The utility of IgA antibody to human immunodeficiency virus type 1 in early diagnosis of vertically transmitted infection SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID HIV-INFECTION; ENZYME-IMMUNOASSAY; INFANTS AB Objective: To determine the sensitivity and specificity of anti-human immunodeficiency virus (HIV) IgA in identifying infected infants at or before 6 months of age among the offspring of HIV-infected mothers. Design: Prospective comparison of anti-HIV IgA measurement performed in 2 different laboratories by 2 different methods with the criterion standard of blood culture. Setting: Five centers in the United States and Puerto Rico. Patients: Population-based sample of 156 infants of HIV-infected mothers in the Women and Infants Transmission Study. Main Outcome Measures: Results of anti-HIV IgA test in relation to the infection status of the infants as measured by blood culture. Results: Six-month plasma or serum samples were first tested in the 2 laboratories. The sensitivity and specificity of anti-HIV IgA in detecting infected infants at this age by laboratories 1 and 2 were 69% and 63% and 100% and 99%;, respectively. A look-back study of samples obtained at birth, 1, 2, and 4 months was then performed on all infected children and a matched set of uninfected children. The performance of the test at birth was unsatisfactory in both laboratories (sensitivity 44% and 33%, specificity 43% and 60%), whether peripheral or cord blood was examined. At 1, 2, and 4 months, the sensitivity of the test was lower than at 6 months, but specificity was high. A modest correlation of absent anti-HIV IgA antibody and low percentage of CD4 cells in peripheral blood was seen at 6 months of age. Conclusions: The anti-HIV IgA Lest has moderate sensitivity and high specificity for the diagnosis of HIV infection at 6 months of age in the offspring of infected mothers. C1 UNIV PUERTO RICO,DEPT PEDIAT,SAN JUAN,PR 00936. SUNY HLTH SCI CTR,BROOKLYN,NY. COLUMBIA UNIV COLL PHYS & SURG,DEPT PEDIAT,DIV INFECT DIS,NEW YORK,NY 10032. UNIV ILLINOIS,DEPT PEDIAT,CHICAGO,IL. NEW ENGLAND RES INST,WATERTOWN,MA 02172. THEOBALD SMITH RES INST INC,NEW ENGLAND REG NEWBORN SCREENING PROGRAM,JAMAICA PLAIN,MA. NIAID,VACCINE TRIALS & EPIDEMIOL BRANCH,DIV ACQUIRED IMMUNODEFICIENCY SYNDROME,NIH,BETHESDA,MD 20892. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,NIH,BETHESDA,MD 20892. RP McIntosh, K (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV INFECT DIS,DEPT PEDIAT,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [N01-AI-82506, N01-AI-82507]; NICHD NIH HHS [N01-HD-82917] NR 15 TC 7 Z9 7 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUN PY 1996 VL 150 IS 6 BP 598 EP 602 PG 5 WC Pediatrics SC Pediatrics GA UP413 UT WOS:A1996UP41300006 PM 8646309 ER PT J AU Kanik, KS Yarboro, CH Naparstek, Y Plotz, PH Wilder, RL AF Kanik, KS Yarboro, CH Naparstek, Y Plotz, PH Wilder, RL TI Failure of low-dose intravenous immunoglobulin therapy to suppress disease activity in patients with treatment-refractory rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IMMUNE GLOBULIN AB Objective, Treatment with high-dose (400 mg/kg/day) intravenous immunoglobulin (IVIg) shows benefit in many autoimmune diseases but is very expensive, Low-dose IVIg has also been shown to be effective in inhibiting adjuvant arthritis in the rat, This pilot, randomized, double-blind, placebo-controlled trial was conducted to assess the use of low-dose IVIg in patients with treatment-refractory rheumatoid arthritis (RA). Methods. Twenty patients with active RA were recruited. Ten patients received IVIg and 10 received albumin, Study subjects were given 6 courses of either IVIg (5 mg/kg) or albumin (5 mg/kg), once every 3 weeks, Baseline medications were continued and not changed throughout the study. Results. There were no complications, Five patients dropped out before the 18-week followup visit, No significant differences between treatment groups were noted during the 18-week trial in terms of global activity indices (patient or physician assessment), joint swelling, joint pain or tenderness, erythrocyte sedimentation rate, C-reactive protein level, or rheumatoid factor, The protocol was terminated prematurely because of reported contamination of IVIg by hepatitis C virus, None of the patients showed evidence of hepatitis C infection by serologic analysis or by polymerase chain reaction. Conclusion. Low-dose IVIg, as administered in this trial, does not show a therapeutic effect in patients with refractory RA. C1 NIAMSD,NIH,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. HADASSAH UNIV HOSP,IL-91120 JERUSALEM,ISRAEL. NR 15 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1996 VL 39 IS 6 BP 1027 EP 1029 DI 10.1002/art.1780390621 PG 3 WC Rheumatology SC Rheumatology GA UQ192 UT WOS:A1996UQ19200019 PM 8651966 ER PT J AU Krause, RM AF Krause, RM TI Metchnikoff and syphilis research during a decade of discovery, 1900-1910 SO ASM NEWS LA English DT Article C1 NATL INST HLTH,FOGARTY INT CTR,BETHESDA,MD. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD JUN PY 1996 VL 62 IS 6 BP 307 EP 310 PG 4 WC Microbiology SC Microbiology GA UP718 UT WOS:A1996UP71800019 ER PT J AU Smith, MA AF Smith, MA TI Hippocampal vulnerability to stress and aging: Possible role of neurotrophic factors SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Synaptic Plasticity of the Cortex - Basic Aspects and Implications for Alzheimers Disease CY OCT, 1994 CL FREIBURG, GERMANY DE brain-derived neurotrophic factor; nerve growth factor; neurotrophin-3; glucocorticoid; Alzheimer's disease; aging; excitotoxicity; hippocampus; stress ID NERVE GROWTH-FACTOR; MESSENGER-RNA EXPRESSION; LONG-TERM POTENTIATION; CORTICOTROPIN-RELEASING-FACTOR; TRANSIENT FOREBRAIN ISCHEMIA; INHIBIT GLUCOSE-TRANSPORT; EXCITATORY AMINO-ACIDS; CA3 PYRAMIDAL NEURONS; FACTOR NGF SYNTHESIS; RAT DENTATE GYRUS AB Chronic stress can accelerate age-related damage to the hippocampus. Adrenal glucocorticoids are thought to be responsible for this damage because of their ability to compromise energy metabolism and make neurons more vulnerable to glutamate excitotoxicity. Additional mechanisms by which stress or glucocorticoids could damage the hippocampus are considered in the context of recent evidence that stress regulates neurotrophic factor expression in the brain. Stress has been found to decrease brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus, and this may contribute to stress-induced damage in this and other brain areas. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are increased by stress and glucocorticoids perhaps as a compensatory response to stress-induced damage. Because neurotrophic factors can protect the brain from a variety of traumatic insults, it is likely that they might also be effective in preventing or reversing glucocorticoid-induced damage to the hippocampus. RP Smith, MA (reprint author), NIMH, BIOL PSYCHIAT BRANCH, BLDG 10, ROOM 3N212, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 116 TC 92 Z9 95 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JUN PY 1996 VL 78 IS 1 BP 25 EP 36 DI 10.1016/0166-4328(95)00220-0 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA UR897 UT WOS:A1996UR89700005 PM 8793034 ER PT J AU Kohn, KW AF Kohn, KW TI DNA filter elution: A window on DNA damage in mammalian cells SO BIOESSAYS LA English DT Article ID INTERSTRAND CROSS-LINKING; SINGLE-STRAND BREAKS; ALKALINE ELUTION; DEOXYRIBONUCLEIC-ACID; TOPOISOMERASE-II; L1210 CELLS; HUMAN-TUMOR; XERODERMA PIGMENTOSUM; INTERCALATING AGENTS; PROTEIN AB This personal account traces a series of studies that led from DNA physical chemistry to anticancer drug mechanisms, Chemical crosslinking as a basis for anticancer drug actions had been suspected since the time of the first clinical reports of the effectiveness of nitrogen mustard in 1946, After the elucidation of the DNA helix-coil transition, several nearly concurrent findings in the early 1960s established the paradigm of DNA interstrand crosslinking. The DNA filter elution phenomenon was discovered in the early 1970s, and lent itself to the development of practical assays for DNA crosslinks and other DNA lesions in mammalian cells. The assays allowed studies of the effects of DNA damaging agents at pharmacologically or toxicologically relevant doses, and have been widely applied in studies of mutagenic and chemotherapeutic agents. During the period 1979-1986, DNA filter elution studies led to the paradigm of DNA topoisomerases as targets of anticancer drug action, and this has become one of the most active areas of anticancer drug development. RP Kohn, KW (reprint author), NCI,NIH,MOLEC PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892, USA. NR 73 TC 36 Z9 37 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUN PY 1996 VL 18 IS 6 BP 505 EP 513 DI 10.1002/bies.950180613 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA UV795 UT WOS:A1996UV79500012 PM 8787538 ER PT J AU Bastiani, AM Altemus, M Pigott, TA Rubenstein, C Weltzin, TE Kaye, WH AF Bastiani, AM Altemus, M Pigott, TA Rubenstein, C Weltzin, TE Kaye, WH TI Comparison of obsessions and compulsions in patients with anorexia nervosa and obsessive compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anorexia nervosa; obsessive-compulsive disorders; eating disorders; serotonin; compulsions ID SCALE AB Patients with anorexia nervosa (n = 18) and patients with obsessive-compulsive disorder (OCD) (n = 16) had similar scores on the Yale-Brown Obsessive Compulsive Scale (19 +/- 9 vs. 22 +/- 6). This suggests that these disorders have similar magnitude of impairment from obsessions and compulsions; however, OCD patients endorsed a wide variety of obsessions and compulsions, whereas anorexics tended to endorse symptoms that were related to symmetry and order. C1 UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20007. FU NCRR NIH HHS [5-MOI-RR00084]; NIMH NIH HHS [2-ROI-MH4298] NR 10 TC 47 Z9 47 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 1996 VL 39 IS 11 BP 966 EP 969 DI 10.1016/0006-3223(95)00306-1 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UK321 UT WOS:A1996UK32100008 PM 9162209 ER PT J AU Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD AF Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD TI Calcium, magnesium, and phosphorus content of hair from two populations of rhesus monkeys SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE hair mineral content; monkeys; rhesus monkeys; Macaca mulatta ID MACACA-MULATTA; CAYO-SANTIAGO; TRACE; ZINC; NUTRITION; MINERALS; CATTLE; COPPER AB The use of hair for the assessment of human mineral nutritional status is controversial, yet has potential because of the ease of collection and storage, and the high concentration of minerals in hair. This study generated baseline values for hair macromineral content in the most commonly used primate model for human nutrition and disease, the rhesus monkey. Hair digests from monkeys in Maryland (n=98) and Puerto Rico (n=208) were analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES). Significant differences existed between the two populations for hair calcium (Ca), magnesium (Mg), and phosphorus (P) (P <0.01, P <0.001, P<0.02). Male hair had higher concentrations of Mg in specimens from the Puerto Rican population (P <0.001), whereas hair phosphorus was higher in female hair (P <0.02). There were no significant differences attributable to pregnancy status. Differences in hair content attributable to categorical age were found for Ca and Mg (P <0.001, P <0.01). Significant location differences paralleled dietary differences. These values therefore can be considered reference ranges for hair Ca, Mg, and P for free-ranging and caged rhesus monkeys. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. USDA,HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. US FDA,SAN FRANCISCO DIST OFF,PESTICIDE MET SECT,SAN FRANCISCO,CA. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF BELTSVILLE TECH OPERAT,LAUREL,MD. RP Marriott, BM (reprint author), NIH,OFF DIETARY SUPPLEMENTS,FED BLDG,SUITE 610,7500 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-01293, RR-7-2115]; NIMH NIH HHS [MH3079-01A2] NR 70 TC 3 Z9 3 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD SUM PY 1996 VL 53 IS 1-3 BP 147 EP 165 DI 10.1007/BF02784552 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VA909 UT WOS:A1996VA90900014 PM 8862745 ER PT J AU Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD AF Marriott, BM Smith, JC Jacobs, RM Jones, AOL Altman, JD TI Copper, iron, manganese, and zinc content of hair from two populations of rhesus monkeys SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE hair trace element content; trace elements; rhesus monkeys; monkeys; Macaca mulatta ID TRACE-ELEMENT CONCENTRATIONS; CHILDREN; AGE; SEX; DEFICIENCY; PROTEIN AB The concentrations of the elements copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn) in hair of caged (in Maryland) and free-ranging (in Puerto Rico) rhesus monkey populations were determined. Significant chronological age-related decreases were evident for the trace elements Mn and Zn in both populations (P less than or equal to 0.01) and for Cu and Fe in free-ranging monkeys (P less than or equal to 0.005). The only overall gender difference was higher hair Mn concentration in free-ranging males than in females (P <0.03). There were no significant differences in hair Cu, Fe, or Mn related to pregnancy status. Hair Zn was lower in samples from pregnant than from nonpregnant monkeys from the caged monkeys (P less than or equal to 0.05), but did not differ in the free-ranging monkeys. Comparison of the two populations revealed that hair Zn levels were significantly higher in caged vs free-ranging animals (P <0.001). We attribute this higher hair Zn in the caged monkeys to contact and ingestion of Zn from their galvanized enclosures. Hair iron levels were significantly higher (P <0.001) in free-ranging monkeys, possibly as a result of Fe-rich soil ingestion from their environment. These data support continued investigation of the use of hair as an indicator of the exposure of large groups or populations to potentially high levels of specific minerals, and the use of nonhuman primates as models for the study of trace element deficiency and/or toxicity in humans. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. USDA,HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. US FDA,SAN FRANCISCO DIST OFF,PESTICIDE MET SECT,SAN FRANCISCO,CA. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF BELTSVILLE TECH OPERAT,LAUREL,MD. RP Marriott, BM (reprint author), NIH,OFF DIETARY SUPPLEMENTS,FED BLDG,SUITE 610,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-01293, RR-7-2115]; NIMH NIH HHS [MH3079-01A2] NR 53 TC 4 Z9 4 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD SUM PY 1996 VL 53 IS 1-3 BP 167 EP 183 DI 10.1007/BF02784553 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VA909 UT WOS:A1996VA90900015 PM 8862746 ER PT J AU Leszczynski, DE Steinberger, A AF Leszczynski, DE Steinberger, A TI Cell-cell interactions related to reproductive biology: Report of National Institutes of Health Workshop, June 11, 1995, Bethesda, Maryland SO BIOLOGY OF REPRODUCTION LA English DT Editorial Material C1 UNIV TEXAS,HLTH SCI CTR,SCH MED,OFF FAC AFFAIRS,HOUSTON,TX 77030. RP Leszczynski, DE (reprint author), NIH,DIV RES GRANTS,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUN PY 1996 VL 54 IS 6 BP 1430 EP 1433 DI 10.1095/biolreprod54.6.1430 PG 4 WC Reproductive Biology SC Reproductive Biology GA UL898 UT WOS:A1996UL89800033 PM 8724374 ER PT J AU Faraggi, D Korn, EL AF Faraggi, D Korn, EL TI Competing risks with frailty models when treatment affects only one failure type SO BIOMETRIKA LA English DT Article DE cause-specific hazard ratio; copula; crude cumulative incidence curve; hazard ratio; survival data ID DISTRIBUTIONS; CURVES AB Using a model in which treatment affects only the failure type of primary clinical interest, the use of a: cause-specific analysis is examined when the latent failure times are derived from a frailty model. The relationship between the cause-specific hazard ratio and the marginal hazard ratio is expressed in terms of a local dependence measure of the latent failure times. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP Faraggi, D (reprint author), UNIV HAIFA,DEPT STAT,IL-31999 HAIFA,ISRAEL. NR 14 TC 6 Z9 6 U1 0 U2 1 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 1996 VL 83 IS 2 BP 467 EP 471 DI 10.1093/biomet/83.2.467 PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA UU073 UT WOS:A1996UU07300020 ER PT J AU Dosemeci, A Albers, RW AF Dosemeci, A Albers, RW TI A mechanism for synaptic frequency detection through autophosphorylation of Cam kinase II SO BIOPHYSICAL JOURNAL LA English DT Article ID DEPENDENT PROTEIN-KINASE; LONG-TERM POTENTIATION; POSTSYNAPTIC DENSITY PROTEIN; CA-2+ CALMODULIN; RAT-BRAIN; AREA CA1; CALCIUM; HIPPOCAMPUS; INHIBITION; DEPRESSION AB A model for the regulation of CaM kinase II is presented based on the following reported properties of the molecule: 1) the holoenzyme is composed of 8-12 subunits, each with the same set of autophosphorylation sites; 2) autophosphorylation at one group of sites (A sites) requires the presence of Ca2+ and causes a subunit to remain active following the removal of Ca2+; 3) autophosphorylation at another group of sites (B sites) occurs only after the removal of Ca2+ but requires prior phosphorylation of a threshold number of A sites within the holoenzyme. Because B-site phosphorylation inhibits Ca2+/calmodulin binding, we propose that, for a given subunit, phosphorylation of a B site before an A site prevents subsequent phosphorylation at the A site and thereby locks that subunit in an inactive state. The model predicts that a threshold activation by Ca2+ will initiate an ''autophosphorylation phase.'' Once started, intra-holoenzyme autophosphorylation will proceed, on A sites during periods of high [Ca2+] and on B sites during periods of low [Ca2+]. At ''saturation,'' that is when every subunit has been phosphorylated on a B site, the number of phosphorylated A sites and, therefore, the kinase activity will reflect the relative durations of periods of high [Ca2+] to periods of low [Ca2+] that occurred during the autophosphorylation phase. Using a computer program designed to simulate the above mechanism, we show that the ultimate state of phosphorylation of an array of CaM kinase II molecules could be sensitive to the temporal pattern of Ca2+ pulses. We speculate that such a mechanism may allow arrays of CaM kinase II molecules in postsynaptic densities to act as synaptic frequency detectors involved in setting the direction and level of synaptic modification. C1 NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. RP Dosemeci, A (reprint author), NINCDS,NEUROBIOL LAB,NIH,BLDG 36,2A21,BETHESDA,MD 20892, USA. NR 40 TC 48 Z9 49 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1996 VL 70 IS 6 BP 2493 EP 2501 PG 9 WC Biophysics SC Biophysics GA UP428 UT WOS:A1996UP42800003 PM 8744289 ER PT J AU Matsumura, Y Domeki, M Sugahara, K Kubo, T Roberts, CT LeRoith, D Kato, H AF Matsumura, Y Domeki, M Sugahara, K Kubo, T Roberts, CT LeRoith, D Kato, H TI Nutritional regulation of insulin-like growth factor-I receptor mRNA levels in growing chickens SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE insulin-like growth factor-I; growth factor receptor; chicken; RNase protection assay; starvation ID GENE-EXPRESSION; RAT; BINDING; PROTEIN; LIVER AB Insulin-like growth factor-I (IGF-I) exerts its effect through the IGF-I receptor. To investigate the effects of nutritional status on chicken IGF-I receptor gene expression, a solution hybridization/RNase protection assay for IGF-I receptor mRNA was developed, A cDNA clone corresponding to the carboxyl-terminal region of the IGF-I receptor was obtained by reverse transcription-PCR (RT-PCR). Sequence analysis of the clone showed that this region of the chicken IGF-I receptor is highly divergent from the human IGF-I receptor, IGF-I receptor mRNA was detected in all tissues examined from newly hatched chickens. The rank order of the IGF-I receptor mRNA levels was liver < thigh muscle < stomach < heart < lung < kidney < brain. In 1-week-old chickens, 5 days of starvation caused a 2.5- to 3-fold increase in the mRNA in muscle and kidney, Starvation of 4-week-old chickens for 5 days caused a 1.7 to 2.2-fold increase in IGF-I receptor mRNA levels in kidney, liver, and muscle, In contrast, IGF-I receptor mRNA levels in brain failed to change. The mRNA levels were reduced to the control level by refeeding of the starved chickens for 24 h. These data suggest a tissue- and development-specific response of chicken IGF-I receptor gene expression to nutritional status. C1 UTSUNOMIYA UNIV, FAC AGR, DEPT ANIM SCI, UTSUNOMIYA, TOCHIGI 321, JAPAN. OREGON HLTH SCI UNIV, DEPT PEDIAT, PORTLAND, OR 97201 USA. NIDDKD, DIABET BRANCH, NIH, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 19 TC 30 Z9 32 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD JUN PY 1996 VL 60 IS 6 BP 979 EP 982 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA UU505 UT WOS:A1996UU50500010 PM 8695914 ER PT J AU Brownstein, MJ Carpten, JD Smith, JR AF Brownstein, MJ Carpten, JD Smith, JR TI Modulation of non-templated nucleotide addition by taq DNA polymerase: Primer modifications that facilitate genotyping SO BIOTECHNIQUES LA English DT Article ID DIRECT CLONING; PCR PRODUCTS; VECTORS AB Tag DNA polymerase can catalyze non-templated addition of a nucleotide (principally adenosine) to the 3' end of PCR-amplified products. Recently, we showed that this activity, which is primer-specific, presents a potential source of error in genotyping studies based on the use of short tandem repeat (STR) markers. Furthermore, in reviewing our data, we found that non-templated nucleotide addition adjacent to a 3' terminal C is favored and that addition adjacent to a 3' terminal A is not. It was clear, however, that features of the template in addition to the 3' terminal base also affect the fraction of product adenylated. To define consensus sequences that promote or inhibit product adenylation, we transplanted sequences between the 5' ends of the reverse primers of markers that are adenylated and those of markers that are not adenylated. It proved difficult to identify a single sequence capable of protecting the products of all markers from non-templated addition of nucleotide. On the other hand, placing the sequence GTTTCTT on the 5' end of reverse primers resulted in nearly 100% adenylation of the 3' end of the forward strand. This modification or related ones (called ''PIG-tailing'') should facilitate accurate genotyping and efficient T/A cloning. C1 NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. RP Brownstein, MJ (reprint author), NIMH, NIH, BLDG 36, ROOM 3A17, BETHESDA, MD 20892 USA. RI Brownstein, Michael/B-8609-2009; Smith, Jeff/C-3484-2012 NR 8 TC 829 Z9 844 U1 8 U2 92 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 1996 VL 20 IS 6 BP 1004 EP + PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP432 UT WOS:A1996UP43200013 PM 8780871 ER PT J AU Wilson, WH Kingma, DW Raffeld, M Wittes, RE Jaffe, ES AF Wilson, WH Kingma, DW Raffeld, M Wittes, RE Jaffe, ES TI Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b SO BLOOD LA English DT Article ID ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS; LYMPHOPROLIFERATIVE DISORDERS; TRANSPLANT RECIPIENTS; CLINICAL SPECTRUM; CELL; REARRANGEMENT; GENOMES; LUNG AB Lymphomatoid granulomatosis (LYG) is an angiodestructive lymphoproliferative disorder (LPD) often involving the lungs. Its etiology is uncertain, but a number of previous studies had suggested it is a T-cell LPD associated with Epstein-Barr virus (EBV). Because of the similarity between LYG and nasal angiocentric lymphoma, the term angiocentric immunoproliferative lesion was proposed for both entities. Optimal therapy is unknown, but chemotherapy is often used. We studied four patients with LYG over a 5-year period. Biopsy samples were analyzed by immunohistochemistry, EBV in situ hybridization, and for Ig heavy-chain (IgH) gene rearrangements. Clinically, we assessed EBV serology, lymphocyte subsets, and the efficacy of interferon-alpha 2b (IFN-alpha 2b). All biopsy samples showed an exuberant T-cell infiltrate with scattered atypical large B cells. Double labeling showed EBV in the B cells but not T cells. Clonal IgH gene rearrangements were detected in 2 of 3 patients studied, 1 of whom had three distinct clones, and light-chain restriction showed two clones in an additional patient. All patients had positive EBV serologies and markedly abnormal lymphocyte subsets. With IFN, 3 patients are alive and disease free at 36, 43, and 60 months; 1 patient achieved a partial response for 16 months but discontinued therapy and died with lymphoma. These results indicate that LYG is a T-cell-rich EBV-associated B-cell LPD in which the infiltrating T cells are numerous but reactive. IgH gene rearrangements may be polyclonal, monoclonal, or oligoclonal. Its association with immune defects suggests it is related to posttransplant LPD. However, LYG and nasal angiocentric lymphoma are distinct entities and should no longer be included together under the term angiocentric immunoproliferative lesion. IFN is effective therapy and should be studied further. (C) 1996 by The American Society of Hematology. RP Wilson, WH (reprint author), NCI,MED BRANCH,BLDG 10,ROOM 12N-226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 123 Z9 128 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1996 VL 87 IS 11 BP 4531 EP 4537 PG 7 WC Hematology SC Hematology GA UN797 UT WOS:A1996UN79700007 PM 8639820 ER PT J AU Soma, T Yu, JM Dunbar, CE AF Soma, T Yu, JM Dunbar, CE TI Maintenance of murine long-term repopulating stem cells in ex vivo culture is affected by modulation of transforming growth factor-beta but not macrophage inflammatory protein-1 alpha activities SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM; TGF-BETA; PROGENITOR CELLS; MARROW CULTURES; GENE-TRANSFER; INVIVO; 5-FLUOROURACIL; FACTOR-BETA-1; PROLIFERATION; INFECTION AB Transforming growth factor-beta (TGF-beta) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are both well-described inhibitors of committed and multipotential hematopoietic progenitors. The effect of these cytokines on true stem cell activity in ex vivo culture systems as assayed by murine long-term repopulating activity (LTRA) has not been examined. We studied the stem cell effects of the addition of these cytokines to ex vivo cultures containing interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), using the murine competitive repopulation assay. We also tested the impact of adding an anti-TGF-beta neutralizing antibody, to ask whether abrogation of autocrine/paracrine TGF-beta may protect or enhance the survival of LTRA during ex vivo culture. TGF-beta 1 had significant suppressive effects on both short- and long-term repopulating activities, and anti-TGF-beta antibody had enhancing effects compared with control cultures containing IL-3, IL-6, and SCF alone. MP-1 alpha had no significant effects on either short- or long-term repopulating ability. These data suggest that abrogation of TGF-beta during suspension culture may allow enhanced survival or even expansion of primitive cells ex vivo, with implications for many applications, including gene therapy. This is a US government work. There are no restrictions on its use. C1 NHLBI,NIH,HEMATOL BRANCH,BETHESDA,MD 20892. NR 42 TC 51 Z9 53 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1996 VL 87 IS 11 BP 4561 EP 4567 PG 7 WC Hematology SC Hematology GA UN797 UT WOS:A1996UN79700011 PM 8639824 ER PT J AU Tuscano, J Engel, P Tedder, TF Kehrl, JH AF Tuscano, J Engel, P Tedder, TF Kehrl, JH TI Engagement of the adhesion receptor CD22 triggers a potent stimulatory signal for B cells and blocking CD22/CD22L interactions impairs T-cell proliferation SO BLOOD LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; FAMILY KINASE LYN; MOTH-EATEN MICE; ANTIGEN RECEPTOR; SH2 DOMAIN; ACTIVATION; GENE; MOLECULE; PHOSPHORYLATION; IMMUNOGLOBULIN AB The B-lymphocyte-restricted adhesion protein CD22 mediates sialic acid-dependent cell-cell interactions. Engagement of CD22 on B lymphocytes with a CD22 monoclonal antibody (MoAb) HB22.7 that blocks the binding of CD22 to its ligand(s) directly stimulated B-cell proliferation. In addition, the HB22.7 MoAb costimulated B-cell proliferation with either anti-IgM, interleukin-2 (IL-2), IL-4, or CD40 and triggered predominantly B-cell IgG secretion with IL-2. Even more striking levels of B-cell proliferation occurred with HB22.7 MoAb under culture conditions that enhanced B-B-cell interactions. In contrast, a nonblocking CD22 MoAb (CD22.5) poorly costimulated in similar experiments. The functional differences between the two antibodies likely result from differing abilities to trigger downstream signaling events as significant differences in CD22 tyrosine phosphorylation and the recruitment of the tyrosine kinase p53/56lyn and the tyrosine phosphatase SH-PTP1C were found. Besides their role in B-cell stimulation, CD22/CD22L interactions may also assist in regulating T-cell proliferation because inhibition of CD22-CD22L engagement with the HB22.7 MoAb impaired T-cell proliferation in a costimulatory assay. Thus, CD22/CD22L interactions result in stimulatory signals for both B and T lymphocytes. (C) 1996 by The American Society of Hematology. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710. OI Kehrl, John/0000-0002-6526-159X FU NCI NIH HHS [CA54464]; NHLBI NIH HHS [HL50985]; NIAID NIH HHS [AI26872] NR 53 TC 67 Z9 68 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1996 VL 87 IS 11 BP 4723 EP 4730 PG 8 WC Hematology SC Hematology GA UN797 UT WOS:A1996UN79700029 PM 8639842 ER PT J AU Litvan, I DeLeo, JM Hauw, JJ Daniel, SE Jellinger, K McKee, A Dickson, D Horoupian, DS Lantos, PL Tabaton, M AF Litvan, I DeLeo, JM Hauw, JJ Daniel, SE Jellinger, K McKee, A Dickson, D Horoupian, DS Lantos, PL Tabaton, M TI What can artificial neural networks teach us about neurodegenerative disorders with extrapyramidal features? SO BRAIN LA English DT Article DE artificial neural networks; dystal; neurodegenerative disorders; neuropathology; progressive supranuclear palsy ID PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; DIAGNOSIS; CLASSIFICATION; DEMENTIA; PATHOLOGY; TANGLES; CANCER AB Artificial neural networks (ANNs), computer paradigms that can learn, excel in pattern recognition tasks such as disease diagnosis. Artificial neural networks operate in two different learning modes: supervised, in which a known diagnostic outcome is presented to the ANN, and unsupervised, in which the diagnostic outcome is not presented. A supervised learning ANN could emulate human expert diagnostic performance and identify relevant predictive markers in the diagnostic task, while an unsupervised learning ANN could suggest reasonable alternative diagnostic classification criteria. In the present study, we used ANN methodology to try to overcome the neuropathological difficulties in differentiating the subtypes of progressive supranuclear palsy (PSP), and in differentiating PSP from postencephalitic parkinsonism (PEP) and corticobasal degeneration, or Pick's disease from corticobasal degeneration. First, we applied supervised learning ANN to classify 62 cases of these disorders and to identify diagnostic markers that distinguish them. In a second experiment, we used unsupervised learning ANN to investigate possible alternative nosological classifications. Artificial neural networks input data for each case consisted of values representing histological features, including neurofibrillary tangles, neuronal loss and gliosis found in multiple brain sampling areas. The supervised learning ANN achieved excellent accuracy in classifying PSP but had difficulty classifying the other disorders. This method identified a few features that might help to differentiate PEP, supported currently proposed criteria for Pick's disease, corticobasal degeneration and typical PSP, but detected no features to characterize the atypical subtype of PSP. In general, unsupervised learning ANN supported the present nosological classification for PSP, PEP, Pick's disease and corticobasal degeneration, although it overlapped some groups. Artificial neural networks methodology appears promising for studying neurodegenerative disorders. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. ALBERT EINSTEIN COLL MED,DEPT NEUROPATHOL,NEW YORK,NY. STANDFORD SCH MED,DEPT PATHOL NEUROPATHOL,STANFORD,CA. CASE WESTERN RESERVE UNIV,DIV NEUROPATHOL,CLEVELAND,OH 44106. HOP LA PITIE SALPETRIERE,ASSOC CLAUDE BERNARD,INSERM U360,RAYMOND ESCOUROLLE NEUROPATHOL LAB,PARIS,FRANCE. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. INST PSYCHIAT,PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON,ENGLAND. INST PSYCHIAT,INST NEUROL,DEPT NEUROPATHOL,LONDON,ENGLAND. RP Litvan, I (reprint author), NINCDS,NIH,NEUROEPIDEMIOL BRANCH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Dickson, Dennis W/0000-0001-7189-7917; Litvan, Irene/0000-0002-3485-3445 NR 47 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 1996 VL 119 BP 831 EP 839 DI 10.1093/brain/119.3.831 PN 3 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UX947 UT WOS:A1996UX94700013 PM 8673495 ER PT J AU Sazawal, S Bhatia, K Arya, LS Raina, V Gurbuxani, S Vats, T Magrath, I Bhargava, M AF Sazawal, S Bhatia, K Arya, LS Raina, V Gurbuxani, S Vats, T Magrath, I Bhargava, M TI ALL1 translocation in acute lymphoblastic leukemia (ALL) in Indian patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 ALL INDIA INST MED SCI,DEPT HAEMATOL,NEW DELHI,INDIA. ALL INDIA INST MED SCI,DEPT PEDIAT,NEW DELHI,INDIA. ALL INDIA INST MED SCI,DEPT MED ONCOL,NEW DELHI,INDIA. UNIV KANSAS,MED CTR,LAWRENCE,KS 66045. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 140 EP 140 PG 2 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11400140 ER PT J AU Sazawal, S Bhatia, K Arya, LS Raina, V Sharma, D Vats, T Magrath, I Bhargava, M AF Sazawal, S Bhatia, K Arya, LS Raina, V Sharma, D Vats, T Magrath, I Bhargava, M TI Characterization of immunoglobulin and T cell receptor gene rearrangement patterns in childhood acute lymphoblastic leukemia in India SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 ALL INDIA INST MED SCI,DEPT HAEMATOL,NEW DELHI,INDIA. ALL INDIA INST MED SCI,DEPT PEDIAT,NEW DELHI,INDIA. ALL INDIA INST MED SCI,DEPT MED ONCOL,NEW DELHI,INDIA. UNIV KANSAS,MED CTR,LAWRENCE,KS 66045. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 141 EP 141 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11400141 ER PT J AU Rai, KR Elias, L Shepherd, L Hines, J Peterson, B Kolitz, J Cheson, B Schiffer, C AF Rai, KR Elias, L Shepherd, L Hines, J Peterson, B Kolitz, J Cheson, B Schiffer, C TI High complete remission (CR) rates with fludarabine (F) in a trial comparing F with chlorambucil (C) and with F+C in previously untreated patients (PTS) with active chronic lymphocytic leukemia (CLL): Preliminary results of a North-American intergroup study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 CALGB,CHICAGO,IL. SWOG,CHICAGO,IL. CTG NCIC,CHICAGO,IL. ECOG,CHICAGO,IL. NCI,CHICAGO,IL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 580 EP 580 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11400580 ER PT J AU Haas, OA Henn, T Romanakis, K duManoir, S Lengauer, G AF Haas, OA Henn, T Romanakis, K duManoir, S Lengauer, G TI Comparative genomic hybridization (CGH) as a new diagnostic strategy in hyperdiploid acute lymphoblastic leukemia (ALL) of childhood SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 UNIV KAISERSLAUTERN,INST HUMAN GENET,W-6750 KAISERSLAUTERN,GERMANY. ST ANNA CHILDRENS HOSP,CHILDRENS CANC RES INST,A-1090 VIENNA,AUSTRIA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. JOHNS HOPKINS ONCOL CTR,GENET MOLEC LAB,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 603 EP 603 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11400603 ER PT J AU Jiang, YZ Mavroudis, D Dermime, S Hensel, N Couriel, D Molldrem, J Barrett, AJ AF Jiang, YZ Mavroudis, D Dermime, S Hensel, N Couriel, D Molldrem, J Barrett, AJ TI Alloreactive CD4(+) T lymphocytes can exert cytotoxicity to chronic myeloid leukaemia cells processing and presenting exogenous antigen SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE GVL; CD4(+) CTL; fas antigen; CML; T-cell cloning ID GRAFT-VERSUS-LEUKEMIA; BONE-MARROW TRANSPLANTATION; HOST DISEASE; RECOGNITION; REACTIVITY; DEPLETION; APOPTOSIS; MOLECULES; NECROSIS; INDUCE AB Existing evidence supports that CD4(+) T lymphocytes play a role in the graft-versus-leukaemia (GVL) reaction after allogenic bone marrow transplantation (BMT) for chronic mycloid leukaemia (CML), not only as initiators of the immune response but also as effectors of GVL. In BMT between HLA-identical pairs this CD4-mediated GVL would require CML cells to process and present antigens through MHC class II molecules. To investigate whether CML cells are capable of processing and presenting antigens, and suitable targets for CD4(+) T-cell-mediated cytotoxicity, we generated HLA-DR1-restricted CD4(+) cytotoxic T-cell clones that specifically recognized tuberculous purified protein derivative (PPD). We have shown that CML cell and B lymphoblastoid cell line (B-LCL) cells but not PHA-blasts from patients with CML processed exogenous antigen. PPD, and induced proliferative and cytotoxic CD4(+) T-cell responses. Antigen presentation was blocked by antibodies to HLA-DR but not to MHC class I and by treatment with chloroquine and brefeldin. This indicates that CML cells use a classic MHC class II antigen processing pathway to present PPD antigens to CD4(+) T cells. Cytotoxicity to CML was shown by antibody blocking studies to be mediated mainly throught fas antigen. These findings indicate that donor CD4(+) T cells alone are sufficient to mediate GVL effects following allogeneic BMT for CML. RP Jiang, YZ (reprint author), NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,NATL INST HLTH,BLDG 10,ROOM 7C-103,BETHESDA,MD 20892, USA. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 NR 41 TC 37 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 IS 3 BP 606 EP 612 DI 10.1046/j.1365-2141.1996.d01-1676.x PG 7 WC Hematology SC Hematology GA UN954 UT WOS:A1996UN95400016 PM 8652381 ER PT J AU Rozemuller, H Rombouts, WJC Touw, IP FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM AF Rozemuller, H Rombouts, WJC Touw, IP FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM TI Specific in vitro and in vivo elimination of acute myelocytic leukemia cells by targeting with HuGM-CSF toxin fusion proteins SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,INST HEMATOL,ROTTERDAM,NETHERLANDS. DR DANIEL DEN HOED CANC CTR,3008 AE ROTTERDAM,NETHERLANDS. NCI,MOLEC BIOL LAB,DCBDC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 643 EP 643 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11400643 ER PT J AU Barrett, AJ Malkovska, V AF Barrett, AJ Malkovska, V TI Graft-versus-leukaemia: Understanding and using the alloimmune response to treat haematological malignancies SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; CYTOTOXIC LYMPHOCYTES-T; HOST DISEASE; CELLS; RELAPSE; DONOR; CD4+ C1 WASHINGTON HOSP CTR,WASHINGTON CANC INST,WASHINGTON,DC 20010. RP Barrett, AJ (reprint author), NHLBI,BONE MARROW TRANSPLANT UNIT,HEMATOL BRANCH,NIH,BLDG 10,7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 89 TC 81 Z9 82 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 IS 4 BP 754 EP 761 DI 10.1046/j.1365-2141.1996.d01-1713.x PG 8 WC Hematology SC Hematology GA UU824 UT WOS:A1996UU82400002 PM 8703800 ER PT J AU Nacheva, E Bittner, M Ledbetter, D Jenkins, R Green, A Grace, C AF Nacheva, E Bittner, M Ledbetter, D Jenkins, R Green, A Grace, C TI Comparative genomic hybridisation in relation to molecular and cytogenetic analysis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 UNIV CAMBRIDGE,DEPT HAEMATOL,CAMBRIDGE,ENGLAND. NIH,NATL CTR HUMAN GENOME RES,WASHINGTON,DC. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. DIGITAL SCI LTD,CAMBRIDGE,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 1256 EP 1256 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11401255 ER PT J AU Baudard, M Aran, JM Ambudkar, SV Vieira, W Pastan, I Flotte, T Gottesman, MM AF Baudard, M Aran, JM Ambudkar, SV Vieira, W Pastan, I Flotte, T Gottesman, MM TI In vitro and in vivo expression of an AAV-based vector containing the human multidrug resistance (MDR1) and the glucocerebrosidase (GC) cDNAs SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. HOP HOTEL DIEU,SERV HEMATOL,F-75181 PARIS,FRANCE. JOHNS HOPKINS UNIV HOSP,EUDOWOOD DIV PEDIAT RESP SCI,BALTIMORE,MD 21287. RI Ambudkar, Suresh/B-5964-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 1260 EP 1260 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11401259 ER PT J AU Baudard, M Aran, JM Flotte, T Pang, MG Pastan, I Gottesman, MM Kearns, WG AF Baudard, M Aran, JM Flotte, T Pang, MG Pastan, I Gottesman, MM Kearns, WG TI Integration into the host cell genome and sustained persistence in episomal forms of an AAV based vector containing the human multidrug resistance gene (MDR1) SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. HOP HOTEL DIEU,SERV HEMATOL,F-75181 PARIS,FRANCE. JOHNS HOPKINS UNIV HOSP,EUDOWOOD DIV PEDIAT RESP SCI,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. EASTERN VIRGINIA MED SCH,CTR PEDIAT RES,NORFOLK,VA 23501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 1261 EP 1261 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11401260 ER PT J AU Licht, T Aran, JM Goldenberg, SK Vieira, WD Herrmann, F Gottesman, MM Pastan, I AF Licht, T Aran, JM Goldenberg, SK Vieira, WD Herrmann, F Gottesman, MM Pastan, I TI The MDR1 (Multidrug resistance) gene acts as a drug-selectable marker in hematopoietic progenitor cells: Implications for somatic gene therapy of hematopoietic disorders SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV ULM,MED KLIN,D-89081 ULM,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 1274 EP 1274 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11401273 ER PT J AU Weinstein, EA AF Weinstein, EA TI Symbolic aspects of confabulation following brain injury: Influence of premorbid personality SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article; Proceedings Paper CT Conference on Neuropsychological Assessment and Rehabilitation After Brain Injury - Empirical and Theoretical Foundations CY MAY 05, 1995 CL PHOENIX, AZ ID RETROGRADE-AMNESIA; IMPAIRMENT; DISSOCIATION; MEMORY AB Confabulation following brain injury is discussed in terms of (1) the conditions of brain dysfunction tinder which it occurs; (2) its association with amnesia, the denial syndromes, and reduplicative phenomena; (3) its positive, symbolic, adaptive aspects; and (4) the relationship of the content to current stresses and premorbid experience. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NR 39 TC 17 Z9 18 U1 2 U2 2 PU MENNINGER FOUNDATION PI TOPEKA PA BOX 829, TOPEKA, KS 66601 SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD SUM PY 1996 VL 60 IS 3 BP 331 EP 350 PG 20 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA VJ019 UT WOS:A1996VJ01900004 PM 8885473 ER PT J AU Ginsberg, HS AF Ginsberg, HS TI The ups and downs of adenovirus vectors SO BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article; Proceedings Paper CT Joint Scientific Symposium of the Institute-of-Medicine (IOM)/New-York-Academy-of-Medicine, in Commemoration of the 25th Anniversary of the IOM - Inside Urban Health CY NOV, 1995 CL NEW YORK ACAD MED, NEW YORK, NY SP Inst Med, New York Acad Med HO NEW YORK ACAD MED ID PATHOGENESIS; PNEUMONIA; ANTIGENS AB Owing to the detailed knowledge of the structure of the adenovirus virions, including their DNA genomes, especially types 2 and 5, they are convenient viruses for construction of vectors for gene therapy and vaccine immunization. It is critical to note, however, that adenoviruses produce pathogenic inflammatory responses to infection. The inflammation occurs even if the adenovirus does not replicate when the inoculum is sufficiently large, because only early gene expression is responsible for the pathogenic reaction. The inflammation consists of an early phase, in which tumor necrosis factor alpha (TNF-alpha) plays a major role, and a late phase consisting of an extensive T-cell response. It is important in the construction of adenovirus vectors not to delete a major portion of the early region 3 (E3) because: the E3 19kD glycoprotein markedly reduces the capacity of the Glass I major histocompatibility complex (Class I MHC) from transporting viral antigens to the surfaces of infected cells; and the E3 14.7 kD protein significantly inhibits the production of TNF-alpha and, therefore, reduces the polymorphonuclear response. Unfortunately the first generation of adenovirus gene therapy vectors contained large E3 deletions and, therefore, presented a significant safety problem. Subsequent adenovirus vectors consist of other deletions to overcome this difficulty. C1 NIAID,NIH,TWINBROOK FACIL 2,ROCKVILLE,MD 20852. RP Ginsberg, HS (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY 10027, USA. FU NIAID NIH HHS [AI-12052] NR 14 TC 36 Z9 37 U1 0 U2 0 PU NEW YORK ACAD MEDICINE PI NEW YORK PA 1216 FIFTH AVE, NEW YORK, NY 10029 SN 0028-7091 J9 B NEW YORK ACAD MED JI Bull. N. Y. Acad. med. PD SUM PY 1996 VL 73 IS 1 BP 53 EP 58 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA UU468 UT WOS:A1996UU46800008 PM 8804738 ER PT J AU Hurwitz, SR AF Hurwitz, SR TI Case management study: Heel pain in the adult SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article C1 NIH,CTR CLIN,BETHESDA,MD 20892. RP Hurwitz, SR (reprint author), UNIV VIRGINIA,MED CTR,CHARLOTTESVILLE,VA 22901, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD JUN PY 1996 VL 45 IS 4 BP 1 EP 3 PG 3 WC Rheumatology SC Rheumatology GA UQ617 UT WOS:A1996UQ61700001 PM 8680528 ER PT J AU Sgagias, MK Nieroda, C Yannelli, JR Cowan, KH Danforth, DN AF Sgagias, MK Nieroda, C Yannelli, JR Cowan, KH Danforth, DN TI Upregulation of DF3, in association with ICAM-1 and MHC class II by IFN-gamma in short-term human mammary carcinoma cell cultures SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE cytokine; tumor antigens; breast cancer ID INTERCELLULAR-ADHESION MOLECULE-1; MONOCLONAL-ANTIBODY DF3; BREAST-CANCER; INTERFERON; EXPRESSION; LIGAND; LINES; MUCIN AB This study was designed to determine whether in vitro exposure of isolated short-term human primary and metastatic breast tumor cell cultures to interferon-gamma (IFN-gamma) could enhance expression of the breast tumor associated DF3 antigen in association with the intercellular adhesion molecule 1 (ICAM-1) and MHC class II molecules. Cell cultures were established from primary solid tumors and metastatic cells as previously described (Sgagias et al., 1995). Data show that recombinant human IFN-gamma treatment in vitro, dramatically increased the breast tumor associated DF3 antigen, in association with ICAM-1, and MHC class II antigens in primary breast cancer cell cultures. All primary breast tumor cell cultures constitutively expressed high levels of HLA-class I antigen. Metastatic breast cancer cell cultures expressed high levels of DF3 and recombinant human IFN-gamma treatment, in vitro, upregulated ICAM-1 and MHC class II antigens before and after passage of the metastatic cells through the nude mouse. Metastatic breast cancer cells similar to primary breast cancer cells constitutively expressed high levels of MHC class I antigens. In addition, three LAK cell lines significantly lysed the primary and the metastatic breast tumor cell cultures to the same degree before and after passage of the metastatic cancer cells through the nude mouse. These data indicate the upregulation of the breast tumor associated DF3 antigen in vitro after IFN-gamma treatment and its persistence in vivo, after passage of the metastatic breast cancer cells through the nude mouse. The ability of IFN-gamma to upregulate the breast tumor associated DF3 antigen in association with the ICAM-1 and HLA class II antigens may play an important role in eliciting an immune response which may contribute to the immunodiagnosis, and immunotherapy of breast cancer. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. RP Sgagias, MK (reprint author), NCI,MED BRANCH,MED BREAST CANC SECT,SURG BRANCH,NIH,BLDG 10,ROOM 12C112,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD JUN PY 1996 VL 11 IS 3 BP 177 EP 185 DI 10.1089/cbr.1996.11.177 PG 9 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA UW604 UT WOS:A1996UW60400004 PM 10851535 ER PT J AU Lin, CM Jiang, YQ Chaudhary, AG Rimoldi, JM Kingston, DGI Hamel, E AF Lin, CM Jiang, YQ Chaudhary, AG Rimoldi, JM Kingston, DGI Hamel, E TI A convenient tubulin-based quantitative assay for paclitaxel (Taxol) derivatives more effective in inducing assembly than the parent compound SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE paclitaxel; tubulin-based assay; docetaxel; 2-debenzoyl-2-meta-azidobenzoylpaclitaxel; glutamate ID MICROTUBULE-ASSOCIATED PROTEINS; INVITRO; ANALOGS; POLYMERIZATION AB A room temperature biochemical assay, based on centrifugal removal of tubulin polymer, was developed to permit ready detection of paclitaxel analogs more active than the parent compound and to permit reliable quantification of differences in activity relative to paclitaxel in terms of drug concentration. The assay was validated by comparing paclitaxel to two compounds (docetaxel and 2-debenzoyl-2-meta-azidobenzoylpaclitaxel) known to be more active under multiple reaction conditions. The assay was designed to yield a relatively high EC(50) (23 mu M) for paclitaxel. This was possible because paclitaxel only weakly induced tubulin assembly at room temperature in 0.4 M glutamate without exogenous GTP. Under these same reaction conditions 50% assembly occurred with 4.7 mu M 2-debenzoyl-2-meta-azidobenzoylpaclitaxel and 11 mu M docetaxel. These biochemical EC(50) values were in agreement with the relative cytotoxicity of the three compounds for human Burkitt lymphoma CA46 cells (IC50 values for paclitaxel, docetaxel, and 2-debenzoyl-2-meta-azidobenzoylpaclitaxel were 40, 10, and 3 nM, respectively). C1 NCI,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. OI Kingston, David/0000-0001-8944-246X NR 16 TC 39 Z9 39 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1996 VL 38 IS 2 BP 136 EP 140 DI 10.1007/s002800050461 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA UH686 UT WOS:A1996UH68600004 PM 8616903 ER PT J AU Strickler, HD Goedert, JJ Fleming, M Travis, WD Williams, AE Rabkin, CS Daniel, RW Shah, KV AF Strickler, HD Goedert, JJ Fleming, M Travis, WD Williams, AE Rabkin, CS Daniel, RW Shah, KV TI Simian virus 40 and pleural mesothelioma in humans SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN-BRAIN-TUMORS; SV40 AB It has been reported that DNA of SV40, a virus of Asian macaques that is tumorigenic for rodents and can transform human cells in vitro, is present in pleural mesotheliomas and in several other cancers. To verify these observations, we tested paraffin sections from mesothelioma tissues of 50 patients for SV40 DNA using PCR with two separate sets of primers. The analytic sensitivity for detection of SV40 DNA was 1-10 genome copies. We also tested the specimens for beta-globin by PCR to assess the suitability of the specimen DNAs for amplification, beta-Globin amplification was detected in 48 of the 50 specimens, but SV40 DNA was not detected in any tumors, with either of two SV40 primer sets. Furthermore, sera from 34 additional patients with mesothelioma, 33 patients with osteosarcoma (another cancer reported to be SV40-related) and 35 controls were tested for SV40 antibodies by a plaque neutralization assay. The serological data, like the DNA results, did not support an association of SV40 with mesothelioma or with osteosarcoma; antibodies to SV40 were detected in three mesothelioma patients, in one osteosarcoma patient, acid in one control. These findings call into question the association of SV40 with mesothelioma. C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT MOLEC MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. RP Strickler, HD (reprint author), NCI,DEPT HLTH & HUMAN SERV,PUBL HLTH SERV,NIH,VIRAL EPIDEMIOL BRANCH,EPN 434,BETHESDA,MD 20892, USA. NR 18 TC 96 Z9 98 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1996 VL 5 IS 6 BP 473 EP 475 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UQ208 UT WOS:A1996UQ20800011 PM 8781745 ER PT J AU Hsing, AW Burk, RD Liaw, KL Chen, CJ Zhang, T Schiffman, M Greer, CE You, SL Hsieh, CY Huang, TW Wu, TC OLeary, TJ Seidman, JD Manos, MM AF Hsing, AW Burk, RD Liaw, KL Chen, CJ Zhang, T Schiffman, M Greer, CE You, SL Hsieh, CY Huang, TW Wu, TC OLeary, TJ Seidman, JD Manos, MM TI Interlaboratory agreement in a polymerase chain reaction-based human papillomavirus DNA assay SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. NATL TAIWAN UNIV,INST EPIDEMIOL,TAIPEI,TAIWAN. ROCHE MOL SYST,ALAMEDA,CA 94501. CHIRON CORP,EMERYVILLE,CA 94608. NATL TAIWAN UNIV HOSP,DEPT OBSTET & GYNECOL,TAIPEI,TAIWAN. TAIPEI INST PATHOL,TAIPEI,TAIWAN. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. RP Hsing, AW (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPN 415,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Chen, Chien-Jen/C-6976-2008 NR 6 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1996 VL 5 IS 6 BP 483 EP 484 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UQ208 UT WOS:A1996UQ20800013 PM 8781747 ER PT J AU Trent, JM Salmon, SE AF Trent, JM Salmon, SE TI Floyd H. Thompson (1951-1996): In memoriam SO CANCER GENETICS AND CYTOGENETICS LA English DT Item About an Individual C1 ARIZONA COMPREHENS CANC CTR,TUCSON,AZ. RP Trent, JM (reprint author), NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUN PY 1996 VL 88 IS 2 BP 186 EP 187 DI 10.1016/0165-4608(96)00074-X PG 2 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UR929 UT WOS:A1996UR92900019 ER PT J AU Schutte, M Hruban, RH Hedrick, L Cho, KR Nadasdy, GM Weinstein, CL Bova, GS Isaacs, WB Cairns, P Nawroz, H Sidransky, D Casero, RA Meltzer, PS Hahn, SA Kern, SE AF Schutte, M Hruban, RH Hedrick, L Cho, KR Nadasdy, GM Weinstein, CL Bova, GS Isaacs, WB Cairns, P Nawroz, H Sidransky, D Casero, RA Meltzer, PS Hahn, SA Kern, SE TI DPC4 gene in various tumor types SO CANCER RESEARCH LA English DT Article ID CELL CARCINOMA; BREAST-CANCER; ALLELE LOSS; ALLELOTYPE; HETEROZYGOSITY; EXPRESSION; DCC; APC AB We recently identified a novel tumor-suppressor gene, DPC4, at chromosome 18q21.1 and found that both alleles of DPC4 were inactivated in nearly one-half of the pancreatic carcinomas, Here, we analyzed 338 tumors, originating from 12 distinct anatomic sites, for alterations in the DPC4 gene, Sixty-four specimens were selected for the presence of the allelic loss of 18q and were further analyzed for DPC4 sequence alterations, An alteration of the DPC4 gene sequence was identified in one of eight breast carcinomas and one of eight ovarian carcinomas, These results indicate that whereas DPC4 inactivation is prevalent in pancreatic carcinoma (48%), it is distinctly uncommon (<10%) in the other tumor types examined, The tissue restriction of alterations in DPC4, as in many other tumor-suppressor genes, emphasizes the complexity of rate-limiting checkpoints in human tumorigenesis. C1 JOHNS HOPKINS MED INST,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT UROL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT OTOLARYNGOL,BALTIMORE,MD 21205. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RI Hahn, Stephan/E-3880-2010 FU NCI NIH HHS [CA62924] NR 39 TC 612 Z9 634 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1996 VL 56 IS 11 BP 2527 EP 2530 PG 4 WC Oncology SC Oncology GA UN250 UT WOS:A1996UN25000017 PM 8653691 ER PT J AU Bienstock, RJ Darden, T Wiseman, R Pedersen, L Barrett, JC AF Bienstock, RJ Darden, T Wiseman, R Pedersen, L Barrett, JC TI Molecular modeling of the amino-terminal zinc ring domain of BRCA1 SO CANCER RESEARCH LA English DT Article ID SIMPLEX VIRUS TYPE-1; SECONDARY-STRUCTURE; CRYSTAL-STRUCTURE; DNA RECOGNITION; WT1 GENE; PROTEIN; FINGER; SEQUENCE; BINDING; MOTIF AB The equine herpes virus zinc ring domain nuclear magnetic resonance structure was used for homology-based modeling of the amino-terminal zinc ring domain of the BRCA1 breast and ovarian cancer susceptibility gene. The zinc ring domain of BRCA1 is of particular interest because it is the location of significant and frequently occurring missense (Cys(61)Gly, Cys(64)Gly, and Cys(64)Tyr) and frameshift (185delAG) mutations observed in several high-risk kindreds. The BRCA1 zinc ring domain possesses 54% sequence similarity with the equine herpes virus zinc ring domain. The model structure undergoes little conformational variance after 140 ps of solvated molecular dynamics. This model proposes BRCA1 zinc ring domain residues that mag play a role in DNA binding and/or protein-protein interactions. These predictions provide a point of departure for the design of mutants to probe BRCA1 zinc ring domain functionality. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP Bienstock, RJ (reprint author), NIEHS,LAB QUANTITAT & COMPUTAT BIOL,POB 12233,MAIL DROP 10-03,RES TRIANGLE PK,NC 27709, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 45 TC 32 Z9 32 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1996 VL 56 IS 11 BP 2539 EP 2545 PG 7 WC Oncology SC Oncology GA UN250 UT WOS:A1996UN25000020 PM 8653694 ER PT J AU Harris, CC AF Harris, CC TI p53 tumor suppressor gene: From the basic research laboratory to the clinic - An abridged historical perspective SO CARCINOGENESIS LA English DT Review ID WILD-TYPE P53; HUMAN PAPILLOMAVIRUS TYPE-16; MURINE LEUKEMIA-VIRUS; CELLULAR PROTEIN P53; LARGE-T-ANTIGEN; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; BREAST-CANCER; CDNA CLONE; MOUSE P53 RP Harris, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,NIH,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 268 TC 202 Z9 214 U1 0 U2 6 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1996 VL 17 IS 6 BP 1187 EP 1198 DI 10.1093/carcin/17.6.1187 PG 12 WC Oncology SC Oncology GA UT605 UT WOS:A1996UT60500001 PM 8681432 ER PT J AU Vickers, AEM Lucier, GW AF Vickers, AEM Lucier, GW TI Estrogen receptor levels and occupancy in hepatic sinusoidal endothelial and Kupffer cells are enhanced by initiation with diethylnitrosamine and promotion with 17 alpha-ethinylestradiol in rats SO CARCINOGENESIS LA English DT Article ID GROWTH-FACTOR RECEPTOR; ETHINYL ESTRADIOL; HEPATOCELLULAR-CARCINOMA; ORAL-CONTRACEPTIVES; FEMALE RATS; LIVER-CELLS; METABOLIZING ENZYMES; N-NITROSOMORPHOLINE; TUMOR PROMOTION; POSITIVE FOCI AB We report the presence of estrogen receptors (ER) in rat liver sinusoidal endothelial (SEC) and Kupffer cells (KC), which exhibited comparable saturation kinetics and receptor affinity (K-d) for 17 alpha-estradiol, as characterized for the rat hepatocyte ER, The ER levels in both cell types were significantly decreased by ovariectomy, indicating a regulatory role of estrogens, Initiation of ovariectomized rats with a single dose (200 mg/kg) of diethylnitrosamine (DEN) or saline (S), followed by chronic exposure to 17 alpha-ethinylestradiol (EE(2)), 90 mu g/kg/day for 30 weeks, packed in cholesterol (C) resulted in significant changes of ER levels in both the endothelial and Kupffer cells. The isolation of enriched liver SEC and KC populations by centrifugal elutriation allowed for the evaluation of chronic EE(2) exposure and DEN-induced alterations on each cell type. The DEN-EE(2) regime significantly enhanced gamma-glutamyltranspeptidase activity in SEC (5-fold) and KC (6.6-fold) compared to the S/C treated animals. Nuclear ER levels were elevated 5.1-fold in the SEC and 6.5-fold in the KC, and both cell types exhibited significant increases in the proportion of occupied nuclear ER compared to the S/C derived cells, suggesting that exogenous estrogens could influence SEC and KC function through changes in ER levels and occupancy, ER occupancy was similar to 50 % of the total ER in SEC and KC from DEN-EE(2) rats. Increases in ER and occupancy for SEC and KC were similar to those observed for hepatocytes, Cellular growth was clearly modified in DEN-EE(2) animals as indicated by a 4- to 10-fold increase in the proportion of SEC, KC or hepatocytes in S-phase as shown by flow cytometry, However, unlike hepatocytes, the epidermal growth factor receptor (EGFR) was not detected in SEC or KC using a monoclonal EGFR antibody. These findings suggest that the EGFR at 30 weeks is not involved in EE(2)-mediated stimulation of mitogenesis in SEC and KC which may be different from hepatocytes. In summary, our studies demonstrate that SEC and KC contain significant amounts of high-affinity ER and that ER pathways may modulate some activities of the SEC and KC, but that ER-EGFR interactions may be different in these cells from hepatocytes. C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 63 TC 28 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1996 VL 17 IS 6 BP 1235 EP 1242 DI 10.1093/carcin/17.6.1235 PG 8 WC Oncology SC Oncology GA UT605 UT WOS:A1996UT60500006 PM 8681437 ER PT J AU Stanwell, C Dlugosz, AA Yuspa, SH AF Stanwell, C Dlugosz, AA Yuspa, SH TI Staurosporine induces a complete program of terminal differentiation in neoplastic mouse keratinocytes via activation of protein kinase C SO CARCINOGENESIS LA English DT Article ID MURINE KERATINOCYTES; EPIDERMAL-CELLS; HUMAN-NEUTROPHILS; TUMOR PROMOTERS; CALCIUM; INHIBITOR; INVITRO; POTENT; EXPRESSION; ONCOGENE AB Staurosporine (stsp) is a kinase inhibitor which induces cornified envelope assembly and terminal differentiation in normal and neoplastic mouse keratinocytes. In the tumorigenic cell lines 308 and SP-1 experiments were performed to determine if this effect was due only to activation of transglutaminases (TGases) already residing within the cell, or whether stsp was capable of inducing a full program of differentiation. Assessment of keratinocyte differentiation-specific protein expression in neoplastic cells revealed that expression of the suprabasal marker SPR-1 and the granular markers loricrin and filaggrin were induced by stsp, Protein expression was controlled by changes in mRNA expression, determined by Northern blotting, Transcripts for the TGase isoforms TG(K) and TG(E) were also induced by stsp in SP-1 cells, whereas only TG(K) expression was increased in 308 cells, which appear not to express TG(E). Protein kinase C (PKC) activation is required for differentiation in normal mouse keratinocytes. To determine if stsp induces differentiation in neoplastic cells by regulation of this signaling pathway cells were treated with the specific PKC inhibitor GF 109203X or with different concentrations of bryostatin 1 to down-regulate specific isoforms of PKC prior to and during treatment with stsp, Stsp-induced protein cross-linking and marker expression were inhibited by GF 109203X, suggesting paradoxical activation of PKC by stsp, PKC alpha, epsilon and delta, but not PKC eta and zeta, were down-regulated by treating both cell types with bryostatin; pre-treatment of cells with bryostatin inhibited stsp-induced protein cross-linking and marker expression, suggesting a necessity for the alpha, delta and/or epsilon isoforms in stsp-induced differentiation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV CANC ETIOL,NIH,BETHESDA,MD 20892. NR 39 TC 22 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1996 VL 17 IS 6 BP 1259 EP 1265 DI 10.1093/carcin/17.6.1259 PG 7 WC Oncology SC Oncology GA UT605 UT WOS:A1996UT60500009 PM 8681440 ER PT J AU Pereira, MA Grubbs, CJ Barnes, LH Li, H Olson, GR Eto, I Juliana, M Whitaker, LM Kelloff, GJ Steele, VE Lubet, RA AF Pereira, MA Grubbs, CJ Barnes, LH Li, H Olson, GR Eto, I Juliana, M Whitaker, LM Kelloff, GJ Steele, VE Lubet, RA TI Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a]anthracene-induced mammary cancer in rats SO CARCINOGENESIS LA English DT Article ID ABERRANT CRYPT FOCI; FLAVONOIDS; CARCINOGENICITY; INHIBITION; BENZOPYRENE; BIOASSAY; INVITRO; CELLS AB Curcumin and quercetin were evaluated in rats for their ability to modulate the carcinogenic activity of azoxymethane (AOM) in the colon and 7,12-dimethylbenz[a]anthracene (DMBA) in the mammary gland. In the AOM-induced colon cancer model, male Fischer 344 rats at 8 weeks of age started to receive either curcumin (8 and 16 g/kg) or quercetin (16.8 and 33.6 g/kg) in the diet and 1 week later, were administered AOM (30 mg/kg body wt.) by subcutaneous injection. The animals continued to receive the two agents in the diet until sacrificed 45 weeks later, Curcumin mediated a dose-dependent inhibition of the incidence and multiplicity of adenomas from 47% and 0.58 +/- 0.12 adenomas/rat in the AOM-treated control group to 19% and 0.22 +/- 0.08 and 0.06% and 0.08 +/- 0.06 adenomas/rat for the low and high dose groups, respectively. A low yield of adenocarcinomas (0.06 +/- 0.04 adenocarcinomas/rat) was induced by AOM which was not significantly altered by curcumin. Treatment with quercetin caused a dose-dependent increase in the yield of AOM-induced tumors in the colon from 0.06 +/- 0.04 adenocarcinoma/rat to 0.64 +/- 0.12 and 1.14 +/- 0.17 for the low and high dose groups, respectively. In the DMBA-induced mammary cancer model, curcumin or quercetin was administered at either 10 or 20 g/kg diet, beginning 7 days prior to DMBA and continually throughout the remainder of the experiment. Neither curcumin nor quercetin significantly altered the incidence of animals with tumors or the tumor multiplicity, while the high concentration of both agents significantly increased tumor latency. These results demonstrate different responses to these agents in the two models. While curcumin was highly effective as a chemopreventive agent in the colon model, it was only weakly effective in the mammary model. In contrast, quercetin which was also only weakly effective in the mammary model, caused a dose-dependent enhancement of tumors induced by AOM in the colon model. C1 MED COLL OHIO,CTR ENVIRONM MED,TOLEDO,OH 43614. UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35294. PATHOL ASSOCIATES INC,W CHESTER,OH. NCI,CHEMOPREVENT LAB,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Pereira, MA (reprint author), ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY, USA. FU NCI NIH HHS [N01-CN-25454-02, N01-CN-25457-01] NR 47 TC 186 Z9 190 U1 0 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1996 VL 17 IS 6 BP 1305 EP 1311 DI 10.1093/carcin/17.6.1305 PG 7 WC Oncology SC Oncology GA UT605 UT WOS:A1996UT60500016 PM 8681447 ER PT J AU Abshire, MK Devor, DE Diwan, A Shaughnessy, JD Waalkes, MP AF Abshire, MK Devor, DE Diwan, A Shaughnessy, JD Waalkes, MP TI In vitro exposure to cadmium in rat L6 myoblasts can result in both enhancement and suppression of malignant progression in vivo SO CARCINOGENESIS LA English DT Article ID B6C3F1 MOUSE-LIVER; AP-1 ACTIVITY; ONCOGENE JUN; CELLS; CARCINOGENESIS; METALLOTHIONEIN; TRANSFORMATION; CHLORIDE; INVITRO; LUNG AB Cadmium (Cd), a carcinogenic metal in humans and rodents, has been shown to transform cells in vitro. Cd in certain instances can also be anti-carcinogenic. The effects of Cd have been studied in different mammalian cell culture systems, where it has been shown to increase expression of several proto-oncogenes. In the present study the ability of Cd to affect malignant transformation was systematically investigated in L6 cells. Cells were grown in monolayer culture with concentrations of either 0 or 0.5 mu M CdCl2 in the medium. Cell cultures treated with Cd for 9 weeks showed growth of large colonies in soft agar, while untreated control cells did not. When injected s.c. into athymic nude mice the 9 week Cd-treated cells gave rise to large, highly malignant sarcomas, resulting in high host mortality (9 dead/9 injected, 100%) by 7 weeks. Mice injected with untreated control cells also developed tumors, but of significantly smaller size and growth rate and associated with a lower host mortality (4/10, 40%, P less than or equal to 0.01) by 7 weeks. Tumors resulting from untreated cells averaged similar to 50% the size (e.g. maximum diameter 12.9 mm at 23 days) of those resulting from injection of Cd-treated cells (22.2 mm at 23 days). Northern blot RNA analysis indicated that although there was an increase in c-myc and c-jun expression after 2 weeks of Cd exposure, there was strong down-regulation at 8 weeks of exposure associated with Cd-induced transformation of L6 cells. Cells exposed to high levels of Cd in vitro (1.0 mu M) resulted in decreased tumor growth in vivo compared with control cells, possibly demonstrating the anti-carcinogenic capabilities of Cd. Thus cells exposed to low levels of Cd in vitro showed a very rapid malignant progression in vivo, while higher Cd levels in vitro suppressed in vivo tumor growth, reinforcing the concept that Cd can have both carcinogenic and anti-carcinogenic effects. C1 NCI, FREDERICK CANC RES & DEV CTR, INORGAN CARCINOGENESIS SECT, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL CARCINOGENESIS & DEV PROGRAM, SAIC FREDERICK, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. NR 57 TC 36 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1996 VL 17 IS 6 BP 1349 EP 1356 DI 10.1093/carcin/17.6.1349 PG 8 WC Oncology SC Oncology GA UT605 UT WOS:A1996UT60500023 PM 8681454 ER PT J AU Vaughn, JP Davis, PL Jarboe, MD Huper, G Evans, AC Wiseman, RW Berchuck, A Iglehart, JD Futreal, PA Marks, JR AF Vaughn, JP Davis, PL Jarboe, MD Huper, G Evans, AC Wiseman, RW Berchuck, A Iglehart, JD Futreal, PA Marks, JR TI BRCA1 expression is induced before DNA synthesis in both normal and tumor-derived breast cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MAMMARY EPITHELIAL-CELLS; GROWTH; P53 AB Insight into the function of the BRCA1 tumor suppressor gene may be gained by studying its regulation. In this study, the expression of BRCA1 was examined as a function of the cell cycle in normal and tumor-derived breast epithelial cells. Cells arrested in G(0) or early in G(1) contained low levels of BRCA1 mRNA. After release, populations of cells reached maximal levels of BRCA1 in late G(1) and S phase. Induction of BRCA1 was shown to occur before the onset of DNA synthesis by synchronizing cells at the G(1)-S boundary. Levels of the BRCA1 protein were regulated in a similar manner. No difference was observed between primary cultures of normal mammary epithelial cells and immortalized tumor-derived cell lines. These results suggest that BRCA1 may function at the G(1)-S checkpoint. C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GYNECOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA68438, CA63786, CA61218] NR 24 TC 155 Z9 156 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1996 VL 7 IS 6 BP 711 EP 715 PG 5 WC Cell Biology SC Cell Biology GA UP341 UT WOS:A1996UP34100003 PM 8780884 ER PT J AU Gudas, JM Li, T Nguyen, H Jensen, D Rauscher, FJ Cowan, KH AF Gudas, JM Li, T Nguyen, H Jensen, D Rauscher, FJ Cowan, KH TI Cell cycle regulation of BRCA1 messenger RNA in human breast epithelial cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID LINE; GROWTH; MCF-7; CDNA AB BRCA1 was originally isolated as a gene that conferred susceptibility to early-onset familial breast and ovarian cancers. The function and regulation of this gene is presently unknown. Northern blot analyses using probes that recognize different regions of the BRCA1 cDNA revealed the presence of at least two distinct mRNA species. In synchronized normal and immortalized human mammary epithelial cells, BRCA1 mRNA levels were high in exponentially growing populations, decreased upon growth factor withdrawal, and subsequently increased again in late G(1) just prior to S-phase entry, BRCA1 mRNA levels were found to be dramatically reduced in senescent normal human mammary epithelial cells and in normal human mammary epithelial cells treated with transforming growth factor beta(1). When considered together, these data indicate that expression of BRCA1 mRNA is highly sensitive to changes in growth conditions in vitro, BRCA1 proteins with apparent molecular weights of M(r) 210,000, 185,000, 160,000, 135,000, and 85,000, respectively, were detected at varying levels in all breast epithelial cells examined. Further molecular characterization of the nature and function of the different BRCA1 mRNAs and proteins should increase our understanding of this gene in the etiology of human breast cancers. C1 NCI,MED BRANCH,DIV CANC TREATMENT,MED BREAST CANC SECT,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,MOLEC GENET PROGRAM,PHILADELPHIA,PA 19104. NR 33 TC 131 Z9 132 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1996 VL 7 IS 6 BP 717 EP 723 PG 7 WC Cell Biology SC Cell Biology GA UP341 UT WOS:A1996UP34100004 PM 8780885 ER PT J AU Woodworth, CD Chung, J McMullin, E Plowman, GD Simpson, S Iglesias, M AF Woodworth, CD Chung, J McMullin, E Plowman, GD Simpson, S Iglesias, M TI Transforming growth factor beta 1 supports autonomous growth of human papillomavirus-immortalized cervical keratinocytes under conditions promoting squamous differentiation SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EPITHELIAL-CELLS; CARCINOMA-CELLS; FACTOR-ALPHA; TYPE-16; EXPRESSION; INHIBITION; GENE; AMPHIREGULIN; INDUCTION; BINDING AB Transforming growth factor beta (TGF-beta) inhibits proliferation of keratinocytes cultured from normal anogenital epithelia; however, human papillomavirus (HPV)-immortalized cell lines often exhibit increased resistance. Present results demonstrate that TGF-beta 1 (1-10 pM) stimulates growth of multiple HPV-immortalized cell lines when cultures are maintained under conditions promoting squamous differentiation (MCDB153-LB medium with 1.0 mM calcium and without epidermal growth factor and bovine pituitary extract). Growth stimulation by TGF-beta 1 was not due to altered expression of type I or II receptors, but was increased after extended passage of cells in culture. Differentiation of immortal keratinocytes resulted in induction of RNAs encoding two markers of squamous differentiation, involucrin and keratin 1, and decreased expression of RNAs for the epidermal growth factor (EGF) receptor and two ligands, amphiregulin and TGF-alpha. Growth stimulation by TGF-beta 1 occurred indirectly via establishment of an autocrine loop, TGF-beta 1 increased expression of RNAs encoding the EGF-R and amphiregulin, and also increased numbers of cell-surface EGF-Rs without altering their affinity. In contrast, TGF-beta 1 inhibited autonomous growth and transcription of amphiregulin RNA in normal keratinocytes. Growth stimulation by TGF-beta 1 could be blocked by a monoclonal antibody that competes for binding to the EGF-R or by a mixture of monoclonal antibodies that neutralize amphiregulin activity, confirming the importance of this autocrine pathway, Thus, partial abrogation of the growth inhibitory response to TGF-beta 1 sensitizes HPV-immortalized keratinocytes to a growth stimulatory signal mediated by an EGF-R-dependent pathway involving autocrine stimulation by amphiregulin. C1 SUGEN INC,REDWOOD CITY,CA 94063. RP Woodworth, CD (reprint author), NCI,BIOL LAB,BLDG 37,ROOM 2A23,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. RI PLOWMAN, Greg/E-2012-2011 NR 51 TC 12 Z9 14 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1996 VL 7 IS 6 BP 811 EP 820 PG 10 WC Cell Biology SC Cell Biology GA UP341 UT WOS:A1996UP34100013 PM 8780894 ER PT J AU Shahar, E Folsom, AR Salomaa, VV Stinson, VL McGovern, PG Shimakawa, T Chambless, LE Wu, KK AF Shahar, E Folsom, AR Salomaa, VV Stinson, VL McGovern, PG Shimakawa, T Chambless, LE Wu, KK TI Relation of hormone-replacement therapy to measures of plasma fibrinolytic activity SO CIRCULATION LA English DT Article DE atherosclerosis; hormones; fibrinolysis ID PLASMINOGEN-ACTIVATOR INHIBITOR; CARDIOVASCULAR RISK-FACTORS; IMPROVED LIPOLYTIC EFFICIENCY; CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; POSTMENOPAUSAL WOMEN; MYOCARDIAL-INFARCTION; ENZYMATIC DETERMINATION; HEMOSTATIC CHANGES; TOTAL CHOLESTEROL AB Background The mechanisms by which replacement hormones may reduce the risk of coronary heart disease are not fully understood. Of specific interest is a potential effect of replacement hormones on plasma fibrinolytic activity, a putative determinant of thrombotic events. Methods and Results We investigated the relation of current use of replacement hormones to three measures of plasma fibrinolytic activity: tissue-type plasminogen activator (TPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and D-dimer. The sample was composed of 288 women, free of clinical cardiovascular disease, who were selected for a case-control study of atherosclerosis: 142 women with ultrasonographic evidence of carotid intimal-medial thickening (cases) and 146 control subjects. Twenty percent (59 women) reported current use of replacement hormones. TPA antigen and PAI-1 antigen were highly correlated with each other (r=.67), whereas D-dimer correlated only weakly with TPA or PAI-1. Compared with nonusers, current users of replacement hormones had lower mean levels of TPA and PAI-1 antigens, suggesting enhanced fibrinolytic potential. In the entire sample, the multivariate-adjusted geometric mean values of TPA antigen were 6.3 and 7.3 ng/mL among current users and nonusers, respectively (P=.01); the corresponding values for PAI-1 antigen were 6.1 and 7.5 ng/mL (P=.13). These results were generally consistent for both atherosclerosis cases and their control subjects. D-dimer levels were lower in current hormone users than in nonusers, but the difference was not statistically significant (P>.15) in any of the analyses. Conclusions The use of replacement hormones appears to be associated with enhancement of endogenous fibrinolytic potential. Enhanced plasma fibrinolytic activity among hormone users may explain, in part, the inverse association between hormone replacement therapy and coronary heart disease. C1 NATL PUBL HLTH INST,DEPT EPIDEMIOL & HLTH PROMOT,HELSINKI,FINLAND. UNIV TEXAS,SCH MED,DIV HEMATOL ONCOL,HOUSTON,TX. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV N CAROLINA,COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC. RP Shahar, E (reprint author), UNIV MINNESOTA,DIV EPIDEMIOL,SCH PUBL HLTH,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55455, USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55015, N01-HC-55016] NR 48 TC 61 Z9 61 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 1 PY 1996 VL 93 IS 11 BP 1970 EP 1975 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UM928 UT WOS:A1996UM92800007 PM 8640970 ER PT J AU Aksentijevich, I Cardarelli, CO Pastan, I Gottesman, MM AF Aksentijevich, I Cardarelli, CO Pastan, I Gottesman, MM TI Retroviral transfer of the human MDR1 gene confers resistance to bisantrene-specific hematotoxicity SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC BREAST-CANCER; PHASE-II EVALUATION; BONE-MARROW CELLS; MULTIDRUG-RESISTANCE; TRANSGENIC MICE; DIFFERENTIATION ANTIGENS; DRUG-RESISTANCE; P-GLYCOPROTEIN; EXPRESSION; IDENTIFICATION AB In this work, we demonstrate a protective effect conferred by the human multidrug resistance gene (MDR1) to populations of the murine hematopoietic system against the toxic effects of bisantrene, a novel intercalating cytotoxic agent under investigation as an anticancer agent, In vitro, MDR1-expressing cell lines are highly cross-resistant to bisantrene, and low levels of P-glycoprotein (the MDR1 gene product cell surface protein) confer resistance to the drug, MDR1-positive mice were generated after transplantation of bone marrow cells (BMC) transduced in vitro with a MDR1 retrovirus. Control mice were transplanted with BMC transduced with the neomycin resistance gene, Administration of a single i,v, dose of 50 mg/kg of bisantrene resulted in a decrease of the total WBC count of approximately 40%, In contrast, a decrease of the total WBC count of only 17% was observed in mice transplanted with MDR1-transduced BMC, Immunofluorescence studies with cell lineage-specific monoclonal antibodies showed that bisantrene was specifically toxic for B lymphocytes and macrophages, Double-staining with MRK16 (a monoclonal antibody specific for P-glycoprotein) demonstrated that single dose of bisantrene increased the relative number of MDR1-transduced positive B cells, macrophages, and (to some extent) granulocytes when compared to the number found in MDR1-untreated mice or the bisantrene-treated neomycin-transduced control mice, These results provide in vivo evidence that bisantrene is a hematotoxic drug capable of selecting for MDR1-transduced hematopoietic cells, Bisantrene might be useful for gene therapy as an in vivo selective agent for cells transduced with MDR1 vectors that also coexpress therapeutic genes of interest. C1 NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NCI,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 38 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1996 VL 2 IS 6 BP 973 EP 980 PG 8 WC Oncology SC Oncology GA UP184 UT WOS:A1996UP18400008 PM 9816258 ER PT J AU Hristova, EN Remaley, A Lindsey, H Pienta, P AF Hristova, EN Remaley, A Lindsey, H Pienta, P TI Assessment of the Boehringer Mannheim/Hitachi 914 clinical chemistry analyzer SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NATL INST HLTH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 231 EP 231 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200233 ER PT J AU Hristova, EN Remaley, A Lindsey, H Pienta, P AF Hristova, EN Remaley, A Lindsey, H Pienta, P TI Comparison between BM/Hitachi 914 and Ektachem 700XR for GGT, amylase and lipase. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NATL INST HLTH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 232 EP 232 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200234 ER PT J AU Johnson, CD King, C Hruszkewycz, AM AF Johnson, CD King, C Hruszkewycz, AM TI Evaluation of the Boehringer Mannheim (BM) Hitachi 914 for urine chemistry testing SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,CLIN CHEM SERV,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 233 EP 233 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200235 ER PT J AU Csako, G Rashidian, A Costello, R Nagy, B AF Csako, G Rashidian, A Costello, R Nagy, B TI Assessment of two major pulsed-field gel electrophoretic (PFGE) techniques for the separation of medium-sized dna molecules exemplified by the alleles of the human apolipoprotein(a) SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. RI Nagy, Balint/F-6943-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 434 EP 434 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200435 ER PT J AU Hruszkewycz, AM Delgado, RM Przygodzki, RM Travis, WD Jett, JR Colby, TV Liotta, LA Khan, MA Harris, CC Bennett, WP AF Hruszkewycz, AM Delgado, RM Przygodzki, RM Travis, WD Jett, JR Colby, TV Liotta, LA Khan, MA Harris, CC Bennett, WP TI Rapid base sequence analysis of mutant human K-ras oncogene using semi-automated 'cold' SSCP. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. PITTSBURGH CANC CTR,PITTSBURGH,PA 15213. MAYO CLIN SCOTTSDALE,SCOTTSDALE,AZ 85259. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 435 EP 435 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200436 ER PT J AU Negrusz, A Moore, CM McDonagh, NS Woods, EF Levine, BS Crowell, JA AF Negrusz, A Moore, CM McDonagh, NS Woods, EF Levine, BS Crowell, JA TI Determination of phenethylamine, a phenethyl isothiocyanate marker, in dog plasma using solid phase extraction and GC-MS with chemical ionization. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 UNIV ILLINOIS,CHICAGO,IL 60612. US DRUG TESTING LAB INC,CHICAGO,IL 60612. NCI,ROCKVILLE,MD 20852. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 660 EP 660 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200660 ER PT J AU Csako, G Rehak, NN Elin, RJ AF Csako, G Rehak, NN Elin, RJ TI Failure of an ion-selective method for the measurement of ionized magnesium in patients with severe hypomagnesemia. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 763 EP 763 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200763 ER PT J AU Rehak, NN Cecco, SA Hristova, EN Niemela, JE McKee, MD Rosenberg, SA Elin, RJ AF Rehak, NN Cecco, SA Hristova, EN Niemela, JE McKee, MD Rosenberg, SA Elin, RJ TI Effect of IL-2 therapy on the concentration of serum ionized magnesium. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 764 EP 764 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200764 ER PT J AU Cecco, SA Hristova, EN Niemela, JE Rehak, NN Elin, RJ AF Cecco, SA Hristova, EN Niemela, JE Rehak, NN Elin, RJ TI Analyzer-dependent differences for high or low ionized magnesium and ionized calcium. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 765 EP 765 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200765 ER PT J AU Rehak, NN Cecco, SA Hristova, EN Niemela, JE Herion, D Elin, RJ AF Rehak, NN Cecco, SA Hristova, EN Niemela, JE Herion, D Elin, RJ TI Concentration of serum ionized magnesium in chronic alcoholism. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 766 EP 766 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200766 ER PT J AU Neimela, JE Snader, BM Elin, RJ AF Neimela, JE Snader, BM Elin, RJ TI Method for the determination of ionized magnesium in platelets and correlation with selected parameters. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 767 EP 767 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200767 ER PT J AU Costello, R Lee, V Chesler, R Csako, G AF Costello, R Lee, V Chesler, R Csako, G TI Comparison of three methods for measurement of serum high-density lipoprotein cholesterol (HDL-C). SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,DEPT CLIN PATHOL,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 808 EP 808 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200808 ER PT J AU Chesler, R Costello, R Csako, G AF Chesler, R Costello, R Csako, G TI Four techniques for determination of serum low-density lipoprotein-cholesterol (LDL-C) compared. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 809 EP 809 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200809 ER PT J AU Remaley, AT Hoeg, JM Brewer, HB AF Remaley, AT Hoeg, JM Brewer, HB TI Defective reverse cholesterol transport in tangier disease skin fibroblasts SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 810 EP 810 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200810 ER PT J AU Sampson, M Ruddel, M Elin, RJ AF Sampson, M Ruddel, M Elin, RJ TI The effect of gender and estrogen replacement therapy on the reference interval for serum copper. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 855 EP 855 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200855 ER PT J AU Vreman, HJ Verter, J Oh, W Fanaroff, AA Wright, LL Lemons, JA Shankaran, S Tyson, JE Korones, SB Bauer, CR Stoll, BJ Papile, LA Donovan, EF Ehrenkranz, RA Stevenson, DK AF Vreman, HJ Verter, J Oh, W Fanaroff, AA Wright, LL Lemons, JA Shankaran, S Tyson, JE Korones, SB Bauer, CR Stoll, BJ Papile, LA Donovan, EF Ehrenkranz, RA Stevenson, DK TI Interlaboratory variability of bilirubin measurements SO CLINICAL CHEMISTRY LA English DT Article DE control material; quality control; automated analysis ID NEWBORNS AB During an 8-month study, 14 laboratories used automated analytical systems to measure total bilirubin concentrations in lyophilized bovine specimens containing 38, 169, and 253 mu mol/L bilirubin (2.2, 9.9, and 14.8 mg/dL, respectively), The measured mean +/- SD (n, range) were: 39 +/- 7 mu mol/L (n = 90, 31-53) [2.3 +/- 0.4 mg/dL (1.8-3.1)]; 176 +/- 29 mu mol/L (n = 89, 146-222) [10.3 +/- 1.7 mg/dL (8.5-13.0)]; and 260 +/- 43 mu mol/L (n = 103, 208-316) [15.2 +/- 2.5 mg/dL (12.1-18.5)]. In comparison with target values, measurements were consistently lower at 4, higher at 6, and within +/- 4% at 4 laboratories for each of the three concentrations, The measured values for each concentration remained fairly constant during the study at each laboratory, We conclude that bilirubin measurements differed significantly from the established target values at most of the participating laboratories. C1 STANFORD UNIV,SCH MED,DEPT PEDIAT,STANFORD,CA 94305. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC. BROWN UNIV,WOMEN & INFANTS HOSP,PROVIDENCE,RI. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NICHHD,BETHESDA,MD 20892. INDIANA UNIV,INDIANAPOLIS,IN 46204. WAYNE STATE UNIV,DETROIT,MI. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. UNIV TENNESSEE,MEMPHIS,TN. UNIV MIAMI,MIAMI,FL 33152. EMORY UNIV,ATLANTA,GA 30322. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. UNIV CINCINNATI,CINCINNATI,OH. YALE UNIV,NEW HAVEN,CT. FU NICHD NIH HHS [U01 HD19897, U10 HD27880, U10 HD27904] NR 19 TC 56 Z9 61 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 BP 869 EP 873 PN 1 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UQ783 UT WOS:A1996UQ78300007 PM 8665677 ER PT J AU Rehak, NN Cecco, SA Niemela, JE Hristova, EN Elin, RJ AF Rehak, NN Cecco, SA Niemela, JE Hristova, EN Elin, RJ TI Linearity and stability of the AVL and Nova magnesium and calcium ion-selective electrodes SO CLINICAL CHEMISTRY LA English DT Article DE electrolytes; intermethod comparison ID BLOOD; SERUM AB We studied the stability and linearity of the AVL and Nova Mg and Ca ion-selective electrodes and the relation between the ionized Ca and ionized Mg results reported by each analyzer, The response of the electrodes to different concentrations of Mg and Ca was determined for saline solutions, aqueous solutions, and serum samples, The electrodes from both manufacturers demonstrated acceptable stability for the time of the study, The response of the electrodes was linear within the range specified by each manufacturer, but relative nonlinearity and the values for the linear limits differed between the AVL and Nova analyzers, The ionized Mg results varied with the concentration of Ca, The relation between ionized Ca and ionized Mg results was nonlinear and differed between the AVL and Nova electrodes, Intermethod comparison between the electrodes showed poor agreement for ionized Mg results, especially at low and high concentrations of total Ca and total Mg. RP Rehak, NN (reprint author), NIH,CLIN CHEM SERV,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,RM 2C-407,10 CTR DR,BETHESDA,MD 20892, USA. OI Niemela, Julie/0000-0003-4197-3792 NR 12 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 BP 880 EP 887 PN 1 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UQ783 UT WOS:A1996UQ78300009 PM 8665679 ER PT J AU Sampson, M Ruddel, M Albright, S Elin, RJ AF Sampson, M Ruddel, M Albright, S Elin, RJ TI Positive interference by clot activator with the determination of lithium. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 897 EP 897 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200897 ER PT J AU Rosenberg, PB Rosse, RB Johri, SK Kendrick, K FayMcCarthy, M Collins, JP Tsui, LC Wyatt, RJ Deutsch, SI AF Rosenberg, PB Rosse, RB Johri, SK Kendrick, K FayMcCarthy, M Collins, JP Tsui, LC Wyatt, RJ Deutsch, SI TI Smooth pursuit eye movements in the evaluation of famotidine adjunctive therapy of schizophrenia: A preliminary report SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE famotidine; schizophrenia; smooth pursuit; eye tracking; histamine; H-2 antagonist ID DORSOLATERAL PREFRONTAL CORTEX; PHYSIOLOGIC DYSFUNCTION; TRACKING DYSFUNCTIONS; SYMPTOMS; MARKER; MEMORY; GENE AB Smooth pursuit eye movements (SPEM) are often abnormal in schizophrenic patients and have been proposed as a trait marker of the disorder. We explored the use of SPEM as an outcome measure in an open-label clinical trial of famotidine, an H-2 antagonist, in patients with schizophrenia; famotidine has been proposed as an adjunctive medication, particularly for negative symptoms. Prior studies using SPEM as an outcome measure have not found a significant effect with ''typical'' neuroleptic medication, and one study found greater SPEM dysfunction with clozapine treatment, In this study, 19 schizophrenic subjects were stabilized for at least 1 week on conventional neuroleptic medications and then administered oral famotidine, 100 mg daily, for an additional 3 weeks. SPEM and clinical measures were assessed, Whereas Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessment of Negative Symptoms (SANS) scores decreased significantly with famotidine administration, there was no significant change in SPEM performance over the course of the study, Two subjects (11%) doubled their signal/noise ratio and maintained this increase after famotidine discontinuation, whereas three subjects (17%) approximately halved this ratio and returned to baseline after famotidine discontinuation. SPEM changes were not found to correlate significantly with changes in BPRS or SANS scores. These findings suggest that SPEM dysfunction reflects a ''trait'' rather than clinical ''state'' in schizophrenia, and changes in SPEM performance might not be expected always to parallel changes in clinical ratings. C1 DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC. NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RI Tsui, Lap-chee/A-1081-2010 FU ONDIEH CDC HHS [RA-ND-90-10] NR 24 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JUN PY 1996 VL 19 IS 3 BP 276 EP 281 DI 10.1097/00002826-199619030-00011 PG 6 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA UL220 UT WOS:A1996UL22000011 PM 8726548 ER PT J AU Mofenson, LM AF Mofenson, LM TI The role of antiretroviral therapy in the management of HIV infection in women SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; PHASE-I TRIAL; ZIDOVUDINE THERAPY; 2',3'-DIDEOXYINOSINE DDI; PREGNANT-WOMEN; DOUBLE-BLIND; AZIDOTHYMIDINE AZT; TYPE-1 INFECTION RP Mofenson, LM (reprint author), NICHHD,CLIN RES PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,CTR RES MOTHERS & CHILDREN,NIH,ROCKVILLE,MD, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 112 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 1996 VL 39 IS 2 BP 361 EP 385 DI 10.1097/00003081-199606000-00010 PG 25 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UK023 UT WOS:A1996UK02300008 PM 8734002 ER PT J AU Sartor, O Figg, WD AF Sartor, O Figg, WD TI Mifepristone: Antineoplastic studies SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID ANTAGONIST RU486; BREAST-CANCER; PROGESTERONE-RECEPTOR; RU-486; MENINGIOMAS; ENDOCRINE; ANTIPROGESTINS; AGONIST; GROWTH C1 NCI,BETHESDA,MD 20892. RP Sartor, O (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT HEMATOL ONCOL,1501 KINGS HIGHWAY,SHREVEPORT,LA 71130, USA. RI Figg Sr, William/M-2411-2016 NR 28 TC 13 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 1996 VL 39 IS 2 BP 498 EP 505 DI 10.1097/00003081-199606000-00023 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UK023 UT WOS:A1996UK02300020 PM 8734014 ER PT J AU Sartor, O Cutler, GB AF Sartor, O Cutler, GB TI Mifepristone: Treatment of Cushing's syndrome SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID STEROID RU-486; PROGESTERONE; PITUITARY; PRIMATES C1 NICHHD,NIH,BETHESDA,MD 20892. RP Sartor, O (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT MED,HEMATOL ONCOL SECT,1501 KINGS HIGHWAY,SHREVEPORT,LA 71130, USA. NR 12 TC 41 Z9 42 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 1996 VL 39 IS 2 BP 506 EP 510 DI 10.1097/00003081-199606000-00024 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UK023 UT WOS:A1996UK02300021 PM 8734015 ER PT J AU Wolfe, EJ Cavacini, LA Samore, MH Posner, MR Kozial, C Spino, C Trapnell, CB Ketter, N Hammer, S Gambertoglio, JG AF Wolfe, EJ Cavacini, LA Samore, MH Posner, MR Kozial, C Spino, C Trapnell, CB Ketter, N Hammer, S Gambertoglio, JG TI Pharmacokinetics of F105, a human monoclonal antibody, in persons infected with human immunodeficiency virus type 1 SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NEUTRALIZING ANTIBODIES; HIV-1/GP120; BINDING; HIV-1 AB F105 is a human monoclonal antibody that binds to the CD4 binding site of human immunodeficiency virus type 1 gp120 and neutralizes clinical and laboratory isolates of the human immunodeficiency virus, This phase I study investigated the disposition of the antibody in humans. F105 was administered over a 60-minute period at two dose levels, 100 and 500 mg/m(2). Blood samples were obtained for up to 56 days, The clearance of the antibody was 0.33 ml/min with a corresponding half-life of approximately 13 days, Peak concentrations achieved at the higher dose level were 216.19 +/- 9.62 mu g/ml. The disposition of the drug mas linear for the doses studied, Simulations were performed to design future studies aimed at investigating the efficacy of the antibody, This study concluded that F105 can be administered as a bolus dose every 21 days. C1 UNIV CALIF SAN FRANCISCO,DEPT CLIN PHARM,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,SCH PUBL HLTH,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. US FDA,ROCKVILLE,MD 20857. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-26926]; PHS HHS [A1-27663] NR 13 TC 18 Z9 19 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 1996 VL 59 IS 6 BP 662 EP 667 DI 10.1016/S0009-9236(96)90006-5 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UV547 UT WOS:A1996UV54700007 PM 8681491 ER PT J AU Ognibene, FP AF Ognibene, FP TI Hemodynamic support during sepsis SO CLINICS IN CHEST MEDICINE LA English DT Article ID INTENSIVE-CARE UNIT; SEPTIC SHOCK; NOREPINEPHRINE THERAPY; SUPRANORMAL VALUES; PROSPECTIVE TRIAL; GOALS; PERFORMANCE; SURVIVORS; DOPAMINE; IMPACT AB Hemodynamic support during sepsis should focus on aggressive resuscitation coupled with vasopressors aimed at restoration of blood pressure and end-organ perfusion and preservation. The choice of vasopressors should be based on the degree and persistence of peripheral vasodilatation as well as the degree of cardiac stimulation required. Norepinephrine can and should be used when dopamine fails to improve blood pressure and perfusion after adequate volume resuscitation. Dopamine's role of renovascular preservation remains controversial. Therapeutic strategies aimed at supranormal improvements in cardiac index or oxygen delivery have no documented effect in septic patients and should not be part of their therapy. C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT MED,WASHINGTON,DC 20052. RP Ognibene, FP (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,10 CTR DR MSC 1662,BETHESDA,MD 20892, USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD JUN PY 1996 VL 17 IS 2 BP 279 EP & DI 10.1016/S0272-5231(05)70314-2 PG 11 WC Respiratory System SC Respiratory System GA UQ937 UT WOS:A1996UQ93700009 PM 8792066 ER PT J AU Marrone, A Sallie, R AF Marrone, A Sallie, R TI Genetic heterogeneity of hepatitis C virus - The clinical significance of genotypes and quasispecies behavior SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID POLYMERASE CHAIN-REACTION; 5' NONCODING REGION; NON-B-HEPATITIS; RNA VIRUSES; NON-A; RAPID EVOLUTION; MULLER RATCHET; VIRAL-RNA; SEQUENCE; GENOME AB Knowledge of the molecular biology of the hepatitis C virus (HCV) has increased exponentially since its identification in 1989. Paradoxically, the understanding of many clinical aspects of HCV pathobiology has lagged behind, partly because of lack of suitable models of disease. The genomic variability of HCV is central to viral pathogenesis. This article briefly reviews some clinical and laboratory aspects of HCV variability, such as investigatory method, pitfalls in data interpretation, and possible directions for future research. The profound implications of stable quasispecies behavior, conserved genotype replication, and the unexpectedly low frequency of infection with multiple genotypes in susceptible individuals are discussed. C1 NATL INST HLTH,LIVER DIS SECT,BETHESDA,MD. NR 75 TC 11 Z9 12 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 1996 VL 16 IS 2 BP 429 EP & PG 22 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UQ933 UT WOS:A1996UQ93300012 PM 8792081 ER PT J AU Brant, LJ Pearson, JD Morrell, CH Fox, KM Gajdusek, DC Garruto, RM Plato, CC AF Brant, LJ Pearson, JD Morrell, CH Fox, KM Gajdusek, DC Garruto, RM Plato, CC TI Quantitative and qualitative dermatoglyphics as a basis to study the relationship between Pacific populations SO COLLEGIUM ANTROPOLOGICUM LA English DT Article AB Quantitative and qualitative dermatoglyphic traits are used to study the relationship among selected population samples from Micronesia (Guam, Kapingamarangi and Ponape, Yap), Papua New Guinea (Fore, Iokea, Wosera-Abelam), and the South Pacific region of the Solomon Islands and Vanuatu (Loh, Santa Cruz, Ureparapara). Digital and palmar dermatoglyphic traits (total ridge count, average ab ridge count, digital ridge counts, and digital arches, loops and whorls) of 397 men. were used in a linear discriminant function analysis to attempt to correctly classify these individuals by population and by region. The findings demonstrate that linear discriminant functions using both quantitative and qualitative dermatoglyphic traits can achieve a high correct classification rate both across regions (63-73%) and within Micronesia (74-78%) and Papua New Guinea (79-86%). However, classification rates were not as uniform within the Solomon Islands and Vanuatu (59-81%). Overall, these results suggest that a Linear discriminant function analysis of dermatoglyphics is a useful analytic tool for exploring biological relationships among various indigenous island populations of Australasia. RP Brant, LJ (reprint author), NIA,CTR GERONTOL RES,BALTIMORE,MD 21224, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU SCH BIOLOGICAL ANTHROPOLOGY PI ZAGREB PA MOSE PIJADE 158 P O BOX 291, 41001 ZAGREB, CROATIA SN 0350-6134 J9 COLLEGIUM ANTROPOL JI Coll. Anthropol. PD JUN PY 1996 VL 20 IS 1 BP 1 EP 8 PG 8 WC Anthropology SC Anthropology GA UX113 UT WOS:A1996UX11300001 ER PT J AU Shapiro, BA Wu, JC AF Shapiro, BA Wu, JC TI An annealing mutation operator in the genetic algorithms for RNA folding SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article AB An annealing mutation operator in the genetic algorithms (GA) for RNA folding on a MasPar MP-2 has been designed. The mutation probability descends along a hyperbola with respect to the size of the secondary structure, hence the total number of mutations at Each generation drops linearly. Especially for long sequences with thousands of nucleotides as opposed to hundreds of nucleotides, the new mutation operator can make the distribution of free energies over all processors on MasPar MP-2 converge only after hundreds of generations. Based upon this new, mutation operator, a technique to terminate the GA is also developed. The new mutation operator runs very efficiently. Some variations of the annealing mutation operator are also discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK LMB,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. RP Shapiro, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,MATH BIOL LAB,IMAGE PROC SECT,BLDG 469,RM 150,FREDERICK,MD 21702, USA. NR 15 TC 43 Z9 46 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUN PY 1996 VL 12 IS 3 BP 171 EP 180 PG 10 WC Computer Science, Interdisciplinary Applications SC Computer Science GA VE796 UT WOS:A1996VE79600002 PM 8872384 ER PT J AU Hennessy, M MacQueen, K McKirnan, DJ Buchbinder, S Judson, F Douglas, JM Bartholow, B Sheon, A AF Hennessy, M MacQueen, K McKirnan, DJ Buchbinder, S Judson, F Douglas, JM Bartholow, B Sheon, A TI A factorial survey study to assess the acceptability of HIV vaccine trial designs SO CONTROLLED CLINICAL TRIALS LA English DT Article DE HIV vaccines; clinical trial participation ID CLINICAL-TRIALS; AIDS; COMMUNITY; PROGRAMS AB To aid in the design of human immunodeficiency virus (HIV) vaccine trials that maximize volunteer participation, factorial surveys were administered to 73 gay men who were participants in a larger study assessing HIV vaccine trial feasibility. Factorial surveys are ''vignettes'' that are randomly constructed through the combination of descriptive statements (dimensions) that reflect essential features. In this study, the dimensions define components of clinical trials to assess the efficacy of hypothetical HIV vaccines. Regression analysis shows that anticipated participation was decreased by a sustained vaccine-induced antibody response lasting 3 years, absence of gay men as research subjects in earlier phase trials for the products being tested, and rectal Vaccine administration. Three years of scientific experience with the vaccine encouraged participation. We conclude that willingness to participate in vaccine trials varies systematically with some of their characteristics. Where there are design alternatives for identified negative components, these should be considered. If this is not possible, options for decreasing aversion to such features will need to be evaluated, including appropriate education regarding both the benefits and the risks associated with negatively evaluated features. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV HIV AIDS,ATLANTA,GA 30341. HOWARD BROWN HLTH CLIN,CHICAGO,IL. SAN FRANCISCO DEPT PUBL HLTH,AIDS OFF,SAN FRANCISCO,CA. DENVER DEPT PUBL HLTH,DENVER,CO. NIAID,NIH,VACCINE TRIALS & EPIDEMIOL BRANCH,DIV AIDS,WASHINGTON,DC. RP Hennessy, M (reprint author), EMORY UNIV,DEPT SOCIOL,1555 PIERCE DR,ATLANTA,GA 30322, USA. NR 39 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 1996 VL 17 IS 3 BP 209 EP 220 DI 10.1016/0197-2456(95)00155-7 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VF209 UT WOS:A1996VF20900004 PM 8877256 ER PT J AU Naydeck, BL SuttonTyrrell, K Burek, K Sopko, GS AF Naydeck, BL SuttonTyrrell, K Burek, K Sopko, GS TI Organizational structure and communication strategies of the bypass angioplasty revascularization investigation: A multicenter clinical trial SO CONTROLLED CLINICAL TRIALS LA English DT Article DE organizational structure; communication; management; clinical trials; BARI AB Efficient communication is a challenge for the many operating components of a multicenter randomized clinical trial. Traditional management theory states that communications generally flow along a path established by a hierarchical organizational structure. A multicenter clinical trial does not fit traditional organizational models well and requires modification of traditional communication techniques. While the scientific community typically views a clinical trial as one large and cohesive enterprise, at each site the trial may actually be conducted as a small project related to the medical specialty of the investigator. Therefore overall trial management must be accomplished through collaboration rather than through direct management. In the Bypass Angioplasty Revascularization Investigation (BARI), the BARI clinical coordinating center has designed and utilized several mechanisms that facilitate effective communication and administrative control of a multicenter clinical trial. These mechanisms provide a framework of communication techniques that accommodate the specific needs of a complex organization. C1 UNIV MICHIGAN,MED CTR,DIV CARDIOL,ANN ARBOR,MI. NHLBI,NIH,BETHESDA,MD 20892. RP Naydeck, BL (reprint author), UNIV PITTSBURGH,GSPH,DEPT EPIDEMIOL,BARI CLIN COORDINATING CTR,1271 PARRAN HALL,130 DESOTO DR,PITTSBURGH,PA 15261, USA. NR 12 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 1996 VL 17 IS 3 BP 226 EP 234 DI 10.1016/0197-2456(95)00136-0 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VF209 UT WOS:A1996VF20900006 PM 8877258 ER PT J AU Sirigu, A Zalla, T Pillon, B Grafman, J Agid, Y Dubois, B AF Sirigu, A Zalla, T Pillon, B Grafman, J Agid, Y Dubois, B TI Encoding of sequence and boundaries of scripts following prefrontal lesions SO CORTEX LA English DT Article ID FRONTAL-LOBE DAMAGE; MEMORY; MOVEMENTS AB Script analysis was investigated in patients with lesions in the prefrontal (n=10) and posterior (n=8) cortical regions, and in normal subjects (n=15). The selection and temporal organization of relevant actions belonging to different pre-established sequences were studied in three different situations: (A) script with headers, (B) script with headers and distracters, and (C) scripts without headers. Contrarily to Normals and Posterior patients, Frontal patients committed sequence and boundary errors, and failed to eliminate distracters elements. The analysis of errors suggests two different cognitive modes of representing actions: (1) One using temporal contiguity between actions, that would be mainly under the control of the posterior associative areas; (2) the other, using the goal of the action and its consequences as a binding element between script and context. that would require the intervention of prefrontal cortex. C1 NINCDS, COGNIT NEUROSCI SECT, NIH, BETHESDA, MD 20892 USA. RP Sirigu, A (reprint author), HOP LA PITIE SALPETRIERE, INSERM U289, 47 BD HOP, F-75013 PARIS, FRANCE. OI Grafman, Jordan H./0000-0001-8645-4457 NR 35 TC 103 Z9 104 U1 1 U2 3 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA STATUTO 2/4, 20121 MILAN, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD JUN PY 1996 VL 32 IS 2 BP 297 EP 310 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA UT070 UT WOS:A1996UT07000006 PM 8800616 ER PT J AU Dimitrov, M Grafman, J Hollnagel, C AF Dimitrov, M Grafman, J Hollnagel, C TI The effects of frontal lobe damage on everyday problem solving SO CORTEX LA English DT Article ID LESIONS; BRAIN AB The prefrontal cortex plays an especially important role in human social-cognitive behavior. It has been difficult to quantify deficits in this domain in patients with frontal lobe: lesions using standardized psychological instruments. We administered the Everyday Problem Solving Inventory (EPSI), which is composed of a range of scenarios depicting everyday social problems and their possible solutions, to a group of patients with frontal lobe lesions who were required to rate each of 4 possible solutions to each problem for their effectiveness. Our sample consisted of 27 normal controls (NCs), 33 patients with focal frontal lobe lesions (FLL), and 3 patients with frontal lobe dementia (FLD). The performance of the FLL patients on the EPSI instrument was also compared with their performance on traditional neuropsychological tests. The results indicated that the FLD patients' EPSI rank ordering of social problem solutions was uncorrelated with the performance of NCs and about half of the FLL patients EPSI rank orderings of solutions also varied substantially from those of the NCs. These same FLL patients also had the lowest scores, compared to FLL patients whose judgements on the EPSI were similar to that of the NCs, on a set of neuropsychological tasks sensitive to frontal lobe dysfunction. There was no obvious relationship between locus of lesion within the frontal lobes and performance on the EPSI. These results suggest that some patients with prefrontal lobe lesions may have impaired social judgement that can be directly revealed through the use of a conventional psychological inventor), such as the EPSI. C1 NINCDS,COGNIT NEUROSCI SECT,NIH,MNB,BETHESDA,MD 20892. OI Grafman, Jordan H./0000-0001-8645-4457 NR 26 TC 38 Z9 38 U1 1 U2 5 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA STATUTO 2/4, 20121 MILAN, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD JUN PY 1996 VL 32 IS 2 BP 357 EP 366 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA UT070 UT WOS:A1996UT07000011 PM 8800621 ER PT J AU Sternberg, KJ Lamb, ME Hershkowitz, I AF Sternberg, KJ Lamb, ME Hershkowitz, I TI Child sexual abuse investigations in Israel SO CRIMINAL JUSTICE AND BEHAVIOR LA English DT Article AB This article describes how allegations of child sexual abuse are investigated and adjudicated in Israel. Believing that children may well be harmed by repeated interrogation and demands to testify and be cross-examined, Israeli legislators enacted special provisions several decades ago to ensure that children were spared these traumas. Recent evaluations of the system they established suggest that the protections concerned may have led inadvertently to various practices, including the failure to prosecute, that have not served children well. Possible remedies and a research program related to these issues are described. RP Sternberg, KJ (reprint author), NICHHD, SECT SOCIAL & EMOT DEV, BSA BLDG, ROOM 331, 9190 ROCKVILLE PIKE, BETHESDA, MD 20814 USA. NR 39 TC 22 Z9 22 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0093-8548 J9 CRIM JUSTICE BEHAV JI Crim. Justice Behav. PD JUN PY 1996 VL 23 IS 2 BP 322 EP 337 DI 10.1177/0093854896023002005 PG 16 WC Psychology, Clinical; Criminology & Penology SC Psychology; Criminology & Penology GA UL452 UT WOS:A1996UL45200005 ER PT J AU Qavi, HB Xu, BS Green, MT Lusso, P Pearson, G Ablashi, DV AF Qavi, HB Xu, BS Green, MT Lusso, P Pearson, G Ablashi, DV TI Morphological and ultrastructural changes induced in corneal epithelial cells by HIV-1 and HHV-6 in vitro SO CURRENT EYE RESEARCH LA English DT Article DE human immunodeficiency virus (HIV-1); human herpesvirus-6 (HHV-6); keratinocytes; corneal epithelial cells; lacrimal gland; human ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; AIDS PATIENTS; INFECTION; LINES; TEARS; ENTRY AB Purpose. The purpose of this study was to determine whether HIV-1 and HHV-6 are capable of infecting and inducing morphological and ultrastructural changes in corneal epithelial cells in vitro. Methods. Primary and transformed corneal epithelial cell cultures were infected with HIV-1 or HHV-6 in vitro and analyzed for the presence or absence of viral antigens, DNA sequences, viral particles and inclusions. Results. HIV-1 antigens were detected in 8% of the HIV-1 infected cells and early HHV-6 antigens were present in 12% of the HHV-6 infected cells. The presence of viral DNA sequences in the cultures confirmed these findings. Cells infected with HIV-1 morphologically were not different from uninfected cells, whereas the morphology of HHV-6 infected cells was very similar to cells infected with other human herpesviruses. Cytoplasmic tubuloreticular inclusions were detectable in corneal epithelial cells infected with HIV-1 and intact viral particles were visible only in PBMC used to recover HIV-1 from these cultures. Viral inclusions were also observed in corneal epithelial cells infected with HHV-6. Conclusion. These data indicate that HIV-1 and HHV-6 are capable of infecting corneal epithelial cells in vitro, but the viruses are not entering these cells via CD4 or galC receptors. This basic information is important in determining the pathogenic mechanism(s) involved in the development of AIDS-associated corneal disorders. C1 NIH,NATL CANC CTR INST,TUMOR CELL BIOL LAB,BETHESDA,MD. GEORGETOWN UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC. RP Qavi, HB (reprint author), BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030, USA. FU NEI NIH HHS [EY08082] NR 34 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 1996 VL 15 IS 6 BP 597 EP 604 DI 10.3109/02713689609008899 PG 8 WC Ophthalmology SC Ophthalmology GA UT528 UT WOS:A1996UT52800002 PM 8670762 ER PT J AU Baxevanis, AD Makalowski, W Ouellette, BFF Recipon, H AF Baxevanis, AD Makalowski, W Ouellette, BFF Recipon, H TI World Wide Web sites SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Editorial Material RP Baxevanis, AD (reprint author), NATL INST HLTH,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N-805,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD JUN PY 1996 VL 7 IS 3 BP 356 EP 356 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA UT526 UT WOS:A1996UT52600020 ER PT J AU Francomano, CA McIntosh, I Wilkin, DJ AF Francomano, CA McIntosh, I Wilkin, DJ TI Bone dysplasias in man: Molecular insights SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID STICKLER SYNDROME ARTHROOPHTHALMOPATHY; II PROCOLLAGEN GENE; COL2A1; MUTATION; CARTILAGE; LINKAGE; CODON AB The recent explosion in the number of identified genes involved in the human skeletal dysplasias has dramatically advanced this particular field. While linkage efforts are mapping hereditary disorders of the skeleton at an ever accelerating pace, progress in the Human Genome Project is providing tools for rapid gene discovery after the map location is known. Emerging themes in the molecular analysis of the skeletal dysplasias include the identification of allelic series of disorders and the existence of mutational and genetic heterogeneity in many of these conditions. Allelic series include those conditions caused by mutations in the genes encoding type II collagen (COL2A1), cartilage oligomeric matrix protein (COMP), fibroblast growth factor receptor 3 (FGFR3) and the diastrophic dysplasia sulfate transporter (DTDST). The recognition of these phenomena has initiated the analysis of the relationship between disease phenotype and gene. C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287. NR 57 TC 32 Z9 32 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 1996 VL 6 IS 3 BP 301 EP 308 DI 10.1016/S0959-437X(96)80006-2 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA UR931 UT WOS:A1996UR93100006 PM 8791509 ER PT J AU Dalakas, MC Sivakumar, K AF Dalakas, MC Sivakumar, K TI The immunopathologic and inflammatory differences between dermatomyositis, polymyositis and sporadic inclusion body myositis SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID LYMPHOCYTES-T; GRANZYME-A; MYOPATHIES; RECEPTOR; AIDS AB In polymyositis and sporadic inclusion body myositis, clonal expansion of CD8(+) cells which are primed to recognize previously unknown muscle antigens occurs, Compared with sporadic inclusion body myositis, however, in which the T-cell response may not be antigen driven, there is in polymyositis an overexpression of certain T-cell receptor gene families among the autoinvasive T-cells. Although studies on the endomysial expression of cytokines and cell adhesion molecules have provided additional support for the concept of an ongoing immune process, the site of sensitization and the mechanism by which the autoimmune process is triggered remains to be established, In dermatomyositis, a multiorgan disease, evidence exists that the complement-mediated microvascular injury by the putative antibody may not be limited to the endomysial vessels but may also involve the blood vessels in the dermis. The antigenic target on the endothelial cell in dermatomyositis patients and the pathogenic role of the recently studied anti-Mi-2 antibody directed against a helicase are still to be determined. C1 NINCDS,NEUROMUSC DIS SECT,NIH,BETHESDA,MD. NR 34 TC 37 Z9 37 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 1996 VL 9 IS 3 BP 235 EP 239 DI 10.1097/00019052-199606000-00015 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UY146 UT WOS:A1996UY14600015 PM 8839618 ER PT J AU Bork, P Koonin, EV AF Bork, P Koonin, EV TI Protein sequence motifs SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article AB Protein sequence motifs are signatures of protein families and can often be used as tools for the prediction of protein function. The generalization and modification of already known motifs are becoming major trends in the literature, even though new motifs are still being discovered at an approximately linear rate. The emphasis of motif analysis appears to be shifting from metabolic enzymes, in which motifs are associated with catalytic functions and thus often readily recognizable, to structural and regulatory proteins, which contain more divergent motifs. The consideration of structural information increasingly contributes to the identification of motifs and their sensitivity. Genome sequencing provides the basis for asystematic analysis of all motifs that are present in a particular organism. A systematically derived motif database is therefore feasible, allowing the classification of the majority of the newly appearing protein sequences into known families. C1 MAX DELBRUCK CTR,D-13189 BERLIN,GERMANY. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Bork, P (reprint author), EUROPEAN MOLEC BIOL LAB,MEYERHOFSTR 1,D-69012 HEIDELBERG,GERMANY. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 74 TC 92 Z9 95 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 1996 VL 6 IS 3 BP 366 EP 376 DI 10.1016/S0959-440X(96)80057-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UU654 UT WOS:A1996UU65400014 PM 8804823 ER PT J AU Gibrat, JF Madej, T Bryant, SH AF Gibrat, JF Madej, T Bryant, SH TI Surprising similarities in structure comparison SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID PROTEIN-STRUCTURE; TERTIARY STRUCTURE; STRUCTURE MOTIFS; ALIGNMENT; SEQUENCE; FAMILIES AB Examination of a protein's structural 'neighbors' can reveal distant evolutionary relationships that are otherwise undetectable, and perhaps suggest unsuspected functional properties. In the past, such analyses have often required specialized software and computer skills, but new structural comparison methods, developed in the past two years, increasingly offer this opportunity to structural and molecular biologists in general. These methods are based on similarity-search algorithms that are fast enough to have effectively removed the computer-time limitation for structure-structure search and alignment, and have made it possible for several groups to conduct systematic comparisons of all publicly available structures, and offer this information via the World Wide Web. Furthermore, and perhaps surprisingly given the difficulty of the structure-comparison problem, these groups seem to have converged on quite similar approaches with respect to both fast search algorithms and the identification of statistically significant similarities. C1 NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. INRA,UNITE BIOINFORMAT,F-78350 JOUY EN JOSAS,FRANCE. NR 65 TC 726 Z9 744 U1 0 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 1996 VL 6 IS 3 BP 377 EP 385 DI 10.1016/S0959-440X(96)80058-3 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UU654 UT WOS:A1996UU65400015 PM 8804824 ER PT J AU Berger, MS Taub, DD Orlofsky, A Kleyman, TR CoupayeGerard, B Eisner, D Cohen, SA AF Berger, MS Taub, DD Orlofsky, A Kleyman, TR CoupayeGerard, B Eisner, D Cohen, SA TI The chemokine C10: Immunological and functional analysis of the sequence encoded by the novel second exon SO CYTOKINE LA English DT Article DE chemokines; C10; epitope; FLAG antigen ID GROWTH-FACTOR; CYTOKINE FAMILY; GENE; PROTEIN; BIOLOGY; MEMBER; EXPRESSION; ANTIBODIES; JE AB The gene for C10, a member of the beta-chemokine family of cytokines, contains a novel second exon encoding a 16 amino acid sequence which is inserted into the amino-terminal region of the protein, We propose a model of C10 structure in which the sequence encoded by the second exon is located on the surface of the protein where it interacts with receptors and defines the predominant epitope of the C10 protein, To test this model we produced C10 protein without the sequence encoded by the second exon, termed C10(-). Antisera generated against purified C10 recognized C10 protein but reacted only weakly with C10(-) protein, Recognition of C10 protein by C10 antisera was not blocked by pre-incubation with a peptide encoding the C10 second exon, indicating that the predominant epitope was not simply the amino acid sequence encoded by the second exon, Antibodies generated against a peptide encoding the C10 second exon sequence recognized C10 on Western blots; this reaction was competed both by C10 second exon peptide and by C10 protein, Functional studies demonstrated that both C10/FLAG and C10(-)/FLAG elicit chemotaxis of mouse PECs and human PBMCs, but that C10(-)/FLAG appears to be more potent than C10/FLAG, Thus these data are consistent with our model of C10 in which the sequence encoded by the second exon is located on the surface, participates in defining the predominant epitope, and plays a key role in recognizing or activating chemokine receptors. (C) 1996 Academic Press Limited C1 VET ADM MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. NCI,FCRDC,SAIC FREDERICK,NIH,CLIN SERV PROGRAM,FREDERICK,MD. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NR 30 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN PY 1996 VL 8 IS 6 BP 439 EP 447 DI 10.1006/cyto.1996.0060 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA UV819 UT WOS:A1996UV81900003 PM 8818540 ER PT J AU Franklin, JL Sargent, TD AF Franklin, JL Sargent, TD TI Ventral neural cadherin, a novel cadherin expressed in a subset of neural tissues in the zebrafish embryo SO DEVELOPMENTAL DYNAMICS LA English DT Article DE cell adhesion; cadherins; zebrafish; neural-tube and development ID CELL-ADHESION MOLECULE; POLARITY GENE ARMADILLO; N-CADHERIN; XENOPUS EMBRYOS; CYTOPLASMIC DOMAIN; FLOOR PLATE; BODY AXIS; DROSOPHILA; PROTEIN; WINGLESS AB Cadherins are calcium-binding transmembrane glycoproteins that are important mediators of cell-cell association. Here we describe a novel member of this gene family, zebrafish ventral neural cadherin (VN-cad). Multiple VN-cad transcripts are first detectable by Northern blots at 60% epiboly. In the developing neural tube, VN-cad RNA is first found in the neuroectoderm, directly above the notochord, and later was localized to the neural keel. At the 20-somite stage, VN-cad transcripts are confined to the ventral neural tube, otic vesicle, midbrain, and diencephelon. Transcription of VN-cad RNA continues in adult fish. The embryonic pattern of expression is not significantly disrupted in cyclops or no tail mutants, which lack the floor plate and notochord, respectively. Therefore, neither of these structures is absolutely required for VN-cad expression. The localized pattern of VN-cad expression suggests a possible role for this adhesion molecule in the initial formation and subsequent differentiation of the central nervous system. (C) 1996 Wiley-Liss, Inc.* C1 NICHHD,MOLEC GENET LAB,NIH,BETHESDA,MD 20892. NR 70 TC 17 Z9 17 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 1996 VL 206 IS 2 BP 121 EP 130 DI 10.1002/(SICI)1097-0177(199606)206:2<121::AID-AJA1>3.0.CO;2-K PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA UN730 UT WOS:A1996UN73000001 PM 8725279 ER PT J AU Robinson, GW Smith, GH Gallahan, D Zimmer, A Furth, PA Hennighausen, L AF Robinson, GW Smith, GH Gallahan, D Zimmer, A Furth, PA Hennighausen, L TI Understanding mammary gland development through the imbalanced expression of growth regulators SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mammary development; alveolar differentiation; transgenes ID PROTEIN GENE PROMOTER; TRANSGENIC MICE; HYBRID GENE; TGF-ALPHA; ALVEOLAR DEVELOPMENT; INHIBITION; INDUCTION; BETA; OVEREXPRESSION; MORPHOGENESIS AB Functional differentiation of mammary tissue progresses in distinct phases spanning puberty and pregnancy. Here we have analyzed and compared the effects of transforming growth factor beta 1 (TGF beta 1), TGF alpha, and whey acidic protein (WAP), the Notch-related cell fate protein Int3, and p53 and pRb on mammary development. We chose transgene expression from the WAP gene promoter which is only active in mammary alveolar cells. The imbalanced expression of these molecules specifically altered development and differentiation of the gland. While TGF alpha did not disturb alveolar outgrowth, little or no alveolar structures developed in the presence of Int3. TGF beta 1, WAP, and the expression of SV40 T-antigen-which inactivates p53 and pRb-reduced overall alveolar development. The expression of individual milk protein genes was affected differentially by the transgenes. A WAP-lacZ transgene served as an additional indicator of terminal differentiation of alveolar cells. Homogeneous expression of lacZ was seen in mice transgenic for lacZ, or for TGF alpha and lacZ, In contrast, only a few differentiated cells were observed in the presence of TGF beta 1 and Tag. Thus, the expression of growth regulators in the same defined subset of mammary cells results in distinct developmental changes and a specific pattern of alveolar differentiation. (C) 1996 Wiley-Liss, Inc.* C1 NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21201. RI Zimmer, Andreas/B-8357-2009; Robinson, Gertraud/I-2136-2012 NR 32 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 1996 VL 206 IS 2 BP 159 EP 168 DI 10.1002/(SICI)1097-0177(199606)206:2<159::AID-AJA5>3.0.CO;2-H PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA UN730 UT WOS:A1996UN73000005 PM 8725283 ER PT J AU Haffner, SM DAgostino, R Saad, MF Rewers, M Mykkanen, L Selby, J Howard, G Savage, PJ Hamman, RF Wagenknecht, LE Bergman, RN AF Haffner, SM DAgostino, R Saad, MF Rewers, M Mykkanen, L Selby, J Howard, G Savage, PJ Hamman, RF Wagenknecht, LE Bergman, RN TI Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites - The insulin resistance atherosclerosis study SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; MEXICAN-AMERICANS; PIMA-INDIANS; RISK-FACTORS; C-PEPTIDE; CARDIOVASCULAR RISK; FAT DISTRIBUTION; FASTING INSULIN; MINIMAL MODEL AB The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors, African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites, Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies, Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S-I), glucose effectiveness (S-G), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n = 288), Hispanics (n = 363), and non-Hispanic whites (n = 435) as part of the Insulin Resistance Atherosclerosis Study, Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day, African-Americans and Hispanics were more obese than non-Hispanic whites, Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S-I than non-Hispanic whites, No ethnic difference was observed in S-G. After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S-I, than non-Hispanic whites, In contrast, after adjustment for these covariates, no significant ethnic differences in S-I or fasting insulin levels were observed between Hispanics and non-Hispanic whites, Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites, In this report, the association between S-I and upper body adiposity (waist-to-hip ratio) was similar in each ethnic group, Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups, However, in Hispanics, the greater insulin resistance may be due to greater adiposity and other behavioral factors. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV SO CALIF,SCH MED,DEPT MED,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. UNIV COLORADO,SCH MED,DEPT PREVENT MED BIOMETR,DENVER,CO. UNIV KUOPIO,DEPT MED,SF-70210 KUOPIO,FINLAND. KAISER PERMANENTE,DIV RES,OAKLAND,CA. NHLBI,NIH,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP Haffner, SM (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NHLBI NIH HHS [HL47887, HL47889, HL47890] NR 50 TC 358 Z9 362 U1 2 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1996 VL 45 IS 6 BP 742 EP 748 DI 10.2337/diabetes.45.6.742 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UN724 UT WOS:A1996UN72400007 PM 8635647 ER PT J AU Rodriguez, BL Sharp, DS Curb, JD Lu, GQY Burchfiel, CM Fujimoto, W Huang, BJ Yano, K AF Rodriguez, BL Sharp, DS Curb, JD Lu, GQY Burchfiel, CM Fujimoto, W Huang, BJ Yano, K TI Impaired glucose tolerance, diabetes, and cardiovascular disease risk factor profiles in the elderly. The Honolulu Heart Program SO DIABETES CARE LA English DT Article ID JAPANESE-AMERICAN MEN; ASYMPTOMATIC HYPERGLYCEMIA; ASCERTAINMENT; PREVALENCE; MORTALITY; ANCESTRY; STROKE; HAWAII; START AB OBJECTIVE - The relationship between glucose tolerance status and other cardiovascular disease (CVD) risk factors was evaluated in a cohort of Japanese-American men (n = 3,741) ages 71-93 years who participated in the fourth examination oi the Honolulu Heart Program in 1991-1993. RESEARCH DESIGN AND METHODS - In this cross-sectional study, subjects were classified by reported diabetes and glucose tolerance status using questionnaires and the World Health Organization (WHO) criteria, respectively. RESULTS - The prevalence of reported diabetes was 17%. Among the men who completed an oral glucose tolerance test and had no history oi diabetes (n = 1,900), 23% were diagnosed as diabetic and 39% had impaired glucose tolerance (IGT) by WHO criteria. The CVD risk factor profiles of men with IGT and diabetes were significantly more adverse compared with men with normal glucose tolerance after adjustment for age. The rates of hypertension, mean levels of BMI, waist-io-hip ratio, triglycerides, and fasting insulin were higher in men with IGT and diabetes compared with normal subjects. Opposite trends were observed for HDL cholesterol. Two-hour insulin was significantly higher among men with IGT and previously undiagnosed diabetes. Men with known diabetes had a lower physical activity index and higher fibrinogen levels than normal subjects. No significant differences were observed For current smoking and alcohol intake. Differences in risk factor levels by glucose tolerance status remained after adjustment For age, physical activity, BMI, and waist-to-hip ratio. CONCLUSIONS - These findings show that among elderly men of Japanese ancestry, impaired glucose tolerance and undiagnosed and known diabetes are highly prevalent, and these conditions are associated with adverse CVD Factor profiles. C1 UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DIV CLIN EPIDEMIOL,HONOLULU,HI 96822. NHLBI,NIH,HONOLULU,HI. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. RP Rodriguez, BL (reprint author), HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 24 TC 73 Z9 73 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1996 VL 19 IS 6 BP 587 EP 590 DI 10.2337/diacare.19.6.587 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UN440 UT WOS:A1996UN44000006 PM 8725856 ER PT J AU Csako, G Elin, RJ AF Csako, G Elin, RJ TI Spurious ketonuria due to captopril and other free sulfhydryl drugs - Proposed changes in current guidelines for urine ketone testing in diabetic patients SO DIABETES CARE LA English DT Letter ID THERAPY; MESNA RP Csako, G (reprint author), NIH,WG MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BLDG 10,RM 2C-407,BETHESDA,MD 20892, USA. NR 20 TC 8 Z9 8 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1996 VL 19 IS 6 BP 673 EP 674 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UN440 UT WOS:A1996UN44000025 PM 8725875 ER PT J AU Garza, OT Abati, A Sindelar, WF Pass, HI Hijazi, YM AF Garza, OT Abati, A Sindelar, WF Pass, HI Hijazi, YM TI Cytologic effects of photodynamic therapy in body fluids SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE photodynamic therapy; plural and peritoneal fluids; cytomorphology ID PHASE-I; MACROPHAGES AB Photodynamic therapy (PDT) has been used in phase I clinical trials at the National Institutes of Health for the treatment of malignancies disseminated within the peritoneal and pleural cavities, Review of records revealed 18 patients who were treated with PDT between April 1988-June 1993. Sixty-five pleural and peritoneal fluids, 22 pre- and 43 post-PDT, were available for evaluation. Mesothelial cell changes seen post-PDT included: increased nuclear-to-cytoplasmic ratios in 7/18 (39%), cytomegaly in 9/18 (50%), and multinucleation itt 12/18 (67%), with Touton-like giant cells in 3/18 (17%). Additional changes noted post-PDT comprised histiocytic aggregates in 9/18 patients (50%), with granuloma-like clusters in 3/18 (17%), acute and chronic inflammation in 13/18 (72%), and eosinophilia in 8/18 (44%). Residual tumor was present irt 7/18 (39%) patients post-PDT. In 2 patients with malignant mesothelioma, benign mesothelial cells with cytologic changes post-PDT were difficult to distinguish from malignant cells. Mesothelial cell changes following PDT, specifically increased nuclear-to-cytoplasmic ratios and cytomegaly, should be recognized to avert false-positive diagnoses of tumor In patients with malignant mesothelioma, and less commonly with adenocarcinoma, benign mesothelial cells with changes secondary to PDT may be difficult to distinguish from tumor cells. (C) 1996 Wiley-Liss, Inc. C1 NCI, PATHOL LAB, NIH, CYTOPATHOL SECT, BETHESDA, MD 20892 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 1996 VL 14 IS 4 BP 356 EP 361 DI 10.1002/(SICI)1097-0339(199605)14:4<356::AID-DC14>3.0.CO;2-J PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA UN733 UT WOS:A1996UN73300014 PM 8725138 ER PT J AU Alms, WJ BraunElwert, L James, SP Yurovsky, VV White, B AF Alms, WJ BraunElwert, L James, SP Yurovsky, VV White, B TI Simultaneous quantitation of cytokine mRNAs by reverse transcription-polymerase chain reaction using multiple internal standard cRNAs SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE cytokines; interleukin-2; interleukin-4; interferon-gamma; reverse transcription; polymerase chain reaction ID MESSENGER-RNA; GENE-EXPRESSION; REACTION ASSAY; DNA; LEISHMANIASIS; SUBSETS; CELLS AB Cytokines produced in abnormal amounts or patterns contribute to many immunologically mediated human diseases. We describe a competitive reverse transcription-polymerase chain reaction (RT-PCR) assay to measure interleukin (IL)(1)-2, IL-4, and interferon-gamma (IFN-gamma) mRNAs within the sample. Internal standard cRNAs and native cytokine mRNAs are reverse transcribed and then amplified by PCR in the same reaction tubes to control for tube-to-tube variability in these reactions. In contrast to systems that use a single multigene internal standard cRNA, this method uses separate internal standard cRNAs for IL-2, IL-4, and IFN-gamma, allowing independent dosing of the internal standards, which reduces the number of tubes processed and the amount of starting mRNA required. Internal standards are produced from cytokine cDNAs by the insertion of short segments of DNA. The same oligonucleotide primers are used to amplify internal standard and native cytokine cDNAs. Each internal standard cDNA and its matching native cytokine cDNA are amplified with equal efficiency. The RT-PCR products of the internal standards and native cytokines are distinguished by size. This technique can detect a twofold difference in mRNA levels. Examples of using this technique to measure cytokine mRNAs in peripheral blood mononuclear cells and in bronchoalveolar lavage cells are given. C1 UNIV MARYLAND,SCH MED,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. VET ADM MED CTR,MED SERV,BALTIMORE,MD 21218. VET ADM MED CTR,RES SERV,BALTIMORE,MD 21218. NR 18 TC 6 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD JUN PY 1996 VL 5 IS 2 BP 88 EP 97 DI 10.1097/00019606-199606000-00003 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA UM567 UT WOS:A1996UM56700003 PM 8727095 ER PT J AU Silverman, K Wong, CJ Higgins, ST Brooner, RK Montoya, ID Contoreggi, C UmbrichtSchneiter, A Schuster, CR Preston, KL AF Silverman, K Wong, CJ Higgins, ST Brooner, RK Montoya, ID Contoreggi, C UmbrichtSchneiter, A Schuster, CR Preston, KL TI Increasing opiate abstinence through voucher-based reinforcement therapy SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE heroin abuse; heroin dependence; drug abuse; intravenous drug abuse; treatment; abstinence reinforcement; contingency management ID METHADONE AB Heroin dependence remains a serious and costly public health problem, even in patients receiving methadone maintenance treatment. This study used a within-subject reversal design to assess the effectiveness of voucher-based abstinence reinforcement in reducing opiate use in patients receiving methadone maintenance treatment in an inner-city program. Throughout the study subjects received standard methadone maintenance treatment involving methadone, counseling, and urine monitoring (three times per week). Thirteen patients who continued to use opiates regularly during a 5-week baseline period were exposed to a 12-week program in which they received a voucher for each opiate-free urine sample provided; the vouchers had monetary values that increased as the number of consecutive opiate-free urines increased. Subjects continued receiving standard methadone maintenance for 8 weeks after discontinuation of the voucher program (return-to-baseline). Tukey's posthoc contrasts showed that the percentage of urine specimens that were positive for opiates decreased significantly when the voucher program was instituted (P less than or equal to 0.01) and then increased significantly when the voucher program was discontinued during the return-to-baseline condition (P less than or equal to 0.01). Rates of opiate positive urines in the return-to-baseline condition remained significantly below the rates observed in the initial baseline period (P less than or equal to 0.01). Overall, the study shows that voucher-based reinforcement contingencies can decrease opiate use in heroin dependent patients receiving methadone maintenance treatment. C1 NIDA,NIH,INTRAMURAL RES PROGRAM,CLIN TRIALS SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD. UNIV VERMONT,DEPT PSYCHIAT,BURLINGTON,VT. UNIV ANTIOQUIA,MEDELLIN,COLOMBIA. WAYNE STATE UNIV,DEPT PSYCHIAT & BEHAV NEUROSCI,DETROIT,MI. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Silverman, Kenneth/0000-0003-2724-1413 FU NIDA NIH HHS [P50 DA09258] NR 27 TC 117 Z9 117 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN PY 1996 VL 41 IS 2 BP 157 EP 165 DI 10.1016/0376-8716(96)01246-X PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA UU083 UT WOS:A1996UU08300009 PM 8809505 ER PT J AU Radko, SP Chrambach, A AF Radko, SP Chrambach, A TI Mechanisms of retardation of rigid spherical particles with 3 to 1,085 nm radius in capillary electrophoresis, using buffered polyacrylamide (molecular weight 5 x 10(6)) solutions SO ELECTROPHORESIS LA English DT Article DE capillary electrophoresis; polymer solution; retardation coefficient; field strength; band width ID GEL-ELECTROPHORESIS; POLYMER-SOLUTIONS; ZONE ELECTROPHORESIS; MOBILITY DATA; DNA; MACROMOLECULES; EFFICIENCY AB Subjecting particles in the size range of 3 to 1085 nm radius (R) to capillary electrophoresis in buffered solution of entangled uncrosslinked polyacrylamide (M(r) 5 x 10(6)), it was found that particle size-dependent retardation (''molecular sieving'') becomes electric field- and particle size range-dependent once the particle size exceeds 15-20 nm in radius. The field strength dependence of the retardation coefficient [K-R = d(log mobility)/d(polymer concentration] and the positive or negative sign of dK(R)/dR suggest the existence of two different mechanisms of molecular sieving depending on the particle size range: particles with diameters less than the screening length (or blob size) of the polymer network are thought to penetrate into the available spaces within a discontinuous polymer network; particles with diameters larger than the screening length (or blob size) of the polymer network are thought to undergo size-dependent retardation by exerting shear stress against polymer chains, and displacing them, so as to cause local deformations in a continuous polymer network. A limit in the separating capacity of molecular sieving, due to a sharp increase in the rate of band widening with polymer concentration, was found when the value of the retardation coefficient exceeded 60 (mL/g). C1 NICHHD,SECT MACROMOL ANAL,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. NR 35 TC 26 Z9 26 U1 0 U2 4 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 1996 VL 17 IS 6 BP 1094 EP 1102 DI 10.1002/elps.1150170619 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UX728 UT WOS:A1996UX72800018 PM 8832177 ER PT J AU Bamberger, CM Schulte, HM Chrousos, GP AF Bamberger, CM Schulte, HM Chrousos, GP TI Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids SO ENDOCRINE REVIEWS LA English DT Review ID STEROID-HORMONE RECEPTORS; MAMMARY-TUMOR VIRUS; HEAT-SHOCK PROTEIN; MEDIATED GENE-EXPRESSION; DNA-BINDING DOMAIN; TRANSCRIPTION FACTORS; NEGATIVE REGULATION; ENHANCER ELEMENTS; RESISTANT PRIMATE; POINT MUTATION C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP Bamberger, CM (reprint author), UNIV HAMBURG,INF INST HORMONE & FERTIL RES,GRANDWEG 64,D-22529 HAMBURG,GERMANY. NR 215 TC 607 Z9 623 U1 5 U2 37 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 1996 VL 17 IS 3 BP 245 EP 261 DI 10.1210/er.17.3.245 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP167 UT WOS:A1996UP16700003 PM 8771358 ER PT J AU Chedid, M Hoyle, JR Csaky, KG Rubin, JS AF Chedid, M Hoyle, JR Csaky, KG Rubin, JS TI Glucocorticoids inhibit keratinocyte growth factor production in primary dermal fibroblasts SO ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; GENE-EXPRESSION; OVALBUMIN GENE; RECEPTOR; REVERSES; KGF AB The participation of growth factors in wound healing and tissue repair has been well established. Previous studies demonstrated that the expression of keratinocyte growth factor (KGF) was greatly elevated shortly after injury and that topical application of KGF accelerated healing. Steroidal antiinflammatory agents, specifically glucocorticoids, markedly impair wound healing. The participation of KGF in wound healing led us to examine the effect of glucocorticoids on KGF production. The addition of dexamethasone significantly reduced the level of constitutively produced KGF messenger RNA, protein, and bioactivity in conditioned medium from dermal fibroblasts. This inhibitory effect was observed with a variety of glucocorticoids, whereas nonsteroidal antiinflammatory compounds had little effect on KGF synthesis. The mechanisms by which dexamethasone decreased KGF production include a combination of a diminished transcriptional Fate and destabilization of the KGF messenger RNA. Cytokines such as interleukin-1 alpha, platelet-derived growth factor-BB, and transforming growth factor-alpha, typically up-regulated during wound healing, augment KGF expression by dermal fibroblasts. We determined that dexamethasone also blocked this inductive effect. These results suggest that glucocorticoids could inhibit KGF production in the setting of wound repair, which may contribute to the impair ment of healing associated with glucocorticoid use. RP Chedid, M (reprint author), NCI, CELLULAR & MOLEC BIOL LAB, BLDG 37, ROOM 1E24, BETHESDA, MD 20892 USA. NR 30 TC 45 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1996 VL 137 IS 6 BP 2232 EP 2237 DI 10.1210/en.137.6.2232 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UM802 UT WOS:A1996UM80200006 PM 8641170 ER PT J AU Voigt, P Ma, YJ Gonzalez, D Fairenbach, WH Wetsel, WC BergVonDerEmde, K Hill, DF Taylor, KG Costa, ME Seidah, NG Ojeda, SR AF Voigt, P Ma, YJ Gonzalez, D Fairenbach, WH Wetsel, WC BergVonDerEmde, K Hill, DF Taylor, KG Costa, ME Seidah, NG Ojeda, SR TI Neural and glial-mediated effects of growth factors acting via tyrosine kinase receptors on luteinizing hormone-releasing hormone neurons SO ENDOCRINOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; IMMORTALIZED HYPOTHALAMIC NEURONS; MESSENGER-RNA; INSITU HYBRIDIZATION; FACTOR-ALPHA; GENE-EXPRESSION; DOPAMINERGIC-NEURONS; MITOGENIC ACTIVITY; PROGENITOR CELLS; RAT HYPOTHALAMUS AB It is becoming increasingly evident that the secretory activity of LHRH neurons is regulated not only by transsynaptic inputs but also by trophic molecules of glial and neuronal origin. The present experiments were undertaken to gain insights into the potential cell-cell mechanisms by which basic fibroblast growth factor (bFGF) and transforming growth factor-alpha (TGF-alpha), two growth factors produced in the hypothalamus, may affect LHRH neuronal function. Northern blot analysis showed that the LHRH-producing cell line GT1-7 contains the messenger RNA (mRNA) encoding the type 1 fibroblast growth factor receptor (FGFR-1) but not that encoding the epidermal growth factor (EGF) receptors, which mediates the biological actions of both TGFalpha and EGF. Ligand-induced receptor phosphorylation experiments demonstrated that GT1-7 cells possess biologically active FGFR-1s but not EGF receptors. Exposure of the cells to bFGF resulted not only in FGFR-1 tyrosine phosphorylation, but also in tyrosine phosphorylation of phospholipase C-gamma, one of the initial enzymes in the intracellular signaling cascade initiated by FGFR activation. GT1-7 cells proliferated in response to this activation. Despite the presence of biologically active receptors, bFGF did not significantly stimulate release of the mature LHRH decapeptide. Instead, bFGF increased the steady-state levels of the mRNA encoding the LHRH precursor processing endoprotease PC2, with a time course comparable to that of phorbol esters, suggesting that, as shown in the companion paper, the actions of the growth factor on LHRH neurons involve facilitation of the initial step in LHRH prohormone processing. The increase in PC2 gene expression was not accompanied by changes in LHRH mRNA levels. Unlike these direct actions of bFGF on GT-1 cells, TGFalpha appears to act indirectly via astroglial intermediacy. Exposure of GT1-7 cells to TGFalpha or EGF failed to affect several parameters of cellular activity including LHRH release, LHRH and PC2 mRNA levels, and cell proliferation. In contrast, astrocyte culture medium conditioned by treatment with TGFalpha led to sustained stimulation of LHRH release with no changes in LHRH gene expression and a transient increase in PC2 mRNA levels. Although no definitive evidence for the presence of FGFR-1 in normal LHRH neurons could be obtained by either double immunohistochemistry or double in situ hybridization procedures, fetal LHRH neurons in primary culture responded to bFGF with neurite outgrowth. Thus, normal LHRH neurons may have an FGFR-1 content too low for detection by regular histochemical procedures, and/or detectable expression of the receptor may be confined to a much earlier developmental stage. The mitogenic effect of bFGF on GT1-7 cells supports this possibility and suggests a role for FGF in the cell proliferation events that precede acquisition of the LHRH neuronal phenotype. It appears that once this phenotype is established, bFGF may promote the differentiation of LHRH neurons. The results also suggest that the secretory capacity of LHRH neurons develops under a dual trophic influence, one on peptide processing exerted directly by bFGF on early neurons, and another on LHRH release, exerted by TGFalpha via the intermediacy of astroglial cells. C1 OREGON REG PRIMATE RES CTR, DIV NEUROSCI, BEAVERTON, OR 97006 USA. INST RECH CLIN MONTREAL, MONTREAL, PQ H2W 1R7, CANADA. NIEHS, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. RI Seidah, Nabil/I-3596-2013 OI Seidah, Nabil/0000-0001-6503-9342 FU NCRR NIH HHS [RR00163]; NICHD NIH HHS [HD-18185, HD-25123] NR 87 TC 64 Z9 65 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1996 VL 137 IS 6 BP 2593 EP 2605 DI 10.1210/en.137.6.2593 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UM802 UT WOS:A1996UM80200050 PM 8641214 ER PT J AU Wetsel, WC Hill, DF Ojeda, SR AF Wetsel, WC Hill, DF Ojeda, SR TI Basic fibroblast growth factor regulates the conversion of pro-luteinizing hormone-releasing hormone (pro-LHRH) to LHRH in immortalized hypothalamic neurons SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; CARBOXYPEPTIDASE-E; GENE-EXPRESSION; FACTOR-ALPHA; FACTOR-I; SECRETION; RAT; ACTIVATION; CELLS; RECEPTOR AB Growth factors are commonly associated with the regulation of cellular proliferation and differentiation. In established cells, growth factors can also serve as trophic agents. Immortalized LHRH neurons contain basic fibroblast growth factor (bFGF) receptors. Although these receptors are coupled to activation of protein kinase C, and phorbol esters are strong activators of protein kinase C-stimulated LHRH release. bFGF did not influence LHRH secretion from these cells. To clarify this discrepancy, the effects of bFGF and phorbol ester on pro-LHRH biosynthesis, protein processing, and secretion were examined in GT1-7 cells. Phorbol ester stimulated LHRH secretion, whereas bFGF either had no effect or stimulated LHRH release depending upon the antiserum used. Pro-LHRH levels in lysate and medium were depressed by phorbol esters; concentrations in bFGF-treated cells were somewhat lower than those in unstimulated controls. HPLC analyses revealed that both agents enhanced the release of LHRH intermediate products into the medium. C-Terminally extended forms of LHRH, especially LHRH-[Gly(11)], were prominent in medium from bFGF-stimulated neurons. Levels of LHRH were depressed relative to those in the control or phorbol ester groups. These data indicate that phorbol esters control the biosynthesis, secretion, and, to some extent, processing of pro-LHRH. The effects of bFGF are novel because this factor regulates processing of the prohormone so that LHRH-intermediate products are predominantly secreted instead of LHRH. By enhancing the secretion of these intermediates over that of LHRH, bFGF can control the biological activity of the decapeptide and regulate LHRH neuronal function. C1 OREGON REG PRIMATE RES CTR, DIV NEUROSCI, BEAVERTON, OR 97006 USA. RP Wetsel, WC (reprint author), NIEHS, CELLULAR & MOLEC PHARMACOL LAB, HORMONE ACT WORKGRP, BLDG 19-03, POB 12233, RES TRIANGLE PK, NC 27709 USA. FU NCRR NIH HHS [RR-00163]; NICHD NIH HHS [HD-25123, HD-18185] NR 45 TC 35 Z9 36 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1996 VL 137 IS 6 BP 2606 EP 2616 DI 10.1210/en.137.6.2606 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UM802 UT WOS:A1996UM80200051 PM 8641215 ER PT J AU Martinez, A Weaver, C Lopez, J Bhathena, SJ Elsasser, TH Miller, MJ Moody, TW Unsworth, EJ Cuttitta, F AF Martinez, A Weaver, C Lopez, J Bhathena, SJ Elsasser, TH Miller, MJ Moody, TW Unsworth, EJ Cuttitta, F TI Regulation of insulin secretion and blood glucose metabolism by adrenomedullin SO ENDOCRINOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; GASTRIN-RELEASING PEPTIDE; ISLET AMYLOID POLYPEPTIDE; CELL LUNG-CANCER; HYPOTENSIVE PEPTIDE; ENDOCRINE PANCREAS; ENZYMES PAM; RAT; LOCALIZATION; CLONING AB Adrenomedullin (AM), a recently discovered hypotensive peptide, is expressed in the endocrine pancreas of different species, as demonstrated by immunocytochemistry. Electron microscopic studies with double immunogold showed colocalization of AM and pancreatic polypeptide. A homogeneous expression of AM receptor was found throughout the islet using in situ hybridization. Six different insulin producing cell lines have been analyzed by reverse transcription-PCR and showed expression of both AM and its receptor. Two experimental models have been used to study the effects of AM in pancreatic physiology. 1) Analysis of isolated rat islets shows that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was able to increase insulin release B-fold; this effect was reversed by the addition of synthetic AM. 2) Oral glucose tolerance tests showed that iv injection of AM reduces the levels of insulin in the bloodstream with a concomitant increase in circulating glucose. These studies implicate AM as a newly defined actor of the insulin regulatory system that could hi involved in disorders such as diabetes and obesity. C1 FU JEN CATHOLIC UNIV, COLL MED, TAIPEI, TAIWAN. UNIV AUTONOMA MADRID, DEPT BIOL, MADRID, SPAIN. USDA ARS, BELTSVILLE, MD 20705 USA. RP Martinez, A (reprint author), NCI, BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,NIH, 9610 MED CTR DR, ROOM 300, ROCKVILLE, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 42 TC 139 Z9 143 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1996 VL 137 IS 6 BP 2626 EP 2632 DI 10.1210/en.137.6.2626 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UM802 UT WOS:A1996UM80200053 PM 8641217 ER PT J AU Carter, DE Pena, C Varady, R Suk, WA AF Carter, DE Pena, C Varady, R Suk, WA TI Environmental health and hazardous waste issues related to the US-Mexico border SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article AB Environmental health and environmental quality issues along the U.S.-Mexico border have been of concern for several years. The enactment of the North American Free Trade Agreement and the presence of the maquiladoras (foreign-owned industries using imported raw materials) have intensified those concerns recently. Efforts to assess these issues are complicated by the fact that many of the issues affecting the border region are within federal jurisdiction, but the problems are regional and local in nature. Thus, state and local governments become involved with public concerns about real and potential problems. One major problem is that environmental health data from this region are lacking, particularly from Mexico. Some new agencies such as the Border Environment Cooperation Commission, the United States-Mexico Border Health Commission, and the North American Commission on Environmental Cooperation have joined several existing agencies at the federal and state level to address environmental quality and health. Several studies have been initiated to determine air and water quality, but little is being done in the areas of hazardous waste and health assessment. Several problems are anticipated in the generation of such data, such as its format and accessibility. Data gaps and research needs are discussed. C1 UNIV ARIZONA,UDALL CTR STUDIES PUBL POLICY,TUCSON,AZ 85721. NIEHS,RES TRIANGLE PK,NC 27709. RP Carter, DE (reprint author), UNIV ARIZONA,COLL PHARM,DEPT PHARMACOL TOXICOL,1703 E MABEL,POB 210207,TUCSON,AZ 85721, USA. OI Varady, Robert/0000-0002-3521-9649 NR 9 TC 14 Z9 14 U1 1 U2 6 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1996 VL 104 IS 6 BP 590 EP 594 DI 10.2307/3433077 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UT985 UT WOS:A1996UT98500003 PM 8793340 ER PT J AU Gaillard, WD Zeffiro, T Fazilat, S DeCarli, C Theodore, WH AF Gaillard, WD Zeffiro, T Fazilat, S DeCarli, C Theodore, WH TI Effect of valproate on cerebral metabolism and blood flow: An F-18-2-deoxyglusose and O-15 water positron emission tomography study SO EPILEPSIA LA English DT Article DE valproate; positron emission tomography; cerebral blood flow; cerebral metabolism ID CULTURED MAMMALIAN NEURONS; PETIT-MAL ANTICONVULSANTS; GLUCOSE-METABOLISM; SODIUM VALPROATE; THALAMIC NEURONS; POTASSIUM CONDUCTANCE; ANTIEPILEPTIC DRUGS; CALCIUM CURRENT; ACID; CARBAMAZEPINE AB We compared the effect of valproate (VPA) on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF), measured with F-18-2-deoxyglucose ((18)FDG) and O-15 water positron emission tomography (PET), in 10 normal volunteers. Mean VPA dose was 17.7 mg/kg, and mean VPA level was 82.1 mg/L (+/-16.5) for 4 weeks. VPA reduced global CMRGlc by 9.4% (9.60 +/- 0.76 vs. 8.59 +/- 1.02 mg Glc/min/100 g, p < 0.05) and regionally in all anatomic areas (p < 0.05 for 11 of 26 areas), VPA diminished global CBF by 14.9% (56.55 +/- 6.70 vs. 47.48 +/- 4.42 ml/min/100 g, p < 0.002) and regionally in all anatomic areas (p < 0.05 for 12 of 26 areas). No significant correlation was noted between VPA level and either global CMRGlc or CBF. The effect of VPA on global CMRGlc is similar to that of carbamazepine (CBZ) and phenytoin but less than that of phenobarbital, valium, or combination therapy with VPA and CBZ. VPA reduced regional CBF (rCBF) but not CMRGlc in the thalamus, an effect that may be associated with VPA's mechanism of action against generalized seizures. C1 NINCDS,EPILEPSY RES BRANCH,NIH,BETHESDA,MD. NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. RI DeCarli, Charles/B-5541-2009 NR 54 TC 82 Z9 82 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 1996 VL 37 IS 6 BP 515 EP 521 DI 10.1111/j.1528-1157.1996.tb00602.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA UN420 UT WOS:A1996UN42000002 PM 8641226 ER PT J AU Kirkby, RD Forbes, RA Subramaniam, S AF Kirkby, RD Forbes, RA Subramaniam, S TI Modification of kainate-induced behavioral and electrographic seizures following inhibition of nitric oxide synthase in mice SO EPILEPSY RESEARCH LA English DT Article DE limbic; frontal cortex; reticular formation; audiogenic seizure; tectum; pons; NMDA ID DEEP PREPIRIFORM CORTEX; ACID-INDUCED SEIZURES; NMDA RECEPTORS; KAINIC ACID; NO SYNTHASE; RATS; EPILEPSY; POTENTIATION; MOUSE AB We assessed the effects of N-omega-nitro-L-arginine-methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on behavioral and electrographic seizures elicited in mice by convulsant doses of kainate. In Expt. 1, L-NAME dose-dependently potentiated the convulsant effects of kainate (44 mg/kg s.c.), transforming long-latency clonic convulsions into short-latency fits of wild-running, and increased the incidence of kainate-induced mortality. The proconvulsant effects of L-NAME (5 mg/kg i.p.) did not reflect shortened latency to kainate-induced epileptiform afterdischarge recorded via electrodes chronically implanted into the hippocampus, amygdala, frontal cortex or mesencephalic reticular formation (Expt. 2). We also observed a dramatic uncoupling of behavioral and electrographic seizures in mice treated with L-NAME 30 min prior to kainate: 4/6 mice treated with L-NAME failed to express afterdischarge from any of the sites assessed during fits of wild-running. The proconvulsant effects of L-NAME were dependent on the route of administration of kainate, as the inhibitor of NOS failed to alter behavioral (clonic) or electrographic seizures elicited by intrahippocampal kainate (1 nmol, Expt. 3) yet shortened latency to fits of wild-running following i.c.v. kainate (1 nmol, Expt. 4) and reduced the dose of systemic kainate required for either clonic convulsions or wild-running (Expt. 5), The observations that L-NAME potentiates kainate-induced wild-running but not necessarily clonus suggest the involvement of tectopontine mechanisms. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT ANESTHESIOL,BETHESDA,MD 20810. RP Kirkby, RD (reprint author), NINCDS,NEURONAL EXCITABIL SECT,EPIDEMIOL RES BRANCH,NIH,10-5C205,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JUN PY 1996 VL 24 IS 2 BP 79 EP 90 DI 10.1016/0920-1211(96)00003-4 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA UR508 UT WOS:A1996UR50800003 PM 8796356 ER PT J AU Kirkby, RD Carroll, DM Grossman, AB Subramaniam, S AF Kirkby, RD Carroll, DM Grossman, AB Subramaniam, S TI Factors determining proconvulsant and anticonvulsant effects of inhibitors of nitric oxide synthase in rodents SO EPILEPSY RESEARCH LA English DT Article DE kainate; picrotoxin; GABA; strain difference; 7-nitroindozole; N omega-nitroarginine-L-methyl ester; seizure ID DEEP PREPIRIFORM CORTEX; ARGININE METHYL-ESTER; ACID-INDUCED SEIZURES; NMDA RECEPTORS; NO SYNTHASE; POTENTIATION; RATS AB Although a majority of studies suggest that inhibitors of nitric oxide synthase (NOS) are proconvulsant, a substantial minority indicate the opposite (i.e. that inhibitors of NOS are anticonvulsant). As a consequence, the role of endogenous nitric oxide (NO) in the expression of seizures is unclear. In the present series of experiments, we therefore assessed factors governing pro- and anticonvulsant effects of inhibitors of NOS. In mice receiving systemic injections of kainate or picrotoxin, we confirmed the hypothesis that the effects of inhibitors of NOS vary with the model of seizure: Whereas 7-nitroindazole (7-NI) reduced the latency and increased the severity of kainate-induced convulsions (Expt. 1), both 7-NI and N-omega-nitro-L-arginine methyl ester (L-NAME) slightly delayed clonus following the systemic administration of picrotoxin at doses greater than or equal to 3.5 mg/kg but not at doses less than or equal to 3.0 mg/kg (Expts. 2-5). Paradoxically, L-NAME but not 7-NI significantly reduced the CD50 of picrotoxin, which was approximately 2 mg/kg in control mice (Expt. 4), revealing inhibitor-specific interactions with the dose of the convulsant. Finally, we determined in rats that the effects of L-NAME on kainate-induced seizures vary as a function of genetic factors: L-NAME significantly potentiated kainate-induced convulsions in Sprague-Dawley rats but not in Wistar rats (Expt. 6). RP Kirkby, RD (reprint author), NINCDS,NEURONAL EXCITABIL SECT,EPILEPSY RES BRANCH,NIH,BLDG 10-5C205,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 63 Z9 63 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JUN PY 1996 VL 24 IS 2 BP 91 EP 100 DI 10.1016/0920-1211(96)00005-8 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA UR508 UT WOS:A1996UR50800004 PM 8796357 ER PT J AU Umar, A Kunkel, TA AF Umar, A Kunkel, TA TI DNA-replication fidelity, mismatch repair and genome instability in cancer cells SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Review DE DNA-replication fidelity; mismatch repair; genome instability; mutator phenotype; cancer ID ESCHERICHIA-COLI; LAGGING-STRAND; MUTATION; EXTRACTS; MISALIGNMENT; PROBABILITY; ERRORS AB It has been suggested that an early event in the multistep progression of a normal cell to a tumor eel could be a defect that leads to an elevated mutation rate, thus providing a pool of mutants upon which selection could act to yield a tumor. Such a mutator phenotype could result from a defect in any of several DNA transactions, including those that determine the DNA replication error rate or the ability to correct replication errors. Recent evidence for the latter is the mutator phenotype observed in tumor cells of patients having a hereditary form of colon cancer. These patients have a germline mutation in genes required for post-replication DNA mismatch repair. A second mutation arises somatically, yielding a greatly elevated mutation rate due to an inability to correct DNA replication errors. This connection between cancer, DNA replication errors and defective mismatch repair is the subject of this review: wherein we consider the key steps and principles for high fidelity replication and how their perturbation results in genome instability. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 81 TC 187 Z9 190 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUN 1 PY 1996 VL 238 IS 2 BP 297 EP 307 DI 10.1111/j.1432-1033.1996.0297z.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ814 UT WOS:A1996UQ81400001 PM 8681938 ER PT J AU Baudard, M Pastan, I Gottesman, MM AF Baudard, M Pastan, I Gottesman, MM TI Transfer of the MDR1 gene into haematopoietic cells SO EUROPEAN JOURNAL OF CANCER LA English DT Article ID MULTIDRUG-RESISTANCE GENE; HEMATOPOIETIC STEM-CELLS; BONE-MARROW CELLS; DRUG-RESISTANCE; TRANSGENIC MICE; PERIPHERAL-BLOOD; P-GLYCOPROTEIN; EXPRESSION; PHENOTYPE; CHEMOTHERAPY C1 HOP HOTEL DIEU,SERV HEMATOL,F-75004 PARIS,FRANCE. NCI,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. RP Baudard, M (reprint author), NCI,CELL BIOL LAB,NIH,BLDG 37,ROOM 1B23,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 52 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUN PY 1996 VL 32A IS 6 BP 1019 EP 1023 DI 10.1016/0959-8049(96)00064-0 PG 5 WC Oncology SC Oncology GA UT296 UT WOS:A1996UT29600013 PM 8763343 ER PT J AU Tuscano, JM Engel, P Tedder, TF Agarwal, A Kehrl, JH AF Tuscano, JM Engel, P Tedder, TF Agarwal, A Kehrl, JH TI Involvement of p72syk kinase, p53/56lyn kinase and phosphatidyl inositol-3 kinase in signal transduction via the human B lymphocyte antigen CD22 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD22; p72syk; p53/56lyn; phosphatidyl inositol-3 kinase ID PROTEIN-TYROSINE KINASES; RECEPTOR ZETA-CHAIN; T-CELL; ADHESION MOLECULE; ACTIVATION; ASSOCIATION; COMPLEX; IDENTIFICATION; STIMULATION; INTERACTS AB CD22 is a B lymphocyte-specific membrane protein that functions as an adhesion molecule via its interactions with a subset of alpha 2-6-linked sialic acid-containing glycoproteins. Engagement of CD22 with a monoclonal antibody (HB22.23) that blocks the binding of CD22 to its ligands results in rapid CD22 tyrosine phosphorylation and in increased association of CD22 with p53/56lyn kinase, p85 phosphatidyl inositol-3 kinase, and p72syk kinase. Synthetic peptides that span various regions of the intracellular portion of CD22 were used to map potential kinase binding sites. All three kinases associated with a tyrosine-phosphorylated peptide that spans tyrosine amino acid residues 822 and 842, implicating this as an important region in mediating CD22 signal transduction. In addition, purified p56lyn directly bound to the same peptide. Engagement of CD22 with HB22.23 was sufficient to stimulate normal B cell proliferation. This study further substantiates the importance of CD22 as a B lymphocyte signaling molecule and begins to unravel the mechanisms by which CD22 cross-linking can alter B cell function. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27706. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 45 TC 70 Z9 71 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1996 VL 26 IS 6 BP 1246 EP 1252 DI 10.1002/eji.1830260610 PG 7 WC Immunology SC Immunology GA UQ062 UT WOS:A1996UQ06200009 PM 8647200 ER PT J AU Wessels, H Lamb, ME Hwang, CP AF Wessels, H Lamb, ME Hwang, CP TI Cause and causality in daycare research: An investigation of group differences in Swedish child care SO EUROPEAN JOURNAL OF PSYCHOLOGY OF EDUCATION LA English DT Article DE causal explanation; day care; longitudinal studies; multivariate analysis ID PRESCHOOLERS; DETERMINANTS AB One of the most important goals of child care research has been to determine whether or not nonparental care has adverse effects on child development. Answering this question involves making causal attributions about the origins of differences between groups of children who have experienced divergent nonparental care arrangements. Some of the problems researchers face when trying to demonstrate causal relationships are illustrated in this paper using data from the Goteborg Child Care Study, a comprehensive, prospective, longitudinal study comparing the developmental trajectories of children in exclusive home care, family daycare, and center daycare. It is argued that the discovery of significant differences between groups must initiate extensive efforts to validate and interpret the findings. Focusing on the specific characteristics of prospective longitudinal studies, the article shows what measures can be taken to avoid the misinterpretation of group differences that are actually attributable to pre-selection effects or confounding variables. By rigorously identifying such confounds, researchers can accumulate support for hypothesized causal relationships, but they cannot 'prove' them because unknown and unmeasured confounding variables may always have important effects. C1 UNIV GOTHENBURG,DEPT PSYCHOL,S-40020 GOTHENBURG,SWEDEN. RP Wessels, H (reprint author), NICHHD,SECT SOCIAL & EMOT DEV,9190 ROCKVILLE PIKE,BETHESDA,MD 20850, USA. NR 38 TC 0 Z9 0 U1 0 U2 1 PU INST SUPERIOR PSICOLOGIA APLICADA PI LISBOA PA RUA JARDIM DO TABACO, 44, LISBOA 1100, PORTUGAL SN 0256-2928 J9 EUR J PSYCHOL EDUC JI Eur. J. Psychol. Educ. PD JUN PY 1996 VL 11 IS 2 BP 231 EP 245 PG 15 WC Psychology, Educational SC Psychology GA UR987 UT WOS:A1996UR98700011 ER PT J AU McGraw, SA Sellers, DE Stone, EJ Bebchuk, J Edmundson, EW Johnson, CC Bachman, KJ Luepker, RV AF McGraw, SA Sellers, DE Stone, EJ Bebchuk, J Edmundson, EW Johnson, CC Bachman, KJ Luepker, RV TI Using process data to explain outcomes - An illustration from the child and adolescent trial for cardiovascular health (CATCH) SO EVALUATION REVIEW LA English DT Article ID PROMOTION PROGRAMS; PREVENTION AB The purpose of this article is to illustrate the use of process evaluation for understanding study outcomes. Data from the Child and Adolescent Trial for Cardiovascular Health (CATCH), a large school-based field trial, are used. Teacher characteristics, measures of classroom curriculum implementation, and competing influences are linked to changes in dietary knowledge, intentions, and self-efficacy of students in the intervention schools. Multiple regression analyses indicate that teacher characteristics did not predict program implementation. Teacher characteristics and program fidelity, or the number of modifications made to the classroom curriculum during implementation, had direct and independent effects on student outcomes. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV TEXAS,AUSTIN,TX 78712. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. UNIV CALIF SAN DIEGO,SCH MED,SAN DIEGO,CA 92103. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. RP McGraw, SA (reprint author), NEW ENGLAND RES INST,9 GALEN ST,WATERTOWN,MA 02172, USA. FU NHLBI NIH HHS [U01-HL-39852, U01-HL-39880, U01-HL-39906] NR 31 TC 42 Z9 42 U1 2 U2 2 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0193-841X J9 EVALUATION REV JI Eval. Rev. PD JUN PY 1996 VL 20 IS 3 BP 291 EP 312 DI 10.1177/0193841X9602000304 PG 22 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA UR273 UT WOS:A1996UR27300004 PM 10182206 ER PT J AU Kirkman, LA Su, XZ Wellems, TE AF Kirkman, LA Su, XZ Wellems, TE TI Plasmodium falciparum isolation of large numbers of parasite clones from infected blood samples SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID GENETIC DIVERSITY; MALARIA PARASITES; EASTERN SUDAN; SENSITIVITY; RESISTANCE; PROTEINS; VILLAGE; CLONING; CROSS RP Kirkman, LA (reprint author), NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892, USA. OI Su, Xinzhuan/0000-0003-3246-3248 NR 19 TC 27 Z9 28 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUN PY 1996 VL 83 IS 1 BP 147 EP 149 DI 10.1006/expr.1996.0058 PG 3 WC Parasitology SC Parasitology GA UT265 UT WOS:A1996UT26500016 PM 8654543 ER PT J AU Cara, A Cereseto, A Fiorentini, S Gusella, L Reitz, MS AF Cara, A Cereseto, A Fiorentini, S Gusella, L Reitz, MS TI Low levels of reverse transcriptase associated with one integrase defective mutant of HIV-1 SO FUNDAMENTAL AND CLINICAL IMMUNOLOGY LA English DT Article DE HIV-1; integrase; protease; reverse transcriptase ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRODUCTIVE INFECTION; VIRAL REPLICATION; GENE-EXPRESSION; PROTEIN; MUTATIONS; DNA; MACROPHAGES; INVITRO; DOMAINS AB We have analyzed the importance of the integrase (IN) protein of the human immunodeficiency virus (HIV-1) in stages of viral replication other than integration of the reverse transcribed viral genome. After transient transfection into Heta-Tat cells of a plasmid containing an IN defective HIV-1 provirus, pLW/INT-, the levels of virus-associated reverse transcriptase (RT) activity and protein recovered in the supernatant were constantly lower than those of the parental wild-type plasmid pLW/C. The amount of cell-associated RT, however, was higher after transfection of pLW/INT- compared to the wild-type. In contrast to the results obtained with RT, similar amounts of p24 and gp120(env) proteins from both the wild-type and the IN defective viruses were present in both the supernatant and associated with cells. Pulse-chase experiments indicated that the p55(gag) precursor was cleaved faster in HeLa-Tat cells transfected with pLW/INT- compared to pLW/C. These data suggest that truncation of the IN protein affects the efficiency of proteolytic processing of the viral protease and indicate the importance of the IN protein for proper proteolytic processing of the viral protease and indicate the importance of the IN protein for proper proteolytic processing (Fund. Clin. Immunol. 4: 61-66, 1996). C1 IST GIANNINA GASLINI,MOL BIOL LAB,I-16148 GENOA,ITALY. UNIV MARYLAND,INST BIOTECHNOL,BALTIMORE,MD 21201. UNIV MARYLAND,INST HUMAN VIROL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. RP Cara, A (reprint author), NCI,TUMOR CELL BIOL LAB,NIH,BLDG 37,RM 6A09,37 CONVENT DR,BETHESDA,MD 20892, USA. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 21 TC 1 Z9 1 U1 0 U2 0 PU EDI ERMES SRL PI MILAN PA VIALE ENRICO FORLANIN 65, 20134 MILAN, ITALY SN 1122-9438 J9 FUND CLIN IMMUNOL JI Fundam. Clin. Immunol. PD JUN PY 1996 VL 4 IS 2 BP 61 EP 66 PG 6 WC Immunology SC Immunology GA VH183 UT WOS:A1996VH18300002 ER PT J AU Mannen, H Tsoi, SCM Pickford, DB Donald, JA Guillette, LJ Li, SSL AF Mannen, H Tsoi, SCM Pickford, DB Donald, JA Guillette, LJ Li, SSL TI Sequences of the lizard cDNAs encoding lactate dehydrogenase (LDH) isozymes A (muscle) and B (heart) SO GENE LA English DT Article DE protein; gene; phylogenetic tree; reptile ID EVOLUTIONARY IMPLICATIONS; TESTIS AB The nucleotide and deduced amino acid sequences of cDNAs encoding L-lactate dehydrogenase (LDK) isozymes A (muscle) and B (heart) from the lizard, Sceloporus undulatus, were determined. The evolutionary relationships among LDH isozymes from animals, plants and bacteria are presented. C1 NIEHS,GENET LAB,NIH,RES TRIANGLE PK,NC 27709. UNIV FLORIDA,DEPT ZOOL,GAINESVILLE,FL 32611. RI Donald, John/B-4656-2012; Pickford, Daniel/D-5391-2014 OI Donald, John/0000-0001-5930-2642; Pickford, Daniel/0000-0002-5778-4630 NR 8 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 1 PY 1996 VL 171 IS 2 BP 303 EP 304 DI 10.1016/0378-1119(96)00180-1 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UR518 UT WOS:A1996UR51800030 PM 8666293 ER PT J AU Max, SI Chowdhury, BA Fraser, CM AF Max, SI Chowdhury, BA Fraser, CM TI Sequence analysis of the 5'-untranslated region of the human H-1 histamine receptor-encoding gene SO GENE LA English DT Article DE recombinant DNA; polymerase chain reaction; DNA motifs; genomic DNA AB A clone containing the H-1 histamine receptor (H(1)HR)-encoding gene was isolated from a human genomic DNA library. The 5'-UTR of the H(1)HR gene reported here differs upstream from bp - 142 from that reported previously [Fukui et al., Biochem. Biophys. Res. Comm. 201 (1994) 894-901]. PCR amplification utilizing primer pairs derived from the 5'-UTR reported herein amplified a DNA fragment of the expected size from human genomic DNA whereas 5'-UTR primers derived from the Fukui et al. sequence did not yield a PCR product. The 5'-UTR of H(1)HR contains potential TATA and CCAAT boxes, a CACCC sequence, potential GREs and other DNA-binding motifs. C1 INST GENOM RES,DEPT MOLEC & CELLULAR BIOL,ROCKVILLE,MD 20850. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. OI Fraser, Claire/0000-0003-1462-2428 NR 4 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 1 PY 1996 VL 171 IS 2 BP 309 EP 310 DI 10.1016/0378-1119(96)00036-4 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UR518 UT WOS:A1996UR51800033 PM 8666296 ER PT J AU deMedinaceli, L AF deMedinaceli, L TI Statistical analyses and reliability of the sciatic functional index SO GENERAL PHARMACOLOGY LA English DT Letter ID TRACKS C1 IEBM,NANCY,FRANCE. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032. RP deMedinaceli, L (reprint author), CHU NANCY BRABOIS,IEBM,F-54511 NANCY,FRANCE. NR 4 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-3623 J9 GEN PHARMACOL JI Gen. Pharmacol. PD JUN PY 1996 VL 27 IS 4 BP 741 EP 741 DI 10.1016/0306-3623(95)02076-4 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU740 UT WOS:A1996UU74000030 PM 8853313 ER PT J AU Liu, PP Wijmenga, C Hajra, A Blake, TB Kelley, CA Adelstein, RS Bagg, A Rector, J Cotelingam, J Willman, CL Collins, FS AF Liu, PP Wijmenga, C Hajra, A Blake, TB Kelley, CA Adelstein, RS Bagg, A Rector, J Cotelingam, J Willman, CL Collins, FS TI Identification of the chimeric protein product of the CBFB-MYHII fusion gene in Inv(16) leukemia cells SO GENES CHROMOSOMES & CANCER LA English DT Article ID SMOOTH-MUSCLE MYOSIN; ACUTE MYELOMONOCYTIC LEUKEMIA; HEAVY-CHAIN ISOFORMS; ABNORMAL EOSINOPHILS; CDNA CLONING; INVERSION; CHROMOSOME-16; ASSOCIATION; EXPRESSION AB An expressed gene formed by fusion between the CBFB transcription factor gene and the smooth muscle myosin heavy chain gene MYHI I is consistently detected by reverse transcription polymerase chain reaction (RT-PCR) in patients who have acute myeloid leukemia (AML) subtype M4Eo with an inversion of chromosome I Ci, We have previously shown that a CBFB-MYHI I cDNA construct can produce a chimeric protein and transform NIH 3T3 cells. However, the presence of the chimeric protein in patient cells has not been demonstrated previously. Here, we show that such chimeric proteins can be identified in vivo, primarily in the nuclei of the leukemic cells, by use of antibodies against the C-terminus of the smooth muscle myosin heavy chain and the fusion junction peptide. A very high molecular weight protein/DNA complex is generated when nuclear extracts from patient cells are used in electrophoretic mobility shift assays, as seen in NIH 3T3 cells transfected with the CBFB-MYHI I cDNA. Immunofluorescence staining shows that the proteins are organized in vivo into novel structures within cell nuclei, One isoform of the transcript of the CBFB-MYHI I fusion gene, containing the MHC,,, C-terminus, was the predominant form in all five cases studied. (C) 1996 Wiley-Liss, Inc.* C1 NHLBI, NIH, MOLEC CARDIOL LAB, BETHESDA, MD USA. GEORGETOWN UNIV, MED CTR, DEPT PATHOL, WASHINGTON, DC 20007 USA. NATL NAVAL MED CTR, DEPT LAB MED, BETHESDA, MD USA. UNIV NEW MEXICO, SCH MED, DEPT PATHOL, ALBUQUERQUE, NM 87131 USA. RP Liu, PP (reprint author), NIH, LAB GENE TRANSFER,NATL CTR HUMAN GENOME RES, BLDG 49,ROOM 3A18,49 CONVENT DR, MSC 4470, BETHESDA, MD 20892 USA. RI Liu, Paul/A-7976-2012; Wijmenga, Cisca/D-2173-2009; OI Liu, Paul/0000-0002-6779-025X; Adelstein, Robert/0000-0002-8683-2144 FU NCI NIH HHS [CA63102] NR 38 TC 42 Z9 44 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 1996 VL 16 IS 2 BP 77 EP 87 DI 10.1002/(SICI)1098-2264(199606)16:2<77::AID-GCC1>3.0.CO;2-# PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UV196 UT WOS:A1996UV19600001 PM 8818654 ER PT J AU Ma, WP Crouch, RJ AF Ma, WP Crouch, RJ TI Escherichia coli RNase HI inhibits murine leukaemia virus reverse transcription in vitro and yeast retrotransposon Ty1 transposition in vivo SO GENES TO CELLS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKEMIA-VIRUS; RIBONUCLEASE-H; ELEMENT TRANSPOSITION; NUCLEOTIDE-SEQUENCE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; TEMPLATE BINDING; DNA; PARTICLES AB Background: Reverse transcription, which converts an RNA genome into double-stranded DNA, requires both the polymerase and RNase H activities of reverse transcriptase (RT). In vitro, poorly processive RT dissociates from partially copied RNA-DNA hybrids, that are usually extended by a second RT molecule, Despite similar structures, RNase HI of Escherichia coli can degrade RNA-DNA hybrids that are resistant to RNase H of RT. E. coli RNase HI is used to determine the accessibility to and requirement for RNA-DNA hybrids in reverse transcription in vivo and in vitro. Results: In the presence of E. coli RNase HI, reverse transcription yields incomplete cDNA molecules due to degradation of RNA-DNA hybrids, Delivery of E. coli RNase HI to Ty1 particles via fusion to the capsid protein can reduce retrotransposition by more than 99%, also indicating inhibition of DNA synthesis in vivo. Conclusion: Inhibition of both reverse transcription in vitro and retrotransposition in vivo by E. coli RNase HI indicates that the poor processivity of RT exposes RNA-DNA hybrids critical for reverse transcription to degradation, Targeting a cellular RNase H to HIV may help define the site(s) of RNA-DNA hybrids that are susceptible to nonretroviral RNase H and may be useful for gene therapy to inhibit retroviral replication. C1 NICHHD, NIH, GENET MOL LAB, BETHESDA, MD 20892 USA. NR 39 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-9597 EI 1365-2443 J9 GENES CELLS JI Genes Cells PD JUN PY 1996 VL 1 IS 6 BP 581 EP 593 DI 10.1046/j.1365-2443.1996.d01-265.x PG 13 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VC847 UT WOS:A1996VC84700008 PM 9078387 ER PT J AU Porter, G Westmoreland, J Priebe, S Resnick, MA AF Porter, G Westmoreland, J Priebe, S Resnick, MA TI Homologous and homeologous intermolecular gene conversion are not differentially affected by mutations in the DNA damage or the mismatch repair genes RAD1, RAD50, RAD51, RAD52, RAD54, PMS1 and MSH2 SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAK; SPONTANEOUS MITOTIC RECOMBINATION; SACCHAROMYCES-CEREVISIAE; ECTOPIC RECOMBINATION; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; SHUTTLE VECTORS; YEAST; CHROMOSOME; PROTEIN AB Mismatch repair (MMR) genes or genes involved in both DNA damage repair and homologous recombination might affect homeologous vs. homologous recombination differentially. Spontaneous mitotic gene conversion between a chromosome and a homologous or homeologous donor sequence (14% diverged) on a single copy plasmid was examined in wild-type Saccharomyces cerevisiae strains and in MMR or DNA damage repair mutants. Homologous recombination in rad51, rad52 and rad54 mutants was considerably reduced, while there was little effect of rad1, rad50, pms1 and msh2 null mutations. DNA divergence resulted in no differential effect on recombination rates in the wild type or the mutants; there was only a five- to 10-fold reduction in homeologous relative to homologous recombination regardless of background. Since DNA divergence is known to affect recombination in some systems, we propose that differences in the role of MMR depends on the mode of recombination and/or the level of divergence. Based on analysis of the recombination breakpoints, there is a minimum of three homologous bases required at a recombination junction. A comparison of Rad(+) vs. rad52 strains revealed that while all conversion tracts are continuous, elimination of RAD52 leads to the appearance of a novel class of very short conversion tracts. C1 NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. NR 67 TC 35 Z9 35 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 1996 VL 143 IS 2 BP 755 EP 767 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA UN684 UT WOS:A1996UN68400012 PM 8725224 ER PT J AU Ayyagari, R Nestorowicz, A Li, Y Chandrasekharappa, S Chinault, C vanTuinen, P Smith, RJH Hejtmancik, JF Permutt, MA AF Ayyagari, R Nestorowicz, A Li, Y Chandrasekharappa, S Chinault, C vanTuinen, P Smith, RJH Hejtmancik, JF Permutt, MA TI Construction of a YAC contig encompassing the Usher syndrome type 1C and familial hyperinsulinism loci on chromosome 11p14-15.1 SO GENOME RESEARCH LA English DT Article ID PHYSICAL MAP; HUMAN GENOME; LIBRARY; LINKAGE; GENES; HYBRIDS; REGION AB The Usher syndrome type 1C (USH1C) and familial hyperinsulinism (HI) loci have been assigned to chromosome 11p14-15.1, within the interval D11S419-D1151310. We have constructed a yeast artificial chromosome (YAC) contig, extending from D11S926 to D11S899, which encompasses the critical regions for both USH1C and HI and spans an estimated genetic distance of approximate to 4 cM. A minimal set of six YAC clones constitute the contig, with another 22 YACs confirming the order of sequence-tagged sites (STSs) and position of YACs on the contig. A total of 40 STSs, including 10 new STSs generated from YAC insert-end sequences and inter-Alu PCR products, were used to order the clones within the contig. This physical map provides a resource for identification of gene transcripts associated with USH1C, HI, and otter genetic disorders that map to the D11S926-D11S899 interval. C1 WASHINGTON UNIV,SCH MED,DIV ENDOCRINOL & METAB,ST LOUIS,MO 63110. NEI,NIH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. BAYLOR COLL MED,CTR HUMAN GENOME,HOUSTON,TX 77030. MED COLL WISCONSIN,PATHOL & CYTOGENET LAB,MILWAUKEE,WI 53226. UNIV IOWA,DEPT OTOLARYNGOL HEAD & NECK SURG,IOWA CITY,IA 52242. FU NIDCD NIH HHS [R01-DC02046]; NIDDK NIH HHS [DK16746] NR 45 TC 18 Z9 18 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JUN PY 1996 VL 6 IS 6 BP 504 EP 514 DI 10.1101/gr.6.6.504 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UQ899 UT WOS:A1996UQ89900004 PM 8828039 ER PT J AU Mock, BA Connelly, MA McBride, OW Kozak, CA Marcu, KB AF Mock, BA Connelly, MA McBride, OW Kozak, CA Marcu, KB TI Plasmacytoma-associated neuronal glycoprotein, Pang, maps to mouse chromosome 6 and human chromosome 3 SO GENOMICS LA English DT Article ID GENES; LOCALIZATION AB A new member of the immunoglobulin/fibronectin superfamily of adhesion molecules, Pang (plasmacytoma-associated neuronal glycoprotein), was recently isolated from a plasmacytoma. In previous studies, Pang was found to be normally expressed in the brain and ectopically activated by intracisternal A-type particle long terminal repeats in plasmacytomas. In this study, Pang was initially mapped to mouse Chr 6 by somatic cell hybrid analysis and further positioned on the chromosome between Wnt7a and Pcp1. Southern blot analysis of human-rodent somatic cell hybrids together with predictions from the mouse map location indicate that human PANG is located at 3p26. (C) 1996 Academic Press, Inc. C1 NCI,NIH,BIOCHEM LAB,BETHESDA,MD 20892. NIAID,NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT BIOCHEM & CELL BIOL,STONY BROOK,NY 11794. RP Mock, BA (reprint author), NCI,NIH,GENET LAB,BLDG 37,ROOM 2B-08,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA 36246, N01-CB-21075] NR 13 TC 4 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1996 VL 34 IS 2 BP 226 EP 228 DI 10.1006/geno.1996.0271 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UP846 UT WOS:A1996UP84600012 PM 8661054 ER PT J AU Naruse, K Ueno, M Satoh, T Nomiyama, H Tei, H Takeda, M Ledbetter, DH VanCoillie, E Opdenakker, G Gunge, N Sakaki, Y Iio, M Miura, R AF Naruse, K Ueno, M Satoh, T Nomiyama, H Tei, H Takeda, M Ledbetter, DH VanCoillie, E Opdenakker, G Gunge, N Sakaki, Y Iio, M Miura, R TI A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2 SO GENOMICS LA English DT Article ID FAMILY; EXPRESSION; CYTOKINES AB CC chemokines are cytokines that attract and activate leukocytes. The human genes for the CC chemokines are clustered on chromosome 17. To elucidate the genomic organization of the CC chemokine genes, we constructed a YAC contig comprising 34 clones. The contig was shown to contain all 10 CC chemokine genes reported so far, except for one gene whose nucleotide sequence is not available. The contig also contains 4 CC chemokine-like genes, which were deposited in GenBank as ESTs and are here referred to as NCC-1, NCC-2, NCC-3, and NCC-4. Within the contig, the CC chemokine genes were localized in two regions. In addition, the CC chemokine genes were more precisely mapped on chromosome 17q11.2 using a somatic cell hybrid cell DNA panel containing various portions of human chromosome 17. Interestingly, a reciprocal translocation t(Y; 17) breakpoint, contained in the hybrid cell line Y1741, lay between the two chromosome 17 chemokine gene regions covered by our YAC contig. From these results, the order and the orientation of CC chemokine genes on chromosome 17 were determined as follows: centromere-neurofibromatosis 1-(MCP-3, MCP-1, NCC-1, I-309)-Y1741 breakpoint-RANTES-(LD78 gamma, AT744.2, LD78 beta)-(NCC-3, NCC-2, AT744.1, LD78 alpha)-NCC-4-retinoic acid receptor alpha-telomere. (C) 1996 Academic Press, Inc. C1 KUMAMOTO UNIV,SCH MED,DEPT BIOCHEM,KUMAMOTO 860,JAPAN. PREFECTURAL UNIV KUMAMOTO,FAC HUMAN LIFE SCI,DEPT FOOD SCI & NUTR,KUMAMOTO 862,JAPAN. KUMAMOTO INST TECHNOL,DEPT APPL MICROBIAL TECHNOL,KUMAMOTO 860,JAPAN. UNIV TOKYO,INST MED SCI,CTR HUMAN GENOME,MINATO KU,TOKYO 108,JAPAN. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. RI Nomiyama, Hisayuki/F-2840-2013 OI Nomiyama, Hisayuki/0000-0002-2716-4043 NR 22 TC 94 Z9 96 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1996 VL 34 IS 2 BP 236 EP 240 DI 10.1006/geno.1996.0274 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UP846 UT WOS:A1996UP84600015 PM 8661057 ER PT J AU Kimmelman, AC Ross, DA Liang, BC AF Kimmelman, AC Ross, DA Liang, BC TI Loss of heterozygosity of chromosome 10p in human gliomas SO GENOMICS LA English DT Article ID GLIOBLASTOMA-MULTIFORME AB Molecular loss of heterozygosity studies on human gliomas have shown several regions on chromosome 10 frequently deleted in higher grade tumors, suggesting that chromosome 10 may contain several tumor suppressor genes. We assessed loss of heterozygosity with microsatellite markers in 20 gliomas, consisting of various grades and containing two chromosome 10 copies. The locus that exhibited the most loss (69%) was the region bordered by D10S249 and D105558 and inclusive of D10S594, with a linkage distance of 3 cM. This region was noted to be deleted in various grades of tumor, including low- and high-grade tumors. These results suggest that chromosome region 10p15 is involved in human gliomas of diverse grades and that this region may harbor genes important in the development of and progression to the malignant phenotype. (C) 1996 Academic Press, Inc. C1 NCI,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. UNIV MICHIGAN,MED CTR,DEPT SURG,NEUROSURG SECT,ANN ARBOR,MI 48109. NR 20 TC 47 Z9 47 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1996 VL 34 IS 2 BP 250 EP 254 DI 10.1006/geno.1996.0277 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UP846 UT WOS:A1996UP84600018 PM 8661060 ER PT J AU Bronstein, JM Kozak, CA Chen, XN Wu, S Danciger, M Korenberg, JR Farber, DB AF Bronstein, JM Kozak, CA Chen, XN Wu, S Danciger, M Korenberg, JR Farber, DB TI Chromosomal localization of murine and human oligodendrocyte-specific protein genes SO GENOMICS LA English DT Article ID NERVOUS-SYSTEM; MYELIN; BIOLOGY; VIRUS; MICE AB Oligodendrocyte-specific protein (OSP) is a recently described protein present only in myelin of the central nervous system, Several inherited disorders of myelin are caused by mutations in myelin genes but the etiology of many remain unknown, We mapped the location of the mouse OSP gene to the proximal region of chromosome 3 using two sets of multilocus crosses and to human chromosome 3 using somatic cell hybrids, Fine mapping with fluorescence in situ hybridization placed the OSP gene at human chromosome 3q26.2-q26.3. To date, there are no known inherited neurological disorders that localize to these regions. (C) 1996 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DIV MED GENET,AHMANSON DEPT PEDIAT,CEDARS SINAI RES INST,LOS ANGELES,CA 90024. LOYOLA MARYMOUNT UNIV,LOS ANGELES,CA 90045. NIAID,BETHESDA,MD 20892. RP Bronstein, JM (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,RNRC,710 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. FU NEI NIH HHS [EY08285]; NHGRI NIH HHS [R29 HG00037-06]; NINDS NIH HHS [NS01596] NR 24 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1996 VL 34 IS 2 BP 255 EP 257 DI 10.1006/geno.1996.0278 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UP846 UT WOS:A1996UP84600019 PM 8661061 ER PT J AU Mann, EA Swenson, ES Copeland, NG Gilbert, DJ Jenkins, NA Taguchi, T Testa, JR Giannella, RA AF Mann, EA Swenson, ES Copeland, NG Gilbert, DJ Jenkins, NA Taguchi, T Testa, JR Giannella, RA TI Localization of the guanylyl cyclase C gene to mouse chromosome 6 and human chromosome 12p12 SO GENOMICS LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; HEAT-STABLE ENTEROTOXIN; DNA-SEQUENCES; RECEPTOR C1 UNIV CINCINNATI,COLL MED,VET AFFAIRS MED CTR,DIV DIGEST DIS,CINCINNATI,OH 45220. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. FU NCI NIH HHS [CA-06927] NR 11 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1996 VL 34 IS 2 BP 265 EP 267 DI 10.1006/geno.1996.0284 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UP846 UT WOS:A1996UP84600025 PM 8661067 ER PT J AU Bliss, JM Garon, CF Silver, RP AF Bliss, JM Garon, CF Silver, RP TI Polysialic acid export in Escherichia coli K1: The role of KpsT, the ATP-binding component of an ABC transporter, in chain translocation SO GLYCOBIOLOGY LA English DT Article DE ABC-transporter; dominant negative mutation; Escherichia coli K1; KpsT; polysialic acid ID GENE-CLUSTER; POLYSACCHARIDE ANTIGEN; NUCLEOTIDE-SEQUENCE; NEONATAL MENINGITIS; GROWTH TEMPERATURE; CAPSULAR ANTIGEN; INNER-MEMBRANE; PROTEIN; MUTATIONS; BACTERIA AB The polysialic acid (polySia) capsule of Escherichia coli K1 is a key virulence determinant of the organism, allowing it to evade host defenses, The proteins necessary for expression of the capsule are encoded by the 17 kb kps gene cluster, This cluster contains two genes, kpsM and kpsT, that are required for polySia transport across the cytoplasmic membrane. KpsM is a hydrophobic integral inner membrane protein, while KpsT is a peripheral inner membrane protein that binds ATP. They belong to the ATP-binding cassette (ABC) superfamily of transporters. To study the role of KpsT in polySia translocation, we used PCR mutagenesis to isolate dominant negative mutations of plasmid-encoded kpsT, All mutations mapped to the same glutamic acid residue at position 150, adjacent to Walker motif B of KpsT, Wild-type (kps(+)) cells harboring one such allele, E150G, did not transport polySia to the cell surface but accumulated intracellular polysaccharide and produced small colonies containing cells that grew as long filaments, The E150G protein still bound ATP as shown by 8-azidoATP photolabeling assays, We combined the E150G allele with each of five mutations isolated previously in kpsT, Mutations that disrupt ATP-binding (K44E) or alter regions of the protein thought to interact with KpsM (G84D, S126F) suppressed the dominant negative phenotype while mutations in the C-terminal portion of the protein (C163Y, H181Y) did not suppress. These studies have allowed the development of a working model for the role of KpsT in polySia chain translocation. C1 UNIV ROCHESTER,MED CTR,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642. NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,NIH,HAMILTON,MT 59840. RI Bliss, Joseph/C-7446-2013 FU OHS HRSA HHS [ST32GM07102]; PHS HHS [2T326M07356, A126655] NR 54 TC 38 Z9 38 U1 2 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD JUN PY 1996 VL 6 IS 4 BP 445 EP 452 DI 10.1093/glycob/6.4.445 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX829 UT WOS:A1996UX82900019 PM 8842709 ER PT J AU Reed, E Sarosy, G Kohn, E Christian, M Link, CJ Goldspiel, B Davis, P Jacob, J Maher, M AF Reed, E Sarosy, G Kohn, E Christian, M Link, CJ Goldspiel, B Davis, P Jacob, J Maher, M TI A phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary SO GYNECOLOGIC ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; TAXOL; CISPLATIN; AGENT; TRIAL; CELLS AB We have conducted a disease specific phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary. This was done to take advantage of the cellular and molecular synergism between paclitaxel and DNA-damaging agents, with the hope of avoiding paclitaxel-cisplatin toxicities. Paclitaxel was given as a 24-hr CIVI, after which cyclophosphamide was given as a 60-min infusion. Cycles of therapy were repeated every 3 weeks; and granulocyte colony-simulating factor (G-CSF) was given in a ''flexible'' dosing fashion. Starting doses were 170 mg/m(2) paclitaxel and 750 mg/m(2) cyclophosphamide. Dose-limiting toxicity (DLT) was seen at the doses of 250 mg/m(2) paclitaxel and 1250 mg/m(2) cyclophosphamide. DLT was cumulative thrombocytopenia. There were six nonhematologic grade 3 or 4 toxicities experienced in the study. Eleven of 20 evaluable patients (55%) have achieved an objective response (4 CCR;7 PR). Three of four CCRs were confirmed by negative findings at peritoneoscopy, The median number of prior therapies was 2 (range 1-4) and 17 individuals had platinum-refractory disease. We conclude that paclitaxel followed by cyclophosphamide is an active combination in recurrent ovarian cancer and that further study is needed to determine if this combination is truly better than paclitaxel alone. (C) 1996 Academic Press, Inc. RP Reed, E (reprint author), NCI,CLIN PHARMACOL BRANCH,MED OVARIAN CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 31 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 1996 VL 61 IS 3 BP 349 EP 353 DI 10.1006/gyno.1996.0155 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA UN885 UT WOS:A1996UN88500010 PM 8641614 ER PT J AU Balistreri, WF Grand, R Hoofnagle, JH Suchy, FJ Ryckman, FC Perlmutter, DH Sokol, RJ AF Balistreri, WF Grand, R Hoofnagle, JH Suchy, FJ Ryckman, FC Perlmutter, DH Sokol, RJ TI Biliary atresia: Current concepts and research directions - Summary of a symposium SO HEPATOLOGY LA English DT Editorial Material ID REOVIRUS TYPE-3 INFECTION; HEPATOCYTE GROWTH-FACTOR; INTRAHEPATIC BILE-DUCTS; LEFT-RIGHT ASYMMETRY; LIVER-TRANSPLANTATION; NEONATAL HEPATITIS; TYROSINE KINASE; RAT HEPATOCYTES; RECEPTOR; SURGERY AB Biliary atresia (BA) is the end result of a destructive, inflammatory process that affects intra- and extrahepatic bile duets, leading to fibrosis and obliteration of the biliary tract with the development of biliary cirrhosis. It is the commonest cause of chronic cholestasis in infants and children, and therefore is the most frequent indication for li ver transplantation in this age group. The disease occurs worldwide, affecting an estimated 1 in 8,000 to 12,000 live births. At present, there is no specific therapy for BA; however, sequential surgical therapy begins with creation of a hepatoportoenterostomy (HPE); in those with end-stage liver disease, liver transplantation is indicated. Since most candidates are young children of small size, there is a shortage of size-matched donors for liver transplantation. At present, an increased awareness to ensure early diagnosis and development of methods to prevent progressive fibrosis are needed. These considerations are dependent on detailed studies of the pathogenesis of BA Recent studies have focused on normal and altered bite duct morphogenesis and the role of various factors (infectious or toxic agents and metabolic insults) in isolation or in combination with a genetic or immunologic susceptibility in the etiology of BA. C1 TUFTS NEW ENGLAND MED CTR,FLOATING HOSP CHILDREN,BOSTON,MA. NIDDKD,NIH,BETHESDA,MD 20892. CHILDRENS HOSP YALE NEW HAVEN,NEW HAVEN,CT. ST LOUIS CHILDRENS HOSP,ST LOUIS,MO 63178. UNIV COLORADO,SCH MED,DENVER,CO. RP Balistreri, WF (reprint author), CHILDRENS HOSP,MED CTR,DEPT PEDIAT GI & NUTR,3333 BURNET AVE,CINCINNATI,OH 45229, USA. NR 93 TC 200 Z9 216 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1996 VL 23 IS 6 BP 1682 EP 1692 DI 10.1002/hep.510230652 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UQ898 UT WOS:A1996UQ89800052 PM 8675193 ER PT J AU Hardwick, JP Chen, LP AF Hardwick, JP Chen, LP TI Something completely different? cDNA cloning of three new forms of rat brain cytochrome P450 belonging to the CYP4F subfamily - Comment SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP Hardwick, JP (reprint author), NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JUN PY 1996 VL 15 IS 6 BP 543 EP 544 PG 2 WC Toxicology SC Toxicology GA UP505 UT WOS:A1996UP50500016 PM 8793542 ER PT J AU Ning, Y Rosenberg, M Biesecker, LG Ledbetter, DH AF Ning, Y Rosenberg, M Biesecker, LG Ledbetter, DH TI Isolation of the human chromosome 22q telomere and its application to detection of cryptic chromosomal abnormalities SO HUMAN GENETICS LA English DT Article ID DNA; TRANSLOCATIONS; POLYMORPHISM; SEQUENCE; CLONING; KB AB A number of human telomeres have been successfully cloned using a modified yeast artificial chromosome (YAC) vector (half-YAC) cloning strategy, but to date, human chromosome 22q has not been identified by this approach. We used an alternative approach of genomic walking, starting from a subtelomeric sequence, TelBam3.4, present on a number of human chromosomes including 22q. This approach was successful in the development of a cosmid contig representing the terminal 140 kb of human chromosome 22q, providing telomeric closure of the genetic and physical maps for 22q. The most distal region of the contig contains subtelomeric repeats which crosshybridize to a number of chromosomes, while the proximal sequences are unique for 22q. The unique sequence cosmid was used as a 22qter-specific probe for fluorescence in situ hybridization (FISH) analysis, which confirmed that this cosmid was distal to the most telomeric marker previously available for chromosome 22. In addition, this cosmid was used to document a 22q terminal deletion that was not detectable by conventional cytogenetic analysis. Unique telomere-specific FISH probes such as this one will have significant diagnostic value in the detection of cryptic deletions and translocations in patients with unexplained mental retardation and other patient populations. C1 NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. NR 23 TC 26 Z9 26 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1996 VL 97 IS 6 BP 765 EP 769 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA UK898 UT WOS:A1996UK89800013 PM 8641694 ER PT J AU Wei, MH Popescu, NC Lerman, MI Merrill, MJ Zimonjic, DB AF Wei, MH Popescu, NC Lerman, MI Merrill, MJ Zimonjic, DB TI Localization of the human vascular endothelial growth factor gene, VEGF at chromosome 6p12 SO HUMAN GENETICS LA English DT Article ID ANGIOGENESIS; INVIVO AB Using overlapping cosmids representing the vascular endothelial growth factor (VEGF) locus, the VEGF gene was mapped by fluorescence in situ hybridization to chromosome 6p12. This localization permits linkage analysis and the identification of gene interaction in the region, as well as alterations of the VEGF structure or expression in cancer cells with chromosome abnormalities. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NCI,BIOL LAB,NIH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 20 TC 35 Z9 44 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1996 VL 97 IS 6 BP 794 EP 797 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA UK898 UT WOS:A1996UK89800017 PM 8641698 ER PT J AU LaRocque, R Robinson, MA AF LaRocque, R Robinson, MA TI Diversity in the human T cell receptor beta chain SO HUMAN IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; JUNCTIONAL REGIONS; VARIABLE REGIONS; GENE SEGMENTS; RECOMBINATION; RECOGNITION; SEQUENCES; SELECTION; ALPHA; MICE C1 NIAID,IMMUNOGENET LAB,TWINBROOK 2 FACIL,ROCKVILLE,MD 20852. NR 51 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JUN-JUL PY 1996 VL 48 IS 1-2 BP 3 EP 11 DI 10.1016/0198-8859(96)00083-3 PG 9 WC Immunology SC Immunology GA UY579 UT WOS:A1996UY57900002 PM 8824568 ER PT J AU Currier, JR Deulofeut, H Barron, KS Kehn, PJ Robinson, MA AF Currier, JR Deulofeut, H Barron, KS Kehn, PJ Robinson, MA TI Mitogens, superantigens, and nominal antigens elicit distinctive patterns of TCRB CDR3 diversity SO HUMAN IMMUNOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN T-CELLS; V-BETA; ALPHA-CHAIN; PEPTIDE; RECOGNITION; SPECIFICITY; MUTATIONS; SEGMENTS; REGIONS AB The third complementarity-determining region (CDR3) is the only nongermline-encoded hypervariable region of the T cell receptor beta (TCRB) chain, and it is the region that has been predicted to confer fine specificity of che TCR for peptide-MHC complexes. For this reason analysis of TCRB CDR3 heterogeneity may provide insight into immune mechanisms operative in infectious and autoimmune diseases. PBMC stimulated with either mitogen (PHA), superantigen (TSST-1), or nominal antigen (tetanus toxoid) have been compared with unstimulated PBMC using a two-dimensional approach. Analysis of che expressed TCRBV gene repertoire CDR3 length profile coupled with SSCP methodology enabled the discrimination of sequences with the same CDR3 length. For both freshly isolated and PHA-stimulated PBMC, a normally distributed spectrum of CDR3 lengths (five or more produces) was observed. These products differed by 3 bp (1 amino acid) due to the strict requirement for in-frame rearrangements in the CDR3 region of TCR. By contrast, tetanus toxoid-stimulated PBMC had restricted profiles for most TCRBV families after as few as 7 days of incubation The oligoclonal nature of samples showing CDR3 length restriction was revealed by SSCP analysis and confirmed by sequence determination Superantigen stimulation resulted in unique patterns of diversity, which included polyclonal expansion of specific TCRBV families as well as oligoclonal expansion of most other TCRBV families. These data reveal complex yet distinct patterns of TCR diversity in response to different T cell activation stimuli. C1 NIAID,IMMUNOGENET LAB,TWINBROOK 2 FACIL,ROCKVILLE,MD 20852. NR 32 TC 50 Z9 55 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JUN-JUL PY 1996 VL 48 IS 1-2 BP 39 EP 51 DI 10.1016/0198-8859(96)00076-6 PG 13 WC Immunology SC Immunology GA UY579 UT WOS:A1996UY57900006 PM 8824572 ER PT J AU ONeill, ME Marietta, J Nishimura, D Wayne, S VanCamp, G VanLaer, L Negrini, C Wilcox, ER Chen, A Fukushima, K Ni, L Sheffield, VC Smith, RJH AF ONeill, ME Marietta, J Nishimura, D Wayne, S VanCamp, G VanLaer, L Negrini, C Wilcox, ER Chen, A Fukushima, K Ni, L Sheffield, VC Smith, RJH TI Gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6 SO HUMAN MOLECULAR GENETICS LA English DT Article ID CLONING AB Late-onset non-syndromic hearing impairment is the most common type of neurological dysfunction in the elderly. It can be either acquired or inherited, although the relative impact of heredity on this type of loss is not known. To date, nine different genes have been localized, but none has been cloned. Using an extended American family in which a gene for autosomal dominant late-onset non-syndromic hearing impairment is segregating, we have identified a new locus, DFNA10, on chromosome 6. C1 UNIV IOWA,DEPT OTOLARYNGOL,IOWA CITY,IA 52242. UNIV IOWA,DEPT PEDIAT,IOWA CITY,IA 52242. UNIV ANTWERP,DEPT MED GENET,B-2610 ANTWERP,BELGIUM. NIDOCD,NIH,ROCKVILLE,MD 20850. RI Van Camp, Guy/F-3386-2013 OI Van Camp, Guy/0000-0001-5105-9000 NR 25 TC 42 Z9 45 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1996 VL 5 IS 6 BP 853 EP 856 DI 10.1093/hmg/5.6.853 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UQ072 UT WOS:A1996UQ07200019 PM 8776603 ER PT J AU Sharer, LR Saito, Y DaCunha, A Ung, PC Gelbard, HA Epstein, LG Blumberg, BM AF Sharer, LR Saito, Y DaCunha, A Ung, PC Gelbard, HA Epstein, LG Blumberg, BM TI In situ amplification and detection of HIV-1 DNA in fixed pediatric aids brain tissue SO HUMAN PATHOLOGY LA English DT Article DE in situ PCR; HIV-1 infection; pediatric brain; AIDS encephalopathy ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; FRONTAL-CORTEX; III INFECTION; CHILDREN; ENCEPHALOPATHY; INSITU; TYPE-1; CELLS AB To examine whether latent infection by HIV-1 occurs in the central nervous system, we optimized a procedure for amplification and detection of HIV-1 DNA in situ, in formalin-fixed brain tissue from a child with severe HIV-1-associated progressive encephalopathy and severe HIV-1 encephalitis. By the use of a two-step technique, which involved polymerase chain reaction with incorporation of digoxigenin-labeled nucleotides followed by in situ hybridization with biotinylated probes, we found infection of numerous mononuclear cells and astrocytes in the cerebral white matter as as well as of perineuronal satellite cells in basal ganglia, but not of neurons. Following PCR amplification, nuclear signal was found in 10 to 20 times as many cells as in parallel, control experiments using conventional. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. UNIV ROCHESTER,MED CTR,DEPT NEUROL,LAB MOL NEUROVIROL,ROCHESTER,NY 14642. RP Sharer, LR (reprint author), UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PATHOL,185 S ORANGE AVE,NEWARK,NJ 07103, USA. FU NEI NIH HHS [EY09217]; NIAID NIH HHS [AI32305]; NINDS NIH HHS [NS28754] NR 30 TC 33 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 1996 VL 27 IS 6 BP 614 EP 617 DI 10.1016/S0046-8177(96)90172-0 PG 4 WC Pathology SC Pathology GA UQ842 UT WOS:A1996UQ84200019 PM 8666375 ER PT J AU Deng, YJ AF Deng, YJ TI MAb NPYI-46.1, NPYI-125.3, NPYII-1.2, NPYII-14.1, NPYII-269.3, NPYII-287.3, antineuropeptide Y (NPY) SO HYBRIDOMA LA English DT Article RP Deng, YJ (reprint author), NIDR,ORAL MED LAB,NATL INST HLTH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1996 VL 15 IS 3 BP 254 EP 254 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA UX055 UT WOS:A1996UX05500026 ER PT J AU Svetkey, LP Timmons, PZ Emovon, O Anderson, NB Preis, L Chen, YT AF Svetkey, LP Timmons, PZ Emovon, O Anderson, NB Preis, L Chen, YT TI Association of hypertension with beta(2)- and alpha(2c10)-adrenergic receptor genotype SO HYPERTENSION LA English DT Article DE receptors, adrenergic; hypertension, essential; genetics; race ID DNA POLYMORPHISM; SENSITIVITY AB The adrenergic receptors have been implicated in the pathogenesis of essential hypertension. We hypothesized that hypertension is associated with variants at the beta(2)-adrenergic receptor locus and at one of the alpha(2)-adrenergic receptor loci. In unrelated individuals, we measured untreated blood pressure and characterized each subject as hypertensive or normotensive. We then used genomic DNA to identify beta(2)- and alpha(2c10)-adrenergic receptor restriction fragment length polymorphisms. In 175 subjects (49% with hypertension, 55% black), both hypertension and race were associated with genotype at the beta(2) locus (chi(2) for hypertension=11, P=.004; chi(2) for race=8.8, P=.012). The association with hypertension persisted in each race group separately (blacks only: chi(2)=9.6, P=.008; whites only: chi(2)=14.2, P=.001). This association persisted in a logistic model that controlled for race (P=.01). Genotype was also significantly associated with baseline systolic, diastolic, and mean arterial blood pressures (p=.05, .01, and .02, respectively). These data suggest that the beta(2)-adrenergic receptor gene is a candidate gene for hypertension in blacks and whites. We also genotyped subjects at the alpha(2)-adrenergic receptor coded on chromosome 10. There was no association between hypertension and genotype at the alpha(2c10) locus in the total group or in blacks, but there was significant association in whites (chi(2)=6.7, P=.03). These data suggest that the beta(2)- and alpha(2c10)-adrenergic receptor genes may contribute, in a race-specific manner, to the inheritance of essential hypertension. Linkage studies in related individuals are needed to confirm these findings. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. NIH,BETHESDA,MD 20892. FU NHLBI NIH HHS [R01-HL-50176, R29-HL-46218]; NIA NIH HHS [P20-AG-12058] NR 14 TC 85 Z9 88 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1996 VL 27 IS 6 BP 1210 EP 1215 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UP223 UT WOS:A1996UP22300004 PM 8641726 ER PT J AU Seidel, J Gandler, WR Green, MV AF Seidel, J Gandler, WR Green, MV TI Characteristics of a pair of small field-of-view LSO scintillation cameras SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1995 Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC) CY OCT 21-28, 1995 CL SAN FRANCISCO, CA ID DOPED LUTETIUM OXYORTHOSILICATE AB We created two miniature scintillation cameras by coupling identical, thin LSO crystals to position sensitive photomultiplier tubes (PSPMTs). The performance of these cameras was established in both single photon and coincidence imaging modes and in relation to similar gamma cameras equipped with NaI(Tl) crystals. The intrinsic spatial resolution of the LSO cameras was 2.3 mm at 140 keV and 1.2 mm at 511 keV. The coincidence time resolution was 3 ns with an energy resolution of 16.5% at 511 keV. With no sources present, an intrinsic event rate of 300/sec/cm(3) of LSO from Lu-176 was observed. Although this background count rate may be a limitation in some applications, LSO PSPMT scintillation cameras offer several important performance advantages over similar NaI(Tl) and BGO cameras that include improved count rate performance, coincidence timing, stopping power relative to NaI, and energy resolution relative to BGO. C1 NATL INST HLTH,DEPT NUCL MED,BETHESDA,MD 20892. NATL INST HLTH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NR 14 TC 16 Z9 16 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1996 VL 43 IS 3 BP 1968 EP 1973 DI 10.1109/23.507255 PN 2 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA UT044 UT WOS:A1996UT04400166 ER PT J AU Germain, RN Castellino, F Han, RC Sousa, CR Romagnoli, P SadeghNasseri, S Zhong, GM AF Germain, RN Castellino, F Han, RC Sousa, CR Romagnoli, P SadeghNasseri, S Zhong, GM TI Processing and presentation of endocytically acquired protein antigens by MHC class II and class I molecules SO IMMUNOLOGICAL REVIEWS LA English DT Review ID COMPLEX-CLASS-II; HLA-DR MOLECULES; INVARIANT CHAIN PEPTIDES; CELL-SURFACE EXPRESSION; ALPHA-BETA-HETERODIMERS; HISTOCOMPATIBILITY ANTIGENS; INTRACELLULAR-TRANSPORT; ENDOPLASMIC-RETICULUM; ALLELIC POLYMORPHISM; EXOGENOUS ANTIGEN RP Germain, RN (reprint author), NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BLDG 10,ROOM 11N311,10 CTR DR,MSC-1892,BETHESDA,MD 20892, USA. RI Romagnoli, Paola/K-2237-2014; OI Sadegh-Nasseri, Scheherazade/0000-0002-8127-1720 NR 116 TC 82 Z9 86 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1996 VL 151 BP 5 EP 30 DI 10.1111/j.1600-065X.1996.tb00701.x PG 26 WC Immunology SC Immunology GA VD096 UT WOS:A1996VD09600001 PM 8872483 ER PT J AU Detels, R Mann, D Carrington, M Hennessey, K Wu, ZY Hirji, KF Wiley, D Visscher, BR Giorgi, JV AF Detels, R Mann, D Carrington, M Hennessey, K Wu, ZY Hirji, KF Wiley, D Visscher, BR Giorgi, JV TI Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 1st International Summit on Immunological Correlates of Protection from HIV Infection and Disease CY 1995 CL LE MT PELERIN, SWITZERLAND SP EC Centralized Facil Preclin HIV 1 Vaccine Dev DE HIV-1; genetics; resistance; cellular immunity ID MULTICENTER AIDS COHORT; HOMOSEXUAL MEN; VIRUS-REPLICATION; INFECTION; DNA AB Studies in both monkeys and humans have suggested that transient infection with HIV-I can occur without provoking: a measurable humoral immune response. The objective of this study was to look for genetic and immunologic correlates of transient HIV-1 infection in antibody-negative men from whom HIV-I had been isolated. The distributions of MHC class I, class II, and TAP (transporter protein associated with antigen processing) region genes were compared between 23 persistently seronegative men from whom HIV-1 was isolated al least once (isol +/Ab-) and 137 men who seroconverted. A subset of 13 of the 23 isol +/Ab- men were compared to 27 seronegative men for distribution of CD25(+)CD4(+) and CD25(+)CD8(+) cells in the absence of exogenous immunologic stimulation. The prevalences of the TAP1.4 and a combination of TAP1.4 and TAP2.3 variants were significantly higher in the isol +/Ab- men. The proportion of CD8(+) cells that expressed CD25(+) antigen was also significantly higher in the isol +/Ab- men than in the seronegative men. We conclude that isol +/Ab- men may be genetically and immunologically distinct from HIV-1 susceptible men. We hypothesize that activated CD8(+) cells may have cleared HIV-1 infection in these men through genetically mediated influences of the TAP genes on the presentation of peptides by HLA class I molecules. C1 UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES CTR MULTICTR AIDS COHORT STUDY,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,AIDS INST,LOS ANGELES,CA 90024. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. FU FIC NIH HHS [TW00013]; NIAID NIH HHS [N01-AI-72631, U01-AI-35040] NR 23 TC 16 Z9 16 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN PY 1996 VL 51 IS 1-2 BP 29 EP 33 DI 10.1016/0165-2478(96)02551-5 PG 5 WC Immunology SC Immunology GA UW653 UT WOS:A1996UW65300006 PM 8811341 ER PT J AU Heeney, J Bogers, W Buijs, L Dubbes, R tenHaaft, P Koornstra, W Niphuis, H Nara, P Teeuwsen, V AF Heeney, J Bogers, W Buijs, L Dubbes, R tenHaaft, P Koornstra, W Niphuis, H Nara, P Teeuwsen, V TI Immune strategies utilized by lentivirus infected chimpanzees to resist progression to AIDS SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 1st International Summit on Immunological Correlates of Protection from HIV Infection and Disease CY 1995 CL LE MT PELERIN, SWITZERLAND SP EC Centralized Facil Preclin HIV 1 Vaccine Dev DE AIDS; pathogenesis; chimpanzees; disease resistance; T-cell activation; MHC class II; CD4 cell renewal ID SIMIAN IMMUNODEFICIENCY VIRUS; PROGRAMMED CELL-DEATH; RHESUS-MONKEYS; CERCOCEBUS-ATYS; HIV; RETROVIRUS; TYPE-1; DYSFUNCTION; LYMPHOCYTES; INDIVIDUALS AB HIV-1 infected chimpanzees are relatively resistant to the development of AIDS despite their close genetic relatedness to humans and their susceptibility to HIV-I infection. We have systematically studied possible reasons for their relative ability to maintain T helper (Th) cell numbers and immune competence in the presence of chronic HIV-1 infection. Factors which may alone or together cause the loss in T-cell dependent immunity include: (i) the loss of Th cell function; (ii) the loss of Th cells; and (iii) the loss of capacity for Th cell renewal. Differences in the in vivo and in vitro responses of T lymphocytes from chimpanzees and humans were compared for evidence of HIV-1 related T-cell dysfunction. In contrast to HIV infected individuals, HIV-I infected chimpanzees maintained strong Th cell proliferative and cytokine responses after receiving tetanus toroid boosts. In addition there was no abnormal Th1 to Th2 shift as is suggested to occur in AIDS patients. There was no evidence of Th cell dysfunction such as increased level of programmed cell death (PCD) or immune activation in HIV-I infected chimpanzees in contrast to HIV-1 infected asymptomatic humans. Anergy could be induced with HIV-I gp120 in human but not chimpanzee Th lymphocytes. We then asked if there was a direct loss of chimpanzee CD4(+) cells due to HIV-1 infection in vitro. Infection of chimpanzee CD4(+) lymphocyte cultures with HIV-1 in the absence of CD8(+) cells resulted in marked cytopathic effect with complete lysis and loss of cells within 3 weeks. We concluded that most chronic HIV-I infected chimpanzees were able to maintain relatively stable CD4(+) lymphocyte numbers despite CD4(+) lymphocyte destruction due to direct effects of the virus. Furthermore, there was no evidence of indirect Th cell loss, since neither increased levels of anergy nor apoptosis were observed. Lymph node biopsies from HIV-1 infected chimpanzees revealed that MHC class II rich regions of lymph nodes remained intact, in contrast to the involution of these regions in infected humans. This suggested that chimpanzees may maintain the capacity for Th cell renewal by preserving this MHC class II lymphoid environment. The data presented in this paper suggests that chimpanzees may preserve this critical MHC class II-Th cell environment by dramatically suppressing extra-cellular virus load and that this may be in part mediated by soluble lentivirus suppressing factors. C1 NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. RP Heeney, J (reprint author), BIOMED PRIMATE RES CTR,DEPT VIROL,POB 3306,NL-2280 HG RIJSWIJK,NETHERLANDS. OI Heeney, Jonathan/0000-0003-2702-1621 NR 30 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN PY 1996 VL 51 IS 1-2 BP 45 EP 52 DI 10.1016/0165-2478(96)02554-0 PG 8 WC Immunology SC Immunology GA UW653 UT WOS:A1996UW65300009 PM 8811344 ER PT J AU Clerici, M Shearer, GM AF Clerici, M Shearer, GM TI Correlates of protection in HIV infection and the progression of HIV infection to AIDS SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 1st International Summit on Immunological Correlates of Protection from HIV Infection and Disease CY 1995 CL LE MT PELERIN, SWITZERLAND SP EC Centralized Facil Preclin HIV 1 Vaccine Dev DE AIDS; cytokines; disease progression; HIV; immunology; interleukin ID PROGRAMMED CELL-DEATH; T-HELPER CELL; IMMUNODEFICIENCY-VIRUS; IMMUNOENDOCRINOLOGICAL HYPOTHESIS; PATHOGENESIS; RESPONSES; THERAPY; LYMPHOCYTES; APOPTOSIS; SURVIVAL AB Exposure to human immunodeficency virus (HIV) can result in HIV infection which is defined by seroconversion and the detection of HIV-specific antibodies. Nevertheless, in every cohort at risk for HIV infection, individuals are present in whom seroconversion is not observed despite multiple documented exposures to HIV. Recent studies have shown that HIV-specific T-lymphocytes are present in the peripheral blood of these HIV-exposed seronegative individuals, suggesting that cell-mediated immunity (CMI) could have a protective role in the prevention of HIV infection. In most individuals who seroconvert, HIV infection is followed by a long period of clinically asymptomatic latency which ultimately results in the development of acquired immunodeficency syndrome (AIDS). Although this progression is observed in the majority of HIV-infected individuals, individuals exist who are asymptomatic and have relatively high CD4 counts despite long-lasting HIV infection. Analogous to that observed in seronegative HIV-exposed individuals, strong HIV-specific CMI seems to be characteristic of these HIV-seropositive (HIV+) long-term non-progressors (LTNP). Because strong HIV-specific CMI is present in HIV-seronegative individuals exposed to HIV and in HIV+ LTNP, we believe that HIV-specific CMI may be the main correlate of protection against HIV infection and against the progression of HIV infection to AIDS. C1 NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Clerici, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,VIA VENEZIAN 1,I-20133 MILAN,ITALY. NR 44 TC 31 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN PY 1996 VL 51 IS 1-2 BP 69 EP 73 DI 10.1016/0165-2478(96)02557-6 PG 5 WC Immunology SC Immunology GA UW653 UT WOS:A1996UW65300012 PM 8811347 ER PT J AU Haigwood, NL Watson, A Sutton, WF McClure, J Lewis, A Ranchalis, J Travis, B Voss, G Letvin, NL Hu, SL Hirsch, VM Johnson, PR AF Haigwood, NL Watson, A Sutton, WF McClure, J Lewis, A Ranchalis, J Travis, B Voss, G Letvin, NL Hu, SL Hirsch, VM Johnson, PR TI Passive immune globulin therapy in the SIV/macaque model: Early intervention can alter disease profile SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 1st International Summit on Immunological Correlates of Protection from HIV Infection and Disease CY 1995 CL LE MT PELERIN, SWITZERLAND SP EC Centralized Facil Preclin HIV 1 Vaccine Dev DE AIDS; SIV/macaque model; passive antibody therapy; RT-QC-PCR; primate lentiviruses; humoral immune responses; HIV therapy; long term non-progressors ID IMMUNODEFICIENCY-VIRUS-INFECTION; SIV ENVELOPE; ANTIBODIES; IMMUNIZATION; MACAQUES; IMMUNOTHERAPY; PROTECTION; PREVENTION; CHALLENGE AB One of the major questions in AIDS is the role that the host immune system and the virus play in the dynamics of infection and the development of AIDS in an infected individual. In order to test the role of antibody in controlling viral infection, high-dose SIV-immune globulin was passively transferred to infected macaques early in infection. Immune globulin purified from the plasma of an SIV-infected long-term non-progressor macaque (SIVIG) or a pool of normal immune globulin (normal Ig) was infused into SIVsmE660-infected macaques (170 mg/kg) at one and fourteen days post infection. Animals were monitored for SIV-specific antibodies, viremia, plasma antigenemia, and clinical course. All animals were infected by SIV. At 16 months post infection; five macaques in the combined control groups have been euthanized,one as a rapid progressor with debilitating disease at 20 weeks post infection. Four macaques from the comparison groups have signs of AIDS, accompanied by high and increasing levels of virus and p27 antigenemia. One of the ten control animals had a very low virus load in plasma and peripheral blood and lymph node mononuclear cells at all times tested and has remained disease-free. In the SIVIG treatment group, two macaques were euthanized at 18-20 weeks due to AIDS, rapid progressors to disease. Three macaques in the SIVIG group had an initial high level of virus in plasma, peripheral blood mononuclear cells (PBMC), and lymph node mononuclear cells (LNMC), which dropped to baseline at 6 weeks post infection and has remained very low or negative for 16 months, a disease profile which has not been observed in untreated animals in this model to date. These macaques have remained clinically healthy. The sixth treated animal is also healthy, with very low virus burden that is detectable only by nested set polymerase chain reaction (PCR). All SIVIG-treated macaques had no delectable p27 plasma antigenemia for the first 10 weeks of infection, demonstrating that the IgG effectively complexed with the virus. The immunological correlates in the treated animals include development of de novo virus-specific antibodies and/or cytotoxic T cell (CTL), both of which are hallmarks of long term non-progressors. The two SIVIG-treated macaques that progress to disease rapidly had no detectable de novo humoral immune responses, as is often seen in rapid HIV disease in humans. Envelope-specific and virus neutralizing antibodies alone were not sufficient to prevent disease progression, as the plasma of both non-progressors as well as progressors had high titers of envelope-specific and neutralizing antibodies against SIVsmE660. Poor clinical prognosis was associated with moderate to high and increasing virus loads in plasma, PBMC, and lymph nodes. Good clinical prognosis correlated with low or undetectable post acute viremia in the peripheral blood and lymph nodes. We hypothesize that SIVIG reduced the spread of virus by eliminating or reducing plasma virus through immune complexes during the first four to 8 weeks of infection and then maintaining this low level of viremia until the host immune response was capable of virus control. Reduction of virus burden early in infection by passive IgG can alter disease outcome in SIV infection of macaques. Modifications of this strategy may lead to effective early treatment of HIV-1 infection in humans. C1 CHILDRENS HOSP, RES FDN, COLUMBUS, OH 43205 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, BOSTON, MA 02215 USA. NIAID, INFECT DIS LAB, NIH, ROCKVILLE, MD 20852 USA. RP Haigwood, NL (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST, DEPT IMMUNODEFICIENCY & IMMUNOSUPPRESS, 3005 1ST AVE, SEATTLE, WA 98121 USA. RI Hu, Shiu-Lok/A-3196-2008; Johnson, Philip/A-6892-2009 OI Hu, Shiu-Lok/0000-0003-4336-7964; NR 22 TC 114 Z9 115 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN PY 1996 VL 51 IS 1-2 BP 107 EP 114 DI 10.1016/0165-2478(96)02563-1 PG 8 WC Immunology SC Immunology GA UW653 UT WOS:A1996UW65300018 PM 8811353 ER PT J AU Hu, SL Polacino, P Stallard, V Klaniecki, J Pennathur, S Travis, BM Misher, L Kornas, H Langlois, AJ Morton, WR Benveniste, RE AF Hu, SL Polacino, P Stallard, V Klaniecki, J Pennathur, S Travis, BM Misher, L Kornas, H Langlois, AJ Morton, WR Benveniste, RE TI Recombinant subunit vaccines as an approach to study correlates of protection against primate lentivirus infection SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 1st International Summit on Immunological Correlates of Protection from HIV Infection and Disease CY 1995 CL LE MT PELERIN, SWITZERLAND SP EC Centralized Facil Preclin HIV 1 Vaccine Dev DE AIDS; vaccine; SIV; envelope; core; recombinant vaccinia virus ID HUMAN-IMMUNODEFICIENCY-VIRUS; SIV INFECTION; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; MACAQUES; CHIMPANZEES; HIV-1; ANTIBODIES; GP160; IMMUNIZATION AB Using pathogenic simian immunodeficiency virus (SIV) infection of macaques as a model, we explored the limits of the protective immunity elicited by recombinant subunit vaccines and examined factors that affect their efficacy. Envelope gp160 vaccines, when used in a live recombinant virus-priming and subunit-protein-boosting regimen, protected macaques against a low-dose, intravenous infection by a cloned homologous virus SIVmne E11S. The same regimen was also effective against intrarectal challenge by the same virus and against intravenous challenge by E11S grown on primary macaque peripheral blood mononuclear cells (PBMC). However; only limited protection was observed against uncloned SIVmne. Priming with live recombinant virus was more effective than immunization with subunit gp160 alone, indicating a potential advantage of native antigen presentation and the possible role of cell-mediated immunity in protection. Whole gp160 was more effective than the surface antigen (gp130), even though both antigens elicited similar levels of neutralizing antibodies. Animals immunized with the core (gag-pol) antigens failed to generate any neutralizing antibody and were all infected following challenge. However, their proviral load was 10-100-fold lower than that of the control animals, indicating that immune mechanisms such as cytotoxic T lymphocytes (CTL) may play a role. Finally, animals immunized with both the core and the envelope antigens generated significant protective immunity, even with relatively low neutralizing antibodies. Taken together, these results indicate that multiple mechanisms may contribute to protection. It may therefore be advantageous to incorporate multiple antigens in the design of recombinant subunit vaccines against acquired immunodeficiency syndrome (AIDS). C1 WASHINGTON REG PRIMATE RES CTR,SEATTLE,WA 98195. DUKE UNIV,MED CTR,DURHAM,NC 27710. NCI,FREDERICK,MD 21702. RP Hu, SL (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,3005 1ST AVE,SEATTLE,WA 98121, USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [AI26503] NR 21 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUN PY 1996 VL 51 IS 1-2 BP 115 EP 119 DI 10.1016/0165-2478(96)02564-3 PG 5 WC Immunology SC Immunology GA UW653 UT WOS:A1996UW65300019 PM 8811354 ER PT J AU Brines, R HoffmanGoetz, L Pedersen, BK AF Brines, R HoffmanGoetz, L Pedersen, BK TI Can you exercise to make your immune system fitter? SO IMMUNOLOGY TODAY LA English DT Article AB It is clear that exercise has effects on immune parameters. However, it remains a matter of some debate as to whether these effects can be translated into clinically relevant strategies for improved human health. This issue was addressed at a recent symposium*. C1 UNIV WATERLOO,DEPT HLTH STUDIES,WATERLOO,ON N2L 3G1,CANADA. RIGSHOSP,DEPT INFECT DIS M7722,DK-2200 COPENHAGEN N,DENMARK. RP Brines, R (reprint author), NCI,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20205, USA. NR 3 TC 43 Z9 46 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUN PY 1996 VL 17 IS 6 BP 252 EP 254 DI 10.1016/0167-5699(96)80538-X PG 3 WC Immunology SC Immunology GA UQ708 UT WOS:A1996UQ70800003 PM 8962624 ER PT J AU DeSimone, C Famularo, G Cifone, G Mitsuya, H AF DeSimone, C Famularo, G Cifone, G Mitsuya, H TI HIV-I infection and cellular metabolism SO IMMUNOLOGY TODAY LA English DT Article AB A recent meeting* focused on the role of cellular metabolism in the pathogenesis of human immunodeficiency virus type I (HIV-1) infection an din the disease progression to AIDS. C1 NCI,EXPT RETROVIROL SECT,MED BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. RP DeSimone, C (reprint author), UNIV LAQUILA,DEPT EXPTL MED,I-67100 LAQUILA,ITALY. OI CIFONE, Maria Grazia/0000-0002-9923-5445 NR 28 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUN PY 1996 VL 17 IS 6 BP 256 EP 258 DI 10.1016/0167-5699(96)80540-8 PG 3 WC Immunology SC Immunology GA UQ708 UT WOS:A1996UQ70800005 PM 8962626 ER PT J AU DeLaCadena, RA MajlufCruz, A Stadnicki, A Agosti, JM Colman, RW Suffredini, AF AF DeLaCadena, RA MajlufCruz, A Stadnicki, A Agosti, JM Colman, RW Suffredini, AF TI Activation of the contact and fibrinolytic systems after intravenous administration of endotoxin to normal human volunteers: Correlation with the cytokine profile SO IMMUNOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 14th International Symposium on Bradykinin and Related Kinins (KININ 95) CY SEP 10-15, 1995 CL DENVER, CO DE kallikrein-kinin system; endotoxin; fibrinolysis; cytokines ID TUMOR-NECROSIS-FACTOR; SEPTIC SHOCK; FACTOR-XII; INTERLEUKIN-1; RECEPTOR; ENDOTHELIUM; PLASMINOGEN; COAGULATION; INHIBITORS; BACTEREMIA AB Severe progressive failure of multiple organ systems has emerged during the past three decades as a common cause of death among patients in intensive care units. Sepsis is now better defined as systemic inflammatory response syndrome (SIRS), but its mortality rate has not changed and it continues to be a major health problem. Endotoxin interacts with plasma proteins and contributes to the pathophysiology of SLRS. Information is limited on the effect of endotoxin on human coagulation and fibrinolytic proteins in vivo, as well as on the cell response involved in the cytokine cascade. For this reason we performed quantitative assays to establish the sequence of events that occurs in vivo in the regulation of the contact and fibrinolytic pathways as well as in the cytokine cascade as a response to a single dose administration of endotoxin to normal non-smoking human volunteers. C1 IMMUNEX CORP,SEATTLE,WA. NATL INST HLTH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD. TEMPLE UNIV,SCH MED,SOL SHERRY THROMBOSIS RES CTR,PHILADELPHIA,PA 19140. RP DeLaCadena, RA (reprint author), TEMPLE UNIV,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19140, USA. FU NHLBI NIH HHS [HL 45486]; PHS HHS [2681-05] NR 30 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD JUN PY 1996 VL 33 IS 1-3 BP 231 EP 237 DI 10.1016/0162-3109(96)00064-1 PG 7 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA VA298 UT WOS:A1996VA29800049 PM 8856155 ER PT J AU Chang, YC Penoyer, LA KwonChung, KJ AF Chang, YC Penoyer, LA KwonChung, KJ TI The second capsule gene of Cryptococcus neoformans, CAP64, is essential for virulence SO INFECTION AND IMMUNITY LA English DT Article ID SEROTYPE-A; MULTICATALYTIC PROTEINASE; POLYSACCHARIDE; MUTANTS; URA5; PROTEASOMES AB The extracellular polysaccharide capsule produced by Cryptococcus neoformans is essential for its pathogenicity. We have isolated and characterized a gene, CAP64, which is required for capsule formation. An encapsulated strain created by complementation of the cap64 mutation produced fatal infection of mice within 25 days, while the cap64 acapsular strain was avirulent. Gene deletion of CAP64 from a wild-type strain resulted in the loss of capsule as well as virulence. Contour-clamped homogeneous electric field gel analysis indicates that CAP64 is located on chromosome III, which is different from the localization of another capsule-related gene, CAP59. The nonlinkage between CAP64 and CAP59 was also supported by classical recombinational analysis. Database searches did not reveal any sequence with high similarity to CAP64. We also found that the CAP64 locus is contiguous to a convergently transcribed gene which has significant similarity to the gene encoding the yeast proteasome subunit, PRE1. The distance between the cDNA ends of these two genes is only 22 bp. This study confirms the previous molecular genetic evidence that capsule is an essential factor for the virulence of C. neoformans in the murine model. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NR 28 TC 173 Z9 189 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1996 VL 64 IS 6 BP 1977 EP 1983 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UN189 UT WOS:A1996UN18900014 PM 8675296 ER PT J AU Grunvald, E Chiaramonte, M Hieny, S Wysocka, M Trinchieri, G Vogel, SN Gazzinelli, RT Sher, A AF Grunvald, E Chiaramonte, M Hieny, S Wysocka, M Trinchieri, G Vogel, SN Gazzinelli, RT Sher, A TI Biochemical characterization and protein kinase C dependency of monokine-inducing activities of Toxoplasma gondii SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MESSENGER-RNA EXPRESSION; CELL STIMULATORY FACTOR; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; IFN-GAMMA; MACROPHAGE ACTIVATION; PLASMODIUM-CHABAUDI; MURINE MACROPHAGES; ACCESSORY CELLS AB Previous reports have indicated that the early induction of interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-alpha), IL-1 beta, and IL-10 is crucial for the establishment and regulation of host cell-mediated immunity to the intracellular protozoan parasite Toxoplasma gondii. In this study, we demonstrate that a soluble tachyzoite extract (soluble tachyzoite antigen) can trigger the expression of these four monokines by murine inflammatory macrophages. Further characterization revealed that the parasite molecules in soluble tachyzoite antigen responsible for monokine induction are heat stable at 100 degrees C but differ in sensitivity to protease digestion. Thus, the tachyzoite factors that stimulate TNF-alpha and IL-1 beta expression were found to be more resistant to treatment with proteinase K than those responsible for IL-12 and IL-10 induction. Similarly, while the factors responsible for the induction of all four monokines were found to be sensitive to periodate oxidation, the TNF-alpha-stimulating activity was partially resistant to treatment with the compound at a low concentration (1 mM). A further dichotomy in monokine induction signals was inferred from experiments with isoquinoline sulfonamide protein kinase inhibitors. The latter work suggested that the pathways for TNF-alpha and IL-1 beta are protein kinase C dependent, while expression of IL-12 and expression of IL-10 share distinct signal transduction mechanisms involving other kinases. Together, these data argue that monokine induction by T, gondii is mediated by glycoproteins that may belong to distinct groups in terms of their biochemical properties and intracellular signaling pathways. C1 NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. UNIV FED MINAS GERAIS,DEPT BIOCHEM & IMMUNOL,BR-30161970 BELO HORIZONT,MG,BRAZIL. FU NIAID NIH HHS [AI 18797] NR 48 TC 86 Z9 88 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1996 VL 64 IS 6 BP 2010 EP 2018 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UN189 UT WOS:A1996UN18900019 PM 8675301 ER PT J AU Hackstadt, T AF Hackstadt, T TI The biology of rickettsiae SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY LA English DT Review DE rickettsiae; parasites; typhus; Rocky Mountain spotted fever ID MOUNTAIN-SPOTTED-FEVER; MURINE TYPHUS RICKETTSIAE; FIELD GEL-ELECTROPHORESIS; PHOSPHOLIPASE-A ACTIVITY; HUMAN-ENDOTHELIAL-CELLS; OUTER-MEMBRANE PROTEIN; LISTERIA-MONOCYTOGENES; MONOCLONAL-ANTIBODIES; ACTIN POLYMERIZATION; COXIELLA-BURNETII AB Rickettsiae are bacterial obligate intracellular parasites ranging from harmless endosymbionts to the etiologic agents of some of the most devastating diseases known to mankind. Rickettsiae are primarily associated with arthropod vectors in which they may exist commensally and, in most cases, only accidentally infect humans. These fascinating microbes are the prototypical obligate intracellular parasites. Other than being extremely fastidious in their growth requirements, however, rickettsiae are typical gram-negative bacteria. Only a few intracellular parasites multiply within the cytoplasm of eukaryotic cells. In this environment, rickettsiae are provided with a rich source of biosynthetic precursors not normally encountered by free-living bacteria and have evolved a number of unique mechanisms to transport such metabolites as nucleotides and nucleotide sugars. The physiologic basis for their obligate parasitism, however, has remained elusive for >90 years. Other than the obvious property of replicating inside eukaryotic cells, the molecular mechanisms of cellular damage are ill defined. The typhus-group rickettsiae multiply within host cells to great numbers without profound damage until lysis occurs. In contrast, the spotted fever-group rickettsiae spread rapidly from cell to cell by an actin-based motility. This property, in itself, is not sufficient to cause cell death, because avirulent spotted fever-group rickettsiae also spread by actin-based movement but do not cause lysis of the host cell. Despite the obvious limitations imposed by their obligate intracellular lifestyle and the current lack of methods for genetic manipulation, there are enough interesting biological properties of rickettsiae to offer an attractive area for research. RP Hackstadt, T (reprint author), NIAID, HOST PARASITES INTERACT SECT, INTRACELLULAR PARASITES LAB, ROCKY MT LABS, NIH, HAMILTON, MT 59840 USA. NR 154 TC 106 Z9 110 U1 3 U2 10 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1056-2044 J9 INFECT AGENT DIS JI Infect. Agents Dis.-Rev. Issues Comment. PD JUN PY 1996 VL 5 IS 3 BP 127 EP 143 PG 17 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV215 UT WOS:A1996UV21500001 PM 8805076 ER PT J AU Schwan, TG AF Schwan, TG TI Ticks and Borrelia: Model systems for investigating pathogen-arthropod interactions SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY LA English DT Review DE ticks; Borrelia; lyme disease; relapsing fever ID LYME-DISEASE SPIROCHETE; MAJOR SURFACE-PROTEINS; WHITE-FOOTED MICE; IXODES-DAMMINI; ANTIGENIC VARIATION; BURGDORFERI TRANSMISSION; EXPERIMENTAL-INFECTION; MONOCLONAL-ANTIBODY; ACTIVE IMMUNIZATION; MOLECULAR ANALYSIS AB Blood-feeding arthropods transmit numerous types of infectious agent and parasite that have a tremendous impact on human health and mortality throughout the world. These vector-borne pathogens display a wide array of evolutionary patterns that allow them to infect and to be successfully transmitted by ticks, mites, and hematophagous insects. The vector's method of feeding, type of development, and host preference are also critical factors for the transfer of zoonotic agents from wild animal reservoirs to susceptible humans. Ticks are obligate blood-feeders in all life stages and biologically transmit many infectious agents. in North America, two ticks that are involved in the maintenance and transmission of pathogenic spirochetes include Ixodes scapularis (family Ixodidae) and Ornithodoros hermsi (family Argasidae). These ticks are the respective vectors of the Lyme disease spirochete Borrelia burgdorferi and a relapsing fever spirochete, Borrelia hermsii. Little is known concerning how these and related species of Borrelia adapt to successfully alternate between warm-blooded vertebrates and ticks; however, the possibility that borrelial surface proteins are differentially expressed in their different hosts is an exciting area of current research. RP Schwan, TG (reprint author), NIAID,MICROBIAL STRUCT & FUNCT LAB,ROCKY MT LABS,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 120 TC 44 Z9 44 U1 2 U2 10 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1056-2044 J9 INFECT AGENT DIS JI Infect. Agents Dis.-Rev. Issues Comment. PD JUN PY 1996 VL 5 IS 3 BP 167 EP 181 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV215 UT WOS:A1996UV21500004 PM 8805079 ER PT J AU Rolston, KVI Rubenstein, EB Freifeld, A AF Rolston, KVI Rubenstein, EB Freifeld, A TI Early empiric antibiotic therapy for febrile neutropenia patients at low risk SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID CANCER-PATIENTS; FEVER; COMBINATION; EPISODES AB Infection continues to be a frequent cause of morbidity in febrile neutropenic patients. The risk of developing complications or of death is substantially different in various subsets of febrile neutropenic patients. Recently developed risk-assessment strategies have enabled clinicians to identify ''low-risk'' febrile neutropenic patients, based on a set of clinical criteria, at the onset of a febrile episode. Various therapeutic options including (1) early discharge from the hospital, (2) a switch from parenteral to oral antibiotic regimens, and (3) outpatient parenteral and/or oral antibiotic therapy have been evaluated in these ''low-risk'' patients. Initial results are promising, and further refinements in risk-assessment models and antimicrobial regimens are likely to make ambulatory management of low-risk febrile neutropenic patients the new standard of care. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD. RP Rolston, KVI (reprint author), UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT MED SPECIALTIES,HOUSTON,TX 77030, USA. NR 29 TC 30 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1996 VL 10 IS 2 BP 223 EP & DI 10.1016/S0891-5520(05)70297-X PG 16 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV398 UT WOS:A1996UV39800002 PM 8803619 ER PT J AU Bergen, GA Shelhamer, JH AF Bergen, GA Shelhamer, JH TI Pulmonary infiltrates in the cancer patient - New approaches to an old problem SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID BONE-MARROW TRANSPLANTATION; CYTOMEGALO-VIRUS INFECTION; ACUTE NONLYMPHOCYTIC LEUKEMIA; RESPIRATORY SYNCYTIAL VIRUS; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; INTERSTITIAL PNEUMONITIS; BRONCHOALVEOLAR LAVAGE; IMMUNE GLOBULIN; RISK-FACTORS AB A variety of etiologies may produce pulmonary infiltrates in a patient with cancer. Infectious etiologies, of an ever-increasing number, are always of paramount concern due to their high mortality in this patient population. Patients may be rendered immunosuppressed for prolonged periods of time and therefore are highly susceptible to infection. We present an overview of the many causes of pulmonary infiltrates in the cancer patient and an approach to diagnosis and treatment. C1 JAMES A HALEY VET HOSP,TAMPA,FL 33612. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP Bergen, GA (reprint author), UNIV S FLORIDA,COLL MED,JAMES A HALEY VET HOSP 111J,DIV INFECT DIS & TROP MED,TAMPA,FL 33612, USA. NR 141 TC 23 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1996 VL 10 IS 2 BP 297 EP & DI 10.1016/S0891-5520(05)70300-7 PG 30 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV398 UT WOS:A1996UV39800005 PM 8803622 ER PT J AU Chanock, SJ Gorlin, JB AF Chanock, SJ Gorlin, JB TI Granulocyte transfusions - Time for a second look SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; COLONY-STIMULATING FACTOR; PROGRAMMED CELL-DEATH; LEUKOCYTE TRANSFUSIONS; POLYMORPHONUCLEAR LEUKOCYTES; HUMAN NEUTROPHILS; INFECTION; SURVIVAL; THERAPY; NEUTROPENIA AB Among the available therapies to support neutropenic patients with infection, granulocyte transfusions have generated considerable controversy. Plagued by the inconvenience of harvesting cells, infusion-associated toxicity, and marginal efficacy, granulocyte transfusions, once in vogue in the 1980s, had been relegated to a secondary role. Several recent developments, however, have given new impetus to re-evaluating the role of granulocyte transfusions. The two most notable reasons include the ability to increase the number of circulating granulocytes in the donor by treatment with one or two doses of recombinant hematopoietic growth factors, such as granulocyte- and granulocyte-macrophage colony stimulating factor, and improvements in the efficiency of the collection process. Armed with these advances, it is an appropriate time to review the existing data and consider studies designed to determine the appropriate role of granulocyte transfusions in neutropenic hosts. C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA. RP Chanock, SJ (reprint author), NCI,NIH,PEDIAT BRANCH,10-13N240,BETHESDA,MD 20892, USA. NR 66 TC 26 Z9 27 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1996 VL 10 IS 2 BP 327 EP & DI 10.1016/S0891-5520(05)70301-9 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV398 UT WOS:A1996UV39800006 PM 8803623 ER PT J AU Walsh, TJ Hiemenz, JW Anaissie, E AF Walsh, TJ Hiemenz, JW Anaissie, E TI Recent progress and current problems in treatment of invasive fungal infection sin neutropenic patients SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID LIPOSOMAL-AMPHOTERICIN-B; BONE-MARROW TRANSPLANTATION; CENTRAL NERVOUS-SYSTEM; COLONY-STIMULATING FACTOR; CANDIDA-KRUSEI INFECTION; ACUTE-LEUKEMIA; PULMONARY ASPERGILLOSIS; CEREBROSPINAL-FLUID; CANCER-PATIENTS; RISK-FACTORS AB Patients who are receiving cytotoxic chemotherapy for neoplastic diseases, including those receiving allogeneic bone marrow transplantation, are predisposed to develop invasive fungal infections as the result of host defense impairments due to intensive cytotoxic chemotherapy, ablative radiation therapy, corticosteroids, cyclosporine, and the underlying neoplastic process. This article reviews the current approaches and problems in diagnosis, treatment, and prevention of invasive fungal infections in neutropenic patients. C1 UNIV TEXAS,MD ANDERSON CANC CTR,INFECT DIS SECT,HOUSTON,TX 77030. H LEE MOFFITT CANC CTR & RES INST,DIV BONE MARROW TRANSPLANTAT,TAMPA,FL. H LEE MOFFITT CANC CTR & RES INST,DIV INFECT TRANSPLANTAT,TAMPA,FL. H LEE MOFFITT CANC CTR & RES INST,DIV TROP MED,TAMPA,FL. RP Walsh, TJ (reprint author), NCI,INFECT DIS SECT,PEDIAT BRANCH,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. NR 181 TC 104 Z9 106 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1996 VL 10 IS 2 BP 365 EP & DI 10.1016/S0891-5520(05)70303-2 PG 37 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV398 UT WOS:A1996UV39800008 PM 8803625 ER PT J AU Bornstein, MH TamisLeMonda, CS Pascual, L Haynes, OM Painter, KM Galperin, CZ Pecheux, MG AF Bornstein, MH TamisLeMonda, CS Pascual, L Haynes, OM Painter, KM Galperin, CZ Pecheux, MG TI Ideas about parenting in Argentina, France, and the United States SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID CHILD; MOTHER; INTERVENTION; COMPETENCE; CULTURES; INFANTS; MODEL; JAPAN; STYLE AB Central to a concept of culture is the expectation that different peoples possess different ideas and behave in different ways with respect to child rearing. In this study, we investigated ideas that Argentine, French, and US American mothers hold about their own and their husbands' actual child rearing, as well as what they consider to be ideal child rearing, in three parenting domains: social, didactic, and limit setting. For each domain, we analysed mothers' reports of their actual behaviours and of their husbands' actual behaviours; mothers' ideal expectations of their own and their husbands' behaviours; and mothers' dissonance with respect to parenting (i.e. the extent to which mothers' actual and their husbands' actual behaviours each agrees with mothers' ideal expectations for themselves and for their husbands). The results showed consistent parent, country, as well as parent-by-country effects, interpretable in terms of overarching cultural beliefs. The study of parents' ideas contributes to understanding why and how parents behave the way they do toward children, and provides insights into the broader social context of child development. C1 NYU, NEW YORK, NY 10012 USA. UNIV BELGRANO, BUENOS AIRES, DF, ARGENTINA. UNIV PARIS 05, PARIS, FRANCE. CNRS, F-75700 PARIS, FRANCE. RP Bornstein, MH (reprint author), NICHHD, CHILD & FAMILY RES, BLDG 31, ROOM B2B15, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 75 TC 47 Z9 49 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0165-0254 EI 1464-0651 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD JUN PY 1996 VL 19 IS 2 BP 347 EP 367 PG 21 WC Psychology, Developmental SC Psychology GA UN915 UT WOS:A1996UN91500007 ER PT J AU Matsuzawa, M Weight, FF Potember, RS Liesi, P AF Matsuzawa, M Weight, FF Potember, RS Liesi, P TI Directional neurite outgrowth and axonal differentiation of embryonic hippocampal neurons are promoted by a neurite outgrowth domain of the B2-chain of laminin SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE neurite outgrowth; axonal differentiation; embryo; hippocampus; laminin ID COPLANAR MOLECULAR ASSEMBLIES; TO-SUBSTRATUM ADHESION; NERVOUS-SYSTEM; EXTRACELLULAR-MATRIX; NEUROBLASTOMA-CELLS; RETINAL AXONS; RAT-BRAIN; C-ELEGANS; S-LAMININ; B2 CHAIN AB Molecular cues involved in directional neurite outgrowth and axonal differentiation of embryonic hippocampal neurons were studied on substrates coated in a striped 5 mu m pattern with synthetic peptides from a neurite outgrowth (RDIAEIIKDI, P1543) and cell attachment (CDPGYIGSR, P364) domain of the B2- and B1-chains of laminin, respectively. Both peptides supported neuronal attachment, but only the B2-chain-derived P1543 promoted expression of a mature neuronal phenotype. Directional neurite outgrowth and axonal differentiation of embryonic hippocampal neurons were selectively induced by striped substrates of the B2-chain-derived P1543. Axonal differentiation was determined by expression of a phosphorylated epitope of the 200 kDa neurofilament protein in the longer ''axonal'' neurite of the bipolar embryonic hippocampal neurons. Ethanol (100 mM), a neuroactive compound known to delay neuronal development, impaired both directional neurite outgrowth and expression of a phosphorylated epitope of the 200 kDa neurofilament protein on a patterned P1543 substratum. The present results provide direct evidence that a 10 amino acid peptide (P1543), derived from a neurite outgrowth domain of the B2-chain of laminin, may be an axonal guidance and differentiation factor for embryonic hippocampal neurons in vitro. Published by Elsevier Science Ltd. C1 NIAAA, MOL & CELLULAR NEUROBIOL LAB, ROCKVILLE, MD 20852 USA. RIKEN, FRONTIER RES PROGRAM, WAKO, SAITAMA 35101, JAPAN. JOHNS HOPKINS UNIV, APPL PHYS LAB, LAUREL, MD 21205 USA. NR 77 TC 37 Z9 37 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUN PY 1996 VL 14 IS 3 BP 283 EP 295 DI 10.1016/0736-5748(96)00014-7 PG 13 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA UZ849 UT WOS:A1996UZ84900012 PM 8842805 ER PT J AU Weeks, BS Burbelo, P Jucker, M Weiner, MA Roque, E Kleinman, HK AF Weeks, BS Burbelo, P Jucker, M Weiner, MA Roque, E Kleinman, HK TI Laminin stimulates expression of two mitochondrial proteins during neurite outgrowth SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE laminin; neurite outgrowth; mitochondria; chargerin ID RAT-LIVER MITOCHONDRIA; CHARGERIN-II A6L; CYTOCHROME-OXIDASE; OXIDATIVE-PHOSPHORYLATION; ENERGY TRANSDUCTION; ATP SYNTHASE; HISTOCHEMICAL-LOCALIZATION; HYDROPHOBIC PROTEIN; ALZHEIMERS-DISEASE; BRAIN AB Differential hybridization was utilized with mRNA from NG108-15 cells cultured on either tissue culture plastic or laminin for 4 hr to identify genes whose mRNA was increased by laminin, a potent stimulator of neurite outgrowth. Two of the 16 laminin-induced clones, cytochrome b and chargerin II, are mitochondrial proteins. Northern blotting confirmed that laminin increased the mRNA levels of cytochrome b and chargerin II several fold. Antibody to chargerin II stained both processes and cell bodies of the cerebellar Purkinje cells and localized in the mitochondria of NG108-15 cells, which also showed increased protein levels in the presence of laminin. In addition, higher levels of chargerin II protein were detected in the newborn brain compared to the adult. However, inhibitors of mitochondrial protein synthesis did not affect lamininin-mediated neurite outgrowth. These data suggest that the increased synthesis of mitochondrial enzymes observed with laminin treatment may not be necessary for the formation of neurites. Copyright (C) 1996 ISDN. C1 UNIV PENN,DEPT MED,DIV INFECT DIS,PHILADELPHIA,PA 19104. NIDR,NIH,BETHESDA,MD 20892. HAMILTON COLL,DEPT BIOL,CLINTON,NY 13323. RP Weeks, BS (reprint author), SWISS FED INST TECHNOL,DEPT NEUROBIOL,ZURICH,SWITZERLAND. RI Burbelo, Peter/B-1027-2009 NR 55 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUN PY 1996 VL 14 IS 3 BP 365 EP 374 DI 10.1016/0736-5748(96)00019-6 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA UZ849 UT WOS:A1996UZ84900017 PM 8842810 ER PT J AU Andrieu, N Goldstein, AM AF Andrieu, N Goldstein, AM TI Use of relatives of cases as controls to identify risk factors when an interaction between environmental and genetic factors exists SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE odds ratios; genetic susceptibility; environmental exposure; relatives; interactions AB Background. The difficulty in detecting relevant risk factors for chronic diseases (such as breast and colon cancer) may be due to heterogeneity in the populations of studied cases, and one source of heterogeneity may be differential genetic susceptibility predisposing to differential environmental sensitivity. Method. The purpose of this investigation is to determine whether the estimates of odds ratios are modified by using relatives as controls when risk factors interact with an underlying genetic factor. Results. We demonstrate that using relative controls in matched case-control studies produces odds ratios different from population-based odds ratios, This difference is dependent on the amount of interaction between the genetic and environmental factors and on the genetic correlation between relatives, Conclusion. In the case of a common disease, the use of relatives as controls could be helpful in detecting interaction between an exposure and an underlying genetic factor when the genetic factor is common. C1 NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP Andrieu, N (reprint author), INST GUSTAVE ROUSSY,INSERM U351,UNITE RECH EPIDEMIOL CANC,F-94805 VILLEJUIF,FRANCE. RI ANDRIEU, Nadine/H-4255-2014 NR 6 TC 15 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 1996 VL 25 IS 3 BP 649 EP 657 DI 10.1093/ije/25.3.649 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VC482 UT WOS:A1996VC48200025 PM 8671569 ER PT J AU Newton, DL Pearson, JW Xue, Y Smith, MR Fogler, WE Mikulski, SM Alvord, WG Kung, HF Long, DL Rybak, SM AF Newton, DL Pearson, JW Xue, Y Smith, MR Fogler, WE Mikulski, SM Alvord, WG Kung, HF Long, DL Rybak, SM TI Anti-tumor ribonuclease, combined with or conjugated to monoclonal antibody MRK16, overcomes multidrug resistance to vincristine in vitro and in vivo SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE anti-tumor ribonuclease; multidrug resistance; antibody conjugates ID P-30 PROTEIN; CYTOTOXIC RIBONUCLEASE; DRUG-RESISTANCE; TRANSGENIC MICE; CELL-LINE; CANCER; INVITRO; IMMUNOTOXINS; ONCONASE(R); ADRIAMYCIN AB Onconase, a ribonuclease isolated from Rana pipiens oocytes and early embryos, is a member of the RNase A superfamily. Onconase has anti-neoplastic properties both in vitro and in vivo, and is undergoing clinical evaluation. In the present study, Onconase was combined with or conjugated to MRK16, an anti-P-glycoprotein (Pgp) monoclonal antibody. The interaction of these combinations with vincristine (VCR) against parental and multidrug resistant (MDR), Pgp expressing, human colon carcinoma cells caused increased VCR cytotoxicity in vitro and enhanced survival of athymic nude mice given transplants of drug resistant HT-29(mdr1) cells in vivo. The results suggest that combination treatment with Onconase and other agents that modulate the chemosensitivity of Pgp-expressing human tumor cells has the potential to overcome MDR. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. SAIC,BCDP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEI,FREDERICK,MD 21702. ALFACELL CORP,BLOOMFIELD,NJ 07003. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. NR 37 TC 12 Z9 12 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 1996 VL 8 IS 6 BP 1095 EP 1104 PG 10 WC Oncology SC Oncology GA UL272 UT WOS:A1996UL27200011 PM 21544469 ER PT J AU Saeki, T Takashima, S Hosokawa, S Moriwaki, S Nagasako, K Masaki, T Salomon, DS Ishitsuka, H AF Saeki, T Takashima, S Hosokawa, S Moriwaki, S Nagasako, K Masaki, T Salomon, DS Ishitsuka, H TI Differential expression of platelet-derived endothelial cell growth factor (thymidine phosphorylase) in nonpolypoid and polypoid lesions of the colon SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE platelet-derived endothelial cell growth factor; epidermal growth factor receptor; transforming growth factor alpha; nonpolypoid growth tumor; colon neoplasm ID FACTOR-ALPHA; COLORECTAL TUMORS; CARCINOMA; LINES AB To clarify the relationship between angiogenesis and the early development of colon cancer, expression of platelet-derived endothelial cell growth factor (PD-ECGF), a known angiogenic and endothelial cell chemotactic factor, was examined in 119 human colon premalignant adenomas and colon carcinomas. Localization of PD-ECGF was assessed by immunocytochemistry in 70 nonpolypoid growth (NPG) lesions that represented 29 carcinomas (NPG carcinomas) and 41 adenomas (NPG adenomas) and 49 polypoid growth (PC) lesions that included 15 carcinomas (PG carcinomas) and 34 adenomas (PC adenomas). Simultaneously, the expression of tranforming growth factor alpha (TGF alpha) and epidermal growth factor receptor (EGFR) were examined in serial sections from these lesions. Twenty (68.9%) of 29 NPC carcinomas and 20 (48.7%) of 41 NPC adenomas exhibited positive staining for PD-ECGF, whereas 15 (100%) of 15 PG carcinomas and 27 (79.4%) of 34 PG adenomas expressed PD-ECGF. There was a statistically significant difference in the frequency of PD-ECGF expression between NPG adenomas and PG adenomas (p<0.01). In addition, the incidence of PD-ECGF expression was higher in PG carcinomas than in NPG carcinomas (p<0.05). Positive staining for TGF alpha and EGFR was detected in 14 (48.2%) and 10 (34.5%) of 29 NPG carcinomas, respectively, whereas, 17 (41.5%) and 13 (31.7%) of 41 NPG adenomas expressed TGF alpha and EGFR, respectively. A significant trend for coexpression of PD-ECGF and TGF alpha was detected in either NPG adenomas (p<0.05) or PG adenomas (p<0.01). These data demonstrate that PD-ECGF may be involved in the early stages of colon cancer development during the adenoma-carcinoma transition and additionally that angiogenesis which may be induced by PD-ECGF and/or TGF alpha could play an important role of colon cancer development. C1 NATL SHIKOKU CANC CTR HOSP,DEPT SURG,MATSUYAMA,EHIME 790,JAPAN. GUNMA CANC CTR,MAEBASHI,GUMMA,JAPAN. UNIV TOKYO,DEPT SURG,TOKYO,JAPAN. NATL CANC INST,NIH,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD. NIPPON ROCHE RES CTR,DEPT ONCOL,KAMAKURA,KANAGAWA 247,JAPAN. NATL SHIKOKU CANC CTR HOSP,DEPT PATHOL,MATSUYAMA,EHIME 790,JAPAN. NATL SHIKOKU CANC CTR HOSP,DEPT INTERNAL MED,MATSUYAMA,EHIME 790,JAPAN. RP Saeki, T (reprint author), NATL SHIKOKU CANC CTR HOSP,DEPT CLIN RES,13 HORINOUCHI,MATSUYAMA,EHIME 790,JAPAN. NR 31 TC 8 Z9 8 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 1996 VL 8 IS 6 BP 1105 EP 1111 PG 7 WC Oncology SC Oncology GA UL272 UT WOS:A1996UL27200012 PM 21544470 ER PT J AU Bei, R Moretti, A Visco, V DeFilippi, R Tsang, KY Frati, L Muraro, R AF Bei, R Moretti, A Visco, V DeFilippi, R Tsang, KY Frati, L Muraro, R TI Cell mediated cytotoxicity of human colon carcinoma cells by a monoclonal antibody (R4) recognizing the carcinoembryonic antigen (CEA) and CEA-related molecules SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE monoclonal antibody; ADCC; CEA; NCA; colon carcinoma ID CYTO-TOXICITY; ANTICARCINOEMBRYONIC ANTIGEN; COLORECTAL-CARCINOMA; LUNG CARCINOMAS; HUMAN-MELANOMA; EXPRESSION; ENHANCEMENT; EPITOPES; FAMILY; GENE AB We report a novel anti-CEA monoclonal antibody (MAb) designated R4, which mediates antibody-dependent cell-mediated cytotoxicity (ADCC) of human colon carcinoma cells and displays differential reactivity for human carcinomas versus the normal counterparts. R4 (IgG1) reacted with the cell surface of 6 colon carcinoma cell lines expressing CEA. Western blot analysis and epitope mapping using native and baculovirus recombinant CEA and non specific cross-reacting antigen (NCA) demonstrated that MAb R4 recognizes a proteinic epitope located on the 3' end of the domain I shared by CEA and NCA molecules. Immunohistochemical analysis demonstrated an intense staining of MAb R4 with the majority of the neoplastic tissues tested, including colon (13/13), stomach (2/2), breast (9/10), lung (7/10) and endometrial (2/4) carcinomas, whereas no reactivity with the correspondent normal tissues was observed. Using human PBLs from healthy donors as effector cells, we have shown that MAb R4 mediated antibody dependent-cell mediated cytotoxicity (ADCC) of human carcinoma cells LS-174T, CBS and WiDr. This activity was enhanced after PBLs activation with interleukin-2 (IL-2). The specificity of MAb R4 for an epitope shared by two tumor overexpressed antigens, CEA and NCA, resulting in an intense reactivity with neoplastic cells and the peculiar property to mediate ADCC, indicate that MAb R4 might be a novel powerful reagent for diagnostic and immunotherapy of carcinoma patients. C1 UNIV ROMA LA SAPIENZA,DIPARTIMENTO MED SPERIMENTALE & PATOL,I-00161 ROME,ITALY. NATL CANC INST,NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD. UNIV G DANNUNZIO,INST HUMAN PATHOL & SOCIAL MED,CHIETI,ITALY. NR 41 TC 11 Z9 11 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 1996 VL 8 IS 6 BP 1127 EP 1135 PG 9 WC Oncology SC Oncology GA UL272 UT WOS:A1996UL27200015 PM 21544473 ER PT J AU Ferguson, JH AF Ferguson, JH TI The NIH Consensus Development Program - The evolution of guidelines SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article ID CONFERENCES AB The U.S. National institutes of Health (NIH) Consensus Development Program (CDP) Guidelines have undergone some modifications over the program's 18-year history. They have never been published in archival form. This article reviews the evolution oi the NIH CDP Guidelines and then presents the complete 1995 version. RP Ferguson, JH (reprint author), NIH,OFF MED APPLICAT RES,FED BLDG,ROOM 618,BETHESDA,MD 20892, USA. NR 24 TC 25 Z9 25 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SUM PY 1996 VL 12 IS 3 BP 460 EP 474 PG 15 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA VE728 UT WOS:A1996VE72800006 PM 8840666 ER PT J AU Borras, T Tamm, ER Zigler, JS AF Borras, T Tamm, ER Zigler, JS TI Ocular adenovirus gene transfer varies in efficiency and inflammatory response SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE adenovirus; anterior segment cells; gene transfer; inflammation; lens organ cultures ID CRYSTALLIN; CATARACTS; LENS; SPECIFICITY; MUTATION; DELETION; BINDING; RABBIT; CELLS; EYE AB Purpose, To study the effects of adenoviral gene transfer to the tissues of the anterior segment in vitro by rat and monkey lens organ cultures and in vivo by single injection into the anterior chamber of rabbits. Methods. In vitro, intact lens cultures were exposed to 1 to 4 x 10(8) pfu Av1LacZ4 and Av1Luc1 in TC199 medium containing no serum or growth factors. Av1LacZ4 and AvlLucl are replica tion-deficient adenovirus vectors, carrying the reporter genes Escherichia coli LacZ and firefly luciferase, respectively. In vivo, The anterior chambers of eight rabbits were injected once with 20 mu l Av1LacZ4 (8 x 10(8) pfu) and evaluated 48 hours after injection. Enzyme activity of the reporter genes was measured biochemically and histochemically. Results, In organ cultures, adenovirus delivers reporter genes efficiently to the ciliary processes but penetrates poorly into the capsulated lenses. Viral receptors, however, are present in rat lens epithelium, as in primary trabecular meshwork and other lens cell lines. In vivo, gene transfer was evident in corneal endothelium, iris anterior surface, and trabecular meshwork, Presence of the virus did not affect lens transparency or provoke external discomfort signs, Infected corneal endothelial cells were swollen and partly detached; 3 of 8 infected eyes showed a severe inflammatory response in chamber angle, anterior uvea, and limbal conjunctiva. Conclusions, These findings reveal the distinct gene transfer potential of each of the tissues of the anterior segment and emphasize the need to address the inflammatory response to these first-generation adenoviral vectors. C1 NEI,MOLEC & DEV BIOL LAB,NIH,BETHESDA,MD 20892. RP Borras, T (reprint author), NEI,LAB MECHANISMS OCULAR DIS,NIH,BLDG 6,ROOM 237,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 80 Z9 83 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1996 VL 37 IS 7 BP 1282 EP 1293 PG 12 WC Ophthalmology SC Ophthalmology GA UP572 UT WOS:A1996UP57200009 PM 8641831 ER PT J AU Arora, JK Lysz, TW Zelenka, PS AF Arora, JK Lysz, TW Zelenka, PS TI A role for 12(S)-HETE in the response of human lens epithelial cells to epidermal growth factor and insulin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE epidermal growth factor; human lens epithelial cells; 12(S)-hydroxyeicosatetraenoic acid; insulin; 12-lipoxygenase ID PLATELET-ACTIVATING FACTOR; ARACHIDONIC-ACID; MOLECULAR-CLONING; 12-LIPOXYGENASE; METABOLITES; EXPRESSION; PROTEINS AB Purpose. To determine whether the 12-lipoxygenase pathway of arachidonic acid metabolism is present in the human lens and whether 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) plays a role in regulating proto-oncogene expression and DNA synthesis in human lens epithelial cells (HLECs). Methods, Second- and third-passage primary cultures of HLECs were used for analysis. Human cataract epithelia were obtained from surgery. 12-lipoxygenase mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the PCR product was sequenced. The 12-lipoxygenase protein was detected by immunoblotting. 12(S)-HETE was detected in HLEG-conditioned medium by radioimmunoassay. For studies of growth factor-induced mitogenesis, HLECs were serum starved, then stimulated with 15 ng/ml epidermal growth factor (EGF) and 1 mu g/ml insulin or with 0.3 mu M 12(S)-HETE. The 12-lipoxygenase inhibitor, cinnamyl-3, 4-dihydroxy-alpha-cyanocinnamate (CDC, 10 mu M) was used to block endogenous 12-lipoxygenase activity. Expression of c-fos mRNA was determined by RT-PCR, and DNA synthesis was measured by H-3-thymidine incorporation. Results. 12-lipoxygenase mRNA and protein were detected in HLECs and in human cataract tissues. 12(S)-HETE was released into the medium by HLECs in the presence of EGF-insulin. Stimulation of c-fos mRNA expression and DNA synthesis by EGF-insulin was inhibited when the la-lipoxygenase pathway was blocked by CDC, This inhibition was reversed completely by exogenously added 12(S)-HETE. However, exogenous 12(S)-HETE was unable to stimulate HLEC DNA synthesis in the absence of growth factors. Conclusions, The 12-lipoxygenase pathway of arachidonic acid metabolism is present in human lens epithelial cells. 12(S)-HETE does not stimulate HLEC DNA synthesis in the absence of growth factors but enables the cellular response to EGF and insulin. C1 NEI,LMDB,NATL INST HLTH,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT SURG & ANAT,NEWARK,NJ 07103. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT CELL BIOL,NEWARK,NJ 07103. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT INJURY SCI,NEWARK,NJ 07103. NR 31 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1996 VL 37 IS 7 BP 1411 EP 1418 PG 8 WC Ophthalmology SC Ophthalmology GA UP572 UT WOS:A1996UP57200021 PM 8641843 ER PT J AU Kessler, HA Hurwitz, S Farthing, C Benson, CA Feinberg, J Kuritzkes, DR Bailey, TC Safrin, S Steigbigel, RT Cheeseman, SH McKinley, GF Wettlaufer, B Owens, S Nevin, T Korvick, JA Valentine, F DeHolczer, L Weaver, D Pottage, J Urbanski, P Bartlett, JG Becker, R Rexroad, V Schooley, R Ray, G Powderly, W Gould, M Royal, M Calo, J Coleman, R Mariuz, P Weissman, E Burk, RA Avato, J Mangini, L Grieco, M AF Kessler, HA Hurwitz, S Farthing, C Benson, CA Feinberg, J Kuritzkes, DR Bailey, TC Safrin, S Steigbigel, RT Cheeseman, SH McKinley, GF Wettlaufer, B Owens, S Nevin, T Korvick, JA Valentine, F DeHolczer, L Weaver, D Pottage, J Urbanski, P Bartlett, JG Becker, R Rexroad, V Schooley, R Ray, G Powderly, W Gould, M Royal, M Calo, J Coleman, R Mariuz, P Weissman, E Burk, RA Avato, J Mangini, L Grieco, M TI Pilot study of topical trifluridine for the treatment of acyclovir-resistant mucocutaneous herpes simplex disease in patients with AIDS (ACTG 172) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE herpes simplex; acyclovir; resistance; trifluridine; topical; HIV ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ALTERED SUBSTRATE-SPECIFICITY; VIRUS-INFECTIONS; CONTINUOUS-INFUSION; FOSCARNET THERAPY; THYMIDINE KINASE; TRIFLUOROTHYMIDINE; INVITRO; MUTANTS; TYPE-2 AB Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1% ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29%) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had greater than or equal to 50% reduction in lesion area. The overall estimated median time to 50% healing was 2.4 weeks. Ten (42%) patients discontinued treatment for reasons other than primary treatment failure and seven (29%) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area(p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33%) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients. C1 RUSH MED COLL,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. HARVARD UNIV,SCH PUBL HLTH,STAT & DATA ANAL CTR,BOSTON,MA 02115. NYU,BELLVUE HOSP CTR,DEPT MED,NEW YORK,NY. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794. COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP CTR,DEPT MED,NEW YORK,NY. FRONTIER SCI & TECHNOL RES FDN INC,AMHERST,MA. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01605. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,DENVER,CO 80202. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. RP Kessler, HA (reprint author), RUSH MED COLL,INFECT DIS SECT,DEPT MED,600 S PAULINA,ST 143 ACFAC,CHICAGO,IL 60612, USA. NR 36 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN 1 PY 1996 VL 12 IS 2 BP 147 EP 152 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UP366 UT WOS:A1996UP36600007 PM 8680885 ER PT J AU Kaplan, JE Khabbaz, RF Murphy, EL Hermansen, S Roberts, C Lal, R Heneine, W Wright, D Matijas, L Thomson, R Rudolph, D Switzer, WM Kleinman, S Busch, M Schreiber, GB Williams, AE Nass, CC Ownby, HE Shafer, AW Kleinman, SH Hutching, S Busch, MP Gilcher, RO Smith, JW Thomson, RA Nemo, GJ Zuck, TF AF Kaplan, JE Khabbaz, RF Murphy, EL Hermansen, S Roberts, C Lal, R Heneine, W Wright, D Matijas, L Thomson, R Rudolph, D Switzer, WM Kleinman, S Busch, M Schreiber, GB Williams, AE Nass, CC Ownby, HE Shafer, AW Kleinman, SH Hutching, S Busch, MP Gilcher, RO Smith, JW Thomson, RA Nemo, GJ Zuck, TF TI Male-to-female transmission of human T-cell lymphotropic virus types I and II: Association with viral load SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE human T-lymphotropic virus; HTLV; HTLV-I; HTLV-II; sexual transmission; viral load ID HTLV-I; SEXUAL TRANSMISSION; SYNTHETIC PEPTIDES; LEUKEMIA-VIRUS; ANTIBODY; EPITOPES; MYELOPATHY; INFECTION; HIV-1 AB Risk factors for male-to-female sexual transmission of human T-lymphotropic virus types I and II (HTLV-I/II) were investigated among HTLV-seropositive volunteer blood donors and their long-term (greater than or equal to 6 month) sex partners. Direction of transmission in concordantly seropositive pairs was assessed by analyzing risk factors for HTLV infection. Donors and their partners were also questioned regarding sexual behaviors during their relationships; HTLV antibody titers and viral load were determined for specimens from male partners. Among 31 couples in whom HTLV-infected men likely transmitted infection to their partners (11 HTLV-I and 20 HTLV-II) and 25 male-positive, female-negative couples (8 HTLV-I and 17 HTLV-II), HTLV transmitter men had been in their relationships longer (mean 225 months vs. 122 months) and had higher viral loads (geometric mean 257,549 vs. 2,945 copies/300,000 cells for HTLV-I; 5,541 vs. 118 copies/300,000 cells for HTLV-II) than non-transmitters (P = 0.018 and P = 0.001 for duration of relationship and viral load, respectively, logistic regression analysis). Transmitter men also tended to have higher antibody titers against various env and whole virus proteins than non-transmitters. The identification of high viral load and duration of relationship as risk factors provides a biologically plausible framework in which to assess risk of sexual transmission of the HTLVs. C1 CTR DIS CONTROL & PREVENT,RETROVIRUS DIS BRANCH,DIV VIRAL & RICKETTSIAL DIS,NATL CTR INFECT DIS,ATLANTA,GA 30341. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. WESTAT CORP,ROCKVILLE,MD 20850. SRA TECHNOL INC,ROCKVILLE,MD. AMER RED CROSS,BLOOD SERV,SO CAL REG,LOS ANGELES,CA 90006. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA. NHLBI,NIH,BETHESDA,MD 20892. HOLLAND LAB BIOMED SCI,ROCKVILLE,MD. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. AMER RED CROSS,BLOOD SERV,GREATER CHESAPEAKE & POTOMAC REG,WASHINGTON,DC. AMER RED CROSS,BLOOD SERV,SE MICHIGAN REG,WASHINGTON,DC. UNIV CALIF SAN FRANCISCO,MED CTR,SAN FRANCISCO,CA 94143. OKLAHOMA BLOOD INST,OKLAHOMA CITY,OK. HOXWORTH BLOOD CTR,CINCINNATI,OH. FU NHLBI NIH HHS [N01 HB 97077, N01 HB 47114, HB97079] NR 40 TC 83 Z9 85 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN 1 PY 1996 VL 12 IS 2 BP 193 EP 201 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UP366 UT WOS:A1996UP36600014 PM 8680892 ER PT J AU GeaBanacloche, JC Metcalfe, DD AF GeaBanacloche, JC Metcalfe, DD TI Ciprofloxacin desensitization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID ANAPHYLACTOID REACTIONS C1 UNIV AUTONOMA MADRID,CLIN PUERTA HIERRO,SERV MED INTERNA 1,MADRID,SPAIN. RP GeaBanacloche, JC (reprint author), NIAID,LAB ALLERG DIS,NIH,BLDG 10,ROOM 11S231,10 CTR DR,MSC 1888,BETHESDA,MD 20892, USA. NR 5 TC 26 Z9 28 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1996 VL 97 IS 6 BP 1426 EP 1427 DI 10.1016/S0091-6749(96)70218-X PG 2 WC Allergy; Immunology SC Allergy; Immunology GA VD607 UT WOS:A1996VD60700038 PM 8648046 ER PT J AU Freeman, BD Correa, R Karzai, W Natanson, C Patterson, M Banks, S Fitz, Y Danner, RL Wilson, L Eichacker, PQ AF Freeman, BD Correa, R Karzai, W Natanson, C Patterson, M Banks, S Fitz, Y Danner, RL Wilson, L Eichacker, PQ TI Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E-coli pneumonia in rats SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE monoclonal antibody 1b6; CD11b/CD18; recombinant granulocyte colony-stimulating factor; oxygen toxicity; Escherichia coli ID COLONY-STIMULATING FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; REDUCES ORGAN INJURY; INDUCED LUNG INJURY; MONOCLONAL-ANTIBODY; LEUKOCYTE ADHESION; SEPTIC SHOCK; HEMORRHAGIC-SHOCK; HUMAN-NEUTROPHILS; CD18 AB We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O-2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O-2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb, 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004), Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O-2 concentration, during E. coli pneumonia (1.74 x 1.20 and 2.39 x/divided by 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 x 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 x 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection. C1 NIH,CRIT CARE MED DEPT,BETHESDA,MD 20892. NR 56 TC 54 Z9 54 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 1996 VL 80 IS 6 BP 2066 EP 2076 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA UV413 UT WOS:A1996UV41300030 PM 8806915 ER PT J AU Marconi, RT Casjens, S Munderloh, UG Samuels, DS AF Marconi, RT Casjens, S Munderloh, UG Samuels, DS TI Analysis of linear plasmid dimers in Borrelia burgdorferi sensu late isolates: Implications concerning the potential mechanism of linear plasmid replication SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE AGENT; POLYMERASE CHAIN-REACTION; SP-NOV; DNA; IDENTIFICATION; CHROMOSOME; SPIROCHETE; PROTEIN AB The Borrelia genome is composed of a linear chromosome and a number of variable circular and linear plasmids. Atypically large linear plasmids of 92 to 105 kb have been identified in several Borrelia burgdorferi sensu late isolates and characterized. These plasmids carry the p27 and ospAB genes, which in other isolates reside on a 50-kb plasmid. Here we demonstrate that these plasmids are dimers of the 50-kb ospAB plasmid (pAB50). The 94-kb plasmid from isolate VS116, pVS94, was an exception and did not hybridize with any plasmid gene probes. When this plasmid was used as a probe, homologous sequences in other isolates were not detected, suggesting that it is unique to isolate VS116. These analyses provide insight into the mechanism of linear plasmid replication and the mechanisms by which plasmid variability can arise. C1 UNIV UTAH,MED CTR,DEPT ONCOL SCI,SALT LAKE CITY,UT 84132. UNIV MINNESOTA,DEPT ENTOMOL,ST PAUL,MN 55108. NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. RP Marconi, RT (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MICROBIOL & IMMUNOL,RICHMOND,VA 23298, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 NR 39 TC 39 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1996 VL 178 IS 11 BP 3357 EP 3361 PG 5 WC Microbiology SC Microbiology GA UN518 UT WOS:A1996UN51800051 PM 8655522 ER PT J AU Stevenson, B Tilly, K Rosa, PA AF Stevenson, B Tilly, K Rosa, PA TI A family of genes located on four separate 32-kilobase circular plasmids in Borrelia burgdorferi B31 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; POLYMERASE CHAIN-REACTION; MOLECULAR ANALYSIS; LINEAR-PLASMID; OSPC GENE; PROTEINS; AGENT; ALIGNMENT; STRAINS AB We have identified four loci Borrelia burgdorferi B31 that contain open reading frames capable of encoding six proteins that are related to the antigenic proteins OspE and OspF. We have designated these proteins Erp, for OspEF-related protein, and named their respective genes erp. The erpA erpB genes are linked, as ar erpC and erpD, and the pairs probably constitute tow operons. The erpG and erpH genes appear to be monocistronic. The ErpA and ErpC proteins are expressed by B. burgdorferi B31 in culture and are recognized by polyclonal antiserum raised against the OspE protein of B. burgdorferi N40. The four erp loci are ach located on different 32-kb circular plasmids that contain additional DNA sequences that are homologous to each other and to an 8.3-kb circular plasmid of B. burgdorferi sensu lato Ip21. All four 32-kb plasmids can be maintained within a single bacterium, which may provide a model for the study of plasmid replication and segregation in B. burgdorferi. RP Stevenson, B (reprint author), NIAID, ROCKY MT LABS, MICROBIAL STRUCT & FUNCT LAB, NIH, 903 S 4TH ST, HAMILTON, MT 59840 USA. NR 57 TC 110 Z9 110 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1996 VL 178 IS 12 BP 3508 EP 3516 PG 9 WC Microbiology SC Microbiology GA UQ346 UT WOS:A1996UQ34600014 PM 8655548 ER PT J AU Frank, EG Gonzalez, M Ennis, DG Levine, AS Woodgate, R AF Frank, EG Gonzalez, M Ennis, DG Levine, AS Woodgate, R TI In vivo stability of the Umu mutagenesis proteins: A major role for RecA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PHAGE-LAMBDA-REPRESSOR; ESCHERICHIA-COLI; SOS MUTAGENESIS; DIRECTED CLEAVAGE; DNA; MUTANTS; GENES; OVERPRODUCTION; POLYNUCLEOTIDE; PURIFICATION AB The Escherichia coli Umu proteins play critical roles in damage-inducible SOS mutagenesis. To avoid any gratuitous mutagenesis, the activity of the Umu proteins is normally kept to a minimum by tight transcriptional and posttranslational regulation, We have, However, previously observed that compared with an isogenic RecA(+) strain, the steady-state levels of the Umu proteins are elevated in a recA730 background (R.Woodgate and D. G. Ennis, Mol. Gen. Genet. 229:10-16, 1991). We have investigated this phenomenon further and find that another coprotease-constitutive (recA*) mutant, a recA432 strain, exhibits a similar phenotype. Analysis revealed that the increased steady-state levels of the Umu proteins in the rec4* strains do indeed reflect an in vivo stabilization of the proteins, We have investigated the basis for the phenomenon and find that the mutant RecA* protein stabilizes the Umu proteins by not only converting the labile UmuD protein to the much more stable (and mutagenically active) UmuD' protein but by directly stabilizing UmuD' itself, In contrast, UmuC does not appear to be directly stabilized by RecA* but is instead dramatically stabilized in the presence of UmoD'. On the basis of these observations, we suggest that formation of a UmuD'C-RecA*-DNA quaternary complex protects the UmuD'C proteins from proteolytic degradation and as a consequence helps to promote the switch from error-free to error-prone mechanisms of DNA repair. C1 NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. CALTECH,DIV BIOL,PASADENA,CA 91125. NR 47 TC 46 Z9 47 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1996 VL 178 IS 12 BP 3550 EP 3556 PG 7 WC Microbiology SC Microbiology GA UQ346 UT WOS:A1996UQ34600019 PM 8655553 ER PT J AU Radziszewska, B Richardson, JL Dent, CW Flay, BR AF Radziszewska, B Richardson, JL Dent, CW Flay, BR TI Parenting style and adolescent depressive symptoms, smoking, and academic achievement: Ethnic, gender, and SES differences SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE parenting style; adolescent adjustment; ethnicity; gender; socioeconomic status ID SCHOOL; FAMILY; SOCIALIZATION; INVOLVEMENT; CHILDREN; MOOD AB This paper examines whether the relationship between parenting style and adolescent depressive symptoms, smoking, and academic grades varies according to ethnicity, gender and socioeconomic status. Four parenting styles are distinguished, based on patterns of parent-adolescent decision making: autocratic (parents decide), authoritative (joint process but parents decide), permissive (joint process but adolescent decides), and unengaged (adolescent decides). The sample included 3993 15-year-old White, Hispanic, African-American, and Asian adolescents. Results are generally consistent with previous findings. adolescents with authoritative parents had the best outcomes and those with unengaged parents were least well adjusted, while the permissive and the autocratic styles produced intermediate results. For the most part, this pattern held across ethnic and sociodemographic subgroups. There was one exception, suggesting that the relationship between parenting styles, especially the unengaged style, and depressive symptoms may vary according to gender and ethnicity. More research is needed to replicate and explain this pattern in terms of ecological factors, cultural norms, and socialization goals and practices. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. UNIV ILLINOIS,SCH PUBL HLTH,CHICAGO,IL. RP Radziszewska, B (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,PREVENT RES BRANCH,6100 EXECUT BLVD,ROOM 7B05,BETHESDA,MD 20892, USA. RI Flay, Brian/A-8517-2008 OI Flay, Brian/0000-0002-5209-2766 NR 32 TC 115 Z9 118 U1 2 U2 33 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD JUN PY 1996 VL 19 IS 3 BP 289 EP 305 DI 10.1007/BF01857770 PG 17 WC Psychology, Clinical SC Psychology GA UJ350 UT WOS:A1996UJ35000005 PM 8740470 ER PT J AU Siegel, KL Kepple, TM Caldwell, GE AF Siegel, KL Kepple, TM Caldwell, GE TI Improved agreement of foot segmental power and rate of energy change during gait: Inclusion of distal power terms and use of three-dimensional models SO JOURNAL OF BIOMECHANICS LA English DT Article DE mechanical energy; power; foot; gait ID EXPENDITURE PROBLEM; FRACTIONS APPROACH; TRANSFERS; WALKING; STANCE AB Traditional models used to calculate foot segmental power have yielded poor agreement between foot power and the rate of energy change during the stance phase of gait and limited the applicability of foot segmental power analyses to swing phase only. The purpose of this study was to improve the agreement of foot segmental power and rate of energy change by using more inclusive models to calculate foot segmental power and energy The gait of 15 adult subjects was studied and models were used to calculate foot segmental power that included either the proximal terms only (Model P, the most common method in the literature) or both proximal and distal terms (Model PD, a mathematically complete model). Power and energy terms were computed in two ways, from sagittal plane vector components only (two-dimensional condition) and from complete three-dimensional components (three-dimensional condition). Results revealed that the more inclusive the model, the higher the agreement of foot power and rate of energy change. During stance phase, Model P produced poor agreement (r(c) = 0.108) for both two-dimensional and three-dimensional conditions, Model PD-2D yielded higher agreement (r(c) = 0.645), and Model PD-3D exhibited nearly perfect agreement (r(c) = 0.956). The advantages of a segmental power analysis include the ability to identify the mechanisms of energy transfer into and out of the foot during movement. The results of this study suggest that foot power analyses are valid when using Model PD-3D to describe foot function during locomotion. Published by Elsevier Science Ltd. C1 UNIV MASSACHUSETTS,DEPT EXERCISE SCI,AMHERST,MA 01003. RP Siegel, KL (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,BIOMECH LAB,BLDG 10,RM 6S235,BETHESDA,MD 20892, USA. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 23 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD JUN PY 1996 VL 29 IS 6 BP 823 EP 827 DI 10.1016/0021-9290(96)83336-7 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA UK442 UT WOS:A1996UK44200016 PM 9147982 ER PT J AU Luck, LA Vance, JE OConnell, TM London, RE AF Luck, LA Vance, JE OConnell, TM London, RE TI F-19 NMR relaxation studies on 5-fluorotryptophan- and tetradeutero-5-fluorotryptophan-labeled E-coli glucose/galactose receptor SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE glucose/galactose receptor; GGR; F-19 NMR; fluorotryptophan; protein dynamics ID NUCLEAR-MAGNETIC-RESONANCE; GALACTOSE CHEMOSENSORY RECEPTOR; D-LACTATE DEHYDROGENASE; ESCHERICHIA-COLI; BINDING-PROTEIN; DIHYDROFOLATE-REDUCTASE; STRUCTURAL-CHANGE; SPIN RELAXATION; LIGAND-BINDING; SPECTROSCOPY AB F-19 NMR relaxation studies have been carried out on a fluorotryptophan-labeled E. coli periplasmic glucose/galactose receptor (GGR). The protein was derived from E. coli grown on a medium containing a 50:50 mixture of 5-fluorotryptophan and [2,4,6,7-H-2(4)]-5-fluorotryprophan. As a result of the large gamma-isotope shift, the two labels give rise to separate resonances, allowing relaxation contributions of the substituted indole protons to be selectively monitored. Spin-lattice relaxation rates were determined at field strengths of 11.75 T and 8.5 T, and the results were analyzed using a model-free formalism. In order to evaluate the contributions of chemical shift anisotropy to the observed relaxation parameters, solid-state NMR studies were performed on [2,4,6,7-H-2(4)]-5-fluorotryptophan. Analysis of the observed F-19 powder pattern lineshape resulted in anisotropy and asymmetry parameters of Delta sigma = -93.5 ppm and eta = 0.24. Theoretical analyses of the relaxation parameters are consistent with internal motion of the fluorotryptophan residues characterized by order parameters S-2 of similar to 1, and by correlation rimes for internal motion similar to 10(-11) s. Simultaneous least squares fitting of the spin-lattice relaxation and line-width data with tau(i) set al 10 ps yielded a molecular correlation time of 20 ns for the glucose-complexed GCR, and a mean order parameter S-2=0.89 for fluorotryptophan residues 183, 127, 133, and 195. By contrast, the calculated order parameter for FTrp(284), located on the surface of the protein, was 0.77. Significant differences among the spin-lattice relaxation rates of the five fluorotryptophan residues of glucose-complexed GGR were also observed, with the order of relaxation rates given by: R(1F)(183)>R(1F)(127)similar to R(1F)(133)similar to R(1F)(195)>R(1F)(284). Although such differences may reflect motional variations among these residues, the effects are largely predicted by differences in the distribution of nearby hydrogen nuclei, derived from crystal structure data. In the absence of glucose, spin-lattice relaxation rates for fluorotryptophan residues 183, 127, 133, and 195 were found to decrease by a mean of 13%, while the value for residue 284 exhibits an increase of similar magnitude relative to the liganded molecule. These changes are interpreted in terms of a slower overall correlation time for molecular motion, as well as a change in the internal mobility of FTrp(284), located in the hinge region of the receptor. C1 NIEHS,MOL BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. NR 40 TC 19 Z9 20 U1 2 U2 13 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUN PY 1996 VL 7 IS 4 BP 261 EP 272 PG 12 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA VB120 UT WOS:A1996VB12000001 PM 8765734 ER PT J AU Copie, V Battles, JA Schwab, JM Torchia, DA AF Copie, V Battles, JA Schwab, JM Torchia, DA TI Secondary structure of beta-hydroxydecanoyl thiol ester dehydrase, a 39-kDa protein, derived from H-alpha, C-alpha, C-beta and CO signal assignments and the chemical shift index: Comparison with the crystal structure SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE triple-resonance spectroscopy; NMR signal assignment; Chemical Shift Index; protein secondary structure ID TRIPLE-RESONANCE NMR; SIDE-CHAIN RESONANCES; C-13/N-15-ENRICHED PROTEINS; SEQUENTIAL ASSIGNMENT; BACKBONE ASSIGNMENTS; THIOESTER DEHYDRASE; LARGER PROTEINS; N-15; C-13; SPECTROSCOPY AB Nearly complete backbone H-1, N-15 and C-13 Signal assignments are reported for beta-hydroxydecanoyl thiol ester dehydrase, a 39-kDa homodimer containing 342 amino acids. Although N-15 relaxation data show that the protein has a rotational correlation time of 18 ns, assignments were derived from triple-resonance experiments recorded at 500 MHz and pH 6.8, without deuteration. The Chemical Shift Index, CSI, identified two long helices and numerous beta-strands in dehydrase. The CSI predictions are in close agreement with the secondary structure identified in the recently derived crystal structure, particularly when one takes account of the numerous bulges in the beta-strands. The assignment of dehydrase and a large deuterated protein [Yamazaki et al. (1994) J. Am. Chem. Sec, 116, 11655-11666] suggest that assignment of 40-60 kDa proteins is feasible. Hence, further progress in understanding the chemical shift/structure relationship could open the way to determine the structures of such large proteins. C1 PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. NIDR,STRUCT MOL BIOL UNIT,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM36286] NR 29 TC 13 Z9 13 U1 0 U2 3 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUN PY 1996 VL 7 IS 4 BP 335 EP 340 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA VB120 UT WOS:A1996VB12000008 PM 8765740 ER PT J AU Geering, K Beggah, A Good, P Girardet, S Roy, S Schaer, D Jaunin, P AF Geering, K Beggah, A Good, P Girardet, S Roy, S Schaer, D Jaunin, P TI Oligomerization and maturation of Na,K-ATPase: Functional interaction of the cytoplasmic NH2 terminus of the beta subunit with the alpha subunit SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NA+-K+-ATPASE; INTRACELLULAR-TRANSPORT; XENOPUS-OOCYTES; PRIMARY SEQUENCE; EXPRESSION; PROTEINS; LAEVIS; CHAIN; NA,K-PUMP; LOCATION AB Subunit assembly plays an essential role in the maturation of oligomeric proteins. In this study, we have characterized the main structural and functional consequences of the assembly of alpha and beta subunits of Na,K-ATPase. Xenopus oocytes injected with alpha and/or beta cRNA were treated with brefeldin A, which permitted the accumulation of individual subunits or alpha-beta complexes in the ER. Only alpha subunits that are associated with beta subunits become resistant to trypsin digestion and cellular degradation. Similarly, assembly with beta subunits is necessary and probably sufficient for the catalytic alpha subunit to acquire its main functional properties at the level of the ER, namely the ability to adopt different ligand-dependent conformations and to hydrolyze ATP in an Na+- and K+-dependent, ouabain-inhibitable fashion. Not only the alpha but also the beta subunit undergoes a structural change after assembly, which results in a global increase in its protease resistance. Furthermore, extensive and controlled proteolysis assays on wild-type and NH2-terminally modified beta subunits revealed a K+-dependent interaction of the cytoplasmic NH2 terminus of the beta subunit with the or subunit, which is likely to be involved in the modulation of the K+-activation of the Na,K-pump transport activity. Thus, we conclude that the ER assembly process not only establishes the basic structural interactions between individual subunits, which are required for the maturation of oligomeric proteins, but also distinct, functional interactions, which are involved in the regulation of functional properties of mature proteins. C1 NICHHD, NATL INST HLTH, DEPT HLTH & HUMAN SERV, BETHESDA, MD 20892 USA. RP UNIV LAUSANNE, INST PHARMACOL & TOXICOL, RUE BUGNON 27, CH-1005 LAUSANNE, SWITZERLAND. NR 38 TC 122 Z9 123 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1996 VL 133 IS 6 BP 1193 EP 1204 DI 10.1083/jcb.133.6.1193 PG 12 WC Cell Biology SC Cell Biology GA UT407 UT WOS:A1996UT40700005 PM 8682858 ER PT J AU Moursi, AM Damsky, CH Lull, J Zimmerman, D Doty, SB Aota, SI Globus, RK AF Moursi, AM Damsky, CH Lull, J Zimmerman, D Doty, SB Aota, SI Globus, RK TI Fibronectin regulates calvarial osteoblast differentiation SO JOURNAL OF CELL SCIENCE LA English DT Article DE fibronectin; osteoblast differentiation; RGD sequence; fetal rat calvarial osteoblast ID HEPARIN-BINDING DOMAIN; EXTRACELLULAR-MATRIX; SIGNAL TRANSDUCTION; GENE-EXPRESSION; ALKALINE-PHOSPHATASE; CELL-INTERACTION; SARCOMA CELLS; BONE-CELLS; ADHESION; INTEGRIN AB The secretion of fibronectin by differentiating osteoblasts and its accumulation at sites of osteogenesis suggest that fibronectin participates in bone formation. To test this directly, we determined whether fibronectin-cell interactions regulate progressive differentiation of cultured fetal rat calvarial osteoblasts. Spatial distributions of alpha 5 integrin subunit, fibronectin, osteopontin (bone sialoprotein I) and osteocalcin (bone Gla-protein) were similar in fetal rat calvaria and mineralized, bone-like nodules formed by cultured osteoblasts. Addition of antifibronectin antibodies to cultures at confluence reduced subsequent formation of nodules to less than 10% of control values, showing that fibronectin is required for normal nodule morphogenesis. Anti-fibronectin antibodies selectively inhibited steady-state expression of mRNA for genes associated with osteoblast differentiation; mRNA levels for alkaline phosphatase and osteocalcin were suppressed, whereas fibronectin, type I collagen and osteopontin were unaffected. To identify functionally relevant domains of fibronectin, we treated cells with soluble fibronectin fragments and peptides. Cell-binding fibronectin fragments (type III repeats 6-10) containing the Arg-Gly-Asp (RGD) sequence blocked both nodule initiation and maturation, whether or not they contained a functional synergy site. In contrast, addition of the RGD-containing peptide GRGDSPK alone did not inhibit nodule initiation, although it did block nodule maturation. Thus, in addition to the RGD sequence, other features of the large cell-binding fragments contribute to the full osteogenic effects of fibronectin. Nodule formation and osteoblast differentiation resumed after anti-fibronectin antibodies or GRGDSPK peptides were omitted from the media, showing that the inhibition was reversible and the treatments were not cytotoxic. Outside the central cell-binding domain, peptides from the IIICS region and antibodies to the N terminus did not inhibit nodule formation. We conclude that osteoblasts interact with the central cell-binding domain of endogenously produced fibronectin during early stages of differentiation, and that these interactions regulate both normal morphogenesis and gene expression. C1 UNIV CALIF SAN FRANCISCO,DEPT STOMATOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. NASA,AMES RES CTR,MOFFETT FIELD,CA 94035. HOSP SPECIAL SURG,NEW YORK,NY 10021. NIDR,BETHESDA,MD 20892. FU NIDCR NIH HHS [P50-DE10306, T32 DE07204] NR 50 TC 219 Z9 224 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 1996 VL 109 BP 1369 EP 1380 PN 6 PG 12 WC Cell Biology SC Cell Biology GA UU359 UT WOS:A1996UU35900020 PM 8799825 ER PT J AU Jarnik, M Kartasova, T Steinert, PM Lichti, U Steven, AC AF Jarnik, M Kartasova, T Steinert, PM Lichti, U Steven, AC TI Differential expression and cell envelope incorporation of small proline-rich protein 1 in different cornified epithelia SO JOURNAL OF CELL SCIENCE LA English DT Article DE terminal differentiation; cornified cell envelope; immuno-electron microscopy; epidermal keratinocyte; covalent cross-linking (transglutaminase); loricrin; small proline-rich protein ID CROSS-LINKED ENVELOPE; EPIDERMAL DIFFERENTIATION; STRATUM-CORNEUM; KERATINOCYTE DIFFERENTIATION; MOLECULAR CHARACTERIZATION; MAMMALIAN EPIDERMIS; HISTIDINE-RICH; HUMAN LORICRIN; BASIC-PROTEIN; FILAGGRIN AB In the final stages of terminal differentiation in the epidermis and other squamous epithelia, a similar to 15 nm thick protein layer called the cornified cell envelope (CE) assembles on the keratinocytes' inner surface. Its constituent proteins are covalently crosslinked by the action of transglutaminases. Recent studies have indicated that the expression of CE precursor proteins may vary in different tissues. To investigate such variations further, we have studied the CEs of two different keratinizing epithelia of mouse: epidermis and forestomach, with particular focus on their contents of loricrin and the small proline-rich proteins (SPRs). To this end, we have applied electron microscopic immunocytochemistry and estimated the CE protein compositions by mathematical modeling of their amino acid compositions. Ultrastructurally, forestomach resembles the epidermis in having well defined cornified and granular layers. Minor but significant differences are: in forestomach, striated material resembling lamellar granules is intercalated between the cornified squames; and in forestomach granular layer cells, loricrin-containing L-granules are more abundant, and filaggrin-containing F-granules less abundant than in epidermis. In forestomach, dense labeling with anti-SPR1 antibody was observed at the margin of cornified layer cells; and in the granular layer, diffuse but positive labeling of both cytoplasm and nucleus. In contrast, epidermis was uniformly negative. Isolated forestomach CEs (but not epidermal CEs), labeled positively on the cytoplasmic side, consistent with the presence of covalently crosslinked SPR1. Our compositional analysis predicts the content of loricrin in forestomach CEs to be very high (similar to 65%), as in the epidermis, and accompanied by similar to 18% content of total SPRs. Of these, a substantial proportion should be SPR1, according to our immunolabeling data. In contrast, epidermal CEs are calculated to have a much lower amount of SPRs or SPR-like proteins (similar to 8%), with a negligible content of SPR1. Thus both kinds of CEs have loricrin as their major constituent but differ in their respective complements of SPRs, which are thought to inter-connect loricrin molecules in the final phase of CE assembly. Applying a basic concept of materials science, it may be that the observed differences in their SPR contents reflect differences in the mechanical and chemical properties required for the function of the respective CEs. C1 NIAMSD,STRUCT BIOL RES LAB,NIH,BETHESDA,MD 20892. NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. NR 58 TC 37 Z9 37 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 1996 VL 109 BP 1381 EP 1391 PN 6 PG 11 WC Cell Biology SC Cell Biology GA UU359 UT WOS:A1996UU35900021 PM 8799826 ER PT J AU Giedd, JN Allen, AJ Behr, R AF Giedd, JN Allen, AJ Behr, R TI Opportunities on the Internet for child and adolescent psychopharmacologists: Net access and mailing lists SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article AB The Internet, a system linking computers around the world, provides clinical and research psychopharmacologists with a convenient and efficient way to exchange information and offers a growing number of services to facilitate patient care. These opportunities are not theoretical, not in the future, and not for a select few. Many patients are already benefitting from practitioners who have sought guidance for their clinical work on the Internet. This article describes, for the novice user, how to begin the Internet journey. It also discusses psychopharmacology-related mailing lists, including a site that specializes in child and adolescent psychopharmacology. Subsequent articles will (1) show how to use Medlines to conduct literature searches and retrieve abstracts and articles from the computer screen, (2) describe ways to enter and traverse the World Wide Web (the ''multimedia'' portion of Internet), and (3) survey the use of ''Web browsers'' to find specialized psychopharmacology resources and databases, electronic journals, pertinent bulletin boards, and support services for patients and families-all with an emphasis on direct benefits to the practicing psychopharmacologist. RP Giedd, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. 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 5 TC 3 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SUM PY 1996 VL 6 IS 2 BP 147 EP 150 DI 10.1089/cap.1996.6.147 PG 4 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA VD562 UT WOS:A1996VD56200006 PM 9231307 ER PT J AU Danesi, R LaRocca, RV Cooper, MR Ricciardi, MP Pellegrini, A Soldani, P Kragel, PJ Paparelli, A DelTacca, M Myers, CE AF Danesi, R LaRocca, RV Cooper, MR Ricciardi, MP Pellegrini, A Soldani, P Kragel, PJ Paparelli, A DelTacca, M Myers, CE TI Clinical and experimental evidence of inhibition of testosterone production by suramin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROSTATE-CANCER; GROWTH-FACTOR; RAT TESTIS; CELLS; PITUITARY; INVITRO AB The effect of suramin on testosterone production was evaluated in cancer patients, adult male rats, rat Leydig cells, and NCI-H295 human adrenal cancer cells. Testosterone plasma levels markedly decreased in 14 patients receiving suramin as a therapy for refractory cancer, and in 8 of them, the plasma LH and/or FSH levels increased beyond the normal range. The hCG stimulation test (5000 IU, im) was performed in 8 patients and induced an average 2.1-fold increase in testosterone levels over baseline values. Testicular histology after suramin treatment was available in 1 patient who died of progressive disease; this revealed atrophy of seminiferous tubules and reduced Leydig cells in the interstitium. A significant reduction in plasma testosterone was also observed in rats given 18 mg/kg suramin, ip, twice weekly for 8 weeks, whereas plasma LH and FSH levels did not change significantly. Cytohistochemistry of testes from suramin-treated rats showed a reduced number of SP-hydroxysteroid dehydrogenase-positive cells within the interstitium compared to controls, and light microscopy revealed severe impairment of spermatogenesis. Suramin inhibited the production of testosterone by isolated rat Leydig cells as well as the conversion of pregnenolone to progesterone by the 3 beta-hydroxysteroid dehydrogenase enzyme extracted from rat testes, with 50% inhibitory concentrations (IC50 values) of 108.2 and 87.5 mu g/mL, respectively. Furthermore, suramin reduced the release of testosterone into the culture medium of NCI-H295 adrenal cancer cells with IC50 values of 91.2 and 83.9 mu g/mL, after 6 and 12 days, respectively. These data provide the first evidence in patients that suramin treatment produces a marked reduction in the circulating levels of testosterone, a result that was also obtained in experimental models. C1 UNIV PISA, SCUOLA SUPER STUDI & PERFERZIONAMENTO S ANNA, I-56127 PISA, ITALY. UNIV PISA, DIPARTIMENTO SCI ANAT ANIM, I-56126 PISA, ITALY. UNIV PISA, IST ANAT UMANA, I-56126 PISA, ITALY. NCI, CLIN PHARMACOL BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, PATHOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV VIRGINIA, DIV HEMATOL ONCOL, CHARLOTTESVILLE, VA 22908 USA. RP Danesi, R (reprint author), UNIV PISA, IST FARMACOL MED, VIA ROMA 55, I-56126 PISA, ITALY. OI SOLDANI, PAOLA/0000-0003-1703-0962 NR 25 TC 7 Z9 7 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1996 VL 81 IS 6 BP 2238 EP 2246 DI 10.1210/jc.81.6.2238 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UQ022 UT WOS:A1996UQ02200041 PM 8964858 ER PT J AU Papanicolaou, DA Tsigos, C Oldfield, EH Chrousos, GP AF Papanicolaou, DA Tsigos, C Oldfield, EH Chrousos, GP TI Acute glucocorticoid deficiency is associated with plasma elevations of interleukin-6: Does the latter participate in the symptomatology of the steroid withdrawal syndrome and adrenal insufficiency? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CUSHINGS-SYNDROME; ENDOTOXIN; RESPONSES; HORMONE; SURGERY; INVIVO; HUMANS AB The cytokines tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and IL-6 are secreted at inflammatory sites in tandem and play a crucial role in the inflammatory and wound-healing processes. All three cytokines are potent activators of the hypothalamic-pituitary-adrenal axis, through which they restrain inflammation, whereas IL-6 itself plays a role in the termination of inflammation as well. To test the hypothesis that endogenous glucocorticoids exert a negative tonic effect on the secretion of these cytokines, we studied 17 patients with Cushing's disease and. 2 patients with primary adrenal Cushing's syndrome before and after surgery. Plasma TNF alpha, IL-1 beta and IL-6 were measured before surgery, while the patients were hypercortisolemic; on postoperative day 4 or 5, when they were hypocortisolemic; and on postoperative day 9 or 10, when they were receiving glucocorticoid replacement. During severe hypocortisolism, on postoperative day 4 or 5, plasma IL-6 levels rose significantly, compared to the preoperative values (P < 0.001). During the same interval, TNF alpha and IL-1 beta also rose, albeit to a lesser extent. Over the same interval, patients with severe hypocortisolism experienced temperature elevation, fatigue, somnolence, flu-like symptoms, and anorexia, symptoms that have been traditionally attributed to glucocorticoid deficiency; these were also experienced by subjects that received recombinant human IL-6. There was no postoperative increase in any of the cytokines studied in the patients who were not hypocortisolemic after surgery and who also lacked the corresponding symptomatology. Plasma IL-6 concentrations decreased significantly, albeit not to normal levels, in the hypocortisolemic group of patients on postoperative day 9 or 10, when they were receiving glucocorticoid replacement. We conclude that the peripheral levels of IL-6 and, to a lesser extent, those of TNF alpha and IL-1 beta are tonically inhibited by basal levels of glucocorticoids. The increased IL-6 production that occurs when cortisol levels fall might explain the symptomatology of acute glucocorticoid deficiency. RP Papanicolaou, DA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262, 10 CTR DR, MSC 1862, BETHESDA, MD 20892 USA. NR 25 TC 81 Z9 84 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1996 VL 81 IS 6 BP 2303 EP 2306 DI 10.1210/jc.81.6.2303 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UQ022 UT WOS:A1996UQ02200051 PM 8964868 ER PT J AU Iribarren, C Sharp, DS Curb, JD Yano, K AF Iribarren, C Sharp, DS Curb, JD Yano, K TI High uric acid: A metabolic marker of coronary heart disease among alcohol abstainers? SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE serum uric acid; alcohol intake; abstinence; coronary heart disease; cohort study; interaction ID RISK-FACTORS; JAPANESE MEN; CARDIOVASCULAR-DISEASE; HONOLULU HEART; HAWAII; HYPERURICEMIA; ASSOCIATION; STROKE; ASCERTAINMENT; EPIDEMIOLOGY AB The association between serum uric acid level and risk of coronary heart disease (CHD) over 21 years was investigated among 6411 middle aged Japanese-American men who were participants in the Honolulu Heart Program. In an age stratified Cox regression model, high serum uric acid (quartile 4 [> 6.7 mg/dl], relative to quartile 1 [< 5.0 mg/dl]) was a significant predictor of definite CHD (RR = 1.33; 95% confidence interval = 1.08-1.63; p = 0.006), However, when adjustment for confounders (body mass index, heavy alcohol consumption, triglycerides, diastolic blood pressure, blood glucose, and the ratio of animal to vegetable protein) was made, the association of high uric acid with coronary events was substantially reduced and became nonsignificant (RR = 1.14; 95% confidence interval = 0.92-1.42; P = 0.21). There was a significant interaction between serum uric acid and drinking status (P = 0.03). Thus, the risk of definite CHD associated with high urate levels (quartile 4), relative to low levels (quartile 1), was elevated in the abstainers (RR = 1.40; 95% confidence interval = 1.01-1.93; P = 0.02), but not in light and moderate drinkers (RR = 1.11; 95% confidence interval = 0.79-1.55; P = 0.58) or among the heavy drinkers (> 40 mi of ethanol/day; RR = 0.57; 95% confidence interval = 0.27-1.21; p = 0.08). It is concluded that elevated uric acid may be associated with higher CHD among alcohol abstainers. Whether raised urate is an etiological factor for CHD or a manifestation of existing arterial disease in nondrinkers deserves further investigation. C1 NHLBI,NIH,BETHESDA,MD 20892. KUAKINI MED CTR,HONOLULU,HI 96817. UNIV HAWAII,HONOLULU,HI 96817. RP Iribarren, C (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [N01-HL-02901, N01-HV-02901] NR 62 TC 31 Z9 32 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 1996 VL 49 IS 6 BP 673 EP 678 DI 10.1016/0895-4356(96)00034-0 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UR415 UT WOS:A1996UR41500013 PM 8656229 ER PT J AU Haupt, R Novakovic, B Fears, TR Byrne, J Robinson, LL Tucker, MA Reaman, GH AF Haupt, R Novakovic, B Fears, TR Byrne, J Robinson, LL Tucker, MA Reaman, GH TI Can protocol-specified doses of chemotherapy and radiotherapy be used as a measure of treatment actually received? A CCG/NIH study on long term survivors of acute lymphocytic leukemia SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE acute lymphocytic leukemia; survivors; clinical trials; compliance; radiation; chemotherapy ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CANCER; CHILDHOOD; CHILDREN; THERAPY AB In a cohort of 593 long-term survivors of acute lymphocytic leukemia identified through the Children's Cancer Group (CCG), treatment abstracts were obtained and compared to protocol information on radiation therapy and intravenous chemotherapy. This was done in order to evaluate the actual compliance to protocol specified treatment, and assess if protocol specified doses can be used in studies of late effects of treatment, The compliance to protocol specified type of treatment ranged between 95.3% (intrathecal methotrexate) and 98.6% (adriamycin) for chemotherapy, and between 94.1% (cranial radiation) and 97.0% (extended held radiation) for radiation. Concordance with the protocol specified chemotherapy dose (+/- 25%) was 57.5% for adriamycin, 91.3% for daunomycin, and 48.5% for cyclophosphamide. When concordance was low, most patients received doses that were lower than expected. Concordance with chemotherapy was significantly lower for high dose regimens than for low dose regimens. Concordance with protocol specified radiation dose (+/- 10%) was 87.4% for cranial radiation, 87.8% for spinal radiation, and 85.7% for extended held radiation. Concordance with treatment did not differ by gender, relapse status, or age at diagnosis. In this cohort of leukemia survivors, the validity of type of treatment was greater than the validity of dosage. Great care should be used when drawing conclusions about effects of treatment dosage. Although costly and time consuming, it appears that chart reviews are the most appropriate way to collect information about dose-related effects of therapy. C1 G GASLINI CHILDRENS HOSP,DEPT HEMATOL ONCOL,GENOA,ITALY. NCI,GENET EPIDEMIOL & BIOSTAT BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,CLIN CANC EPIDEMIOL PROGRAM,WASHINGTON,DC 20010. UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN 55455. RI Haupt, Riccardo/C-2237-2012; Tucker, Margaret/B-4297-2015 NR 9 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 1996 VL 49 IS 6 BP 687 EP 690 PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UR415 UT WOS:A1996UR41500015 PM 8656231 ER PT J AU Stewart, DM TreiberHeld, S Kurman, CC Facchetti, F Notarangelo, LD Nelson, DL AF Stewart, DM TreiberHeld, S Kurman, CC Facchetti, F Notarangelo, LD Nelson, DL TI Studies of the expression of the Wiskott-Aldrich syndrome protein SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE immunodeficiency, congenital; antibodies, monoclonal; immunoblotting; immunohistochemistry; mutation ID DEPENDENT CELLULAR CYTOTOXICITY; ESCHERICHIA-COLI; B-CELLS; LYMPHOCYTES; PLATELETS; DEFECT AB The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by thrombocytopenia, eczema, disorders in cell-mediated and humoral immunity, and a proclivity to lymphoproliferative disease. The gene responsible encodes a 53-kD proline-rich protein of unknown function (WASP). We produced a FLAG-WASP fusion protein that was used to immunize mice and produce mAbs against WASP. Using monoclonal anti-WASP in Western immunoblots, we have determined that WASP is present in the cytoplasmic but not nuclear fraction of normal human peripheral blood mononuclear cells, in normal human platelets, in T lymphocytes, non-T lymphocytes, and monocytes. The protein is produced in the B cell immunoblastic cell line DS-1, in normal EBV-transformed B cell lines, and in HEL92.1.7, but is barely detectable in MOLT-4 and not detectable in K562. WASP was present in two of four EBV-transformed cell lines from WAS patients. Splenic tissue immunostaining was performed in two patients, and the results correlated with the results of the Western blots. Sequence analysis of WASP cDNA from two patients who produce WASP show mutations causing amino acid substitutions. These studies establish a foundation for further studies aimed at understanding the function of WASP. C1 NCI,NATL INST HLTH,METAB BRANCH,BETHESDA,MD 20892. UNIV BRESCIA,DEPT PATHOL,I-25123 BRESCIA,ITALY. UNIV BRESCIA,DEPT PEDIAT,I-25123 BRESCIA,ITALY. RI Facchetti, Fabio/E-7190-2010; Notarangelo, Luigi/F-9718-2016 OI Facchetti, Fabio/0000-0003-4975-2388; Notarangelo, Luigi/0000-0002-8335-0262 NR 42 TC 96 Z9 98 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1996 VL 97 IS 11 BP 2627 EP 2634 DI 10.1172/JCI118712 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UQ238 UT WOS:A1996UQ23800029 PM 8647957 ER PT J AU Quinn, TC Welsh, L Lentz, A Crotchfelt, K Zenilman, J Newhall, J Gaydos, C AF Quinn, TC Welsh, L Lentz, A Crotchfelt, K Zenilman, J Newhall, J Gaydos, C TI Diagnosis by AMPLICOR PCR of Chlamydia trachomatis infection in urine samples from women and men attending sexually transmitted disease clinics SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; REACTION ASSAY; SPECIMENS; URETHRITIS; ANTIGENS; CULTURES AB Screening of urine specimens from men for Chlamydia trachomatis infection by a commercial PCR assay (AMPLICOR C. trachomatis Test; Roche Diagnostic Systems, Inc., Branchburg, N.J.) is a sensitive and specific noninvasive diagnostic assay, Since screening of women for C. trachomatis infection with the AMPLICOR C. trachomatis Test has been limited to use with endocervical swab specimens, we conducted an evaluation of the AMPLICOR C. trachomatis Test for the detection of C. trachomatis using female urine samples and compared the results with those obtained by in vitro culture and PCR of endocervical swab specimens. For 713 men we compared the performance of AMPLICOR C. trachomatis Test with urine specimens with that of culture of urethral specimens. For specimens that were PCR positive and culture negative, two additional tests were used to resolve the discrepancies: direct fluorescent-antibody assay (DFA) of sediment from a spun endocervical specimen culture vial and major outer membrane protein-based PCR of the sediment from the endocervical specimen culture vial. Of 525 urine specimens from females, 67 (12.8%) were PCR positive, and 41 (7.8%) endocervical specimens from the 525 women were culture positive. After resolution of the discrepancies, the resolved sensitivity of the urine PCR was 93.3%, whereas the sensitivity of endocervical swab specimen culture was 67.3%. Of 468 female endocervical swab specimens, 47 (10.0%) had a positive PCR result and 33 (7.0%) were culture positive, The resolved sensitivity of the endocervical swab specimen PCR was 86%. Of 415 matched female urine and endocervical swab specimens, there were 49 confirmed infections; 30 (61.2%) specimens were positive by culture of the endocervical swab specimen, 40 (81.6%) were positive by confirmed endocervical swab specimen PCR, 43 (87.8%) were positive by confirmed urine PCR, and all 49 (100%) were positive by either endocervical swab specimen PCR or urine PCR. For men, the resolved sensitivity of the urine PCR was 88%, add the sensitivity of culture was only 50.7%. These results indicate that urine PCR is highly sensitive for the detection of C. trachomatis in both women and men and provides a noninvasive technique for routine screening for chlamydial infection. C1 NIAID, NIH, BETHESDA, MD 20892 USA. BALTIMORE CITY DEPT HLTH, BALTIMORE, MD USA. CTR DIS CONTROL & PREVENT, ATLANTA, GA 30341 USA. RP Quinn, TC (reprint author), JOHNS HOPKINS UNIV, DIV INFECT DIS, ROSS BLDG ROOM 1159, 720 RUTLAND AE, BALTIMORE, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 44 TC 86 Z9 88 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1996 VL 34 IS 6 BP 1401 EP 1406 PG 6 WC Microbiology SC Microbiology GA UL311 UT WOS:A1996UL31100010 PM 8735088 ER PT J AU Yu, B Carrasquillo, J Milenic, D Chung, Y Perentesis, P Feuerestein, I Eggensperger, D Qi, CF Paik, C Reynolds, J Grem, J Curt, G Siler, K Schlom, J Allegra, C AF Yu, B Carrasquillo, J Milenic, D Chung, Y Perentesis, P Feuerestein, I Eggensperger, D Qi, CF Paik, C Reynolds, J Grem, J Curt, G Siler, K Schlom, J Allegra, C TI Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: Influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADIOLABELED MONOCLONAL-ANTIBODIES; BONE-MARROW DOSIMETRY; B-CELL LYMPHOMA; COLORECTAL-CANCER; CEA ANTIBODIES; THERAPY; RADIOIMMUNOTHERAPY; LOCALIZATION; CARCINOMA; EPITOPES AB Purpose: COL-1 is a high-affinity murine monoclonal antibody (MAg) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (I-131) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. Patients and Methods: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of OL-1 labeled with I-131, with doses from 10 mCi/m(2) to 75 mCi/m(2), in this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean +/- SD, 500 +/- 639). Results: Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions greater than or equal to 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm(2)) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting, The maximal-tolerated dose is 65 mCi/m(2), The correlation between dose (millicuries per square meter) and thrombocytopenia was melds stronger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. Conclusion: I-131-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear I-131-labeled COL-1 more rapidly from the circulation and experience less myelosuppression. C1 NCI,NAVY MED ONCOL BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 56 TC 30 Z9 31 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1996 VL 14 IS 6 BP 1798 EP 1809 PG 12 WC Oncology SC Oncology GA UP725 UT WOS:A1996UP72500007 PM 8656248 ER PT J AU Kramlinger, KG Post, RM AF Kramlinger, KG Post, RM TI Cutaneous eruptions as part of the ''anticonvulsant hypersensitivity syndrome'' - Reply SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter RP Kramlinger, KG (reprint author), NIH,BIOL PSYCHIAT BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1996 VL 16 IS 3 BP 264 EP 264 DI 10.1097/00004714-199606000-00023 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UR184 UT WOS:A1996UR18400023 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI Lateral bias for rotational behavior in tufted capuchin monkeys (Cebus apella) SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article ID CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; CIRCLING BEHAVIOR; HAND; ASSOCIATIONS; PREFERENCES; HYPOTHESIS; HANDEDNESS; PATHOLOGY; PROGRAM AB This research examined lateral bias for rotational behavior in tufted capuchin monkeys (Cebus apella). A symmetrical distribution of rotational bias was noted, with approximately equal numbers of subjects preferring to turn to the right and to the left. As a group, adults did not exhibit a lateral rotational bias. Immatures preferentially rotated to the left. Across subjects, the strength of rotational bias was positively related to the incidence of right-eyed looking. Rotational bias was not related to hand preference. The finding of analogous age-dependent patterns of rotational bias in capuchins and in humans suggests that the rotational behavior of Cebus apella can be used to model an asymmetric response pattern that has been linked to development in Home sapiens. RP Westergaard, GC (reprint author), NICHHD,CTR ANIM HLTH,COMPARAT ETHOL LAB,NIH,POB 529,POOLESVILLE,MD 20837, USA. NR 27 TC 18 Z9 18 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7036 J9 J COMP PSYCHOL JI J. Comp. Psychol. PD JUN PY 1996 VL 110 IS 2 BP 199 EP 202 PG 4 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA UR829 UT WOS:A1996UR82900012 PM 8681533 ER PT J AU Singer, M Needle, R AF Singer, M Needle, R TI Preventing aids among drug users: Evaluating efficacy SO JOURNAL OF DRUG ISSUES LA English DT Article ID RISK C1 NIDR,BETHESDA,MD 20892. NR 13 TC 3 Z9 3 U1 0 U2 1 PU J DRUG ISSUES INC PI TALLAHASSEE PA PO BOX 4021, TALLAHASSEE, FL 32315 SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SUM PY 1996 VL 26 IS 3 BP 521 EP 523 PG 3 WC Substance Abuse SC Substance Abuse GA VM056 UT WOS:A1996VM05600001 ER PT J AU Toretsky, JA Helman, LJ AF Toretsky, JA Helman, LJ TI Involvement of IGF-II in human cancer SO JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID GROWTH FACTOR-II; FACTOR-BINDING PROTEIN-2; WILMS-TUMOR; HUMAN NEUROBLASTOMA; CELL-LINE; HUMAN RHABDOMYOSARCOMA; AUTOCRINE GROWTH; GENE-EXPRESSION; MESSENGER-RNA; SOMATOMEDIN RECEPTOR RP Toretsky, JA (reprint author), NCI,PEDIAT BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 148 TC 132 Z9 136 U1 0 U2 2 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUN PY 1996 VL 149 IS 3 BP 367 EP 372 DI 10.1677/joe.0.1490367 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP485 UT WOS:A1996UP48500001 PM 8691094 ER PT J AU Weng, NP Levine, BL June, CH Hodes, RJ AF Weng, NP Levine, BL June, CH Hodes, RJ TI Regulated expression of Telomerase activity in human T lymphocyte development and activation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CALCIUM IONOPHORES; HUMAN FIBROBLASTS; CYCLOSPORINE-A; HERBIMYCIN-A; SIGNAL; INHIBITOR AB Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CDS plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of Src protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion. C1 NIA,NIH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. RP Weng, NP (reprint author), NCI,EXPTL IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4-B17,BETHESDA,MD 20892, USA. RI Levine, Bruce/D-1688-2009 NR 48 TC 297 Z9 311 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1996 VL 183 IS 6 BP 2471 EP 2479 DI 10.1084/jem.183.6.2471 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UT401 UT WOS:A1996UT40100008 PM 8676067 ER PT J AU Veronese, FD Arnott, D Barnaba, V Loftus, DJ Sakaguchi, K Thompson, CB Salemi, S Mastroianni, C Sette, A Shabanowitz, J Hunt, DF Appella, E AF Veronese, FD Arnott, D Barnaba, V Loftus, DJ Sakaguchi, K Thompson, CB Salemi, S Mastroianni, C Sette, A Shabanowitz, J Hunt, DF Appella, E TI Autoreactive cytotoxic T lymphocytes in human immunodeficiency virus type 1-infected subjects SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HIV-1 TAT; CELL; GENE; EXPRESSION; INFECTION; MOLECULES; HLA-A2.1; PROTEINS AB A subtractive analysis of peptides eluted from major histocompatibility complex (MHC) class I human histocompatibility leukocyte antigen (HLA)-A2.1 molecules purified from either human immunodeficiency virus type-1 (HIV-1)-infected or uninfected cells was performed using micro high-performance liquid chromatography and mass spectrometry. Three peptides unique to infected cells were identified and found to derive from a single protein, human vinculin, a structural protein not known to be involved in viral pathogenesis. Molecular and cytofluorometric analyses revealed vinculin mRNA and vinculin protein overexpression in B and T lymphocytes from HIV-1-infected individuals. Vinculin peptide-specific CTL activity was readily elicited from peripheral blood lymphocytes of the majority of HLA-A2.1(+), HIV+ patients tested. Our observations suggest that atypical vinculin expression and MHC class I-mediated presentation of vinculin-derived peptides accompany HIV infection of lymphoid cells in vivo, with a resultant induction of antivinculin CTL in a significant portion of HIV+ (HLA-A2.1(+)) individuals. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22903. UNIV ROMA LA SAPIENZA,CATTEDRA MED INTERNA,MED CLIN 1,I-00161 ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT MALATTIE INFETT & TROP,I-00161 ROME,ITALY. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. CYTEL CORP,DEPT IMMUNOL,SAN DIEGO,CA 92121. RI salemi, simonetta/I-9546-2012; Hunt, Donald/I-6936-2012; OI Hunt, Donald/0000-0003-2815-6368; MASTROIANNI, Claudio Maria/0000-0002-1286-467X NR 25 TC 34 Z9 34 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1996 VL 183 IS 6 BP 2509 EP 2516 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UT401 UT WOS:A1996UT40100012 ER PT J AU Neurath, MF Fuss, I Kelsall, BL Presky, DH Waegell, W Strober, W AF Neurath, MF Fuss, I Kelsall, BL Presky, DH Waegell, W Strober, W TI Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; II COLLAGEN; SUPPRESSION; CELLS; ARTHRITIS; RATS; GENE AB In previous studies we showed that a chronic colitis associated with a Th1 T cell response can be induced by the rectal administration of the haptenizing reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). We report here that oral administration of haptenized colonic proteins (HCP) before rectal administration of TNBS effectively suppresses the ability of the latter to induce colitis. This suppression (oral tolerance) appears to be due to the generation of mucosal T cells producing TGF-beta and Th2-type cytokines after oral HCP administration. Peyer's patch and lamina propria CD4+ T cells from HCP-fed animals stimulated with anti-CD3/anti-CD28 had a 5-10-fold increase in their production of TGF-beta and secreted increased amounts of IL-4 and IL-10 but lower levels of IFN-gamma in comparison to T cells from ovalbumin-fed control animals. In addition, the colons of HCP-fed mice showed strikingly increased TGF-beta but decreased IL-12 expression by immunohistochemical studies and isolated mononuclear cells from HCP-fed animals secreted less IL-12 heterodimer. Finally, and most importantly, the suppressive effect of orally administered HCP was abrogated by the concomitant systemic administration of anti-TGF-beta or rIL-12 suggesting a reciprocal relationship between IL-12 and TGF-beta on tolerance, induction in TNBS-induced colitis. In parallel studies we demonstrated that TNBS-induced colitis can be transferred to naive recipient animals with purified CD4+ T cells from the colon of TNBS-treated animals and that such animals develop lethal pancolitis when exposed to very low doses of TNBS. Feeding of HCP suppressed this sensitivity to TNBS, indicating that oral feeding can suppress the response of pre-committed T cells in vivo. These studies suggest for the first time that TGF-beta production can abrogate experimental granulomatous colitis even after such colitis is established, and thus, that regulation of TGF-beta levels may have relevance to the treatment of human inflammatory bowel disease. C1 NIAID, MUCOSAL IMMUN SECT, NIH, LCI, BETHESDA, MD 20892 USA. HOFFMANN LA ROCHE INC, NUTLEY, NJ 07110 USA. CELTRIX PHARMACEUT INC, SANTA CLARA, CA 95052 USA. NR 30 TC 334 Z9 337 U1 0 U2 1 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 JUN 1 PY 1996 VL 183 IS 6 BP 2605 EP 2616 DI 10.1084/jem.183.6.2605 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UT401 UT WOS:A1996UT40100022 PM 8676081 ER PT J AU Candotti, F Oakes, SA Johnston, JA Notarangelo, LD OShea, JJ Blaese, RM AF Candotti, F Oakes, SA Johnston, JA Notarangelo, LD OShea, JJ Blaese, RM TI In vitro correction of JAK3-deficient severe combined immunodeficiency by retroviral-mediated gene transduction SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RECEPTOR GAMMA-CHAIN; FUNCTIONAL COMPONENT; IL-2 RECEPTOR; BONE-MARROW; CONSTRUCTION; VIRUS; CELLS AB Mutations affecting the expression of the Janus family kinase JAK3 were recently shown to be responsible for autosomal recessive severe combined immunodeficiency (SCID). JAX3-deficient patients present with a clinical phenotype virtually indistinguishable fi-om boys affected by X-linked SCID, a disease caused by genetic defects of the common gamma chain (gamma(c)) that is a shared component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. The specific interaction of JAK3 and gamma(c) represents the biochemical basis for the similarities between these two immunodeficiencies. Both forms of SCID are characterized by recurrent, severe infections leading to death in infancy unless successfully treated by allogeneic bone marrow transplantation. Because of the potentially lethal complications associated with allogeneic bone marrow transplantation and the frequent lack of suitable marrow donors, the development of alternative forms of therapy is highly desirable. To this end, we investigated a retroviral-mediated gene correction approach for JAK3-deficiency. A vector carrying a copy of JAK3 cDNA was constructed and used to transduce B cell lines derived from patients with JAK3-deficient SCID. We demonstrate restoration of JAK3 expression and phosphorylation upon IL-2 and IL-4 stimulation. Furthermore, patients' cells transduced with JAK3 acquired the ability to proliferate normally in response to IL-2. These data indicate that the biological defects of JAK3-deficient cells can be efficiently corrected in vitro by retroviral-mediated gene transfer, thus providing the basis for future investigation of gene therapy as treatment for JAK3-deficient SCID. C1 NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. NIAMSD,LYMPHOCYTE CELL BIOL SECT,ARTHRITIS & RHEUMATISM BRANCE,NIH,BETHESDA,MD 20892. UNIV BRESCIA,DEPT PEDIAT,I-25123 BRESCIA,ITALY. RP Candotti, F (reprint author), NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,NIH,BLDG 10,RM 10C103-MSC 1852,10 CTR DR,BETHESDA,MD 20892, USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU Telethon [A.042] NR 42 TC 49 Z9 49 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1996 VL 183 IS 6 BP 2687 EP 2692 DI 10.1084/jem.183.6.2687 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UT401 UT WOS:A1996UT40100032 PM 8676091 ER PT J AU Forthofer, MS Kessler, RC Story, AL Gotlib, IH AF Forthofer, MS Kessler, RC Story, AL Gotlib, IH TI The effects of psychiatric disorders on the probability and timing of first marriage SO JOURNAL OF HEALTH AND SOCIAL BEHAVIOR LA English DT Article ID MENTAL-HEALTH-SERVICES; SEX; DEPRESSION; TRANSITION AB While studies of psychopathology have begun to consider social consequences of psychiatric disorders during the past decade, marriage has received little attention, despite evidence that it influences life quality. The present paper examines the effects of clinically significant psychiatric disorders on the probability and timing of first marriage and whether the relationships between psychiatric disorders and marriage differ by type of disorder, gender, and birth cohort. Psychiatric disorders are found to have substantial effects on entry into first marriage. These effects are the same for men and women across all cohorts. Individual psychiatric disorders have similar effects on entry into first marriage. Psychiatric disorders are positively associated with early first marriage, which is strongly related to adverse consequences, and negatively associated with on-time and late first marriage, which are related to benefits such as financial security and social support. These results highlight the importance of early interventions for psychiatric disorders-if not for the purposes of primary prevention, then for the purposes of preventing the cumulation of adversities that occur secondarily through early marriage. C1 UNIV MICHIGAN,SURVEY RES CTR,ANN ARBOR,MI 48109. UNIV S CAROLINA,AIKEN,SC. NORTHWESTERN UNIV,CLIN TRAINING,EVANSTON,IL 60208. RP Forthofer, MS (reprint author), UNIV MICHIGAN,NIMH TRAINING PROGRAM PSYCHOSOCIAL FACTORS MENTAL,ANN ARBOR,MI 48109, USA. FU NIMH NIH HHS [R01 MH46376, R01 MH49098] NR 50 TC 67 Z9 68 U1 28 U2 31 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036-2981 SN 0022-1465 J9 J HEALTH SOC BEHAV JI J. Health Soc. Behav. PD JUN PY 1996 VL 37 IS 2 BP 121 EP 132 DI 10.2307/2137268 PG 12 WC Public, Environmental & Occupational Health; Psychology, Social SC Public, Environmental & Occupational Health; Psychology GA UQ279 UT WOS:A1996UQ27900002 PM 8690874 ER PT J AU Boehme, SA Lenardo, MJ AF Boehme, SA Lenardo, MJ TI TCR-mediated death of mature T lymphocytes occurs in the absence of p53 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-CYCLE; INDUCED APOPTOSIS; INHIBITOR; PROTEIN; KINASES; GENE; P21 AB The p53 protein plays an important role in various forms of thymocyte apoptosis, however its role in mature T lymphocyte death caused by TCR stimulation has not been examined, We demonstrate here that T cell blasts derived from mice containing a germ-line deficiency of the p53 tumor suppressor gene are susceptible to TCR-induced apoptosis to the same degree as wild-type T cells, TCR stimulation of both resting and proliferating T cells results in up-regulated expression of the p53-induced genes Bar and p21, and the induction of these genes appears reduced in T cells that are deficient in p53, Thus, while activation of p53-dependent genes following TCR stimulation is defective in p53(-/-) T cells, there is no impairment in their ability to undergo apoptosis, These results suggest that TCR-mediated apoptosis of mature T cells takes place via a pathway that is independent of p53. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 40 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1996 VL 156 IS 11 BP 4075 EP 4078 PG 4 WC Immunology SC Immunology GA UM244 UT WOS:A1996UM24400002 PM 8666771 ER PT J AU Rigby, MR Bortell, R Stevens, LA Moss, J Kanaitsuka, T Shigeta, H Mordes, JP Greiner, DL Rossini, AA AF Rigby, MR Bortell, R Stevens, LA Moss, J Kanaitsuka, T Shigeta, H Mordes, JP Greiner, DL Rossini, AA TI Rat RT6.2 and mouse Rt6 locus 1 are NAD(+): Arginine ADP ribosyltransferases with Auto-ADP ribosylation activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DIFFERENTIATION MARKER RT6; SKELETAL-MUSCLE; CELLS; LYMPHOCYTES; HOMOLOG; SURFACE AB RT6 is a glycosylphosphatidylinositol-linked protein found on the surface of mature rat T lymphocytes, Cells that express RT6 have an immunoregulatory function and modulate the expression of autoimmune diabetes mellitus in the BioBreeding rat, A homologue of the rat RT6 gene, designated Rt6, has been identified in the mouse, but expression of mouse Rt6 protein has not been documented. Rat RT6 is known to be a nicotinamide adenine dinucleotide (NAD(+)) glycohydrolase. We now report that rat RT6.2 and recombinant mouse Rt6 locus 1 proteins possess auto-ADP ribosylation activity. in addition, mouse Rt6 but not rat RT6, catalyzes the ADP ribosylation of exogenous accepters such as histones. The ADP-ribosyl-protein bonds in auto-ADP-ribosylated rat RT6.2, auto-ADP-ribosylated mouse Rt6, and ADP-ribosylhistone synthesized by Rt6 were stable to HgCl2 and HCl, but labile to NH2OH, consistent with ADP ribosylarginine linkages, To determine if these enzymatic activities could affect the function of rat T cells, the effect of substrate availability on lymphocyte proliferation was examined, An inverse correlation was observed between NAD(+) concentration in the medium and the ability of rat T cells to respond to anti-CD3, Con A, and PMA plus ionomycin. The data suggest that lymphocyte surface ADP ribosyltransferases could be involved in signaling and immunoregulatory processes. C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,WORCESTER,MA 01605. UNIV MASSACHUSETTS,MED CTR,PROGRAM BIOMED SCI,WORCESTER,MA 01605. NHLBI,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK36024, DK41235, DK25306] NR 43 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1996 VL 156 IS 11 BP 4259 EP 4265 PG 7 WC Immunology SC Immunology GA UM244 UT WOS:A1996UM24400027 PM 8666796 ER PT J AU Ahuja, SS Brown, MR Fleisher, TA Ahuja, SK Malech, HL AF Ahuja, SS Brown, MR Fleisher, TA Ahuja, SK Malech, HL TI Autocrine activation of hemopoietic progenitor-derived myelo-monocytic cells by IFN-gamma gene transfer SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; INTERFERON-GAMMA; MESSENGER-RNA; PROLIFERATION; INVITRO; NEUTROPHILS; SUPPRESSION; EXPRESSION; TOLERANCE; INDUCTION AB Immunomodulatory cytokines have been used with success as adjunctive therapy in genetic disorders such as chronic granulomatous disease and infectious diseases such as leishmaniasis and leprosy, As the first step toward developing novel methods to deliver immunomodulatory cytokines, we used retrovirus-mediated somatic gene transfer techniques to produce IFN-gamma from human peripheral blood CD34(+) hemopoietic progenitor (PBHP) cells. After transduction, the PBHP cells were made to differentiate toward myelo-monocytic lineages, Only the PBHP-derived myelo-monocytic cells that were transduced with the IFN-gamma cDNA produced IFN-gamma (4 +/- 1.3 ng of IFN-gamma/10(6) PBHP cells), Despite a reduction in the proliferation of IFN-gamma-transduced PBHP cells as well as a decrease in erythroid colony formation, there was an enhancement of monocyte differentiation and activation, Monocytes differentiated from the IFN-gamma-transduced PBHP cells demonstrated 1) up-regulation of MHC class I and II Ag expression, 2) increased Fc gamma RI expression, and 3) enhanced superoxide production in response to both opsonized zymosan (25-fold) and phorbol ester (3-fold), Furthermore, a Functional response to a monocyte-specific chemokine, monocyte chemotactic protein-1 (mobilization of intracellular Ca2+) was seen only in the IFN-gamma-transduced cells, Thus, PBHP cells transduced with IFN-gamma cDNA produce not only biologically active IFN-gamma, but also enhanced monocyte differentiation, resulting in an activated state that includes unique functions, such as responsiveness to monocyte chemotactic protein-1, These transduced activated monocytes may be specifically suited to cellular therapy requiring homing to sites of inflammation where their antimicrobicidal, cytotoxic, and APC functions plays an important role in host defense against foreign pathogens. C1 NIH,DEPT CLIN PATHOL,CTR CLIN,BETHESDA,MD 20892. RP Ahuja, SS (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N113,BETHESDA,MD 20892, USA. NR 31 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1996 VL 156 IS 11 BP 4345 EP 4353 PG 9 WC Immunology SC Immunology GA UM244 UT WOS:A1996UM24400037 PM 8666806 ER PT J AU Barker, TD Weissman, D Daucher, JA Roche, KM Fauci, AS AF Barker, TD Weissman, D Daucher, JA Roche, KM Fauci, AS TI Identification of multiple and distinct CD8(+) T cell suppressor activities - Dichotomy between infected and uninfected individuals, evolution with progression of disease, and sensitivity to gamma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTI-HIV ACTIVITY; IMMUNODEFICIENCY-VIRUS REPLICATION; LYMPHOCYTES-T; CD4+ CELLS; CD8+ CELLS; INHIBITION; MECHANISM; THERAPY AB Using an in vitro model system that reflects the cellular interactions occurring in the microenvironment of lymphoid organs (i.e., the interaction between dendritic cells (DC) and CD4(+) T lymphocytes), the ability of CD8(+) T cells to inhibit HIV replication was investigated. DC, the most potent APC in the paracortical region of lymphoid organs, were cocultured with autologous, unstimulated CD4(+) T cells resulting in viral replication in the absence of exogenous stimulation. Using two variations of DC cocultures, one an acute infection system and the other an endogenous infection system, two sets of activities were identified, One activity was expressed in both HIV-infected and -uninfected individuals, and a second was found only in HIV-infected individuals. These activities can be differentiated further by their evolution or lack thereof with disease progression in infected individuals and their sensitivity to gamma irradiation. Furthermore, the results indicate that CD8(+) T cell modulation of HIV replication in CD4(+) T cells is a multifactorial phenomenon involving both inhibitory and stimulatory effects on HIV replication. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NR 34 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1996 VL 156 IS 11 BP 4476 EP 4483 PG 8 WC Immunology SC Immunology GA UM244 UT WOS:A1996UM24400054 PM 8666823 ER PT J AU Valentine, FT Kundu, S Haslett, PAJ Katzenstein, D Beckett, L Spino, C Borucki, M Vasquez, M Smith, G Korvick, J Kagan, J Merigan, TC AF Valentine, FT Kundu, S Haslett, PAJ Katzenstein, D Beckett, L Spino, C Borucki, M Vasquez, M Smith, G Korvick, J Kagan, J Merigan, TC TI A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with >=400/mm(3) CD4 T lymphocytes (AIDS clinical trials group protocol 137) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-RESPONSE; NEUTRALIZING ANTIBODIES; SYNTHETIC PEPTIDES; RECOMBINANT GP160; ENVELOPE PROTEIN; INDIVIDUALS; ANTIGENS; INVITRO; CELLS; IDENTIFICATION AB Immune responses provoked by human immunodeficiency virus (HIV) infection ultimately are insufficient to control the disease and do not include strong lymphocyte-proliferative responses to HIV antigens or antibodies to many viral epitopes. A randomized double-blind, placebo-controlled trial evaluated the immunogenicity of recombinant HIV envelope vaccine (rgp160) in HIV-infected subjects with greater than or equal to 400/mm(3) CD4 T cells. Controls received hepatitis B vaccine. Of subjects receiving rgp160, 98% developed lymphocyte-proliferative responses to the immunogen, 33% to a different envelope protein, and 56% and 60% to p24 and p66, respectively. All doses of vaccine (20, 80, 320, 1280 mu g) induced new responses. New antibodies to epitopes on rgp160 developed only in recipients of higher doses of rgp160. CD4 T cell percentages declined less rapidly in recipients of rgp160 than in controls. Vaccination of HIV-infected subjects with rgp160 results in cellular and humoral immune responses to HIV that infection itself had not stimulated. C1 STANFORD UNIV,STANFORD AIDS CTR,STANFORD,CA 94305. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. MICROGENESYS,MERIDEN,CT. NIAID,NIH,BETHESDA,MD. RP Valentine, FT (reprint author), NYU,DEPT MED,MED CTR,DIV INFECT DIS & IMMUNOL,550 1ST AVE,NEW YORK,NY 10016, USA. OI Valentine, Fred/0000-0002-6046-5913 FU NCRR NIH HHS [RR-00096]; NIAID NIH HHS [AI-27665, AI-32429] NR 49 TC 42 Z9 42 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1336 EP 1346 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500006 PM 8648205 ER PT J AU Dillner, J Kallings, I Brihmer, C Sikstrom, P Koskela, P Lehtinen, M Schiller, JT Sapp, M Mardh, PA AF Dillner, J Kallings, I Brihmer, C Sikstrom, P Koskela, P Lehtinen, M Schiller, JT Sapp, M Mardh, PA TI Seropositivities to human papillomavirus types 16, 18, or 33 capsids and to Chlamydia trachomatis are markers of sexual behavior SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; INFECTION; WOMEN; DETERMINANTS; TRANSMISSION; DNA AB The association of seropositivity to human papillomavirus (HPV) capsids of types 11, 16, 18, or 33 with sexual behavior was investigated. Among 1002 women visiting family planning or youth clinics in Sweden, an age-matched subsample of 274 women stratified according to lifetime number of sex partners was analyzed. The proportion of HPV-16-seropositive subjects increased linearly at similar to 4% per partner (P <.001), from 4% among those with 1 lifetime partner to 35% among those with >5 lifetime partners. Also, HPV-33 and HPV-18 seroprevalences were linearly dependent on the number of partners (P <.001, increase with 4% per partner, and P =.008, increase with similar to 3% per partner, respectively), providing serologic confirmation that the important mode of transmission of HPV-16, -18, or -33 infection in women is sexual, HPV serology appears to be suitable as a marker of sexual behavior in populations. C1 SWEDISH INST INFECT DIS CONTROL,DEPT BACTERIOL,STOCKHOLM,SWEDEN. DANDERYD HOSP,DEPT OBSTET & GYNECOL,STOCKHOLM,SWEDEN. UNIV UPPSALA HOSP,DEPT BACTERIOL,UPPSALA,SWEDEN. ESKILSTUNA CENT HOSP,DEPT OBSTET & GYNECOL,ESKILSTUNA,SWEDEN. NATL PUBL HLTH INST,OULU,FINLAND. NATL PUBL HLTH INST,HELSINKI,FINLAND. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. UNIV MAINZ,DEPT MED MICROBIOL,W-6500 MAINZ,GERMANY. RP Dillner, J (reprint author), KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,BOX 280,S-17177 STOCKHOLM,SWEDEN. NR 31 TC 128 Z9 131 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1394 EP 1398 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500012 PM 8648211 ER PT J AU Nomura, A Stemmermann, GN Chyou, PH Tabor, E AF Nomura, A Stemmermann, GN Chyou, PH Tabor, E TI Hepatitis B and C virus serologies among Japanese Americans with hepatocellular carcinoma SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PREVALENCE; ANTIBODIES AB A cohort of 5924 Japanese American men was examined between 1967 and 1970 for hepatocellular carcinoma (HCC). By 1992, 24 incident cases of HCC were histologically confirmed in the group, Frozen serum samples from the 24 men with HCC and 72 age-matched controls were tested for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen, antibodies to HBsAg, and antibodies to hepatitis C virus. HBsAg was detected in 15 (62.5%) of 24 HCC cases compared with 2 (2.8%) of 72 controls (odds ratio, 43.0; 95% confidence interval, 5.7-325.5). None of the cases and only 1 control had antibody to hepatitis C virus. This study demonstrates a strong association between hepatocellular carcinoma and hepatitis B virus infection, but not with hepatitis C virus infection, among men of Japanese ancestry in Hawaii. C1 UNIV CINCINNATI,SCH MED,DEPT PATHOL,CINCINNATI,OH. NATL CANC INST,NATL INST HLTH,BETHESDA,MD. RP Nomura, A (reprint author), KUAKINI MED CTR,JAPAN HAWAII CANC STUDY,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NCI NIH HHS [CA-33644] NR 14 TC 15 Z9 15 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1474 EP 1476 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500024 PM 8648223 ER PT J AU Sei, S Akiyoshi, H Bernard, J Venzon, DJ Fox, CH Schwartzentruber, DJ Anderson, BD Kopp, JB Mueller, BU Pizzo, PA AF Sei, S Akiyoshi, H Bernard, J Venzon, DJ Fox, CH Schwartzentruber, DJ Anderson, BD Kopp, JB Mueller, BU Pizzo, PA TI Dynamics of virus versus host interaction in children with human immunodeficiency virus type 1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LYMPH-NODES; INDIVIDUALS AB To investigate the dynamic interplay between human immunodeficiency virus type 1 (HIV-1) replication and the extent of immune destruction in HIV-1-infected children, virus burden in lymphoid tissues (LN) and peripheral blood was compared with changes in LN architecture and cytokine levels constitutively expressed in LN. In agreement with results of a preliminary study, the plasma HIV-1 RNA level correlated with the amount of provirus in LN. However, the level was also associated with a degree of destruction of lymphoid follicular architecture and an alteration of immune cytokine expression, Expression of interleukin (IL)-4 was higher in LN with higher virus replication. Reduction of plasma viremia was associated with an increase in IL-2 mRNA levels in LN. These findings suggest that measurable virus burden in the peripheral blood is not a simple reflection of viral replication in LN but is also influenced by the extent of progressive immune destruction. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIDDKD,KIDNEY DIS SECT,NIH,BETHESDA,MD 20892. MOL HISTOL LABS INC,GAITHERSBURG,MD. RP Sei, S (reprint author), NCI,PEDIAT BRANCH,NIH,BLDG 10,ROOM 13N240,10 CTR DR MSC1928,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008; OI Kopp, Jeffrey/0000-0001-9052-186X NR 15 TC 16 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1485 EP 1490 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500027 PM 8648226 ER PT J AU McCarthy, JS Zhong, M Gopinath, R Ottesen, EA Williams, SA Nutman, TB AF McCarthy, JS Zhong, M Gopinath, R Ottesen, EA Williams, SA Nutman, TB TI Evaluation of a polymerase chain reaction-based assay for diagnosis of Wuchereria bancrofti infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FILARIASIS AB To assess the utility of a polymerase chain reaction (PCR)-based method for diagnosis of Wuchereria bancrofti infection, blood, plasma, and paraffin-embedded tissue samples were tested using a PCR-based assay that detects a W. bancrofti-specific repetitive DNA sequence. The assay was positive in 100 mu L of blood from 40 of 42 microfilaria-positive subjects, the 2 subjects with negative assays having microfilarial counts of 1. Samples from 127 uninfected subjects were PCR-negative. The assay was also positive in 7 of 10 daytime samples in regions where infection is nocturnally periodic; PCR amplification from paraffin-embedded sections established the diagnosis of W. bancrofti infection in another 2 cases. A microtiter ELISA plate-based method was developed for rapid evaluation of large numbers of samples. These results suggest that this PCR-based assay will be useful in diagnosis of W. bancrofti infection in a variety of clinical settings. C1 SMITH COLL,NORTHAMPTON,MA 01063. RP McCarthy, JS (reprint author), NIH,PARASIT DIS LAB,BLDG 4 ROOM 126,BETHESDA,MD 20892, USA. RI yu, yan/C-2322-2012 NR 12 TC 43 Z9 44 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1510 EP 1514 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500033 PM 8648232 ER PT J AU Padian, NS Abrams, J Skurnick, JH VanDevanter, NL OBrien, TR AF Padian, NS Abrams, J Skurnick, JH VanDevanter, NL OBrien, TR TI Risk factors for susceptibility to heterosexual human immunodeficiency virus infection in women - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 UNIV CALIF SAN FRANCISCO,DEPT OBSTET GYNECOL & REPROD SCI,SAN FRANCISCO,CA 94143. HENRY FORD HLTH SCI CTR,DIV BIOSTAT RES EPIDEMIOL & MED INFORMAT,DETROIT,MI. UNIV MED & DENT NEW JERSEY,DEPT PREVENT MED & COMMUNITY HLTH,NEWARK,NJ 07103. COLUMBIA UNIV,SCH PUBL HLTH,SOCIOMED SCI DIV,NEW YORK,NY. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. NR 3 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1521 EP 1521 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500038 ER PT J AU Therond, P Gerbaud, P Dimon, S Anderson, WB EvainBrion, D Raynaud, F AF Therond, P Gerbaud, P Dimon, S Anderson, WB EvainBrion, D Raynaud, F TI Antioxidant enzymes in psoriatic fibroblasts and erythrocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE psoriasis; superoxide dismutases; free radicals; fibroblasts; erythrocytes ID SUPEROXIDE-DISMUTASE ACTIVITY; KERATINOCYTES; CATALASE; INCREASE; DISEASE; CELLS AB Antioxidant enzyme activities in fibroblasts and erythrocytes prepared from normal and psoriatic patients were measured and compared. The most significant differences were noted in superoxide dismutase (SOD) activities. A dramatic (5.2-fold) increase in Mn-SOD activity along with a lesser (1.8-fold) increase in CuZn-SOD activity was observed in fibroblasts from lesional and nonlesional psoriatic skin. The increase of Mn-SOD activity was correlated with an increase of both protein and mRNA. A slight (1.2-fold) increase in CuZn-SOD activity was also found in psoriatic as compared to normal red blood cells, while Mn-SOD activity was not present in these cells. In contrast, both glutathione peroxidase and catalase activities were only slightly (1.3-fold) increased in psoriatic fibroblasts, with no appreciable change noted in psoriatic erythrocytes. Likewise, glutathione levels were observed to be similar in normal and psoriatic cells. The increases in SOD activities did not appear to correlate with the severity of the disease as expressed by the Psoriatic Area Severity Index score or with plasma inflammatory markers, These results demonstrate that antioxidant enzyme activities, particularly Mn-SOD in fibroblasts and CuZn-SOD in erythrocytes, are significantly elevated in cells from psoriatic patients. C1 UNIV PARIS 05,FAC SCI PHARMACEUT & BIOL,INSERM U427,F-75270 PARIS 06,FRANCE. HOP BICETRE,SERV BIOCHIM,F-94275 LE KREMLIN BICETR,FRANCE. NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. NR 33 TC 39 Z9 39 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1996 VL 106 IS 6 BP 1325 EP 1328 DI 10.1111/1523-1747.ep12349055 PG 4 WC Dermatology SC Dermatology GA UR404 UT WOS:A1996UR40400028 PM 8752678 ER PT J AU Kim, HO Hawes, C Towers, P Jacobson, KA AF Kim, HO Hawes, C Towers, P Jacobson, KA TI Radiolabeling and efficient synthesis of tritiated 2-chloro-N-6(3-iodobenzyl)adenosine-5'-N-methyluronamide, a potent, selective A(3) adenosine receptor agonist SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE adenosine derivatives; radioligands; adenosine receptors; tritium; nucleosides ID MOLECULAR-CLONING; RAT AB We recently reported that 2-substitution of N-6-benzyladenosine-5'-uronamides greatly enhances selectivity of agonists for rat A, adenosine receptors (J. Med. Chem. 1994, 37, 3614-3621). Specifically, 2-Chloro-N-6-(3-iodobenzyl)adenosine-5'-N-methyluron-amide (2-Cl-IB-MECA), which displayed a K-l value of 0.33 nM, is the most selective for A(3) receptors yet reported with selectivity versus A(1) and A(2a) receptors of 2500- and 1400-fold, respectively. In order to obtain pharmacological tools for the study of A(3) adenosine receptors, two routes for radiolabeling of 2-Cl-IB-MECA through incorporation of tritium at the 5'-methylamido group were compared. One route formed a 2',3'-protected nucleoside 5'-carboxylic acid (9), which was condensed with methylamine and deprotected. The more efficient synthesis started from D-ribose and provided 2-Cl-IB-MECA (12) in six steps with an overall yield of 5.6%. Tritium was introduced in the penultimate step by heating N-6-(3-iodobenzyl)-2-chloro-2',3'-di-O-acetyl-5'-(methoxycarbonyl) adenosine (17) with [H-3]methylamine in methanol at 60 degrees C for 2 h. The specific activity of [H-3]2-Cl-IB-MECA was 29 Ci/mmol with a radiochemical purity of 99%. C1 NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. AMERSHAM INT PLC,CARDIFF LABS,CARDIFF CF4 7YT,S GLAM,WALES. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20] NR 14 TC 5 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 1996 VL 38 IS 6 BP 547 EP 560 DI 10.1002/(SICI)1099-1344(199606)38:6<547::AID-JLCR870>3.3.CO;2-P PG 14 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA UQ632 UT WOS:A1996UQ63200005 PM 23598401 ER PT J AU DeRenzo, EG AF DeRenzo, EG TI Competence to consent - White,BC SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Book Review C1 NATL INST HLTH,CTR CLIN,BETHESDA,MD. RP DeRenzo, EG (reprint author), BIOETH PROGRAM,BETHESDA,MD, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SUM PY 1996 VL 24 IS 2 BP 156 EP 157 DI 10.1111/j.1748-720X.1996.tb01849.x PG 2 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA VL689 UT WOS:A1996VL68900011 ER PT J AU Letterio, JJ Roberts, AB AF Letterio, JJ Roberts, AB TI Transforming growth factor-beta 1-deficient mice: Identification of isoform-specific activities in vivo SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE TGF-beta isoforms; development; homeostasis; autoimmunity; wound healing; knockout mice ID BETA TGF-BETA; MYELIN BASIC-PROTEIN; LYMPHOCYTES-B; T-CELLS; EXPRESSION; ENCEPHALOMYELITIS; INFLAMMATION; INVOLVEMENT; ACTIVATION; TOLERANCE AB A remarkable range of activities has been ascribed to the family of proteins known as transforming growth factor-beta (TGF-beta). Each plays an important role in development and homeostasis, influencing mesenchymal-epithelial interactions, regulating cellular differentiation, and maintaining control of cell proliferation, Although in vitro comparisons of activity demonstrate a high degree of functional similarity, recent studies of mice with a targeted deletion of the TGF-beta 1 gene reveal that true isoform-specific activities do exist in vivo and that the three mammalian isoforms are not functionally redundant, This approach has defined a unique role for TGF-beta 1 in the establishment and maintenance of normal immune function, shed new Light on the relevance of endogenous TGF-beta 1 to the normal wound healing process, and expanded the list of known mechanisms of TGF-beta 1 activity to include endocrine functions, Thus, the TGF-beta 1-deficient mouse allows the definition of isoform-specific activities, providing an invaluable window through which to view the principal functions of TGF-beta 1 in vivo. RP Letterio, JJ (reprint author), NCI,CHEMOPREVENT LAB,NIH,BLDG 41,ROOM C629,BETHESDA,MD 20892, USA. NR 52 TC 66 Z9 66 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 1996 VL 59 IS 6 BP 769 EP 774 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA UV313 UT WOS:A1996UV31300001 PM 8691059 ER PT J AU Wahl, SM Feldman, GM McCarthy, JB AF Wahl, SM Feldman, GM McCarthy, JB TI Regulation of leukocyte adhesion and signaling in inflammation and disease SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article ID PROTEIN TYROSINE PHOSPHORYLATION; TUMOR-NECROSIS-FACTOR; CELL-ADHESION; ENDOTHELIAL-CELLS; GROWTH-FACTOR; P-SELECTIN; EXTRACELLULAR-MATRIX; ALPHA-4 INTEGRIN; HEPARAN-SULFATE; HUMAN MONOCYTES AB Cell adhesion molecules provide the foundation for cell communication, trafficking, and immune surveillance central to host defense, These adhesion molecules which include selectins, integrins and members of the Ig superfamily, provide a recognition system between leukocytes, endothelial cells and matrix molecules. Leukocyte-endothelial interactions initiate recruitment at sites of injury, infection and inflammation, Cell-cell and cell-matrix interactions also influence leukocyte phenotype and function. Dysregulation of these adhesion and signal transduction pathways can contribute to continued recruitment and persistent leukocyte activation with unresolved inflammation, Based on the pivotal role adhesive interactions play, the adhesion molecules provide potential targets for intervention, Selected synthetic fibronectin peptides, which inhibit leukocyte integrin binding and signal transduction in vibro, block recruitment and activation to limit inflammation in vivo. C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. UNIV MINNESOTA,DEPT PATHOL & MED,MINNEAPOLIS,MN 55455. RP Wahl, SM (reprint author), NIDR,NIH,CELL IMMUNOL SECT,BLDG 30,RM 331,BETHESDA,MD 20892, USA. NR 94 TC 58 Z9 60 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 1996 VL 59 IS 6 BP 789 EP 796 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA UV313 UT WOS:A1996UV31300004 PM 8691062 ER PT J AU Brand, K Dugi, KA Brunzell, JD Nevin, DN SantamarinaFojo, S AF Brand, K Dugi, KA Brunzell, JD Nevin, DN SantamarinaFojo, S TI A novel A->G mutation in intron I of the hepatic lipase gene leads to alternative splicing resulting in enzyme deficiency SO JOURNAL OF LIPID RESEARCH LA English DT Article DE expression studies; hepatic lipase deficiency; premature atherosclerosis; splicing defect ID HUMAN LIPOPROTEIN-LIPASE; HIGH-DENSITY LIPOPROTEIN; MESSENGER-RNA; TRIGLYCERIDE LIPASE; PLASMA-LIPOPROTEINS; ENDOTHELIAL LIPASE; BASE SUBSTITUTION; APOLIPOPROTEIN-B; CDNA SEQUENCE; GLOBIN GENE AB We have identified the underlying molecular defect in a patient with hepatic lipase (HL) deficiency presenting with hypertriglyceridemia and premature cardiovascular disease. DNA sequencing of polymerase chain reaction (PCR) amplified DNA and digestion with BsrI established homozygosity for an A --> G mutation in intron I of the patient's hepatic lipase gene. This mutation introduces an additional AG motif within a potential branch lariat signal located 13 bp upstream of the native 3' splice site. Two minigene constructs (normal and mutant) consisting of exons 1 and 2 as well as 192 bp of intron I of HL were generated by the overlap PCR extension method and transfected in human 293 cells, Sequence analysis of reverse transcribed, amplified cDNA generated from total RNA isolated from transfected cells demonstrated the presence of abnormally spliced products containing 13 and 78 additional bases as well as the accumulation of unspliced mRNA. No normally spliced mRNA was identified. Thus, the A --> G mutation disrupts normal splicing of intron I and generates a new AG site that is utilized as an alternative 3' splice signal leading to the most prominent RT-PCR product in vitro. Translation of these alternatively spliced products leads to premature termination resulting in the synthesis of a truncated, non-functional enzyme. The absence of normal HL protein in post heparin plasma of this patient was confirmed by Western blotting. DNA restriction analysis demonstrated that all four of the proband's children, who exhibit HL activity levels between those of the HL-deficient father and the mother with normal HL activity, are heterozygotes for the splice site mutation. Thus, our studies establish the functional significance of a novel mutation in the HL gene of a patient presenting with HL deficiency. C1 NHLBI, MOLEC DIS BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV WASHINGTON, DEPT MED, DIV METAB ENDOCRINOL & NUTR, SEATTLE, WA 98195 USA. FU NCRR NIH HHS [RR37]; NIDDK NIH HHS [DK 02456] NR 57 TC 43 Z9 43 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUN PY 1996 VL 37 IS 6 BP 1213 EP 1223 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UU476 UT WOS:A1996UU47600006 PM 8808756 ER PT J AU Basser, PJ Pierpaoli, C AF Basser, PJ Pierpaoli, C TI Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID WATER AB Quantitative-diffusion-tensor MRI consists of deriving and displaying parameters that resemble histological or physiological stains, i.e., that characterize intrinsic features of tissue microstructure and microdynamics. Specifically, these parameters are objective, and insensitive to the choice of laboratory coordinate system. Here, these two properties are used to derive intravoxel measures of diffusion isotropy and the degree of diffusion anisotropy, as well as intervoxel measures of structural similarity, and fiber-tract organization from the effective diffusion tensor, (D) under bar, which is estimated in each voxel. First, (D) under bar is decomposed into its isotropic and anisotropic parts, [D] (I) under bar and (D) under bar - [D] (I) under bar, respectively (where [D] = Trace((D) under bar)/3 is the mean diffusivity, and (I) under bar is the identity tensor). Then, the tensor (dot) product operator is used to generate a family of new rotationally and translationally invariant quantities. Finally, maps of these quantitative parameters are produced from high-resolution diffusion tensor images (in which (D) under bar is estimated in each voxel from a series of 2D-FT spin-echo diffusion-weighted images) in living cat brain. Due to the high inherent sensitivity of these parameters to changes in tissue architecture (i.e., macromolecular, cellular, tissue, and organ structure) and in its physiologic state, their potential applications include monitoring structural changes in development, aging, and disease. (C) 1996 Academic Press, Inc. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. RP Basser, PJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N17,13 S DR,BETHESDA,MD 20892, USA. RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 NR 30 TC 2411 Z9 2478 U1 6 U2 99 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD JUN PY 1996 VL 111 IS 3 BP 209 EP 219 DI 10.1006/jmrb.1996.0086 PG 11 WC Physics, Atomic, Molecular & Chemical SC Physics GA UQ678 UT WOS:A1996UQ67800001 PM 8661285 ER PT J AU Casavola, V Guerra, L Reshkin, SJ Jacobson, KA Verrey, F Murer, H AF Casavola, V Guerra, L Reshkin, SJ Jacobson, KA Verrey, F Murer, H TI Effect of adenosine on Na+ and Cl- currents in A(6) monolayers. Receptor localization and messenger involvement SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE adenosine receptors; A6 cells; chloride channels; sodium transport; cAMP; calcium ID NEPHRON CELL-LINE; ARGININE-VASOPRESSIN; CHLORIDE SECRETION; EPITHELIAL-CELLS; STIMULATED CAMP; APICAL MEMBRANE; A6 EPITHELIA; KIDNEY; TRANSPORT; CULTURE AB The effect of adenosine regulation on sodium and chloride transport was examined in cultured A(6) renal epithelial cells. Adenosine and its analogue N-6-cyclopentyladenosine (CPA) had different effects on shea-circuit current (I-sc) depending on the side of addition. Basolateral CPA addition induced an approximately threefold increase of the I-sc that reached a maximum effect 20 min after addition and was completely inhibited by preincubation with either an A(2) selective antagonist, CSC, or the sodium channel blocker, amiloride. Apical CPA addition induced a biphasic I-sc response characterized by a rapid fourfold transient increase over its baseline followed by a decline and a plateau phase that were amiloride insensitive. The A(1) adenosine antagonist, CPX, completely prevented this response. This I-sc response to apical CPA was also strongly reduced in Cl--free media and was significantly inhibited either by basolateral bumetanide or apical DPC preincubation. Only basolateral CPA addition was able to induce an increase in cAMP level. CPA, added to cells in suspension, caused a rapid rise in [Ca2+](i) that was antagonized by CPX, not affected by CSC and prevented by thapsigargin preincubation. These data suggest that basolateral CPA regulates active sodium transport via A(2) adenosine receptors stimulating adenylate cyclase while apical CPA regulates Cl- secretion via A(1) receptor-mediated changes in [Ca2+](i). C1 UNIV ZURICH,DEPT PHYSIOL,CH-8057 ZURICH,SWITZERLAND. NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP Casavola, V (reprint author), UNIV BARI,INST GEN PHYSIOL,VIA AMENDOLA 165-A,I-70126 BARI,ITALY. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031127-01, Z99 DK999999] NR 36 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUN PY 1996 VL 151 IS 3 BP 237 EP 245 DI 10.1007/s002329900074 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA UQ308 UT WOS:A1996UQ30800004 PM 8661511 ER PT J AU Kohno, H Bocchinfuso, WP Gandini, O Curtis, SW Korach, KS AF Kohno, H Bocchinfuso, WP Gandini, O Curtis, SW Korach, KS TI Mutational analysis of the estrogen receptor ligand-binding domain: Influence of ligand structure and stereochemistry on transactivation SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID DIETHYLSTILBESTROL METABOLITES; SACCHAROMYCES-CEREVISIAE; ESTRADIOL-BINDING; LACZ FUSIONS; ANALOGS; YEAST; EXPRESSION; IDENTIFICATION; UTERUS; PROBES AB The mouse estrogen receptor (mER) exhibits ligand stereochemical specificity for indenestrol A (IA), a stilbestrol estrogen. IA has a chiral C3 methyl group, and the mER preferentially binds the S-enantiomer (IA-S). resulting in elevated biological activity when compared with the IA-R enantiomer. To elucidate the mechanisms for this stereochemical recognition, we have constructed a series of mERs with individual amino acid substitutions at Met521, His528, Met532, and Val537. The abilities of yeast-expressed wild-type and mutant mERs to transactivate an estrogen-responsive reporter gene construct were measured in the presence of diethylstilbestrol (DES) and IA enantiomers. The concentration of IA-S required to induce half-maximal transactivation by wild-type mER was 10-fold lower than IA-R, which is attributed to the 15-fold greater binding affinity for IA-S. Wild-type mER displayed similar dose-response curves for IA-R and demethyl IA, which lacks a C3 methyl group, demonstrating that the presence and correct orientation of the C3 methyl group on the IA compound is required for high-affinity ligand binding and transcriptional activity. Each mutant exhibited a reduced preference for IA-S enantiomer with respect to transactivation, suggesting that this region of the mER functions in ligand stereochemical recognition and activation. A mutation at Met532 diminished DES- and IA-S-induced transactivation by 7.5-fold and 40-fold respectively, with minimal change on their binding affinity. These data suggest that Met532 is required for transactivation induced by the potent agonist, IA-S, and the M532G mutation effectively uncouples IA-S ligand binding from transactivation. Use of these stereochemically different ligands in combination with mutagenesis of the mER demonstrates that ligand structure could influence transactivation by specifically altering the conformation of the mER AF-2 region. RP Kohno, H (reprint author), NIEHS,RECEPTOR BIOL SECT,REPROD & DEV TOXICOL LAB,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 43 TC 16 Z9 16 U1 0 U2 2 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD JUN PY 1996 VL 16 IS 3 BP 277 EP 285 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UQ641 UT WOS:A1996UQ64100008 PM 8782086 ER PT J AU Davidson, A Moody, TW Gozes, I AF Davidson, A Moody, TW Gozes, I TI Regulation of VIP gene expression in general - Human lung cancer cells in particular SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE vasoactive intestinal peptide (VIP); non small cell lung carcinoma (NSCLC); forskolin; phorbol 12-myristate 13-acetate (PMA); autocrine growth factor, VIP mRNA ID VASOACTIVE-INTESTINAL-PEPTIDE; RAT SUPRACHIASMATIC NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; CILIARY NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR; NEURO-BLASTOMA CELLS; ANTERIOR-PITUITARY; CYCLIC-AMP; SYMPATHETIC NEURONS; RNA EXPRESSION AB Vasoactive intestinal peptide (VIP) is a neuropeptide of multiple functions affecting development and aging. In cancer, for example, VIP was found to function as an autocrine growth factor in nonsmall cell lung cancer (NSCLC) promotion. Furthermore, a VIP hybrid antagonist (neurotensin(6-17)-VIP7-28) was found to inhibit NSCLC growth. In the present study, the expression of VIP mRNA was studied using human lung cancer cells. RNA prepared from 19 cell Lines was fractionated by 1% agarose gel electrophoresis followed by blotting onto nitrocellulose membranes and hybridization to a VIP-specific RNA probe. VIP mRNA was detected in about 50% of the cell Lines tested with a greater abundance in NSCLC. Cultures of the NSCLC NCI-H727 cell line were treated with forskolin, an activator of cyclic AMP (cAMP), and separately with the tumor promoter phorbol 12-myristate 13-acetate (PMA). Northern blot hybridization analysis showed an increase in VIP mRNA levels after 4 h treatment with 50 mu M forskolin. Incubation with PMA also showed a significant increase in the levels of VIP transcripts. Cultures were then incubated with PMA in the presence of actinomycin D, a transcription blocker. Results indicated that PMA treatment may induce both VIP mRNA synthesis as well as VIP mRNA stabilization, and suggested a 4-5 h half-life for the VIP mRNA in the absence of PMA. Thus, lung cancer tumor proliferation may be regulated, in part, at the level of VIP gene expression. C1 TEL AVIV UNIV, SACKLER SCH MED, DEPT CLIN BIOCHEM, IL-69978 TEL AVIV, ISRAEL. NCI, BIOMARKERS & PREVENT RES BRANCH, ROCKVILLE, MD 20850 USA. NR 77 TC 14 Z9 14 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD SUM PY 1996 VL 7 IS 2 BP 99 EP 110 DI 10.1007/BF02736790 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VC290 UT WOS:A1996VC29000003 PM 8873894 ER PT J AU Werner, H Roberts, CT Rauscher, FJ LeRoith, D AF Werner, H Roberts, CT Rauscher, FJ LeRoith, D TI Regulation of insulin-like growth factor I receptor gene expression by the Wilms' tumor supressor WT1 SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE IGF-I receptor; WT1; tumor suppressors; Wilms' tumor; transcription; gene expression ID SUPPRESSOR WT1; TRANSCRIPTIONAL REPRESSION; PROMOTER ACTIVITY; IGF-1 RECEPTOR; PRODUCT; REGION; BINDING; KIDNEY; CELLS; LOCUS AB The insulin-like growth factor I receptor (IGF-I-R) has been implicated in the etiology and/or progression of Wilms' tumor, or nephroblastoma, a pediatric neoplasm of the kidney that is often associated with deletion or mutation of the WT1 tumor suppressor gene. The levels of IGF-I-R mRNA in the tumors were sixfold higher than in normal adjacent kidney tissue and were inversely correlated to the levels of WT1 mRNA, suggesting that the expression of the IGF-I-R gene is under inhibitory control by WT1. Cotransfection of an IGF-I-R promoter-luciferase reporter construct together with a WT1 expression vector resulted in a dose-dependent suppression of promoter activity. Multiple WT1 binding sites were mapped in the 5'-flanking and 5'-untranslated regions of the IGF-I-R gene using gel retardation and DNaseI footprinting assays. Thus, suppression of the IGF-I-R promoter by WT1 involves multiple interactions of its zinc finger domain with sites located both upstream and downstream of the transcription initiation site. Finally, we showed that expression of the endogenous IGF-I-R gene is decreased in G401 cells stably transfected with a WT1 expression vector. Reduction in expression of the IGF-I-R gene is associated with a decrease in a number of IGF-I-mediated biological effects. Thus, deletion or mutation of the WT1 gene in Wilms' tumor and other malignancies can result in overexpression of the receptor, with enhanced autocrine/paracrine activation by locally produced or circulating IGFs. C1 OREGON HLTH SCI UNIV, DEPT PEDIAT, PORTLAND, OR 97201 USA. WISTAR INST ANAT & BIOL, PHILADELPHIA, PA 19104 USA. RP Werner, H (reprint author), NIDDKD, DIABET BRANCH, SECT MOL & CELLULAR PHYSIOL, NIH, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 48 TC 16 Z9 17 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD SUM PY 1996 VL 7 IS 2 BP 111 EP 123 DI 10.1007/BF02736791 PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VC290 UT WOS:A1996VC29000004 PM 8873895 ER PT J AU Burgess, E Dorn, LD Haaga, DAF Chrousos, G AF Burgess, E Dorn, LD Haaga, DAF Chrousos, G TI Sociotropy, autonomy, stress, and depression in Cushing syndrome SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID PERSONALITY; DISORDERS; HORMONE; SCALE AB Cognitive theory ascribes nonendogenous depression to latent dysfunctional beliefs activated by stressors impinging upon core values (e.g., rejection for a sociotropic person). To address ambiguities in past tests of the theory, this study measured personality (Sociotropy-Autonomy Scale) and recent stressors (Life Experience Survey and Hassles Scale) among 14 Cushing syndrome patients and 12 controls. Patients scored nonsignificantly higher in sociotropy, and sociotropy correlated positively with depression among patients. Because depression in Cushing syndrome presumably results from biological dysfunction rather than from the interaction of personality and relevant stressors, these results imply that sociotropy may be a consequence of depression as opposed to a contributory cause. There was no congruence between personality and types of stressors reported, which suggests that mood-dependent recall does not account for past evidence of congruence. C1 AMERICAN UNIV, DEPT PSYCHOL, WASHINGTON, DC 20016 USA. NICHHD, DEV ENDOCRINOL BRANCH, WASHINGTON, DC USA. UNIV PITTSBURGH, SCH NURSING, DEPT HLTH PROMOT & DEV, PITTSBURGH, PA 15261 USA. NR 33 TC 7 Z9 7 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUN PY 1996 VL 184 IS 6 BP 362 EP 367 DI 10.1097/00005053-199606000-00006 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UR837 UT WOS:A1996UR83700006 PM 8642386 ER PT J AU Rall, JE AF Rall, JE TI The astonishing hypothesis: The scientific search for the soul - Crick,F SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP Rall, JE (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUN PY 1996 VL 184 IS 6 BP 384 EP 385 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UR837 UT WOS:A1996UR83700013 ER PT J AU Fitzgibbon, EJ Calvert, PC Dieterich, M Brandt, T Zee, DS AF Fitzgibbon, EJ Calvert, PC Dieterich, M Brandt, T Zee, DS TI Torsional nystagmus during vertical pursuit SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article DE smooth pursuit; ocular torsion; nystagmus; cerebellum; ocular motor; cross-coupling ID EYE-MOVEMENTS; RESPONSES; HUMANS AB We examined three patients with cavernous angioma within the middle cerebellar peduncle. Each patient had an unusual ocular motor finding: the appearance of a strong torsional nystagmus during vertical pursuit. The uncalled-for torsion changed direction when vertical pursuit changed direction. In one patient, we recorded eye movements with the magnetic field technique using a combined direction and torsion eye coil. The slow-phase velocity of the inappropriate torsional nystagmus was linearly related to the slow-phase velocity of vertical smooth pursuit, and changed direction when vertical pursuit changed direction. This torsional nystagmus also appeared during fixation suppression of the vertical vestibule-ocular reflex (VOR), but was minimal during vertical head rotation when fixing a stationary target in the light. We suggest that inappropriately directed eye movements during pursuit might be another ocular motor sign of cerebellar dysfunction. Furthermore, we speculate that the signals used for vertical smooth pur suit are, at some stage, encoded in a semicircular canal VOR coordinate framework. To illustrate, for the vertical semicircular canals, vertical and torsional motion are combined on the same cells, with the anterior semicircular canals mediating upward movements and the posterior semicircular canals mediating downward movements. For the right labyrinth, however, both vertical semicircular canals produce clockwise slow phases (ipsilateral eye intorts, contralateral eye extorts). The opposite is true for the vertical semicircular canals in the left labyrinth; counterclockwise slow phases are produced. Hence, to generate a pure vertical VOR, the anterior or posterior semicircular canals on both sides of the head must be excited so that opposite-directed torsional components cancel. Thus, if pursuit were organized in a way similar to the VOR, pure vertical pursuit would require that oppositely-directed torsional components cancel in normals. If this did not happen, a residual torsional nystagmus could appear during attempted vertical pursuit. C1 JOHNS HOPKINS UNIV, DEPT NEUROL, BALTIMORE, MD 21218 USA. GEORGE WASHINGTON UNIV, DEPT NEUROL & NEUROSURG, WASHINGTON, DC USA. UNIV MUNICH, KLINIKUM GROSSHADERN, DEPT NEUROL, W-8000 MUNICH, GERMANY. RP Fitzgibbon, EJ (reprint author), NEI, NIH, BLDG 49, ROOM 2A50, BETHESDA, MD 20892 USA. FU NEI NIH HHS [EY0-1849] NR 20 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 1996 VL 16 IS 2 BP 79 EP 90 PG 12 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA UT349 UT WOS:A1996UT34900001 PM 8797162 ER PT J AU Festoff, BW Nelson, PG Brenneman, DE AF Festoff, BW Nelson, PG Brenneman, DE TI Prevention of activity-dependent neuronal death: Vasoactive intestinal polypeptide stimulates astrocytes to secrete the thrombin-inhibiting neurotrophic serpin, protease nexin I SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE serine proteases; thrombin; serpin; apoptosis; cell death; neuropeptide; neurotrophic ID GLIA-DERIVED NEXIN; NERVE GROWTH-FACTOR; SPINAL-CORD; NEURITE OUTGROWTH; ELECTRICAL-ACTIVITY; ALZHEIMERS-DISEASE; PERIPHERAL-NERVE; TROPHIC FACTORS; TERM SURVIVAL; RAT-BRAIN AB Neuronal cell death occurs as a programmed, naturally occurring mechanism and is the primary regressive event in central nervous system development, Death of neurons also occurs on an injury-induced basis after trauma and in human neurodegenerative diseases, Classical neurotrophic factors can reverse this phenomenon in experimental models prompting initiation of clinical trials in conditions such as amyotrophic lateral sclerosis and Alzheimer's disease, The glial-derived protease nexin I (PNI), a known promoter of neurite outgrowth in cell culture and a potent inhibitor of serine proteases, also enhances neuronal cell survival, PNI, in nanomolar concentrations, rescues spinal cord motor neurons from both naturally-occurring programmed cell death in the chick embryo as well as following injury in the neonatal mouse. The potent neuromodulator, vasoactive intestinal polypeptide (VIP), influences neuronal survival through glial-mediated factors and also induces secretion of new ly synthesized astrocyte PNI. We now report that subnanomolar amounts of PNI enhance neuronal survival in mixed spinal cord cell culture, especially when neuronal cells were made electrically silent by administration of tetrodotoxin, The mediation of this effect is by inhibition of the multifunctional serine protease, thrombin, because hirudin, a thrombin-specific inhibitor, has the same effect, In addition, spinal cord neurons are exquisitely sensitive to thrombin because picomolar and lower levels of the coagulation factor causes neuronal death, Thus, PNI is an astrocyte-derived, thrombin-inhibiting, activity-dependent neurotrophic agent, enhanced secretion of which by VIP may be one approach to treat neurological disorders. (C) 1996 John Wiley & Sons, Inc.* C1 UNIV KANSAS,MED CTR,DEPT NEUROL,KANSAS CITY,KS 66103. NICHHD,DEV NEUROBIOL LAB,NEUROBIOL SECT,BETHESDA,MD. NICHHD,DEV NEUROBIOL LAB,SECT DEV & MOLEC PHARMACOL,BETHESDA,MD. RP Festoff, BW (reprint author), VET ADM MED CTR,NEUROBIOL RES LAB,KANSAS CITY,MO 64128, USA. NR 71 TC 74 Z9 79 U1 2 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD JUN PY 1996 VL 30 IS 2 BP 255 EP 266 DI 10.1002/(SICI)1097-4695(199606)30:2<255::AID-NEU7>3.0.CO;2-4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA UM555 UT WOS:A1996UM55500007 PM 8738754 ER PT J AU Kawai, N McCarron, RM Spatz, M AF Kawai, N McCarron, RM Spatz, M TI Effect of hypoxia on Na+-K+-Cl- cotransport in cultured brain capillary endothelial cells of the rat SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE hypoxia; oligomycin; Na+,K+-ATPase; Na+-K+-Cl- cotransport; brain capillary endothelial cells ID MIDDLE CEREBRAL-ARTERY; POTASSIUM CONCENTRATION; SODIUM-TRANSPORT; BLOOD; ISCHEMIA; BARRIER; EDEMA; OCCLUSION; VESSELS; FLUID AB The effect of hypoxia on Na+,K+-ATPase and Na+-K+-Cl- cotransport activity in cultured rat brain capillary endothelial cells (RBECs) was investigated by measuring Rb-86(+) uptake as a tracer for K+. RBECs expressed both Na+,K+-ATPase and Na+-K+-Cl- cotransport activity (4.6 and 5.5 nmol/mg of protein/min, respectively). Hypoxia (24 h) decreased cellular ATP content by 43.5% and reduced Na+,K+-ATPase activity by 38.9%, whereas it significantly increased Na+-K+-Cl- cotransport activity by 49.1% in RBECs. To clarify further the mechanism responsible for these observations, the effect of oligomycin-induced ATP depletion on these ion transport systems was examined. Exposure of RBECs to oligomycin led to a time-dependent decrease of cellular ATP content (by similar to 65%) along with a complete inhibition of Na+,K+-ATPase and a coordinated increase of Na+-K+-Cl- cotransport activity (up to 100% above control values). Oligomycin augmentation of Na+-K+-Cl- cotransport activity was not observed in the presence of 2-deoxy-D-glucose (a competitive inhibitor of glucose transport and glycolysis) or in the absence of glucose. These results strongly suggest that under hypoxic conditions when Na+,K+-ATPase activity is reduced, RBECs have the ability to increase K+ uptake through Na+-K+Cl- cotransport. C1 NINCDS, STROKE BRANCH, NIH, BETHESDA, MD 20892 USA. NR 29 TC 29 Z9 29 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1996 VL 66 IS 6 BP 2572 EP 2579 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UL589 UT WOS:A1996UL58900042 PM 8632184 ER PT J AU Bennett, MC Mlady, GW Kwon, YH Rose, GM AF Bennett, MC Mlady, GW Kwon, YH Rose, GM TI Chronic in vivo sodium azide infusion induces selective and stable inhibition of cytochrome c oxidase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE complex IV; electron transport chain; mitochondria; oxidative metabolism; rats ID NITRIC-OXIDE; SUPEROXIDE DISMUTASE; TISSUE PREPARATIONS; GUANYLATE CYCLASE; STRIATUM; ACID AB The effect of chronic subcutaneous infusion of sodium azide on the activity of mitochondrial respiratory chain enzymes was investigated in Sprague-Dawley rats. Treatment with similar to 1 mg/kg/h sodium azide induced chronic, partial inhibition of cytochrome c oxidase, whereas the activities of respiratory complexes I and III were not significantly affected. The inhibition of cytochrome c oxidase was evident by 7 days after infusion began, and the effect was stable for at least 3 weeks, The selectivity of azide for cytochrome c oxidase is discussed in the context of other findings of azide effects on enzymes. The results of the present study indicate that the sodium azide infusion paradigm described here provides a useful tool for the evaluation of selective and stable cytochrome oxidase inhibition in vivo. C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. UNIV COLORADO, HLTH SCI CTR, DEPT PHARMACOL, DENVER, CO 80262 USA. UNIV COLORADO, HLTH SCI CTR, NEUROSCI TRAINING PROGRAM, DENVER, CO 80262 USA. VET AFFAIRS MED CTR, MED RES SERV, DENVER, CO USA. FU NIA NIH HHS [AG10755] NR 26 TC 45 Z9 45 U1 0 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1996 VL 66 IS 6 BP 2606 EP 2611 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UL589 UT WOS:A1996UL58900046 PM 8632188 ER PT J AU Fitzpatrick, JH Kintner, D Anderson, M Westler, WM Emoto, SE Gilboe, DD AF Fitzpatrick, JH Kintner, D Anderson, M Westler, WM Emoto, SE Gilboe, DD TI NMR studies of P-i-containing extracellular and cytoplasmic compartments in brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE intracellular pH; 2-deoxyglucose; 2-deoxyglucose-6-phosphate ID NUCLEAR-MAGNETIC-RESONANCE; INTRACELLULAR PH; RAT-BRAIN; GLUCOSE-UTILIZATION; DOG BRAIN; HYPOXIA; METABOLITES; ASTROCYTES; TRANSPORT; P-31-NMR AB The inorganic phosphate (P-i) NMR peak in brain has an irregular shape, which suggests that it represents more than a single homogeneous pool of P-i. To test the ability of the Marquardt-Levenberg (M-L) nonlinear curve fit algorithm software (Peak-Fit) to separate multiple peaks, locate peak centers, and estimate peak heights, we studied simulated P-i spectra with defined peak centers, areas, and signal-to-noise (S/N) ratios ranging from co to 5.8. As the S/N ratio decreased below 15, the M-L algorithm located peak centers accurately when they were detected; however, small peaks tended to grow smaller and disappear, whereas the amplitudes of larger peaks increased. We developed an in vitro three-compartment model containing a mixture of P-i buffer, phosphocreatine, phosphate diester, and phosphate monoester (PME), portions of which were adjusted to three different pHs before addition of agar. Weighed samples of each buffered gel together with phospholipid extract and bone chips were placed in an NMR tube and covered with mineral oil. Following baseline correction, it was possible to separate the P-i peaks arising from the three compartments with different pH values if each peak made up 10-35% of total P-i area. In vivo, we identified the plasma compartment by intraarterial infusion of P-i. It was assumed that intracellular compartments contained high-energy phosphates and took up glucose. Based on these assumptions we subjected the brains to complete ischemia and observed that P-i compartments at pH 6.82, 6.92, 7.03, and 7.13 increased markedly in amplitude. If the brain cells took up and phosphorylated 2-deoxyglucose (2-DG), 2-DG-6-phosphate (2-DG-6-P) would appear in the PME portion of the spectrum ionized according to pH(i). Four 2-DG-6-P peaks with calculated pH values of 6.86, 6.94, 7.04, and 7.15 did appear in the spectrum, thereby confirming that the four larger P-i peaks represented intracellular spaces. C1 UNIV WISCONSIN,SCH MED,DEPT NEUROL SURG,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT ANESTHESIOL,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT BIOCHEM,MADISON,WI 53706. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. FU NCRR NIH HHS [RR02781, RR08438, RR02301] NR 22 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1996 VL 66 IS 6 BP 2612 EP 2620 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UL589 UT WOS:A1996UL58900047 PM 8632189 ER PT J AU Heils, A Teufel, A Petri, S Stober, G Riederer, P Bengel, D Lesch, KP AF Heils, A Teufel, A Petri, S Stober, G Riederer, P Bengel, D Lesch, KP TI Allelic variation of human serotonin transporter gene expression SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE serotonin transporter; promoter; repeat element polymerphism; allelic variation; gene transcription ID IMIPRAMINE BINDING; CLONING; SITES AB Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5-HT) system. By directing the magnitude and duration of postsynaptic responses, carrier-facilitated 5-HT transport into and release from the presynaptic neuron are essential for the fine tuning of serotonergic neurotransmission. Interest in the mechanism of environmental factor-, disease-, and therapy-induced modification of 5-HT transporter (5-HTT) function and its impact on early brain development, event-related synaptic plasticity, and neurodegeneration is widespread and intensifying. We have recently characterized the human and murine 5-HTT genes and performed functional analyses of their 5'-flanking regulatory regions. A tandemly repeated sequence associated with the transcriptional apparatus of the human 5-HTT gene displays a complex secondary structure, represses promoter activity in nonserotonergic neuronal cells, and contains positive regulatory components. We now report a novel polymorphism of this repetitive element and provide evidence for allele-dependent differential 5-HTT promoter activity. Allelic variation in 5-HTT-related functions may play a role in the expression and modulation of complex traits and behavior. C1 UNIV WURZBURG,DEPT PSYCHIAT,D-97080 WURZBURG,GERMANY. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 29 TC 1473 Z9 1521 U1 10 U2 89 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1996 VL 66 IS 6 BP 2621 EP 2624 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UL589 UT WOS:A1996UL58900048 PM 8632190 ER PT J AU Litvan, I Mangone, CA McKee, A Verny, M Parsa, A Jellinger, K DOlhaberriague, L Chaudhuri, KR Pearce, RKB AF Litvan, I Mangone, CA McKee, A Verny, M Parsa, A Jellinger, K DOlhaberriague, L Chaudhuri, KR Pearce, RKB TI Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: A clinicopathological study SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE progressive supranuclear palsy; natural history; survival ID GAZE PALSY; DISEASE; MANIFESTATION; PARKINSONISM; DEMENTIA AB Objective-To analyse the natural history of progressive supranuclear palsy (PSP or Steele-Richardson-Olszewski syndrome) and clinical predictors of survival in 24 patients with PSP confirmed by necropsy, who fulfilled the NINDS criteria for a neuropathological diagnosis of typical PSP. Methods-Patients were selected from the research and clinical files of seven medical centres involving tertiary centres of Austria, England, France, and the United States. Clinical features were analysed in detail. The patients' mean age at onset of PSP was 63 (range 45-73) years. Results-The most frequent clinical features (occurring in at least 75% of the patients) were early postural instability and falls, vertical supranuclear palsy, akinetic-rigid predominant parkinsonian disorder characterised by symmetric bradykinesia and axial rigidity unrelieved by levodopa, pseudobulbar palsy, and frontal release signs. Occasionally, segmental dystonia or myoclonus were described, but neither aphasia nor alien limb syndrome was reported. Fractures occurred in 25% of the patients hut were unrelated to the severity of the gait or to the presence of falls. Median survival time was 5.6 (range 2-16.6) years. Onset of falls during the first year, early dysphagia, and incontinence predicted a shorter survival time. Age at onset, sex, early onset of dementia, vertical supranuclear palsy, or axial rigidity had no effect on prognosis of survival. Pneumonia was the most common immediate cause of death. PSP was most often clinically misdiagnosed as Parkinson's disease. Errors in diagnosis suggest that PSP is underdiagnosed. Conclusion-Progressive onset of early postural instability with falls or supranuclear vertical palsy in the fifth decade, should suggest the diagnosis of PSP. Onset of falls during the first year are emphasised, as they could lead to an early diagnosis and influence the prognosis of patients with PSP. Whether appropriate treatment of the dysphagia could prolong the survival of PSP patients needs to be explored. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA. HOP LA PITIE SALPETRIERE,INSERM U360,RAYMOND ESCOUROLLE NEUROPATHOL LAB,PARIS,FRANCE. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. INST NEUROL,PARKINSONS DIS SOC,BRAIN TISSUE BANK,LONDON WC1N 3BG,ENGLAND. RP Litvan, I (reprint author), NINCDS,NIH,NEUROEPIDEMIOL BRANCH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 54 TC 200 Z9 206 U1 0 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUN PY 1996 VL 60 IS 6 BP 615 EP 620 DI 10.1136/jnnp.60.6.615 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA UP452 UT WOS:A1996UP45200004 PM 8648326 ER PT J AU Fleck, MW Bahring, R Patneau, DK Mayer, ML AF Fleck, MW Bahring, R Patneau, DK Mayer, ML TI AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GLUTAMATE-OPERATED CHANNELS; SUBUNIT; PERMEABILITY; INTERNEURONS; MODULATION AB 1. The kinetics of onset of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization by glutamate, and the extent of attenuation of AMPA receptor desensitization by cyclothiazide. showed pronounced cell-to-cell variation in cultures of rat hippocampal neurons. Cultures prepared from area CAl stratum radiatum tended to show weaker modulation by cyclothiazide than cultures prepared from the whole hippocampus. 2. Kinetic analysis of concentration jump responses to glutamate revealed multiple populations of receptors with fast (approximate to 400 ms), intermediate (approximate to 2-4 s): and slow (> 20 s) time constants for recovery from modulation by cyclothiazide. The amplitudes of these components varied widely between cells, suggesting the existence of at least three populations of AMPA receptor subtypes, the relative density of which varied from cell to cell. 3. The complex patterns of sensitivity to cyclothiazide seen in hippocampal neurons could be reconstituted by assembly of recombinant AMPA receptor subunits generated from cDNAs encoding the flip (i) and flop (o) splice variants of the GluR-A and GluR-B subunits. Recovery from modulation by cyclothiazide was slower for GluR-A(i)B(i) and GluR-A(a)B(i) than for GluR-A(i)B(o) and GluR-A(o)B(o). 4. Coexpression of the flip and flop splice variants of GluR-A, in the absence of GluR-B, revealed that heteromeric AMPA receptors with intermediate sensitivity to cyclothiazide, similar to responses observed for the combinations GluR-A(o)B(i) or GluR-A(i)B(o), could be generated independently of the presence of the GluR-B subunit. However, recovery from modulation by cyclothiazide was twofold slower for GluR-A(i)B(i) than for homomeric GluR-A(i), indicating eating that the GluR-A and GluR-B subunits are not functionally equivalent in controlling sensitivity to cyclothiazide. 5. These results demonstrate that AMPA receptors expressed in hippocampal neurons are assembled in a variety of subunit and splice variant combinations that might serve as a mechanism to fine-tune the kinetics of synaptic transmission. C1 NICHHD,NIH,LCMN,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. RI Bahring, Robert/F-7146-2010; Mayer, Mark/H-5500-2013 NR 35 TC 58 Z9 58 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1996 VL 75 IS 6 BP 2322 EP 2333 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UT301 UT WOS:A1996UT30100013 PM 8793745 ER PT J AU Munoz, DP Waitzman, DM Wurtz, RH AF Munoz, DP Waitzman, DM Wurtz, RH TI Activity of neurons in monkey superior colliculus during interrupted saccades SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID OCULOMOTOR BURST GENERATOR; ORIENTING GAZE SHIFTS; ALERT SQUIRREL-MONKEY; NEURAL NETWORK MODEL; HEAD-FREE CAT; EYE-MOVEMENTS; TECTORETICULOSPINAL SYSTEM; FIXATION CELLS; ON-DIRECTIONS; SINGLE UNITS AB 1. Recent studies of the monkey superior colliculus (SC) have identified several types of cells in the intermediate layers (including burst, buildup, and fixation neurons) and the sequence of changes in their activity during the generation of saccadic eye movements. On the basis of these observations, several hypotheses about the organization of the SC leading to saccade generation have placed the SC in a feedback loop controlling the amplitude and direction of the impending saccade. We tested these hypotheses about the organization of the SC by perturbing the system while recording the activity of neurons within the SC. 2. We applied a brief high-frequency train of electrical stimulation among the fixation cells in the rostral pole of the SC. This momentarily interrupted the saccade in midflight: after the initial eye acceleration, the eye velocity decreased (frequently to 0) and then again accelerated. Despite the break in the saccade, these interrupted saccades were of about the same amplitude as normal saccades. The postinterruption saccades were usually initiated immediately after the termination of stimulation and occurred regardless of whether the saccade target was visible or not. The velocity-amplitude relationship of the preinterruption component of the saccade fell slightly above the main sequence for control saccades of that amplitude, whereas postinterruption saccades fell near the main sequence. 3. Collicular burst neurons are silent during fixation and discharge a robust burst of action potentials for saccades to a restricted region of the visual field that define a closed movement field. During the stimulation-induced saccadic interruption, these burst neurons all showed a pause in their high-frequency discharge. During an interrupted saccade to a visual target, the typical saccade-related burst was broken into two parts: the first part of the burst began before the initial preinterruption saccade: the second burst began before the postinterruption saccade, 4. We quantified three aspects of the resumption of activity of burst neurons following saccade interruption: I)the total number of spikes in the pre- and postinterruption bursts was very similar to the total number of spikes in the control saccade burst; 2) the increase hi total duration of the burst (preinterruption period + interruption + postinterruption period) was highly correlated with the increase in total saccade duration (preinterruption saccade + interruption;postinterruption saccade); and 3) the time course of the postinterruption saccade and the resumed cell discharge both followed the same monotonic trajectory as the control saccade in most cells. 5. The same population of burst neurons was active for both the preinterruption and the postinterruption saccades, provided that the stimulation was brief enough to allow the postinterruption saccade to occur immediately. If the postinterruption saccade was delayed by >100 ms, then burst neurons at a new and more rostral locus related to such smaller saccades became active in association with the smaller remaining saccade, We interpret this shift in active locations within the SC as a termination of the initial saccadic error command and the triggering of a new one. 6. Buildup neurons usually had two aspects to their discharge a high-frequency burst for saccades of the optimal amplitude and direction (similar to burst neurons), and a low-frequency discharge for saccades of optimal direction whose amplitudes were equal to or greater than the optimal (different from burst neurons). The stimulation-induced interruption in saccade trajectory differentially affected these two components of buildup neuron discharge. The high-frequency burst component was affected in a manner very similar to the burst neurons. However,the low-frequency component was only transiently affected by the stimulation and resumed immediately after the stimulation, regardless of whether the postinterruption saccade was initiated immediately or delayed beyond 150 ms. These observations indicate that buildup neurons might carry two independent signals: a high-frequency burst component that is similar to that in burst neurons, and a low-frequency discharge related to the rostral spread of activity across the SC. 7. The activity of fixation neurons in the rostral pole contralateral to the site of stimulation, which typically paused for saccades and resumed their tonic discharge at the end of the saccade, showed a more prolonged pause during the interrupted saccades. The time of resumption of fixation cell discharge remained highly correlated with the termination of the postinterruption saccade, 8. We believe that these observations support the hypotheses that place the SC ina feedback loop controlling the amplitude and direction of saccades. In addition, the observations provide further evidence on the role of the SC in saccade generation: the fixation cells in the rostral SC inhibit the activity of the burst and buildup cells in the caudal SC; the burst neurons provide the signal for the total desired change in eye position rather than instantaneous motor error; and the activity of burst cells is held at one locus within the SC for a limited time (100-150 ms) for each saccade and only then can be released to a new site within the SC. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. QUEENS UNIV,DEPT PHYSIOL,MRC,GRP SENSORY MOTOR PHYSIOL,KINGSTON,ON K7L 3N6,CANADA. UNIV CONNECTICUT,MED CTR,NEWINGTON,CT 06111. VET ADM MED CTR,DEPT NEUROL,NEWINGTON,CT 06111. FU NEI NIH HHS [EY-9481] NR 52 TC 67 Z9 67 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1996 VL 75 IS 6 BP 2562 EP 2580 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UT301 UT WOS:A1996UT30100032 PM 8793764 ER PT J AU Moss, HA Wolters, PL Brouwers, P Hendricks, ML Pizzo, PA AF Moss, HA Wolters, PL Brouwers, P Hendricks, ML Pizzo, PA TI Impairment of expressive behavior in pediatric HIV-infected patients with evidence of CNS disease SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE pediatric HIV-infected; encephalopathy; behavioral ratings; impaired expressive behavior ID CENTRAL-NERVOUS-SYSTEM; PROPHYLACTIC TREATMENT; CHILDREN; INFUSION; LEUKEMIA; INFANTS AB Rated observations of videotapes were made of 16 variables representing 5 behavioral domains (task orientation, positive social-emotional, motor skills, expressive speech, and activity) on a sample of 83 HIV-infected children. Comparisons were made on the rated behaviors between children classified as either encephalopathic or nonencephalopathic. Analyses were conducted separately for infants (M age = 1.80 years) and older children (M age = 5.15 years). The nonencephalopathic infants exhibited higher activity levels and were superior in motor and verbal skills and showed more social and emotional responsiveness than did the encephalopathic group. The older nonencephalopathic children functioned in a more adaptive and appropriate manner than did the encephalopathic children in all domains of behavior. Independently made Q-sort ratings of behaviors during developmental testing were highly correlated with conceptually congruent ratings of the videotaped behaviors. C1 MED ILLNESS COUNSELING CTR,CHEVY CASE,MD. RP Moss, HA (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [NCI-CM-17529] NR 31 TC 16 Z9 19 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JUN PY 1996 VL 21 IS 3 BP 379 EP 400 DI 10.1093/jpepsy/21.3.379 PG 22 WC Psychology, Developmental SC Psychology GA UL059 UT WOS:A1996UL05900007 PM 8935240 ER PT J AU Knapp, RJ Santoro, G DeLeon, IA Lee, KB Edsall, SA Waite, S Malatynska, E Varga, E Calderon, SN Rice, KC Rothman, RB Porreca, F Roeske, WR Yamamura, HI AF Knapp, RJ Santoro, G DeLeon, IA Lee, KB Edsall, SA Waite, S Malatynska, E Varga, E Calderon, SN Rice, KC Rothman, RB Porreca, F Roeske, WR Yamamura, HI TI Structure-activity relationships for SNC80 and related compounds at cloned human delta and mu opioid receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUANINE-NUCLEOTIDES; CELL-MEMBRANES; AGONIST; BW373U86; BINDING; SODIUM; NG108-15; ASSAY; 7315C AB The racemic compound (+/-)-BW373U86 {(+/-)-4-((alpha R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1 -piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride} is a-potent delta opioid receptor agonist in the mouse vasdeferens assay with little mu or kappa opioid receptor activity in the guinea pig ileum tissue preparation, In contrast, radioligand binding studies show that (+/-)-BW373U86 is only about 10-fold selective for delta over mu opioid receptors. Studies of the enantiomeric forms of (+/-)-BW373U86 and derivatives (SNC8O and related compounds) show that some of these isomers are significantly better in both receptor binding and pharmacological selectivity than (+/-)-BW373U86. In this study we have determined the binding affinities of 10 different SNC80-related compounds at cloned human delta and mu opioid receptors and measured the potency of SNC80 for the inhibition of forskolin-stimulated adenylyl cyclase. The most selective delta receptor ligand (SNC162) differed from SNC80 by the absence of the 3-methoxy substitution of the benzyl ring. The K-i for SNC162 at the delta receptor (0.625 nM) was over 8700-fold lower than that at the mu receptor (5500 nM), making this the most selective delta receptor ligand available. Reduction of the allyl side chain of SNC80 to produce radiolabeled [H-3]SNC121 allowed direct measurement of the association and dissociation rate constants. SNC80 was 26-fold less potent than [D-Pen(2), pCI-Phe(4), n-Pen(5)]enkephalin in the delta receptor adenylyl cyclase inhibition assay, but showed full agonish activity with an EG(50) value of 9.2 nM. The regulation of SNC80 binding affinity to the delta receptor by GTP analogs is undetectabie in [H-3]naltrindole binding inhibition studies, but direct binding studies with [H-3]SNC121 in the presence of 100 mu M 5'-guanylylimidotriphosphate show a 55% reduction in maximum binding site density consistent with a lower affinity for a part of the receptor population. Addition of 120 mM sodium chloride reduces SMC80 affinity nearly 40-fold in [H-3]naltrindole binding inhibition studies. The results of these studies define specific structural features of these compounds responsible for opioid receptor interactions and suggest a possibly novel mechanism for delta receptor activation. C1 UNIV ARIZONA,HLTH SCI CTR,COLL MED,DEPT PHARMACOL,TUCSON,AZ 85724. NIDA,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. FU NIDA NIH HHS [DA-08657, DA-06284] NR 27 TC 46 Z9 46 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 1996 VL 277 IS 3 BP 1284 EP 1291 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UQ526 UT WOS:A1996UQ52600013 PM 8667189 ER PT J AU Lipton, JA AF Lipton, JA TI The Dentist Scientist Award program and prosthodontics SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Academy-of-Prosthodontics CY 1995 CL TUCSON, AZ SP Acad Prosthodont AB The Dentist Scientist Award (DSA) program was startled by the National Institute of Dental Research (NIDR) in 1984 to prepare dentists for careers as clinical research scientists who would be highly skilled investigators and potential leaders in the full scope of oral health research. The DSA program provides support for dentists to undertake 5 years of intensive preparation in a course of study that includes basic and clinical science components integrated with a supervised research experience. From 1984 to 1994, the NIDR has invested $66.1 million dollars in the individual and institutional Dentist Scientist Awards programs. Almost 250 people have been or are involved now in the DSA career development activity. Men comprise 72% of the recipients and women 28%. RP Lipton, JA (reprint author), NIDR, DIV EXTRAMURAL RES, NATL INST HLTH, NATCHER BLDG ROOM 4AN-18J, BETHESDA, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JUN PY 1996 VL 75 IS 6 BP 666 EP 670 DI 10.1016/S0022-3913(96)90254-1 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UP213 UT WOS:A1996UP21300016 PM 8725844 ER PT J AU Slavkin, HC AF Slavkin, HC TI Synthesis at the cutting edge of inquiry SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Editorial Material RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SUM PY 1996 VL 56 IS 4 BP 169 EP 170 DI 10.1111/j.1752-7325.1996.tb02431.x PG 2 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA VP554 UT WOS:A1996VP55400001 PM 8906698 ER PT J AU Duncan, MD Harmon, JW Duncan, KLK AF Duncan, MD Harmon, JW Duncan, KLK TI Actin disruption inhibits bombesin stimulation of focal adhesion kinase (pp125(FAK)) in prostate carcinoma SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 08-11, 1995 CL DEARBORN, MI SP Assoc Acad Surg ID TYROSINE PHOSPHORYLATION; CELLS; CANCER; CYTOSKELETON; PEPTIDE; GROWTH AB Jasplakinolide is a member of a new class of antitumor agents targeting the actin cytoskeleton with activity against prostate cancer. Focal adhesion kinase (FAK) is an actin-associated mediator of mitogenic peptides. We hypothesized that the neuropeptide bombesin would activate FAK in prostate carcinoma, and that disruption of the actin network would block FAK activation and inhibit cell growth. Methods: PC-3 human prostate carcinoma cells were exposed to 50-200 nM jasplakinolide (Jas) or cytochalasin E (CyE) in cytotoxicity experiments. FAR phosphorylation was measured in cells stimulated with 0.01-10 nM bombesin; separate cells were pretreated 6 hr with 50-500 nM Jas or CyE. Cell lysates and anti-FAK immuno-precipitates were subjected to SDS-PAGE, Western blotting, and detection with anti-actin or anti-phosphotyrosine. Depolymerized G-actin was separated from total actin by ultracentrifugation. Cytoskeletal changes were confirmed by fluorescence microscopy. Results: Jas (GI(50) = 47 +/- 7 nM) and CyE (GI(50) = 61 +/- 20 nM) potently inhibited PC-3 growth (P < 0.01 vs control). Bombesin rapidly stimulated tyrosine phosphorylation of FAK in a dose dependent manner. FAK phosphorylation was inhibited to near-basal levels (50% of bombesin stimulated) by 500 nM Jas (63%) and 500 nM CyE (61%). Conclusions: Bombesin stimulated FAK in prostate carcinoma cells. Jasplakinolide, which induced over-polymerization of actin, and CyE, which depolymerizes actin, both inhibited bombesin-stimulated phosphorylation of FAK and inhibited PC-3 cell growth. Actin-disrupting agents block FAK signal transduction, which may be critical to their antitumor activity in prostate carcinoma. (C) 1996 Academic Press, Inc. C1 GEORGETOWN UNIV,DEPT SURG,WASHINGTON,DC 20422. NCI,TOXICOL & PHARMACOL BRANCH,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP Duncan, MD (reprint author), VET AFFAIRS MED CTR,SURG SERV,WASHINGTON,DC 20422, USA. RI Duncan, Kimberly /C-3655-2013 NR 28 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1996 VL 63 IS 1 BP 359 EP 363 DI 10.1006/jsre.1996.0276 PG 5 WC Surgery SC Surgery GA UU471 UT WOS:A1996UU47100065 PM 8661226 ER PT J AU Jensen, PS Watanabe, HK Richters, JE Roper, M AF Jensen, PS Watanabe, HK Richters, JE Roper, M TI Practitioner questions about research - Reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter RP Jensen, PS (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1996 VL 35 IS 6 BP 698 EP 699 DI 10.1097/00004583-199606000-00002 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UN376 UT WOS:A1996UN37600002 ER PT J AU Meyer, MC Leonard, HL Allen, AJ Swedo, SE Rapoport, J Richter, D Hamburger, SD Tucker, E AF Meyer, MC Leonard, HL Allen, AJ Swedo, SE Rapoport, J Richter, D Hamburger, SD Tucker, E TI TCA cardiotoxicity: The latest - Reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 BROWN UNIV,PROVIDENCE,RI 02912. INST JUVENILE RES,CHICAGO,IL. NIH,ROCKVILLE,MD. RP Meyer, MC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1996 VL 35 IS 6 BP 702 EP 702 DI 10.1097/00004583-199606000-00007 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UN376 UT WOS:A1996UN37600007 ER PT J AU Dorn, LD Burgess, ES Susman, EJ vonEye, A DeBellis, MD Gold, PW Chrousos, GP AF Dorn, LD Burgess, ES Susman, EJ vonEye, A DeBellis, MD Gold, PW Chrousos, GP TI Response to oCRH in depressed and nondepressed adolescents: Does gender make a difference? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE adolescent depression; gender; corticotropin-releasing hormone ID CORTICOTROPIN-RELEASING HORMONE; ONTARIO CHILD HEALTH; SEX-DIFFERENCES; CORTISOL SECRETION; MAJOR DEPRESSION; BIOCHEMICAL MANIFESTATIONS; STRESS; PREVALENCE; DISORDER; SAMPLE AB Objective: To examine the hypothesis that hypothalamic-pituitary-adrenal responses to stress vary across gender, contributing to gender differences in the prevalence of depression. Method: This study examined gender differences between depressed (n = 21) and control (n = 20) adolescents in adrenocorticotropic hormone (ACTH) and cortisol response to two ovine corticotropin-releasing hormone (oCRH) tests, at baseline and following a cognitive stressor. Results: Boys had higher(p < .05) measures of ACTH than girls, regardless of depression status, whereas corresponding cortisol parameters were similar in both groups. Cortisol measures were higher (p < .05) at time 1 than at time 2 in both groups, a phenomenon that might reflect the novelty of the situation. Conclusions: Gender differences in hormone responses may be related to differences in peripheral metabolism of ACTH, resulting in changes of immunoreactivity but not bioactivity or a different set point of the hypothalamic-pituitary-adrenal axis. The pattern of ACTH and cortisol responses to oCRH and the 24-hour excretion of free cortisol was normal in adolescents with depression, probably reflecting normal negative feedback mechanisms at this age or that most of these patients suffer from atypical rather than melancholic depression. C1 BROWN UNIV,BUTLER HOSP,PROVIDENCE,RI 02912. PENN STATE UNIV,BIOBEHAV HLTH PROGRAM,UNIVERSITY PK,PA 16802. MICHIGAN STATE UNIV,RES OUTREACH METHODOL PROGRAM,E LANSING,MI 48824. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP Dorn, LD (reprint author), UNIV PITTSBURGH,DEPT HLTH PROMOT & DEV,3500 VICTORIA ST,440 VICTORIA BLDG,PITTSBURGH,PA 15261, USA. NR 70 TC 37 Z9 37 U1 5 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1996 VL 35 IS 6 BP 764 EP 773 DI 10.1097/00004583-199606000-00016 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UN376 UT WOS:A1996UN37600016 PM 8682757 ER PT J AU Free, K Alechina, I ZahnWaxler, C AF Free, K Alechina, I ZahnWaxler, C TI Affective language between depressed mothers and their children: The potential impact of psychotherapy SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE psychotherapy; maternal depression; affective language ID PARENTAL DEPRESSION; YOUNG-CHILDREN; PSYCHOPATHOLOGY; PSYCHOANALYSIS; CONVERSATIONS; SEVERITY; STATES; RISK AB Objective: To determine whether depressed mothers who had had psychotherapy were more able to communicate accurately about emotions than depressed mothers who had not had treatment. Method: Three groups of mother-child pairs were studied: mothers without psychiatric diagnosis or treatment (n = 31), depressed mothers without treatment (n = 10), and depressed mothers with psychotherapy (n = 43). Photographs of infants expressing emotions were viewed and discussed by the mother-child pair and were rated independently. Results: A comparison by analysis of variance and Duncan procedures revealed significant differences between groups in both mothers' and children's accuracy scores. Mothers who had had psychotherapy were more able to interpret emotional expression with accuracy (p < .05), particularly about negative emotions such as anger and sadness (p < .01), than were the mothers of the depressed no treatment group. Depressed mothers without treatment were more inaccurate (for example, sadness interpreted as anger). Conclusions: Psychotherapy may contribute to the depressed mother's achievement of accuracy in speaking with her child about emotions. The depressed mother whose depressive illness goes untreated is more inclined to be inaccurate and may pass these inclinations on to her child. The generality of the psychotherapy Variable makes these findings preliminary. C1 WASHINGTON PSYCHOANALYT INST,WASHINGTON,DC. MOSCOW MV LOMONOSOV STATE UNIV,MOSCOW,RUSSIA. BALTIMORE WASHINGTON PSYCHOANALYT INST,LAUREL,MD. RP Free, K (reprint author), NIMH,4905 HAMPDEN LANE,SUITE 102,BETHESDA,MD 20814, USA. NR 62 TC 9 Z9 9 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1996 VL 35 IS 6 BP 783 EP 790 DI 10.1097/00004583-199606000-00018 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UN376 UT WOS:A1996UN37600018 PM 8682759 ER PT J AU Mulcahy, D Dakak, N Zalos, G Andrews, NP Proschan, M Waclawiw, MA Schenke, WH Quyyumi, AA AF Mulcahy, D Dakak, N Zalos, G Andrews, NP Proschan, M Waclawiw, MA Schenke, WH Quyyumi, AA TI Patterns and behavior of transient myocardial ischemia in stable coronary disease are the same in both men and women: A comparative study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SUDDEN CARDIAC DEATH; CIRCADIAN VARIATION; HEART-RATE; DAILY LIFE; ARTERY DISEASE; MORNING INCREASE; BLOOD-PRESSURE; INFARCTION; ONSET; THRESHOLD AB Objectives. This study sought to compare the circadian variations in transient ischemic activity, mean heart rate and ischemic threshold between women and men with coronary artery disease. Background. There is a circadian variation in ischemic activity, onset of myocardial infarction and sudden cardiac death in patients with coronary artery disease, but studies assessing ischemia have incorporated predominantly male subjects. Methods. Thirty-one women and 45 men underwent at least 48 h of ambulatory ST segment monitoring. Results. There was a similar and significant circadian variation in ischemic activity in both women and men (p < 0.0001 and p < 0.0001, respectively), with a trough at night, a surge in the morning and a peak between 1 and 2 PM, corresponding to a similar circadian variation in mean hourly heart rate (p < 0.0001) that was not different between men and women (p = 0.28, power to detect a shift 99.9%). Mean heart rate at onset of ischemia (ischemic threshold) had similar variability in women and men (p = 0.96), and harmonic regression analysis confirmed a significant circadian variation (p < 0.0001), with a trough at night and a peak during activity hours. Heart rate increased significantly in the 5 min before ischemia throughout the 24 h (p < 0.0001), with no gender differences in the pattern of preonset to onset heart rate changes over time (p = 0.52); the smallest differences were recorded in the middle of the night. The majority of ischemic episodes (80%) had a heart rate increase >5 beats/min in the 5 min before ischemia, but there were no gender differences. Conclusions. Women with coronary artery disease have a pattern of ischemic activity and underlying pathophysiologic mechanisms very similar to men. The importance of increase in myocardial oxygen demand in the genesis of ischemia in both men and women is reflected by similar magnitude of heart rate increases before ischemia. The lower ischemic threshold during the nocturnal hours, when blood pressure is also lower, is consistent with a circadian variation in underlying coronary vascular tone. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,OFF BIOSTAT RES,NIH,BETHESDA,MD 20892. NR 37 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN PY 1996 VL 27 IS 7 BP 1629 EP 1636 DI 10.1016/0735-1097(96)00061-7 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UM598 UT WOS:A1996UM59800012 PM 8636547 ER PT J AU Rising, R Tataranni, PA Snitker, S Ravussin, E AF Rising, R Tataranni, PA Snitker, S Ravussin, E TI Decreased ratio of fat to carbohydrate oxidation increasing age in Pima Indians SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE respiratory quotient; age; energy expenditure; body composition ID RESTING METABOLIC-RATE; ENERGY-EXPENDITURE; BODY-COMPOSITION; OBESE WOMEN; WEIGHT-GAIN; MEN AB Background: Some metabolic changes related to age may increase the prevalence of obesity. Previous studies have shown that a low relative metabolic rate and a low ratio of fat to carbohydrate utilization are predictors of body weight gain. However, a possible relationship between age and energy substrate utilization (respiratory quotient; RQ = VCO2/VO2 has not been reported. Objective: To determine whether RQ increases and therefore fat oxidation decreases with age in Pima Indian men, independent of body fat and energy balance. Methods: We analyzed longitudinal data collected in seven non-diabetic Pima Indian men (31 +/- 6 years, 167 +/- 8 cm, 111.0 +/- 23.7 kg and 41 +/- 9% fat at baseline) who had repeated measurements of 24-hour RQ 7 years apart. On both admissions, subjects were fed a weight maintenance diet (50% carbohydrate, 30% fat and 20% protein) for 3 days before spending 1 day within a respiratory chamber for measurements of 24-hour energy expenditure, basal metabolic rate, sleeping metabolic rate and 24-hour RQ. Paired t-test was used to determine differences between the first and last measurement of 24-hour RQ. Cross-sectional data in 131 Pima Indian men (28 +/- 9 years, 171 +/- 6 cm, 94.5 +/- 24.4 kg, and 32 +/- 9% fat) were also analyzed to determine the relationship between 24-hour RQ and age. Multiple regression analysis was used to adjust 24-hour RQ for differences in energy balance (intake/expenditure in %) and percent body fat and metabolic rate for differences in body size and composition. Results: Over a 7-year period, mean unadjusted and adjusted 24-hour RQ increased (p < 0.01). Cross-sectional data analysis showed that both the unadjusted (r = 0.19, p < 0.03) and adjusted (r = 0.19, p < 0.03) 24-hour RQ correlated with increasing age while adjusted BMR (r = -0.21, p < 0.02) correlated inversely with age. Conclusions: Despite a higher body fat content, older individuals utilize less fat than their younger counterparts. Reduced fat utilization and decreased BMR with age may both contribute to increasing obesity in older individuals. C1 NIDDKD,CLIN DIABET & NUTR SECT,NIH,PHOENIX,AZ 85016. NR 23 TC 17 Z9 18 U1 1 U2 1 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 1996 VL 15 IS 3 BP 309 EP 312 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UN099 UT WOS:A1996UN09900016 PM 8935448 ER PT J AU Slavkin, HC AF Slavkin, HC TI Notes on a 'silent disease' SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 1996 VL 127 IS 6 BP 801 EP 803 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UQ240 UT WOS:A1996UQ24000030 PM 8708284 ER PT J AU Gloth, FM Tobin, JD Smith, CE Meyer, JN AF Gloth, FM Tobin, JD Smith, CE Meyer, JN TI Nutrient intakes in a frail homebound elderly population in the community vs a nursing home population SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID MAGNESIUM-DEFICIENCY C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV GERIATR MED & GERONTOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS BAYVIEW MED CTR, BALTIMORE, MD USA. NIA, GERONTOL RES CTR, APPL PHYSIOL SECT, NIH, BALTIMORE, MD 21224 USA. RP Gloth, FM (reprint author), UNION MEM HOSP, DIV GERIATR, 201E UNIV PKWY, BALTIMORE, MD 21218 USA. NR 13 TC 5 Z9 5 U1 1 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 1996 VL 96 IS 6 BP 605 EP 607 DI 10.1016/S0002-8223(96)00167-8 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VF443 UT WOS:A1996VF44300026 PM 8655912 ER PT J AU Hays, JC Blazer, DG Foley, DJ AF Hays, JC Blazer, DG Foley, DJ TI Risk of napping: Excessive daytime sleepiness and mortality in an older community population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID LATE LIFE; PREVALENCE; DEPRESSION; DURATION; PATTERNS; EEG AB OBJECTIVE: To describe the demographic and health-related factors related to excessive daytime sleepiness. To estimate the risk of mortality associated with excessive daytime sleepiness independent of nighttime sleep problems and other factors that limit survival. DESIGN: Four-year prospective cohort study with annual interviews. SETTING: One urban and four rural counties in northcentral North Carolina. PARTICIPANTS: Adults 65 years and older (n = 3962) living in the community. MAIN OUTCOME MEASURES: Excessive daytime sleepiness was measured as, ''How often do you get so sleepy during the day or evening that you have to take a nap!'' Mortality was based on continuous surveillance of the population by held investigators and abstraction of death certificates. RESULTS: Point prevalence of excessive daytime sleepiness in this population was 25.2%. Frequent daytime nappers were more likely than infrequent nappers to report nighttime sleep complaints and were more likely to be male and urban-dwellers, to report more depressive symptoms, more limited physical activity, and more functional impairment, and were more likely to be overweight. Of the frequent nappers, 23.9% died, compared with 15.4% of infrequent nappers. In an adjusted Cox proportional hazard model, the 4-year mortality rate was accelerated 1.73 times among older people who nap most of the time and make two or more errors on a cognitive status examination. CONCLUSION: Excessive napping is associated with impaired sleep hygiene as well as with a broad range of activity-related health deficits among community-dwelling older adults. Frequent napping was associated with impaired sleep hygiene, male gender, urban-dwelling, depressive symptoms, physical activity deficits, functional impairment, and excess weight. Mortality risk was elevated selectively among the most cognitively impaired subjects. C1 NIA,NIH,BETHESDA,MD 20892. RP Hays, JC (reprint author), DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,BOX 3875C,DURHAM,NC 27710, USA. NR 46 TC 124 Z9 126 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 1996 VL 44 IS 6 BP 693 EP 698 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA UP692 UT WOS:A1996UP69200013 PM 8642162 ER PT J AU Follmann, D AF Follmann, D TI A simple multivariate test for one-sided alternatives SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE clinical trial; hypothesis test; multiple endpoints; order restrictions ID MULTIPLE ENDPOINTS; CLINICAL-TRIALS AB A simple test for multivariate normal data is proposed that has good power for alternatives where the mean vector tends to be positive; The test rejects if the quadratic form of the sample mean vector exceeds its 2 alpha critical value and the sum of the elements of the mean vector exceeds zero. The proposed test is shown to have type I error rare equal to alpha whether or not the covariance matrix is known. Tight bounds on the power of the proposed test are provided, and the test is compared to three likelihood ratio tests. RP Follmann, D (reprint author), NHLBI, OFF BIOSTAT RES, BLDG 10, BETHESDA, MD 20892 USA. NR 13 TC 46 Z9 46 U1 1 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 1996 VL 91 IS 434 BP 854 EP 861 DI 10.2307/2291680 PG 8 WC Statistics & Probability SC Mathematics GA UP552 UT WOS:A1996UP55200053 ER PT J AU Moses, AV Stenglein, SG Strussenberg, JG Wehrly, K Chesebro, B Nelson, JA AF Moses, AV Stenglein, SG Strussenberg, JG Wehrly, K Chesebro, B Nelson, JA TI Sequences regulating tropism of human immunodeficiency virus type 1 for brain capillary endothelial cells map to a unique region on the viral genome SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; IMMUNE-DEFICIENCY SYNDROME; T-CELL; PRODUCTIVE INFECTION; MACROPHAGE TROPISM; AIDS PATIENTS; NERVOUS-SYSTEM; ENVELOPE GENE; VPR GENE; HIV-1 AB Two infectious molecular clones of human immunodeficiency virus type 1, NL4-3 and JR-CSF, differ in their abilities to productively infect human brain capillary endothelial (HBCE) cells. The phenotypes of recombinants between these two molecular strains were examined to identify viral sequences responsible for the difference in HBCE cell tropism between the two parental strains. Our results indicate that HBCE cell tropism maps to a region that encompasses the C1 region of env and includes overlapping reading frames for the accessory genes vpr, vpu, tat, and rev. This region was unique for HBCE cell tropism and did not cosegregate with either macrophage or T-cell line tropism. However, several recombinant clones displayed dual tropism for both HBCE cells and macrophages. These endothelial cell- and macrophage-tropic strains may have a unique pathogenic advantage by entering the brain via HBCE cells and subsequently infecting microglial cells with high efficiency, leading to the induction of human immunodeficiency virus dementia. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RP Moses, AV (reprint author), OREGON HLTH SCI UNIV,DEPT MICROBIOL & IMMUNOL,L220,3181 SW SAM JACKSON PK RD,PORTLAND,OR 97201, USA. FU NIMH NIH HHS [NIMH 47680] NR 56 TC 46 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3401 EP 3406 PG 6 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400010 PM 8648671 ER PT J AU Otteken, A Earl, PL Moss, B AF Otteken, A Earl, PL Moss, B TI Folding, assembly, and intracellular trafficking of the human immunodeficiency virus type 1 envelope glycoprotein analyzed with monoclonal antibodies recognizing maturational intermediates SO JOURNAL OF VIROLOGY LA English DT Article ID CHAIN BINDING-PROTEIN; ENDOPLASMIC-RETICULUM; BREFELDIN-A; OLIGOMERIC STRUCTURE; CYSTEINE RESIDUES; DISULFIDE BONDS; GOLGI PROTEINS; TRANSPORT; CELLS; CD4 AB Monoclonal antibodies (MAbs) that bind linear or conformational epitopes on monomeric or oligomeric human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins were screened for their recognition of maturational intermediates. On the basis of reactivities with gp160 at different times after pulse-labeling, the MAbs were sorted into groups that exhibited binding which was immediate and constant, immediate but transient, delayed, late, or very late, This grouping was consistent with the selectivity of the MAbs for structural features of gp160, Thus, a MAb to the V3 loop reacted with envelope proteins at all times, in accord with the relative conformational independence and accessibility of the epitope. Several MAbs that preferentially react with monomeric gp160 exhibited diminished binding after the pulse, A 10-min lag occurred before gp160 reacted with conformational MAbs that inhibited CD4 binding, The availability of epitopes for other conformational MAbs, including some that react equally with monomeric and oligomeric gp160 and some that react better with oligomeric forms, was half-maximal in 30 min and closely followed the kinetics of gp160 oligomerization, Remarkably, there was a 1- to 2-h delay before gp160 reacted with stringent oligomer-specific MAbs, After 4 h, approximately 20% of the gp160 was recognized by these MAbs. Epitopes recognized by monomer-specific or CD4-blocking MAbs but not by oligomer-dependent MAbs were present on gp160 molecules associated with the molecular chaperone BiP/GRP78, MAbs with a preference for monomers reacted with recombinant or HIV-1 envelope proteins in the endoplasmic reticulum, whereas the oligomer-specific MAbs recognized them in the Golgi complex, Additional information regarding gp160 maturation and intracellular trafficking was obtained by using brefeldin A, dithiothreitol, and a low temperature. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 48 TC 62 Z9 63 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3407 EP 3415 PG 9 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400011 PM 8648672 ER PT J AU Mulloy, JC Crowley, RW Fullen, J Leonard, WJ Franchini, G AF Mulloy, JC Crowley, RW Fullen, J Leonard, WJ Franchini, G TI The human T-cell leukemia/lymphotropic virus type 1 p12(I) protein binds the interleukin-2 receptor beta and gamma(c) chains and affects their expression on the cell surface SO JOURNAL OF VIROLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; LEUKEMIA-LYMPHOMA VIRUS; PAPILLOMAVIRUS-E5 TRANSFORMING PROTEIN; TROPICAL SPASTIC PARAPARESIS; VACUOLAR H+-ATPASE; HTLV-I; ERYTHROPOIETIN RECEPTOR; BOVINE PAPILLOMAVIRUS; MESSENGER-RNA; FUNCTIONAL COMPONENT AB p12(I) is a small hydrophobic protein encoded by the human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) that interacts with the I6-kDa component of the H+ vacuolar ATPase and cooperates with bovine papillomavirus 1 E5 oncoprotein in cell transformation. Just as an important step in E5 action appears to be its binding to the platelet-derived growth factor receptor, it was found that p12(I) binds specifically to both the beta and gamma(c) chains of the interleukin-2 receptor (IL-2R). The IL-2R beta and gamma(c) chains associated with p12(I) are endoglycosidase-H sensitive, suggesting that their interaction occurs in a pre-Golgi compartment. p12(I) stabilizes the immature forms of the IL-2R beta and gamma(c) chains and decreases their cell surface expression. The interactions of p12(I) with IL-2R beta and gamma(c) may have important implications in the immunosuppressive effect of HTLV-1 in vivo as well as in the ligand-independent HTLV-1-mediated T-cell proliferation. C1 NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NR 65 TC 75 Z9 79 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3599 EP 3605 PG 7 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400033 PM 8648694 ER PT J AU Tan, W Schalling, M Zhao, CP Luukkonen, M Nilsson, M Fenyo, EM Pavlakis, GN Schwartz, S AF Tan, W Schalling, M Zhao, CP Luukkonen, M Nilsson, M Fenyo, EM Pavlakis, GN Schwartz, S TI Inhibitory activity of the equine infectious anemia virus major 5' splice site in the absence of Rev SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL MESSENGER-RNA; CAPRINE ARTHRITIS-ENCEPHALITIS; LONG TERMINAL REPEAT; GENE-EXPRESSION; LENTIVIRUS TAT; EXON SEQUENCES; TYPE-1 AFFECTS; U6 SNRNA; U1 SNRNA AB The major 5' splice site of equine infectious anemia virus (EIAV) conforms to the consensus 5' splice site in eight consecutive positions and is located immediately upstream of the gag AUG. Our results show that the presence of this 5' splice site on the EIAV gag mRNA decreases Gag production 30- to 60-fold. This is caused by inefficient nuclear mRNA export and inefficient mRNA utilization. Inhibition could be overcome by providing human immunodeficiency virus type 1 Rev/Rev-responsive element, human T-cell leukemia virus type 1 Rex/Rex-responsive element, or simian retrovirus type 1 constitutive transport element. In addition, inhibition could be abolished by introducing single point mutations in the 5' splice site or by moving the 5' splice site away from its natural position immediately upstream of the gag AUG. This demonstrates that both maintenance of a perfect consensus 5' splice site and its proper location on the mRNA are important for inhibitory activity of the EIAV major 5' splice site. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT MOLEC MED,NEUROGENET UNIT,S-17176 STOCKHOLM,SWEDEN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000] NR 86 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3645 EP 3658 PG 14 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400038 PM 8648699 ER PT J AU Hirsch, VM Fuerst, TR Sutter, G Carroll, MW Yang, LC Goldstein, S Piatak, M Elkins, WR Alvord, WG Montefiori, DC Moss, B Lifson, JD AF Hirsch, VM Fuerst, TR Sutter, G Carroll, MW Yang, LC Goldstein, S Piatak, M Elkins, WR Alvord, WG Montefiori, DC Moss, B Lifson, JD TI Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: Effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODIES; RHESUS MACAQUES; INFECTION; DISEASE; RNA; DNA; PROTECTION; VIRULENCE; CHALLENGE; GENES AB The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses. Three distinct patterns of viral replication observed during and following primary viremia accounted for significant differences in survival times. High-level primary plasma viremia with subsequently increasing viremia was associated with rapid progression to AIDS (n = 2). A high-level primary plasma virus load with a transient decline and subsequent progressive increase in viremia in the post-acute phase of infection was associated with progression to AIDS within a year (n = 6). Low levels of primary plasma viremia followed by sustained restriction of virus replication were associated with maintenance of normal lymphocyte subsets and intact lymphoid architecture (n = 4), reminiscent of the profile observed in human immunodeficiency virus type 1-infected long-term nonprogressors. Three of four macaques that showed this pattern had been immunized with an SIV recombinant derived from the attenuated vaccinia virus, modified vaccinia virus Ankara. These data link the dynamics and extent of virus replication to disease course and suggest that sustained suppression of virus promotes long-term, asymptomatic survival of SIV-infected macaques. These findings also suggest that vaccine modulation of host immunity may have profound beneficial effects on the subsequent disease course, even if sterilizing immunity is not achieved. C1 NIAID, INFECT DIS LAB, ROCKVILLE, MD 20852 USA. NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. BECTON DICKINSON DIAGNOST INSTRUMENT SERV, SPARKS, MD USA. SAIC, DATA MANAGEMENT SERV, FREDERICK, MD USA. SAIC, LAB RETROVIRAL PATHOGENESIS, FREDERICK, MD USA. NCI, FREDERICK CANC RES CTR, FREDERICK, MD 21702 USA. DUKE UNIV, MED CTR, DEPT SURG, DURHAM, NC 27710 USA. FU NIAID NIH HHS [AI35467] NR 57 TC 279 Z9 281 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3741 EP 3752 PG 12 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400048 PM 8648709 ER PT J AU Roper, RL Payne, LG Moss, B AF Roper, RL Payne, LG Moss, B TI Extracellular vaccinia virus envelope glycoprotein encoded by the A33R gene SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA; NUCLEOTIDE-SEQUENCE; MARKER RESCUE; HEMAGGLUTININ; MUTANTS; DNA; IDENTIFICATION; DISSEMINATION; POLYPEPTIDE; EXPRESSION AB With the aid of three monoclonal antibodies (MAbs), a glycoprotein specifically localized to the outer envelope of vaccinia virus was shown to be encoded by the A33R gene. These MAbs reacted with a glycosylated protein that migrated as 23- to 28-kDa and 55-kDa species under reducing and nonreducing conditions, respectively. The protein recognized by the three MAbs was synthesized by all 11 orthopoxviruses tested: eight strains of vaccinia virus (including modified vaccinia virus Ankara) and one strain each of cowpox, rabbitpox, and ectromelia viruses. The observation that the protein synthesized by ectromelia virus-infected cells reacted with only one of the three MAbs provided a means of mapping the gene encoding the glycoprotein, By transfecting vaccinia virus DNA into cells infected with ectromelia virus and assaying for MAb reactivity, we mapped the glycoprotein to the A33R open reading frame. The amino acid sequence and hydrophilicity plot predicted that the A33R gene product is a type II membrane protein with two asparagine-linked glycosylation sites. Triton X-114 partitioning experiments indicated that the A33R gene product is an integral membrane protein. The ectromelia virus homolog of the vaccinia virus A33R gene was sequenced, revealing 90% predicted amino acid identity. The vaccinia and variola virus homolog sequences predict 94% identical amino acids, the latter having one fewer internal amino acid. Electron microscopy revealed that the A33R gene product is expressed on the surface of extracellular enveloped virions but not on the intracellular mature form of virus. The conservation of this protein and its specific incorporation into viral envelopes suggest that it is important for virus dissemination. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. INST VIRUS RES,CAMBRIDGE,MA 02138. NR 46 TC 108 Z9 111 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3753 EP 3762 PG 10 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400049 PM 8648710 ER PT J AU Lavignon, M Evans, L AF Lavignon, M Evans, L TI A multistep process of leukemogenesis in moloney murine leukemia virus-infected mice that is modulated by retroviral pseudotyping and interference SO JOURNAL OF VIROLOGY LA English DT Article ID FOCUS-FORMING VIRUSES; C-MYC; MONOCLONAL-ANTIBODIES; ENV GENE; RECOMBINANT VIRUSES; POLYTROPIC MULVS; CELL-LINES; AKR/J MICE; FRIEND; MCF AB Mixed retroviral infections frequently exhibit pseudotyping, in which the genome of one virus is packaged in a virion containing SU proteins encoded by another virus, Infection of mice by Moloney murine leukemia virus (M-MuLV), which induces lymphocytic leukemia, results in a mixed viral infection composed of the inoculated ecotropic M-MuLV and polytropic MuLVs generated by recombination of M-MuLV with endogenous retroviral sequences, In this report, we describe pseudotyping which occurred among the polytropic and ecotropic MuLVs in M-MuLV-infected mice, Infectious center assays of polytropic MuLVs released from splenocytes or thymocytes of infected mice revealed that polytropic MuLVs were extensively pseudotyped within ecotropic virions, Late in the preleukemic stage, a dramatic change in the extent of pseudotyping occurred in thymuses, Starting at about 5 weeks, there was an abrupt increase in the number of thymocytes that released nonpseudotyped polytropic viruses, A parallel increase in thymocytes that released ecotropic M-MuLV packaged within polytropic virions was also observed, Analyses of the clonality of preleukemic thymuses and thymomas suggested that the change in pseudotyping characteristics was not the result of the emergence of tumor cells, Examination of mice infected with M-MuLV, Friend erythroleukemia virus, and a Friend erythroleukemia virus-M-MuLV chimeric virus suggested that the appearance of polytropic virions late in the preleukemic stage correlated with the induction of lymphocytic leukemia, We discuss different ways in which pseudotypic mixing may facilitate leukemogenesis, including a model in which the kinetics of thymic infection, modulated by pseudotyping and viral interference, facilitates a stepwise mechanism of leukemogenesis. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 58 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3852 EP 3862 PG 11 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400060 PM 8648721 ER PT J AU Barsov, EV Hughes, SH AF Barsov, EV Hughes, SH TI Gene transfer into mammalian cells by a Rous sarcoma virus-based retroviral vector with the host range of the amphotropic murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID CHICKEN GERM LINE; PUROMYCIN-RESISTANCE; CONSTRUCTION; INFECTIVITY; EXPRESSION; INSERTION; GLYCOPROTEIN; PSEUDOTYPES; RNA; DNA AB We have constructed and characterized a Rous sarcoma virus-based retroviral vector with the host range of the amphotropic murine leukemia virus (MLV), The chimeric retroviral genome was created by replacing the env coding region in the replication-competent retroviral vector RCASBP(A) with the env region from an amphotropic MLV, The recombinant vector RCASBP-M(4070A) forms particles containing MLV Env glycoproteins, The vector replicates efficiently in chicken embryo fibroblasts and is able to transfer genes into mammalian cells, Vector stocks with titers exceeding 10(6) CFU/ml on mammalian cells can be easily prepared by passaging transfected chicken embryo fibroblasts. Since the vector is inherently defective in mammalian cells, it appears to have the safety features required for gene therapy. RP Barsov, EV (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 58 TC 38 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3922 EP 3929 PG 8 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400068 PM 8648729 ER PT J AU Men, RH Bray, M Clark, D Chanock, RM Lai, CJ AF Men, RH Bray, M Clark, D Chanock, RM Lai, CJ TI Dengue type 4 virus mutants containing deletions in the 3' noncoding region of the RNA genome: Analysis of growth restriction in cell culture and altered viremia pattern and immunogenicity in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; VACCINE; CANDIDATE; IMMUNIZATION; ATTENUATION; EXPRESSION; VIRULENCE; PROTEINS; NS5 AB The dengue type 4 virus (DEN4) genome contains a 384-nucleotide (nt) 3' noncoding sequence in which the last 81 nt, predicted to form a secondary structure, are thought to be essential for virus replication, Immediately upstream of the secondary structure, short RNA sequences that are conserved among mosquito-borne flaviviruses have been identified, A series of deletions that range from 30 to 262 nt were introduced into this upstream region of full-length DEN4 cDNA to create viable deletion mutants, some of which might prove to be useful for inclusion in a live attenuated virus vaccine, When studied by an infectious-center assay, most full-length RNA transcripts of the deletion constructs exhibited reduced infectivity when transfected into simian LLC-MK(2) cells compared with the full-length RNA transcripts of wild-type parental virus, Deletion mutations that extended as far as the 5' boundary of the 3' noncoding region and whose 3' boundary did not extend beyond the last 113 nt of the 3' end mere viable, With the exception of mutant 3'd 303-183, which contained a deletion of nt 303 to 183 from the 3' terminus, deletion mutants produced plaques that appeared late on simian LLC-MK(2) cells or exhibited a small-plaque morphology on mosquito C6/36 cells compared with the wild-type virus, These mutants also replicated less efficiently and attained a lower titer in LLC-MK(2) cells than parental wild-type virus, Significantly, mutant 3'd 303-183 grew to a high titer and was least restricted in growth, Mutant 3'd 303-183 and four other moderately to severely restricted mutants were selected for evaluation of infectivity and immunogenicity in rhesus monkeys, There was a suggestion that occurrence and duration of viremia were reduced for some of the deletion mutants compared with the wild-type virus, However, more convincing evidence for attenuation of some of the mutants was provided by an analysis of antibody response to infection. Mutant 3'd 303-183 induced an antibody response equivalent to that stimulated by wild-type virus, whereas other mutants induced low to moderate levels of antibodies, as measured by radioimmunoprecipitation and virus neutralization. The immunogenicity of these 3' DEN4 deletion mutants in monkeys appeared to correlate with their efficiency of growth in simian LLC-MK(2) cells, One or more mutants described in this paper may prove to be useful for immunization of humans against disease caused by dengue virus. C1 NIAID,INFECT DIS LAB,MOL VIRAL BIOL SECT,BETHESDA,MD 20892. NR 33 TC 232 Z9 248 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3930 EP 3937 PG 8 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400069 PM 8648730 ER PT J AU Bray, M Men, RH Lai, CJ AF Bray, M Men, RH Lai, CJ TI Monkeys immunized with intertypic chimeric dengue viruses are protected against wild-type virus challenge SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURAL PROTEINS; ENCEPHALITIS; PATHOGENESIS; MICE; CONSTRUCTION; RESPONSES; VACCINE; GENES AB Dengue epidemics caused by the four dengue virus serotypes continue to pose a major public health problem in most tropical and subtropical regions, A safe and effective vaccine against dengue is still not available, The current strategy for dengue immunization favors the use of a vaccine containing each of the four serotypes, We previously employed full-length dengue type 4 virus (DEN4) cDNA to construct a viable intertypic dengue virus of type 1 or type 2 antigenic specificity that contained the genes for the capsid-premembrane-envelope (C-pre-M-E) structural proteins of DEN1 or pre-M and E structural proteins of DENZ substituting for the corresponding DEN4 genes, Chimeras DEN1/DEN4 and DEN2/DEN4, which express the nonstructural proteins of DEN4 and the C-pre-III-E structural proteins of DEN1 or the pre-hl-E structural proteins of DEN2, and therefore the antigenicity of type 1 or type 2, were used to immunize rhesus monkeys, Other monkeys were inoculated with parental DEN1, DENZ, or cDNA-derived DEN4. Three of four monkeys immunized with DEN1/DEN4 developed neutralizing antibodies against DEN1 and were protected against subsequent DEN1 challenge, All four monkeys immunized with DEN2/DEN4 developed antibodies against DEN2 and were protected against subsequent DEN2 challenge, DEN1- and DEN2-immunized monkeys were protected against homologous virus challenge, but DEN4-immunized animals became viremic on cross-challenge with DEN1 or DEN2, In a second experiment, eight monkeys were immunized with equal mixtures of DEN1/DEN4 and DEN2/DEN4, Each of these monkeys developed neutralizing antibodies against both DEN1 and DENZ and were protected against subsequent challenge with DEN1 or DEN2, Chimeric dengue viruses similar to those described here could be used to express serotype-specific antigens in a live attenuated tetravalent human vaccine. C1 NIAID,MOL VIRAL BIOL SECT,INFECT DIS LAB,BETHESDA,MD 20892. NR 28 TC 63 Z9 71 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 4162 EP 4166 PG 5 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400100 PM 8648761 ER PT J AU McCarthy, CR AF McCarthy, CR TI A new look at animal-to-human organ transplantation SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID HEART C1 GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. RP McCarthy, CR (reprint author), NIH,OFF PROTECT RES RISKS,BETHESDA,MD 20892, USA. NR 15 TC 2 Z9 2 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD JUN PY 1996 VL 6 IS 2 BP 183 EP 188 DI 10.1353/ken.1996.0013 PG 6 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA VJ145 UT WOS:A1996VJ14500005 PM 10158033 ER PT J AU Pritchard, JB Miller, DS AF Pritchard, JB Miller, DS TI Renal secretion of organic anions and cations SO KIDNEY INTERNATIONAL LA English DT Article ID BASOLATERAL MEMBRANE-VESICLES; MULTIDRUG-RESISTANCE GENE; PARA-AMINOHIPPURATE; TRANSPORT; TETRAETHYLAMMONIUM; TUBULES; TISSUES; URATE; ACID AB The renal proximal tubule actively transports charged, potentially toxic xenobiotics from blood to lumen. Basolateral uptake of organic anions is indirectly coupled to the sodium gradient through Na-dicarboxylate cotransport and dicarboxylate-organic anion exchange. Upon entry, a significant fraction of intracellular organic anion is sequestered within vesicles. Disruption of the cellular microtubular network can lead to both diminished vesicular movement and reduced transepithelial secretion. Luminal efflux of organic anions is energetically downhill, but carrier mediated. Both anion exchange and potential driven transport are present, but neither completely accounts for transport from cell to lumen. For organic cations, basolateral entry is downhill via potential driven facilitated diffusion. Intracellular sequestration of organic cations in vesicles is substantial, but its role in secretion is uncertain. Multiple carriers are available to drive organic cations uphill into the tubular lumen. The classical system indirectly taps the energy of the luminal Na gradient to drive organic cation efflux via Na+-H+ and proton-organic cation exchange. In addition, the multidrug resistance ATPase can pump organic cations into the tubular lumen. Thus, although much detailed information has been added over the last 50 years, it is not yet possible to provide a detailed, quantitative understanding of these important excretory systems. RP Pritchard, JB (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,COMPARAT MEMBRANE PHARMACOL SECT,MD 19-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 29 TC 98 Z9 99 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1996 VL 49 IS 6 BP 1649 EP 1654 DI 10.1038/ki.1996.240 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA UL899 UT WOS:A1996UL89900027 PM 8743470 ER PT J AU Burg, MB AF Burg, MB TI Coordinate regulation of organic osmolytes in renal cells SO KIDNEY INTERNATIONAL LA English DT Article ID ALDOSE REDUCTASE; MEDULLARY CELLS; TRANSPORT; NACL; TAURINE; RAT AB Adaptation of cells to prolonged hypertonicity generally involves accumulation of compatible organic osmolytes. Renal medullary cells in vivo and in tissue culture accumulate several different organic osmolytes, including sorbitol, inositol, betaine, and glycerophosphocholine (GPC) in response to hypertonicity. For the total concentration of these organic osmolytes to be appropriate for the ambient tonicity, an increase in one should cause the others to fall, minimizing changes in their total concentration. The experiments presented here demonstrate this in tissue culture and investigate the mechanisms involved. Sorbitol is synthesized from glucose, catalyzed by aldose reductase. Betaine is transported into the cells. Hypertonicity increases transcription of the aldose reductase and betaine transporter genes, ultimately elevating cell sorbitol and betaine. If aldose reductase is inhibited, which prevents accumulation of sorbitol, betaine transporter gene expression increases, resulting in a higher cell betaine that compensates for the lower sorbitol. Conversely, when cell betaine is altered by changing its concentration in the medium, aldose reductase transcription changes reciprocally, resulting in compensating changes in cell sorbitol. Hypertonicity increases GPC by inhibiting GPC:choline phosphodiesterase (GPC:PDE), an enzyme that degrades GPC. When cell betaine or inositol is increased by raising its concentration in the medium, GPC:PDE activity rises, reducing cell GPC. Thus, the total of the osmolytes, rather than the level of any individual one, is maintained. RP Burg, MB (reprint author), NHLBI,NIH,BLDG 10,ROOM 6N307,10 CTR DR MSC 1598,BETHESDA,MD 20892, USA. NR 20 TC 29 Z9 29 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1996 VL 49 IS 6 BP 1684 EP 1685 DI 10.1038/ki.1996.247 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA UL899 UT WOS:A1996UL89900034 PM 8743477 ER PT J AU Knepper, MA Wade, JB Terris, J Ecelbarger, CA Marples, D Mandon, B Chou, CL Kishore, BK Nielsen, S AF Knepper, MA Wade, JB Terris, J Ecelbarger, CA Marples, D Mandon, B Chou, CL Kishore, BK Nielsen, S TI Renal aquaporins SO KIDNEY INTERNATIONAL LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; WATER PERMEABILITY; RAT-KIDNEY; COLLECTING DUCT; CHANNEL; VASOPRESSIN; TRANSPORT; SEGMENTS; HORMONE; LIMB AB Aquaporins (AQPs) are a newly recognized family of transmembrane proteins that function as molecular water channels. At least four aquaporins are expressed in the kidney where they mediate rapid water transport across water-permeable epithelia and play critical roles in urinary concentrating and diluting processes. AQP1 is constitutively expressed at extremely high levels in the proximal tubule and descending limb of Henle's loop. AQP2, -3 and -4 are expressed predominantly in the collecting duct system. AQP2 is the predominant water channel in the apical plasma membrane and AQP3 and -4 are found in the basolateral plasma membrane. Short-term regulation of collecting duct water permeability by vasopressin is largely a consequence of regulated trafficking of AQP2-containing vesicles to and from the apical plasma membrane. C1 AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS,DENMARK. UNIV MARYLAND,COLL MED,DEPT PHYSIOL,BALTIMORE,MD 21201. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. RP Knepper, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BLDG 10,ROOM 6N307,10 CTR DR MSC 1598,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK08832-02, DK-32839] NR 47 TC 123 Z9 126 U1 1 U2 3 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1996 VL 49 IS 6 BP 1712 EP 1717 DI 10.1038/ki.1996.253 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA UL899 UT WOS:A1996UL89900040 PM 8743483 ER PT J AU Nielsen, S Marples, D Frokiaer, J Knepper, M Agre, P AF Nielsen, S Marples, D Frokiaer, J Knepper, M Agre, P TI The aquaporin family of water channels in kidney: An update on physiology and pathophysiology of aquaporin-2 SO KIDNEY INTERNATIONAL LA English DT Article ID COLLECTING DUCT; RAT-KIDNEY; EXPRESSION; CLONING; CHIP AB The long-standing problem of membrane water transport has been advanced by the recognition of a new family of water transport proteins, the ''aquaporins'' [1-3]. Not surprisingly, water transport is a major process in kidney physiology, and the biology of aquaporins is most thoroughly understood in that organ. We reviewed in detail the status of aquaporins in the kidney only one year ago [4], but the subsequent progress has dictated the need for an update. This seems especially appropriate in honor of the 100th birthday of Homer Smith, the pioneer whose foresight initiated this field. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. RP Nielsen, S (reprint author), AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. NR 43 TC 67 Z9 69 U1 1 U2 6 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1996 VL 49 IS 6 BP 1718 EP 1723 DI 10.1038/ki.1996.254 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA UL899 UT WOS:A1996UL89900041 PM 8743484 ER PT J AU Goelz, MF Thigpen, JE Mahler, J Rogers, WP Locklear, J Weigler, BJ Forsythe, DB AF Goelz, MF Thigpen, JE Mahler, J Rogers, WP Locklear, J Weigler, BJ Forsythe, DB TI Efficacy of various therapeutic regimens in eliminating Pasteurella pneumotropica from the mouse SO LABORATORY ANIMAL SCIENCE LA English DT Article ID MICE; ENROFLOXACIN; RATS AB Pasteurella pneumotropica, a gram-negative opportunistic pathogen, can be isolated from the oropharynx, intestinal tract, and reproductive tract of clinically normal mice and has been associated with various clinical syndromes, including conjunctivitis, infections of the reproductive tract, otitis, and subcutaneous abscess formation, Enrofloxacin, a fluoroquinolone bactericidal antimicrobial, has been shown to be effective in eliminating P. multocida from rabbits, We sought to determine whether enrofloxacin would eliminate P. pneumotropica from mice known to be asymptomatically infected with the agent, Pasteurella pneumotropica-positive (culture and immunofluorescence assay) male (n = 55) and female (n = 55) C57BL/6N mice mere randomly assigned to one of seven treatment groups or to a control group, These groups were designed to evaluate the efficacy of enrofloxacin administered orally via the drinking water or parenterally at three dosages (8.5, 25.5, and 85.0 mg/kg of body weight per day) over a 14-day treatment period, A tetracycline-treated group (60 mg/kg per day) and an untreated control group were included for comparisons, Repeated oropharyngeal swab and fecal specimens were obtained for culture through posttreatment day 30, and specimens from numerous enteric and reproductive organs collected during necropsy were used to evaluate group differences, Enrofloxacin eliminated evidence of P. pneumotropica from all sites when administered at 25.5 or 85 mg/kg but not at 8.5 mg/kg by either route for at least 30 days after treatment, Tetracycline-treated and control groups remained consistently culture-positive throughout the study, We concluded that the oral route may be a more practical method for treating large numbers of mice, Enrofloxacin may be a practical and inexpensive alternative to cesarian rederivation or embryo transfer for the elimination of P. pneumotropica in mice. C1 NIEHS,EXPT PATHOL LAB,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,COLL VET MED,RALEIGH,NC 27606. RP Goelz, MF (reprint author), NIEHS,COMPARAT MED BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 41 TC 28 Z9 29 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD JUN PY 1996 VL 46 IS 3 BP 280 EP 285 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA UT159 UT WOS:A1996UT15900005 PM 8799933 ER PT J AU OSullivan, MG Anderson, DK Lund, JE Brown, WP Green, SW Young, NS Brown, KE AF OSullivan, MG Anderson, DK Lund, JE Brown, WP Green, SW Young, NS Brown, KE TI Clinical and epidemiological features of simian parvovirus infection in cynomolgus macaques with severe anemia SO LABORATORY ANIMAL SCIENCE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; CHILDREN; MONKEYS AB We recently identified a simian parvovirus (SPV) in cynomolgus monkeys with severe anemia, We describe here the clinical and epidemiological findings in the original outbreak and in a second episode of anemia involving monkeys in a drug safety study at a separate facility, The major clinical findings associated with SPV infection were a severe normocytic, normochromic anemia, In the original episode the anemia was predominantly nonregenerative, whereas in the second outbreak there was an initial strong, regenerative response, In the absence of predisposing factors, SPV infection was mild or inapparent. However, the presence of concurrent acute infection with type D simian retrovirus in the original episode is believed to have been a major predisposing factor for the development of immunodeficiency and persistent SPV infection, culminating in severe anemia, It is unclear whether simian retrovirus infection played a role in the second episode, but it is possible that the drug used may have been a factor, because severely anemic monkeys were in the high drug dosage group, We conclude that SPV should be considered in the differential diagnosis of severe anemia in monkeys. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. UPJOHN CO,KALAMAZOO,MI 49001. RP OSullivan, MG (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. NR 17 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD JUN PY 1996 VL 46 IS 3 BP 291 EP 297 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA UT159 UT WOS:A1996UT15900007 PM 8799935 ER PT J AU Kopp, JB Factor, VM Motes, M Nagy, P Sanderson, N Bottinger, EP Klotman, PE Thorgeirsson, SS AF Kopp, JB Factor, VM Motes, M Nagy, P Sanderson, N Bottinger, EP Klotman, PE Thorgeirsson, SS TI Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease SO LABORATORY INVESTIGATION LA English DT Article ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; EXPERIMENTAL GLOMERULONEPHRITIS; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; FACTOR GENE; RAT-KIDNEY; FACTOR-BETA-1; EXPRESSION; GLOMERULOSCLEROSIS AB Several lines of evidence suggest that local production of transforming growth factor-beta (TGF-beta) contributes to renal disease, particularly to the accumulation of the extracellular matrix protein that characterizes glomerulosclerosis and interstitial fibrosis. We have examined whether elevated levels of circulating TGF-beta adversely affect the kidney. We have studied mice that are transgenic for an active form of TGF-beta 1 under the control of murine albumin promoter and enhancer DNA sequences. These mice express the transgene exclusively in the liver and have elevated plasma concentrations of TGF-beta 1. Renal disease was seen in two of three lines of Alb/TGF-beta 1 transgenic mice; these two lines had the highest levels of hepatic transgene expression and the highest plasma TGF-beta 1 levels. Histologic abnormalities, which included mesangial expansion and thickened capillary loops, were noted in the glomeruli by 3 weeks of age. Interstitial fibrosis and tubular atrophy appeared subsequently. Mice from Line 25, the line with highest levels of TGF-beta 1, developed proteinuria by 5 weeks of age. These mice subsequently manifested nephrotic syndrome with ascites and progressive azotemia; uremic death occurred in more than 25% of the mice by 15 weeks of age. The glomeruli contained immune deposits in subendothelial and mesangial locations, but complement deposition was infrequent. Ultrastructural examination revealed an increase in extracellular matrix material, including collagen fibrils, in subendothelial and mesangial locations. Increased levels of circulating TGF-beta 1 induced progressive renal disease that was characterized by mesangial expansion, accumulation of glomerular immune deposits and matrix proteins, and interstitial fibrosis in this transgenic mouse model. These data suggest that chronically elevated circulating levels of TGF-beta 1 induce progressive glomerulosclerosis. C1 NCI, EXPTL CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. NCI, CHEMOPREVENT LAB, NIH, BETHESDA, MD 20892 USA. CUNY MT SINAI SCH MED, DIV NEPHROL, NEW YORK, NY 10029 USA. RP Kopp, JB (reprint author), NIDDKD, KIDNEY DIS SECT,METAB DIS BRANCH,NIH,BLDG 10, ROOM 3N116, BETHESDA, MD 20892 USA. RI Mozes, Miklos/E-9003-2011; OI Kopp, Jeffrey/0000-0001-9052-186X NR 29 TC 337 Z9 348 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 1996 VL 74 IS 6 BP 991 EP 1003 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA UQ738 UT WOS:A1996UQ73800002 PM 8667617 ER PT J AU Giannelli, G Brassard, J Foti, C StetlerStevenson, WG FalkMarzillier, J ZamboninZallone, A Schiraldi, O Quaranta, V AF Giannelli, G Brassard, J Foti, C StetlerStevenson, WG FalkMarzillier, J ZamboninZallone, A Schiraldi, O Quaranta, V TI Altered expression of basement membrane proteins and their integrin receptors in lichen planus: Possible pathogenetic role of gelatinases A and B SO LABORATORY INVESTIGATION LA English DT Article ID TISSUE INHIBITOR; MONOCLONAL-ANTIBODIES; INTERSTITIAL COLLAGENASE; ALPHA-6-BETA-4 INTEGRIN; CELL-INTERACTIONS; ALPHA-3-BETA-1; HEMIDESMOSOMES; KERATINOCYTES; ADHESION; MATRIX AB Lichenoid lesions of the skin are characterized by a band-like dermal inflammatory infiltrate and structural alterations of the basement membrane (BM). The etiopathogenesis of these lesions, of which lichen planus (LP) is perhaps the prototypic example, is unknown. Acute cases of LP are accompanied by the destruction of epidermal BM, degeneration of basal keratinocytes with loss of tonofilaments and hemidesmosomes, vesicular alterations, and even blister formation. Chronic LP is characterized by hyperkeratosis and acanthosis in the epidermis, fibrosis, and dense infiltrate in dermis. We found that acute LP lesions are characterized by uneven or absent immunostaining for laminin-5, laminin-l, and collagen type IV. Distribution and activity of gelatinases matrix metalloproteinase (MMP)-9 and MMP-2, and a specific inhibitor of MMP-2, tissue inhibitor of metalloprotein-2, were analyzed. The expression and activity of MMP-2 were increased, whereas tissue inhibitor of metalloprotein-2 expression was weak in the involved areas during the acute phase of LP. Moreover, we demonstrated in vitro that MMP-2 is directly capable of digesting laminin-5 gamma 2 chains to yield a 80-kd fragment. We also observed a weak or absent staining of all examined integrin receptors in the acute LP lesions. In chronic lesions, the staining of BM components was similar to normal controls. in these sections, normal expression of gelatinases and inhibitor was observed. There was, however, up-regulation and altered polarity of integrin receptors. These results indicate a link between overexpression of gelatinases, BM disruption, and altered integrin expression. In LP, the digestion of BM by MMP-2 may contribute to the pathogenesis by inducing altered integrin expression in basal keratinocytes and ultimately blister formation. C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. UNIV BARI, INST MED CLIN 2, BARI, ITALY. UNIV BARI, DERMATOL CLIN, BARI, ITALY. UNIV BARI, INST HUMAN ANAT, BARI, ITALY. NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. RP Giannelli, G (reprint author), Scripps Res Inst, DEPT CELL BIOL, 10666 N TORREY PINES RD, SBR-12, LA JOLLA, CA 92037 USA. RI giannelli, gianluigi/A-8169-2012; Stetler-Stevenson, William/H-6956-2012; Quaranta, Vito/G-6512-2016; OI Stetler-Stevenson, William/0000-0002-5500-5808; Quaranta, Vito/0000-0001-7491-8672; Foti, Caterina/0000-0001-6196-9788; Giannelli, Gianluigi/0000-0002-5140-8060 FU NIDCR NIH HHS [DE 10063]; NIGMS NIH HHS [GM 46902] NR 63 TC 39 Z9 40 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 1996 VL 74 IS 6 BP 1091 EP 1104 PG 14 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA UQ738 UT WOS:A1996UQ73800011 PM 8667613 ER PT J AU Sallie, R Shaw, J Mutimer, D AF Sallie, R Shaw, J Mutimer, D TI GBV-C virus and fulminant hepatic failure SO LANCET LA English DT Letter C1 QUEEN ELIZABETH MED CTR,LIVER RES LABS,BIRMINGHAM,W MIDLANDS,ENGLAND. QUEEN ELIZABETH MED CTR,LIVER & BILIARY UNIT,BIRMINGHAM,W MIDLANDS,ENGLAND. RP Sallie, R (reprint author), NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD 20892, USA. NR 4 TC 70 Z9 70 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 1 PY 1996 VL 347 IS 9014 BP 1552 EP 1552 DI 10.1016/S0140-6736(96)90704-7 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UN473 UT WOS:A1996UN47300044 PM 8684121 ER PT J AU Ishikawa, Y Tsukuma, H Miller, RW AF Ishikawa, Y Tsukuma, H Miller, RW TI Low rates of Paget's disease of bone and osteosarcoma in elderly Japanese SO LANCET LA English DT Letter C1 CTR CANC & CARDIOVASC DIS,DEPT FIELD RES,OSAKA,JAPAN. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP Ishikawa, Y (reprint author), JAPANESE FDN CANC RES,INST CANC,DEPT PATHOL,TOKYO 170,JAPAN. NR 3 TC 6 Z9 8 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 1 PY 1996 VL 347 IS 9014 BP 1559 EP 1559 DI 10.1016/S0140-6736(96)90714-X PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UN473 UT WOS:A1996UN47300057 PM 8684133 ER PT J AU Santini, G Congiu, AM Nati, S Pierluigi, D Spriano, M Chisesi, T Rossi, E Vimercati, R Sertoli, MR Figari, O Gobbi, M Piaggio, G Vassallo, F Benvenuto, F Soracco, M Miglino, M Bruni, R Ravetti, JL Truini, M AF Santini, G Congiu, AM Nati, S Pierluigi, D Spriano, M Chisesi, T Rossi, E Vimercati, R Sertoli, MR Figari, O Gobbi, M Piaggio, G Vassallo, F Benvenuto, F Soracco, M Miglino, M Bruni, R Ravetti, JL Truini, M TI Mobilization/transplantation of peripheral blood progenitor cells for aggressive non-Hodgkin's lymphoma with marrow involvement SO LEUKEMIA LA English DT Article; Proceedings Paper CT 9th Symposium on Molecular Biology of Hematopoiesis and Treatment of Leukemias and Lymphomas CY JUN 23-27, 1995 CL GENOA, ITALY SP Menarini Int Fdn DE aggressive NHL; high-dose CY; PBPC rescue ID HIGH-DOSE CYCLOPHOSPHAMIDE; AUTOLOGOUS BONE-MARROW; TRANSPLANTATION; CHEMOTHERAPY; COMBINATION; CISPLATIN; REGIMEN; THERAPY AB Thirty-five aggressive non-Hodgkin's lymphomas (NHL) with marrow involvement received high-dose cyclophosphamide (7 g/m(2)) and G-CSF in order to collect peripheral blood progenitor cells (PBPC). Fourteen patients were in partial remission, 16 patients were in relapse ('sensitive', 12; 'resistant', 4) and five patients were refractory to conventional treatment. A good yield of PBPC was obtained in 30 patients, while a low number of CD34(+) cells and of CFU-GM was seen in two cases. Two patients entered progression and one patient died. Thirty patients underwent PBPC autografting. Twenty-nine out of 35 (83%) patients entered complete remission (CR). Two patients died in CR of infection following marrow aplasia 3 and 6 months after autografting. At 3 years the probability of survival and disease-free survival (DFS) are 62 and 51%, respectively. C1 OSPED SAN MARTINO GENOVA,DEPT HEMATOL,GENOA,ITALY. OSPED SAN MARTINO GENOVA,DEPT PATHOL,GENOA,ITALY. OSPED CIVILE,DIV HEMATOL,VENICE,ITALY. NATL CANC INST,GENOA,ITALY. UNIV GENOA,INST HEMATOL,GENOA,ITALY. RI Miglino, Maria Angelica/B-9519-2012 OI Miglino, Maria Angelica/0000-0003-4979-115X NR 13 TC 6 Z9 6 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 1996 VL 10 SU 2 BP S88 EP S91 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA UZ467 UT WOS:A1996UZ46700021 PM 8649061 ER PT J AU Levy, LA Gabel, SA London, RE AF Levy, LA Gabel, SA London, RE TI Synthesis and characterization of two improved NMR indicators for cytosolic Ca2+:3FBAPTA and 35FBAPTA SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE F-19 NMR; FBAPTA; intracellular calcium indicators; calcium ion indicators ID INTRACELLULAR FREE CALCIUM; PERFUSED RAT-HEART; F-19 NMR; SELECTIVE INVERSION; FREE MAGNESIUM; CELLS; SPECTROSCOPY; LEAD; CHELATORS; ISCHEMIA AB Fluorinated derivatives of the calcium-selective chelator BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] are popular NMR probes for cytosolic calcium ion concentration. Two such derivatives were synthesized and evaluated, 3FBATA [1,2,-bis(2-amino-3-fluorophenoxy)ethane- N,N,N',N'-tetraacetic acid] and 35FBAPTA [1,2-bis(amino-3,5-difluorophenoxy)ethane- N,N,N'N'-tetraacetic acid]. The dissociation constant ratios obtained at 37 degrees C. Hence, 3FBAPTA binds calciums ion more tightly than 5FBAPTA [1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid, the currently most frequently utilized indicator], while the doubly substituted derivative exhibits intermediate affinity. The dissociation rate constants for the calcium complexes measured at 37 degrees C exhibit a simular trend, with k(-1)(5)>k(-1)(35)>k(-1)(3). Both of the additional derivatives exhibit slow exchange kinetics, and should be superior fluorine NMR probes owing to the decreased T-1 values and, in the case of 35FBAPTA, the presence of two calcium-sensitive fluorine nuclei which are measured simultaneously. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 39 TC 2 Z9 2 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD JUN PY 1996 VL 34 IS 6 BP 440 EP 446 DI 10.1002/(SICI)1097-458X(199606)34:6<440::AID-OMR901>3.0.CO;2-M PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA UQ910 UT WOS:A1996UQ91000004 ER PT J AU Marine, JC Gilbert, DJ Bellefroid, EJ Martial, JA Ihle, JN Copeland, NG Jenkins, NA AF Marine, JC Gilbert, DJ Bellefroid, EJ Martial, JA Ihle, JN Copeland, NG Jenkins, NA TI Chromosomal location of fifteen unique mouse KRAB-containing zinc finger loci SO MAMMALIAN GENOME LA English DT Article ID PROTEIN GENES; LINKAGE MAP; LOCALIZATION; EXPRESSION; ORGANIZATION; CELLS; SEQUENCES; RECEPTOR; GENOME; FAMILY AB The mammalian genome contains hundreds if not thousands of zinc finger protein (ZSp) genes. While the function of most of these genes remains to be determined, it is clear that a few of them play important roles in gene regulation and development. In studies described here, we have used an interspecific mouse backcross mapping panel to determine the chromosomal location of 15 KRAB-containing zinc finger loci. These loci map to nine different mouse autosomes and the X Chromosome (Chr). Two Chrs, 7 and 9, contain cosegregating pairs of KRAB-containing Zfp genes, indicating that the KRAB-containing Zfp genes have evolved through processes involving regional as well as genome-wide duplication events. C1 NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. UNIV LIEGE, INST CHIM B6, LAB BIOL MOL & GENIE GENET, B-4000 SART, BELGIUM. UNIV GOTTINGEN, INST BIOCHEM & MOLEK BIOL, D-37073 GOTTINGEN, GERMANY. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. RI Marine, Jean Christophe/J-2237-2015; Marine, Jean-Christophe/K-3292-2016 OI Marine, Jean-Christophe/0000-0003-2433-9837 FU NCI NIH HHS [CA1020]; PHS HHS [P30C21765] NR 39 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUN PY 1996 VL 7 IS 6 BP 413 EP 416 DI 10.1007/s003359900123 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UT093 UT WOS:A1996UT09300003 PM 8662221 ER PT J AU Liao, X Ma, C Trask, B Massa, H Gilbert, DJ Staudt, LM Jenkins, NA Copeland, NG AF Liao, X Ma, C Trask, B Massa, H Gilbert, DJ Staudt, LM Jenkins, NA Copeland, NG TI LAF4 maps to mouse chromosome 1 and human chromosome 2q11.2-q12 SO MAMMALIAN GENOME LA English DT Article C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NCI,METAB BRANCH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA 98195. NR 8 TC 9 Z9 9 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUN PY 1996 VL 7 IS 6 BP 467 EP 468 DI 10.1007/s003359900137 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UT093 UT WOS:A1996UT09300019 PM 8662235 ER PT J AU Brown, DJ Clark, GC Gardner, GR VanBeneden, RJ AF Brown, DJ Clark, GC Gardner, GR VanBeneden, RJ TI Identification of dioxin-specific binding proteins in marine bivalves SO MARINE ENVIRONMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 8th International Symposium on Pollutant Responses in Marine Organisms (PRIMO 9) CY APR 02-05, 1995 CL PACIFIC GROVE, CA SP Univ Calif Davis, US EPA, Ctr Ecol Hlth Res, Univ Calif Davis, Superfund Basic Sci Res Program, NOAA, Natl Marine Fisheries Serv, NW Fisheries Sci Ctr, State Calif Fish & Gam Off Oil Spill Prevent & Response, Vet Serv, US Natl Inst Environm Hlth Sci, Monterey Bay Aquarium, Calif Sea Grant Program ID POLYCYCLIC AROMATIC-HYDROCARBONS; AH RECEPTOR; HERBICIDES; OYSTER AB Epidemiological investigations of germ cell tumors of Maine soft shell clams (Mya arenaria) and hard shell clams (Mercenaria spp.) from Florida demonstrate the prevalence of histogenically similar gonadal cancers as high as 40 and 60%, respectively. Human mortality rates due to ovarian cancer from the same areas are significantly greater than the national average. Since further investigation revealed that there was a heavy use of herbicides at these sites, we proposed to investigate their possible role in the etiology of the clam tumors. One avenue of investigation was to determine whether clams had a mechanism similar to the vertebrate Ah receptor which could be activated by halogenated aromatic hydrocarbons (HAH). We used the TCDD photoaffinity analog [(125)-I]-2-azido-3-iono-7,8-dibromodibenzo-p-dioxin to detect two cytosolic proteins (28 and 39 kDa) in Mercenaria mercenaria and one (35 kDa) in Mya arenaria which specifically bound this ligand. Expression of both proteins in Mercenaria is tissue specific with the highest levels observed in cytosols from gill and gonad. Females exhibit higher levels of the 39 kDa protein in gonadal tissue than do the males. Studies to determine the relationship of these proteins to vertebrate Ah receptors, as well as their possible role in gonadal tumor development, are in progress. Cpyright (C) 1996 Elsevier Science Ltd C1 UNIV MAINE,DEPT ZOOL,ORONO,ME 04469. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. NIEHS,DURHAM,NC 27709. US EPA,NARRAGANSETT,RI 02882. NR 18 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0141-1136 J9 MAR ENVIRON RES JI Mar. Environ. Res. PD JUN-OCT PY 1996 VL 42 IS 1-4 BP 7 EP 11 DI 10.1016/0141-1136(95)00049-6 PG 5 WC Environmental Sciences; Marine & Freshwater Biology; Toxicology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Toxicology GA UU369 UT WOS:A1996UU36900003 ER PT J AU Duncan, MK Li, X Ogino, H Yasuda, K Piatigorsky, J AF Duncan, MK Li, X Ogino, H Yasuda, K Piatigorsky, J TI Developmental regulation of the chicken beta B1-crystallin promoter in transgenic mice SO MECHANISMS OF DEVELOPMENT LA English DT Article DE beta B1-crystallin; chloramphenicol acetyl transferase; transgenic mice ID TISSUE-SPECIFIC EXPRESSION; A-CRYSTALLIN PROMOTER; LENS-SPECIFIC EXPRESSION; DELTA-CRYSTALLIN; CHLORAMPHENICOL ACETYLTRANSFERASE; ALPHA-CRYSTALLIN; ENHANCER ELEMENT; MAMMALIAN-CELLS; MESSENGER-RNAS; GENE AB The cis-elements responsible for the high-level, lens-specific expression of the chicken beta B1-crystallin gene were investigated by generating mice harboring beta B1-crystallin promoter/chloramphenicol acetyl transferase (CAT) transgenes. Deletion of promoter sequences -434/-153 and -152/-127 as well as site-directed mutagenesis of the PL1 (-116/-102) and PL2 (-90/-76) elements significantly decreased CAT gene expression in the lenses of adult transgenic mice. Transfection studies using multimerized PLI and PL2 elements fused to the chicken B-actin basal promoter indicated that PL1 is a general activating element while PL2 is involved in the lens-specificity of the chicken beta B1-crystallin promoter. CAT histochemistry demonstrated that the chicken beta B1-crystallin promoter (-434/+30) was active in both primary and secondary lens fiber cells from 12.5 days post coitum (dpc) until adulthood, Activity of the -152/+30/CAT transgene was relatively low and confined to the primary lens fiber cells of 16.5 dpc mice. Together, these data suggest that the reduced activity of this promoter in the adult lens is due both to this developmentally restricted expression pattern and a reduction in promoter activity, RNA hybridization studies demonstrated that the chicken beta B1-crystallin/CAT (-434/+30) transgene was expressed at similar levels in the same cells as the endogenous mouse beta B1-crystallin gene in 16.5 dpc transgenic mouse embryos. These data show a strict conservation of the lens-specific spatial and temporal regulation of the chicken and mouse beta B1-crystallin genes. C1 NEI,NATL INST HLTH,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NARA INST SCI & TECHNOL,GRAD SCH BIOMED SCI MOL & DEV BIOL,IKOMA 63001,JAPAN. NR 43 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUN PY 1996 VL 57 IS 1 BP 79 EP 89 DI 10.1016/0925-4773(96)00533-3 PG 11 WC Developmental Biology SC Developmental Biology GA UW166 UT WOS:A1996UW16600007 PM 8817455 ER PT J AU Sallie, R AF Sallie, R TI Gene identification by chromosomal in-situ hybridization, microdissection and polymerase chain reaction amplification SO MEDICAL HYPOTHESES LA English DT Article ID SATELLITE DNA INSITU; HEMOCHROMATOSIS AB This paper describes a theoretical method by which candidate genes for inherited diseases can be identified by polymerase chain reaction amplification and subsequent cloning of organ-specific complementary deoxyribonucleic acid libraries hybridized in situ to, and subsequently dissected from, the cognate chromosome. A specific application of this technique to isolate genes related to genetic haemochromatosis is outlined. C1 NIH,LIVER UNIT,BETHESDA,MD 20892. NR 13 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUN PY 1996 VL 46 IS 6 BP 533 EP 535 DI 10.1016/S0306-9877(96)90127-9 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UT642 UT WOS:A1996UT64200010 PM 8803937 ER PT J AU Prentice, RL Rossouw, JE Johnson, SR Freedman, LS McTiernan, A AF Prentice, RL Rossouw, JE Johnson, SR Freedman, LS McTiernan, A TI The role of randomized controlled trials in assessing the benefits and risks of long-term hormone replacement therapy: Example of the women's health initiative SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE benefits versus risks; hormone replacement therapy; postmenopausal women; randomized controlled trials; research strategies ID BREAST-CANCER; DISEASE AB Observational studies suggest that hormone replacement therapy among postmenopausal women may have important benefits, particularly in relation to heart disease and bone fractures, but may also convey important risks, most notably for breast cancer. The magnitude of these potential benefits and risks and the prevalence of use of hormone replacement therapy in the United States make the question of benefits versus risks a very pressing public health issue. This public health importance, along with the fact that reliable answers are likely to depend on accurate quantitative assessments of the impact of hormone replacement therapy on a range of clinical outcomes? implies a critical role for randomized controlled clinical trials of adequate size, duration, and quality in an overall replacement hormone research strategy. Some limitations of cohort and case-control studies of long-term hormone replacement therapy are briefly mentioned toward establishing the need for the type of logistically complicated clinical trial included in the Women's Health Initiative. This is followed by a description of the hormone replacement therapy component of the Women's Health Initiative Clinical Trial, along with some comments on the methods to be used for benefit-versus-risk monitoring and analysis of this trial. It is recommended that long-term hormone replacement therapy, in the form of estrogen alone for hysterectomized women or estrogen plus progestin for women with a uterus, should be prescribed conservatively until more reliable data on risks and benefits are available from randomized controlled trials or from other sources. C1 WOMENS HLTH INITIAT PROJECT OFF,BETHESDA,MD. UNIV IOWA,SCH MED,IOWA CITY,IA 52242. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Prentice, RL (reprint author), FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,1124 COLUMBIA ST,SEATTLE,WA 98104, USA. NR 15 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SUM PY 1996 VL 3 IS 2 BP 71 EP 76 DI 10.1097/00042192-199603020-00003 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UM133 UT WOS:A1996UM13300003 ER PT J AU Schmidt, MI Watson, RL Duncan, BB Metcalf, P Brancati, FL Sharrett, AR Davis, CE Heiss, G AF Schmidt, MI Watson, RL Duncan, BB Metcalf, P Brancati, FL Sharrett, AR Davis, CE Heiss, G TI Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; URIC-ACID CONCENTRATION; BODY-FAT DISTRIBUTION; ADIPOSE-TISSUE; PLASMA-INSULIN; BLOOD-PRESSURE; GLUCOSE-INTOLERANCE; METABOLIC SYNDROME; DISEASE MORTALITY; RESISTANCE AB Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P <.001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P <.001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P <.001 for most) and of body mass index (1.6 to 4.5, P <.05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults. Copyright (C) 1996 by W.B. Saunders Company. C1 UNIV MISSISSIPPI, MED CTR, DEPT PREVENT MED, DIV EPIDEMIOL, JACKSON, MS 39216 USA. UNIV FED RIO GRANDE SUL, FAC MED, DEPT SOCIAL MED, PORTO ALEGRE, RS, BRAZIL. UNIV N CAROLINA, SCH PUBL HLTH, DEPT EPIDEMIOL, CHAPEL HILL, NC USA. UNIV N CAROLINA, SCH PUBL HLTH, DEPT BIOSTAT, CHAPEL HILL, NC USA. NHLBI, BETHESDA, MD 20892 USA. JOHNS HOPKINS MED INST, WELCH CTR PREVENT EPIDEMIOL & CLIN RES, BALTIMORE, MD 21205 USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 64 TC 139 Z9 150 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 1996 VL 45 IS 6 BP 699 EP 706 DI 10.1016/S0026-0495(96)90134-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP075 UT WOS:A1996UP07500006 PM 8637443 ER PT J AU Fertig, JB Allen, JP AF Fertig, JB Allen, JP TI Health behavior correlates of hazardous drinking by army personnel SO MILITARY MEDICINE LA English DT Article ID SMOKING CESSATION; ALCOHOL-CONSUMPTION; NUTRITIONAL-STATUS; TOBACCO; SMOKERS AB The current investigation determined that military personnel who drink heavily differ from those who drink moderately in the practice of nine behaviors often associated with unhealthy lifestyle. In particular, excessive drinkers were found to smoke more, drive dangerously more frequently, and consume saturated fats more often. The project further found that the relationship of excessive drinking to these activities is mediated by age, marital status, and race, although not by gender or rank. Implications of the findings for prevention and treatment are suggested. RP Fertig, JB (reprint author), NIAAA,WILLCO BLDG,SUITE 505,6000 EXECUT BLVD MSC 7003,BETHESDA,MD 20892, USA. NR 34 TC 9 Z9 9 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUN PY 1996 VL 161 IS 6 BP 352 EP 355 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA UP825 UT WOS:A1996UP82500016 PM 8700332 ER PT J AU Kiefer, MC Crawford, KA Boley, LJ Landsberg, KE Gibson, HL Kaslow, DC Barr, PJ AF Kiefer, MC Crawford, KA Boley, LJ Landsberg, KE Gibson, HL Kaslow, DC Barr, PJ TI Identification and cloning of a locus of serine repeat antigen (sera)-related genes from Plasmodium vivax SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium vivax; cysteine-like proteinase; xerine repeat antigen (SERA); malaria vaccine ID BLOOD STAGE ANTIGEN; MOLECULAR-CLONING; CYSTEINE PROTEASES; SERA PROTEINS; AOTUS MONKEYS; FALCIPARUM; SEQUENCES; STRETCH AB Polymerase chain reaction (PCR) primers based on the cysteine proteinase-like active site regions of the Plasmodium falciparum serine repeat antigen (SERA) were used to identify related sequences within the genome of P. vivax. Molecular cloning and sequence analysis of similar to 25 kb of P. vivax genomic DNA revealed a cluster of five repeated SERA-like genes (V-SERA-1-5), each encoding a cysteine proteinase-related protein. In addition to DNA sequence homology, significant similarities in deduced intron/exon organizations were also observed. The characteristic polyserine sequence found in SERA was not present in any of the deduced V-SERA sequences. Instead, in this region of the five genes, considerable sequence differences were found, suggesting the potential for antigenic variation in the V-SERA molecules. In common with SERA, however, the codon at the position corresponding to the active site cysteine residue of active mammalian and plant cysteinyl proteinases was found to be that of a serine residue in each of the V-SERA genes. Furthermore, in four of the five genes, including the expressed V-SERA-5 gene, the codon for the active site histidine residue was changed to that of a leucine residue. These critical differences reinforce the concept-that a biological activity other than proteolysis is likely to be the primary function of the proteins encoded by this family of genes. C1 CHIRON CORP,EMERYVILLE,CA 94608. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD. NR 34 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 1996 VL 78 IS 1-2 BP 55 EP 65 DI 10.1016/S0166-6851(96)02607-2 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA UW159 UT WOS:A1996UW15900006 PM 8813677 ER PT J AU Williamson, KC Fujioka, H Aikawa, M Kaslow, DC AF Williamson, KC Fujioka, H Aikawa, M Kaslow, DC TI Stage-specific processing of Pfs230, a Plasmodium falciparum transmission-blocking vaccine candidate SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; Pfs230; immunodominance; vaccine candidate ID ANTIBODIES; ANTIGENS; TARGET; BIOSYNTHESIS; MALARIA; PROTEIN AB During Plasmodium falciparum gametocytogenesis, Pfs230, a malaria transmission-blocking vaccine candidate, is expressed as a 360 kDa protein localized to the parasitophorous vacuole/parasite plasma membrane. When gametocytes emerge from red blood cells, as they do when taken up in a blood meal by a mosquito, Pfs230 is processed from a 360 kDa form to a 310 kDa form the latter of which is exposed on the exterior surface of gametes. The 50 kDa portion of Pfs230, removed from the amino-terminus of the 360 kDa form, contains 25 contiguous glutamates and an EEVG(16) repeat. Analogous to other P. falciparum proteins, the repeat region appears to be immunodominant. As the gamete emerges from the red blood cell and is exposed to the antibodies in the blood meal, cleavage of the immunodominant region of Pfs230 may contribute to an immune evasion strategy by the parasite. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NIAID,MALARIA VACCINE SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RP Williamson, KC (reprint author), LOYOLA UNIV,DEPT BIOL,DH812,6525 N SHERIDAN RD,CHICAGO,IL 60626, USA. FU NIAID NIH HHS [AI-35827] NR 16 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 1996 VL 78 IS 1-2 BP 161 EP 169 DI 10.1016/S0166-6851(96)02621-7 PG 9 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA UW159 UT WOS:A1996UW15900015 PM 8813686 ER PT J AU Michelotti, GA Michelotti, EF Pullner, A Duncan, RC Eick, D Levens, D AF Michelotti, GA Michelotti, EF Pullner, A Duncan, RC Eick, D Levens, D TI Multiple single-stranded cis elements are associated with activated chromatin of the human c-myc gene in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC-FINGER PROTEINS; TRANSCRIPTIONAL CONTROL; DNA-REPLICATION; BINDING PROTEIN; DOWN-REGULATION; LEUKEMIA-CELLS; HL60 CELLS; 1ST EXON; PROMOTER; EXPRESSION AB Transcription activation and repression of eukaryotic genes are associated with conformational and topological changes of the DNA and chromatin, altering the spectrum of proteins associated with an active gene. Segments of the human c-myc gene possessing non-B structure in vivo were located with enzymatic and chemical probes. Sites hypersensitive to cleavage with the single-strand-specific S1 nuclease or the single-strand-selective agent potassium permanganate included the major promoters P1 and P2 as well as the far upstream sequence element (FUSE) and CT elements, which bind, respectively, the single-strand-specific factors FUSE-binding protein and heterogeneous nuclear ribonucleoprotein Ii in vitro. Active and inactive c-myc genes yielded different patterns of S1 nuclease and permanganate sensitivity, indicating alternative chromatin configurations of active and silent genes. The melting of specific cis elements of active c-myc genes in vivo suggested that transcriptionally associated torsional strain might assist strand separation and facilitate factor binding. Therefore, the interaction of FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K with supercoiled DNA was studied. Remarkably, both proteins recognize their respective elements torsionally strained but not as linear duplexes. Single-strand- or supercoil-dependent gene regulatory proteins may directly link alterations in DNA conformation and topology with changes in gene expression. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT,INST KLIN MOL BIOL & TUMORGENET,D-81377 MUNICH,GERMANY. RI Levens, David/C-9216-2009; Duncan, Robert/I-8168-2015 OI Levens, David/0000-0002-7616-922X; Duncan, Robert/0000-0001-8409-2501 NR 70 TC 169 Z9 169 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1996 VL 16 IS 6 BP 2656 EP 2669 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UL974 UT WOS:A1996UL97400013 PM 8649373 ER PT J AU ElKharroubi, A Martin, MA AF ElKharroubi, A Martin, MA TI cis-acting sequences located downstream of the human immunodeficiency virus type 1 promoter affect its chromatin structure and transcriptional activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LONG TERMINAL REPEAT; I-HYPERSENSITIVE SITES; MICROCOCCAL NUCLEASE; DNASE-I; POSITIONED NUCLEOSOMES; PHO5 PROMOTER; MMTV PROMOTER; ACTIVATION; ENHANCER; MECHANISM AB We have examined the roles of AP-1, AP-3-like, DBF1, and Sp1 binding sites, which are located downstream of the human immunodeficiency virus type 1 (HIV-1) promoter, in regulating basal transcriptional activity directed by the integrated viral long terminal repeat (LTR), Point mutations affecting all four of these elements functionally inactivated the HIV-1 LTR when it was constrained in a chromatin configuration, Analyses of the chromatin structures of the transcriptionally active wild-type and inactive mutated HIV-1 promoters revealed several differences, In the active promoter, the 3' half of the U3 region, including the basal promoter, the enhancer, and the putative upstream regulatory sequences are situated within a nuclease-hypersensitive region. However, the far upstream U3 region appears to be packaged into a nuclease-resistant nucleosomal structure, whereas the R, U5, and gag leader sequences are associated with a region of altered chromatin that is sensitive to restriction endonucleases, In the inactive template, only the basal promoter and enhancer element remain sensitive to nucleases, and the adjacent upstream and downstream regions are incorporated into nuclease-resistant nucleosomal structures, Taken together, these results indicate that the chromatin structure of the integrated HIV-1 LTR plays a critical role in modulating basal transcriptional activity. RP ElKharroubi, A (reprint author), NIAID,MOLEC MICROBIOL LAB,NIH,BLDG 4,ROOM 337,4 CTR DR,MSC 0460,BETHESDA,MD 20892, USA. NR 52 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1996 VL 16 IS 6 BP 2958 EP 2966 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UL974 UT WOS:A1996UL97400047 PM 8649407 ER PT J AU Malik, KF Kim, J Hartman, AL Kim, P Young, WS AF Malik, KF Kim, J Hartman, AL Kim, P Young, WS TI Binding preferences of the POU domain protein Brain-4: Implications for autoregulation SO MOLECULAR BRAIN RESEARCH LA English DT Article DE transcription factor; POU; hypothalamus; neuropeptide; gene regulation; in situ hybridization; autoregulation ID THYROTROPIN-RELEASING-HORMONE; MESSENGER-RNA; PARAVENTRICULAR NUCLEUS; FLANKING SEQUENCES; GENE; RAT; EXPRESSION; REGION; HYPOTHALAMUS; ACTIVATOR AB The POU domain-containing transcription factor Brain-4 (Brn-4, RHS-2) was examined for its sites of expression and DNA binding preferences. In the rat, Brn-4 is expressed in 76 and 65% of vasopressin neurons in the paraventricular and supraoptic nuclei, respectively; but in only 10% of corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus. From these data we speculate that genes expressed within vasopressinergic neurons are more likely to be regulated by Brn-4 than those in corticotropin-releasing factor neurons. Random oligonucleotide site selection indicates Brn-4 prefers binding the DNA element CAATATGCTAAT and is inflexible in its spacing requirement between putative CAATAT and TAAT half sites, preferring 2 nucleotides between these elements. Electrophoretic mobility shift and DNase I footprinting analyses show five regions between nucleotides -457 and +22 of the Brn-4 promoter that are bound by Brn-4. Furthermore, Brn-4 can transactivate from this region of the Brn-4 promoter, suggesting that Brn-4 expression may be autoregulated. C1 NINCDS,SECT DEV GENET,BETHESDA,MD 20892. RP Malik, KF (reprint author), NIMH,CELL BIOL LAB,NIH,BLDG 36,RM 2D10,BETHESDA,MD 20892, USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 33 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN PY 1996 VL 38 IS 2 BP 209 EP 221 DI 10.1016/0169-328X(95)00308-F PG 13 WC Neurosciences SC Neurosciences & Neurology GA UQ907 UT WOS:A1996UQ90700004 ER PT J AU PernasAlonso, R Schaffner, AE PerroneCapano, C Orlando, A Morelli, F Hansen, CT Barker, JL Esposito, B Cacucci, F diPorzio, U AF PernasAlonso, R Schaffner, AE PerroneCapano, C Orlando, A Morelli, F Hansen, CT Barker, JL Esposito, B Cacucci, F diPorzio, U TI Early upregulation of medium neurofilament gene expression in developing spinal cord of the wobbler mouse mutant SO MOLECULAR BRAIN RESEARCH LA English DT Article DE choline acetyltransferase; spinal muscular atrophy of childhood; motoneuron development; mrna stabilization; neurofilament overexpression; neuromuscular diseases; RT-PCR; transcriptional regulation ID MOTOR-NEURON DISEASE; TRANSGENIC MICE; NF-L; PROTEIN; CELLS; RAT; POLYPEPTIDES; SEQUENCES; SYSTEM AB Homozygous wobbler mouse mutants develop a progressive paralysis due to spinal motoneuron degeneration. To understand the molecular aspect underlying the genetic defect we have studied the embryonic (from E13) and postnatal expression of the three neurofilament and choline acetyltransferase genes in each member from several wild-type (wt) and wobbler (wr) progenies. There are no variations among wt littermates at all ages studied. In contrast, analyses of neurofilament mRNA reveals a 3-4-fold increase of medium neurofilament (NFM) mRNA in wobbler mice (wr/wr). The pattern of increased NFM mRNA during development, prior to the appearance of the wobbler phenotype, among littermates (from heterozygous carriers) conforms to a mendelian inheritance of a single gene defect 1:2:1 (wr/wr:wr/+:+/+). Light and heavy neurofilament mRNA levels are also increased later in development exclusively in those individuals with high NFM mRNA values indicating that increase of the latter is associated with increase of the light and heavy subunit expression. Also NF proteins are increased. Expression of choline acetyltransferase gene is instead always comparable to normal control. Our study provides novel insights into the nature of the wobbler defect, strengthening the hypothesis that neurofilament accumulation plays a pivotal role in the etiopathogenesis of motoneuron degeneration. C1 NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NIH,VET RES BRANCH,BETHESDA,MD 20892. RP PernasAlonso, R (reprint author), CNR,INT INST GENET & BIOPHYS,VIA MARCONI 10,I-80125 NAPLES,ITALY. RI Morelli, Francesco/P-5657-2015; Perrone-Capano, Carla/O-7708-2015 OI Morelli, Francesco/0000-0002-5149-6291; Perrone-Capano, Carla/0000-0002-6327-9753 FU Fondazione Telethon NR 44 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN PY 1996 VL 38 IS 2 BP 267 EP 275 DI 10.1016/0169-328X(95)00344-R PG 9 WC Neurosciences SC Neurosciences & Neurology GA UQ907 UT WOS:A1996UQ90700010 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Use of transgenic animals in carcinogenesis studies SO MOLECULAR CARCINOGENESIS LA English DT Editorial Material RP Gonzalez, FJ (reprint author), NCI,MOLEC MED LAB,BLDG 37,RM 3E24,BETHESDA,MD 20892, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUN PY 1996 VL 16 IS 2 BP 63 EP 67 DI 10.1002/(SICI)1098-2744(199606)16:2<63::AID-MC1>3.0.CO;2-O PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA UQ805 UT WOS:A1996UQ80500001 PM 8645427 ER PT J AU Dey, BR Frick, K Lopaczynski, W Nissley, SP Furlanetto, RW AF Dey, BR Frick, K Lopaczynski, W Nissley, SP Furlanetto, RW TI Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; TYROSINE KINASES; PHOSPHATIDYLINOSITOL 3'-KINASE; PROTEIN; RAS; DOMAIN; PHOSPHORYLATION; ASSOCIATION; BINDS; SRC AB We have used the yeast two-hybrid system to study the interaction between the IGF-I receptor and two putative substrates, IRS-1 and She. In addition, we have identified Grb10 as a protein that binds to the insulin-like growth factor I (IGF-I) receptor. This two-hybrid system (the interaction trap) utilizes a hybrid protein containing the LexA DNA-binding domain fused to the intracellular portion of the IGF-I receptor (LexA-IGFIR beta) and hybrids containing an activation domain fused to either IRS-1 (Ad-IRS-1), Shc (Ad-Shc), or a cDNA library. A positive interaction of LexA-IGFIR beta with the activation domain hybrid results in activation of reporter genes, LacZ and LEU2, in the yeast. Western blotting of extracts from transformed yeast demonstrated that the LexA-IGFIR beta fusion protein was expressed and phosphorylated on tyrosine residues. Coexpression of LexA-IGFIR beta with Ad-IRS-1 resulted in strong activation of both reporter genes; activation did not occur with a kinase-negative receptor mutant. IRS-1 residues 160-516 were sufficient for this strong interaction. Coexpression of LexA-IGFIR beta with Ad-Shc also resulted in strong activation of both LacZ and LEU2 reporter genes. This interaction was also dependent upon a tyrosine kinase-active receptor and required tyrosine 950 in the juxtamembrane region of the receptor. An N-terminal fragment of Shc (amino acids 1-232) interacted almost as strongly as full-length Shc whereas the Shc SH2 domain only activated the more sensitive LEU2 reporter. Full-length Shc was phosphorylated on tyrosine when coexpressed with IGFIR beta but not when coexpressed with the kinase-negative receptor mutant. To identify additional proteins that interact with the IGFIRs, a human fetal brain cDNA library was screened using the interaction trap system. This analysis identified partial cDNAs for Grb10. Coexpression of LexA-IGFIR beta with Ad-Grb10 resulted in strong activation of both LacZ and LEU2 reporter genes; this interaction was dependent upon a tyrosine kinase-active receptor but did not require tyrosine 950. C1 UNIV ROCHESTER, DEPT PEDIAT, SCH MED & DENT, DIV PEDIAT ENDOCRINOL, ROCHESTER, NY 14642 USA. NCI, METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NR 56 TC 98 Z9 98 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1996 VL 10 IS 6 BP 631 EP 641 DI 10.1210/me.10.6.631 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP812 UT WOS:A1996UP81200004 PM 8776723 ER PT J AU Shi, HP Teng, C AF Shi, HP Teng, C TI Promoter-specific activation of mouse lactoferrin gene by epidermal growth factor involves two adjacent regulatory elements SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR; PROTEIN-KINASE; C-FOS; 12-O-TETRADECANOYL PHORBOL-13-ACETATE; TRANSCRIPTION FACTOR; RAT FIBROBLASTS; TRANSIN GENE; EXPRESSION; JUN; INHIBITION AB The mouse lactoferrin gene responded to forskolin, 12-O-tetradecanoyl phorbol-13-acetate, and epidermal growth factor (EGF) stimulation via two adjacent enhancer elements, the cAMP response element (CRE) and EGF response element (EGFRE), collectively referred to as the mitogen response unit. In this report, we examined the minimal promoter and enhancer elements of the mouse lactoferrin gene that are required for EGF-induced transcriptional activation. We found that the CRE and noncanonical TATA box (ATAAA) are the minimal promoter elements for basal activity of the chloramphenicol acetyltransferase (CAT) reporter construct whereas the EGFRE is needed for an additional activity induced by EGF in transiently transfected human endometrial carcinoma RL95-2 cells (RL95-2). The EGFRE, however, did not function in heterologous promoters [SV 40 and thymidine kinase (TK)]. Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95-2 cells. In transiently transfected cells, EGF and forskolin showed synergistic effects on the CAT reporter that contained both response elements. Mutation made at either element or insertion of extra nucleotides between the two elements severely affected EGF-stimulated activity. Nuclear protein prepared from RL95-2 cells formed three complexes (A, B, and C) with the oligonucleotides containing both EGFRE and CRE in electrophoretic mobility shift assay. A new complex (E) was detected with the nuclear protein of EGF-treated cells. By oligonucleotide competition experiments, we demonstrated that the complex E was generated by protein bound to CRE. EGF-induced binding activity could be abolished by calf intestinal alkaline phosphatase but not by the protein synthesis inhibitor, cycloheximide. Therefore, binding of a preexisting phosphoprotein to the CRE region could be one of the requirements for EGF-induced mouse lactoferrin gene promoter activity. C1 NIEHS, GENE REGULAT GRP, REPROD & DEV TOXICOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NR 47 TC 27 Z9 28 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1996 VL 10 IS 6 BP 732 EP 741 DI 10.1210/me.10.6.732 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP812 UT WOS:A1996UP81200014 PM 8776733 ER PT J AU Grossmann, M Szkudlinski, MW Dias, JA Xia, HY Wong, R Puett, D Weintraub, BD AF Grossmann, M Szkudlinski, MW Dias, JA Xia, HY Wong, R Puett, D Weintraub, BD TI Site-directed mutagenesis of amino acids 33-44 of the common alpha-subunit reveals different structural requirements for heterodimer expression among the glycoprotein hormones and suggests that cyclic adenosine 3',5'-monophosphate production and growth promotion are potentially dissociable functions of human thyrotropin SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID THYROID-STIMULATING HORMONE; HUMAN CHORIONIC-GONADOTROPIN; BETA-SUBUNIT; RECEPTOR-BINDING; LUTEINIZING-HORMONE; REGION; CELLS; CHORIOGONADOTROPIN; SUBSTITUTION; SEQUENCE AB Amino acid residues 33-44 of the common alpha-subunit of the glycoprotein hormones have been implicated in heterodimerization as well as high affinity receptor binding of human (h) CG. In the present study, we compared the role of specific amino acids within this region for glycoprotein hormone heterodimer formation, using a transient transfection system to coexpress different mutant alpha-subunit constructs with the beta-subunit of either hTSH, hCG, or hFSH. Our results identified a crucial role for alpha Pro(38) in the heterodimer expression of hTSH as well as hFSH, similar to what had been described for hCG. In contrast, alpha Ala(36), which had been critical for hCG, was not essential for hTSH heterodimer expression and less important for hFSH, whereas alpha Phe(33) and alpha Arg(35) appeared uniquely important for hFSH. Furthermore, we assessed the role of these residues for bioactivity and receptor binding of hTSH. Mutation of the surface-exposed residues alpha Arg(42)-Ser(43)-Lys(44), which form part of a unique alpha-helical structure, to Ala(42)-Ala(43)-Ala(44), decreased TSH receptor binding using porcine thyroid membranes as well as rat FRTL-5 cells. Residues alpha Phe(33) and alpha Arg(35), in contrast, were not important for high affinity binding of hTSH. In the signal transduction of hTSH, alpha Ala(36) was necessary for efficient growth induction in FRTL-5 cells but not for cAMP production in either FRTL-5 cells or Chinese hamster ovary cells expressing the human TSH receptor (JP09). Similarly, residues alpha Arg(42)-Ser(43)-Lys(44) were more important for hTSH-mediated induction of cell growth than cAMP production. Mutating alpha Arg(35) to Ala reduced cAMP induction but not receptor binding of hTSH. In summary, using site-directed mutagenesis, we identified a domain, residues 33-44 of the common a-subunit, important in heterodimer expression, receptor binding, and activation of hTSH. The comparison of the relative roles of specific amino acids within this region in hTSH with hCG and hFSH highlights previously unrecognized differences in the structural requirements for heterodimer expression among the members of the glycoprotein hormone family. Moreover, our findings revealed a novel role for residues alpha 33-44 in triggering different postreceptor events, suggesting that cAMP production and growth promotion may, at least in part, be dissociable functions of hTSH. C1 NEW YORK STATE DEPT HLTH, WADSWORTH CTR LABS & RES, ALBANY, NY 12201 USA. UNIV GEORGIA, DEPT BIOCHEM & MOLEC BIOL, ATHENS, GA 30602 USA. UNIV MARYLAND, SCH MED, DEPT MED, DIV ENDOCRINOL, BALTIMORE, MD 21201 USA. MED BIOTECHNOL CTR, INST HUMAN VIROL, BALTIMORE, MD 21201 USA. RP Grossmann, M (reprint author), NIDDKD, MOL & CELLULAR ENDOCRINOL BRANCH, NIH, BLDG 10, ROOM 8 D14, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-18407] NR 49 TC 31 Z9 32 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1996 VL 10 IS 6 BP 769 EP 779 DI 10.1210/me.10.6.769 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP812 UT WOS:A1996UP81200018 PM 8776737 ER PT J AU Hammerschmidt, S Muller, A Sillmann, H Muhlenhoff, M Borrow, R Fox, A vanPutten, J Zollinger, WD GerardySchahn, R Frosch, M AF Hammerschmidt, S Muller, A Sillmann, H Muhlenhoff, M Borrow, R Fox, A vanPutten, J Zollinger, WD GerardySchahn, R Frosch, M TI Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): Correlation with bacterial invasion and the outbreak of meningococcal disease SO MOLECULAR MICROBIOLOGY LA English DT Article ID POLYSIALIC ACID CAPSULE; ESCHERICHIA-COLI K1; FRAMESHIFT MUTATION; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; DNA-SEQUENCE; GONORRHOEAE; EXPRESSION; POLYSACCHARIDE; PROTEIN AB A mechanism of capsular polysaccharide phase variation in Neisseria meningitidis is described. Meningococcal cells of an encapsulated serogroup B strain were used in invasion assays. Only unencapsulated variants were found to enter epithelial cells, Analysis of one group of capsule-deficient variants indicated that the capsular polysaccharide was re-expressed at a frequency of 10(-3). Measurement of enzymatic activities involved in the biosynthesis of the alpha-2,8 polysialic acid capsule showed that polysialyltransferase (PST) activity was absent in these capsule-negative variants. Nucleotide sequence analysis of siaD revealed an insertion or a deletion of one cytidine residue within a run of (dC)(7). residues at position 89, resulting in a frameshift and premature termination of translation. We analysed unencapsulated isolates from carriers and encapsulated case isolates collected during an outbreak of meningococcal disease. Further paired blood-culture isolates and unencapsulated nasopharyngeal isolates from patients with meningococcal meningitis were examined. In all unencapsulated strains analysed we found an insertion or deletion within the oligo-(dC) stretch within siaD, resulting in a frameshift and loss of capsule formation. All encapsulated isolates, however, had seven dC residues at this position, indicating a correlation between capsule phase variation and bacterial invasion and the outbreak of meningococcal disease. C1 HANNOVER MED SCH,INST MED MIKROBIOL,D-30623 HANNOVER,GERMANY. WITHINGTON HOSP,PUBL HLTH LAB,MANCHESTER M20 2LR,LANCS,ENGLAND. NIAID,ROCKY MT LABS,NIH,HAMILTON,MT 59840. MAX PLANCK INST BIOL,D-72076 TUBINGEN,GERMANY. WALTER REED ARMY MED CTR,DEPT BACTERIAL DIS,WASHINGTON,DC 20307. RI Frosch, Matthias/H-2411-2013; OI van Putten, Jos/0000-0002-4126-8172 NR 52 TC 164 Z9 169 U1 1 U2 8 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 1996 VL 20 IS 6 BP 1211 EP 1220 DI 10.1111/j.1365-2958.1996.tb02641.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA UU880 UT WOS:A1996UU88000010 PM 8809773 ER PT J AU Lee, IJ Jeong, KS Roberts, BJ Kallarakal, AT FernandezSalguero, P Gonzalez, FJ Song, BJ AF Lee, IJ Jeong, KS Roberts, BJ Kallarakal, AT FernandezSalguero, P Gonzalez, FJ Song, BJ TI Transcriptional induction of the cytochrome P4501A1 gene by a thiazolium compound, YH439 SO MOLECULAR PHARMACOLOGY LA English DT Article ID DNA-BINDING FORM; AH-RECEPTOR; DIOXIN RECEPTOR; REGULATORY ELEMENTS; P-450C GENE; PROTEINS; CLONING; CYP1A1; LIGAND; IDENTIFICATION AB The molecular mechanism of induction of cytochromes P4501A1/2 (CYP1A1/2) by a synthetic compound YH439 was studied in rodents as well as in cultured hepatoma cells. CYP1A1-mediated ethoxyresorufin-O-deethylase activity and amounts of its immunoreactive protein were increased in a time- and concentration-dependent manner after a single dose of YH439 (150 mg/kg). Northern blot analyses revealed that YH439 rapidly increased (less than or equal to 2 hr) the levels of CYP1A1/2 mRNAs, resulting in an increase in CYP1A protein level by >6-fold at 8 hr after injection. After YH439 administration, the levels of CYP1A1 and CYP1A2 mRNAs peaked at 8 hr and 16 hr, respectively, before returning to control levels at 16 and 24 fir. The CYP1A protein level, on the other hand, reached a maximum at 24 hr after YH439 treatment and returned to near-control levers at 72 hr. Nuclear run-on analyses revealed that YH439 induces CYP1A1/2 gene transcription as early as 2 hr after YH439 treatment. Cytosolic electrophoretic mobility shift assays suggested that YH439 activates the CYP1A1/2 genes through the aryl hydrocarbon (Ah) receptor and the xenobiotic response elements. The dependency on the Ah receptor for the induction of CYP1A1/2 by YH439 was confirmed by the lack of CYP1A1/2 induction in the Ah receptor knock-out mice (Ahr(-/-)) as well as in murine hepatoma cells without a functional Ah receptor. Molecular structural analysis of YH439 and several other compounds indicated that the planarity and size of a molecule are important in its interaction with the Ah receptor and subsequent CYP1A1/2 induction. YH439 is a thiazolium compound with little aromaticity and with a two-dimensional structure different from that of the Ahs. Therefore, it represents a new class of Ah receptor ligand and CYP1A inducer. C1 NIAAA,CLIN STUDIES LAB,NIH,ROCKVILLE,MD 20852. NCI,MOLEC CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Lee, IJ (reprint author), NIAAA,NEUROGENET LAB,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 41 TC 35 Z9 35 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1996 VL 49 IS 6 BP 980 EP 988 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UQ061 UT WOS:A1996UQ06100005 PM 8649358 ER PT J AU Glasgow, WC Hill, EM Mcgown, SR Tomer, KB Eling, TE AF Glasgow, WC Hill, EM Mcgown, SR Tomer, KB Eling, TE TI Regulation of 13(S)-hydroxyoctadecadienoic acid biosynthesis in syrian hamster embryo fibroblasts by the epidermal growth factor receptor tyrosine kinase SO MOLECULAR PHARMACOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; EGF RECEPTOR; PHOSPHOLIPASE-C; MESSENGER-RNA; PROSTAGLANDIN SYNTHASE; MITOGENIC RESPONSE; ENDOTHELIAL-CELLS; ARACHIDONIC-ACID; PROTEIN-KINASE; LINOLEIC-ACID AB Metabolism of arachidonic and linoleic acid can be regulated by polypeptide growth factors in a variety of cell types. In Syrian hamster embryo (SHE) fibroblasts, epidermal growth factor (EGF) stimulates the conversion of exogenous linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). inhibition of 13-HODE biosynthesis blocks the EGF-mitogenic response in SHE cells, and 13-HODE and its hydroperoxy precursor are potent and highly specific enhancers of EGF-dependent DNA synthesis. We demonstrated that EGF stimulates a biphasic production and release of endogenous 13-HODE. Through development of a stable isotope-dilution GC/MS assay for 13-HODE, we observed 13-HODE production as early as 5 min after EGF stimulation, and this initial phase peaked at 1 hr. A second rise in 13-HODE formation was seen at 2-4 hr, and this phase plateaued at 4-6 hr at a level of 30-40 ng/10(6) cells. EGF stimulation of 13-HODE biosynthesis is not mediated by transcriptional or translational regulation of the inducible form of prostaglandin H synthase. Based on enzyme inhibitor studies and structural characterization of products, the linoleate metabolite is apparently formed by an n-6 lipoxygenase that remains to be characterized. EGF stimulation of 13-HODE formation is linked with activation of the EGF receptor tyrosine kinase. Inhibition of EGF receptor tyrosine kinase activity with methyl-2,5-dihydroxycinnamate blocked EGF-dependent linoleic acid metabolism and EGF-regulated DNA synthesis. Potentiation of the EGF receptor tyrosine phosphorylation cascade through treatment of SHE cells with the tyrosine phosphatase inhibitor vanadate resulted in a 3-fold increase in EGF-stimulated 13-HODE production and a corresponding enhancement of the EGF mitogenic response. The coupling of EGF-regulated linoleic acid metabolism with the EGF receptor tyrosine kinase activity suggests the importance of specific linoleate compounds in mediating mitogenic signal transduction. RP Glasgow, WC (reprint author), NIEHS, NIH, LAB MOLEC BIOPHYS, POB 12233, MD E4-09, RES TRIANGLE PK, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 47 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1996 VL 49 IS 6 BP 1042 EP 1048 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UQ061 UT WOS:A1996UQ06100012 PM 8649342 ER PT J AU Chiba, P Ecker, G Schmid, D Drach, J Tell, B Goldenberg, S Gekeler, V AF Chiba, P Ecker, G Schmid, D Drach, J Tell, B Goldenberg, S Gekeler, V TI Structural requirements for activity of propafenone-type modulators in P-glycoprotein-mediated multidrug resistance SO MOLECULAR PHARMACOLOGY LA English DT Article ID DRUG-RESISTANCE; CELLS; EXPRESSION; MDR1/P-GLYCOPROTEIN; REVERSAL AB The sodium channel blocker propafenone and a series of analogs have been identified as effective modulators of P-glycoprotein-mediated multidrug resistance in human tumor cells. A series of closely related structural homologues showed a highly significant correlation between lipophilicity and pharmacological effect. Reduction of the carbonyl group as well as conversion to a methylether led to a remarkable decrease in activity, whereby lipophilicity lost its predictive character as the main determinant for modulator potency. Similarly, the relative positioning of the acyl- and propanolamine side chains also influences activity, so the distance between carbonyl group and nitrogen atom seems important. C1 UNIV VIENNA,DEPT PHARMACEUT CHEM,A-1090 VIENNA,AUSTRIA. UNIV VIENNA,DEPT INTERNAL MED,A-1090 VIENNA,AUSTRIA. NCI,CELL BIOL LAB,NIH,BETHESDA,MD. BYK GULDEN LOMBERG GMBH,CONSTANCE,GERMANY. RP Chiba, P (reprint author), UNIV VIENNA,INST MED CHEM,DEPT MED CHEM,WAHRINGERSTR 10,A-1090 VIENNA,AUSTRIA. RI Schmid, Diethart/C-5049-2009; OI Schmid, Diethart/0000-0002-2225-9836; Ecker, Gerhard/0000-0003-4209-6883 NR 29 TC 105 Z9 106 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1996 VL 49 IS 6 BP 1122 EP 1130 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UQ061 UT WOS:A1996UQ06100022 PM 8649352 ER PT J AU McKnight, RA Spencer, M Wall, RJ Hennighausen, L AF McKnight, RA Spencer, M Wall, RJ Hennighausen, L TI Severe position effects imposed on a 1 kb mouse whey acidic protein gene promoter are overcome by heterologous matrix attachment regions SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE matrix attachment regions; whey acidic protein; WAP; position effects; transcription; lysozyme gene ID TRANSGENIC MICE; HYBRID GENE; BOUNDARIES; LACTATION; ASSAY AB Matrix attachment regions (MARs) have been shown to participate in the insulation of transcription elements from surrounding chromatin in tissue culture cells and transgenic mice. A whey acidic protein (WAP) transgene containing 1 kb promoter sequence was active in mammary tissue from 1 out of 17 lines of mice, demonstrating that the transcription elements were highly susceptible to position effects. To test whether MARs could insulate this WAP gene promoter and thereby restore transcription, we ligated MARs from the chicken lysozyme gene to the WAP transgene. Seven of the nine lines generated exhibited WAP transgene activity, expression was confined to mammary tissue, and correct regulation was observed in three of the four lines analyzed. This study provides strong additional evidence that the MAR fragments from the chicken lysozyme gene have the capacity to insulate transgenes from severe position effects. (C) 1996 Wiley-Liss, Inc. C1 NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. USDA ARS,BELTSVILLE,MD. NR 23 TC 43 Z9 44 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JUN PY 1996 VL 44 IS 2 BP 179 EP 184 DI 10.1002/(SICI)1098-2795(199606)44:2<179::AID-MRD6>3.0.CO;2-K PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA UP077 UT WOS:A1996UP07700006 PM 9115715 ER PT J AU Ravits, J Hallett, M Nilsson, J Polinsky, R Dambrosia, J AF Ravits, J Hallett, M Nilsson, J Polinsky, R Dambrosia, J TI Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes SO MUSCLE & NERVE LA English DT Article DE autonomic function; multisystem atrophy; pure autonomic failure; sympathetic skin response; Valsalva ratio; sinus arrhythmia ID SYMPATHETIC SKIN-RESPONSE; MULTIPLE SYSTEM ATROPHY; R INTERVAL VARIATION; NERVOUS-SYSTEM; DIABETIC NEUROPATHY; PERIPHERAL NEUROPATHY; SUDOMOTOR FUNCTION; VALSALVA MANEUVER; HEART; DYSFUNCTION AB Three electrophysiological tests of autonomic function were performed in patients with autonomic nervous system dysfunction to define test sensitivities and specificities, The skin sympathetic response, Valsalva ratio, and heart rate variation with deep breathing were studied in 10 patients with multiple system atrophy (MSA) and in 7 patients with pure (also called progressive or primary) autonomic failure (PAF); control subjects were 17 normal individuals of similar age. Thirteen patients had abnormal skin sympathetic responses, and 16 had abnormal Valsalva ratios, Fourteen patients had an abnormal variation of the heart rate with deep breathing. Taking the three tests together, binary logistic regression for distinguishing between patients and normal subjects correctly classified 91% of the 33 individuals for whom there were complete data with sensitivity of 88% and specificity of 94%. However, only 69% of the patients could be correctly classified by a logistic regression for discriminating between MSA and PAF, Electromyography (EMG) studies showed that 7 of 8 patients with MSA but only 2 of 7 patients with PAF (both multiparous women) had denervation of the rectal sphincter muscle, The EMG study is, therefore, valuable in men, but has a high false positive rate in women, probably because of pudendal nerve injury from parturition. (C) 1996 John Wiley & Sons, Inc. C1 NINCDS,NIH,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,NIH,CLIN NEUROPHARMACOL SECT,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NINCDS,NIH,MATH STAT SECT,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. NR 55 TC 23 Z9 27 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUN PY 1996 VL 19 IS 6 BP 758 EP 763 DI 10.1002/(SICI)1097-4598(199606)19:6<758::AID-MUS11>3.0.CO;2-H PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UH519 UT WOS:A1996UH51900011 PM 8609927 ER PT J AU Smith, ML Fornace, AJ AF Smith, ML Fornace, AJ TI Mammalian DNA damage-inducible genes associated with growth arrest and apoptosis SO MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY LA English DT Review DE p53; GADD45; DNA repair; apoptosis ID CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; C-MYC; PROTEIN; P53; INDUCTION; AGENTS; RADIATION; NEUROBLASTOMA; AMPLIFICATION AB Mammalian cells are exposed to a wide variety of genotoxic stresses from both endogenous and exogenous sources. Cells typically exhibit cell cycle delays, or checkpoints, in response to acute genotoxic stress. Other types of cellular responses to DNA damage include apoptosis and probably increases in DNA repair levels. These response pathways are altered in cancer cells, by genetic alterations such as overexpression or mutation of oncogenes, or loss of tumor suppressor gene functions. As cancer chemotherapy relies primarily on the selective killing of cancer cells by DNA-damaging agents, genetic alterations affecting cellular stress response pathways may affect the outcome of cancer treatment. RP Smith, ML (reprint author), NCI,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,NIH,BLDG 37,ROOM 5C09,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 143 TC 112 Z9 117 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1110 J9 MUTAT RES-REV GENET JI Mutat. Res.-Rev. Genet. Toxicol. PD JUN PY 1996 VL 340 IS 2-3 BP 109 EP 124 DI 10.1016/S0165-1110(96)90043-3 PG 16 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA UU701 UT WOS:A1996UU70100005 PM 8692176 ER PT J AU Sikorski, RS Peters, R AF Sikorski, RS Peters, R TI Antibodies on the Web SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Sikorski, RS (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 1996 VL 14 IS 6 BP 775 EP 775 DI 10.1038/nbt0696-775a PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UM766 UT WOS:A1996UM76600038 ER PT J AU Goldman, D AF Goldman, D TI Why mice drink SO NATURE GENETICS LA English DT Editorial Material RP Goldman, D (reprint author), NIAAA,NEUROGENET LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 9 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1996 VL 13 IS 2 BP 137 EP 138 DI 10.1038/ng0696-137 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UN395 UT WOS:A1996UN39500004 PM 8640212 ER PT J AU Lei, KJ Chen, HW Pan, CJ Ward, JM Mosinger, B Lee, EJ Westphal, H Mansfield, BC Chou, JY AF Lei, KJ Chen, HW Pan, CJ Ward, JM Mosinger, B Lee, EJ Westphal, H Mansfield, BC Chou, JY TI Glucose-6-phosphatase dependent substrate transport in the glycogen storage disease type-1a mouse SO NATURE GENETICS LA English DT Article ID MICROSOMAL GLUCOSE-6-PHOSPHATASE; LIVER-TRANSPLANTATION; SYSTEM; DISRUPTION; MUTATIONS; DEFECT; GENE; MICE; IB AB Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. A G6Pase knockout mouse which mimics the pathophysiology of human GSD-1a patients was created to understand the pathogenesis of this disorder, to delineate the mechanisms of G6Pase catalysis, and to develop future therapeutic approaches. By examining G6Pase in the liver and kidney, the primary gluconeogenic tissues, we demonstrate that glucose-6-P transport and hydrolysis are performed by separate proteins which are tightly coupled. We propose a modified translocase catalytic unit model for G6Pase catalysis. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21702. NR 30 TC 151 Z9 152 U1 3 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1996 VL 13 IS 2 BP 203 EP 209 DI 10.1038/ng0696-203 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA UN395 UT WOS:A1996UN39500020 PM 8640227 ER PT J AU Lancaster, JM Wooster, R Mangion, J Phelan, CM Cochran, C Gumbs, C Seal, S Barfoot, R Collins, N Bignell, G Patel, S Hamoudi, R Larsson, C Wiseman, RW Berchuck, A Iglehart, JD Marks, JR Ashworth, A Stratton, MR Futreal, PA AF Lancaster, JM Wooster, R Mangion, J Phelan, CM Cochran, C Gumbs, C Seal, S Barfoot, R Collins, N Bignell, G Patel, S Hamoudi, R Larsson, C Wiseman, RW Berchuck, A Iglehart, JD Marks, JR Ashworth, A Stratton, MR Futreal, PA TI BRCA2 mutations in primary breast and ovarian cancers SO NATURE GENETICS LA English DT Letter C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. NIEHS,MOLEC CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC 27709. INST CANC RES,HADDOW LABS,SECT MOL CARCINOGENESIS,SURREY,ENGLAND. INST CANC RES,CHESTER BEATTY LABS,LONDON SW3 6JB,ENGLAND. KAROLINSKA HOSP,DEPT MOLEC MED,ENDOCRINE TUMOR UNIT,S-10401 STOCKHOLM,SWEDEN. MCGILL UNIV,MONTREAL GEN HOSP,DEPT HUMAN GENET & MED,MONTREAL,PQ H3G 1A4,CANADA. INST CANC RES,HADDOW LABS,CRC,CTR BIOL MOLEC,SURREY,ENGLAND. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC. FU NCI NIH HHS [1R21-CA66228, P50-CA68438, R21-CA68348] NR 13 TC 257 Z9 259 U1 0 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1996 VL 13 IS 2 BP 238 EP 240 DI 10.1038/ng0696-238 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA UN395 UT WOS:A1996UN39500028 PM 8640235 ER PT J AU Chuang, DM Ishitani, R AF Chuang, DM Ishitani, R TI A role for GAPDH in apoptosis and neurodegeneration SO NATURE MEDICINE LA English DT Letter C1 JOSAI UNIV,GRP CELLULAR NEUROBIOL,SAKADO,SAITAMA 35002,JAPAN. RP Chuang, DM (reprint author), NIMH,MOLEC NEUROBIOL SECT,BIOL PSYCHIAT BRANCH,NIH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 0 TC 27 Z9 29 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1996 VL 2 IS 6 BP 609 EP 610 DI 10.1038/nm0696-609 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UN691 UT WOS:A1996UN69100006 PM 8640541 ER PT J AU Dimitrov, DS AF Dimitrov, DS TI Fusin - A place for HIV-1 and T4 cells to meet SO NATURE MEDICINE LA English DT Editorial Material ID AIDS RP Dimitrov, DS (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. NR 8 TC 29 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1996 VL 2 IS 6 BP 640 EP 641 DI 10.1038/nm0696-640 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UN691 UT WOS:A1996UN69100029 PM 8640552 ER PT J AU Sarver, N Cairns, S AF Sarver, N Cairns, S TI Ribozyme trans-splicing and RNA tagging: Following the messenger SO NATURE MEDICINE LA English DT Editorial Material ID TETRAHYMENA RIBOZYME; BINDING-SITE; SPECIFICITY; SEQUENCE RP Sarver, N (reprint author), NIAID,DIV AIDS,TARGETED INTERVENT BRANCH,BETHESDA,MD 20892, USA. NR 12 TC 11 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1996 VL 2 IS 6 BP 641 EP 642 DI 10.1038/nm0696-641 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UN691 UT WOS:A1996UN69100030 PM 8640553 ER PT J AU Ptitsyn, O AF Ptitsyn, O TI How molten is the molten globule? SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID FOLDED APOMYOGLOBIN INTERMEDIATE; STRUCTURAL CHARACTERIZATION; CYTOCHROME-C; ALPHA-LACTALBUMIN; EQUINE LYSOZYME; PROTEIN; STATE; EXCHANGE; NMR; NUCLEATION AB New evidence for partial specific tertiary interactions within an apomyoglobin folding intermediate force reexamination of the role of specific contacts in stabilizing the molten globule. C1 NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RP Ptitsyn, O (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NR 42 TC 62 Z9 62 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUN PY 1996 VL 3 IS 6 BP 488 EP 490 DI 10.1038/nsb0696-488 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UN670 UT WOS:A1996UN67000003 PM 8646529 ER PT J AU Liani, M Salvati, F Tresca, E Golato, M Capasso, A AF Liani, M Salvati, F Tresca, E Golato, M Capasso, A TI Increased expression of GPIb and GPIIb/IIIa platelet surface glycoproteins in renal transplant patients SO NEPHRON LA English DT Letter C1 SAN MASSIMO HOSP,DEPT NEPHROL,PENNE,ITALY. SAN MASSIMO HOSP,DEPT CLIN PATHOL,PENNE,ITALY. SS IMMACOLATA HOSP,DEPT INTERNAL MED & NEPHROL,GUARDIAGRELE,CHIETI,ITALY. RENZETTI HOSP,DEPT CLIN PATHOL,LANCIANO,ITALY. NATL CANC INST,GENOA,ITALY. NR 2 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD JUN PY 1996 VL 73 IS 2 BP 360 EP 360 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA UN785 UT WOS:A1996UN78500060 PM 8773391 ER PT J AU Liani, M Salvati, F Tullio, D Golato, M Fini, N Tresca, E Capasso, A AF Liani, M Salvati, F Tullio, D Golato, M Fini, N Tresca, E Capasso, A TI Anti-atherosclerotic properties of antihypertensive drugs: Effect of antihypertensive therapy on platelet receptors for von Willebrand factor and for fibrinogen SO NEPHRON LA English DT Letter ID VONWILLEBRAND-FACTOR; ESSENTIAL-HYPERTENSION; MICROALBUMINURIA; ISRADIPINE C1 SAN MASSIMO HOSP,DEPT NEPHROL,PENNE,ITALY. SAN MASSIMO HOSP,DEPT CLIN PATHOL,PENNE,ITALY. SS IMMACOLATA HOSP,DEPT INTERNAL MED & NEPHROL,GUARDIAGRELE,CHIETI,ITALY. RENZETTI HOSP,DEPT CARDIOL,LANCIANO,ITALY. RENZETTI HOSP,DEPT CLIN PATHOL,LANCIANO,ITALY. NATL CANC INST,GENOA,ITALY. NR 17 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD JUN PY 1996 VL 73 IS 2 BP 361 EP 362 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA UN785 UT WOS:A1996UN78500061 PM 8773392 ER PT J AU McIntosh, AR Bookstein, FL Haxby, JV Grady, CL AF McIntosh, AR Bookstein, FL Haxby, JV Grady, CL TI Spatial pattern analysis of functional brain images using partial least squares SO NEUROIMAGE LA English DT Article ID PET IMAGES; CONNECTIVITY AB This paper introduces a new tool for functional neuroimage analysis: partial least squares (PLS). It is unique as a multivariate method in its choice of emphasis for analysis, that being the covariance between brain images and exogenous blocks representing either the experiment design or some behavioral measure, What emerges are spatial patterns of brain activity that represent the optimal association between the images and either of the blocks, This process differs substantially from other multivariate methods in that rather than attempting to predict the individual values of the image pixels, PLS attempts to explain the relation between image pixels and task or behavior, Data from a face encoding and recognition PET rCBF study are used to illustrate two types of PLS analysis: an activation analysis of task with images and a brain-behavior analysis, The commonalities across the two analyses are suggestive of a general face memory network differentially engaged during encoding and recognition, PLS thus serves as an important extension by extracting new information from imaging data that is not accessible through other currently used univariate and multivariate image analysis tools. (C) 1996 Academic Press, Inc. C1 UNIV MICHIGAN,INST GERONTOL,ANN ARBOR,MI 48109. NIMH,PSYCHOL & PSYCHOPATHOL LAB,FUNCT BRAIN IMAGING SECT,NIH,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP McIntosh, AR (reprint author), UNIV TORONTO,BAYCREST CTR,ROTMAN RES INST,3560 BATHURST ST,TORONTO,ON M6A 2E1,CANADA. RI Rohlf, F/A-8710-2008; McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662 FU NIDA NIH HHS [DA-09009] NR 32 TC 616 Z9 618 U1 1 U2 22 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 1996 VL 3 IS 3 BP 143 EP 157 DI 10.1006/nimg.1996.0016 PN 1 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UQ769 UT WOS:A1996UQ76900001 PM 9345485 ER PT J AU Bonson, KR Buckholtz, JW Murphy, DL AF Bonson, KR Buckholtz, JW Murphy, DL TI Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE LSD; hallucinogen; antidepressant; serotonin reuptake inhibitor; human studies ID LYSERGIC-ACID DIETHYLAMIDE; DISCRIMINATIVE STIMULUS PROPERTIES; ANTI-DEPRESSANT TREATMENT; HALLUCINOGENIC DRUG-INTERACTIONS; 5-HT RECEPTOR SUBPOPULATIONS; RAT-BRAIN; DOPAMINE-RECEPTORS; FRONTAL-CORTEX; BETA-ADRENOCEPTORS; BINDING-SITES AB This study investigates the possible interactions of antidepressant agents and hallucinogens in humans through structured interviews using a standardized questionnaire. Volunteer subjects recruited through announcements placed on the Internet or other sources were asked to describe the somatic, hallucinatory, and psychological effects of self-administered LSD prior to and during chronic administration of an antidepressant. Twenty-eight out of 32 subjects (88%) who had taken an antidepressant with inhibitory effects on serotonin (5-HT) reuptake (fluoxetine, paroxetine, sertraline, trazodone) for over 3 weeks had a subjective decrease or virtual elimination of their responses to LSD. An additional subject who had taken fluoxetine for only 1 week had an increased response to LSD. These data are in contrast to our previous study that reported increased responses to LSD during chronic administration of tricyclic antidepressants or lithium. Possible mechanisms of action for the effects from serotonergic antidepressants involve 5-HT2 and 5-HT1A receptors, changes in extracellular brain serotonin concentrations, and changes in brain catecholamine systems. RP Bonson, KR (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,BETHESDA,MD 20892, USA. RI Buckholtz, Joshua /E-7299-2010 OI Buckholtz, Joshua /0000-0002-9418-8686 NR 98 TC 31 Z9 32 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 1996 VL 14 IS 6 BP 425 EP 436 DI 10.1016/0893-133X(95)00145-4 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UL728 UT WOS:A1996UL72800002 PM 8726753 ER PT J AU Kreiss, DS Anderson, LA Walters, JR AF Kreiss, DS Anderson, LA Walters, JR TI Apomorphine and dopamine D-1 receptor agonists increase the firing rates of subthalamic nucleus neurons SO NEUROSCIENCE LA English DT Article DE SKF 38393; SKF 82958; basal ganglia; electrophysiology; autoradiography ID QUANTITATIVE AUTORADIOGRAPHIC LOCALIZATION; CEREBRAL GLUCOSE-UTILIZATION; NIGRA PARS RETICULATA; BASAL GANGLIA; SUBSTANTIA-NIGRA; HORSERADISH-PEROXIDASE; EFFERENT PROJECTIONS; MICROSCOPIC ANALYSIS; PARKINSONS-DISEASE; MOVEMENT-DISORDERS AB The present study investigated the regulation of spontaneous neuronal activity in the subthalamic nucleus by dopamine receptors using in vivo extracellular single unit recording techniques. Subthalamic nucleus neuronal firing rates were doubled by systemic administration of the nonselective dopamine receptor agonist apomorphine. The response to apomorphine was attenuated in animals anesthetized with chloral hydrate or ketamine. The dopamine D-2/D-3 receptor agonist quinpirole did not alter subthalamic nucleus neuronal firing rates. Firing rates were increased by the D-1 receptor agonists SKF 38393 and SKF 82958 two- to three-fold; these increases were reversed by the D-1 receptor antagonist, SCH 23390. Autoradiographic studies using [I-125]SCH 23982 indicated that D-1 family receptors were located along the ventral edge of the subthalamic nucleus and the dorsal aspect of the cerebral peduncle. Local administration of SKF 82958 into the subthalamic nucleus doubled neuronal firing rates; these increases were reversed by systemic administration of SCH 23390. Infusion of SCH 23390 into the subthalamic nucleus prevented systemic SKF 38393 from increasing the firing rates of subthalamic nucleus neurons. These results indicate that apomorphine and D-1 receptor agonists exert an excitatory influence on subthalamic nucleus neuronal activity. In addition, the excitation induced by D-1 receptor agonists appears to be mediated, at least in part, by D-1 receptors located in the vicinity of the subthalamic nucleus. The data suggest that basal ganglia output under conditions of increased dopamine receptor stimulation is influenced by the activation of excitatory subthalamic efferent pathways, as opposed to suppression of these pathways as predicted by current models of basal ganglia function. C1 NINCDS,EXPTL THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 95 TC 102 Z9 105 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN PY 1996 VL 72 IS 3 BP 863 EP 876 DI 10.1016/0306-4522(95)00583-8 PG 14 WC Neurosciences SC Neurosciences & Neurology GA UH118 UT WOS:A1996UH11800026 PM 9157332 ER PT J AU Salazar, AM Levy, HB Ondra, S Kende, M Scherokman, B Brown, D Mena, H Martin, N Schwab, K Donovan, D Dougherty, D Pulliam, M Ippolito, M Graves, M Brown, H Ommaya, A AF Salazar, AM Levy, HB Ondra, S Kende, M Scherokman, B Brown, D Mena, H Martin, N Schwab, K Donovan, D Dougherty, D Pulliam, M Ippolito, M Graves, M Brown, H Ommaya, A TI Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: An open pilot study SO NEUROSURGERY LA English DT Article DE dsRNA; interferon; malignant glioma; oligoadenylate; poly-ICLC; tumor suppressors ID DOUBLE-STRANDED-RNA; POLY-L-LYSINE; HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-KINASE; 2',5'-OLIGOADENYLATE SYNTHETASE; RADIATION-THERAPY; INTERFERON-ALPHA; BREAST-CANCER; POLY(I,C)-LC; COMPLEX AB POLYINOSINIC-POLYCYTIDYLIC ACID STABILIZED with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for less than or equal to 56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients (66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2',5'-oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies. C1 UNIFORMED SERV UNIV HLTH SCI, WASHINGTON, DC USA. NIAID, WASHINGTON, DC USA. USA, MED RES INST INFECT DIS, WASHINGTON, DC 20310 USA. ARMED FORCES INST PATHOL, WASHINGTON, DC 20306 USA. NATL NAVAL MED CTR, WASHINGTON, DC USA. RP Salazar, AM (reprint author), WALTER REED ARMY MED CTR, DEF & VET HEAD INJURY PROGRAM, BLDG 7, ROOM 224, WASHINGTON, DC 20307 USA. NR 41 TC 81 Z9 82 U1 2 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1996 VL 38 IS 6 BP 1096 EP 1103 DI 10.1097/00006123-199606000-00006 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UM763 UT WOS:A1996UM76300012 PM 8727138 ER PT J AU Kim, HC Pennypacker, KR Bing, GY Bronstein, D McMillian, MK Hong, JS AF Kim, HC Pennypacker, KR Bing, GY Bronstein, D McMillian, MK Hong, JS TI The effects of dextromethorphan on kainic acid-induced seizures in the rat SO NEUROTOXICOLOGY LA English DT Article DE anticonvulsants; dextromethorphan; AP-1 transcription factors; fos-related antigen; c-Jun ID NEURONAL DAMAGE; TRANSCRIPTION FACTORS; NEUROTOXICITY; DEXTRORPHAN; HIPPOCAMPUS; EXPRESSION; RECEPTORS; BRAIN; ANTAGONISTS; PATTERNS AB Several studies have shown that dextromethorphan (DM) has both anticonvulsant and proconvulsant effects depending on the animal model. In this study, we examined the effects of DM on three parameters associated with kainic acid (KA)induced seizures: cell loss in the hippocampus, increased AP-I DNA binding activity and increased c-Jun and fos-related antigen (FRA) expression. KA administration (8 mg/kg, ip) produced robust behavioral convulsions lasting 4-6 hr. Pretreatment with DM (12.5-75 mg/kg, po) 15 min before KA injections reduced the seizures as well as mortality in a dose-dependent manner. Histological studies revealed a severe loss of cells in the CA1 and CA3 fields of the hippocampus in KA-treated rats. DM pretreatment also reduced this cell loss in a dose-dependent fashion. Biochemical studies showed that DM pretreatment also attenuated the KA-induced in crease of AP-1 binding activity and c-Jun/FRA expression in the hippocampus. These results indicate that DM is an effective antagonist of KA. (C) 1996 Intox Press Inc. C1 NIEHS,SECT NEUROPHARMACOL,LAB ENVIRONM NEUROSCI,NIH,RES TRIANGLE PK,NC 27709. RI bing, guoying/F-7084-2012; Pennypacker, Keith/I-5092-2012; OI Bing, Guoying/0000-0003-0609-8152 NR 42 TC 37 Z9 38 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SUM PY 1996 VL 17 IS 2 BP 375 EP 385 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA VB792 UT WOS:A1996VB79200008 PM 8856734 ER PT J AU Schmitt, TJ Zawia, N Harry, GJ AF Schmitt, TJ Zawia, N Harry, GJ TI GAP-43 mRNA expression in the developing rat brain: Alterations following lead-acetate exposure SO NEUROTOXICOLOGY LA English DT Article DE lead acetate; growth associated protein-43 (GAP-43); development ID GROWTH-ASSOCIATED PROTEIN; DENDRITIC DEVELOPMENT; NERVOUS-SYSTEM; AXON GROWTH; NEURONS; CELLS; CONES; IMMUNOCYTOCHEMISTRY; HIPPOCAMPUS; PLASTICITY AB The developmental neurotoxicity of environmental lead exposure manifests as alterations in neural functioning and perturbed axonal and dendritic development. To examine the hypothesis that such lead-induced alterations in the neural network are associated with an altered mRNA expression of a specific neural cell growth associated protein, mRNA levels of GAP-43 (growth associated protein 43) were measured in the cortex and hippocampus of developing Long-Evans hooded rats following various lead exposure paradigms. Postnatal developmental profiles (PND 6, 9, 12, 15, 20, and 25) of mRNA expression were generated following either prenatal (gestational day 13 to birth), postnatal(postnatal day I to postnatal day 20), or perinatal (gestational day 13 to postnatal day 20) exposure to lead acetate (0.2% in the drinking water of the dam). In control rats, GAP-43 mRNA levels displayed a distinct developmentally regulated profile of expression in both the cortex and hippocampus, characterized by an elevated level of expression within the first week of life. This peak level of expression was significantly depressed following either postnatal or perinatal exposure to lead acetate, while prenatal lead exposure produced an initial elevation of GAP-43 mRNA on postnatal day 6 followed by a sharp decline. These data suggest that lead exposure results in altered mRNA expression of a specific neural cell growth associated protein critical to the normal process of development, This perturbation in expression may play a role in the previously reported effects of lead acetate on axonal elongation during development of the nervous system and the subsequent alteration in nervous system functioning. (C) 1996 Inter Press, Inc. C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC. FU NIEHS NIH HHS [T32 ES07126, N01-ES-25331] NR 41 TC 17 Z9 19 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SUM PY 1996 VL 17 IS 2 BP 407 EP 414 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA VB792 UT WOS:A1996VB79200011 PM 8856737 ER PT J AU Vigano, MA Staudt, LM AF Vigano, MA Staudt, LM TI Transcriptional activation by Oct-3: Evidence for a specific role of the POU-specific domain in mediating functional interaction with Oct-1 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING SPECIFICITY; GLUCOCORTICOID RECEPTOR; TRANSACTIVATOR VP16; MOUSE EMBRYOGENESIS; REGULATORY PROTEIN; SEQUENCE ELEMENTS; COMMON FACTOR; HOMEO DOMAIN; HISTONE H2B; I-POU AB Oct-3, a member of the POU family of transcription factors, is expressed in pluripotent cells of early mammalian embryos and in undifferentiated embryonal carcinoma cell lines. Using a variety of Oct-3 mutants, we have identified two different domains of Oct-3 which activate transcription in transfected mammalian cells. One of these domains, located in the C-terminal part of the protein, plays a major role in transcriptional activation when Oct-3 is bound to its cognate site, the octamer motif. An Oct-3 mutant containing a single amino acid substitution in the POU homeodomain is unable to bind the octamer target in vitro, yet is still able to activate transcription in an octamer-dependent manner. We provide evidence that transactivation by this mutant involves protein-protein interactions with the ubiquitous octamer binding factor Oct-1. This interaction requires the POU-specific domain of Oct-3 and allows recruitment of Oct-3 to the target promoter even in the absence of Oct-3 DNA binding. C1 NCI,NIH,METAB BRANCH,BETHESDA,MD 20892. RP Vigano, MA (reprint author), IST SCI SAN RAFFAELE,DIBIT,MILAN,ITALY. FU Telethon [TGT06S01, TGT95000]; Fondazione Telethon NR 50 TC 30 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 1 PY 1996 VL 24 IS 11 BP 2112 EP 2118 DI 10.1093/nar/24.11.2112 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UR379 UT WOS:A1996UR37900019 PM 8668543 ER PT J AU Tornwall, ME Salminen, I Aro, A Pietinen, P Haukka, J Albanes, D Virtamo, J AF Tornwall, ME Salminen, I Aro, A Pietinen, P Haukka, J Albanes, D Virtamo, J TI Effect of serum and dietary fatty acids on the short-term risk of acute myocardial infarction in male smokers SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Article DE myocardial infarction; cholesterol esters; phospholipids; diet; thrombogenesis ID CORONARY HEART-DISEASE; PLATELET-FUNCTION; ADIPOSE-TISSUE; FISH CONSUMPTION; AGGREGATION; MEN; CHOLESTEROL; MORTALITY; PLASMA; LIPIDS AB The short-term associations between fatty acids of serum cholesterol esters, phospholipids and diet and the risk of acute myocardial infarction (AMI) were investigated in a nested case-control study. The subjects were male smokers aged 50-69 years, from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study in Finland. Dietary assessment and blood sampling took place at baseline. Definite AMI was verified in 189 men within one year of baseline. The 481 control men were drawn randomly from those without AMI. No associations were observed between serum or dietary linoleic acid or n-3 fish fatty acids, and the risk of AMI. The proportions of gamma-linolenic and dihomo-gamma-linolenic acids of serum cholesterol esters were inversely associated with the risk of AMI (odds patios in the highest tertile 0.57 and 0.59, respectively), but serum phospholipid fatty acids showed no corresponding associations. The intake of arachidonic acid was positively associated with the risk of AMI (odds ratio in the highest tertile 1.69), but no such association was found for serum values. lit conclusion, we found only minor associations between serum and dietary fatty acids and the one-year risk of AMI. However, the homogeneity of the study population may have obscured associations. C1 NATL PUBL HLTH INST,DEPT NUTR,SF-00300 HELSINKI,FINLAND. NATL CANC INST,BETHESDA,MD. RP Tornwall, ME (reprint author), NATL PUBL HLTH INST,CANC PREVENT UNIT,MANNERHEIMINTIE 166,SF-00300 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 NR 34 TC 2 Z9 2 U1 0 U2 3 PU MEDIKAL PRESS S R L PI MILAN PA VIA LUIGI ZOJA, 30, 20153 MILAN, ITALY SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD JUN PY 1996 VL 6 IS 2 BP 73 EP 80 PG 8 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA UW354 UT WOS:A1996UW35400003 ER PT J AU De Luca, LM AF De Luca, LM TI Beta-carotene increases lung cancer incidence in cigarette smokers SO NUTRITION REVIEWS LA English DT Review ID VITAMIN-E; VEGETABLES; RISK; SKIN AB Clinical trials were designed to validate the protective effect of beta-carotene in populations of cigarette smokers at high risk for lung cancer development. Strikingly an increase in lung cancer resulted following beta-carotene supplementation in two separate studies in Finland and the United States. These trials were conducted without any evidence that beta-carotene prevents lung cancer in animal models. C1 NCI, DIV CANC PREVENT & CONTROL, CANC PREVENT FELLOWSHIP PROGRAM, BETHESDA, MD 20892 USA. RP De Luca, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, DIFFERENTIAT CONTROL SECT, BLDG 37, ROOM 3A-17, BETHESDA, MD 20892 USA. NR 17 TC 33 Z9 33 U1 0 U2 0 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD JUN PY 1996 VL 54 IS 6 BP 178 EP 180 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VE203 UT WOS:A1996VE20300004 PM 8810825 ER PT J AU Steven, H Yamashita, T Rhew, K Ludlow, CL AF Steven, H Yamashita, T Rhew, K Ludlow, CL TI Assessing the clinical utility of the magnetic stimulator for measuring response latencies in the laryngeal muscles SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID FACIAL-NERVE; CONDUCTION; EXCITES AB Our purpose was to assess the use of magnetic stimulation for measuring conduction time of the recurrent and superior laryngeal nerves in 10 normal volunteers (7 male, 3 female). Subjects underwent laryngeal electromyography and magnetic stimulation of the vagus nerve bilaterally at the mastoid tip with a figure 8 coil. Mean muscle response latencies were measured and examined for consistent differences. Thyroarytenoid muscle response latencies were consistently longer than those in the cricothyroid muscle. Left thyroarytenoid muscle latencies were consistently longer than those on the right in agreement with bilateral asymmetry of these nerves. No appreciable differences were observed in cricothyroid muscle latencies when the right side was compared with the left. Results were consistent and reproducible within a broad range, but appreciable intersubject variability was observed. The limited sample size was unable to support a correlation with anthropometric variables, although an association was indicated. Magnetic stimulation with this technique has great potential for use in neurolaryngologic studies. C1 NIDOCD,VOICE & SPEECH SECT,BETHESDA,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 19 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 1996 VL 114 IS 6 BP 761 EP 767 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA UR253 UT WOS:A1996UR25300010 ER PT J AU Johnson, EO Kamilaris, TC Calogero, AE Gold, PW Chrousos, GP AF Johnson, EO Kamilaris, TC Calogero, AE Gold, PW Chrousos, GP TI Effects of early parenting on growth and development in a small primate SO PEDIATRIC RESEARCH LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; MARMOSETS CALLITHRIX-JACCHUS; REPRODUCTIVE SUCCESS; SHORT STATURE; RESPONSIVENESS; SEPARATION; STRESS; ATTACHMENT; SECRETION; MULTIPLE AB We report here a study of the impact of caregiver-infant relationships on physical growth and behavioral development in a small primate, the common marmoset. Somatic growth was assessed from measurements of body weight, knee-heel length, head-tail length, head circumference, and pudendal pad width in females or testis volume in males obtained from unanesthetized monkeys. Behavioral information was gathered by focal animal samples for discrete rearing behaviors. Our data suggest that the frequency of positive parental behaviors during infancy is correlated with stature when the monkeys reach 10 and 20 wk of age. Furthermore, we found that juveniles that were mistreated by their parents during infancy were smaller in body weight, knee-heel length, and head-tail length, and they demonstrated abnormal social behavior. Finally, to address whether the apparent decreased growth observed in the young animals that had experienced negative parenting was also associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function, we examined the plasma ACTH and cortisol responses to synthetic ovine corticotropin-releasing hormone (oCRH) in these animals. relationships on physical growth and behavioral development in We found that the incremental cortisol response to exogenous a small primate, the common marmoset. Somatic growth was oCRH was significantly lower in the young adults that had assessed from measurements of body weight, knee-heel length, experienced negative parenting during infancy compared with those who bad nonabusive parents, indicating altered hypothalamic-pituitary-adrenal axis function in these animals. Our findings suggest that the quality of parental care influences later growth and behavior in the young marmoset. C1 NICHHD,NIH,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,NIH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. FU NIMH NIH HHS [5F31 MH-09594-03] NR 50 TC 25 Z9 25 U1 3 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JUN PY 1996 VL 39 IS 6 BP 999 EP 1005 DI 10.1203/00006450-199606000-00012 PG 7 WC Pediatrics SC Pediatrics GA UN555 UT WOS:A1996UN55500012 PM 8725261 ER PT J AU Long, RM AF Long, RM TI What are ''reinvention activities''? How is the NIH participating? What changes can be expected at the NIH? How can I get current information? SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material RP Long, RM (reprint author), NIH,NIGMS,PHARMACOL & PHYSIOL SCI BRANCH,PHARMACOL PHYSIOL & BIOL CHEM DIV,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUN PY 1996 VL 13 IS 6 BP 813 EP 814 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA UQ725 UT WOS:A1996UQ72500001 PM 8792415 ER PT J AU Daly, AK Brockmoller, J Broly, F Eichelbaum, M Evans, WE Gonzalez, FJ Huang, JD Idle, JR IngelmanSundberg, M Ishizaki, T JacqzAigrain, E Meyer, UA Nebert, DW Steen, VM Wolf, CR Zanger, UM AF Daly, AK Brockmoller, J Broly, F Eichelbaum, M Evans, WE Gonzalez, FJ Huang, JD Idle, JR IngelmanSundberg, M Ishizaki, T JacqzAigrain, E Meyer, UA Nebert, DW Steen, VM Wolf, CR Zanger, UM TI Nomenclature for human CYP2D6 alleles SO PHARMACOGENETICS LA English DT Review DE allele nomenclature; CYP2D6 ID POOR METABOLIZERS; DRUG-METABOLISM; GENE; DEBRISOQUINE; LOCUS; IDENTIFICATION; POPULATION; HYDROXYLATION; POLYMORPHISM; PHENOTYPE AB To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described, Based on recommendations for human genome nomenclature, we propose that alleles be designated by CYP2D6 followed by an asterisk and a combination of roman letters and arabic numerals distinct for each allele with the number specifying the key mutation and, where appropriate, a letter specifying additional mutations, Criteria for classification as a separate allele and protein nomenclature are also presented. C1 HUMBOLDT UNIV BERLIN, INST KLIN PHARMAKOL, KLINIKUM CHARITE, D-10098 BERLIN, GERMANY. CTR HOSP REG & UNIV LILLE, HOP CALMETTE, LAB BIOCHIM & BIOL MOL, F-59037 LILLE, FRANCE. DR MARGARETE FISCHER BOSCH INST CLIN PHARMACOL, D-70376 STUTTGART, GERMANY. ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT, MEMPHIS, TN 38101 USA. NCI, MOLEC CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. NATL CHENG KUNG UNIV, DEPT PHARMACOL, TAINAN 70101, TAIWAN. KAROLINSKA INST, DEPT MED BIOCHEM & BIOPHYS, S-17177 STOCKHOLM, SWEDEN. INT MED CTR JAPAN, RES INST, DEPT CLIN PHARMACOL, SHINJUKU KU, TOKYO 162, JAPAN. HOP ROBERT DEBRE, INSERM U120, F-75019 PARIS, FRANCE. HOP ROBERT DEBRE, DEPT CLIN PHARMACOL, F-75019 PARIS, FRANCE. UNIV BASEL, BIOCTR, ABT PHARMAKOL, CH-4056 BASEL, SWITZERLAND. UNIV CINCINNATI, MED CTR, DEPT ENVIRONM HLTH, CINCINNATI, OH 45267 USA. HAUKELAND HOSP, CTR MOL MED, DR EINAR MARTENS RES GRP BIOL PSYCHIAT, N-5021 BERGEN, NORWAY. UNIV DUNDEE, NINEWELLS HOSP & MED SCH, BIOMED RES CTR, DUNDEE DD1 9SY, SCOTLAND. RP Daly, AK (reprint author), UNIV NEWCASTLE UPON TYNE, SCH MED, PHARMACOGENET RES UNIT, FRAMLINGTON PL, NEWCASTLE UPON TYNE NE2 4HH, TYNE & WEAR, ENGLAND. RI Steen, Vidar/A-6190-2008; Daly, Ann/H-3144-2011; Zanger, Ulrich/A-9364-2012; OI Daly, Ann/0000-0002-7321-0629; Zanger, Ulrich/0000-0002-5276-2002; Idle, Jeff/0000-0002-6143-1520 NR 40 TC 364 Z9 377 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JUN PY 1996 VL 6 IS 3 BP 193 EP 201 DI 10.1097/00008571-199606000-00001 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA UV426 UT WOS:A1996UV42600001 PM 8807658 ER PT J AU Enk, CD Mahanty, S Blauvelt, A Katz, SI AF Enk, CD Mahanty, S Blauvelt, A Katz, SI TI UVB induces IL-12 transcription in human keratinocytes in vivo and in vitro SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; CYTOKINE PRODUCTION; NK CELLS; FACTOR INTERLEUKIN-12; FACTOR NKSF/IL-12; MESSENGER-RNA; TH1 CELLS; INDUCTION; RESPONSES AB Human epidermal cells produce a wide range of cytokines, including those characteristic of Th2-like responses such as interleukin (IL)-4 and IL-10. As well, keratinocytes have such as IL-12. Exposure to UVB has profound effects on the skin and systemic immune system, which is in part mediated by secretion of tumor necrosis factor (TNF)-alpha by epidermal cells. Because IL-12 induces production of TNF-alpha by certain cells of the immune system, we sought to determine whether UVB is an inducer of IL-12 gene expression in epidermal cells. Human epidermal cells were exposed to UVB radiation in vivo, isolated by suction blister technique and trypsinization and transcription of the IL- p35 and p40 chains was examined by RT-PCR. We found the p35 chain of IL-12 to be constitutively expressed and the p40 chain inducible by UVB irradiation. Because epidermis consists of a heterogenous cell population with distinct cytokine repertoires, we sought to determine the cellular source of the IL-12 message after UVB exposure. After depleting UVB-exposed epidermal cells for DR cells, no reduction in the IL-12 activity was detected, suggesting that keratinocytes are a source of IL-12 transcripts in UVB-exposed human epidermis. This was supported by the up-regulation of IL-12 p40 transcripts in UV-irradiated cultured keratinocytes that were devoid of DR cells. Up-regulation of IL-12 p40 gene expression by UVB as demonstrated here, taken together with the finding that keratinocytes also up-regulate IL-10 transcripition, suggest that there is a complex interplay between Th1- and Th2-like epidermis-derived cytokines following exposure to UVB. C1 NCI,DERMATOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 42 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1996 VL 63 IS 6 BP 854 EP 859 DI 10.1111/j.1751-1097.1996.tb09642.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UQ162 UT WOS:A1996UQ16200027 PM 8992506 ER PT J AU Berkolaiko, G Havlin, S Larralde, H Weiss, GH AF Berkolaiko, G Havlin, S Larralde, H Weiss, GH TI Expected number of distinct sites visited by N Levy flights on a one-dimensional lattice SO PHYSICAL REVIEW E LA English DT Article ID DIFFUSION; TRAPS AB We calculate asymptotic forms for the expected number of distinct sites, [S-N(n)], visited by N noninteracting n-step symmetric Levy flights in one dimension. By a Levy flight we mean one in which the probability of making a step of j sites is proportional to 1/\j\(1+alpha) in the limit j-->infinity. All values of alpha>O are considered. In our analysis each Levy flight is initially at the origin and both N and n are assumed to be large. Different asymptotic results are obtained for different ranges in cu. When n is fixed and N-->infinity we find that [S-N(n)] is proportional to (Na-2)(1/(1+alpha)) for alpha<1 and to N-1/(1+alpha)n(1/alpha) for alpha>1. When alpha exceeds 2 the second moment is finite and one expects the results of Larralde et al. [Phys. Rev. A 45, 7128 (1992)] to be valid. We give results for both fixed n and N-->infinity and N fixed and n-->infinity. In the second case the analysis leads to the behavior predicted by Larralde et al. C1 BAR ILAN UNIV,MINERVA CTR,IL-52900 RAMAT GAN,ISRAEL. BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. UNIV CAMBRIDGE,CAVENDISH LAB,CAMBRIDGE CBS 0HE,ENGLAND. NIH,PSL DCRT,BETHESDA,MD 20205. RP Berkolaiko, G (reprint author), VORONEZH STATE UNIV,DEPT MATH,VORONEZH 394693,RUSSIA. NR 16 TC 19 Z9 19 U1 1 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JUN PY 1996 VL 53 IS 6 BP 5774 EP 5778 DI 10.1103/PhysRevE.53.5774 PN A PG 5 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA UR606 UT WOS:A1996UR60600034 ER PT J AU Sastry, S Debenedetti, PG Sciortino, F Stanley, HE AF Sastry, S Debenedetti, PG Sciortino, F Stanley, HE TI Singularity-free interpretation of the thermodynamics of supercooled water SO PHYSICAL REVIEW E LA English DT Article ID LIQUID WATER; TE; COMPRESSIBILITY; TRANSITION; STABILITY; BEHAVIOR; PHASE; MODEL AB The pronounced increases in isothermal compressibility, isobaric heat capacity, and in the magnitude of the thermal expansion coefficient of liquid water upon supercooling have been interpreted either in terms of a continuous, retracing spinodal curve bounding the superheated, stretched, and supercooled states of liquid water, or in terms of a metastable, low-temperature critical point. Common to these two scenarios is the existence of singularities associated with diverging density fluctuations at low temperature. We show that the increase in compressibility upon lowering the temperature of a liquid that expands on cooling, like water, is not contingent on any singular behavior, but rather is a thermodynamic necessity. We perform a thermodynamic analysis for an anomalous liquid (i.e., one that expands when cooled) in the absence of a retracing spinodal and show that one may in general expect a locus of compressibility extrema in the anomalous regime. Our analysis suggests that the simplest interpretation of the behavior of supercooled water consistent with experimental observations is free of singularities. We then develop a waterlike lattice model that exhibits no singular behavior, while capturing qualitative aspects of the thermodynamics of water. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20952. UNIV ROMA LA SAPIENZA,DIPARTIMENTO FIS,I-00185 ROME,ITALY. IST NAZL FIS MAT,I-00185 ROME,ITALY. BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215. BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. RP Sastry, S (reprint author), PRINCETON UNIV,DEPT CHEM ENGN,PRINCETON,NJ 08544, USA. RI Sciortino, Francesco/B-4768-2012 NR 30 TC 392 Z9 395 U1 2 U2 36 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JUN PY 1996 VL 53 IS 6 BP 6144 EP 6154 DI 10.1103/PhysRevE.53.6144 PN B PG 11 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA UR607 UT WOS:A1996UR60700012 ER PT J AU Lewis, KM Sherer, DM Goncalves, LF Fromberg, RA Eglinton, GS AF Lewis, KM Sherer, DM Goncalves, LF Fromberg, RA Eglinton, GS TI Mid-trimester prenatal sonographic: Diagnosis of a pericardial cyst SO PRENATAL DIAGNOSIS LA English DT Article DE prenatal diagnosis; ultrasound; pericardial cyst ID INTRAPERICARDIAL TERATOMA; FETAL ECHOCARDIOGRAPHY; INUTERO; TUMOR; MASS AB Prenatal diagnosis of pericardial masses are infrequent and usually consist of intrapericardial teratomas or haemangiomas. We present the first report of prenatal diagnosis of a suspected pericardial cyst at 14 weeks' gestation which was subsequently confirmed by neonatal computed tomography. C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,NICHHD,NIH,INTRAMURAL DIV,PERINATOL RES FACIL,WASHINGTON,DC 20007. FU NICHD NIH HHS [N01-HD-3-3198] NR 19 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD JUN PY 1996 VL 16 IS 6 BP 549 EP 553 DI 10.1002/(SICI)1097-0223(199606)16:6<549::AID-PD879>3.0.CO;2-9 PG 5 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA UU846 UT WOS:A1996UU84600009 PM 8809897 ER PT J AU Leshner, AI DeLeon, PH AF Leshner, AI DeLeon, PH TI The power of science in furthering professional practice: Opportunities for those with vision SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Editorial Material RP Leshner, AI (reprint author), NIDA,LEXINGTON,KY 40583, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD JUN PY 1996 VL 27 IS 3 BP 219 EP 220 PG 2 WC Psychology, Multidisciplinary SC Psychology GA UL525 UT WOS:A1996UL52500001 ER PT J AU Edwin, SS Romero, RJ Munoz, H Branch, DW Mitchell, MD AF Edwin, SS Romero, RJ Munoz, H Branch, DW Mitchell, MD TI 5-Hydroxyeicosatetraenoic acid and human parturition SO PROSTAGLANDINS LA English DT Article DE 5-hydroxyeicosatetraenoic acid; interleukin-1 beta; amniotic fluid; acetylsalicylic acid; preterm labor ID ARACHIDONATE LIPOXYGENASE METABOLITES; AMNIOTIC-FLUID; PRETERM LABOR; FETAL MEMBRANES; INFECTION; BIOSYNTHESIS; TISSUES; CALCIUM; ONSET; CELLS AB 5-Hydroxyeicosatetraenoic acid (5-HETE) is an arachidonic acid (AA) metabolite derived from the lipoxygenase pathway which is capable of inducing uterine contractions. The purpose of this study was to determine a). whether 5-HETE concentrations in amniotic fluid increase before or after the onset of labor and b). whether acetylsalicylic acid (ASA) could modulate the production of 5-HETE by human amnion cells. 5-HETE concentrations are increased in amniotic fluid before the onset of labor. Furthermore, ASA treatment as expected inhibited PGE(2), but also significantly increased 5-HETE production by amnion cells. 5-HETE concentrations on average increased by greater than 2.5 fold (p < 0.001) in amniotic fluid prior to spontaneous labor when compared with samples obtained from the same patients earlier in gestation and therefore may be important in mechanisms regulating the onset of labor. ASA provokes an increase in 5-HETE biosynthesis by amnion cells: control media 2.60 +/- 1.5, ASA treatment alone 5.17 +/- 0.20, IL-1 beta alone 6.39 +/- 2.1, and ASA + IL-1 beta 8.95 +/- 1.2 (mean +/- SEM) picograms per microgram protein per 16 hours. These findings may explain in part why cyclooxygenase inhibitors are not always successful in treating women with preterm labor. C1 NICHHD,PERINATAL RES BRANCH,BETHESDA,MD 20892. UNIV AUCKLAND,DEPT PHARMACOL & CLIN PHARMACOL,AUCKLAND,NEW ZEALAND. RP Edwin, SS (reprint author), UNIV UTAH,SCH MED,DEPT OBSTET & GYNECOL,SALT LAKE CITY,UT 84132, USA. RI Mitchell, Murray/A-8639-2010 OI Mitchell, Murray/0000-0002-6167-7176 NR 19 TC 17 Z9 17 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0090-6980 J9 PROSTAGLANDINS JI Prostaglandins PD JUN PY 1996 VL 51 IS 6 BP 403 EP 412 DI 10.1016/0090-6980(96)00046-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VD029 UT WOS:A1996VD02900004 PM 8873235 ER PT J AU Kuszewski, J Gronenborn, AM Clore, GM AF Kuszewski, J Gronenborn, AM Clore, GM TI Improving the quality of NMR and crystallographic protein structures by means of a conformational database potential derived from structure databases SO PROTEIN SCIENCE LA English DT Article DE conformational databases; NMR; protein structure determination; refinement; X-ray ID NUCLEAR-MAGNETIC-RESONANCE; INTERPROTON DISTANCE DATA; 3-DIMENSIONAL STRUCTURES; MOLECULAR-DYNAMICS; COUPLING-CONSTANTS; FACTOR REFINEMENT; FORCE-FIELD; R-FACTOR; SPECTROSCOPY; GEOMETRY AB A new conformational database potential involving dihedral angle relationships in databases of high-resolution highly refined protein crystal structures is presented as a method for improving the quality of structures generated from NMR data. The rationale for this procedure is based on the observation that uncertainties in the description of the nonbonded contacts present a key limiting factor in the attainable accuracy of protein NMR structures and that the nonbonded interaction terms presently used have poor discriminatory power between high- and low-probability local conformations. The idea behind the conformational database potential is to restrict sampling during simulated annealing refinement to conformations that are likely to be energetically possible by effectively limiting the choices of dihedral angles to those that are known to be physically realizable. In this manner, the variability in the structures produced by this method is primarily a function of the experimental restraints, rather than an artifact of a poor nonbonded interaction model. We tested this approach with the experimental NMR data (comprising an average of about 30 restraints per residue and consisting of interproton distances, torsion angles, (3)J(HN alpha) coupling constants, and C-13 chemical shifts) used previously to calculate the solution structure of reduced human thioredoxin (Qin J, Clore GM, Gronenborn AM, 1994, Structure 2:503-522). Incorporation of the conformational database potential into the target function used for refinement (which also includes terms for the experimental restraints, covalent geometry, and nonbonded interactions in the form of either a repulsive, repulsive-attractive, or 6-12 Lennard-Jones potential) results in a significant improvement in various quantitative measures of quality (Ramachandran plot, side-chain torsion angles, overall packing). This is achieved without compromising the agreement with the experimental restraints and the deviations from idealized covalent geometry that remain within experimental error, and the agreement between calculated and observed H-1 chemical shifts that provides an independent NMR parameter of accuracy. The method is equally applicable to crystallographic refinement, and should be particular useful during the early stages of either an NMR or crystallographic structure determination and in cases where relatively few experimental restraints can be derived from the measured data (due, for example, to broad lines in the NMR spectra or to poorly diffracting crystals). C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 57 TC 189 Z9 194 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUN PY 1996 VL 5 IS 6 BP 1067 EP 1080 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP617 UT WOS:A1996UP61700009 PM 8762138 ER PT J AU Panlilio, LV Weiss, SJ Schindler, CW AF Panlilio, LV Weiss, SJ Schindler, CW TI Cocaine self-administration increased by compounding discriminative stimuli SO PSYCHOPHARMACOLOGY LA English DT Article DE self-administration; stimulus control; incentive-motivation; additive summation; cocaine; rat ID REINFORCEMENT; OPERANT AB Presenting independently established discriminative stimuli in compound can substantially increase response rates under food and shock-avoidance schedules. To determine whether this effect extends to drug self-administration, rats were trained to press a lever to receive cocaine intravenously. A tone and a light were independently established as discriminative stimuli for cocaine self-administration, then presented in combination in a stimulus-compounding test. Compared to tone and light alone, the tone-plus-light compound stimulus increased responding approximately three-fold when cocaine was withheld during testing, and it increased drug intake approximately two-fold when cocaine was made available during testing. Compounding did not increase responding after training in a truly random control condition where tone and light were presented uncorrelated with the availability of cocaine. The results obtained with this animal model of drug abuse define conditions under which combinations of environmental stimuli might substantially increase human drug use. C1 AMERICAN UNIV,DEPT PSYCHOL,WASHINGTON,DC 20016. RP Panlilio, LV (reprint author), NIDA,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,NIH,DIV INTRAMURAL RES,POB 5180,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA 05555-02] NR 35 TC 67 Z9 67 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 1996 VL 125 IS 3 BP 202 EP 208 DI 10.1007/BF02247329 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UT063 UT WOS:A1996UT06300003 PM 8815954 ER PT J AU Jezzard, P Duewell, S Balaban, RS AF Jezzard, P Duewell, S Balaban, RS TI MR relaxation times in human brain: Measurement at 4 T SO RADIOLOGY LA English DT Article DE brain, MR; magnetic resonance (MR); high-field-strength imaging; magnetic resonance (MR); pulse sequences; magnetic resonance (MR), relaxometry ID MECHANISMS; 1.5-T AB PURPOSE: To determine the values for relaxation times in human brain for magnetic resonance (MR) imaging at 4 T. MATERIALS AND METHODS: T1 measurements were made with a progressive saturation sequence, an implementation of the Look-Locker sequence, and an inversion-recovery (IR) interleaved echo-planar imaging (IEPI) sequence. T2 measurements were made with a standard spin-echo (SE) sequence and an SE IEPI sequence. RESULTS: The T1 measurements yielded values of 1,724 msec +/- 51 for gray matter, 1,043 msec +/- 27 for white matter, and 4,550 msec +/- 800 msec for cerebrospinal fluid. The deep gray matter regions had T1 values of 1,458 +/- 38 (caudate nucleus) and 1,372 +/- 60 (putamen). The T2 measurements yielded results of 63 msec +/- 6.2 for gray matter and 49.8 msec +/- 2.2 for white matter. CONCLUSION: The T1 values measured at 4 T show a higher value than predicted from extrapolation at lower field strengths. The T2 measurements showed a slight decrease in values over those measured at lower field strength. The gain in signal-to-noise ratio from the higher field strength may be substantially offset by these altered relaxation time values to a degree that is sequence dependent. RP Jezzard, P (reprint author), NHLBI,CARDIAC ENERGET LAB,BLDG 10,RM B1D161,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Jezzard, Peter/0000-0001-7912-2251 NR 21 TC 88 Z9 88 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1996 VL 199 IS 3 BP 773 EP 779 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL526 UT WOS:A1996UL52600034 PM 8638004 ER PT J AU Duewell, S Wolff, SD Wen, H Balaban, RS Jezzard, P AF Duewell, S Wolff, SD Wen, H Balaban, RS Jezzard, P TI MR imaging contrast in human brain tissue: Assessment and optimization at 4 T SO RADIOLOGY LA English DT Article DE brain, MR; magnetic resonance (MR); high-field-strength imaging; magnetic resonance (MR), pulse sequences; magnetic resonance (MR), relaxometry ID FIELD-DEPENDENCE; RELAXATION; SPECTROSCOPY; TESLA; 1.5-T; POWER; 4-T AB PURPOSE: To evaluate multiple magnetic resonance (MR) imaging sequences for their ability to provide T1- and T2-weighted images at a field strength of 4 T, and to validate previously obtained relaxation time measurements. MATERIALS AND METHODS: Different spin-echo, inversion-recovery (IR), gradient-recalled acquisition in the steady state (GRASS), and magnetization transfer contrast-enhanced GRASS sequences were evaluated in a single section, each in at least four volunteers. Also, interleaved echo-planar imaging (IEPI) and interleaved gradient-recalled echo (IGRE) sequences were analyzed and compared with standard sequences. RESULTS: Predicted contrast behavior, according to MR relaxation time measurements, was found to agree well with that of the validation experiments. Fair T1 contrast can be achieved on MR images at 4 T, contrary to early predictions. Under other conditions, however, such as partially spin-density-weighted parameters, lower contrast is observed at the high field strength when compared with conventional field strengths. CONCLUSION: The longer T1 values at higher field strengths have a substantial effect on image contrast. Depending on the sequence and parameters chosen, good image contrast can be realized at 4 T. IEPI and hybrid IR IGRE sequences are useful in shortening the prolonged examination times owing to the longer T1 values at higher field strengths. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010; OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997; Jezzard, Peter/0000-0001-7912-2251 NR 30 TC 47 Z9 47 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1996 VL 199 IS 3 BP 780 EP 786 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL526 UT WOS:A1996UL52600035 PM 8638005 ER PT J AU Blazka, ME Bruccoleri, A Simeonova, PP Germolec, DR Pennypacker, KR Luster, M AF Blazka, ME Bruccoleri, A Simeonova, PP Germolec, DR Pennypacker, KR Luster, M TI Acetaminophen-induced hepatotoxicity is associated with early changes in AP-1 DNA binding activity SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; C-JUN; TRANSCRIPTION FACTORS; EXPRESSION; LIVER; FOS; RAT; REGENERATION; INDUCTION; GENES AB The AP-1 transcription factor family, which is involved in early response genes, consists of two groups of proteins, Fos-related antigens (fra) and Jun proteins. AP-1 is usually expressed at low basal cellular levels, but can be up-regulated by a variety of exogenous stimuli which results in synthesis of Fos and Jun proteins and increased AP-1 DNA binding activity. Changes in early immediate gene responses are associated with liver necrosis, inflammation and repair, although investigations into their role in drug-induced hepatotoxicity have not been actively examined. In the present studies, we determined that exposure to necrogenic doses of acetaminophen (APAP) was associated with increased AP-1 DNA binding activity in mouse liver. The APAP-induced hepatic AP-1 DNA binding complex had affinity for both the consensus AP-1 and CRE sequences. Furthermore, c-jun, but not c-fos, mRNA transcripts were transiently increased following exposure to hepatotoxic doses of APAP. When endotoxin was administered to mice in order to elicit a hepatic inflammatory response without necrosis, increases in c-jun expression occurred without accompanying changes in AP-1 activity, indicating a different mechanism of action. When compared to conventional indicators of hepatotoxicity, such as plasma levels of liver-associated enzymes, changes in gene expression occurred much earlier and, at least with AP-1 activity, remained activated following normalization of liver enzyme levels. These studies suggest that the AP-1 transcription factor and associated genes are associated in the hepatotoxic response of liver to APAP and may serve as useful molecular biomarkers for chemical-induced hepatotoxicity. C1 UNIV S FLORIDA,DEPT THERAPEUT & PHARMACOL,TAMPA,FL 33612. NIOSH,TOXICOL & MOL BIOL BRANCH,MORGANTOWN,WV 26505. RP Blazka, ME (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 20 TC 18 Z9 18 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PD JUN PY 1996 VL 92 IS 3 BP 259 EP 273 PG 15 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA UX359 UT WOS:A1996UX35900001 PM 8827825 ER PT J AU McKenzie, R Straus, SE AF McKenzie, R Straus, SE TI Vaccine therapy for herpes simplex virus infections: An historical perspective SO REVIEWS IN MEDICAL VIROLOGY LA English DT Article ID RECURRENT GENITAL HERPES; TYPE-1 GLYCOPROTEIN-D; PLACEBO-CONTROLLED TRIAL; GUINEA-PIGS; INVIVO BEHAVIOR; PROTECTION; EFFICACY; MICE; IMMUNOTHERAPY; IMMUNIZATION RP McKenzie, R (reprint author), NIAID,MED VIROL SECT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892, USA. NR 64 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD JUN PY 1996 VL 6 IS 2 BP 85 EP 96 DI 10.1002/(SICI)1099-1654(199606)6:2<85::AID-RMV167>3.0.CO;2-E PG 12 WC Virology SC Virology GA UX247 UT WOS:A1996UX24700006 ER PT J AU Lenfant, C AF Lenfant, C TI Asthma and pregnancy report on the working group from national asthma education program (NIH, USA) - Foreword SO REVUE FRANCAISE D ALLERGOLOGIE ET D IMMUNOLOGIE CLINIQUE LA French DT Editorial Material RP Lenfant, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0335-7457 J9 REV FR ALLERGOL JI Rev. Fr. Allergol. Immunol. Clin. PD JUN PY 1996 VL 36 IS 4 BP 364 EP 364 PG 1 WC Allergy SC Allergy GA UY621 UT WOS:A1996UY62100001 ER PT J AU Welp, E Partanen, T Kogevinas, M Andersen, A Bellander, T Biocca, M Coggon, D Fontana, V Kolstad, H Lundberg, I Lynge, E Spence, A Ferro, G Boffetta, P Saracci, R AF Welp, E Partanen, T Kogevinas, M Andersen, A Bellander, T Biocca, M Coggon, D Fontana, V Kolstad, H Lundberg, I Lynge, E Spence, A Ferro, G Boffetta, P Saracci, R TI Exposure to styrene and mortality from nonmalignant diseases of the genitourinary system SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE cohort study; nephritis; nephrosis; occupational health; solvent ID RENAL-FAILURE; NEPHROTOXICITY; GLOMERULONEPHRITIS; SOLVENTS; COHORT AB Objective A historical cohort study was carried out to investigate mortality from nonmalignant diseases of the genitourinary system among workers in the reinforced plastics industry, where high workroom concentrations of styrene are encountered. Methods The external comparisons in this report were based on an average of 12.6 years of retrospective follow-up of 35 443 workers who were first employed in the reinforced plastics industry during 1945-1991 and were known to have been exposed to styrene in their work. For the internal comparisons, 2641 subjects with incomplete occupational histories were excluded, leaving 32 802 subjects. Previous individual exposure histories to styrene were reconstructed through job histories and environmental and biological monitoring data. Results Mortality from nonmalignant diseases of the genitourinary system (N = 20) was associated with average exposure to styrene (P for trend 0.05). Weaker increasing trends in risk were seen for time since first exposure and cumulative exposure, while no increase was identified for duration of exposure. There was a significant increasing trend in mortality from nephritis and nephrosis (N = 5), associated with an increasing average level of exposure to styrene (P for trend 0.03). No clear trend was observed for time since first exposure, duration of exposure, or cumulative exposure. Conclusions In this large cohort study of workers exposed to styrene, mortality from nonmalignant diseases of the genitourinary system increased as the average intensity of exposure increased. This finding indicates that other data should be scrutinized. C1 INT AGCY RES CANC,UNIT ENVIRONM CANC EPIDEMIOL,F-69372 LYON 08,FRANCE. UNIV WASHINGTON,DEPT ENVIRONM HLTH,SEATTLE,WA 98195. FINNISH INST OCCUPAT HLTH,HELSINKI,FINLAND. IMIM,DEPT EPIDEMIOL & PUBL HLTH,BARCELONA,SPAIN. CANC REGISTRY NORWAY,OSLO,NORWAY. KAROLINSKA HOSP,DEPT OCCUPAT HLTH,STOCKHOLM,SWEDEN. CTR STUDY & PREVENT CANC,FLORENCE,ITALY. SEDI,PRESDIO MULTIZONALE PREVENZ,BOLOGNA,ITALY. UNIV SOUTHAMPTON,MRC,ENVIRONM EPIDEMIOL UNIT,SOUTHAMPTON,HANTS,ENGLAND. NATL CANC INST,GENOA,ITALY. AARHUS UNIV,INST EPIDEMIOL & SOCIAL MED,AARHUS,DENMARK. DANISH CANC SOC,COPENHAGEN,DENMARK. HLTH & SAFETY EXECUT,BOOTLE,ENGLAND. CNR,INST CLIN PHYSIOL,PISA,ITALY. RI Kogevinas, Manolis/C-3918-2017 NR 16 TC 4 Z9 4 U1 0 U2 1 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD JUN PY 1996 VL 22 IS 3 BP 223 EP 226 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UW576 UT WOS:A1996UW57600010 PM 8837269 ER PT J AU StetlerStevenson, WG Hewitt, R Corcoran, M AF StetlerStevenson, WG Hewitt, R Corcoran, M TI Matrix metalloproteinases and tumor invasion: From correlation and causality to the clinic SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE extracellular matrix; invasion; metastases; proteases; TIMPs ID C-TERMINAL DOMAIN; TISSUE INHIBITOR; GENE-EXPRESSION; IV COLLAGENASE; GELATINASE-A; CELL-LINE; CARCINOMA; METASTASIS; TIMP-2; PROGRESSION AB Tumor cell invasion is now viewed as dysregulated physiologic invasion. Investigators have started to define the molecular events that are involved in this process. We find that there are many functional similarities with molecular events involved in physiologic process such as angiogenesis and wound healing. Matrix metalloproteinase activity is a common denominator in these pathologic conditions and in normal responses. Studies using endogenous metalloproteinase inhibitors suggest that targeting matrix metalloproteinase activity may prevent tumor cell dissemination. The development and pre-clinical testing of novel, low molecular weight matrix metalloproteinase inhibitors support this concept and suggest that an. exciting new era of cancer therapy is on the horizon. RP StetlerStevenson, WG (reprint author), NCI,PATHOL LAB,EXTRACELLULAR MATRIX PATHOL SECT,DIV CLIN SCI,BLDG 10,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 58 TC 255 Z9 261 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 1996 VL 7 IS 3 BP 147 EP 154 DI 10.1006/scbi.1996.0020 PG 8 WC Oncology SC Oncology GA UM654 UT WOS:A1996UM65400007 PM 8773300 ER PT J AU Safar, J AF Safar, J TI Spectroscopic conformational studies of prion protein isoforms and the mechanism of transformation SO SEMINARS IN VIROLOGY LA English DT Article DE conformation; pathway; prion protein; protein folding; scrapie amyloid ID CREUTZFELDT-JAKOB DISEASE; SECONDARY STRUCTURE; PRECURSOR PROTEINS; CIRCULAR-DICHROISM; SCRAPIE AGENT; VIRUS-LIKE; INFECTIVITY; INACTIVATION; LIPOSOMES; TRANSITIONS AB The agent responsible for transmission of spongiform encephalopathies (prion diseases) has unique biological and physical properties, and its essential component is the prion protein (scrapie amyloid). The recent developments in structural chemistry and molecular biology of the prion. protein provide strong evidence for the central role of an abnormal post-translational protein folding mechanism in the transmission and pathogenesis of disease. During the course of disease, the normal chromosomal PrP gene product containing a predominantly alpha-helical secondary structure is transformed into a protein with more secondary structure in beta-sheets. As a result, the protein acquires different physical properties and the ability to form amyloid. Understanding this apparently conformational conversion mechanism may advance the investigation of other neurodegenerative disorders and brain amyloidoses. Here we review current knowledge of the structural chemistry of the prion protein and explore the mechanism of its replication. RP Safar, J (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892, USA. RI Safar, Jiri/G-6512-2013 NR 37 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD JUN PY 1996 VL 7 IS 3 BP 207 EP 214 DI 10.1006/smvy.1996.0026 PG 8 WC Virology SC Virology GA UQ756 UT WOS:A1996UQ75600007 ER PT J AU Wickner, RB Masison, DC Edskes, HK AF Wickner, RB Masison, DC Edskes, HK TI [URE3] and [PSI] as prions of Saccharomyces cerevisiae: Genetic evidence and biochemical properties SO SEMINARS IN VIROLOGY LA English DT Article DE nitrogen repression; SUP35; termination of translation; URE2; ureidosuccinate ID SUP35 GENE; FRAMESHIFT SUPPRESSION; SCRAPIE PRION; PROTEIN PRP; YEAST; IDENTIFICATION; MUTATIONS; MUTANTS AB We have proposed that the yeast non-Mendelian elements [URE3] and [PSI] are prions, altered forms of Ure2p and Sup35p, respectively. Both are curable, but can arise again in the cured strains. The relation of the ure2 and sup35 mutations to [URE3] and [PSI] is that expected of prions, not that expected of nucleic acid replicons. Overproduction of Ure2p and Sup35p increases by 100-fold the frequency with which [URE3] nad [PSI] arise, respectively. The N-terminal 65 amino acid residues of Ure2p are necessary for the [URE3] change and Ure2p becomes partially protease-resistant in [URE3] strains. The chaperone, Hsp104, is necessary for the propagation of [PSI], but when overexpressed cures [PSI]. RP Wickner, RB (reprint author), NIDDK,SECT GENET SIMPLE EUKARYOTES,BIOCHEM PHARMACOL LAB,NIH,BLDG 8,ROOM 225,8 CTR DR,MSC 0830,BETHESDA,MD 20892, USA. NR 49 TC 7 Z9 7 U1 2 U2 7 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD JUN PY 1996 VL 7 IS 3 BP 215 EP 223 DI 10.1006/smvy.1996.0027 PG 9 WC Virology SC Virology GA UQ756 UT WOS:A1996UQ75600008 ER PT J AU Scheffel, U Steinert, C Kim, SE Ehlers, MD Boja, JW Kuhar, MJ AF Scheffel, U Steinert, C Kim, SE Ehlers, MD Boja, JW Kuhar, MJ TI Effect of dopaminergic drugs on the in vivo binding of [H-3]WIN 35,428 to central dopamine transporters SO SYNAPSE LA English DT Article DE in vivo binding; DA transporter; [H-3]WIN35,428; L-DOPA; d-amphetamine; alpha-methyl-DL-p-tyrosine; gamma-butyrolactone; L-deprenyl; haloperidol; apomorphine; bromocriptine ID POSITRON EMISSION TOMOGRAPHY; F-18 GBR 13119; COCAINE RECOGNITION SITES; INVIVO MICRODIALYSIS; RAT STRIATUM; KINETIC-PROPERTIES; PREFRONTAL CORTEX; SUBSTANTIA-NIGRA; UPTAKE INHIBITOR; REUPTAKE SITES AB [C-11]WIN 35,428 (also designated [C-11]CFT) is now being used in several positron emission tomography (PET) centers to image dopamine (DA) transporter sites in the mammalian brain. Whether and to what extent in vivo WIN 35,428 binding is influenced by intra- and extrasynaptic dopamine levels are largely unknown. The purpose of the present study was to evaluate the effects of various drugs, known to affect DA levels and release, on the binding of [H-3]WIN 35,428 to central DA transporters in the mouse brain. D-Amphetamine, which releases DA from neurons and blocks the DA transporter directly, inhibited striatal [H-3]WIN 35,428 binding in dose-dependent manner. Similarly, alpha-methyl-DL-p-tyrosine, an inhibitor of tyrosine hydroxylase, blocked [H-3]WIN 35,428 binding, possibly via competitive inhibition by the metabolite p-hydroxyamphetamine. Specific binding of [H-3]WIN 35,428 was insensitive to changes in synaptic DA levels caused by pretreatment of the animals with high doses of D-2 receptor agonists (apomorphine, bromocriptine), antagonists (haloperidol) or the inhibitor of dopaminergic neuron firing gamma-butyrolactone (GEL). High doses (> 50 mg/kg) of L-DOPA (in combination with benserazide), however, reduced [H-3]WIN 35,428 binding significantly, yet for a relatively short time (approximately 2.5 h). Chronic treatment with L-deprenyl elicited no changes in in vivo [H-3]WIN 35,428 accumulation in the striatum. Neurotoxic damage of DA neurons caused by administration of high doses of amphetamine was detected in the striatum by a significant reduction in [H-3]WIN 35,428 binding 7 days after cessation of amphetamine treatment. Thus, [H-3]WIN 35,428 binding was only affected by neurotoxic loss of neurons, by administration of uptake inhibitors, or by some treatments which significantly elevate DA levels. Compounds which inhibit DA release or deplete DA acutely do not increase [H-3]WIN 35,428 binding, suggesting that normal or ''resting'' levels of DA are not sufficient to alter [H-3]WIN 35,428 binding in vivo. These findings are important for our understanding of the function and regulation of the DA transporter, as well as the in vivo binding of the radioligand [H-3/C-11]WIN 35,428. Moreover, they will be important for the interpretation of PET studies in which [C-11]WIN 35,428 is used to assess the integrity of dopaminergic neurons. (C) 1996 Wiley-Liss, Inc. C1 JOHNS HOPKINS MED INST, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. NIDA, ADDICT RES CTR, NEUROSCI BRANCH, BALTIMORE, MD 21224 USA. RP Scheffel, U (reprint author), JOHNS HOPKINS MED INST, DEPT RADIOL, DIV NUCL MED, BALTIMORE, MD 21205 USA. RI Kim, Sang Eun/J-5401-2012 FU NIDA NIH HHS [DA 06309]; NINDS NIH HHS [NS 15080] NR 72 TC 31 Z9 31 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD JUN PY 1996 VL 23 IS 2 BP 61 EP 69 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UH493 UT WOS:A1996UH49300001 PM 8723710 ER PT J AU Nagi, DK Knowler, WC Hanson, RL Ali, VM Yudkin, JS AF Nagi, DK Knowler, WC Hanson, RL Ali, VM Yudkin, JS TI Plasminogen activator inhibitor (PAI-1) and non-insulin-dependent diabetes in Pima Indians, South Asians and Europeans - Populations at varying risk of NIDDM and coronary artery disease SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID MYOCARDIAL-INFARCTION; RAPID INHIBITOR; HIGH PREVALENCE; HEART-DISEASE; RESISTANCE; PLASMA; MELLITUS; CAUCASIANS; PROINSULIN AB Activity of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of fibrinolysis, is raised in non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to excess macrovascular disease. We investigated the association of PAI-1 activity with NIDDM in Pima Indians, a racial group with low risk of coronary artery disease, but in whom the impact of NIDDM on the occurrence of coronary artery disease is similar to other racial groups. We studied 308 (136 non-diabetic, 172 diabetic) Pima Indians from Arizona, and 138 (98 non-diabetic, 40 diabetic) South Asians and 129 (80 non-diabetic, 49 diabetic) Europeans living in North London. PAI-1 activity was measured by a spectrophotometric assay, and insulin, intact proinsulin and des 31,32 proinsulin concentrations were measured employing highly specific monoclonal antibody-based assays. Compared with non-diabetic subjects, PAI-1 activity was significantly higher in subjects with NIDDM among South Asians (22.8 +/- 7.3 vs. 17.4 +/- 6.9 AU/ml, p < 0.001) and Europeans (23.1 +/- 6.6 vs. 16.5 +/- 6.1 AU/ml, p < 0.001) but not among Pima Indians (19.5 +/- 9.6 vs. 18.5 +/- 8.6 AU/ml, ns). The association of PAI-1 activity with diabetes remained statistically significant when controlled for age, sex, body mass index and waist-hip ratio, serum triglyceride and fasting insulin concentrations in South Asians (p < 0.001) and Europeans (p < 0.001). The relationships of PAI-1 activity with clinical and biochemical variables were similar in the three racial groups other than for fasting and 2 h plasma glucose concentrations which were significantly associated with PAI-1 activity in South Asians (partial r = 0.32 and 0.31) and Europeans (partial r = 0.44 and 0.50) but not in Pima Indians (partial r = 0.11 and 0.15). In Pima Indians with NIDDM, PAI-1 activity was similar in those treated with sulphonylureas, insulin, or no drugs for diabetes. In conclusion, the association of PAI-1 with diabetes differs in racial groups who are at different risk of NIDDM and ischaemic heart disease. Previously reported differences in the prevalence of ischaemic heart disease between diabetic and non-diabetic Pima Indians, and between non-diabetic subjects from the three racial groups, are unlikely to be due to differences in PAI-1 activity. C1 NIDDKD, DIABET & ARTHRITIS EPIDEMIOL SECT, PHOENIX, AZ USA. UCL, SCH MED, DEPT MED, LONDON W1N 8AA, ENGLAND. RI Yudkin, John/C-1988-2008; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 42 TC 15 Z9 15 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1996 VL 75 IS 6 BP 921 EP 927 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA UV560 UT WOS:A1996UV56000011 PM 8822587 ER PT J AU Thomsen, M Cullen, M Carrington, M Foissac, A Abbal, M dePreval, C CrouauRoy, B CambonThomsen, A AF Thomsen, M Cullen, M Carrington, M Foissac, A Abbal, M dePreval, C CrouauRoy, B CambonThomsen, A TI Localization of the recombination points in a family with two DR/DP recombinations SO TISSUE ANTIGENS LA English DT Article DE allele; HLA-D antigen; major histocompatibility complex; recombination linkage disequilibrium; family study; mixed lymphocyte culture ID CLASS-II REGION; MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN MHC; HLA-DP; POLYMORPHISM; POPULATION; GENES; MAP AB In a family with a maternal DR/GLO recombination, cellular DP typing showed it to be located between DR and DP. RFLB studies done during the 9th international histocompatibility workshop gave anomalous segregation patterns of DPA and DPB bands that could be interpreted as being due to a second, paternal DR/DP recombination. This assumption was confirmed later by PCR-SSO typing. A more precise mapping has been done by new markers showing the maternal recombination to be within the TAP2 locus and the paternal recombination to be between DQB1 and DQB3. This supports earlier suggestions of a hot spot of recombination in the TAP region. The recombinations involve parental haplotypes that presently show DR/DP linkage disequilibrium in the French population and it is proposed that DR/DP recombinations occur randomly while B/DR recombinations preferentially occur on haplotypes without strong linkage disequilibrium. Existing DR/DP linkage disequilibria in a given population will thus be broken down with time. The mixed lymphocyte culture response towards an isolated DP difference was tested in this and another DR/DP recombinant family. It showed that an alloresponse towards DP may be highly variable and this suggests that it might be important to define the rules for the strength of this reaction and the possible implications for allotransplantation. C1 CHU PURPAN,UNITE RECH REPONSE IMMUNITAIRE & COMPLEXE MAJEUR,F-31052 TOULOUSE,FRANCE. CHU PURPAN,CTR IMMUNOPATHOL & GENET HUMAINE,F-31052 TOULOUSE,FRANCE. CHU RANGUEIL,IMMUNOL LAB,F-31054 TOULOUSE,FRANCE. NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC,FCDRC,FREDERICK,MD 21701. RP Thomsen, M (reprint author), CHU PURPAN,INSERM U395,F-31052 TOULOUSE,FRANCE. RI Thomsen, Mogens/B-7651-2011 OI Thomsen, Mogens/0000-0002-4546-0129 NR 33 TC 4 Z9 4 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUN PY 1996 VL 47 IS 6 BP 492 EP 497 DI 10.1111/j.1399-0039.1996.tb02591.x PG 6 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA UT073 UT WOS:A1996UT07300007 PM 8813738 ER PT J AU Tabacova, S Hunter, ES Gladen, BC AF Tabacova, S Hunter, ES Gladen, BC TI Developmental toxicity of inorganic arsenic in whole embryo culture: Oxidation state, dose, time, and gestational age dependence SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID SODIUM ARSENITE; MOUSE EMBRYOS; PREGNANT MICE; ORGANOGENESIS; METABOLISM AB Arsenic is a known teratogen and developmental toxicant in many animal models, The aim of the present study was to determine the influence of arsenic oxidation state, concentration, duration of exposure, and embryonic gestational age on arsenic-induced developmental toxicity. For these studies whole embryo culture was used since this experimental model allows an assessment of the direct effect of the toxicant on the embryo and precise control of the variables of interest. ICR and CD1 mouse embryos were prepared for whole embryo culture and exposed to concentrations of trivalent (1, 2, 5, 7.5, 10, 20, and 30 mu M of sodium arsenite) and pentavalent arsenic: (5, 10, 20, 50, and 100 mu M of sodium arsenate) at different developmental stages (3, 4-6, 8-10, or 20-23 pairs of somites) and for different exposure periods (1, 4, 6, or 24 hr). Embryonic growth, development, malformation rates, and viability were evaluated. A comparison of the ED50s of the two oxidation states showed that arsenite was about three times more potent than arsenate with respect to both malformations and lethality. The pattern of malformations was similar for both arsenite and arsenate and involved nonclosure of the cranial neural tube, prosencephalic hypoplasia, dysmorphogenesis of the optic and otic anlagen, and pharyngeal arch defects. ICR conceptuses were more sensitive than CD1s with regard to perturbation in embryonic growth by both forms of arsenic. ICRs were also more sensitive to otic, pharyngeal arch, and somite dysmorphogenesis induced by arsenite. With increasing gestational age there was an increasing resistance to arsenic-induced effects. In comparison to the 4-6 somite stage, the ED50 for induction of dysmorphogenesis was increased about twice at the 8-10 somite and over three Limes ill 20-23 somite stage embryos. Exposure to arsenite/arsenate for a 1-hr period. was sufficient to induce maldevelopment, A 6-hr exposure induced prosencephalic, otic, and optic abnormal development at a rate similar to that produced by a 24-hr exposure. The malformation pattern produced by exposure to arsenite/arsenate in vitro closely corresponds to that produced by maternal administration at the same gestational stage. This indicates that the arsenic embryopathy may be the result of a direct impact of the agent on the conceptus. (C) 1996 Academic Press, Inc. C1 NIEHS,DEV TOXICOL GRP,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. NR 17 TC 20 Z9 20 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN PY 1996 VL 138 IS 2 BP 298 EP 307 DI 10.1006/taap.1996.0128 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UQ791 UT WOS:A1996UQ79100012 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Carriers for precipitating nucleic acids SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID DNA AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column provides some tips for the precipitation of DNA and RNA samples, For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 7 TC 14 Z9 14 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 1996 VL 21 IS 6 BP 224 EP 225 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ659 UT WOS:A1996UQ65900008 PM 8744357 ER PT J AU Hogue, CWV Ohkawa, H Bryant, SH AF Hogue, CWV Ohkawa, H Bryant, SH TI A dynamic look at structures: WWW-Entrez and the Molecular Modeling Database SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID RESOLUTION; TOOL RP Hogue, CWV (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. RI Hogue, Christopher/B-6726-2008 NR 14 TC 51 Z9 50 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 1996 VL 21 IS 6 BP 226 EP 229 DI 10.1016/S0968-0004(96)80021-1 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ659 UT WOS:A1996UQ65900009 PM 8744358 ER PT J AU Kallioniemi, OP AF Kallioniemi, OP TI Comparative genomic hybridization gaining in popularity SO TRENDS IN GENETICS LA English DT Editorial Material C1 UNIV TAMPERE,INST MED TECHNOL,SF-33101 TAMPERE,FINLAND. RP Kallioniemi, OP (reprint author), NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20852, USA. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUN PY 1996 VL 12 IS 6 BP 237 EP 238 DI 10.1016/0168-9525(96)81445-4 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UN429 UT WOS:A1996UN42900013 ER PT J AU Walther, MM Eanes, ED Delaney, TF Travis, WD AF Walther, MM Eanes, ED Delaney, TF Travis, WD TI Bladder calcifications after photodynamic therapy: Analysis of a rare complication SO UROLOGY LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; PHOTORADIATION THERAPY; CALCIUM-OXALATE; TUMORS; MICROCALCIFICATIONS; EXPERIENCE; DIAGNOSIS; CANCER; INSITU; BENIGN AB Objectives. We analyzed bladder calcifications occurring after photodynamic therapy administered for the treatment of superficial bladder cancer, a finding not previously reported after this treatment. Methods. Bladder biopsies from 20 patients undergoing photodynamic therapy were evaluated. Bladder calcifications were identified in 2 patients and analyzed for composition. Results. One patient had diffuse microcrystalline deposition in two biopsies composed of calcium oxalate monohydrate A. A second patient had a focal stone at a healing biopsy site composed of monoclinic calcium hydrogen phosphate dihydrate (brushite) (66%), calcium oxalate (25%), hydroxyapatite (6%), and protein (3%). Conclusions. Rare calcium oxalate and brushite calcifications were identified after photodynamic therapy and presumed to occur because of tissue injury associated with treatment. C1 NCI,NIH,RADIAT ONCOL BRANCH,PATHOL LAB,BETHESDA,MD 20898. NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. RP Walther, MM (reprint author), NCI,NIH,SB,DCS,UROL ONCOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2B-43,10 CTR DR,BETHESDA,MD 20898, USA. NR 39 TC 6 Z9 7 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 1996 VL 47 IS 6 BP 831 EP 835 DI 10.1016/S0090-4295(96)00047-7 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA UT256 UT WOS:A1996UT25600011 PM 8677572 ER PT J AU Devi, SJN AF Devi, SJN TI Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model SO VACCINE LA English DT Article DE conjugate vaccine; Cryptococcus neoformans; humoral protection ID CAPSULAR POLYSACCHARIDE; SOLUBLE POLYSACCHARIDE; MONOCLONAL-ANTIBODIES; PASSIVE-IMMUNIZATION; MICE; IMMUNOGENICITY; MENINGITIS; VIRULENCE; AIDS AB The encapsulated yeast, Cryptococcus neoformans, causes life-threatening meningoencephalitis in immunocompromised humans, especially in AIDS patients. Fatality and relapse rates remain quite high despite aggressive therapy, A conjugate vaccine composed of the cryptococcal capsular glucuronoxylomannan covalently coupled to tetanus toxoid (GXM-TT) was constructed and evaluated. The vaccine elicited high levels of capsular antibodies rut mice by active and passive immunizations and conferred 70-80% protection against a moderate challenge with 10(3) C. neoformans. Monitoring of serum GXM and anti-GXM antibody levels and of incidence of cryptococcal isolation from various organs of mice suggested that presence of vaccine-induced antibodies during the first 4-6 weeks of infection is critical for clearance of cryptococci from various organs, for limiting serum GXM titers from reaching immunosuppressive levels and ultimately for survival. GXM-TT is the first defined fungal vaccine to confer antibody-mediated protection against a systemic mycosis in an animal model. GXM-TT is being evaluated for safety and immunogenicity in healthy and HIV-infected human volunteers at the National Institutes of Health. C1 NICHHD,NIH,DEV & MOL IMMUN LAB,BETHESDA,MD 20892. NR 29 TC 85 Z9 86 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD JUN PY 1996 VL 14 IS 9 BP 841 EP 844 DI 10.1016/0264-410X(95)00256-Z PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VA098 UT WOS:A1996VA09800001 PM 8843625 ER PT J AU Lawrence, JA Steeg, PS AF Lawrence, JA Steeg, PS TI Mechanisms of tumor invasion and metastasis SO WORLD JOURNAL OF UROLOGY LA English DT Article ID PROSTATE CARCINOMA-CELLS; E-CADHERIN EXPRESSION; UROKINASE RECEPTOR; BASEMENT-MEMBRANE; ENDOTHELIAL-CELLS; ADHESION MOLECULE; CELLULAR ADHESION; TISSUE INHIBITOR; BREAST-CARCINOMA; ANGIOGENESIS AB Metastasis is the cascade of events involved in the transition of a malignancy from a localized tumor to the establishment of a distant foci. In this review we define the known stages and the factors involved. The multiplicity of steps involved allows many opportunities for therapeutic intervention. Current research has focused on interruption of a step or a series of steps to limit the spread of cancer. With emphasis on the urologic malignancies, we outline the research thus far accomplished in the field of metastasis. RP Lawrence, JA (reprint author), NCI, PATHOL LAB, WOMENS CANC SECT, BLDG 10, ROOM 2A33, BETHESDA, MD 20892 USA. NR 84 TC 36 Z9 39 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD JUN PY 1996 VL 14 IS 3 BP 124 EP 130 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA UT040 UT WOS:A1996UT04000002 PM 8806190 ER PT J AU Dong, JT RinkerSchaeffer, CW Ichikawa, T Barrett, JC Isaacs, JT AF Dong, JT RinkerSchaeffer, CW Ichikawa, T Barrett, JC Isaacs, JT TI Prostate cancer - Biology of metastasis and its clinical implications SO WORLD JOURNAL OF UROLOGY LA English DT Article ID NORMAL HUMAN CHROMOSOME-11; E-CADHERIN EXPRESSION; HARVEY-RAS ONCOGENE; NIH 3T3 CELLS; NUDE-MICE; SUPPRESSES TUMORIGENICITY; TRANSMEMBRANE PROTEINS; DECREASED EXPRESSION; SYNCYTIUM FORMATION; MOLECULAR-CLONING AB Prostate cancer is one of the most commonly diagnosed cancers and is a major cause of cancer death in men. Although the majority of the diagnosed prostate cancers will remain localized and never produce clinical symptoms during the lifetime of the host, a subset of these cancers will progress to a more malignant state requiring therapeutic intervention. Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. Once this has occurred, definitive therapy is required before the initially localized metastatic cells escape from the prostate. At present, metastatic prostate cancer is incurable. Therefore, there is an urgent need to develop molecular markers that can be used to predict the metastatic potential of prostate cancers. Using somatic cell hybridization, we have demonstrated that acquisition of metastatic ability requires both the loss of metastasis-suppressor funct ion(s) and the activation of oncogenes. In further studies using microcell-mediated chromosomal transfer, we located genes on human chromosome, 8, 10cen-q23, 11p11.2-13, and 17pter-q23, which, when introduced into rat prostatic cancer cells, are capable of suppressing their metastatic ability without affecting their tumorigenicity or growth rate in vivo. Initially we focused upon the human chromosome 11p11.2-13 region to clone metastasis-suppressor gene(s) positionally. One such gene, termed KAI-1, encodes a membrane glycoprotein. KAI-1 has been mapped to the p11.2 region of human chromosome II by fluorescence in-situ hybridization analysis. Expression of KAI-1 has been detected in all normal human tissues thus far tested, including prostate tissue. When introduced into rat metastatic prostatic cancer cells, KAI-1 significantly suppressed the metastasis without affecting the tumor growth rate, KAI-1 expression is high in human normal prostate and benign prostatic hyperplasia but is dramatically lower in cancer cell lines derived from metastatic prostate tumors. C1 JOHNS HOPKINS UNIV HOSP,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. CHIBA UNIV,DEPT UROL,CHIBA,JAPAN. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 63 TC 33 Z9 36 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD JUN PY 1996 VL 14 IS 3 BP 182 EP 189 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA UT040 UT WOS:A1996UT04000009 PM 8806197 ER PT J AU Sanders, JM Burka, LT Matthews, HB AF Sanders, JM Burka, LT Matthews, HB TI Comparative metabolism and disposition of ethoxyquin in rat and mouse .1. Disposition SO XENOBIOTICA LA English DT Article ID ANTIOXIDANT ETHOXYQUIN; OXIDATION-PRODUCTS; EXCRETION; LIVER; 6-ETHOXY-2,2,4-TRIMETHYL-1,2-DIHYDROQUINOLINE; NEPHROTOXICITY; INDUCTION; KIDNEY AB 1. The biological fate of the antioxidant [3-C-14]ethoxyquin (EQ) was investigated in the male F344 rat and the B6C3F(1) mouse following either p.o. or i.v. administration. 2. The disposition of single doses up to 25 mg/kg was similar in the rat and mouse. About 90% of a total dose was excreted in urine and faeces within 24 h post-dosing. In contrast, no more than 60% of a higher dose of 250 mg/kg was excreted within 24 h following p.o. administration. 3. Metabolism of EQ was rapid in both the rat and mouse following either p.o. or i.v. administration. Little or no parent compound was detected in cumulative 24-h excreta. 5. EQ-derived radioactivity bioaccumulated in some tissues following repeated exposure to rat of either 25 or 250 mg/kg by gavage. However, the fold-increases in concentrations of EQ-derived radioactivity in tissues following repeated administration of the higher dose were generally less than those observed following repeated administration of the lower dose. Repeated high dose administration may overcome delayed gastric emptying (observed following single dose administration of 250 mg/kg) and/or lead to auto-induction of EQ metabolism. C1 NIEHS,EXPTL TOXICOL PROGRAM,CHEM BRANCH,RES TRIANGLE PK,NC 27709. NR 27 TC 7 Z9 7 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUN PY 1996 VL 26 IS 6 BP 583 EP 595 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UU761 UT WOS:A1996UU76100002 PM 8810030 ER PT J AU Burka, LT Sanders, JM Matthews, HB AF Burka, LT Sanders, JM Matthews, HB TI Comparative metabolism and disposition of ethoxyquin in rat and mouse .2. Metabolism SO XENOBIOTICA LA English DT Article ID ANTIOXIDANT ETHOXYQUIN; OXIDATION-PRODUCTS; BILIARY-EXCRETION; 6-ETHOXY-2,2,4-TRIMETHYL-1,2-DIHYDROQUINOLINE; ACETAMINOPHEN; LIVER AB 1. The major pathways of ethoxyquin (EQ) metabolism in both the rat and mouse are O-deethylation and conjugation to endogenous substrates. 2. The two major EQ-derived metabolites excreted in rat urine were in the form of sulphate conjugates, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate, and 1,2,3,4-tetrahydro-3,6-dihydroxy-4-methylene-2,2-dimethylquinoline sulphate. The latter apparently arises from an intramolecular rearrangement of the 3,4-epoxide of ethoxyquin. 3. Mouse urine contained one major glucuronide, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline glucuronide as well as one major sulphate conjugate, 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline sulphate. 4. EQ-derived radioactivity was excreted in rat bile, mainly as GSH conjugates, with little unchanged EQ present. Two of the biliary metabolites are glutathione conjugates of ethoxyquin 3,4-epoxide; the third appears to be a conjugate of either ethoxyquin 7,8-epoxide or 2,2,4-trimethylquinol-6-one. RP Burka, LT (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,CHEM BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 20 TC 21 Z9 22 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUN PY 1996 VL 26 IS 6 BP 597 EP 611 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA UU761 UT WOS:A1996UU76100003 PM 8810031 ER PT J AU Brooks, PC Stromblad, S Sanders, LC vonSchalscha, TL Aimes, RT StetlerStevenson, WG Quigley, JP Cheresh, DA AF Brooks, PC Stromblad, S Sanders, LC vonSchalscha, TL Aimes, RT StetlerStevenson, WG Quigley, JP Cheresh, DA TI Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3 SO CELL LA English DT Article ID EXTRACELLULAR-MATRIX; IV COLLAGENASE; ADHESION MOLECULES; UROKINASE RECEPTOR; TUMOR PROGRESSION; METASTASIS; VITRONECTIN; BINDING; EXPRESSION; INHIBITOR AB Cellular invasion depends on cooperation between adhesive and proteolytic mechanisms. Evidence is provided that the matrix metalloproteinase MMP-2 can be localized in a proteolytically active form on the surface of invasive cells, based on its ability to bind directly integrin alpha v beta 3. MMP-2 and alpha v beta 3 were specifically colocalized on angiogenic blood vessels and melanoma cells in vivo. Expression of alpha v beta 3 on cultured melanoma cells enabled their binding to MMP-2 in a proteolytically active form, facilitating cell-mediated collagen degradation. In vitro, these proteins formed an SDS-stable complex that depended on the noncatalytic C-terminus of MMP-2, since a truncation mutant lost the ability to bind alpha v beta 3. These findings define a single cell-surface receptor that regulates both matrix degradation and motility, thereby facilitating directed cellular invasion. C1 Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA. SUNY STONY BROOK, DEPT PATHOL, STONY BROOK, NY 11794 USA. NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. RP Brooks, PC (reprint author), Scripps Res Inst, DEPT IMMUNOL, IMM24 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA-45726, CA-50286]; NHLBI NIH HHS [HL-54444] NR 59 TC 1235 Z9 1267 U1 5 U2 53 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 31 PY 1996 VL 85 IS 5 BP 683 EP 693 DI 10.1016/S0092-8674(00)81235-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UP344 UT WOS:A1996UP34400009 PM 8646777 ER PT J AU Hong, SY IlBak, C Ryu, JH Song, BJ Huh, JW AF Hong, SY IlBak, C Ryu, JH Song, BJ Huh, JW TI Interaction of alpha-ketoglutarate dehydrogenase complex with allosteric regulators detected by a fluorescence probe, 1,1'-bi(4-aniline)naphihalene-5,5'-disulfonic acid, an inhibitor of catalytic activity SO JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE 1,1'-bi(4-aniline)naphthalene-5,5'-disulfonic acid fluorescence; inhibition; alpha-ketoglutarate dehydrogenase complex; ligand interaction ID 2-OXOGLUTARATE DEHYDROGENASE; PYRUVATE-DEHYDROGENASE; ADENINE-NUCLEOTIDES; BOVINE KIDNEY; ISOCITRATE DEHYDROGENASE; CONFORMATIONAL STATES; RAT-HEART; BINDING; ANALOGS; MITOCHONDRIA AB The interaction of alpha-ketoylutarate dehydrogenase complex (alpha-KGDC) with a hydrophobic fluorescent probe [1.1'-bi(4-aniline)naphthalene-5,5'-disulfonic acid] (bis-ANS) was studied. The purified alpha-KGDC was potently inhibited by bis-ANS with an apparent half maximal inhibitory concentration (IC50) of 9.8 mu M at pH 8.0. The catalytic activities of both the E1o and E2o subunits were predominantly inhibited while that of the E3 component was hardly affected. The binding of bis-ANS to the enzyme caused a marked enhancement and blue shift from 523 nm to 482 nm in the fluorescence emission spectrum. The dissociation constant (K-d) and the number of binding sites (n) were calculated to be 0.87 mM and 158, respectively. Allosteric regulators such as purine nucleotides and divalent cations further increased the fluorescence intensity of thr bis-ANS-alpha-KGDC binary complex. These data suggest that the binding of these allosteric regulators to alpha-KGDC may cause the conformational changes in the enzyme and that bis-ANS could be used as a valuable probe to study the interaction of the multi-enzyme complex and its allosteric regulators. C1 KOREA GREEN CROSS CORP, CENT RES INST, YONGIN, SOUTH KOREA. SUNGKYUNKWAN UNIV, DEPT GENET ENGN, SUWON, SOUTH KOREA. DONG A PHARMACEUT CO, RES LABS, YONGIN, SOUTH KOREA. SOOK MYONG WOMENS UNIV, COLL PHARM, SEOUL, SOUTH KOREA. NIAAA, NIH, NEUROGENET LAB, ROCKVILLE, MD 20852 USA. NR 35 TC 1 Z9 2 U1 0 U2 0 PU BIOCHEMICAL SOC REPUBLIC KOREA PI SEOUL PA 538 DOWHA-DONG, SUNG-JEE BLDG B705, MAPO-KU, SEOUL 121-743, SOUTH KOREA SN 1225-8687 J9 J BIOCHEM MOL BIOL JI J. Biochem. Mol. Biol. PD MAY 31 PY 1996 VL 29 IS 3 BP 230 EP 235 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN501 UT WOS:A1996UN50100009 ER PT J AU Damaj, BB McColl, SR Mahana, W Crouch, MF Naccache, PH AF Damaj, BB McColl, SR Mahana, W Crouch, MF Naccache, PH TI Physical association of G(i2)alpha with interleukin-8 receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUTROPHIL-ACTIVATING PEPTIDE-2; G-PROTEIN; CHEMOTACTIC CYTOKINES; GENE-EXPRESSION; HIGH-AFFINITY; GRO-ALPHA; FIBROBLASTS; BINDING; CELLS; LEUKOCYTES AB Interleukin-8 (IL-8), one of the major mediators of the inflammatory response, belongs to a family of chemokines that includes NAP-2 (neutrophil-activating peptide-2) and Gro-alpha and whose biological activities are directed to a great extent toward neutrophils. Two distinct receptors have been described with overlapping, but not identical, binding affinities for IL-8, NAP-2, and Gro-alpha. This study was designed to examine the intracellular pathways activated upon the occupation of each of the IL-8 receptors (IL-8R). The formation of a physical coupling between IL-8 receptors and the alpha-subunit of heterotrimeric G proteins was tested in neutrophils by examining the presence of the former in anti-G alpha immune precipitates. The addition of IL-8 to a suspension of human neutrophils led to a time-dependent detection of IL-8 in anti-G(i2)alpha (raised against amino acids 159-168 (LERIAQSDYI) of G(i2)alpha) and anti-G(t) alpha (raised against the COOH-terminal 10 amino acids (KENLKDCGLF) of G(t) alpha), but not anti-G(q), immunoprecipitates. Similar results were obtained in human 293 cells stably transfected with IL-8RA or IL-8RB. The peptide derived from the COOH-terminal sequence of G(t) inhibited the co-immunoprecipitation of IL-8R and G(i) observed in response to the anti-G(t) alpha and anti-G(i2)alpha antibodies. On the other hand, the G(i2)alpha peptide only inhibited the immunoprecipitation induced by the anti-G(i2)alpha antibody. Peptides derived from G(i1)alpha or G(i3)alpha had no effect in this assay. The introduction of the anti-G(i2)alpha or anti-(t) alpha antibodies or their neutralizing peptides, but not the G(i1)alpha or G(i3)alpha peptides, into 293 IL-8RA or 293 IL-8RB cells completely blocked the calcium responses obtained upon stimulation with IL-8. These results demonstrate that the occupation of either type of IL-8 receptor leads to a physical coupling to the alpha-subunit of G(i2). In addition, the use of the subunit-specific peptides identified two functionally important but distinct regions of G(i) alpha, one involved in receptor/G(i) alpha interaction (KENLKDCGLF) and the other mediating downstream signal transmission (LERIAQSDYI). Finally, the results of this study also validate the use of the transfected 293 cell line as a model for the study of the signal transduction pathway(s) initiated by IL-8. C1 CHU LAVAL,CTR RECH RHUMATOL & IMMUNOL,CTR RECH,ST FOY,PQ G1V 4G2,CANADA. UNIV LAVAL,FAC MED,DEPT MED,ST FOY,PQ G1V 4G2,CANADA. UNIV ADELAIDE,DEPT MICROBIOL & IMMUNOL,ADELAIDE,SA 5001,AUSTRALIA. NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,DIV NEUROSCI,CANBERRA,ACT 2601,AUSTRALIA. NR 43 TC 59 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 31 PY 1996 VL 271 IS 22 BP 12783 EP 12789 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN474 UT WOS:A1996UN47400016 PM 8662698 ER PT J AU Cioce, V Csaky, KG Chan, AML Bottaro, DP Taylor, WG Jensen, R Aaronson, SA Rubin, JS AF Cioce, V Csaky, KG Chan, AML Bottaro, DP Taylor, WG Jensen, R Aaronson, SA Rubin, JS TI Hepatocyte growth factor (HGF)/NK1 is a naturally occurring HGF scatter factor variant with partial agonist antagonist activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY RECEPTOR; EPITHELIAL-CELLS; MOLECULAR-CLONING; FIBROBLAST GROWTH; MET RECEPTOR; MESSENGER-RNA; HORMONE GENE; PROTEIN; IDENTIFICATION; PURIFICATION AB Hepatocyte growth factor/scatter factor (HGF/SF) stimulates cell proliferation, motility, and morphogenesis by activation of its receptor, the c-Met tyrosine kinase. HGF/SF is structurally related to plasminogen, including an amino-terminal hairpin loop, four kringle domains, and a serine protease-like region. A truncated HGF/SF isoform, designated HGF/NK2, which extends through the second kringle domain and behaves as a competitive HGF/SF antagonist, was previously shown to be encoded by an alternative HGF/SF transcript. In this study, we describe a second naturally occurring HGF/SF variant, HGF/NK1, consisting of the HGF/SF amino-terminal sequence and first kringle domain. This product is encoded by a 2-kilobase alternative transcript containing intronic sequence that was contiguous with exon K1b. Analysis of baculovirus-expressed HGF/NR1 revealed that this isoform possesses the heparin binding properties of HGF/SF and modest mitogenic and scattering activity relative to HGF/SF. However, at a 40-fold molar excess, HGF/NK1 inhibited HGF/SF-dependent DNA synthesis. HGF/NK1 stimulated tyrosine phosphorylation of Met, and covalent affinity crosslinking demonstrated a direct HGF/NK1-receptor interaction. These findings establish that the HGF/SF gene encodes multiple alternative products, which include not only a mitogenic agonist (HGF/SF) and a pure antagonist (HGF/NK2) but also a molecule with partial agonist/antagonist properties. C1 NCI, DBS, LCMB, NIH, BETHESDA, MD 20892 USA. MT SINAI MED CTR, DERALD H RUTTENBERT CANC CTR, NEW YORK, NY 10029 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 62 TC 107 Z9 108 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 MAY 31 PY 1996 VL 271 IS 22 BP 13110 EP 13115 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN474 UT WOS:A1996UN47400065 PM 8662798 ER PT J AU Johren, O Saavedra, JM AF Johren, O Saavedra, JM TI Gene expression of angiotensin II receptor subtypes in the cerebellar cortex of young rats SO NEUROREPORT LA English DT Article DE cerebellum; AT(1A), AT(1B), AT(2) receptors; Purkinje cells; in situ hybridization; [I-125]Sar(1)-AngII binding ID MESSENGER-RNA; BRAIN; LOCALIZATION; CLONING; AT1A AB BOTH AT(1) and AT(2) receptors were detected in the cerebellar cortex of 2-week-old rats by [I-125]Sar(1)-angiotensin II binding. In contrast, using in situ hybridization histochemistry we found only AT(1A) and AT(1B) but not AT(2) receptor mRNA in the cerebellar cortex of young rats. Expression of AT(1A) and AT(1B) receptor mRNA was restricted to Purkinje cells and no expression of mRNA coding for either receptor subtype was found in the molecular or granular cell layers. Our results suggest that AT(1) receptors may be located on dendrites of Purkinje cells expressing AT(1A) and AT(1B) receptor mRNA, whereas the AT(2) receptor binding in the molecular layer may be located on nerve terminals of fibers projecting to the cerebellar cortex from distant areas. RP Johren, O (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,10 CTR DR,MSC 1514,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. RI Johren, Olaf/G-6967-2011 NR 24 TC 13 Z9 13 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 31 PY 1996 VL 7 IS 8 BP 1349 EP 1352 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VW303 UT WOS:A1996VW30300003 PM 8856673 ER PT J AU Thomas, DA Ren, K Besse, D Ruda, MA Dubner, R AF Thomas, DA Ren, K Besse, D Ruda, MA Dubner, R TI Application of nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, on injured nerve attenuates neuropathy-induced thermal hyperalgesia in rats SO NEUROSCIENCE LETTERS LA English DT Article DE nitric oxide synthase; N-omega-nitro-L-arginine methyl ester; hyperalgesia; neuropathic pain ID MOUSE; PAIN AB This study tested the ability of a nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), to attenuate behavioral hyperalgesia in a rat model of neuropathic pain [Bennett, G.J. and Xie, Y.-K., Pain, 33 (1988) 87-107]. A mononeuropathy was produced by chronic constriction injury (CCI) of the sciatic nerve. Thermal hyperalgesia was assessed by a reduction of paw withdrawal latency to a noxious heat source. Following CCI, there was significant hyperalgesia in groups of rats treated with D-NAME (n = 7), an inactive isomer of L-NAME,saline (n = 7) or systemic L-NAME (n = 10). In contrast, when L-NAME was applied directly and continuously to the site of CCI (5.0 mu g/mu l per h for up to 2 weeks) via an osmotic pump implanted at the time of the injury, no significant thermal hyperalgesia was observed (n = 8). The results suggest the involvement of nitric oxide in the development and maintenance of thermal hyperalgesia in a rat model of neuropathy. The blockade of nitric oxide production at the site of injury may provide a new approach for treatment of neuropathic pain. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. NR 17 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 31 PY 1996 VL 210 IS 2 BP 124 EP 126 DI 10.1016/0304-3940(96)12670-7 PG 3 WC Neurosciences SC Neurosciences & Neurology GA UQ242 UT WOS:A1996UQ24200014 PM 8783289 ER PT J AU Cahill, L Haigler, HJ AF Cahill, L Haigler, HJ TI Hippocampal cell death SO SCIENCE LA English DT Letter C1 NIMH,ROCKVILLE,MD 20857. RP Cahill, L (reprint author), UNIV CALIF IRVINE,CTR NEUROBIOL LEARNING & MEMORY,IRVINE,CA 92717, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 31 PY 1996 VL 272 IS 5266 BP 1251 EP 1251 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN472 UT WOS:A1996UN47200007 PM 8650532 ER PT J AU Haynes, BF Pantaleo, G Fauci, AS AF Haynes, BF Pantaleo, G Fauci, AS TI Correlates of protective viruses damaging to HIV infection - Reply SO SCIENCE LA English DT Article C1 NIAID,NIH,BETHESDA,MD 20892. RP Haynes, BF (reprint author), DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 31 PY 1996 VL 272 IS 5266 BP 1362 EP 1362 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN472 UT WOS:A1996UN47200057 ER PT J AU Hoofnagle, JH Lau, D AF Hoofnagle, JH Lau, D TI Chronic viral hepatitis - Benefits of current therapies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RECOMBINANT INTERFERON-ALFA; CONTROLLED TRIAL RP Hoofnagle, JH (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 10 TC 40 Z9 40 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 30 PY 1996 VL 334 IS 22 BP 1470 EP 1471 DI 10.1056/NEJM199605303342210 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UM493 UT WOS:A1996UM49300010 PM 8618588 ER PT J AU Proschan, MA AF Proschan, MA TI On the distribution of the unpaired t-statistic with paired data SO STATISTICS IN MEDICINE LA English DT Article AB I derive the exact distribution of the unpaired t-statistic computed when the data actually come from a paired design. I use this to prove a result Diehr er al. obtained by simulation, namely that the type I error rate of this procedure is no greater than alpha regardless of the sample size. I provide a formula to use in computation of power and type I error rate. RP Proschan, MA (reprint author), NHLBI,ROCKLEDGE CTR 2,6701 ROCKLEDGE DR,MSC 7938,BETHESDA,MD 20892, USA. NR 14 TC 15 Z9 15 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 1996 VL 15 IS 10 BP 1059 EP 1063 DI 10.1002/(SICI)1097-0258(19960530)15:10<1059::AID-SIM219>3.0.CO;2-2 PG 5 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UP287 UT WOS:A1996UP28700008 PM 8783442 ER PT J AU Linet, MS Nyren, O Gridley, G Mellemkjaer, L McLaughlin, JK Olsen, JH Adami, HO Fraumeni, JF AF Linet, MS Nyren, O Gridley, G Mellemkjaer, L McLaughlin, JK Olsen, JH Adami, HO Fraumeni, JF TI Risk of cancer following splenectomy SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NON-HODGKIN-LYMPHOMA; TRANSPLANT RECIPIENTS; RHEUMATOID-ARTHRITIS; SPLENIC FUNCTION; MORTALITY; LEUKEMIA AB Only 2 small population-based studies have previously evaluated cancer risk in splenectomized patients. Our objective was thus to investigate cancer incidence following splenectomy for external trauma or for surgical treatment of non-malignant conditions of adjacent organs. Using the unique personal identification number assigned to each Swedish resident, we linked centralized hospitalization records with nationwide total population and cancer incidence data. We excluded cancers diagnosed within the first 12 months after splenectomy and computed standardized incidence ratios for 1,295 patients (contributing 14,390 person-years) splenectomized for external trauma and for 985 patients (contributing 8,911 person-years) whose splenectomy accompanied surgical treatment of nonmalignant conditions of adjacent organs (mostly peptic ulcers), using age-, sex- and period-specific rates for cancer incidence derived from the entire Swedish population. Patients undergoing splenectomy for external trauma had no significant excess of total or site-specific cancers. Individuals splenectomized in conjunction with surgery for non-malignant conditions of adjacent organs had a non-significant 40% elevated risk of total cancer, with significant increases of lung and ovarian cancers. The excesses of lung and ovarian cancers may be due to chance, but we could not exclude the conditions for which the surgery was performed, other treatments or common predisposing factors (such as cigarette smoking, which has been linked with both peptic ulcer and lung cancer). (C) 1996 Wiley-Liss, Inc. C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. INT EPIDEMIOL INST,ROCKVILLE,MD. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Linet, MS (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPN 415,6130 EXECUT BLVD MSC7368,BETHESDA,MD 20892, USA. NR 28 TC 30 Z9 31 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 29 PY 1996 VL 66 IS 5 BP 611 EP 616 DI 10.1002/(SICI)1097-0215(19960529)66:5<611::AID-IJC5>3.0.CO;2-W PG 6 WC Oncology SC Oncology GA UN037 UT WOS:A1996UN03700005 PM 8647621 ER PT J AU Quinton, TM Brown, KD Dean, WL AF Quinton, TM Brown, KD Dean, WL TI Inositol 1,4,5-trisphosphate-mediated Ca2+ release from platelet internal membranes is regulated by differential phosphorylation SO BIOCHEMISTRY LA English DT Article ID AMP-DEPENDENT PHOSPHORYLATION; PROTEIN KINASE-C; CYCLIC-AMP; TRISPHOSPHATE RECEPTOR; SIGNAL TRANSDUCTION; CA-2+ RELEASE; CALCIUM; STIMULATION; VESICLES; LIVER AB Platelets are activated by an increase in cytosolic Ca2+, and a portion of this increase is derived from inositol 1,4,5-trisphosphate (InsP(3))-mediated Ca2+ release from internal stores via the InsP(3) receptor. Cytosolic cAMP inhibits platelet activation, and experiments were designed to determine if cAMP-dependent phosphorylation affects the rate of InsP(3)-mediated Ca2+ release. Western blotting of platelet internal membranes with anti-InsP(3) receptor and anti-actin binding protein antibodies revealed that the platelet contains type 1 InsP(3) receptor and that it is distinct from actin binding protein. The platelet InsP(3) receptor was shown to be phosphorylated by endogenous, membrane-bound kinases as well as by exogenous protein kinase A. Prior phosphorylation of the InsP(3) receptor by endogenous kinases inhibited additional protein kinase A-dependent phosphorylation by 60%. Furthermore, endogenous phosphorylation resulted in a 2-fold increase in the InsP(3)-mediated Ca2+ release rate relative to dephosphorylated controls. Following endogenous phosphorylation, additional phosphorylation by protein kinase A returned the Ca2+ release rate to control values, while protein kinase A-dependent phosphorylation of dephosphorylated membranes did not affect the release rate. These results suggest that the InsP(3) receptor within intact platelets is phosphorylated by endogenous kinases which results in a high InsP(3)-mediated Ca2+ release rate, and that increases in cAMP result in additional phosphorylation that inhibits Ca2+ release, thus contributing to inhibition of platelet activation. C1 UNIV LOUISVILLE, SCH MED, DEPT BIOCHEM, LOUISVILLE, KY 40292 USA. NATL CTR HUMAN GENOME RES, LAB GENE TRANSFER, NIH, BETHESDA, MD 20892 USA. NR 49 TC 23 Z9 23 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 MAY 28 PY 1996 VL 35 IS 21 BP 6865 EP 6871 DI 10.1021/bi960128m PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN288 UT WOS:A1996UN28800040 PM 8639638 ER PT J AU Brinkmann, U Brinkmann, E Gallo, M Scherf, U Pastan, I AF Brinkmann, U Brinkmann, E Gallo, M Scherf, U Pastan, I TI Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis SO BIOCHEMISTRY LA English DT Article ID ELONGATION FACTOR-II; DIPHTHERIA-TOXIN; DNA FRAGMENTATION; ADP-RIBOSYLATION; CELL-LYSIS; THYMOCYTES; CYTOLYSIS; LIGAND AB We have previously isolated by expression/selection cloning plasmids containing human cDNAs that rendered MCF-7 breast cancer cells resistant to immunotoxins, Pseudomonas exotoxin (PE), and diphtheria toxin (DT) [Brinkmann et al. (1995) Mel. Med. I, 206-216]. Here we describe that one of these resistant plasmids, which contains an antisense cDNA fragment homologous to the yeast chromosome segregation gene CSE1 [CAS; Brinkmann et al. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 10427-10431], reduces the intracellular content of the human CSE1 homologue CAS protein. CAS reduction confers resistance not only to the ADP-ribosylating toxins PE and DT, but also to tumor necrosis factor alpha and beta. The resistance was observed as reduced apoptosis. CAS antisense did not affect the cell death induced by staurosporine, cycloheximide, or etoposide. The observation that CAS antisense can interfere with apoptosis mediated by TNF and ADP-ribosylating toxins suggests that CAS may play a role in selected pathways of apoptosis. RP Brinkmann, U (reprint author), NCI,MOLEC BIOL LAB,DBS,NIH,BLDG 37,ROOM 4E16,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 46 TC 71 Z9 73 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 28 PY 1996 VL 35 IS 21 BP 6891 EP 6899 DI 10.1021/bi952829+ PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN288 UT WOS:A1996UN28800043 PM 8639641 ER PT J AU Nielsen, S Terris, J Smith, CP Hediger, MA Ecelbarger, CA Knepper, MA AF Nielsen, S Terris, J Smith, CP Hediger, MA Ecelbarger, CA Knepper, MA TI Cellular and subcellular localization of the vasopressin-regulated urea transporter in rat kidney SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEDULLARY COLLECTING DUCT AB The renal urea transporter (RUT) is responsible for urea accumulation in the renal medulla, and consequently plays a central role in the urinary concentrating mechanism. To study its cellular and subcellular localization, we prepared affinity-purified, peptide-derived polyclonal antibodies against rat RUT based on the cloned cDNA sequence. Immunoblots using membrane fractions from rat renal inner medulla revealed a solitary 97-kDa band. Immunocytochemistry demonstrated RUT labeling of the apical and subapical regions of inner medullary collecting duct (IMCD) cells, with no labeling of outer medullary or cortical collecting ducts. Immunoelectron microscopy directly demonstrated labeling of the apical plasma membrane and of subapical intracellular vesicles of IMCD cells, but no labeling of the basolateral plasma membrane. Immunoblots demonstrated RUT labeling in both plasma membrane and intracellular vesicle-enriched membrane fractions from inner medulla, a subcellular distribution similar to that of the vasopressin-regulated water channel, aquaporin-2.In the outer medulla, RUT labeling was seen in terminal portions of short-loop descending thin limbs. Aside from IMCD and descending thin limbs, no other structures were labeled in the kidney. These results suggest that: (i) the RUT provides the apical pathway for rapid, vasopressin-regulated urea transport in the IMCD, (ii) collecting duct urea transport may be increased by vasopressin by stimulation of trafficking of RUT-containing vesicles to the apical plasma membrane, and (iii) the rat urea transporter may provide a pathway for urea entry into the descending limbs of short-loop nephrons. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. AARHUS UNIV,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. NR 26 TC 154 Z9 155 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 28 PY 1996 VL 93 IS 11 BP 5495 EP 5500 DI 10.1073/pnas.93.11.5495 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN253 UT WOS:A1996UN25300058 PM 8643603 ER PT J AU Gabrilovich, DI Nadaf, S Corak, J Berzofsky, JA Carbone, DP AF Gabrilovich, DI Nadaf, S Corak, J Berzofsky, JA Carbone, DP TI Dendritic cells in antitumor immune responses .2. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors SO CELLULAR IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; PRESENTING CELLS; T-CELLS; IMMUNOTHERAPY; GENERATION; MOUSE AB Antitumor CTL responses were studied in a model tumor bearing a mutant human p53 gene. We found ineffective induction of antitumor CTL in mice bearing these tumors associated with measurable defects in the function of dendritic cells (DC) from these animals, In this study we investigate the mechanism of this defect in mature DC and find that functional DC can be generated by growth from the bone marrow of tumor-bearing animals. Tumor cell supernatants did not affect the function of mature DC obtained from the spleen of tumor-bearing animals, but significantly suppressed the ability to generate functional DC from the bone marrow of control mice in vitro. This suggests that tumor cells may release factors which block early stages of DC maturation from precursors. DC generated from the bone marrow of tumor-bearing mice showed normal potential to stimulate allogeneic T cells, to stimulate anti-mutant p53 peptide-specific cytotoxic T cells, and to induce anti-p53 CTL responses in vivo in control mice. Repeated immunization with peptide-pulsed DC generated from the bone marrow of control mice (every 4-5 days) blocked progression of established tumors. Immunization of mice with peptide-pulsed DC obtained from the spleen of tumor-bearing mice (4 weeks after tumor injection) did not affect the tumor growth, whereas immunization with peptide-pulsed DC generated from bone marrow of tumor-bearing mice resulted in significantly prolonged survival and delayed tumor growth. Tumor progression was associated with change of the balance Th1/Th2 cells in favor of the Th2-like cytokine profile, while effective immunization was associated with a shift to the Th1 phenotype. Thus, frequent immunization of mice with mutant p53 peptide-pulsed DC generated from stem cells of tumor-bearing hosts can induce effective antitumor CTL responses associated with production of Th1 cells and lead to significant antitumor effects. (C) 1996 Academic Press, Inc. C1 NCI,NIH,BETHESDA,MD 20892. RP Gabrilovich, DI (reprint author), UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235, USA. NR 27 TC 182 Z9 189 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY 25 PY 1996 VL 170 IS 1 BP 111 EP 119 DI 10.1006/cimm.1996.0140 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UP125 UT WOS:A1996UP12500014 PM 8665591 ER PT J AU Gomathi, L Fairwell, T Krishna, GA Ferretti, JA Subramanian, S AF Gomathi, L Fairwell, T Krishna, GA Ferretti, JA Subramanian, S TI Three-dimensional structure of some synthetic calmodulin fragments using high resolution NMR, CD, IR and molecular modelling SO CURRENT SCIENCE LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; CALCIUM-BINDING PROTEINS; TROPONIN-C; TRYPTIC FRAGMENTS; CONFORMATIONAL CHANGE; CIRCULAR-DICHROISM; REFINED STRUCTURE; CA-2+ BINDING; ION BINDING; DOMAIN-III AB High resolution two-dimensional NMR complemented by Fourier transform IR and circular dichroism has been employed for the elucidation of three-dimensional Solution structure of several synthetic peptides corresponding to the calcium binding domains of the 148 residue protein calmodulin. The synthetic fragments correspond to the amino acid sequences in the calcium binding domain of the native protein as well as permutation and combination of loops and helices among the four binding sites, The results indicate that the characteristic helix-loop-helix (EF hand motif) is largely lost in fragmenting the peptide, although parts of the peptides show secondary structural characteristics that imply rapid equilibrium between loose helical and beta turn structure. The results also bring about a better ordering of the structure of calcium binding site I when the middle loop is exchanged for the loop in the site IV. Attempts have also been made to simulate the solution structure of some of the fragments using molecular modelling, The modelling studies also bring about a distinct increase in the secondary structural content upon exchanging the loop between calcium binding sites I and IV. C1 INDIAN INST TECHNOL,REG SOPHISTICATED INSTRUMENTAT CTR,MADRAS 600036,TAMIL NADU,INDIA. INDIAN INST TECHNOL,DEPT CHEM,MADRAS 600036,TAMIL NADU,INDIA. NHLBI,NIH,BETHESDA,MD 20892. NR 85 TC 2 Z9 2 U1 2 U2 3 PU CURRENT SCIENCE ASSN PI BANGALORE PA C V RAMAN AVENUE, PO BOX 8005, BANGALORE 560 080, INDIA SN 0011-3891 J9 CURR SCI INDIA JI Curr. Sci. PD MAY 25 PY 1996 VL 70 IS 10 BP 910 EP 927 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UP177 UT WOS:A1996UP17700011 ER PT J AU Struewing, JP Tarone, RE Brody, LC Li, FP Boice, JD AF Struewing, JP Tarone, RE Brody, LC Li, FP Boice, JD TI BRCA1 mutations in young women with breast cancer SO LANCET LA English DT Letter C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. DANA FARBER CANC INST,BOSTON,MA 02115. RP Struewing, JP (reprint author), NCI,BETHESDA,MD 20892, USA. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 5 TC 28 Z9 28 U1 1 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 25 PY 1996 VL 347 IS 9013 BP 1493 EP 1493 DI 10.1016/S0140-6736(96)91732-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UM485 UT WOS:A1996UM48500071 PM 8676668 ER PT J AU Imafuku, I Kamei, M Kanazawa, I Mouradian, MM Okazawa, H AF Imafuku, I Kamei, M Kanazawa, I Mouradian, MM Okazawa, H TI POU transcription factors differentially regulate the D-1A dopamine receptor gene in cultured cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DOMAIN; PROTEIN; EXPRESSION; ACTIVATION; PRODUCTS; BINDING; REGION; OCT-1 AB Transcription is regulated by complex interactions between cis-elements and transcription factors. In this study, we found that members of the POU transcription factor family differentially regulate a cis-element of the human D-1A dopamine receptor gene. The differences in transactivating abilities among POU factors are derived neither from their different binding affinities to the responsive element nor from their interaction with other types of transcription factors, suggesting the participation of coactivators. We also observed that POU family members, when expressed simultaneously, act competitively on this regulatory element. Our findings demonstrate that members of the same transcription factor family result in different outcomes in cultured cells. These observations suggest a novel model for in vivo gene regulation by different members of a transcription factor family through a single cis-element. (C) 1996 Academic Press, Inc. C1 UNIV TOKYO,DEPT NEUROL,MOL NEUROBIOL GRP,TOKYO,JAPAN. NINCDS,EXPTL THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X NR 24 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 24 PY 1996 VL 222 IS 3 BP 736 EP 741 DI 10.1006/bbrc.1996.0813 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UP427 UT WOS:A1996UP42700014 PM 8651914 ER PT J AU Spiegel, S Milstien, S AF Spiegel, S Milstien, S TI Sphingoid bases and phospholipase D activation SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article DE phosphatidic acid; sphingolipids metabolites; signal transduction ID PROTEIN-KINASE-C; PHOSPHATIDIC-ACID PHOSPHOHYDROLASE; CELL-FREE SYSTEM; SWISS 3T3 CELLS; HUMAN-NEUTROPHILS; GROWTH-FACTOR; PLASMA-MEMBRANE; PHOSPHATIDYLCHOLINE BREAKDOWN; PHOSPHOINOSITIDE HYDROLYSIS; GLYCEROLIPID SYNTHESIS AB There is increased interest in physiological functions and mechanisms of action of sphingolipids metabolites, ceramide, sphingosine, and sphingosine-1-phosphate (SPP), members of a new class of lipid second messengers. This review summarizes current knowledge regarding the role of these sphingolipids metabolites in the actions of growth factors and focuses on the second messenger roles of sphingosine and its metabolite, SPP, in the regulation of cell growth. We also discuss possible interactions with intermediates of the well known glycerophospholipid cycle. Sphingosine and SPP generally provide positive mitogenic signals whereas ceramide has been reported to induce apoptosis and cell arrest in several mammalian cell lines. Stimulation of phospholipase D leading to an increase in phosphatidic acid, a positive regulator of cell growth, by sphingosine and SPP, and its inhibition by ceramide; might be related to their opposite effects on cell growth. This also indicates that sphingolipid turnover could regulate the diacylglycerol cycle. Cross-talk between sphingolipid turnover pathways and the diacylglycerol cycle increases complexity of signaling pathways leading to cellular proliferation and adds additional sites of regulation. C1 NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP GEORGETOWN UNIV, MED CTR, DEPT BIOCHEM & MOLEC BIOL, 357 BASIC SCI BLDG, 3900 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. FU NCI NIH HHS [CA61774]; NIGMS NIH HHS [R0I GM43880] NR 87 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 EI 1873-2941 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD MAY 24 PY 1996 VL 80 IS 1-2 BP 27 EP 36 DI 10.1016/0009-3084(96)02543-1 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV999 UT WOS:A1996UV99900004 PM 8681426 ER PT J AU Hahn, H Christiansen, J Wicking, C Zaphiropoulos, PG Chidambaram, A Gerrard, B Vorechovsky, I Bale, AE Toftgard, R Dean, M Wainwright, B AF Hahn, H Christiansen, J Wicking, C Zaphiropoulos, PG Chidambaram, A Gerrard, B Vorechovsky, I Bale, AE Toftgard, R Dean, M Wainwright, B TI A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLOOR PLATE; PROTEIN; GENE; NOTOCHORD AB Drosophila patched is a segment polarity gene required for the correct patterning of larval segments and imaginal discs during fly development and has a close functional relationship with hedgehog. We have isolated a complete human PATCHED cDNA sequence, which encodes a putative protein of 1296 amino acids, and displays 39% identity and 60% similarity to the Drosophila PATCHED protein, Hydropathy analysis suggests that human PATCHED is an integral membrane protein with a pattern of hydrophobic and hydrophilic stretches nearly identical to that of Drosophila patched, In the developing mouse embryo, patched is initially detected within the ventral neural tube and later in the somites and limb buds, Expression in the limb buds is restricted to the posterior ectoderm surrounding the zone of polarizing activity, The results show that patched is expressed in target tissues of sonic hedgehog, a murine homolog of Drosophila hedgehog suggesting that patched/hedgehog interactions have been conserved during evolution. Human PATCHED maps to human chromosome 9q22.3, the candidate region for the nevoid basal cell carcinoma syndrome. Patched expression is compatible with the congenital defects observed in the nevoid basal cell carcinoma syndrome. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP,FREDERICK,MD 21702. UNIV QUEENSLAND,CTR CELLULAR & MOLEC BIOL,BRISBANE,QLD 4072,AUSTRALIA. CTR NUTR & TOXICOL,KAROLINSKA INST,DEPT BIOSCI,S-17157 HUDDINGE,SWEDEN. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Christiansen, Jeffrey/0000-0002-8146-1225; Wicking, Carol/0000-0002-7225-3803 NR 25 TC 152 Z9 157 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12125 EP 12128 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000003 PM 8647801 ER PT J AU Beard, WA Osheroff, WP Prasad, R Sawaya, MR Jaju, M Wood, TG Kraut, J Kunkel, TA Wilson, SH AF Beard, WA Osheroff, WP Prasad, R Sawaya, MR Jaju, M Wood, TG Kraut, J Kunkel, TA Wilson, SH TI Enzyme-DNA interactions required for efficient nucleotide incorporation and discrimination in human DNA polymerase beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; MUTAGENESIS AB In the crystal structure of a substrate complex, the side chains of residues Asn(279), Tyr(271), and Arg(283) of DNA polymerase beta are within hydrogen bonding distance to the bases of the incoming deoxynucleoside 5'-triphosphate (dNTP), the terminal primer nucleotide, and the templating nucleotide, respectively (Pelletier, H., Sawaya, M., R., Kumar, A., Wilson, S. H., and Kraut, J. (1994) Science 264, 1891-1903), We have altered these side chains through individual site-directed mutagenesis, Each mutant protein was expressed in Escherichia coli and was soluble, The mutant enzymes were purified and characterized to probe their role in nucleotide discrimination and catalysis, A reversion assay was developed on a short (5 nucleotide) gapped DNA substrate containing an opal codon to assess the effect of the amino acid substitutions on fidelity, Substitution of the tyrosine at position 271 with phenylalanine or histidine did not influence catalytic efficiency (k(cat)/K-m) or fidelity, The hydrogen bonding potential between the side chain of Asn(279) and the incoming nucleotide was removed by replacing this residue with alanine or leucine, Although catalytic efficiency was reduced as much as 17-fold for these mutants, fidelity was not, In contrast, both catalytic efficiency and fidelity decreased dramatically for all mutants of Arg(283) (Ala > Leu > Lys), The fidelity and catalytic efficiency of the alanine mutant of Arg(283) decreased 160- and 5000-fold, respectively, relative to wild-type enzyme, Sequence analyses of the mutant DNA resulting from short gap filling synthesis indicated that the types of base substitution errors produced by the wild-type and R283A mutant were similar and indicated misincorporations resulting in frequent T . dGTP and A . dGTP mispairing. With R283A, a dGMP was incorporated opposite a template thymidine as often as the correct nucleotide. The x-ray crystallographic structure of the alanine mutant of Arg(283) verified the loss of the mutated side chain, Our results indicate that specific interactions between DNA polymerase beta and the template base, but not hydrogen bonding to the incoming dNTP or terminal primer nucleotide, are required for both high catalytic efficiency and nucleotide discrimination. C1 UNIV TEXAS, MED BRANCH, SEALY CTR MOL SCI, GALVESTON, TX 77555 USA. NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. UNIV CALIF SAN DIEGO, DEPT CHEM, LA JOLLA, CA 92093 USA. RI Wood, Thomas/B-6172-2012 FU NIEHS NIH HHS [ES06676, ES06839]; NIGMS NIH HHS [GM52982] NR 29 TC 173 Z9 174 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12141 EP 12144 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000007 PM 8647805 ER PT J AU Chacko, S Padlan, EA Portolano, S McLachlan, SM Rapoport, B AF Chacko, S Padlan, EA Portolano, S McLachlan, SM Rapoport, B TI Structural studies of human autoantibodies - Crystal structure of a thyroid peroxidase autoantibody Fab SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EGG-WHITE LYSOZYME; 3-DIMENSIONAL STRUCTURE; HUMAN-IMMUNOGLOBULIN; RESOLUTION; FRAGMENT; CLONING; DISEASE; GENES; EXPRESSION; REPERTOIRE AB The three-dimensional structure of the Fab of TR1.9, a high-affinity IgG1,kappa human autoantibody to thyroid peroxidase, was determined crystallographically to a resolution of 2.0 Angstrom. The combining site was found to be relatively flat, like other antibodies to large proteins, Sequence differences from the most closely related germline genes mainly occur at positions occupied by residues with outward-pointing side chains. An increased deformability of the second and third complementarity determining regions of the heavy chain may result from the replacement of two germline asparagines and the presence of several glycines, and may allow ''induced fit'' in the binding to antigen. Four exposed charged residues, resulting from the use of a particular D (diversity) and J (joining) segments in the assembly of the heavy chain, may contribute to the high affinity of antigen binding. The crystal structure of TR1.9 Fab is the first for a human IgG high-affinity autoantibody. C1 NIDDK,NIH,MOLEC BIOL LAB,BETHESDA,MD 20895. UNIV CALIF SAN FRANCISCO,THYROID MOL BIOL UNIT 111T,SAN FRANCISCO,CA 94121. VET AFFAIRS MED CTR,SAN FRANCISCO,CA 94121. FU NIDDK NIH HHS [DK 36182] NR 48 TC 28 Z9 28 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12191 EP 12198 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000015 PM 8647813 ER PT J AU Beard, WA Minnick, DT Wade, CL Prasad, R Won, RL Kumar, A Kunkel, TA Wilson, SH AF Beard, WA Minnick, DT Wade, CL Prasad, R Won, RL Kumar, A Kunkel, TA Wilson, SH TI Role of the ''helix clamp'' in HIV-1 reverse transcriptase catalytic cycling as revealed by alanine-scanning mutagenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; MECHANISM; TEMPLATE; KINETICS; DNA; TERMINATION; INHIBITOR; SEQUENCE; BINDING AB Residues 259-284 of HIV-1 reverse transcriptase exhibit sequence homology with other nucleic acid polymerases and have been termed the ''helix clamp'' (Hermann, T., Meier, T., Gotte, M., and Heumann, H. (1994) Nucleic Acids Res, 22, 4625-4633), since crystallographic evidence indicates these residues are part of two alpha-helices (alpha H and alpha I) that interact with DNA. Alanine-scanning mutagenesis has previously demonstrated that several residues in alpha H make important interactions with nucleic acid and influence frameshift fidelity. To define the role of alpha I (residues 278-286) during catalytic cycling, we performed systematic site directed mutagenesis from position 277 through position 287 by changing each residue, one by one, to alanine, Each mutant protein was expressed and, except for L283A and T286A, was soluble. The soluble mutant enzymes were purified and characterized, In contrast to alanine mutants of alpha H, alanine substitution in alpha I did not have a significant effect on template . primer (T . P) binding as revealed by a lack of an effect on K-m,K-T . P, K-i for 3'-azido-2',3'-dideoxythymidine 5'-triphosphate, k(off,T . P), and processivity. Consistent with these observations, the fidelity of the mutant enzymes was not influenced. However, alanine mutagenesis of alpha I lowered the apparent activity of every mutant relative to wild-type enzyme, Titration of two mutants exhibiting the lowest activity with T . P (L282A and R284A) demonstrated that these mutant enzymes could bind T . P stoichiometrically and tightly, In contrast, active site concentrations determined from ''burst'' experiments suggest that the lower activity is due to a smaller population of enzyme bound productively to T . P. The putative electrostatic interactions between the basic side chains of the helix clamp and the DNA backbone are either very weak or kinetically silent, In contrast, interactions between several residues of alpha H and the DNA minor groove, 3-5 nucleotides from the 3'-primer terminus, are suggested to be critical for DNA binding and fidelity. C1 UNIV TEXAS, MED BRANCH, SEALY CTR MOL SCI, GALVESTON, TX 77555 USA. NIEHS, GENET MOLEC LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NR 36 TC 45 Z9 45 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12213 EP 12220 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000019 PM 8647817 ER PT J AU Tiffany, HL Handen, JS Rosenberg, HF AF Tiffany, HL Handen, JS Rosenberg, HF TI Enhanced expression of the eosinophil-derived neurotoxin ribonuclease (RNS2) gene requires interaction between the promoter and intron SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GRANULE DEFICIENCY; 1ST INTRON; TRANSCRIPTIONAL REGULATION; MOLECULAR-CLONING; CATIONIC PROTEIN; COLLAGEN GENE; HL-60 CELLS; ELEMENTS; SEQUENCE; CONTAINS AB The eosinophil-derived neurotoxin (EDN/RNS2) is a member of the mammalian ribonuclease gene family and is one of four proteins found in the large specific granules of human eosinophilic leukocytes. The gene encoding EDN consists of two exons, including a noncoding exon 1, separated by a single intron from the coding sequence in exon 2. We have identified a functional promoter of the EDN gene and shown that optimal expression depends on interaction between the pro meter and one or more sequence elements found in the single intron. Cells of the clone 15 eosinophilic variant of the human promyelocytic HL-60 cell line were transfected with constructs that included the promoter region of the EDN gene alone, promoter with exon 1, and promoter with both exon 1 and the intron positioned 5' to the chloramphenicol acetyltransferase (CAT) reporter gene (constructs referred to as PrCAT, PrExCAT, and PrExInCAT, respectively). Although reporter gene activity from either PrCAT or PrExCAT was only 2-3 fold higher than baseline (CAT alone), inclusion of the single intron (PrExInCAT) resulted in a 28-fold increase in reporter gene activity in uninduced clone 15 cells, and an 80-fold in activity when clone 15 cells were induced to differentiate toward eosinophils with butyric acid. The intron-mediated enhancer activity was reproduced in other human hematopoietic cell lines (K562, Jurkat, U937, and HL-60), but was not found in human 293 kidney cells, suggesting that the function of the enhancer element(s) may be tissue-specific. A significant portion of the observed enhancer activity resides in the first 60 base pairs the the intron, which includes consensus binding sites for both AP-1 and NF-ATp transcription factors, and a 15-base pair segment that is identical to a sequence found in the promoter of the gene encoding the neutrophil granule protein, lactoferrin. The noncoding exon 1/single intron/coding exon 2 genomic structure is a common feature among the mammalian ribonucleases; this finding suggests the possibility of a conserved mechanism of regulation in this gene family. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,GRAD PROGRAM GENET,WASHINGTON,DC 20052. NR 39 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12387 EP 12393 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000044 PM 8647842 ER PT J AU Redowicz, MJ Korn, ED Rau, DC AF Redowicz, MJ Korn, ED Rau, DC TI Nucleotides increase the internal flexibility of filaments of dephosphorylated Acanthamoeba myosin II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MICROSECOND ROTATIONAL MOTIONS; ACTIVATED ATPASE ACTIVITY; 3 PHOSPHORYLATION SITES; RABBIT PSOAS MUSCLE; HEAVY-CHAIN; ELECTRIC BIREFRINGENCE; STRUCTURAL DIFFERENCE; INTEGRAL-EQUATIONS; SKINNED FIBERS; ACTIN AB The actin-activated Mg2+-ATPase activity of Acanthamoeba myosin II minifilaments is dependent both on Mg2+ concentration and on the state of phosphorylation of three serine sites at the C-terminal end of the heavy chains. Previous electric birefringence experiments on minifilaments showed a large dependence of signal amplitude on the phosphorylation state and Mg2+ concentration, consistent with large changes in filament flexibility. These observations suggested that minifilament stiffness was important for function. We now report that the binding of nucleotides to dephosphorylated minifilaments at Mg2+ concentrations needed for optimal activity increases the flexibility by about 10-fold, as inferred from the birefringence signal amplitude increase. An increase in flexibility with nucleotide binding is not observed for dephosphorylated minifilaments at lower Mg2+ concentrations or for phosphorylated minifilaments at any Mg2+ concentration examined. The relaxation times for minifilament rotations that are sensitive to the conformation myosin heads are also observed to depend on phosphorylation, Mg2+ concentration, and nucleotide binding. These latter experiments indicate that the actin activated Mg2+-ATPase activity of Acanthamoeba myosin II correlates with both changes in myosin head conformation and the ability of minifilaments to cycle between stiff and flexible conformations coupled to nucleotide binding and release. C1 NIDDK,OFF DIRECTOR,NIH,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012; Redowicz, Maria Jolanta/R-4083-2016 NR 40 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12401 EP 12407 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000046 PM 8647844 ER PT J AU Ibeanu, GC Ghanayem, BI Linko, P Li, LP Pedersen, LG Goldstein, JA AF Ibeanu, GC Ghanayem, BI Linko, P Li, LP Pedersen, LG Goldstein, JA TI Identification of residues 99, 220, and 221 of human cytochrome P450 2C19 as key determinants of omeprazole hydroxylase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; AMINO-ACID; SUBSTRATE-SPECIFICITY; LAURATE (OMEGA-1)-HYDROXYLASE; SEQUENCE REQUIREMENTS; CATALYTIC ACTIVITY; MOLECULAR-MODEL; ENZYMES; BINDING; 15-ALPHA-HYDROXYLASE AB Human P450 2C19 is selective for 4'-hydroxylation of S-mephenytoin and 5-hydroxylation of omeprazole, while the structurally homologous P450 2C9 has low activity toward these substrates. To identify the critical amino acids that determine the specificity of human P450 2C19, we constructed chimeras of P450 2C9 replacing various proposed substrate binding sites (SRS) with those of P450 2C19 and then replaced individual residues of P450 2C9 by site directed mutagenesis. The 339 NH2-terminal amino acid residues (SRS-1--SRS-4) and amino acids 160-383 (SRS-2--SRS-5) of P450 2C19 conferred omeprazole 5-hydroxylase activity to P450 2C9. In contrast, the COOH terminus of P450 2C19 (residues 340-490 including SRS-5 and SRS-6), residues 228-339 (SRS-3 and SRS-4) and residues 292-383 (part of SRS-4 and SRS-B) conferred only modest increases in activity. A single mutation Ile(99) --> His increased omeprazole 5-hydroxylase to similar to 51% of that of P450 2C19. A chimera spanning residues 160-227 of P450 2C19 also exhibited omeprazole 5-hydroxylase activity which was dramatically enhanced by the mutation Ile(99) --> His, A combination of two mutations, Ile(99) --> His and Ser(200) --> Pro, converted P450 2C9 to an enzyme with a turnover number for omeprazole 5-hydroxylation, which resembled that of P450 2C19. Mutation of Pro(221) --> Thr enhanced this activity. Residue 99 is within SRS-1, but amino acids 220 and 221 are in the F-G loop and outside any known SRS. Mutation of these three amino acids did not confer significant S-mephenytoin 5-hydroxylase activity to P450 2C9, although chimeras containing SRS-1--SRS-4 and SRS-2--SRS-5 of P450 2C19 exhibited activity toward this substrate. Our results thus indicate that amino acids 99, 220, and 221 are key residues that determine the specificity of P450 2C19 for omeprazole. C1 NIEHS,NIH,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 46 TC 77 Z9 77 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12496 EP 12501 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000059 PM 8647857 ER PT J AU Bai, RL Pei, XF Boye, O Getahun, Z Grover, S Bekisz, J Nguyen, NY Brossi, A Hamel, E AF Bai, RL Pei, XF Boye, O Getahun, Z Grover, S Bekisz, J Nguyen, NY Brossi, A Hamel, E TI Identification of cysteine 354 of beta-tubulin as part of the binding site for the A ring of colchicine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 2,4-DICHLOROBENZYL THIOCYANATE; ANTIMITOTIC AGENT; TAXOL; PROTEIN; CHROMATOGRAPHY; CONFORMATIONS; SEPARATION; MUTANTS; NMR AB The colchicine analog 3-chloroacetyl-3-demethylthiocolchicine (3CTC) is a competitive inhibitor of colchicine binding to tubulin, binds to tubulin at 37 degrees C, but not at 0 degrees C, and covalently reacts with beta-tubulin at 37 degrees C, but not at 0 degrees C, in a reaction inhibited by colchicine site drugs. The approximate intramolecular distance be tween the oxygen at position C-3 in 3CTC and the chlorine atom of the 3-chloroacetyl group is 3 Angstrom. Using decylagarose chromatography, we purified beta-tubulin that had reacted with 3-(chloromethyl-[C-14]carbonyl)-3-demethylthiocolchicine ([C-14]3CTC). This beta-tubulin was digested with formic acid, cyanogen bromide, endoproteinase Glu-C, or endoproteinase Lys C, and the radiolabeled peptide(s) were isolated. The sequences of these peptides indicated that as much as 90% of the covalent reaction between the [C-14]3CTC and beta-tubulin occurred at cysteine 354. This finding indicates that the C-3 oxygen atom of colchicinoids is within 3 Angstrom of the sulfur atom of the Cys-354 residue, suggests that the colchicine A ring lies between Cys-354 and Cys-239, based on the known 9 Angstrom distance between these residues, and may indicate that the tropolone C ring lies between the peptide region containing Cys-239 and the amino-terminal beta-tubulin sequence, based on the labeling pattern observed following direct photoactivation of tubulin-bound colchicine. C1 NCI,MOLEC PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NIDDK,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. US FDA,CTR BIOL EVALUAT & RES,FACIL BIOTECHNOL RESOURCES,BETHESDA,MD 20892. NR 37 TC 82 Z9 90 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12639 EP 12645 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000078 PM 8647876 ER PT J AU Filburn, CR Edris, W Tamatani, M Hogue, B Kudryashova, I Hansford, RG AF Filburn, CR Edris, W Tamatani, M Hogue, B Kudryashova, I Hansford, RG TI Mitochondrial electron transport chain activities and DNA deletions in regions of the rat brain SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE myopathies; electron transport; mitochondrial DNA; oxidative phosphorylation ID CYTOCHROME-C-OXIDASE; SKELETAL-MUSCLE; OXIDATIVE DAMAGE; HUMAN HEARTS; AGE; MUTATIONS; DISEASE; TISSUES; ACCUMULATION; INCREASE AB Deletions in human mitochondrial DNA cause various mitochondrial myopathies and increase markedly with age in highly oxidative tissues, but exhibit a differential distribution in the brain. In order to determine whether a similar pattern occurs in rat brain the levels of a 4.8 kb deletion and electron transport complex activities were measured in the striatum, hippocampus, cerebellum, and cerebral cortex of young adult and senescent male Wistar rats. Deletion-containing mtDNA was present at relatively similar levels (0.0003%) in all regions in 6 mo rats, but increased 25-, 7-, 3-, and 2-fold in the striatum, hippocampus, cerebral cortex, and cerebellum, respectively, of 22-23 mo old rats. To assess the relationship between fractional occurrence of a deletion and oxidative phosphorylation capacity, the activities of mitochondrial respiratory chain complexes I, III, IV and V, the mitochondrial ATP-ase, each of which contains subunits encoded in mtDNA, were determined in homogenates. No age-related decrements in activity were observed in any of the brain regions. Thus, while mtDNA deletions increase with age and to a large extent mirror the pattern observed in the human brain, they appear to have no effect on capacity for oxidative phosphorylation of distinct brain regions. Any reductions in capacity that may be present are likely to occur only at the level of individual cells. C1 NIA,CARDIOVASC SCI LAB,CTR GERONTOL RES,BALTIMORE,MD 21224. RP Filburn, CR (reprint author), NIA,LAB BIOL SCI,CTR GERONTOL RES,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 39 TC 37 Z9 39 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD MAY 24 PY 1996 VL 87 IS 1 BP 35 EP 46 DI 10.1016/0047-6374(96)01696-X PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA UK067 UT WOS:A1996UK06700004 PM 8735905 ER PT J AU Huff, J Bucher, J Barrett, JC AF Huff, J Bucher, J Barrett, JC TI Methylene chloride SO SCIENCE LA English DT Letter ID FEMALE B6C3F1 MICE; INDUCED LUNG; INHALATION; TUMORS; EXPOSURE; LIVER; RATS RP Huff, J (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 15 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 24 PY 1996 VL 272 IS 5265 BP 1083 EP 1084 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UM889 UT WOS:A1996UM88900003 PM 8638144 ER PT J AU TorrenceCampbell, C Bowen, WD AF TorrenceCampbell, C Bowen, WD TI Differential solubilization of rat liver sigma(1) and sigma(2) receptors: Retention of sigma(2) sites in particulate fractions SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sigma receptor; liver, rat; solubilization; CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate; (+)-pentazocine; DTG (1,3-di-o-tolylguanidine) ID GUINEA-PIG BRAIN; BINDING-SITES; H-3 (+)-PENTAZOCINE; MEMBRANES; IDENTIFICATION; (+)-SKF-10,047; DEXTROMETHORPHAN; ENDOCRINE; AFFINITY; POTENT AB Rat liver membranes (crude P-2 membranes) were solubilized in 10 mM Tris-HCl, pH 7.4 containing 7 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). The soluble fraction was designated the Extract 1. The 105 000 x g pellet was washed once, and then extracted a second time (Extract 2). The various resulting fractions were assayed for sigma (sigma) binding characteristics, using [H-3](+)-pentazocine to label sigma(1), sites and [H-3]1,3-di-o-tolylguanidine (DTG) in the presence of 1 mu M dextrallorphan to label sigma(2) sites. Both of the extracts and resultant pellets (Pellet 1 and Pellet 2) contained sigma(1) and sigma(2) receptors, as indicated by the pharmacological profiles upon competition studies. The K-d and B-max values for sigma(1) activity in the original P-2 membranes were 8.3 +/- 0.73 nM and 5333 +/- 572 fmol/mg protein; K-d and B-max for sigma(2) activity was 19 +/- 0.17 nM and 9190 +/- 800 fmol/mg protein. There were no changes in the radioligand K-d values of the two sites in the subsequent soluble and particulate fractions. However, while the sigma(1) and sigma(2) B-max values in extracts and pellets were generally on the same order as those of P-2 membranes, the actual sigma(2) to sigma(1) B-max ratio varied markedly across the fractions. The ratio of sigma(2)/sigma(1) binding in Extract 1 and Extract 2 was 0.86 and 0.68, respectively, compared to a ratio of 1.7 in the original P-2. However, the ratio in Pellet 2 was 3.8, twice that of the original P-2 membranes. Furthermore, the B-max value for sigma(1) sites in Pellet 2 did not change, whereas the sigma(2) B-max increased 1.8 fold relative to the original P-2 membranes. The changes in sigma(2)/sigma(1) binding ratio in extracts were observed using two different assay methods for soluble receptors (retention on polyethyleneimine-coated filters and polyethylene glycol precipitation) and is therefore not an artifact of assay procedure. These data suggest that, relative to sigma(1) receptors, sigma(2) receptors are more resistant to solubilization and become somewhat enriched in the particulate fractions. This supports the notion that sigma(1) and sigma(2) receptors are distinct macromolecules and may indicate different modes of association with the cell membrane. C1 NIDDKD,UNIT RECEPTOR BIOCHEM & PHARMACOL,MED CHEM LAB,BETHESDA,MD 20892. NR 48 TC 15 Z9 16 U1 0 U2 0 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 MAY 23 PY 1996 VL 304 IS 1-3 BP 201 EP 210 DI 10.1016/0014-2999(96)00109-4 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU452 UT WOS:A1996UU45200027 PM 8813603 ER PT J AU Hardy, BJ Gutierrez, A Lesiak, K Seidl, E Widmalm, G AF Hardy, BJ Gutierrez, A Lesiak, K Seidl, E Widmalm, G TI Structural analysis of the solution conformation of methyl 4-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside by molecular mechanics and ab initio calculation, stochastic dynamics simulation, and NMR spectroscopy SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID AQUEOUS-SOLUTION; DIRECT SCF; BETA-CELLOBIOSIDE; INTERNAL MOTIONS; FORCE-FIELD; D-GLUCOSE; WATER; OLIGOSACCHARIDES; OPTIMIZATION; RELAXATION AB Unambiguous determination of the solution conformation of carbohydrates is an important current research challenge. In general, we wish to test the hypothesis that the connecting linkages of these molecules may have significantly greater flexibility than in the crystalline state. In this study we specifically focus on the conformation of the disaccharide methyl 4-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside using 1D and 2D NOESY experiments and molecular modeling. In particular we attempt to discover if ''folded'' conformations of this molecule exist in addition to the more expected crystalline ''extended'' conformations. The modeling calculations, both ab initio and molecular mechanics, indicate that the folded conformations are low in energy and can reasonably be expected to exist in solution if solvent effects, which are difficult to predict accurately, are not too large. The NMR data do not support the existence of the folded conformations in solution as a major population. Minor populations of folded conformations cannot, however, be clearly ruled out by the data. We assert that the glycosidic linkage flexibility hypothesis is not yet disproven for this linkage. C1 FDA BIOPHYS LAB, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. NIH, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. UNIV STOCKHOLM, ARRHENIUS LAB, DEPT ORGAN CHEM, S-10691 STOCKHOLM, SWEDEN. RP Hardy, BJ (reprint author), UNIV OXFORD, PHYS & THEORET CHEM LAB, S PARKS RD, OXFORD OX1 3QZ, ENGLAND. NR 48 TC 21 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD MAY 23 PY 1996 VL 100 IS 21 BP 9187 EP 9192 DI 10.1021/jp953139i PG 6 WC Chemistry, Physical SC Chemistry GA UM677 UT WOS:A1996UM67700081 ER PT J AU Koch, WH Kopsidas, G Meffle, B Levine, AS Woodgate, R AF Koch, WH Kopsidas, G Meffle, B Levine, AS Woodgate, R TI Analysis of chimeric UmuC proteins: Identification of regions in Salmonella typhimurium UmuC important for mutagenic activity SO MOLECULAR & GENERAL GENETICS LA English DT Article DE Escherichia coli; Salmonella typhimurium; SOS mutagenesis; Chimeric proteins; UmuC ID DNA-REPAIR GENES; ESCHERICHIA-COLI; RECA PROTEIN; SOS MUTAGENESIS; CLEAVAGE; OPERON; PLASMID; LT2; UV; ENTEROBACTERIA AB Unlike Escherichia coli, the closely related bacterium Salmonella typhimurium is relatively unresponsive to the mutagenic effects of DNA-damaging agents. Previous experiments have suggested that these phenotypic differences might result from reduced activity of the S. typhimurium UmuC protein. To investigate this possibility, we have taken advantage of the high degree of homology between the UmuC proteins of E. coli and S. typhimurium and have constructed a series of plasmid-encoded chimeric proteins. The possibility that the phenotypic differences might be due to differential expression of the respective UmuC proteins was eliminated by constructing chimeric proteins that retained the first 25 N-terminal amino acids of either of the UmuC proteins (and presumably the same translational signals), but substituting the remaining 397 C-terminal amino acids with the corresponding segments from the reciprocal operon. Constructs expressing mostly E. coli UmuC were moderately proficient for mutagenesis whereas those expressing mostly S. typhimurium UmuC exhibited much lower frequencies of mutation, indicating that the activity of the UmuC protein of S. typhimurium is indeed curtailed. The regions responsible for this phenotype were more precisely localized by introducing smaller segments of the S. typhimurium UmuC protein into the UmuC protein of E. coli. While some regions could be interchanged with few or no phenotypic effects, substitution of residues 212-395 and 396-422 of E. coli UmuC with those from S. typhimurium resulted in reduced mutability, while substitution of residues 26-59 caused a dramatic loss of activity. We suggest, therefore, that the primary cause for the poor mutability of S. typhimurium can be attributed to mutations located within residues 26-59 of the S. typhimurium UmuC protein. C1 NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. US FDA,MOL BIOL BRANCH,WASHINGTON,DC 20204. NR 34 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD MAY 23 PY 1996 VL 251 IS 2 BP 121 EP 129 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UP515 UT WOS:A1996UP51500002 PM 8668121 ER PT J AU Varmus, H Paul, WE AF Varmus, H Paul, WE TI Planning of US AIDS research SO NATURE LA English DT Letter RP Varmus, H (reprint author), NIH,OFF AIDS RES,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 23 PY 1996 VL 381 IS 6580 BP 270 EP 270 DI 10.1038/381270a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UM403 UT WOS:A1996UM40300016 PM 8692260 ER PT J AU Marler, JR AF Marler, JR TI Tissue plasminogen activator for acute ischemic stroke - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Marler, JR (reprint author), NINDS,RT PA STROKE STUDY GRP,NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 23 PY 1996 VL 334 IS 21 BP 1406 EP 1406 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UL251 UT WOS:A1996UL25100023 ER PT J AU Whitcup, SM AF Whitcup, SM TI Kaposi sarcoma of the conjunctiva - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Whitcup, SM (reprint author), NEI,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1545 EP 1545 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900018 ER PT J AU Grimm, RH Flack, JM Grandits, GA Elmer, PJ Neaton, JD Cutler, JA Lewis, C McDonald, R Schoenberger, J Stamler, J AF Grimm, RH Flack, JM Grandits, GA Elmer, PJ Neaton, JD Cutler, JA Lewis, C McDonald, R Schoenberger, J Stamler, J TI Long-term effects on plasma lipids of diet and drugs to treat hypertension SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FACTOR INTERVENTION TRIAL; CORONARY HEART-DISEASE; SERUM-CHOLESTEROL; BLOOD-PRESSURE; MILD HYPERTENSION; RISK; LIPOPROTEINS; MRFIT; PARTICIPANTS; DIURETICS AB Objective.-To compare long-term plasma lipid changes among 6 antihypertensive treatment interventions for stage I (mild) hypertension. Design.-Multicenter, randomized, double-blind, parallel-group clinical trial. Setting.-Four academic clinical research units in the United States. Participants.-A total of 902 men and women, aged 45 to 69 years, with stage I diastolic hypertension (diastolic blood pressure <100 mm Hg), recruited from 11 914 persons screened in their communities. Interventions.-Participants were randomized to 1 of 6 treatment groups: (1) placebo, (2) beta-blocker (acebutolol), (3) calcium antagonist (amlodipine), (4) diuretic (chlorthalidone), (5) alpha(1)-antagonist (doxazosin), and (6) angiotensin-converting enzyme inhibitor (enalapril). All groups received intensive lifestyle counseling to achieve weight loss, dietary sodium and alcohol reduction, and increased physical activity. Main Outcomes Measures.-Changes in plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides from baseline to annual visits through 4 years. Results.-Mean changes in all plasma lipids were favorable in all groups. The degree of weight loss with fat-modified diet and exercise was significantly related to favorable lipid changes. Significant differences (P<.01) among groups for average changes during follow-up in each lipid were observed. Decreases in plasma total cholesterol and LDL cholesterol were greater with doxazosin and acebutolol (for plasma total cholesterol, 0.36 and 0.30 mmol/L [13.8 and 11.7 mg/dL], respectively), less with chlorthalidone and placebo (0.12 and 0.13 mmol/L [4.5 and 5.1 mg/dL], respectively). Decreases in triglycerides were greater with doxazosin and enalapril, least with acebutolol. Increases in HDL cholesterol were greater with enalapril and doxazosin, least with acebutolol. Significant relative increases in plasma total cholesterol with chlorthalidone compared with placebo at 12 months were no longer present at 24 months and beyond, when mean plasma total cholesterol for the chlorthalidone group fell below baseline. Analyses of participants continuing to receive chlorthalidone throughout the 4 years of follow-up indicated this was not due solely to an increasing percentage of participants changing or discontinuing use of medication during follow-up. Conclusions.-Weight loss with a fat-modified diet plus increased exercise produces favorable long-term effects on blood pressure and all plasma lipid fractions of adults with stage I hypertension; blood pressure reduction is enhanced to a similar degree by addition of a drug from any one of 5 classes of antihypertensive medication. These drugs differ quantitatively in influencing the degree of long-term favorable effects on blood lipids obtained with nutritional-hygienic treatment. C1 UNIV MINNESOTA,SCH MED,DIV CARDIOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT INTERNAL MED,DIV GEN MED,MINNEAPOLIS,MN 55455. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,CTR HYPERTENS,WINSTON SALEM,NC. UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV ALABAMA,SCH MED,DEPT MED,BIRMINGHAM,AL. UNIV PITTSBURGH,DEPT MED,PITTSBURGH,PA. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PREVENT MED,CHICAGO,IL 60612. NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,CHICAGO,IL. FU NHLBI NIH HHS [R01-HL34767] NR 33 TC 113 Z9 116 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1549 EP 1556 DI 10.1001/jama.275.20.1549 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900026 PM 8622245 ER PT J AU Levy, D Larson, MG Vasan, RS Kannel, WB Ho, KKL AF Levy, D Larson, MG Vasan, RS Kannel, WB Ho, KKL TI The progression from hypertension to congestive heart failure SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; HYPERTROPHIC CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; DIASTOLIC DYSFUNCTION; UNITED-STATES; FRAMINGHAM; MORTALITY; DISEASE; POPULATION; PREVALENCE AB Objectives.-To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. Design.-Inception cohort study. Setting.-General community. Participants.-Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. Exposure Measures.-Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations. Outcome Measure.-The development of CHF. Results.-A total of 5143 eligible subjects contributed 72 422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years. Conclusions.-Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality. C1 NHLBI,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. RP Levy, D (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC38038] NR 55 TC 1000 Z9 1046 U1 3 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1557 EP 1562 DI 10.1001/jama.275.20.1557 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900027 PM 8622246 ER PT J AU Obarzanek, E Velletri, PA Cutler, JA AF Obarzanek, E Velletri, PA Cutler, JA TI Dietary protein and blood pressure SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID RENAL FUNCTIONAL RESERVE; SPONTANEOUSLY HYPERTENSIVE RATS; NITRIC-OXIDE PATHWAY; AMINO-ACIDS; VEGETARIANS; CHOLESTEROL; DISEASE; HEMODYNAMICS; MECHANISMS; RELEASE AB Objective.-To review published and presented data on the relationship between dietary protein and blood pressure in humans and animals. Data Sources.-Bibliographies from review articles and books on diet and blood pressure that had references to dietary protein. The bibliographies were supplemented with computerized MEDLINE search restricted to English language and abstracts presented at epidemiologic meetings. Study Selection.-Observational and intervention studies in humans and experimental studies in animals. Data Extraction.-In human studies, systolic or diastolic blood pressure were outcome measures, and dietary protein was measured by dietary assessment methods or by urine collections. In animal studies, blood pressure and related physiological effects were outcome measures, and experimental treatment included protein or amino acids. Data Synthesis.-Historically, dietary protein has been thought to raise blood pressure; however, studies conducted in japan raised the possibility of an inverse relationship. Data analyses from subsequent observational studies in the United States and elsewhere have provided evidence of an inverse relationship between protein and blood pressure. However, intervention studies have mostly found no significant effects of protein on blood pressure. Few animal studies have specifically examined the effects of increased dietary protein on blood pressure. Conclusions.-Because of insufficient data and limitations in previous investigations, better controlled and adequately powered human studies are needed to assess the effect of dietary protein on blood pressure. In addition, more research using animal models, in which experimental conditions are highly controlled and detailed mechanistic studies can be performed, is needed to help provide experimental support for or against the protein-blood pressure hypothesis. C1 NHLBI,DIV HEART & VASC DIS,BETHESDA,MD 20892. RP Obarzanek, E (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,2 ROCKLEDGE CTR,MSC 7936,6701 ROCKLEDGE DR,ROOM 8,BETHESDA,MD 20892, USA. NR 52 TC 101 Z9 104 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1598 EP 1603 DI 10.1001/jama.275.20.1598 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900033 PM 8622252 ER PT J AU Lenfant, C AF Lenfant, C TI High blood pressure - Some answers, new questions, continuing challenges SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID DIETARY SALT RP Lenfant, C (reprint author), NHLBI, NIH, ROOM 5A52, BLDG 31, BETHESDA, MD 20892 USA. NR 24 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1996 VL 275 IS 20 BP 1604 EP 1606 DI 10.1001/jama.275.20.1604 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA UL029 UT WOS:A1996UL02900034 PM 8622253 ER PT J AU Balagopalakrishna, C Manoharan, PT Abugo, OO Rifkind, JM AF Balagopalakrishna, C Manoharan, PT Abugo, OO Rifkind, JM TI Production of superoxide from hemoglobin-bound oxygen under hypoxic conditions SO BIOCHEMISTRY LA English DT Article ID ACTIVATED BLEOMYCIN; MECHANISM; AUTOXIDATION; OXYHEMOGLOBIN; MYOGLOBIN; IRON; GENERATION; RADICALS; COMPLEX; DNA AB By low temperature electron paramagnetic resonance we have detected the formation of a free radical signal during incubation of partially oxygenated hemoglobin at 235 K. The observed signal has g(parallel to) = 2.0565 and g(perpendicular to) = 2.0043, consistent with the previously reported values for superoxide. The presence of additional EPR signals for oxygen-17 bound hemoglobin, with ((O17-O17))A(perpendicular to) = 63 G and ((O17-O16))A(perpendicular to) = 94 G under identical conditions, confirms the presence of a radical containing two nonequivalent oxygens as required for a superoxide in magnetically inequivalent environments, The superoxide radical has not previously been directly detected during hemoglobin autoxidation because of its rapid dismutation. Our ability to follow the formation of superoxide for more than 15 min is attributed to its production in the hydrophobic heme pocket where dismutation is slow. The enhanced production of this free radical at intermediate oxygen pressures is shown to coincide with enhanced rates of hemoglobin autoxidation for partially oxygenated intermediates. The formation of superoxide in the heme pocket under these conditions is attributed to enhanced heme pocket flexibility, Greater flexibility facilitates distal histidine interactions which destabilize the iron-oxygen bond resulting in the release of superoxide radical into the heme pocket. C1 NIA,NIH,CELLULAR & MOLEC BIOL LAB,MOLEC DYNAM SECT,CTR GERONTOL RES,BALTIMORE,MD 21224. INDIAN INST TECHNOL,REG SOPHISTICATED INSTRUMENTAT CTR,DEPT CHEM,MADRAS 600036,TAMIL NADU,INDIA. NR 37 TC 87 Z9 90 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 21 PY 1996 VL 35 IS 20 BP 6393 EP 6398 DI 10.1021/bi952875+ PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UM512 UT WOS:A1996UM51200029 PM 8639585 ER PT J AU Keefer, MC Graham, BS McElrath, MJ Matthews, TJ Stablein, DM Corey, L Wright, PF Lawrence, D Fast, PE Weinhold, K Hsieh, RH Chernoff, D Dekker, C Dolin, R AF Keefer, MC Graham, BS McElrath, MJ Matthews, TJ Stablein, DM Corey, L Wright, PF Lawrence, D Fast, PE Weinhold, K Hsieh, RH Chernoff, D Dekker, C Dolin, R TI Safety and immunogenicity of Env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LYMPHOCYTE PROLIFERATIVE RESPONSES; GP160 SUBUNIT VACCINE; RECOMBINANT GP160; NEUTRALIZING ANTIBODIES; ENVELOPE PROTEIN; CD4+; GP120; RECIPIENTS; INDUCTION; CELLS AB We investigated the safety and immunogenicity of a candidate HIV-1 vaccine, Env 2-3 (Chiron Biocine Co.), in combination with an adjuvant emulsion, MF59, with or without an additional immune modulator, MTP-PE, in 78 healthy HIV-1-seronegative adults. Sixteen subjects participated in a dose escalation study of MTP-PE in MP59 without Env 2-3, given at 0 and 1 months; 48 subjects participated in a study of a fixed dose of 30 mu g of Env 2-3 in MF59 with increasing doses of MTP-PE (0, 5, 10, 25, 50, and 100 mu g), and 14 subjects participated in a study of 100 mu g of Env 2-3 in MF59 without MTP-PE. Subjects were assigned to study groups under a randomized, double-blind allocation. Subjects received immunization at 0, 1, and 6 months, and had the option of receiving a fourth dose at 12-18 months. Env 2-3 in MTP-PE/MF59 was associated with significant reactogenicity, in that severe, although self-limited systemic and/or local reactions occurred in 15 of 30 vaccinees. In contrast, Env 2-3 in MF59 without MTP-PE was relatively well tolerated, and severe local and/or systemic reactions occurred in only 2 of 18 subjects, Env 2-3 stimulated serum antibodies to HIV-1 envelope protein (gp120) as detected by Western blot in 39 of 43 subjects and to HIV-1 virus lysate by EIA in 28 of 43 subjects after three injections. The majority of subjects also developed EIA antibodies to recombinant gp120 (SF-2), gp120 (LAI), and V3 peptide (SF-2). Neutralizing antibodies to the homologous SF-2 strain developed in 30 of 43 and 27 of 34 subjects, and fusion inhibition antibodies in 25 of 43 and 15 of 36 subjects after three and four injections, respectively, Lymphoproliferative responses to the immunogen, Env 2-3, were observed in over 80% of the vaccinees examined, and CD4+ cytotoxic T cell activity directed against HIV-1 was noted transiently in 2 of 20 vaccinees. Addition of MTP-PE to Env 2-3 or increasing the dose of Env 2-3 from 30 to 100 mu g did not augment immunogenicity. Env 2-3 in MF59 was well tolerated and immunogenic in HIV-1-seronegative individuals. The addition of MTP-PE significantly increased reactogenicity, but had little, if any, effect on immunogenicity. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT MED,INFECT DIS UNIT,ROCHESTER,NY 14642. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37232. UNIV WASHINGTON,SEATTLE,WA 98144. DUKE UNIV,SCH MED,DURHAM,NC 27710. EMMES CORP,POTOMAC,MD 20854. NIAID,VACCINE RES & PREVENT PROGRAM,DIV AIDS,ROCKVILLE,MD 20892. CHIRON BIOCINE CORP,EMERYVILLE,CA 94608. FU NIAID NIH HHS [N01-AI-05063, N01-AI-05062, N01-AI-15106] NR 36 TC 52 Z9 56 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 20 PY 1996 VL 12 IS 8 BP 683 EP 693 DI 10.1089/aid.1996.12.683 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UK286 UT WOS:A1996UK28600006 PM 8744579 ER PT J AU Kaplan, DT Clay, JR Manning, T Glass, L Guevara, MR Shrier, A AF Kaplan, DT Clay, JR Manning, T Glass, L Guevara, MR Shrier, A TI Subthreshold dynamics in periodically stimulated squid giant axons SO PHYSICAL REVIEW LETTERS LA English DT Article ID PHASE LOCKING; INFORMATION; SYSTEMS; CHAOS AB Action potentials resulting from periodic stimulation of nerve axons occur at intervals that are irregular at moderate stimulation frequencies. Histograms of the intervals are multimodal, as seen in stochastic resonance. At higher stimulation frequencies, the action potentials are suppressed entirely, leaving only subthreshold dynamics. Return maps constructed from data show that both types of response are governed by the same deterministic one-dimensional description, with an unstable subthreshold fixed point largely accounting for the irregular intervals at moderate stimulation frequencies. C1 MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3G 1Y6,CANADA. NATL INST HLTH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. MARINE BIOL LAB,WOODS HOLE,MA 02543. RP Kaplan, DT (reprint author), MCGILL UNIV,CTR NONLINEAR DYNAM,MONTREAL,PQ H3G 1Y6,CANADA. RI Glass, Leon/C-5732-2008 NR 23 TC 112 Z9 115 U1 0 U2 9 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAY 20 PY 1996 VL 76 IS 21 BP 4074 EP 4077 DI 10.1103/PhysRevLett.76.4074 PG 4 WC Physics, Multidisciplinary SC Physics GA UL247 UT WOS:A1996UL24700049 ER PT J AU Dubois, EP Neszmelyi, A Lotter, H Pozsgay, V AF Dubois, EP Neszmelyi, A Lotter, H Pozsgay, V TI A serendipitous synthesis of cyclokojibiose SO TETRAHEDRON LETTERS LA English DT Article DE anomeric effect; cyclooligosaccharide; internal glycosylation; kojibiose; trichloroacetimidate ID FACILE SYNTHESIS; GLYCOSYL AB The fully protected kojibiosyl trichloroacetimidate 5 undergoes intramolecular cyclization accompanied by expulsion of the O-benzyl protecting group upon activation by a Lewis-acid to give the symmetrical, tricyclic compound 6 which is the first member of an as yet unreported group of cyclooligosaccharides. C1 NICHHD,DEV & MOLEC IMMUN LAB,NIH,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,CENT RES INST CHEM,H-1025 BUDAPEST,HUNGARY. UNIV MUNICH,INST PHARMAZEUT BIOL,D-8033 MUNICH,GERMANY. RI Neszmelyi, Andras/C-3104-2009; Neszmelyi, Andras/A-6323-2010 NR 24 TC 5 Z9 5 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 20 PY 1996 VL 37 IS 21 BP 3627 EP 3630 DI 10.1016/0040-4039(96)00653-3 PG 4 WC Chemistry, Organic SC Chemistry GA UN056 UT WOS:A1996UN05600005 ER PT J AU Drake, JC Allegra, CJ Moran, RG Johnston, PG AF Drake, JC Allegra, CJ Moran, RG Johnston, PG TI Resistance to Tomudex (ZD1694): Multifactorial in human breast and colon carcinoma cell lines SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE resistance; Tomudex; thymidylate synthase; folylpolyglutamate synthetase; colon cancer; breast cancer ID THYMIDYLATE SYNTHASE INHIBITOR; FOLYLPOLYGLUTAMATE SYNTHETASE; ACQUIRED-RESISTANCE; MEMBRANE-TRANSPORT; CCRF-CEM; ACID; SYSTEMS; CANCER; QUANTITATION; MECHANISMS AB ZD1694 (Tomudex; TDX) is a quinazoline antifolate that, when polyglutamated, is a potent inhibitor of thymidylate synthase (TS), the enzyme that converts dUMP to dTMP. Continuous exposure of MCF-7 breast and NCl H630 colon cells to TDX, with stepwise increases in TDX up to 2.0 mu M, resulted in stably resistant cell lines (MCF(TDX) and H630(TDX)) that were highly resistant to TDX. Initial studies revealed 34-fold increase in TS protein levels in MCF(TDX) and a 52-fold increase in TS levels in H630(TDX) cell lines. Despite continued exposure of these cells to 2.0 mu M TDX, TS protein and TS mRNA expression decreased to parental levels in H630(TDX) cells, whereas in MCF(TDX) cells TS mRNA expression and TS protein levels remained elevated. Southern blot analysis revealed a 20-fold TS gene amplification in the MCF(TDX) cell line. TDX uptake was 2-fold higher in resistant MCF(TDX) cells than in parental MCF-7 cells, whereas in H630(TDX) cells TDX uptake was 50-fold less than that observed in parental H630 cells. In contrast, no change in the transport of either leucovorin or methotrexate into H630(TDX) cells was noted when compared with the H630 parental cells. In H630(TDX) cells, folylpolyglutamate synthetase (FPGS) activity was 48-fold less compared to parent H630 cells; however, FPGS mRNA expression was similar in both lines. H630(TDX) cells were also highly resistant to ZD9331, a novel quinazoline TS inhibitor that does not require polyglutamation, suggesting that defective transport by the reduced folate carrier was also an important mechanism of resistance in these cells. In MCF(TDX) and H630(TDX) resistant cells, several mechanisms of resistance are apparent: one increased TS expression; the others evolved over time from increased TS expression to decreased FPGS levels and decreased TDX transport. C1 VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,MASSEY CANC CTR,RICHMOND,VA. RP Drake, JC (reprint author), USN HOSP,NCI,MED ONCOL BRANCH,8901 WISCONSIN AVE,BLDG 8,RM 5101,BETHESDA,MD 20889, USA. NR 27 TC 43 Z9 45 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 17 PY 1996 VL 51 IS 10 BP 1349 EP 1355 DI 10.1016/0006-2952(96)00057-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WC031 UT WOS:A1996WC03100013 PM 8787551 ER PT J AU He, WM Craparo, A Zhu, YY ONeill, TJ Wang, LM Pierce, JH Gustafson, TA AF He, WM Craparo, A Zhu, YY ONeill, TJ Wang, LM Pierce, JH Gustafson, TA TI Interaction of insulin receptor substrate-2 (IRS-2) with the insulin and insulin-like growth factor I receptors - Evidence for two distinct phosphotyrosine-dependent interaction domains within IRS-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL TRANSDUCTION; HEMATOPOIETIC-CELLS; PROTEIN; SHC; PHOSPHORYLATION; SITES; ACIDS AB Insulin receptor substrate 2 (IRS-2) has recently been shown to be a substrate of the insulin receptor (IR), In this study we utilize the yeast two-hybrid system and assays of in vitro interaction to demonstrate that IRS-2 interacts directly with the IR and the insulin-like growth factor I receptor, We show that, like IRS-1, the region of IRS-2 that contains the putative phosphotyrosine binding and SAIN elements (188-591) is sufficient for receptor interaction and that this interaction is dependent upon the NPX(p)Y (where (p)Y is phosphotyrosine) motifs within the juxtamembrane domains of the receptors, In addition to this amino-terminal NPX(p)Y-binding domain, an additional domain of strong interaction was identified in the central region of IRS-2 and was localized between amino acids 591 and 733, This interaction was found to be dependent upon receptor phosphorylation but was NPX(p)Y-independent, This region does not appear to have either an SH2 or a phosphotyrosine binding domain, Both of the interactions could also be demonstrated in vitro using IRS-2 glutathione S-transferase fusion proteins, We conclude that IRS-2, unlike IRS-1, can interact with tyrosine phosphorylated receptors such as the IR and insulin-like growth factor I receptor via multiple independent binding motifs, Our findings suggest the existence of a previously unidentified phosphotyrosine dependent binding domain within the central region of IRS-2. C1 UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,PROGRAM MOLEC & CELLULAR BIOL,BALTIMORE,MD 21201. NCI,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK44093]; NIGMS NIH HHS [GM08181] NR 45 TC 116 Z9 117 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 17 PY 1996 VL 271 IS 20 BP 11641 EP 11645 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL250 UT WOS:A1996UL25000012 PM 8662806 ER PT J AU Jin, DJ AF Jin, DJ TI A mutant RNA polymerase reveals a kinetic mechanism for the switch between nonproductive stuttering synthesis and productive initiation during promoter clearance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PSEUDO-TEMPLATED TRANSCRIPTION; ESCHERICHIA-COLI; RIFAMPICIN-RESISTANT; TRANSCRIBING COMPLEX; PYRBI OPERON; BETA-SUBUNIT; INHIBITION; MUTATIONS; INVITRO; ELONGATION AB During transcription initiation from galP2, one of the two promoters of the Escherichia coli galactose operon with an initially transcribed sequence of pppAUUUC, RNA polymerase (RNAP) is known to engage nonproductive stuttering synthesis, which is sensitive to the concentration of UTP. This study examines the effect of this nonproductive synthesis on promoter clearance and determines other parameters that might affect stuttering synthesis by analyzing a mutant RNAP, RpoB3449, that has altered its function at this process at galP2, RpoB3449 has dramatically diminished stuttering synthesis, and consequently, it has increased the rate of productive initiation due to its enhanced rate of promoter clearance of galP2 compared with wild-type RNAP. Thus, a direct linkage between promoter clearance and productive transcription is demonstrated. The mechanism by which the mutant RNAP has altered the switch between nonproductive stuttering synthesis and productive initiation during promoter clearance is studied. Apparently, RpoB3449 has increased its efficiency in incorporating CTP at the +5 position of the galP2 transcript leading to its reduced stuttering synthesis, indicating that the rate of an RNAP incorporating the CTP after a stretch of uridine residues is important for promoter clearance at galP2. Because RpoB3449 demonstrates ''wild-type'' stuttering synthesis at the mutant galP2 promoter, which contains the 6 residue at the +5 position, it indicates that the mutant RNAP has altered in binding CTP at this context, Further experiments indicate that it is the +5 position per se of the galP2 sequence rather than a particular nucleotide at that position that is critical in determining the switch between the two alternate pathways during transcription initiation, A checkpoint model for the switch between nonproductive and productive initiations during promoter clearance is discussed. RP Jin, DJ (reprint author), NCI,MOLEC BIOL LAB,NIH,BLDG 37,RM 2E14,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 17 PY 1996 VL 271 IS 20 BP 11659 EP 11667 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL250 UT WOS:A1996UL25000015 PM 8662641 ER PT J AU Lee, SST Buters, JTM Pineau, T FernandezSalguero, P Gonzalez, FJ AF Lee, SST Buters, JTM Pineau, T FernandezSalguero, P Gonzalez, FJ TI Role of CYP2E1 in the hepatotoxicity of acetaminophen SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED HEPATIC NECROSIS; PARA-BENZOQUINONE IMINE; RIBONUCLEIC-ACID; TREATED RABBITS; HUMAN-LIVER; IN-VITRO; ETHANOL; RAT; CYTOCHROME-P-450; METABOLISM AB CYP2E1, a cytochrome P-450 that is well conserved across mammalian species, metabolizes ethanol and many low molecular weight toxins and cancer suspect agents. The cyp2e1 gene was isolated, and a mouse line that lacks expression of CYP2E1 was generated by homologous recombination in embryonic stem cells. Animals deficient in expression of the enzyme were fertile, developed normally, and exhibited no obvious phenotypic abnormalities, thus indicating that CYP2E1 has no critical role in mammalian development and physiology in the absence of external stimuli. When cyp2e1 knockout mice were challenged with the common analgesic acetaminophen, they were found to be considerably less sensitive to its hepatotoxic effects than wild-type animals, indicating that this P-450 is the principal enzyme responsible for the metabolic conversion of the drug to its active hepatotoxic metabolite. C1 NCI,MOLEC CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Buters, Jeroen/G-5070-2011; OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 42 TC 372 Z9 376 U1 2 U2 21 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 17 PY 1996 VL 271 IS 20 BP 12063 EP 12067 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL250 UT WOS:A1996UL25000072 PM 8662637 ER PT J AU Sheng, HZ Zhadanov, AB Mosinger, B Fujii, T Bertuzzi, S Grinberg, A Lee, EJ Huang, SP Mahon, KA Westphal, H AF Sheng, HZ Zhadanov, AB Mosinger, B Fujii, T Bertuzzi, S Grinberg, A Lee, EJ Huang, SP Mahon, KA Westphal, H TI Specification of pituitary cell lineages by the LIM homeobox gene Lhx3 SO SCIENCE LA English DT Article ID NUCLEOTIDE-SEQUENCE; EXPRESSION; ONTOGENESIS; MESENCHYME; LETHALITY; INVITRO AB During pituitary organogenesis, the progressive differentiation of distinct pituitary-specific cell lineages from a common primordium involves a series of developmental decisions and inductive interactions. Targeted gene disruption in mice showed that Lhx3, a LIM homeobox gene expressed in the pituitary throughout development, is essential for differentiation and proliferation of pituitary cell lineages, In mice homozygous for the Lhx3 mutation, Rathke's pouch formed but failed to grow and differentiate; such mice lacked both the anterior and intermediate robes of the pituitary. The determination of all pituitary cell lineages, except the corticotrophs, was affected, suggesting that a distinct, Lhx3-independent ontogenetic pathway exists for the initial specification of this lineage. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NR 33 TC 333 Z9 338 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 17 PY 1996 VL 272 IS 5264 BP 1004 EP 1007 DI 10.1126/science.272.5264.1004 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL619 UT WOS:A1996UL61900043 PM 8638120 ER PT J AU Ji, BT Hatch, MC Chow, WH McLaughlin, JK Dai, Q Howe, GR Gao, YT Fraumeni, JF AF Ji, BT Hatch, MC Chow, WH McLaughlin, JK Dai, Q Howe, GR Gao, YT Fraumeni, JF TI Anthropometric and reproductive factors and the risk of pancreatic cancer: A case-control study in Shanghai, China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CARCINOMA; HORMONES AB To examine the possible role of body size and reproductive factors in pancreatic cancer, data were analyzed from a population-based case-control study conducted in Shanghai, China. Cases (n = 451) were permanent residents of Shanghai, 30-74 years of age, newly diagnosed with pancreatic cancer between October 1, 1990, and June 30, 1993. Deceased cases (19%) were excluded from the study. Controls (n = 1,552) were randomly selected from permanent Shanghai residents and frequency-matched to cases by gender and age. Information on body size and reproductive and other possible risk factors was collected through personal interviews. After adjustment for age, income, smoking and other confounders, a positive dose-response relation between body mass index and risk of pancreatic cancer was observed in both sexes. Among women, the risk of pancreatic cancer was significantly associated with number of pregnancies and live births. Compared with 0-2 pregnancies or live births, the odds ratio (OR) for 8 or more pregnancies was 1.90, while that for 5 or more births was 1.88. A modest elevation in risk, independent of parity, was associated with early age at first birth. Risk increased over 40% among women with a first birth at or before age 19 years relative to those at age 26 years or older. Ever use of oral contraceptives was associated with excess risk, though based on small numbers of users. Our findings suggest that, in Shanghai, obesity, gravidity, parity and perhaps use of oral contraceptives are associated with moderate increases in risk of pancreatic cancer, indicating that hormonal determinants deserve further investigation. (C) 1996 Wiley-Liss, Inc. C1 COLUMBIA UNIV, SCH PUBL HLTH, DIV EPIDEMIOL, NEW YORK, NY USA. SHANGHAI CANC INST, DEPT EPIDEMIOL, SHANGHAI, PEOPLES R CHINA. RP Ji, BT (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, 6130 EXECUT BLVD, EPN 431, ROCKVILLE, MD 20852 USA. NR 24 TC 77 Z9 78 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD MAY 16 PY 1996 VL 66 IS 4 BP 432 EP 437 PG 6 WC Oncology SC Oncology GA UL260 UT WOS:A1996UL26000004 PM 8635856 ER PT J AU Futscher, BW Foley, NE GleasonGuzman, MC Meltzer, PS Sullivan, DM Dalton, WS AF Futscher, BW Foley, NE GleasonGuzman, MC Meltzer, PS Sullivan, DM Dalton, WS TI Verapamil suppresses the emergence of P-glycoprotein-mediated multi-drug resistance SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN MYELOMA CELLS; TOPOISOMERASE-II; MALIGNANT-MELANOMA; ACUTE-LEUKEMIA; EXPRESSION; CHEMOTHERAPY; CYCLOSPORINE; INVITRO; LINES; GENE AB Selection protocols were designed to determine whether non-cytotoxic chemomodifiers can influence the evolution of the drug-resistant phenotype. To this end, the human multiple myeloma cell line RPMI 8226 (8226/S) was selected with either doxorubicin, verapamil or doxorubicin plus verapamil. Using this approach low-level multi-drug-resistant (MDR) cell lines were obtained when 8226/S was selected with doxorubicin only or doxorubicin plus verapamil but not with verapamil only. The MDR phenotypes obtained were mechanistically distinct. In doxorubicin only-selected cells (8226/dox4), drug resistance was mediated by over-expression of the MDRI gene and its cognate protein P-glycoprotein. In contrast, the drug resistance seen in the doxorubicin plus verapamil-selected cells was mediated through decreases in topoisomerase II protein levels and catalytic activity and not by P-glycoprotein over-expression. Cells selected with verapamil alone did not become resistant to any of the drugs tested. None of the 3 selected cell lines showed any changes in MRP gene expression when compared with 8226/S. Our results indicate that the inclusion of verapamil during drug selection with doxorubicin influences the drug-resistant phenotype by preventing the selection of MDRI/P-glycoprotein-positive cells. (C) 1996 Wiley-Liss, Inc. C1 UNIV ARIZONA,ARIZONA CANC CTR,BONE MARROW TRANSPLANT PROGRAM,TUCSON,AZ 85724. UNIV ARIZONA,DEPT PHARMACOL,TUCSON,AZ 85724. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV S FLORIDA,H LEE MOFFITT CANC CTR,TAMPA,FL 33682. UNIV S FLORIDA,RES INST,TAMPA,FL 33682. FU NCI NIH HHS [CA 17092, CA 43043] NR 43 TC 51 Z9 52 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 16 PY 1996 VL 66 IS 4 BP 520 EP 525 DI 10.1002/(SICI)1097-0215(19960516)66:4<520::AID-IJC16>3.0.CO;2-B PG 6 WC Oncology SC Oncology GA UL260 UT WOS:A1996UL26000016 PM 8635868 ER PT J AU Heiss, JD Doppman, JL Oldfield, EH AF Heiss, JD Doppman, JL Oldfield, EH TI Treatment of vertebral hemangioma by intralesionaz. Injection of absolute ethanol SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Heiss, JD (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 22 Z9 22 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 1996 VL 334 IS 20 BP 1340 EP 1340 DI 10.1056/NEJM199605163342017 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UK880 UT WOS:A1996UK88000027 PM 8609965 ER PT J AU Yong, LC Brown, CC Schatzkin, A Schairer, C AF Yong, LC Brown, CC Schatzkin, A Schairer, C TI Prospective study of relative weight and risk of breast cancer: The breast cancer detection demonstration project follow-up study, 1979 to 1987-1989 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE age factors; body weight; breast neoplasms; obesity; prospective studies; relative weight ID BODY-MASS INDEX; POSTMENOPAUSAL WOMEN; HEIGHT; SIZE; MENOPAUSE; HORMONES; AGE; ASSOCIATION; ESTROGENS; OBESITY AB Despite extensive research on obesity and breast cancer in recent decades, inconsistencies in the literature exist. The authors examined prospectively the relation between adult relative weight (weight (kg)/height (m)(1.5)) and breast cancer risk in a cohort of 54,896 women aged 31-89 years who had previously participated in the Breast Cancer Detection Demonstration Project, During a mean follow-up period of 7 years, 226 of the premenopausal women and 1,198 of the postmenopausal women developed breast cancer, Analysis was performed using Cox proportional hazards regression methods with age as the underlying time variable and adjusted for the effects of potential confounders, Among postmenopausal women, the risk of breast cancer increased with increasing relative weight (p < 0.05 for trend); relative risk for the highest compared with the lowest quintile for relative weight was 1.3 (95% confidence interval (CI) 1.1-1.6), This association was modified by age at diagnosis, with relative risks of 1.1 (95% CI 0.8-1.4), 1.2 (95% CI 0.8-1.7), and 1.8 (95% CI 1.3-2.5), respectively, for women aged <60, 60-64, and greater than or equal to 65 years, The higher risk of breast cancer among the older and overweight women was largely confined to women whose weights were measured during the postmenopausal but not the premenopausal period, This risk pattern was observed among the naturally menopausal women, but was also apparent in the smaller group of women with bilateral oophorectomy or hysterectomy with one ovary retained. Among premenopausal women, adult relative weight was not associated with breast cancer risk. These findings suggest that the inconsistencies in the literature on obesity and breast cancer may be due in part to the differing age distributions of the populations studied. The authors conclude that prevention of obesity throughout adulthood, particularly after menopause, may help reduce breast cancer among older women. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NR 40 TC 56 Z9 58 U1 1 U2 4 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 1996 VL 143 IS 10 BP 985 EP 995 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UJ609 UT WOS:A1996UJ60900004 PM 8629617 ER PT J AU Shakil, AO Alter, HJ AF Shakil, AO Alter, HJ TI Blood donors with antibody to hepatitis C virus - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20892. RP Shakil, AO (reprint author), UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA 15213, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1996 VL 124 IS 10 BP 931 EP 931 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UJ801 UT WOS:A1996UJ80100028 ER PT J AU Morton, RL David, H OConnor, PM Bustin, M AF Morton, RL David, H OConnor, PM Bustin, M TI Chromosomal proteins HMG-14 and HMG-17 are synthesized throughout the S-Phase in Burkitt's lymphoma SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MOBILITY GROUP PROTEINS; CELL-CYCLE; REPLICATION; GENES; PHOSPHORYLATION; CHROMATIN AB Here we test whether the targeting of chromosomal proteins HMG-14 and HMG-17 to transcriptionally active regions is due to coincidence of the synthesis of these proteins with the replication and assembly of active chromatin. Cells from the Burkitt's lymphoma line CA46 were synchronized with mimosine. The mRNA levels and the protein synthesis rates of HMG-14/-17 were determined at various stages during the S phase. The expression pattern of HMG-14/-17 was essentially constant throughout this phase of the cell cycle. The half-life for HMG-14/-17 protein corresponded to the doubling time of the cells. These results indicate that HMG-14/-17 are synthesized throughout S-phase and persist through the cell cycle. Targeting of HMGs to active genes is not simply due to the timing of their synthesis during S phase. (C) 1996 Academic Press, Inc. C1 NATL CANC INST,NIH,BETHESDA,MD 20852. RI Bustin, Michael/G-6155-2015 NR 19 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 15 PY 1996 VL 222 IS 2 BP 368 EP 373 DI 10.1006/bbrc.1996.0798 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UM277 UT WOS:A1996UM27700030 PM 8670211 ER PT J AU Kaufman, M Leto, T Levy, R AF Kaufman, M Leto, T Levy, R TI Translocation of annexin I to plasma membranes and phagosomes in human neutrophils upon stimulation with opsonized zymosan: Possible role in phagosome function SO BIOCHEMICAL JOURNAL LA English DT Article ID FACTOR RECEPTOR-KINASE; CA-2+-DEPENDENT PHOSPHOLIPID-BINDING; NADPH OXIDASE; LIPOCORTIN-I; SUPEROXIDE GENERATION; PROTEIN LIPOCORTIN; RESPIRATORY BURST; ARACHIDONIC-ACID; HL-60 CELLS; AGGREGATION AB Annexin I in the cytosol of resting neutrophils was translocated to the plasma membranes upon addition of opsonized zymosan (OZ), Maximum translocation could be detected 1 min after stimulation with OZ, and decreased thereafter. Subcellular fractionation studies demonstrated that annexin I could not be detected in the granule fractions in either resting or activated cells, but was found in association with the phagosome fraction. The marked translocation of annexin I was unique to OZ, since formyl-Met-leu-Phe induced only slight translocation of annexin I to the plasma membranes, and phorbol 12-myristate 13-acetate had no effect at all. The mechanism regulating the translocation of annexin I is not clear. Annexin I is not phosphorylated in resting or stimulated cells. The correlation between the elevation in the intracellular calcium ion concentration ([Ca2+](i)) and the degree of translocation of annexin I to the plasma membranes induced by the different stimuli, together with the inhibition of these processes by the addition of EGTA, indicate that the translocation of annexin I can probably be attributed to the rise in [Ca2+](i). However, this cannot be the sole mechanism since ionomycin, which caused an increase in [Ca2+](i) similar to that induced by OZ, was less efficient than OZ in inducing translocation of annexin I. The induction of annexin I translocation to the plasma membrane by OZ, which was the only agent that induced phagosome formation, and the detection of annexin I in the phagosome fraction, suggest that annexin I participates in phagosome function. C1 BEN GURION UNIV NEGEV, SOROKA MED CTR KUPAT HOLIM, FAC HLTH SCI, INFECT DIS LAB, IL-84105 BEER SHEVA, ISRAEL. BEN GURION UNIV NEGEV, SOROKA MED CTR KUPAT HOLIM, FAC HLTH SCI, CLIN BIOCHEM UNIT, IL-84105 BEER SHEVA, ISRAEL. NCI, HOST DEF LAB, NIH, BETHESDA, MD 20892 USA. NR 46 TC 28 Z9 28 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 15 PY 1996 VL 316 BP 35 EP 42 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UM293 UT WOS:A1996UM29300006 PM 8645229 ER PT J AU Mardiney, M Malech, HL AF Mardiney, M Malech, HL TI Enhanced engraftment of hematopoietic progenitor cells in mice treated with granulocyte colony-stimulating factor before low-dose irradiation: Implications for gene therapy SO BLOOD LA English DT Article ID BONE-MARROW CELLS; STEM-CELLS; MOUSE; PROLIFERATION; RADIATION; SPLEEN AB Gene therapy for inherited disorders of blood cells will require both efficient methods for stable gene transfer and nonablative bone marrow conditioning regimens to allow engraftment of modified hematopoietic progenitor cells (HPCs). We have used a sensitive murine system for detecting HPC engraftment using congenic C57BL/6 mice that differ at the Ly5 locus, which encodes the leukocyte common antigen. The system relies on the ability of monoclonal antibodies with specificity for Ly5.1 and Ly5.2 (revised nomenclature: CD45.1 and CD45.2, respectively) to distinguish do-nor and recipient peripheral blood leukocytes after transplantation of purified Sca-1(+) bone marrow-derived HPCs. No detectable engraftment occurred in nonirradiated recipient mice, even when as many as 2.0 x 10(6) Sca-1(+)HPCs were transplanted. However, in mice receiving total body irradiation (TBI), engraftment increased as a function of pretransplantation radiation dose, number of transplanted cells, and time after transplantation. Moreover, mice receiving either granulocyte colony-stimulating factor (G-CSF) or G-CSF + stem cell factor before low-dose TBI (160 cGy) exhibited a marked increase in engraftment compared with mice receiving a vehicle control before low-dose TBI (18.9% and 20.6% v 5.6% at 1 month, respectively; 29% and 35% v 15.1% at 4 months, respectively). Use of growth factor pretreatment even allowed TBI doses as low as 30, 70, or 120 cGy to achieve significant engraftment of donor progenitors (0.3%, 1.5%, and 6.8% at 1 month, respectively; 1.7%, 5.8%, and 13.9% at 4 months, respectively). All animals remained healthy during the observation periods. Thus, growth factor preconditioning of the recipient followed by low-dose TBI may provide an optimal balance between safety and efficacy in achieving required levels of engraftment for gene therapy of blood disorders. C1 NIAID,HOST DEF LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 41 TC 54 Z9 54 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4049 EP 4056 PG 8 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900003 PM 8639760 ER PT J AU Emmons, RVB Reid, DM Cohen, RL Meng, G Young, NS Dunbar, CE Shulman, NR AF Emmons, RVB Reid, DM Cohen, RL Meng, G Young, NS Dunbar, CE Shulman, NR TI Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction SO BLOOD LA English DT Article ID SERUM; MICE; IRRADIATION AB Thrombopoietin (TPO), the ligand for c-mpl, stimulates proliferation of committed megakaryocytic progenitors and induces maturation of megakaryocytes. To better understand factors regulating TPO levels, we measured blood levels of TPO in patients with impaired platelet production due to aplastic anemia (AA) and with platelet destructive disorders, including idiopathic thrombocytopenic purpura (ITP), posttransfusion purpura (PTP), drug purpura (DP), and X-linked thrombocytopenia (XLTP). The TPO receptor capture enzyme immunoassay (EIA) used had a detection limit of similar to 150 to 200 pg/mL. TPO was undetectable in 88 of 89 normal individuals. Eighteen of 19 patients with AA and a mean platelet count (MPC) of 18,000/mu L (2,000 to 61,000/mu L) had markedly elevated TPO levels (mean, 1,467 pg/mL; range, 597 to 3,834 pg/mL). Eight AA patients who responded to immunosuppressive therapy with their MPC increasing to 140,000/mu L (92,000 to 175,000/mu L) had substantial decreases in TPO (mean, 440 pg/mL; range, 193 to 771 pg/mL). Initial TPO levels did not differ significantly between responders and nonresponders. In contrast, all 21 patients with ITP and an MPC of 16,000/mu L (1,000 to 51,000/mu L) had undetectable TPO levels, as did 6 patients with acute PTP or DP and 2 patients with XLTP. Megakaryocyte mass, reflected in the rate of platelet production, appears to be the major determinant of TPO levels in thrombocytopenic patients rather than circulating platelet levels per se. Measurement of serum TPO may be useful in differentiating thrombocytopenias due to peripheral destruction from those due to thrombopoietic failure. C1 NIDDKD,CLIN HEMATOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. GENENTECH INC,S SAN FRANCISCO,CA 94080. RP Emmons, RVB (reprint author), NHLBI,HEMATOL BRANCH,NIH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 39 TC 318 Z9 324 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4068 EP 4071 PG 4 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900005 PM 8639762 ER PT J AU Selleri, C Maciejewski, JP Sato, T Young, NS AF Selleri, C Maciejewski, JP Sato, T Young, NS TI Interferon-gamma constitutively expressed in the stromal microenvironment of human marrow cultures mediates potent hematopoietic inhibition SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; CELL-CYCLE STATUS; APLASTIC-ANEMIA; PROGENITOR CELLS; STEM-CELL; GROWTH-FACTORS; FACTOR-ALPHA; INVITRO; GENE; PROLIFERATION AB Clinical and laboratory studies have suggested involvement of interferon-gamma (IFN-gamma) in the pathophysiology of aplastic anemia. T cells from aplastic anemia (AA) patients secrete IFN-gamma in vitro, activated cytotoxic lymphocytes infiltrate aplastic bone marrow (BM), and IFN-gamma mRNA, not detected in normal BM, is present in BM from most AA patients. Many patients respond to immunosuppressive therapy with antithymocyte globulin and cyclosporine. Using long-term BM cultures (LTBMC) as a tissue culture model of hematopoiesis, we show that IFN-gamma is a potent inhibitor in the longterm culture-initiating cell (LTC-IC) assay, the best in vitro surrogate test for human hematopoietic stem cells, as well as of the output of committed progenitor cells (colony-forming unit-granulocyte-macrophage [CFU-GM] and burst-forming unit-erythroid [BFU-E]). In LTBMC, continuous addition of relatively high IFN-gamma concentrations (1.000 U/mL weekly or 200 U/mL every 2 days) was required for inhibition of secondary colony formation, a measure of LTC-IC number and clonogenicity. To mimick local production of IFN-gamma, human stromal cells were engineered by retroviral-mediated gene transfer to express a transduced IFN-gamma gene. IFN-gamma secreted by stromal cells was far more potent than exogenous IFN-gamma in its effects in the LTC-IC assay. For purified CD34(+) cells, culture in the presence of IFN-gamma stroma dramatically reduced secondary colony numbers as well as production of CFU-GM and BFU-E. Supernatants from these cultures contained only about 20 U/ml of IFN-gamma; this quantity of cytokine, when added to LTBMC, had little effect on hematopoiesis. The mechanism of hematopoietic suppression was related to the inhibition of cell cycle progression and induction of apoptosis of CD34(+) cells. There was no apparent effect of local low-level IFN-gamma production on stromal cell function, as reflected in cell morphology, cell surface phenotype, or expression of hematopoietic growth factor genes. LTBMC with genetically altered stromal cells offers an in vitro model of immune suppression of hematopoiesis in AA and may be helpful in testing certain therapeutic modalities. We infer from our data that local production of low levels of inhibitory cytokine is sufficient to markedly inhibit hematopoiesis and to destroy stem cells and more mature progenitor cells. C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 57 TC 144 Z9 152 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4149 EP 4157 PG 9 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900016 PM 8639773 ER PT J AU Yang, J Galipeau, J Kozak, CA Furie, BC Furie, B AF Yang, J Galipeau, J Kozak, CA Furie, BC Furie, B TI Mouse P-selectin glycoprotein ligand-1: Molecular cloning, chromosomal localization, and expression of a functional P-selectin receptor SO BLOOD LA English DT Article ID GRANULE MEMBRANE-PROTEIN; ENDOTHELIAL LIGAND; MONOCLONAL-ANTIBODY; PLATELET ACTIVATION; PLASMA-MEMBRANE; MYELOID CELLS; GMP-140 BINDS; GENE; MUCIN; CARBOHYDRATE AB A mouse homolog of P-selectin glycoprotein ligand-1 (PSGL-1), a P-selectin receptor on myeloid cells, has been cloned using the human cDNA sequence to probe a cDNA library prepared from the mouse WEHI-3 monocytic cell line and a genomic DNA library prepared from 129/SvJ mouse tissue. The gene flanking the entire open reading frame of 397 amino acids is composed of a single exon. Mouse and human PSGL-1 show an overall similarity of 67% and an identity of 50% and contain a similar domain organization. However, there are 10 threonine/serine-rich decameric repeats in mouse PSGL-1 as compared with 15 threonine-rich repeats in human PSGL-1. When the mouse PSGL-1 cDNA is coexpressed with an alpha 1,3/1,4 fucosyltransferase cDNA in COS cells, a functional protein is expressed on the COS cell surface mediating binding to human P-selectin. The mouse PSGL-1 gene, Selpl, was mapped to a position on mouse chromosome 5 (Chr 5). Northern blot analyses of mouse tissues showed moderate expression of a PSGL-1 mRNA species in most tissues including heart, kidney, liver, muscle, ovary, and stomach and high levels of expression in blood, bone marrow, brain, adipose tissue, spleen, and thymus. Whereas certain mouse myeloid cell lines including PU5-1.8, WEHI-3B, and 32DC13 express high levels of PSGL-1 mRNA, only WEHI-3B and 32DC13 bind to P-selectin; this interaction is blocked by anti-PSGL-1 antibody. WEHI-3B cells bind significantly better to P-selectin than to E-selectin. Although comparable P-selectin binding is observed in 32DC13 cells, these cells bind better to E selectin. Binding of 32DC13 cells to E-selectin is not blocked by anti-PSGL-1 antibody. Treatment of WEHI-3B cells with trypsin or neuraminidase abolished their ability to interact with P-selectin. These results indicate that mouse PSGL-1 has structural and functional homology to human PSGL-1 but is characterized by differences in the composition and number of the decameric repeats. PSGL-1 on mouse myeloid cells is critical for high-affinity binding to P-selectin but not to E-selectin. (C) 1996 by The American Society of Hematology. C1 TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP Yang, J (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,CTR HEMOSTASIS & THROMBOSIS RES,DIV HEMATOL ONCOL,BOSTON,MA 02111, USA. FU NHLBI NIH HHS [HL51926] NR 59 TC 79 Z9 81 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4176 EP 4186 PG 11 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900019 PM 8639776 ER PT J AU Arguello, F Sterry, JA Zhao, YZ Alexander, MRA Shoemaker, RH Cohen, HJ AF Arguello, F Sterry, JA Zhao, YZ Alexander, MRA Shoemaker, RH Cohen, HJ TI Serologic markers to monitor the engraftment, growth, and treatment response of human leukemias in severe combined immunodeficient mice SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NUCLEAR MATRIX PROTEINS; DIPHTHERIA-TOXIN; SCID MICE; MITOTIC APPARATUS; BONE-MARROW; CELL; IMMUNOTOXIN; XENOGRAFTS; METASTASIS AB We have investigated human lactate dehydrogenase (LDH) isoenzymes and human nuclear matrix protein 41/7 (NMP 41/7) as potential serologic markers to monitor the course of human leukemia in severe combined immunodeficient (SCID) mice. Following the transplantation of 10(6) human acute lymphoblastic leukemia (ALL) Nalm-6 cells. human specific LDH isoenzymes were measurable in the serum of SCID mice as early as 7 days after transplantation, although serum total LDH increased in some animals as early as 5 days after transplantation. Human NMP 41/7 was measurable in all animals at day 15 after leukemia cell injection. Serum levels of total LDH, human specific LDH and NMP 41/7 increased progressively over time, reaching total LDH levels as high as 50,000 U/L at day 25 after transplantation. To determine whether the levels of LDH and NMP 41/7 in serum were a reflection of human tumor burden, we studied these serologic markers in SCID mice bearing measurable subcutaneous human neuroblastoma tumors, or compared the serum levels of these markers with the number of human leukemia CD10(+) cells in the bone marrow of the SCID mice. The serum levels of total LDH, human specific LDH isoenzymes, and NMP 41/7 correlated well with tumor burden, and they drastically decreased or disappeared from serum after the human leukemia or neuroblastoma cells were selectively killed with a single intravenous (IV) injection of 1 to 3 mu g diphtheria toxin (DT) (the cellular receptor for DT is present on human cells, but not on mouse cells). Paraplegic mice with central nervous system leukemia completely recovered after DT treatment. We conclude that measurements of serum levels of total LDH, human LDH isoenzymes, and NMP 41/7 are sensitive, quantitative, rapid, and easy to perform serologic methods useful to monitor the engraftment, progression, and treatment response of human leukemia in SCID mice. (C) 1996 by The American Society of Hematology. C1 UNIV ROCHESTER,STRONG MEM HOSP,DIV CLIN LABS,ROCHESTER,NY 14642. STANFORD UNIV,SCH MED,DEPT PEDIAT,STANFORD,CA. RP Arguello, F (reprint author), NATL CANC INST,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702, USA. NR 60 TC 15 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4325 EP 4332 PG 8 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900035 PM 8639792 ER PT J AU Puri, RK Leland, P Obiri, NI Husain, SR Kreitman, RJ Haas, GP Pastan, I Debinski, W AF Puri, RK Leland, P Obiri, NI Husain, SR Kreitman, RJ Haas, GP Pastan, I Debinski, W TI Targeting of interleukin-13 receptor on human renal cell carcinoma cells by a recombinant chimeric protein composed of interleukin-13 and a truncated form of pseudomonas exotoxin A (PE38QQR) SO BLOOD LA English DT Article ID HUMAN B-CELLS; IGE SYNTHESIS; EXPRESSION; IL-13; PROLIFERATION; CYTOKINE; INVITRO; IGG4 AB We have previously shown that human renal cell carcinoma (RCC) cells express large numbers of interleukin-13 receptors (IL-13R), a newly described hemopoietic growth factor receptor. To target tumor cells that express IL-13R. we have produced a chimeric protein composed of human IL-13 and a derivative of Pseudomonas exotoxin A, termed PE38QQR. We report here that IL13-PE38QQR is highly cytotoxic to many human RCC cell lines. IL-13R-negative cell lines or cell lines expressing low numbers of IL-13R (<300 sites/cell) that include human bone marrow-derived cells were not susceptible to the cytotoxic effect of IL13-PE38QQR. The sensitivity of RCC cells to IL13-PE38QQR correlated positively with the density of IL-13R. The cytotoxic activity of IL13-PE38QQR was competed by an excess of IL-13 in a protein synthesis inhibition assay and confirmed by a clonogenic assay. Even though IL-13 and IL-4 are homologues and IL-4R and IL-13R have been proposed to share a receptor subunit, IL-4 did not compete for the cytotoxicity mediated by IL13-toxin on RCC. IL13-PE38QQR competes for [I-125]-lL-13 binding sites on RCC cells, although at a lower affinity than the wild-type recombinant cytokine. Human T-cell, B-cell, and monocytic cell lines are unresponsive to the cytotoxic action of IL13-PE38QQR. Thus, our results indicate that IL13-PE38QQR is highly cytotoxic to human RCC cells, although it is not cytotoxic to a variety of normal hematopoietic cells. IL13-PE38QQR should be further investigated preclinically for the treatment of human RCCs. This is a US government work. There are no restrictions on its use. C1 NCI,MOLEC BIOL LAB,DIV CANC BIOL DIAG & CTR,NIH,BETHESDA,MD 20892. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT SURG,DIV NEUROSURG,HERSHEY,PA. SUNY HLTH SCI CTR,DEPT UROL,SYRACUSE,NY 13210. RP Puri, RK (reprint author), US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,NIH,BLDG 29B,BETHESDA,MD 20892, USA. NR 32 TC 95 Z9 96 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4333 EP 4339 PG 7 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900036 PM 8639793 ER PT J AU Nash, G Hutter, RVP Henson, DE AF Nash, G Hutter, RVP Henson, DE TI Practice protocol for the examination of specimens from patients with lung cancer SO CANCER LA English DT Article ID NEEDLE ASPIRATION BIOPSY; PROGNOSTIC IMPLICATIONS; DIAGNOSIS; MEDIASTINOSCOPY; SURVIVAL; STAGE C1 ST BARNABAS HOSP,DEPT PATHOL,LIVINGSTON,NJ 07039. NCI,EARLY DETECT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Nash, G (reprint author), BAYSTATE MED CTR,DEPT PATHOL,SPRINGFIELD,MA 01107, USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1996 VL 77 IS 10 BP 2167 EP 2174 DI 10.1002/(SICI)1097-0142(19960515)77:10<2167::AID-CNCR31>3.0.CO;2-R PG 8 WC Oncology SC Oncology GA UJ262 UT WOS:A1996UJ26200031 ER PT J AU McLaughlin, JP Schlom, J Kantor, JA Greiner, JW AF McLaughlin, JP Schlom, J Kantor, JA Greiner, JW TI Improved immunotherapy of a recombinant carcinoembryonic antigen vaccinia vaccine when given in combination with interleukin-2 SO CANCER RESEARCH LA English DT Article ID LYMPHOCYTES-T; VIRUS-VACCINE; TUMOR-CELLS; INTERFERON; PROTECTION; DEFINITION; RESPONSES; AUGMENTS; THERAPY; GROWTH AB Interleukin-2 (IL-2) has been an effective immune modulator in several active-specific immunotherapy experimental protocols using either viral or oncolysate-based vaccines. In this report, data indicate that IL-2 administration can appreciably augment the therapeutic effect of a single immunization of a recombinant vaccinia virus-carcinoembryonic antigen (rV-CEA) vaccine using a CEA-expressing syngeneic: experimental murine model system. A single rV-CEA immunization of C57BL/6 mice bearing palpable CEA-positive colon adenocarcinoma tumors results in complete tumor regression in approximately 20% of the mice. The addition of a course of low-dose IL-2 results in complete tumor regression in 60-70% of the mice. Moreover, the combination of rV-CEA and IL-2 induces systemic immunity, which protects those tumor-free mice from subsequent rechallenge with the CEA-expressing tumor cells. No such tumor regression or protection was observed in those mice immunized with the wild-type vaccinia vaccine (V-Wyeth) alone or with IL-2 administration alone. Cellular immune assays revealed that the addition of IL-2 to rV-CEA immunization significantly increased the CEA-specific T-cell proliferative responses as well as the cytolytic T-cell responses when compared with rV-CEA immunization alone. The enhanced CEA-specific immune response, coupled with the improved experimental therapeutic outcome following IL-2 administration, suggests that treatment with that cytokine may effectively substitute for multiple rV-CEA immunizations in active-specific immunotherapy clinical protocols directed at CEA-expressing tumors. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 38 TC 66 Z9 67 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1996 VL 56 IS 10 BP 2361 EP 2367 PG 7 WC Oncology SC Oncology GA UK187 UT WOS:A1996UK18700024 PM 8625312 ER PT J AU Vocke, CD Pozzatti, RO Bostwick, DG Florence, CD Jennings, SB Strup, SE Duray, PH Liotta, LA EmmertBuck, MR Linehan, WM AF Vocke, CD Pozzatti, RO Bostwick, DG Florence, CD Jennings, SB Strup, SE Duray, PH Liotta, LA EmmertBuck, MR Linehan, WM TI Analysis of 99 microdissected prostate carcinomas reveals a high frequency of allelic loss on chromosome 8p12-21 SO CANCER RESEARCH LA English DT Article ID DINUCLEOTIDE REPEAT; COLORECTAL-CANCER; LINKAGE MAP; DELETION; GENE; POLYMORPHISMS; LOCI AB To investigate the possible involvement of a tumor suppressor gene(s) on chromosome 8 in prostatic neoplasms, we performed a comprehensive loss of heterozygosity (LOH) study on 99 tumors from 97 prostate cancer patients. One of the carcinomas was a lymph node metastasis; the other 98 were primary carcinomas. Pure populations of carcinoma cells and normal epithelia were procured by tissue microdissection. Two separate tumor foci were obtained from each of two patients. Microsatellite markers from 25 loci on the short arm and one locus on the long arm of chromosome 8 were used for PCR-based LOH analysis on matched normal and tumor DNA samples. The overall LOH on Sp in this study was 85.9% (85 of 99) of carcinomas, The loss was highest at markers D8S133, D8S136, NEFL, and D8S137 (62, 72, 64, and 75%, respectively), which are located at 8p12-21, Seventy-nine of 99 tumors exhibited loss in at least one of these four loci. In contrast, LOH at 8p22 was much lower: 17, 18, 18, and 19% at D8S549, D8S602 D8S254, and D85261, respectively, with 25 of 99 tumors showing deletion in one or more of the four loci. All but 5 tumors with deletions in this more distal region had at least one retained locus between the 8p22 deletion and a more proximal region of loss at 8p12-21; 1 tumor had loss at 8p22 but not 8p12-21. This suggests there may be two distinct regions of loss and, therefore, two tumor suppressor genes on this chromosomal arm. The loss on 8p 12-21 showed little or no correlation with grade or stage of disease. C1 NCI,SURG BRANCH,BETHESDA,MD 20982. NCI,PATHOL LAB,BETHESDA,MD 20982. MAYO CLIN & MAYO FDN,DEPT PATHOL,ROCHESTER,MN 55905. NR 54 TC 228 Z9 235 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1996 VL 56 IS 10 BP 2411 EP 2416 PG 6 WC Oncology SC Oncology GA UK187 UT WOS:A1996UK18700032 PM 8625320 ER PT J AU Howard, G OLeary, DH Zaccaro, D Haffner, S Rewers, M Hamman, R Selby, JV Saad, MF Savage, P Bergman, R AF Howard, G OLeary, DH Zaccaro, D Haffner, S Rewers, M Hamman, R Selby, JV Saad, MF Savage, P Bergman, R TI Insulin sensitivity and atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; diabetes mellitus; insulin; carotid arteries ID INTIMA-MEDIA THICKNESS; MEXICAN-AMERICANS; CAROTID ATHEROSCLEROSIS; BLOOD-PRESSURE; RISK-FACTORS; RESISTANCE; BLACK; MEN; ARTERIES; GLUCOSE AB Background Reduced insulin sensitivity has been proposed as an important risk factor in the development of atherosclerosis. However, insulin sensitivity is related to many other cardiovascular risk factors, including plasma insulin levels, and it is unclear whether an independent role of insulin sensitivity exists. Large epidemiological studies that measure insulin sensitivity directly have not been conducted. Methods and Results The Insulin Resistance Atherosclerosis Study (IRAS) evaluated insulin sensitivity (S-1) by the frequently sampled intravenous glucose tolerance test with analysis by the minimal model of Bergman. IRAS measured intimal-medial thickness (IMT) of the carotid artery as an index of atherosclerosis by use of noninvasive B-mode ultrasonography. These measures, as well as factors that may potentially confound or mediate the relationship between insulin sensitivity and atherosclerosis, were available in relation to 395 black, 457 Hispanic, and 542 non-Hispanic white IRAS participants. There was a significant negative association between S, and the IMT of the carotid artery both in Hispanics and in non-Hispanic whites. This effect was reduced but not totally explained by adjustment for traditional cardiovascular disease risk factors, glucose tolerance, measures of adiposity, and fasting insulin levels. There was no association between S-1 and the IMT of the carotid artery in blacks. The association between S-1 and the IMT was stronger for the internal carotid artery than for the common carotid artery in all ethnic groups. Conclusions Higher levels of insulin sensitivity are associated with less atherosclerosis in Hispanics and non-Hispanic whites but not in blacks. This effect is partially mediated by traditional cardiovascular risk factors. C1 TUFTS NEW ENGLAND MED CTR, DEPT RADIOL, BOSTON, MA USA. UNIV TEXAS, DIV CLIN EPIDEMIOL, SAN ANTONIO, TX 78285 USA. UNIV COLORADO, HLTH SCI CTR, DEPT PREVENT MED & BIOMETR, DENVER, CO 80262 USA. KAISER PERMANENTE, DIV RES, OAKLAND, CA USA. UNIV SO CALIF, MED CTR, DEPT MED, DIV DIABET HYPERTENS & NUTR, LOS ANGELES, CA USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. UNIV SO CALIF, SCH MED, DEPT PHYSIOL & BIOPHYS, LOS ANGELES, CA 90033 USA. RP Howard, G (reprint author), WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI, MED CTR BLVD, WINSTON SALEM, NC 27157 USA. FU NHLBI NIH HHS [HL47887, HL47889, HL47890] NR 37 TC 525 Z9 539 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY 15 PY 1996 VL 93 IS 10 BP 1809 EP 1817 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UK795 UT WOS:A1996UK79500010 PM 8635260 ER PT J AU Guetta, V Cannon, RO AF Guetta, V Cannon, RO TI Cardiovascular effects of estrogen and lipid-lowering therapies in postmenopausal women SO CIRCULATION LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; ENDOTHELIUM-DEPENDENT RELAXATION; MEMBRANE PHOSPHOLIPID PEROXIDATION; PLASMINOGEN-ACTIVATOR INHIBITOR-1; HORMONE-REPLACEMENT THERAPY; VITAMIN-E CONSUMPTION; SMOOTH-MUSCLE CELLS; NITRIC-OXIDE; HYPERCHOLESTEROLEMIC PATIENTS C1 NHLBI, NIH, CARDIOL BRANCH, BETHESDA, MD 20892 USA. NR 153 TC 119 Z9 119 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY 15 PY 1996 VL 93 IS 10 BP 1928 EP 1937 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UK795 UT WOS:A1996UK79500023 PM 8635273 ER PT J AU Boyes, J Felsenfeld, G AF Boyes, J Felsenfeld, G TI Tissue-specific factors additively increase the probability of the all-or-none formation of a hypersensitive site SO EMBO JOURNAL LA English DT Article DE chicken beta(A); chromatin accessibility; epsilon-globin enhancer; erythroid transcription factors; nuclease-hypersensitive site ID RNA POLYMERASE-II; BETA-GLOBIN LOCUS; TRANSCRIPTIONAL REGULATION; CHROMATIN STRUCTURE; DNA-REPLICATION; CONTROL REGION; GENE; PROMOTER; ENHANCER; NUCLEOSOMES AB DNase I-hypersensitive sites lack a canonical nucleosome and have binding sites for various transcription factors, To understand how the hypersensitivity is generated and maintained, we studied the chicken erythroid-specific beta A/epsilon globin gene enhancer, a region where both tissue-specific and ubiquitous transcription factors can bind, Constructions containing mutations of this enhancer were stably introduced into a chicken erythroid cell line. We found that the hypersensitivity was determined primarily by the erythroid factors and that their binding additively increased the accessibility, The fraction of accessible sites in clonal cell lines was quantitated using restriction endonucleases; these data implied that the formation of each hypersensitive site was an all-or-none phenomenon. Use of DNase I and micrococcal nuclease probes further indicated that the size of the hypersensitive site was influeuced by the binding of transcription factors which then determined the length of the nucleosome-free gap. Our data are consistent with a model in which hypersensitive sites are generated stochastically: mutations that reduce the number of bound factors reduce the probability that these factors will prevail over a nucleosome; thus, the fraction of sites in the population that are accessible is also diminished. C1 NIDDK,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NR 38 TC 139 Z9 139 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 1996 VL 15 IS 10 BP 2496 EP 2507 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UM406 UT WOS:A1996UM40600019 PM 8665857 ER PT J AU Sills, TL Crawley, JN AF Sills, TL Crawley, JN TI Individual differences in sugar consumption predict amphetamine-induced dopamine overflow in nucleus accumbens SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE amphetamine; microdialysis; dopamine; individual difference; nucleus accumbens; (rat) ID COCAINE; RATS AB Rats exhibit individual differences in their consumption of sugar and in their response to amphetamine treatments. Intrinsic variation in the functioning of the mesolimbic dopamine system is one potential mechanism underlying the expression of these individual differences. The present experiment examined the relationship between sugar consumption and the dopaminergic response to amphetamine. In vivo microdialysis was used to assess amphetamine-stimulated dopamine overflow in the posterior-medial nucleus accumbens in LOW and HIGH sugar feeders. Sugar consumption correlated significantly with amphetamine-stimulated accumbens-dopamine overflow. HIGH rats exhibited significantly higher levels of amphetamine-stimulated accumbens-dopamine overflow than LOW rats. These results suggest that the propensity to ingest sugar is a predictor of the nucleus accumbens dopaminergic response to amphetamine treatment. RP Sills, TL (reprint author), NIMH,SECT BEHAV NEUROPHARMACOL,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892, USA. NR 14 TC 25 Z9 25 U1 0 U2 2 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 MAY 15 PY 1996 VL 303 IS 3 BP 177 EP 181 DI 10.1016/0014-2999(96)00161-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU200 UT WOS:A1996UU20000004 PM 8813564 ER PT J AU Wang, XW Vermeulen, W Coursen, JD Gibson, M Lupold, SE Forrester, K Xu, GW Elmore, L Yeh, H Hoeijmakers, JHJ Harris, CC AF Wang, XW Vermeulen, W Coursen, JD Gibson, M Lupold, SE Forrester, K Xu, GW Elmore, L Yeh, H Hoeijmakers, JHJ Harris, CC TI The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway SO GENES & DEVELOPMENT LA English DT Article DE p53; TFIIH; XPB; XPD; apoptosis ID WILD-TYPE P53; PROGRAMMED CELL-DEATH; XERODERMA-PIGMENTOSUM; GENETIC-HETEROGENEITY; IONIZING-RADIATION; TUMOR SUPPRESSOR; BINDING-SITE; C-MYC; PROTEIN; REPAIR AB The molecular pathway of p53-dependent apoptosis (programmed cell death) is poorly understood. Because p53 binds to the basal transcription-repair complex TFIIH and modulates its DNA helicase activities, we hypothesized that TFIIH DNA helicases XPB and XPD are members of the p53-mediated apoptotic pathway. Whereas transfer of a wild-type p53 expression vector by microinjection or retroviral infection into primary normal human fibroblasts resulted in apoptosis, primary fibroblasts from individuals with xeroderma pigmentosum (XP), who are deficient in DNA repair and have germ-line mutations in the XPB or XPD gene, but not in the XPA or XPC gene, have a deficiency in the apoptotic response. This deficiency can be rescued by transferring the wild-type XPB or XPD gene into the corresponding mutant cells. XP-D lymphocytes also have a decreased apoptotic response to DNA damage by adriamycin, indicating a physiologically relevant deficiency. The XP-B or XP-D mutant cells undergo a normal apoptotic response when microinjected with the Ich-1(L) and ICE genes. Analyses of p53 mutants and the effects of microinjected anti-p53 antibody, Pab421, indicate that the carboxyl terminus of p53 may be required for apoptosis. Direct microinjection of the p53 carboxy-terminal-derived peptide (amino acid residues 319-393) resulted in apoptosis of primary normal human fibroblasts. These results disclose a novel pathway of p53-induced apoptosis. C1 ERASMUS UNIV ROTTERDAM,CTR MED GENET,DEPT CELL BIOL & GENET,3000 DR ROTTERDAM,NETHERLANDS. RP Wang, XW (reprint author), NCI,NIH,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. RI Wang, Xin/B-6162-2009 NR 96 TC 293 Z9 301 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1996 VL 10 IS 10 BP 1219 EP 1232 DI 10.1101/gad.10.10.1219 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UP168 UT WOS:A1996UP16800005 PM 8675009 ER PT J AU Coon, SL Mazuruk, K Bernard, M Roseboom, PH Klein, DC Rodriguez, IR AF Coon, SL Mazuruk, K Bernard, M Roseboom, PH Klein, DC Rodriguez, IR TI The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): Structure, chromosomal localization, and tissue expression SO GENOMICS LA English DT Article ID PINEAL-GLAND; MELATONIN; RNA; RADIOIMMUNOASSAY; SERUM AB Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, HGMW-approved symbol AANAT; EC 2,3,1.87) is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. We have found that the human AA-NAT gene spans similar to 2.5 kb, contains four exons, and is located at chromosome 17q25. The open reading frame encodes a 23.2-kDa protein that is similar to 80% identical to sheep and rat AA-NAT. The AA-NAT transcript (similar to 1 kb) is highly abundant in the pineal gland and is expressed at lower levels in the retina and hi the Y79 retinoblastoma cell line. AA-NAT mRNA is also detectable at low levels in several brain regions and the pituitary gland, but not in several peripheral tissues examined. Brain and pituitary AA-NAT could modulate serotonin-dependent aspects of human behavior and pituitary function. (C) 1996 Academic Press, Inc. C1 NEI,NIH,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NICHHD,NIH,DEV NEUROBIOL LAB,SECT NEUROENDOCRINOL,BETHESDA,MD 20892. NR 31 TC 80 Z9 83 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1996 VL 34 IS 1 BP 76 EP 84 DI 10.1006/geno.1996.0243 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UM824 UT WOS:A1996UM82400009 PM 8661026 ER PT J AU Lin, KM Thomas, JT McBride, OW Luyten, FP AF Lin, KM Thomas, JT McBride, OW Luyten, FP TI Assignment of a new TGF-beta superfamily member, human cartilage-derived morphogenetic protein-1, to chromosome 20q11.2 SO GENOMICS LA English DT Article ID GENES C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RP Lin, KM (reprint author), NIDR,BONE RES BRANCH,NIH,BLDG 10,ROOM 1A-13,BETHESDA,MD 20892, USA. NR 8 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1996 VL 34 IS 1 BP 150 EP 151 DI 10.1006/geno.1996.0257 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UM824 UT WOS:A1996UM82400023 PM 8661040 ER PT J AU Neuenschwander, S Schwartz, A Wood, TL Roberts, CT Henninghausen, L LeRoith, D AF Neuenschwander, S Schwartz, A Wood, TL Roberts, CT Henninghausen, L LeRoith, D TI Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE apoptosis; lactation; insulin-like growth factors; transgenic whey acidic protein gene ID GROWTH FACTOR-I; MESSENGER-RIBONUCLEIC-ACID; HUMAN-BREAST CANCER; EXPRESSION; HORMONE; RNA; CLONING; INTACT; GENE AB Development of the mammary gland during puberty, pregnancy, and lactation is controlled by steroid and peptide hormones and growth factors. To determine the role of the insulin-like growth factors (IGFs) in this process we developed a transgenic model using the whey acidic protein (WAP) gene to direct expression of rat IGF-I and human IGF binding protein-3 (IGFBP-3) to mammary tissue during late pregnancy and throughout lactation. High levels of expression of transgenic IGF-I and IGFBP-3 were seen in lobular-alveolar cells by in situ hybridization. There was no obvious effect on mammary development during pregnancy and lactation; indeed, mothers were capable of nursing their, pups normally and the only structural difference seen in the mammary glands at peak lactation was an overall smaller size of the alveoli. We also evaluated the role of IGF-I and IGFBP-3 in the remodeling of mammary tissue during involution, Compared with control animals, the process of involution was modified in both transgenic lines, The degree of apoptotic cells was lower in the WAP-IGF-I and WAP-BP-3 expressing mice. In addition, there was a more quiescent pattern of involution with residual lobular secretory ability and a muted host inflammatory reaction with fewer lumenal microcalcifications. These results demonstrate that IGF-I and IGFBP-3 may modulate the involutionary process of the lactating mammary gland. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. PENN STATE UNIV,COLL MED,DEPT ANAT & NEUROSCI,HERSHEY,PA 17033. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. OI Roberts, Charles/0000-0003-1756-5772 NR 32 TC 152 Z9 155 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 15 PY 1996 VL 97 IS 10 BP 2225 EP 2232 DI 10.1172/JCI118663 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UM574 UT WOS:A1996UM57400010 PM 8636401 ER PT J AU Albrecht, FE Drago, J Felder, RA Printz, MP Eisner, GM Robillard, JE Sibley, DR Westphal, HJ Jose, PA AF Albrecht, FE Drago, J Felder, RA Printz, MP Eisner, GM Robillard, JE Sibley, DR Westphal, HJ Jose, PA TI Role of the D-1A dopamine receptor in the pathogenesis of genetic hypertension SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hypertension; dopamine; dopamine receptor; sodium transport; genetics ID NA+-H+ EXCHANGER; SALT-SENSITIVE RATS; ADENYLATE-CYCLASE; BLOOD-PRESSURE; RESPONSES; TUBULE; DEFECT; SPECIFICITY; KIDNEY AB Since dopamine produced by the kidney is an intrarenal regulator of sodium transport, an abnormality of the dopaminergic system may be important in the pathogenesis of hypertension. In the spontaneously hypertensive rat (SHR), in spite of normal renal production of dopamine and receptor density, there is defective transduction of the D-1 receptor signal in renal proximal tubules, resulting in decreased inhibition of sodium transport (Na+/H+ exchanger [NHE] and Na+/K(+)ATPase activity) by dopamine. To determine if impaired D-1 receptor regulation of NHE in proximal tubules is related to hypertension, studies were performed in a F2 generation from female Wistar Kyoto (WKY) and male SHR crosses, A D-1 agonist, SKF 81297, inhibited (37.6+/-4.7%) NHE activity in brush border membranes of normotensive F2s (systolic blood pressure < 140 mm Hg, n = 7) but not in hypertensive F2s (n = 21). Furthermore, a D-1 agonist, SKF 38393, when infused into the renal artery, dose dependently increased sodium excretion in normotensive F2s (n = 3) without altering renal blood flow but was inactive in hypertensive F2s (n = 21). Since the major D-1 receptor gene expressed in renal proximal tubules is the D-1A subtype, we determined the importance of this gene in the control of blood pressure in mice lacking functional D-1A receptors, Systolic blood pressure was greater in homozygous (n = 6) and heterozygous (n = 5) mice compared to normal sex matched litter mate controls (n = 12); moreover, the mice lacking one or both D-1A alleles developed diastolic hypertension. The cosegregation with hypertension of an impaired D-1 receptor regulation of renal sodium transport and the development of elevated systolic and diastolic pressure in mice lacking one or both D-1A alleles suggest a causal relationship of the D-1A receptor gene with hypertension. C1 GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. MONASH UNIV,DEPT ANAT,NEUROSCI UNIT,CLAYTON,VIC 3168,AUSTRALIA. UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92161. UNIV IOWA,MED CTR,DEPT PEDIAT,IOWA CITY,IA 52242. NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RP Albrecht, FE (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. FU NHLBI NIH HHS [HL-23081]; NIDDK NIH HHS [DK-49361, DK447-56] NR 42 TC 140 Z9 144 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 15 PY 1996 VL 97 IS 10 BP 2283 EP 2288 DI 10.1172/JCI118670 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UM574 UT WOS:A1996UM57400017 PM 8636408 ER PT J AU Brenneman, DE Gozes, I AF Brenneman, DE Gozes, I TI A femtomolar-acting neuroprotective peptide SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE activity-dependent neurotrophic factor; vasoactive intestinal peptide; neuronal survival; astrocyte ID VASOACTIVE-INTESTINAL-PEPTIDE; HUMAN IMMUNODEFICIENCY VIRUS; SPINAL-CORD CULTURES; ELECTRICAL-ACTIVITY; ENVELOPE PROTEIN; NEUROTROPHIC FACTOR; NEURONAL SURVIVAL; COAT PROTEIN; HIV; EXPRESSION AB A novel 14-amino acid peptide, with stress-protein-like sequences, exhibiting neuroprotection at unprecedented concentrations, is revealed. This peptide prevented neuronal cell death associated with the envelope protein (GP 120) from HIV, with excitotoxicity (N-methyl d-aspartate), with the beta amyloid peptide (putative cytotoxin in Alzheimer's disease), and with tetrodotoxin (electrical blockade). The peptide was designed to contain a sequence derived from a new neuroprotective protein secreted by astroglial cells in the presence of vasoactive intestinal peptide, The neurotrophic protein was isolated by sequential chromatographic methods combining ion exchange, size separation, and hydrophobic interaction. The protein (mol mass, 14 kD and pI, 8.3+/-0.25) was named activity-dependent neurotrophic factor, as it protected neurons from death associated with electrical blockade. Peptide sequencing led to the synthesis of the novel 14-amino acid peptide that was homologous, but not identical, to an intracellular stress protein, heat shock protein 60. Neutralizing antiserum to heat shock protein 60 produced neuronal cell death that could be prevented by cotreatment with the novel protein, suggesting the existence of extracellular stress-like proteins with neuroprotective properties. These studies identify a potent neuroprotective glial protein and an active peptide that provide a basis for developing treatments of currently intractable neurodegenerative diseases. (J. Clin. Invest. 1996. 97:2299-2307.) C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. RP Brenneman, DE (reprint author), NICHHD,LDN,NIH,SECT DEV & MOL PHARMACOL,BLDG 49,ROOM 5A38,49 CONVENT DR,MSC 4480,BETHESDA,MD 20892, USA. NR 62 TC 216 Z9 219 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 15 PY 1996 VL 97 IS 10 BP 2299 EP 2307 DI 10.1172/JCI118672 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UM574 UT WOS:A1996UM57400019 PM 8636410 ER PT J AU Nelson, N Kanno, Y Hong, C Contursi, C Fujita, T Fowlkes, BJ OConnell, E Li, JH Paul, WE Jankovic, D Sher, AF Coligan, JE Thornton, A Appella, E Yang, YL Ozato, K AF Nelson, N Kanno, Y Hong, C Contursi, C Fujita, T Fowlkes, BJ OConnell, E Li, JH Paul, WE Jankovic, D Sher, AF Coligan, JE Thornton, A Appella, E Yang, YL Ozato, K TI Expression of IFN regulatory factor family proteins in lymphocytes - Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA SIGNAL-TRANSDUCTION; INTERFERON-GAMMA; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; INDUCIBLE GENES; B-CELLS; ALPHA; IRF-1; ELEMENTS; ENHANCER AB Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the IFN regulatory factor (IRF) family. Evidence indicates that this family has a function in the immune system. Unlike other members of the family, ICSBP is expressed exclusively in the immune system. In this work, immunoblot analysis was performed to study expression of ICSBP and other members of the family in various murine lymphocytes. The results show that all IRF family members are expressed constitutively in B cells throughout development, and in resting and activated cells. In contrast, ICSBP expression was undetectable in thymocytes and resting T cells, while all other IRF proteins tested (IRF-1, IRF-2, and ISGF3-gamma) were detected in these cells. Induction of ICSBP (and weakly IRF-1, but not other members) was observed upon activation of T cells following anti-CDS Ab binding or Con A stimulation. Once T cells were activated, ICSBP was expressed stably in both Th1 and Th2 cells. We show that Stat-1, which binds to the IFN-gamma-responsive element of the ICSBP promoter, was induced following anti-CD3 Ab and Con A stimulation. Stat-1 induction was found in T cells of IFN-gamma(+/+), but not of IFN-gamma(-/-) mice, indicating that T cell activation stimulates the Stat pathway of transcription that is mediated through IFN-gamma. IFN-gamma-activated Stat-1 partly accounted for ICSBP induction in activated T cells, as levels of induction were lower in IFN-gamma(-/-) than in IFN+/+ T cells. Taken together, these results show that activation of ICSBP is coupled with T cell activation that is partly due to IFN-gamma-induced Stat-1. C1 NICHHD,LAB MOLEC GROWTH REGULAT,BETHESDA,MD 20892. TOKYO METROPOLITAN INST MED SCI,BYNKYO KU,TOKYO 113,JAPAN. NIAID,CELLULAR & MOLEC IMMUNOL LAB,IMMUNOL LAB,PARASIT DIS LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,LAB IMMUNE CELL BIOL,BETHESDA,MD 20892. RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 65 TC 92 Z9 94 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1996 VL 156 IS 10 BP 3711 EP 3720 PG 10 WC Immunology SC Immunology GA UJ341 UT WOS:A1996UJ34100018 PM 8621906 ER PT J AU Levitsky, HI Montgomery, J Ahmadzadeh, M StaveleyOCarroll, K Guarnieri, F Longo, DL Kwak, LW AF Levitsky, HI Montgomery, J Ahmadzadeh, M StaveleyOCarroll, K Guarnieri, F Longo, DL Kwak, LW TI Immunization with granulocyte-macrophage colony-stimulating factor-transduced, but not B7-1-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; TUMOR-CELLS; B-CELLS; ANTIGEN; INDUCTION; CTLA-4; IMMUNOGLOBULIN; ACTIVATION; INTERLEUKIN-4; COSTIMULATION AB Recently, genetically modified tumor cell vaccines have been described for nonhematopoietic cancers in which the relevant Ags are unknown. Several of these cell-based vaccine strategies have been shown to induce T cell-mediated systemic antitumor immunity, either by enhancing the processing and presentation of tumor Ags by host APCs or by facilitating effective Ag presentation by the tumor vaccine itself. These strategies were compared in a model B cell lymphoma, a tumor derived from APCs, which have the inherent capacity to activate Ag-specific T cells. Eradication of pre-established systemic lymphoma was achieved following immunization with lymphoma cells engineered to produce granulocyte-macrophage (GM)-CSF, and to a lesser extent cells producing IL-4, whereas vaccination with lymphoma cells transfected with the genes encoding IL-2 or B7-1 had no effect. The systemic immunity generated by GM-CSF- or IL-4-transfected lymphoma required both CD4(+) and CD8(+) T cells. Previous immunotherapeutic strategies for the treatment of lymphoma have focused on the generation of Ab responses targeted to the unique Ig Id as a tumor-specific Ag. Anti-idiotypic Abs were undetectable in animals vaccinated with CM-CSF-transduced lymphoma cells. In contrast, such immunization did result in the induction of Id-specific T cell responses. This is the first demonstration that T cell responses specific for a native tumor Ag are generated by CM-CSF-transduced tumor cell-based vaccination, suggesting that B cell lymphoma may be a suitable disease for genetically modified tumor vaccine strategies. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP Levitsky, HI (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,720 RUTLAND AVE,ROSS BLDG,ROOM 364,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [P30 CA06973, K08 CA01595] NR 38 TC 152 Z9 155 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1996 VL 156 IS 10 BP 3858 EP 3865 PG 8 WC Immunology SC Immunology GA UJ341 UT WOS:A1996UJ34100036 PM 8621924 ER PT J AU Rivoltini, L Loftus, DJ Barracchini, K Arienti, F Mazzocchi, A Biddison, WE Salgaller, ML Appella, E Parmiani, G Marincola, FM AF Rivoltini, L Loftus, DJ Barracchini, K Arienti, F Mazzocchi, A Biddison, WE Salgaller, ML Appella, E Parmiani, G Marincola, FM TI Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes - Implications for peptide-based immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; VIRAL PEPTIDES; VIRUS; MOLECULES; DNA; DETERMINANT; RECOGNITION; MUTATIONS; CELLS AB Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-AZ subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (similar to 20%) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50% inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-1(27-35), G9(154,) and G9(280) Flu M1(58-66)) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes. C1 NCI,NIH,DIV CLIN SCI,SURG BRANCH,BETHESDA,MD 20892. NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DEPT EXPTL ONCOL D,MILAN,ITALY. NCI,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,HLA LAB,BETHESDA,MD 20892. NINCDS,NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. OI Rivoltini, Licia/0000-0002-2409-6225 NR 66 TC 73 Z9 73 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1996 VL 156 IS 10 BP 3882 EP 3891 PG 10 WC Immunology SC Immunology GA UJ341 UT WOS:A1996UJ34100039 PM 8621927 ER PT J AU Lukacs, NW Strieter, RM Lincoln, PM Brownell, E Pullen, DM Schock, HJ Chensue, SW Taub, DD Kunkel, SL AF Lukacs, NW Strieter, RM Lincoln, PM Brownell, E Pullen, DM Schock, HJ Chensue, SW Taub, DD Kunkel, SL TI Stem cell factor (c-kit ligand) influences eosinophil recruitment and histamine levels in allergic airway inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE SCHISTOSOMIASIS-MANSONI; HUMAN MAST-CELLS; INTERLEUKIN-4; INVIVO; BASOPHILS; CYTOKINES; RECEPTOR; LINES AB The increased reactivity of mast cells during allergic airway inflammation has been linked to several aspects of pulmonary disease. A primary inducer of mast eel! differentiation, proliferation, and activation has been identified as c-kif ligand or stem cell factor (SCF). In the present study, we used an established murine model of allergic eosinophilic airway inflammation to examine the role of SCF during an Ag-specific airway response. Initial data demonstrates increased SCF protein production at 8 h postchallenge in both lungs and serum of allergen-challenged, but not vehicle-challenged, mice. The immunolocalization of SCF in Ag-challenged lungs suggested that macrophage populations were the primary source of SCF, while epithelial cell regions also stained positive. Intense immunohistochemical staining of macrophages in bronchoalveolar lavage samples recovered from Ag-sensitized mice indicate that these cells may be a significant source of SCF in the lungs. Alveolar macrophages from the airways of normal mice stimulated with either TNF (0,1-10 ng/ml) or IL-4 (10 ng/ml) produced significant levels of SCF. Furthermore, neutralization studies demonstrated that the inhibition of airway SCF during allergen challenge significantly decreased eosinophil, but not neutrophil, infiltration throughout the response. Furthermore, when mice were treated with anti-SCF Ab, histamine levels were significantly reduced at 8 h postchallenge, the time of significant SCF production. Together, these data indicate that the production of SCF during Ag-induced lung inflammation by alveolar macrophages can play a significant role in the subsequent recruitment of eosinophils, possibly via mast cell activation and degranulation. C1 UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,DIV PULM & CRIT CARE,ANN ARBOR,MI 48109. VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,ANN ARBOR,MI 48109. NCI,FREDERICK CANC RES & DEV CTR,CLIN SUPPORT PROGRAM,FREDERICK,MD 21702. BAYER INC,INST MOLEC BIOL,NEW HAVEN,CT 06516. RP Lukacs, NW (reprint author), UNIV MICHIGAN,SCH MED,DEPT PATHOL,DIV PULM & CRIT CARE,1301 CATHERINE ST,ANN ARBOR,MI 48109, USA. FU NHLBI NIH HHS [HL31693, HL02401, HL35276] NR 31 TC 58 Z9 59 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1996 VL 156 IS 10 BP 3945 EP 3951 PG 7 WC Immunology SC Immunology GA UJ341 UT WOS:A1996UJ34100047 PM 8621935 ER PT J AU Tang, T Stevens, BA Cox, BM AF Tang, T Stevens, BA Cox, BM TI Opioid regulation of intracellular free calcium in cultured mouse dorsal root ganglion neurons SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE opioid receptor; intracellular free calcium; dorsal root ganglion neurons ID ACTION-POTENTIAL DURATION; SENSORY NEURONS; DYNORPHIN-A; CURRENTS; CONDUCTANCE AB Opioid agonists induced an increase in the intracellular free calcium concentration ([Ca2+](i)) or an inhibition of K+ (25 mM)-stimulated increase in [Ca2+](i) in different subsets of mouse dorsal root ganglion (DRG) neurons, The total neuronal population was grouped into three classes according to somatic diameter and defined as small (<16 mu m), intermediate (16-25 mu m), or large (>25 mu m) neurons. Substance P-like immunoreactivity was detected mainly in the small and intermediate neurons, The delta, kappa, and mu opioid receptor agonists [D-Ser(2), Leu(5)]enkekphalin-Thr (DSLET), U69593, and [D-Ala(2), MePhe(4), Glyol(5)]enkephalin (DAMGO) each induced a transient increase in [Ca2+](i) in a small fraction (<30%) of neurons, The increases in [Ca2+](i) were blocked by the opioid antagonist naloxone, The dihydropyridine-sensitive calcium channel blocker nifedipine also blocked the increase in [Ca2+](i) induced by 1 mu M DSLET. The rank order of potency (percentage of cells responding to each opioid agonist) was DSLET > U69593 > DAMGO, The opioid-induced increase in [Ca2+](i) was observed mainly in large neurons, with a low incidence in small and intermediate neurons, Opioid agonists also caused inhibition of K+-stimulated increases in [Ca2+](i), which were blocked by naloxone (1 mu M). Inhibition of the K+-stimulated increase by 1 mu M DSLET or U69593 was greater in small and intermediate neurons than in large neurons. (C) 1996 Wiley-Liss, Inc. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 21 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 15 PY 1996 VL 44 IS 4 BP 338 EP 343 PG 6 WC Neurosciences SC Neurosciences & Neurology GA UL385 UT WOS:A1996UL38500004 PM 8739152 ER PT J AU Bal, W Chmurny, GN Hilton, BD Sadler, PJ Tucker, A AF Bal, W Chmurny, GN Hilton, BD Sadler, PJ Tucker, A TI Axial hydrophobic fence in highly-stable Ni(II) complex of des-angiotensinogen N-terminal peptide SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID L-HISTIDINE; SPECTROSCOPY; ALBUMIN; STABILITY; PROTEINS; BINDING; SERUM C1 UNIV LONDON BIRKBECK COLL,DEPT CHEM,GORDON HOUSE & CHRISTOPHER INGOLD LABS,LONDON WC1H 0PP,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. NR 23 TC 58 Z9 59 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 15 PY 1996 VL 118 IS 19 BP 4727 EP 4728 DI 10.1021/ja953988j PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA UL088 UT WOS:A1996UL08800038 ER PT J AU Ziegler, RG Hoover, RN Nomura, AMY West, DW Wu, AH Pike, MC Lake, AJ HornRoss, PL Kolonel, LN Siiteri, PK Fraumeni, JF AF Ziegler, RG Hoover, RN Nomura, AMY West, DW Wu, AH Pike, MC Lake, AJ HornRoss, PL Kolonel, LN Siiteri, PK Fraumeni, JF TI Relative weight, weight change, height, and breast cancer risk in Asian-American women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BODY-FAT DISTRIBUTION; MENSTRUAL EVENTS; NHANES-I; SIZE; EPIDEMIOLOGY; DIET; MASS; ASSOCIATION; OBESITY; GAIN AB Background: Breast cancer incidence rates have historically been four to seven times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, their breast cancer risk rises over several generations and reaches that for white women in the United States, indicating that modifiable exposures are involved. In a previous report on this case-control study of breast cancer in Asian-American women, designed to take advantage of their diversity in risk and lifestyle, we demonstrated a sixfold gradient in risk by migration history, comparable to the international differences in breast cancer incidence rates. Purpose: In this analysis, we have examined the roles of adult height, adiposity, and weight change in breast cancer etiology. Methods: A population-based, case-control study of breast cancer was conducted among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, living in San Francisco-Oakland (CA), Los Angeles (CA), and Oahu (HI) during the period from April 1, 1983, through June 30, 1987. We successfully interviewed 597 (70%) of 852 eligible case subjects and 966 (75%) of 1287 eligible control subjects from August 1985 through February 1989. Subjects were asked about current height, usual adult weight, and usual weight in each decade of life, excluding the most recent 3 years and any periods of pregnancy. Results: Height, recent adiposity (weight in the current decade of life/height(1.5)), and recent weight change (between the current and preceding decades of life) were strong predictors of breast cancer risk after adjustment was made for accepted breast cancer risk factors. Risk doubled (relative risk [RR] = 2.01; 95% confidence interval [CI] = 1.16-3.49) over the 7-inch (17.8-cm) range in height (two-sided P for trend = .003), with comparable effects in both premenopausal and postmenopausal women. Except for reduced risk in the heavy, younger women (weight/height(1.5) > 29 kg/m(1.5) and < 40 years old), risk was positively associated with usual adult adiposity. Trends in risk became more striking as adiposity in each succeeding decade of adult life was considered. Women in their 50s and in the top quintile of adiposity for their age group had twice the breast cancer risk (RR = 2.13; 95% CI = 1.17-3.87) of women in the bottom quintile (two-sided P for trend = .004). Women in their 50s, above the median adiposity for their age group, and with a recent gain of more than 10 pounds had three times the risk (RR = 3.01; 95% CI = 1.45-6.25) of women below the median adiposity and with no recent weight change. Recent weight loss was consistently associated with reduced risk (RRs of approximately 0.7) relative to no recent weight change. Conclusions: Adult adiposity, weight change, and height are critical determinants of breast cancer risk. Increased adiposity and weight gain in the decade preceding diagnosis are especially influential, suggesting that excess weight may function as a late stage promoter, Implications: Weight maintenance and/or reduction as an adult, possibly accompanied by specific changes in diet and physical activity, may have a significant and rapid impact on breast cancer risk. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. UNIV HAWAII,CANC RES CTR HAWAII,PROGRAM EPIDEMIOL,HONOLULU,HI 96813. NO CALIF CANC CTR,UNION CITY,CA. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. NR 55 TC 130 Z9 133 U1 0 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 15 PY 1996 VL 88 IS 10 BP 650 EP 660 DI 10.1093/jnci/88.10.650 PG 11 WC Oncology SC Oncology GA UK186 UT WOS:A1996UK18600010 PM 8627641 ER PT J AU Tross, S Herndon, J Korzun, A Kornblith, AB Cella, DF Holland, JF Raich, P Johnson, A Kiang, DT Perloff, M Norton, L Wood, W Holland, JC AF Tross, S Herndon, J Korzun, A Kornblith, AB Cella, DF Holland, JF Raich, P Johnson, A Kiang, DT Perloff, M Norton, L Wood, W Holland, JC TI Psychological symptoms and disease-free and overall survival in women with stage II breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PERSONALITY AB Background: The possible link between psychological factors and length of cancer survival has generated a literature of contradictory findings, Associations usually have not been found when general psychological symptoms are assessed, Associations usually have been found for predictors related to expressive versus repressive emotional coping (e.g., depression, ''fighting spirit,'' hostility, and type C personality); however, even these associations have been relatively small, when compared with those for medical factors, Yet few studies have adequately controlled for medical and treatment-related factors, Purpose: Within a Cancer and Leukemia Group B (CALGB) national clinical trial of four adjuvant therapy regimens for stage II breast cancer (CALGB 8082), this study prospectively examined the contribution of potential psychological predictors to length of disease-free and overall survival over a 15-year period, Methods: Subjects were 280 women with stage II breast cancer, out of a total of 899, who were randomly assigned to receive CMFVP (cyclophosphamide-methotrexate-fluoro uracil-vincristine-prednisone) for two 6-week cycles or six 4-week cycles, then subsequently randomly assigned to receive or not to receive VATH (vinblastine-doxorubicin-thiotepa-fluoxymesterone). Subjects were recruited during the period between October 1980 and August 1984, inclusive, and followed until January 1996, Prior to chemotherapy, psychological symptoms were assessed using the Symptom Check List-90-Revised (SCL-90-R). SCL-90-R scores were trichotomized into categories representing high, medium, and low distress, Basic base-line sociodemographic data (including age, ethnicity, education, and marital status) and medical data (including lymph node status, estrogen receptor status, menopausal status, and performance status) were collected, Subjects with psychosocial data differed from those without psychosocial data solely in their higher percentage of classification in the mild limitation category of the Zubrod (Eastern Cooperative Oncology Group) performance status rating (subjects with psychosocial data: 14%; subjects without psychosocial data: 8%), Results: In stepwise Cox regression analyses that controlled for sociodemographic and medical variables, there was no significant predictive effect of the level of distress (as measured by the SCL-90-R trichotomized scores) on length of disease-free and overall survival of the study subjects, Risk ratios for low versus high distress were 1.01 (95% confidence interval [CI] = 0.62-1.66) for disease-free survival and 1.03 (95% CI = 0.58-1.82) for overall survival, Conclusions: This study failed to provide evidence that psychological factors contributed to length of disease-free or overall survival of women who received adjuvant chemotherapy (either CMFVP alone or CMFVP followed by VATH) for treatment of stage II breast cancer, Implications: In the context of far more potent medical factors, the contribution of psychological factors to disease-free and overall survival is likely to be relatively small, Future research should focus on specific theory-driven predictors rather than on general psychological symptoms, Moreover, it should be based on clinical studies using a controlled, prospective design, in which the effects of medical factors may be distinguished and psychological predictors are clear antecedents of survival outcomes. C1 DUKE UNIV,MED CTR,CANC & LEUKEMAI GRP B,STAT OFF,DURHAM,NC. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. MT SINAI SCH MED,NEW YORK,NY. W VIRGINIA HLTH SCI CTR,MORGANTOWN,WV. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. EMORY UNIV,SCH MED,ATLANTA,GA 30322. RP Tross, S (reprint author), NEW YORK STATE PSYCHIAT INST & HOSP,HIV CTR CLIN & BEHAV STUDIES,722 W 168TH ST,SUITE 1020,NEW YORK,NY 10032, USA. FU NCI NIH HHS [CA03927, CA12011, CA31946] NR 34 TC 71 Z9 71 U1 3 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 15 PY 1996 VL 88 IS 10 BP 661 EP 667 DI 10.1093/jnci/88.10.661 PG 7 WC Oncology SC Oncology GA UK186 UT WOS:A1996UK18600011 PM 8627642 ER PT J AU Cote, TR Manns, A Hardy, CR Yellin, FJ Hartge, P Lemp, G West, D Singleton, J Young, J Kerndt, P Deapen, D Ginzberg, M AntonCulver, H Lieb, S Hopkins, R Williams, B Liff, J Morgan, D Parkin, W AF Cote, TR Manns, A Hardy, CR Yellin, FJ Hartge, P Lemp, G West, D Singleton, J Young, J Kerndt, P Deapen, D Ginzberg, M AntonCulver, H Lieb, S Hopkins, R Williams, B Liff, J Morgan, D Parkin, W TI Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NERVOUS-SYSTEM LYMPHOMA AB Background: In recent years, brain lymphoma incidence has dramatically increased, presumably because of elevated risk of brain lymphoma among persons with acquired immunodeficiency syndrome (AIDS), Purpose: The objective of this study was to estimate independent incidence and survival rates of brain lymphoma among persons with or without AIDS and to understand the epidemiologic features of this cancer, Methods: We linked AIDS and cancer registry reports at nine state and local health departments and compared the demographics, histology, and survival of brain lymphoma cases among persons with or without AIDS, The data were limited to people under 70 years of age, We calculated the incidence of brain lymphoma among persons with AIDS and compared observed cases with those expected, The differences were statistically analyzed using the Poisson test, Epidemiologic features of brain lymphoma in persons with or without AIDS were compared using the chi-squared test, the Student's t test, and the chi-squared test for linear trend, The logrank test was used to compare survival rates estimated by the Kaplan-Meier technique, All P values were two-sided, Results: We matched 50 989 AIDS registry reports to 859 398 cancer registry reports (data from 1981 to 1990) and found 431 people with both AIDS and brain lymphoma, Among people with AIDS, those developing brain lymphoma versus those without brain lymphoma were more likely to be white (70% versus 59%; P < .001) and had homosexuality as their only human immunodeficiency virus risk factor (75% versus 64%; P < .001), Of the 431 patients, 223 developed brain lymphomas during 47 465 person-years of observation after diagnosis of AIDS, The absolute incidence rate of brain lymphoma among persons with AIDS was 4.7/1000 person-years (95% confidence interval = 4.1-5.3/1000 person-years), 3600-fold higher than the base-line rate in the general population, From 1980 through 1989, overall counts of brain lymphoma increased ninefold, Most of this increase was derived from persons with AIDS, but a substantial increase also occurred among persons without AIDS (0.04/100 000 in 1982 to 0.28/100 000 in 1989) (chi-squared test for trend; P < .05). The median survival was shortest for persons with AIDS and brain lymphoma (2 months), was intermediate for persons with brain lymphoma without AIDS (5-7 months), and was longest for persons with AIDS without brain lymphoma (14 months) (P < .05 for all comparisons), Conclusions: This analysis distinguishes the separate epidemiologies of brain lymphoma incidence among persons with or without AIDS and shows brain lymphoma incidence among persons with AIDS to be several thousand-fold higher than that in the general population, The study documents the overwhelming effect of AIDS-associated brain lymphoma on the overall rate in the general population and demonstrates a significantly rising trend, although of a lesser magnitude, among persons without AIDS, Implications: This study emphasizes a greater need to bring health care resources to this burgeoning epidemic. C1 NCI,DIV CANC ETIOL,VIRAL EPIDEMIOL SECT,BETHESDA,MD. NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD. ATLANCTIC RES CORP,ROCKVILLE,MD. NR 16 TC 148 Z9 159 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 15 PY 1996 VL 88 IS 10 BP 675 EP 679 DI 10.1093/jnci/88.10.675 PG 5 WC Oncology SC Oncology GA UK186 UT WOS:A1996UK18600013 PM 8627644 ER PT J AU Hoover, T Mikovits, J Court, D Liu, YL Kung, HF Raziuddin AF Hoover, T Mikovits, J Court, D Liu, YL Kung, HF Raziuddin TI A nuclear matrix-specific factor that binds a specific segment of the negative regulatory element (NRE) of HIV-1 LTR and inhibits NF-kappa B activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; TRANSCRIPTION FACTOR; TOPOISOMERASE-II; TRANS-ACTIVATION; ATTACHMENT SITES; GENE; SCAFFOLD; PROTEIN; REGION AB The negative regulatory element (NRE) of human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR) is a defined region that has been reported to downregulate LTR-directed HIV gene expression, However, information on the precise role of this region in regulating HIV gene transcription is lacking. We have investigated the possibility that these NRE sequences regulate HIV transcription by a mechanism mediated through a nuclear matrix-specific DNA-protein interaction. We find a nuclear matrix attachment region (MAR) present within the NRE of the HIV-1 LTR that recognizes a sequence-specific DNA-binding protein present in the nuclear matrix of HIV infected cells. Moreover, we also show that the purified DNA-binding nuclear matrix protein (NMP) specifically represses the DNA-binding activity of NF-kappa B. It is likely that the MAR and MAR-enriched specific DNA-binding NMP are brought into juxtaposition by the non-chromatin scaffolding of the nucleus, thus influencing NF-kappa B (and other nuclear proteins) DNA-binding activity through protein-protein and protein-DNA interactions. Our data suggest that one possible role of the NRE could be to act as a matrix attachment site in the nuclear matrix, thus, allowing interaction with a sequence-specific trans-acting factor. The negative effect on NF-kappa B activity due to this MAR-NMP-specific interaction provides a mechanism by which the NRE downregulates HIV gene expression. C1 SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NCI,LAB BIOCHEM PHYSIOL,NIH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 34 TC 22 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 15 PY 1996 VL 24 IS 10 BP 1895 EP 1900 DI 10.1093/nar/24.10.1895 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN986 UT WOS:A1996UN98600016 PM 8657571 ER PT J AU Qin, J Clore, GM Kennedy, WP Kuszewski, J Gronenborn, AM AF Qin, J Clore, GM Kennedy, WP Kuszewski, J Gronenborn, AM TI The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal SO STRUCTURE LA English DT Article DE human thioredoxin; NMR; protein-peptide interaction; Ref-1; solution structure ID DNA-BINDING ACTIVITY; REDOX REGULATION; REPAIR ENZYME; PROTEINS; ENERGY; FOS; NMR AB Background: Human thioredoxin (hTRX) is a 12 kDa cellular redox protein that has been shown to play an important role in the activation of a number of transcriptional and translational regulators via a thiol-redox mechanism. This activity may be direct or indirect via another redox protein known as Ref-1. The structure of a complex of hTRX with a peptide comprising its target from the transcription factor NF kappa B has previously been solved, To further extend our knowledge of the recognition by and interaction of hTRX with its various targets, we have studied a complex between hTRX and a Ref-1 peptide. This complex represents a kinetically stable mixed disulfide intermediate along the reaction pathway. Results: Using multidimensional heteronuclear edited and filtered NMR spectroscopy, we have solved the solution structure of a complex between hTRX and a 13-residue peptide comprising residues 59-71 of Ref-1. the Ref-1 peptide is located in a crescent-shaped groove on the surface of hTRX, the groove being formed by residues in the active-site loop (residues 32-36), helix 3, beta strands 3 and 5, and the loop between beta strands 3 and 4. The complex is stabilized by numerous hydrogen-bonding and hydrophobic interactions that involve residues 61-69 of the peptide and confer substrate specificity. Conclusions: The orientation of the Ref-1 peptide in the hTRX-Ref-1 complex is opposite to that found in the previously solved complex of hTRX with the target peptide from the transcription factor NF kappa B. Orientation is determined by three discriminating interactions involving the nature of the residues at the P--2, P--4 and P--5 binding positions. (P-0 defines the active cysteine of the peptide, Cys65 for Ref-1 and Cys62 for NF kappa B. Positive and negative numbers indicate residues N-terminal and C-terminal to this residue, respectively, and vice versa for NF kappa B as it binds in the opposite orientation.) The environment surrounding the reactive Cys32 of hTRX, as well as the packing of the P-+3 to P--4 residues are essentially the same in the two complexes, despite the opposing orientation of the peptide chains, This versatility in substrate recognition permits hTRX to act as a wide-ranging redox regulator for the cell. C1 NIDDKD,NIH,PHYS CHEM LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 44 TC 140 Z9 141 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD MAY 15 PY 1996 VL 4 IS 5 BP 613 EP 620 DI 10.1016/S0969-2126(96)00065-2 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UP289 UT WOS:A1996UP28900012 PM 8736558 ER PT J AU Bychkova, VE Dujsekina, AE Klenin, SI Tiktopulo, EI Uversky, VN Ptitsyn, OB AF Bychkova, VE Dujsekina, AE Klenin, SI Tiktopulo, EI Uversky, VN Ptitsyn, OB TI Molten globule-like state of cytochrome c under conditions simulating those near the membrane surface SO BIOCHEMISTRY LA English DT Article ID FERRICYTOCHROME-C; STRUCTURAL CHARACTERIZATION; PROTEIN CONFORMATION; CIRCULAR-DICHROISM; PRECURSOR PROTEIN; RETINOL-BINDING; FOLDED STATE; INTERMEDIATE; FLUORESCENCE; SPECTROSCOPY AB Methanol-induced conformational transitions in cytochrome c have been studied by near- and far-UV circular dichroism, Trp fluorescence, microcalorimetry, and diffusion measurements. The existence of at least two cooperative stages of transition has been shown. At the first stage, the native protein is transformed into an intermediate which has only traces of tertiary structure, but has a native-like secondary structure content and is relatively compact; i.e., it has properties of the molten globule state. On the second stage, the alcohol-induced molten globule is transformed into a more helical state, typical of proteins at high alcohol concentrations. The conditions at which the alcohol-induced molten globule exists (moderately low pH and moderately low dielectric constant) could be similar to those existing near negatively charged membrane surfaces. Consequently, these results might explain how the molten globule state can be achieved under physiological conditions. C1 RUSSIAN ACAD SCI,INST HIGH MOL CPDS,ST PETERSBURG 199004,RUSSIA. NCI,NIH,MATH BIOL LAB,BETHESDA,MD 20892. RP Bychkova, VE (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 51 TC 199 Z9 202 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 14 PY 1996 VL 35 IS 19 BP 6058 EP 6063 DI 10.1021/bi9522460 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK926 UT WOS:A1996UK92600013 PM 8634247 ER PT J AU Yadava, A Kumar, S Dvorak, JA Milon, G Miller, LH AF Yadava, A Kumar, S Dvorak, JA Milon, G Miller, LH TI Trafficking of Plasmodium chabaudi adami-infected erythrocytes within the mouse spleen SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOCLONAL-ANTIBODY; MARGINAL ZONE; T-CELLS; MALARIA; IMMUNITY; VINCKEI; BERGHEI; BARRIER; ANTIGEN; MICE AB Plasmodium chabaudi adami causes a nonlethal infection in mice. We found that crisis, the time of rapidly dropping parasitemia, was abrogated by splenectomy, indicating the role of spleen in parasite killing. The factors that mediate spleen-dependent immunity are not known. An earlier study in Plasmodium berghei-infected rats showed an association between increased clearance of heat-treated erythrocytes and the onset of crisis [Wyler, D. J., Quinn, T. C. & Chen, L.-T. (1982) J. Clin. Invest. 67, 1400-1404]. To determine the potential effects of different vascular beds in parasite killing, we studied the distribution of parasitized erythrocytes and bacteria in the spleens of P. chabaudi adami-infected mice during precrisis (a period of rising parasitemia) and during crisis. After intravenous injection, bacteria were localized predominantly in the marginal zone. In contrast, parasitized erythrocytes were found in the red pulp. We also found that during precrisis, a time of no immunity, the uptake of radiolabeled infected erythrocytes by the spleen was increased, not decreased. These data imply that no change occurs in the flow of parasitized erythrocytes through the spleen during the transition to an immune state (crisis). Our observations suggest that immune effector mechanisms, not circulatory changes, account for spleen-dependent parasite killing during a P. chabaudi adami infection in mice. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. INST PASTEUR,UNITE IMMUNOPHISIOL CELLULAIRE,F-75724 PARIS 15,FRANCE. NR 25 TC 35 Z9 37 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4595 EP 4599 DI 10.1073/pnas.93.10.4595 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500015 PM 8643449 ER PT J AU Choi, T Rulong, S Resau, J Fukasawa, K Matten, W Kuriyama, R Mansour, S Ahn, N VandeWoude, GF AF Choi, T Rulong, S Resau, J Fukasawa, K Matten, W Kuriyama, R Mansour, S Ahn, N VandeWoude, GF TI Mos/mitogen-activated protein kinase can induce early meiotic phenotypes in the absence of maturation-promoting factor: A novel system for analyzing spindle formation during meiosis I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAP KINASE; XENOPUS-OOCYTES; MOUSE OOCYTE; CELL-CYCLE; MICROTUBULE DYNAMICS; DROSOPHILA FEMALES; ONCOGENE PRODUCT; PHOSPHORYLATION; INVITRO; EGGS AB Mitogen-activated protein kinase (MAPK) is selectively activated by injecting either mos or MAPK kinase (mek) RNA into immature mouse oocytes maintained in the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). IBMX arrests oocyte maturation, but Mos (or MEK) overexpression overrides this block, Under these conditions, meiosis I is significantly prolonged, and MAPK becomes fully activated in the absence of p34(cdc2) kinase or maturation-promoting factor. In these oocytes, large openings form in the germinal vesicle adjacent to condensing chromatin, and microtubule arrays, which stain for both MAPK and centrosomal proteins, nucleate from these regions. Maturation-promoting factor activation occurs later, concomitant with germinal vesicle breakdown, the contraction of the microtubule arrays into a precursor of the spindle, and the redistribution of the centrosomal proteins into the newly forming spindle poles. These studies define important new functions for the Mos/MAPK cascade in mouse oocyte maturation and, under these conditions, reveal novel detail of the early stages of oocyte meiosis I. C1 UNIV MINNESOTA,SCH MED,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. UNIV COLORADO,DEPT CHEM & BIOCHEM,CB 215,BOULDER,CO 80309. RP Choi, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-46000] NR 45 TC 64 Z9 65 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4730 EP 4735 DI 10.1073/pnas.93.10.4730 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500040 PM 8643471 ER PT J AU Htun, H Barsony, J Renyi, I Gould, DL Hager, GL AF Htun, H Barsony, J Renyi, I Gould, DL Hager, GL TI Visualization of glucocorticoid receptor translocation and intranuclear organization in living cells with a green fluorescent protein chimera SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE steroid receptor; confocal laser scanning microscopy; mouse mammary tumor virus; transcription factor; ultracellular calcium ID MAMMALIAN-CELLS; NUCLEAR MATRIX; DNA; PROGESTERONE; PROMOTER; BINDING; HORMONE; VIEW AB A highly fluorescent mutant form of the green fluorescent protein (GFP) has been fused to the rat glucocorticoid receptor (GR). When GFP-GR is expressed in living mouse cells, it is competent for normal transactivation of the GR-responsive mouse mammary tumor virus promoter. The unliganded GFP-GR resides in the cytoplasm and translocates to the nucleus in a hormone-dependent manner with ligand specificity similar to that of the native GR receptor. Due to the resistance of the mutant GFP to photobleaching, the translocation process can be studied by time-lapse video microscopy. Confocal laser scanning microscopy showed nuclear accumulation in a discrete series of foci, excluding nucleoli. Complete receptor translocation is induced with RU486 (a ligand with little agonist activity), although concentration into nuclear foci is not observed. This reproducible pattern of transactivation-competent GR reveals a previously undescribed intranuclear architecture of GR target sites. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NIDDKD,LAB CELLULAR BIOCHEM & BIOL,NIH,BETHESDA,MD 20892. NR 40 TC 298 Z9 300 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4845 EP 4850 DI 10.1073/pnas.93.10.4845 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500060 PM 8643491 ER PT J AU Federspiel, MJ Swing, DA Eagleson, B Reid, SW Hughes, SH AF Federspiel, MJ Swing, DA Eagleson, B Reid, SW Hughes, SH TI Expression of transduced genes in mice generated by infecting blastocysts with avian leukosis virus-based retroviral vectors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROUS-SARCOMA VIRUS; GERM LINE; TRANSGENIC MICE; CHROMOSOMAL POSITION; LEUKEMIA-VIRUS; ACTIN PROMOTER; DNA-SYNTHESIS; STEM-CELLS; VIRAL-DNA; CHICKEN AB Transgenic mouse lines have been developed that express the tv-a receptor under the control of the chicken beta-actin promoter. These mice express the tv-a receptor in most or all tissues and in the early embryo. An avian leukosis virus (ALV)-based retroviral vector system was used for the efficient delivery of genes into preimplantation mouse embryos from these transgenic lines. Experimental animals could be generated quickly and easily by infecting susceptible blastocysts with ALV-based retroviral vectors. Expression of the delivered genes was controlled by either the constitutive viral promoter contained in the long terminal repeat or an internal nonviral tissue-specific promoter. Mating the infected founder chimeric animals produced animals that carry the ALV provirus as a transgene. A subset of the integrated proviruses expressed the chloramphenicol acetyltransferase reporter gene from either the promoter in the long terminal repeat or an internal promoter, which we believe indicates that many of the sites that are accessible to viral DNA insertion in preimplantation embryos are incompatible with expression in older animals. This approach should prove useful for studies on murine cell lineage and development, providing models for studying oncogenesis, and testing gene therapy strategies. C1 NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LAB,FREDERICK,MD 21702. NR 35 TC 26 Z9 27 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4931 EP 4936 DI 10.1073/pnas.93.10.4931 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500075 PM 8643506 ER PT J AU Rothman, N Bhatnagar, VK Hayes, RB Zenser, TV Kashyap, SK Butler, MA Bell, DA Lakshmi, V Jaeger, M Kashyap, R Hirvonen, A Schulte, PA Dosemeci, M Hsu, F Parikh, DJ Davis, BB Talaska, G AF Rothman, N Bhatnagar, VK Hayes, RB Zenser, TV Kashyap, SK Butler, MA Bell, DA Lakshmi, V Jaeger, M Kashyap, R Hirvonen, A Schulte, PA Dosemeci, M Hsu, F Parikh, DJ Davis, BB Talaska, G TI The impact of interindividual variation in NAT2 activity on benzidine urinary metabolites and urothelial DNA adducts in exposed workers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMORPHIC N-ACETYLTRANSFERASE; BLADDER-CANCER; ACETYLATED METABOLITES; AROMATIC-AMINES; CARCINOGEN; ACTIVATION; BINDING; GENOTYPE; PHENOTYPES; INVIVO AB Several epidemiologic studies indicate that NAT2-related slow N-acetylation increases bladder cancer risk among workers exposed to aromatic amines, presumably because N-acetylation is important for the detoxification of these compounds. Previously, we showed that NAT2 polymorphisms did not influence bladder cancer risk among Chinese workers exposed exclusively to benzidine (BZ), suggesting that NAT2 N-acetylation is not a critical detoxifying pathway for this aromatic amine. To evaluate the biologic plausibility of this finding, we carried out a cross-sectional study of 33 workers exposed to BZ and 15 unexposed controls in Ahmedabad, India, to evaluate the presence of BZ-related DNA adducts in exfoliated urothelial cells, the excretion pattern of BZ metabolites, and the impact of NAT2 activity on these outcomes. Four DNA adducts were significantly elevated in exposed workers compared to controls; of these, the predominant adduct cochromatographed with a synthetic N-(3'phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine standard and was the only adduct that was significantly associated with total BZ urinary metabolites (r = 0.68, P < 0.0001). To our knowledge this is the first report to show that BZ forms DNA adducts in exfoliated urothelial cells of exposed humans and that the predominant adduct formed is N-acetylated, supporting the concept that monofunctional acetylation is an activation, rather than a detoxification, step for BZ. However, because almost all BZ-related metabolites measured in the urine of exposed workers were acetylated among slow, as well as rapid, acetylators (mean +/- SD 95 +/- 1.9% vs. 97 +/- 1.6%, respectively) and NAT2 activity did not affect the levels of any DNA adduct measured, it is unlikely that interindividual variation in NAT2 function is relevant for BZ-associated bladder carcinogenesis. C1 NATL INST OCCUPAT HLTH,AHMEDABAD,GUJARAT,INDIA. VET AFFAIRS MED CTR,ST LOUIS,MO 63125. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63125. NIOSH,CINCINNATI,OH 45267. NIEHS,RES TRIANGLE PK,NC 27709. UNIV CINCINNATI,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. RP Rothman, N (reprint author), NCI,OCCUPAT STUDIES SECT,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [1-P30-ES06096-01] NR 50 TC 73 Z9 74 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 5084 EP 5089 DI 10.1073/pnas.93.10.5084 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500103 PM 8643532 ER PT J AU Parshad, R Sanford, KK Price, FM Melnick, LK Nee, LE Schapiro, MB Tarone, RE Robbins, JH AF Parshad, R Sanford, KK Price, FM Melnick, LK Nee, LE Schapiro, MB Tarone, RE Robbins, JH TI Fluorescent light-induced chromatid breaks distinguish Alzheimer disease cells from normal cells in tissue culture SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA damage and repair; free radicals; xeroderma pigmentosum; antioxidant ID DNA EXCISION-REPAIR; XERODERMA-PIGMENTOSUM; IONIZING-RADIATION; COCKAYNE-SYNDROME; X-IRRADIATION; G2 PHASE; DAMAGE; RADIOSENSITIVITY; LYMPHOCYTES; CANCER AB The neurodegeneration and amyloid deposition of sporadic Alzheimer disease (AD) also occur in familial AD and in all trisomy-21 Down syndrome (DS) patients, suggesting a common pathogenetic mechanism. We investigated whether defective processing of damaged DNA might be that mechanism, as postulated for the neurodegeneration in xeroderma pigmentosum, a disease with defective repair not only of UV radiation-induced, but also of some oxygen free radical-induced, DNA lesions. We irradiated AD and DS skin fibroblasts or blood lymphocytes with fluorescent light, which is known to cause free radical-induced DNA damage. The cells were then treated with either beta-cytosine arabinoside (araC) or caffeine, and chromatid breaks were quantified. At least 28 of 31 normal donors and 10 of 11 donors with nonamyloid neurodegenerations gave normal test results. All 12 DS, 11 sporadic AD, and 16 familial AD patients tested had abnormal araC and caffeine tests, as did XP-A cells. In one of our four AD families, an abnormal caffeine test was found in all 10 afflicted individuals (including 3 asymptomatic when their skin biopsies were obtained) and in 8 of 11 offspring at a 50% risk for AD. Our tests could prove useful in predicting inheritance of familial AD and in supporting, or rendering unlikely, the diagnosis of sporadic AD in patients suspected of having the disease. C1 NCI,NIH,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,NIH,BIOSTAT BRANCH,BETHESDA,MD 20892. NINCDS,NIH,FAMILY STUDIES UNIT,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. NR 34 TC 55 Z9 56 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 5146 EP 5150 DI 10.1073/pnas.93.10.5146 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500115 PM 8643543 ER PT J AU Erickson, JD Schafer, MKH Bonner, TI Eiden, LE Weihe, E AF Erickson, JD Schafer, MKH Bonner, TI Eiden, LE Weihe, E TI Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amine storage; psychostimulants; neurotoxicity; neuroendocrine lineage ID CHROMAFFIN GRANULES; CHRONIC PARKINSONISM; AMINE TRANSPORTER; SEROTONIN; TOXICITY; 1-METHYL-4-PHENYLPYRIDINIUM; METABOLITE; HISTAMINE; MECHANISM; VESICLES AB A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpressed in all chromaffin cells of the adrenal medulla. VMAT2 alone is expressed in histamine storing enterochromaffin-like cells of the oxyntic mucosa of the stomach. The transport characteristics and pharmacology of each VMAT isoform have been directly compared after expression in digitonin-permeabilized fibroblastic (CV-1) cells, providing information about substrate feature recognition by each transporter and the role of vesicular monoamine storage in the mechanism of action of psychopharmacologic and neurotoxic agents in human. Serotonin has a similar affinity for both transporters. Catecholamines exhibit a 3-fold higher affinity, and histamine exhibits a 30-fold higher affinity, for VMAT2. Reserpine and ketanserin are slightly more potent inhibitors of VMAT2-mediated transport than of VMAT1-mediated transport, whereas tetrabenazine binds to and inhibits only VMAT2. N-methyl-4-phenylpyridinium, phenylethylamine, amphetamine, and methylenedioxymethamphetamine are all more potent inhibitors of VMAT2 than of VMAT1, whereas fenfluramine is a more potent inhibitor of VMAT1-mediated monamine transport than of VMAT2-mediated monoamine transport. The unique distributions of hVMAT1 and hVMAT2 provide new markers for multiple neuroendocrine lineages, and examination of their transport properties provides mechanistic insights into the pharmacology and physiology of amine storage in cardiovascular, endocrine, and central nervous system function. C1 NIMH, NIH, CELL BIOL LAB, BETHESDA, MD 20892 USA. UNIV MARBURG, DEPT ANAT & CELL BIOL, MARBURG, GERMANY. RP Erickson, JD (reprint author), NIMH, NIH, MOLEC NEUROSCI SECT, BLDG 36, ROOM 3A-17, BETHESDA, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 44 TC 282 Z9 289 U1 3 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 MAY 14 PY 1996 VL 93 IS 10 BP 5166 EP 5171 DI 10.1073/pnas.93.10.5166 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500119 PM 8643547 ER PT J AU Langlois, JA Harris, T Looker, AC Madans, J AF Langlois, JA Harris, T Looker, AC Madans, J TI Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BONE-MINERAL DENSITY; BODY-MASS INDEX; POST-MENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; MUSCLE STRENGTH; PROXIMAL FEMUR; ESTROGEN USE; SMOKING; THIAZIDE AB Background: Although changes in body weight with aging are common, little is known about the effects of weight change on health in old age. Objectives: To study the effects of weight loss and weight gain from age 50 years to old age on the risk of hip fracture among postmenopausal white women aged 67 years and older and to determine if the level of weight at age 50 years modifies this risk. Methods: The association between weight change and the risk of hip fracture was studied in 3683 community-dwelling white women aged 67 years and older from three sites of the Established Populations for Epidemiologic Studies of the Elderly. Results: Extreme weight loss (10% or more) beginning at age 50 years was associated in a proportional hazards model with increased risk of hip fracture (relative risk [RR], 2.9; 95% confidence interval [CI], 2.0-4.1). This risk was greatest among women in the lowest (RR, 2.3; CI, 1.1-4.8) and middle (RR, 2.8; CI, 1.5-5.3) tertiles of body mass index at age 50 years. Among the thinnest women, even more modest weight loss (5% to <10%) was associated with increased risk of hip fracture (RR, 2.3; CI, 1.0-5.2). Weight gain of 10% or more beginning at age 50 years provided borderline protection against the risk of hip fracture (RR, 0.7; CI, 0.4-1.0). The RRs for weight gain of 10% or more were protective only among women in the middle and high tertiles of body mass index at age 50 years and were not significant (middle tertile RR, 0.8; CI, 0.3-1.8; high tertile RR, 0.6; CI, 0.2-1.9). Conclusions: Weight history is an important determinant of the risk of hip fracture. Weight loss beginning at age 50 years increases the risk of hip fracture in older white women, especially among those who are thin at age 50 years; weight gain of 10% or more decreases the risk of hip fracture. Physicians should include weight history in their assessment of postmenopausal older women for risk of hip fracture. C1 NATL CTR HLTH STAT, HYATTSVILLE, MD 20782 USA. RP Langlois, JA (reprint author), NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG, SUITE 3C-309,7201 WISCONSIN AVE, MSC5, BETHESDA, MD 20892 USA. NR 57 TC 92 Z9 93 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 13 PY 1996 VL 156 IS 9 BP 989 EP 994 DI 10.1001/archinte.156.9.989 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UK585 UT WOS:A1996UK58500007 PM 8624179 ER PT J AU Ha, JH Basile, AS AF Ha, JH Basile, AS TI Modulation of ligand binding to components of the GABA(A) receptor complex by ammonia: Implications for the pathogenesis of hyperammonemic syndromes SO BRAIN RESEARCH LA English DT Article DE ammonia; muscimol; flunitrazepam; GABA(A) receptor; liver failure ID GAMMA-AMINOBUTYRIC-ACID; ISCHEMIC LIVER-FAILURE; HEPATIC-ENCEPHALOPATHY; RAT-BRAIN; BENZODIAZEPINE RECEPTOR; SYNAPTIC TRANSMISSION; SPINAL MOTONEURONS; PYRAMIDAL CELLS; AMINO-ACIDS; METABOLISM AB The effects of 5-2500 mu M concentrations of neutral ammonium salts on the binding of ligands to components of the GABA(A) receptor complex were investigated. [H-3]Flunitrazepam binding to the benzodiazepine receptor was enhanced by ammonium (10-500 mu M), but not sodium tartrate with EC(50) = 98 mu M and E(max) = 31%. Further increasing ammonium tartrate concentrations (500-2500 mu M) decreased [H-3]flunitrazepam binding to control levels. The ammonium tartrate-induced increase in [H-3]flunitrazepam binding was manifested as a 50% decrease in K-d. Furthermore, GABA increased the potency of ammonium tartrate in enhancing [H-3]flunitrazepam binding by 63%. [H-3]Ro 15-1788 and [H-3]Ro 15-4513 binding to the benzodiazepine receptor was not significantly enhanced by ammonium tartrate (E(max) approximate to 13%). Ammonium tartrate also increased, then decreased the binding of 500 nM [H-3]muscimol to the GABA(A) receptor (EC(50) = 52 mu M, E(max) = 30%) in a concentration-dependent manner, but had no effect on [H-3]SR 95-531 binding (E(max) <16%). The ammonium tartrate-induced alterations in [H-3]muscimol binding were demonstrated in saturation assays as the loss of the high affinity binding site and a 27% increase in the B-max of the low affinity binding site. These results indicate that ammonia biphasically enhances, then returns ligand binding to both the GABA and benzodiazepine receptor components of the GABA(A) receptor complex to control levels in a barbiturate-like fashion. This suggests that ammonia may enhance GABAergic neurotransmission at concentrations commonly encountered in hepatic failure, an event preceding the suppression of inhibitory neuronal function observed at higher (>1 mM) ammonia concentrations. This increase in GABAergic neurotransmission is consistent with the clinical picture of lethargy, ataxia and cognitive deficits associated with liver failure and congenital hyperammonemia. C1 NIDDKD,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 51 TC 37 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 13 PY 1996 VL 720 IS 1-2 BP 35 EP 44 DI 10.1016/0006-8993(96)00104-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UQ951 UT WOS:A1996UQ95100005 PM 8782894 ER PT J AU SingerLahat, D Liu, J Wess, J Felder, CC AF SingerLahat, D Liu, J Wess, J Felder, CC TI The third intracellular domain of the m3 muscarinic receptor determines coupling to calcium influx in transfected Chinese hamster ovary cells SO FEBS LETTERS LA English DT Article DE muscarinic receptor; chimeric receptor; Ca2+ influx; CHO-K1 cells ID ARACHIDONIC-ACID RELEASE; CLONED GENES; EXPRESSION; SUBTYPES; HYDROLYSIS; ACTIVATION; SEQUENCE; CYCLASE AB The m2 and m3 muscarinic acetylcholine receptors were expressed in CHO cells and were shown to couple to the release of calcium from intracellular stores, The m3 receptor, but not the m2 receptor, also coupled to calcium influx, Chimeric m2/m3 receptors were used to determine the structural domain of the m3 receptor linked to the regulation of calcium influx. It was found that the third intracellular loop of m3 receptor plays a fundamental role in regulating Ca2+ influx predicted to occur through Ca2+ channels located in the plasma membrane in CHO cells. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NIDDKD,LAB BIOORGAN CHEM,BETHESDA,MD 20892. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 13 PY 1996 VL 386 IS 1 BP 51 EP 54 DI 10.1016/0014-5793(96)00398-5 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UL657 UT WOS:A1996UL65700012 PM 8635603 ER PT J AU Sastry, S AF Sastry, S TI Lyapunov spectra, instantaneous normal mode spectra, and relaxation in the Lennard-Jones liquid SO PHYSICAL REVIEW LETTERS LA English DT Article ID CLUSTERS; DYNAMICS; FLUIDS; CHAOS AB Lyapunov spectra are obtained numerically for the Lennard-Jones liquid for a range of temperatures. An approximation scheme for calculating the Lyapunov spectrum is described, assuming knowledge of (i) the instantaneous normal mode spectrum which characterizes the local potential energy landscape, and (ii) a decorrelation time. The adaptation, for this purpose, of an analytical relation by Newman is described. The temperature dependence of the maximum Lyapunov exponent, calculated with an ansatz for the decorrelation time, is shown to be in excellent agreement with simulation results. C1 NIH,PHYS SCI LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20952. NR 18 TC 18 Z9 18 U1 0 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAY 13 PY 1996 VL 76 IS 20 BP 3738 EP 3741 DI 10.1103/PhysRevLett.76.3738 PG 4 WC Physics, Multidisciplinary SC Physics GA UK560 UT WOS:A1996UK56000020 ER PT J AU Uren, A Yu, JC Li, WQ Chung, IY Mahadevan, D Pierce, JH Heidaran, MA AF Uren, A Yu, JC Li, WQ Chung, IY Mahadevan, D Pierce, JH Heidaran, MA TI Identification of a domain within the carboxyl-terminal region of the beta platelet-derived growth factor (PDGF) receptor that mediates the high transforming activity of PDGF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; GTPASE-ACTIVATING PROTEIN; PHOSPHOLIPASE-C-GAMMA; SIGNAL TRANSDUCTION; TYROSINE KINASES; PHOSPHORYLATION SITES; BINDING; EXPRESSION; SUBUNIT; CELLS AB We have reported previously that a chimeric platelet-derived growth factor receptor (PDGFR) possessing the ligand binding domain of the alpha PDGFR and the intracellular domain of the beta PDGFR (alpha(340)beta(342)R) was markedly more efficient than the wild type alpha PDGFR (alpha RWT) in its ability to enhance PDGF-A transforming activity in NIH/3T3 fibroblasts. To determine the region within the cytoplasmic domain of beta PDGFR that confers this higher transforming activity, we generated several additional alpha/beta PDGFR chimerae. When a chimeric PDGFR possessing the first 933 amino-terminal amino acids from the alpha PDGFR and the final 165 amino acids from the carboxyl-terminal of the beta PDGFR (alpha(933)beta(942)R) was cotransfected with the PDGF-A gene into NIH/3T3 cells, it showed a similar high efficiency to enhance PDGF-A chain transforming activity as alpha(340)beta(342)R. However, when chimeric PDGFRs in which either the kinase insert domain (alpha beta RKI) or the last 79 amino acids from the carboxyl-terminal end of the beta PDGFR (alpha(1024)beta(1028)R) were substituted into alpha PDGFR sequences were cotransfected with PDGF-A, they showed similar low efficiencies in enhancing transforming activity as the alpha RWT. These results predicted that the 86 amino acids following the tyrosine kinase 2 domain of beta PDGFR (amino acid residues 942-1027) were responsible for the higher transforming activity of beta PDGFR. To confirm this finding, we next constructed a chimera in which amino acid residues 942-1028 of the beta PDGFR (alpha beta(942-1028)R) were substituted for those in the alpha PDGFR. Cotransfection experiments indicated that alpha beta(942-1028)R increased transforming activity of PDGF-A to similar extent as the alpha(933)beta(942)R or alpha(340)beta(342)R. Therefore, our findings define a critical domain within the noncatalytic region of beta PDGFR intracellular domain that confers the higher focus forming activity mediated by the beta PDGFR. C1 NCI,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NR 43 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11051 EP 11054 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400005 PM 8626645 ER PT J AU Han, JS Chung, JK Kang, HS Donaldson, J Bae, YS Rhee, SG AF Han, JS Chung, JK Kang, HS Donaldson, J Bae, YS Rhee, SG TI Multiple forms of phospholipase D inhibitor from rat brain cytosol - Purification and characterization of heat-labile form SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLCHOLINE HYDROLYSIS; PLASMA-MEMBRANES; G-PROTEIN; PHOSPHORYLATION; IDENTIFICATION; NEUTROPHILS; ACTIVATION; RECEPTOR; CELLS AB Rat brain cytosol contains proteins that markedly inhibit the activity of partially purified brain membrane phospholipase D (PLD) stimulated by ADP-ribosylation factor (Arf) and phosphatidylinositol 4,5-bisphosphate (PIP2). Sequential chromatography of the brain cytosol yielded four inhibitor fractions, which exhibited different kinetics to heat treatment at 70 degrees C. Purification of the most heat-labile inhibitor to homogeneity yielded two preparations, which displayed apparent molecular masses of 150 kDa and 135 kDa, respectively, on SDS-polyacrylamide gels. Tryptic digests of the 150- and 135-kDa proteins yielded similar elution profiles on a C-18 reverse-phase column, suggesting that the 135-kDa form is a truncated form of the 150-kDa form. Sequences of two tryptic peptides were determined. A data base search revealed no proteins with these sequences. The purified 150-kDa inhibitor negated the PLD activity stimulated by Arf, RhoA, or Cdc42. The concentration required for half-maximal inhibition was 0.4 nM. Concentration dependence on the 150-kDa inhibitor was not affected by changes in the concentrations of Arf, PIP2, or phosphatidylcholine used in the assays, suggesting that the inhibition is not due to competition with the activators or substrate for PLD. The purified inhibitor did not affect the PIP2-hydrolyzing activity of a phospholipase C isozyme that was measured with substrate vesicles of lipid composition identical with that used for the PLD assay. Thus, the mechanism of inhibition appears to be a specific allosteric modification of PLD rather than disruption of substrate vesicles. C1 NHLBI,LAB CELL SIGNALLING,NIH,BETHESDA,MD 20892. NR 34 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11163 EP 11169 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400022 PM 8626662 ER PT J AU Ma, J Saito, H Oka, T Vijay, IK AF Ma, J Saito, H Oka, T Vijay, IK TI Negative regulatory element involved in the hormonal regulation of GlcNAc-1-P transferase gene in mouse mammary gland SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATE N-ACETYLGLUCOSAMINE-1-PHOSPHATE TRANSFERASE; ASPARAGINE-LINKED GLYCOPROTEINS; ACETYL-D-GLUCOSAMINE; BETA-CASEIN; TRANSCRIPTIONAL REPRESSION; RESPONSE ELEMENTS; THYROID-HORMONE; NUCLEAR FACTOR; RETINOIC ACID; PROMOTER AB The gene encoding UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate transferase (GPT), the enzyme that initiates the pathway for the biosynthesis of asparagine-linked glycoproteins, is ubiquitously expressed in eukaryotic cells. However, its expression in the mammary gland is developmentally and hormonally regulated; transcription of the mouse mammary GPT gene is stimulated by the lactogenic hormones, insulin, glucocorticoid, and prolactin. The involvement of cis-acting elements in regulating the expression of the mouse GPT (mGPT) gene was investigated by transient transfections of various GPT promoter/luciferase (Luc) constructs into primary mouse mammary epithelial cells. A series of 5'-deletions of the GPT promoter identified a distal negative regulatory region (base pairs -1057 to -968) and deletion of this region results in enhanced hormonal induction (similar to 7-fold) with no effect on basal promoter activity. Electrophoretic mobility shift assays (EMSA) performed with nuclear extracts from different developmental stages of mouse mammary gland demonstrated that the binding activity of the nuclear proteins to the distal negative regulatory region was predominant in virgin stage as compared with pregnant and lactating stages. EMSA performed with nuclear extracts from virgin explants showed that the binding activity was markedly decreased after cultivation with the combination of the three lactogenic hormones. DNase I footprinting analysis identified two pentamer direct repeat motifs, AGGAA and GAAAC, within the negative regulatory region. EMSA competition experiments showed that mutations within the direct repeats failed to compete for binding of the nuclear proteins to labeled wild type oligonucleotide. Transcription from the promoter containing the mutated direct repeats was increased greatly, consistent with the conclusion that these motifs functions in vivo to repress GPT gene expression. These data suggest the importance of the negative regulatory region in hormonal control of mGPT gene expression in mammary gland. C1 UNIV MARYLAND,DEPT ANIM SCI,COLLEGE PK,MD 20742. NIDDK,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK19682] NR 41 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11197 EP 11203 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400027 PM 8626667 ER PT J AU Welsh, GI Miyamoto, S Price, NT Safer, B Proud, CG AF Welsh, GI Miyamoto, S Price, NT Safer, B Proud, CG TI T-cell activation leads to rapid stimulation of translation initiation factor eIF2B and inactivation of glycogen synthase kinase-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; POLYPEPTIDE-CHAIN INITIATION; RABBIT RETICULOCYTE LYSATE; PROTEIN-SYNTHESIS; LYMPHOCYTE STIMULATION; FACTOR-II; PHOSPHORYLATION; PHYTOHEMAGGLUTININ; MECHANISM; INSULIN AB Mitogenic stimulation of T-lymphocytes causes a rapid activation of protein synthesis, which reflects in part increased expression of many translation components. Their levels, however, rise more slowly than the rate of protein synthesis, indicating an enhancement of the efficiency of their utilization. Initiation factor eIF2B catalyzes a hey regulatory step in the initiation of translation, and we have therefore studied its activity following T-cell activation. eIF2B activity rises quickly, increasing as early as 5 min after cell stimulation. This initial phase is followed by an additional slow but substantial increase in eLF2B activity. The level of eIF2B subunits did not change over the initial rapid phase but did increase at later time points. Northern analysis revealed that levels of eIF2B mRNA only rose during the later phase. The rapid activation of eIF2B following mitogenic stimulation of T-cells is therefore mediated by factors other than its own concentration. The largest (epsilon) subunit of elF2B is a substrate for glycogen synthase kinase 3 (GSK-3), the activity of which rapidly decreases following T-cell activation. Since phosphorylation of eIF2B by GSK-3 appears to inhibit nucleotide exchange in vitro, this provides a potential mechanism by which eIF2B may be activated. C1 UNIV BRISTOL,SCH MED SCI,DEPT BIOCHEM,BRISTOL BS8 1TD,AVON,ENGLAND. NHLBI,MOLEC HEMATOL BRANCH,NIH,BETHESDA,MD 20892. OI Proud, Christopher/0000-0003-0704-6442 FU Wellcome Trust NR 42 TC 82 Z9 83 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11410 EP 11413 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400056 PM 8626696 ER PT J AU Warren, BS Kusk, P Wolford, RG Hager, GL AF Warren, BS Kusk, P Wolford, RG Hager, GL TI Purification and stabilization of transcriptionally active glucocorticoid receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING; PROTEIN; DNA; ACTIVATION; COMPLEXES; INVITRO; INVIVO AB A major obstacle to the purification of glucocorticoid receptor (GR) is the very high nonspecific surface adsorption of this protein. This phenomenon is a property of the GR itself and does not reflect overall protein concentration or buffer conditions. We have observed that the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) is unique in its ability to stabilize the receptor and largely eliminate loss to nonspecific adsorption. We have coupled this observation with a two-step purification method that allows efficient purification and stabilization of transcriptionally active glucocorticoid receptor. For this procedure, the GR first undergoes a major purifica tion by anion exchange chromatography following hormone binding and on-column receptor transformation. Second, the GR is resolved to homogeneity utilizing a hydrophobic interaction chromatography step which consists of a 2.5 M to 0 M NaCl gradient elution of contaminating proteins followed by displacement of GR by CHAPS. GR at both stages of purification was able to activate transcription from the glucocorticoid response element containing the promoter region of the long terminal repeat of the mouse mammary tumor virus. This simple and efficient methodology should be of a considerable advantage for studies of the biology of the active, full-length GR. C1 NCI, MOLEC VIROL LAB, HORMONE ACT & ONCOGENESIS SECT, NIH, BETHESDA, MD 20892 USA. NR 28 TC 20 Z9 20 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11434 EP 11440 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400060 PM 8626700 ER PT J AU Zhang, L Yu, YK Mackin, S Weight, FF Uhl, GR Wang, JB AF Zhang, L Yu, YK Mackin, S Weight, FF Uhl, GR Wang, JB TI Differential mu opiate receptor phosphorylation and desensitization induced by agonists and phorbol esters SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OPIOID RECEPTOR; RAT-BRAIN; EXPRESSION; CLONING AB mu opiate receptors, the principal sites for opiate analgesia and reward, can display compensatory responses to opiate agonist drug administration. Agonist-induced K+ channel responses mediated by these receptors desensitize when examined in Xenopus oocyte expression systems. Mechanisms underlying such processes could include phosphorylation events similar to those re ported to desensitize other G protein-linked receptors. We used C-terminally directed anti-mu receptor antibodies to immunoprecipitate a phosphoprotein with size appropriate for the mu receptor from stably expressing Chinese hamster ovary cells. Phosphorylation of this mu opiate receptor protein was enhanced approximately 5-fold by treatment with the mu agonist morphine. The time course and dose-response relationships between mu receptor phosphorylation and agonist-induced desensitization display interesting parallels. Phosphorylation of mu opiate receptor protein is also enhanced similar to 5-fold by treatment with the protein kinase C activator phorbol 12-myristate 13-acetate. The protein kinase inhibitor staurosporine blocked the effect of phorbol 12-myristate 13-acetate on mu receptor phosphorylation. However, staurosporine failed to block morphine-induced phosphorylation. These observations suggest that several biochemical pathways can lead to mu receptor phosphorylation events that may include mechanisms involved in mu receptor desensitization. C1 UNIV MARYLAND,SCH PHARM,DEPT PHARMACEUT SCI,BALTIMORE,MD 21201. NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,BETHESDA,MD 20892. NATL INST DRUG ABUSE,MOL NEUROBIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 23 TC 140 Z9 140 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11449 EP 11454 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400062 PM 8626702 ER PT J AU Quinn, KA Treston, AM Unsworth, EJ Miller, MJ Vos, M Grimley, C Battey, J Mulshine, JL Cuttitta, F AF Quinn, KA Treston, AM Unsworth, EJ Miller, MJ Vos, M Grimley, C Battey, J Mulshine, JL Cuttitta, F TI Insulin-like growth factor expression in human cancer cell lines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I IGF-I; BINDING-PROTEINS; MESSENGER-RNA; BREAST-CANCER; LUNG-TUMORS; RECEPTORS; LIVER AB The insulin-like growth factors (IGFs), IGF-I and IGF-II, are potent mitogens for human lung and other epithelial cancer cell lines. Previous studies in defined medium lacking added IGF or insulin suggest that an IGF-related ligand can act as an autocrine growth factor for many cancer cell lines through action via the type I IGF receptor (IGF-R). Analysis of RNA isolated from human lung and breast cancer cell lines by reverse transcription of mRNA and polymerase chain reaction reveal that IGF-I and IGF-II mRNAs were co-expressed with IGF-R in the majority of cell lines. IGF-I mRNA was detected in 11/12 small cell lung cancer cell lines (SCLC), 13/14 non-small cell lung cancer (NSCLC) cell lines, and 1/2 breast cancer cell lines. IGF-II mRNA was detected in 8/10 SCLC, 11/12 NSCLC cell lines, and 2/2 breast lines. All cell lines expressed IGF-R. For analysis of IGF peptide secretion, cell lines were adapted to growth in serum/hormone-free culture medium (R(0)), and to avoid interference by IGF-binding proteins, secreted IGF peptides were isolated under acidic conditions and analyzed by Western blotting. Based upon measurement of the sensitivity of the anti-IGF antibodies for detection of recombinant human IGFs, IGF peptides accumulated in conditioned medium at greater than picomolar concentrations should have been readily detected. In three cell lines (two lung and one breast) secreted IGF immunoreactivity was detected as three molecular mass species of 23, 14, and 6 kDa. Isolation and NH4-terminal sequencing of each of these species definitively identified them as differentially processed forms of the IGF-II prohormone. Despite the high frequency of IGF-I gene expression detected by reverse transcription-polymerase chain reaction analysis, only one lung cancer cell line, NCI-N417d, was found that unequivocally secreted IGF-I peptide. This direct sequence determination unambiguously identifies IGF-II as the predominant IGF involved in the autocrine growth stimulation of human lung and breast epithelial tumor cell lines and supports a growing body of literature that implicates IGF-II/IGF-R autocrine loops as a common growth mechanism in epithelial carcinogenesis. C1 NCI,NIH,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. PERKIN ELMER CORP,DIV APPL BIOSYST,FOSTER CITY,CA 94404. NIDCD,NIH,GAITHERSBURG,MD 20850. NR 33 TC 159 Z9 167 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11477 EP 11483 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400066 PM 8626706 ER PT J AU Rahn, T Ronnstrand, L Leroy, MJ Wernstedt, C Tornqvist, H Manganiello, VC Belfrage, P Degerman, E AF Rahn, T Ronnstrand, L Leroy, MJ Wernstedt, C Tornqvist, H Manganiello, VC Belfrage, P Degerman, E TI Identification of the site in the cGMP-inhibited phosphodiesterase phosphorylated in adipocytes in response to insulin and isoproterenol SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; KM CAMP PHOSPHODIESTERASE; RAT ADIPOCYTES; FAT-CELLS; AMP PHOSPHODIESTERASE; GEL-ELECTROPHORESIS; ACTIVATION; LIPOLYSIS; STIMULATION AB Stimulation of rat adipocytes with insulin and isoproterenol results in serine phosphorylation and activation of the adipocyte cGMP-inhibited phosphodiesterase (cGI PDE), events believed to be important in the antilipolytic action of insulin (Degerman, E., Smith, C. J., Tornqvist, H., Vasta, V., Manganiello, V. C., and Belfrage, P. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 533-537). Here we demonstrate, by two-dimensional phosphopeptide mapping, that the major phosphopeptide generated by trypsin, or trypsin followed by Asp-N protease digestion of [P-32]cGI PDE phosphorylated in adipocytes in response to isoproterenol and/or insulin, in each case co-migrates with the phosphopeptide released by the same treatment of M(297)FRRPS((P) under bar)LPCISREQ(310). This peptide was synthesized based on the deduced sequence of the cloned rat adipocyte cGI PDE and phosphorylated by cAMP-dependent protein kinase (protein kinase A). Radiosequencing of authentic and synthetic tryptic P-32-peptides showed that a single site in cGI PDE (Ser(302)) was phosphorylated in adipocytes incubated with isoproterenol and/or insulin. The more than additive phosphorylation and activation of cGI PDE in response to the two hormones found in this report and previously (Smith, C. J., Vasta, V., Degerman, E., Belfrage, P., and Manganiello, V. C. (1991) J. Biol. Chem. 266, 13385-13390) is proposed to reflect cross-talk between their respective signal transduction pathways at the level of the cGI PDE serine protein kinase or upstream regulatory component(s). C1 LUND UNIV,DEPT MOLEC & CELL BIOL,MOLEC SIGNALLING LAB,S-22100 LUND,SWEDEN. UNIV LUND HOSP,DEPT PEDIAT,S-22100 LUND,SWEDEN. CTR BIOMED,LUDWIG INST CANC RES,S-75185 UPPSALA,SWEDEN. NHLBI,NIH,BETHESDA,MD 20892. RI Ronnstrand, Lars/A-2429-2011 NR 43 TC 48 Z9 49 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11575 EP 11580 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400080 PM 8626720 ER PT J AU Yamada, K Rice, KC FlippenAnderson, JL Eissenstat, MA Ward, SJ Johnson, MR Howlett, AC AF Yamada, K Rice, KC FlippenAnderson, JL Eissenstat, MA Ward, SJ Johnson, MR Howlett, AC TI (Aminoalkyl)indole isothiocyanates as potential electrophilic affinity ligands for the brain cannabinoid receptor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANALOGS; PRAVADOLINE; BINDING AB A series of (aminoalkyl)indole compounds, naphthalene analogs of pravadoline (1), has been shown to exhibit cannabinoid agonist activities such as antinociception in animals, inhibition of adenylate cyclase in brain membranes, and binding to the cannabinoid receptor. These pravadoline analogs were selected for the preparation of potential electrophilic affinity ligands based on the synthesis of isothiocyanate derivatives. One isothiocyanatonaphthalene derivative (8) displaced [H-3]CP-55940 binding to a rat brain P2 membrane preparation with an IC50 of 690 nM, which was 10-fold less potent than the parent molecule (IC50 = 73 nM). Isothiocyanate substitution at various positions on the naphthalene moiety of the desmethyl analog 10 gave compounds that displaced [H-3]CP-55940 with IC50 values between 400 and 1000 nM, compared with 46 nM for the parent compound 10. However, 6-isothiocyanato substitution on the indole ring of the desmethyl analog provided isothiocyanate 12 that displaced [H-3]CP-55940 binding with an IC50 of 160 nM. After pretreatment of brain membranes with this high-affinity isothiocyanato ligand followed by washing out the ligand, the membranes were depleted of 90% of the cannabinoid receptor binding capacity. Loss of receptor binding capacity was half-maximal at 300 nM of the derivative under standard assay conditions. As a control, pretreatment with the parent compound at concentrations that were 20 times the K-d failed to alter subsequent binding activity. This study demonstrates that an isothiocyanato (aminoalkyl)-indole (12) can behave as an affinity ligand which binds irreversibly to the cannabinoid receptor in brain and which precludes subsequent binding of the cannabinoid ligand [H-3]CP-55940. C1 ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. SANOFI WINTHROP,SANOFI RES DIV,DEPT MED CHEM,COLLEGEVILLE,PA 19426. TRIMERIS,RES TRIANGLE PK,NC 27709. OI Ward, Susan J/0000-0002-5729-5263; Howlett, Allyn/0000-0002-2810-0164 FU NIDA NIH HHS [R01-DA06312, K05-DA00182] NR 27 TC 12 Z9 12 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 10 PY 1996 VL 39 IS 10 BP 1967 EP 1974 DI 10.1021/jm950932r PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UM248 UT WOS:A1996UM24800008 PM 8642555 ER PT J AU Wang, SM Milne, GWA Yan, XJ Posey, IJ Nicklaus, MC Graham, L Rice, WG AF Wang, SM Milne, GWA Yan, XJ Posey, IJ Nicklaus, MC Graham, L Rice, WG TI Discovery of novel, non-peptide HIV-1 protease inhibitors by pharmacophore searching SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEFICIENCY SYNDROME AIDS; DRUG DESIGN AB Fifteen novel non-peptide HIV-1 protease inhibitors were identified by flexible 3D database pharmacophore searching of the NCI DIS 3D database. The pharmacophore query used in the search was derived directly from the X-ray determined structures of protease/inhibitor complexes. These 15 inhibitors, belonging to nine different chemical classes, are promising leads for further development. The two best inhibitors found, NSC 32180, a ''dimer'' of 4-hydroxycoumarin, and NSC 117027, a ''tetramer'' of 2-hydroxy quinone, had ID50 values of 0.32 and 0.75 mu M for HIV-1 protease inhibition, respectively, and two other inhibitors had ID50 values close to 1 mu M. Among the potent inhibitors, NSC 158393 not only demonstrated activity against HIV-1 protease (ID50 1.7 mu M) but also exhibited promising antiviral activity in HIV-1-infected CEM-SS cells (EC(50) = 11.5 mu M). Validation of the pharmacophore used in the search was accomplished by conformational analysis. The binding modes of the most potent inhibitor found in our studies, NSC 32180, were predicted employing docking and molecular dynamics techniques. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB ANTIVIRAL DRUG METAB,FREDERICK,MD 21702. UNIV DIST COLUMBIA,DEPT CHEM,WASHINGTON,DC 20008. RI Wang, Shaomeng/E-9686-2010; Nicklaus, Marc/N-4183-2014 NR 36 TC 106 Z9 117 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 10 PY 1996 VL 39 IS 10 BP 2047 EP 2054 DI 10.1021/jm950874+ PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UM248 UT WOS:A1996UM24800016 PM 8642563 ER PT J AU Bertha, CM Ellis, M FlippenAnderson, JL Porreca, F Rothman, RB Davis, P Xu, H Becketts, K Rice, KC AF Bertha, CM Ellis, M FlippenAnderson, JL Porreca, F Rothman, RB Davis, P Xu, H Becketts, K Rice, KC TI Probes for narcotic receptor-mediated phenomena .21. Novel derivatives of 3-(1,2,3,4,5,11-hexahydro-3-methyl-2,6-methano-6H-azocino[4,5-b]indol-6- yl)-phenols with improved delta opioid receptor selectivity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BINDING-SITES; AFFINITY; AGONIST; PEPTIDES; BW373U86; ANALOG; BRAIN AB Derivatives of racemic and optically pure levorotatory 3-(1,2,3,4,5,11-hexahydro-3-methyl-2,6-methano-6H-azocino[4,5-b] indol-6-yl)phenols containing methoxy substituents in the C10', C9', and C8' positions (compounds 9-11, respectively) were synthesized and characterized by spectroscopic and X-ray methods. The binding affinities for the mu, delta, and kappa(1) opioid receptors and activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD) functional bioassays were determined for these compounds. A methoxy substituent in the C8' position decreases the binding affinity for both the mu and delta receptors, while a C10' methoxy substituent has little effect on either binding affinity. Interestingly, a methoxy group at the C9' position in the levorotatory series provides compound (-)-10 which exhibits both enhanced in vitro affinity and selectivity for the delta opioid receptor relative to the unsubstituted derivative (-)-8 and is the most selective (mu/delta IC50 ratio 17.9, kappa(1)/delta IC50 ratio 314) and highest affinity (IC50 3.7 nM) delta receptor ligand for this novel class of compounds. The results of the GPI and MVD bioassays are more dramatic and indicate that (-)-10 is an agonist for the delta receptor (IC50 49.0 nM) with substantial selectivity for the delta versus the mu receptor borne out by a GPI/MVD IC50 ratio of >612. C1 NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724. NR 24 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 10 PY 1996 VL 39 IS 10 BP 2081 EP 2086 DI 10.1021/jm950695s PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UM248 UT WOS:A1996UM24800020 PM 8642567 ER PT J AU Crawley, JN AF Crawley, JN TI Galanin-acetylcholine interactions: Relevance to memory and Alzheimer's disease SO LIFE SCIENCES LA English DT Review DE galanin; neuropeptide; acetylcholine; neurotransmitter release; learning and memory; Alzheimer's disease ID NUCLEOTIDE-SEQUENCE ANALYSIS; RAT VENTRAL HIPPOCAMPUS; BASAL FOREBRAIN COMPLEX; CENTRAL NERVOUS-SYSTEM; AGE-RELATED-CHANGES; MESSENGER-RNA; BINDING-SITES; PHOSPHOINOSITIDE TURNOVER; CEREBRAL-CORTEX; NUCLEUS BASALIS AB The neuropeptide, galanin, and its receptors are localized in the cholinergic basal forebrain and its projection areas in mammalian brain. Centrally administered galanin inhibits acetylcholine release in the rat ventral hippocampus, and produces deficits in learning and memory tasks. In Alzheimer's disease, galanin is overexpressed in terminals innervating the nucleus basalis of Meynert cell bodies. Selective galanin receptor antagonists provide a novel approach for increasing cholinergic function, as a potential adjunct to the clinical treatment of dementias. RP Crawley, JN (reprint author), NIMH,SECT BEHAV NEUROPHARMACOL,EXPTL THERAPEUT BRANCH,BLDG 10 ROOM 4N212,BETHESDA,MD 20892, USA. NR 112 TC 102 Z9 105 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAY 10 PY 1996 VL 58 IS 24 BP 2185 EP 2199 DI 10.1016/0024-3205(96)00093-8 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UK527 UT WOS:A1996UK52700001 PM 8649205 ER PT J AU Moran, A Turner, RJ AF Moran, A Turner, RJ TI Evidence that quantal Ca2+ release in HSG cells is not due to 'all-or-none' release from discrete Ca2+ stores with differing sensitivities to IP3 SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Ca2+ release; quantal Ca2+ release; stimulus secretion coupling; IP3 receptor ID INOSITOL 1,4,5-TRISPHOSPHATE; LUMINAL CA2+; PERMEABILIZED HEPATOCYTES; CA-2+ ENTRY; LINE; TRISPHOSPHATE; MOBILIZATION; MECHANISM; RECEPTOR AB We demonstrate that the application of the muscarinic agonist carbachol to the human salivary epithelial cell line HSG elicits the now well-known phenomenon of 'quantal' Ca2+ release; namely, that the application of a submaximal concentration of agonist results in the release of only a portion of the agonist-sensitive intracellular Ca2+ pool. One explanation that has been proposed to account for this effect is that there are multiple intracellular Ca2+ stores, each with a different agonist sensitivity, which release Ca2+ in an 'all-or-none' fashion. We test this hypothesis in intact HSG cells with an experimental protocol designed to preferentially load less-agonist-sensitive stores with Ca-40(2+) and more-agonist-sensitive stores with Ca-45(2+). However, contrary to the expectations of the above explanation, these cells do not preferentially release Ca-45(2+) in response to low concentrations of agonist. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,FAC HLTH SCI,DEPT PHYSIOL,BEER SHEVA,ISRAEL. RI MORAN, ARIE/F-1210-2012 NR 19 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY 10 PY 1996 VL 158 IS 1 BP 53 EP 56 PG 4 WC Cell Biology SC Cell Biology GA UT957 UT WOS:A1996UT95700007 PM 8791284 ER PT J AU Voloshin, ON Wang, LJ CameriniOtero, RD AF Voloshin, ON Wang, LJ CameriniOtero, RD TI Homologous DNA pairing promoted by a 20-amino acid peptide derived from RecA SO SCIENCE LA English DT Article ID SINGLE-STRANDED FRAGMENTS; ESCHERICHIA-COLI; SUPERHELICAL DNA; BRANCH MIGRATION; UVSX PROTEIN; BACTERIOPHAGE-T4; RECOMBINATION; BINDING; YEAST AB The molecular structure of the Escherichia coli RecA protein in the absence of DNA revealed two disordered or mobile loops that were proposed to be DNA binding sites. A short peptide spanning one of these loops was shown to carry out the key reaction mediated by the whole RecA protein: pairing (targeting) of a single-stranded DNA to its homologous site on a duplex DNA. In the course of the reaction the peptide bound to both substrate DNAs, unstacked the single-stranded DNA, and assumed a beta structure. These events probably recapitulate the underlying molecular pathway or mechanism used by homologous recombination proteins. C1 NIDDKD,GENET BIOMED BRANCH,NIH,BETHESDA,MD 20892. NR 42 TC 72 Z9 72 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 10 PY 1996 VL 272 IS 5263 BP 868 EP 872 DI 10.1126/science.272.5263.868 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK757 UT WOS:A1996UK75700058 PM 8629021 ER PT J AU Feng, Y Broder, CC Kennedy, PE Berger, EA AF Feng, Y Broder, CC Kennedy, PE Berger, EA TI HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BACTERIOPHAGE-T7 RNA-POLYMERASE; MOLECULAR-CLONING; HUMAN CD4; REGULATED EXPRESSION; CD4-MEDIATED FUSION; MEMBRANE-FUSION; VACCINIA VIRUS; HUMAN HOMOLOG; MURINE CELLS AB A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy. This protein, designated ''fusin,'' is a putative G protein-coupled receptor with seven transmembrane segments. Recombinant fusin enabled CD4-expressing nonhuman cell types to support HIV-1 Env-mediated cell fusion and HIV-1 infection. Antibodies to fusin blocked cell fusion and infection with normal CD4-positive human target cells. Fusin messenger RNA levels correlated with HIV-1 permissiveness in diverse human cell types. Fusin acted preferentially for T cell line-tropic isolates, in comparison to its activity with macrophage-tropic HIV-1 isolates. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 44 TC 3242 Z9 3336 U1 27 U2 124 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 10 PY 1996 VL 272 IS 5263 BP 872 EP 877 DI 10.1126/science.272.5263.872 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK757 UT WOS:A1996UK75700059 PM 8629022 ER PT J AU Lowe, LA Supp, DM Sampath, K Yokoyama, T Wright, CVE Potter, SS Overbeek, P Kuehn, MR AF Lowe, LA Supp, DM Sampath, K Yokoyama, T Wright, CVE Potter, SS Overbeek, P Kuehn, MR TI Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus SO NATURE LA English DT Article ID MOUSE; LATERALITY; SIDEDNESS; REVERSAL AB VERTEBRATES have characteristic and conserved left-right (L-R) visceral asymmetries, for example the left-sided heart. In humans, alterations of L-R development can have serious clinical implications, including cardiac defects(1). Although little is known about how the embryonic L-R axis is established, a recent study in the chick embryo revealed L-R asymmetric expression of several previously cloned genes, including Cnr-1 (for chicken nodal-related-1), and indicated how this L-R molecular asymmetry might be important for subsequent visceral morphogenesis(2). Here we show that nodal(3) is asymmetrically expressed in mice at similar stages, as is Xnr-1 (for Xenopus nodal related-1)(4) in frogs. We also examine nodal expression in two mouse mutations that perturb L-R development, namely situs inversus viscerum (iv)(5), in which assignment of L-R asymmetry is apparently random and individuals develop either normally or are mirror-image-reverse (situs inversus), and inversion of embryonic turning (inv)(6), in which all individuals develop with situs inversus. In both, nodal expression is strikingly affected, being reversed or converted to symmetry. These results further support a key role for nodal and nodal-related genes in interpreting and relaying L-R patterning information in vertebrates. To our knowledge, our results provide the first direct evidence that iv and inv normally function well before the appearance of morphological L-R asymmetry. C1 NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV CINCINNATI,CHILDRENS HOSP RES FDN,DIV DEV BIOL,CINCINNATI,OH 45229. VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 24 TC 370 Z9 376 U1 1 U2 27 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 9 PY 1996 VL 381 IS 6578 BP 158 EP 161 DI 10.1038/381158a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK139 UT WOS:A1996UK13900050 PM 8610013 ER PT J AU Stanley, SK Ostrowski, MA Justement, JS Gantt, K Hedayati, S Mannix, M Roche, K Schwartzentruber, DJ Fox, CH Fauci, AS AF Stanley, SK Ostrowski, MA Justement, JS Gantt, K Hedayati, S Mannix, M Roche, K Schwartzentruber, DJ Fox, CH Fauci, AS TI Effect of immunization with a common recall antigen on viral expression in patients infected with human immunodeficiency virus type 1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HIV-INFECTION; LYMPHOCYTES; AIDS; DISEASE; CELLS; VIREMIA; AGENTS; MODEL AB Background. Activation of the immune system is a normal response to antigenic stimulation, and such activation enhances the replication of human immunodeficiency virus type 1 (HIV-1). We studied the effect of immunization with a common recall antigen on viral expression in HIV-1-infected patients, on the ability to isolate virus, and on the susceptibility to HIV-1 infection of peripheral-blood mononuclear cells (PBMCs) from control subjects not infected with HIV-1. Methods. Thirteen HIV-1-infected patients and 10 uninfected adults were given a 0.5-ml booster dose of tetanus toroid. Studies were performed to evaluate changes in the degree of plasma viremia, proviral burden, the ability to isolate HIV-1, and the susceptibility of PBMCs to acute infection in vitro. Two patients underwent sequential lymph-node biopsies for the assessment of viral burden in these tissues. Results. All 13 HIV-1-infected patients had transient increases in plasma viremia after immunization, and the proviral burden increased in 11. These changes did not correlate with the base-line CD4+ T-cell counts. The lymph-node tissue also had increases in the proviral burden and viral RNA after immunization. The virus was more easily isolated from PBMCs from nine of the patients after immunization than before immunization. Despite considerable variability in the results, PBMCs from 7 of the 10 normal subjects were more easily infected in vitro with HIV-1 after immunization than before immunization. Conclusions. Activation of the immune system by an ongoing antigen-specific immune response to an exogenous stimulus transiently increases the expression of HIV-1 and may enhance the susceptibility of uninfected subjects to HIV-1. (C) 1996, Massachusetts Medical Society. C1 NCI,DEPT NURSING,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. MOL HISTOL INC,GAITHERSBURG,MD. RP Stanley, SK (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 30,RM 7A03,31 CTR DR,MSC-2520,BETHESDA,MD 20892, USA. NR 31 TC 307 Z9 308 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 9 PY 1996 VL 334 IS 19 BP 1222 EP 1230 DI 10.1056/NEJM199605093341903 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA UJ054 UT WOS:A1996UJ05400003 PM 8606717 ER PT J AU Wilcox, AJ Weinberg, CR Baird, DD AF Wilcox, AJ Weinberg, CR Baird, DD TI Pregnancy and the timing of intercourse - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Wilcox, AJ (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 9 PY 1996 VL 334 IS 19 BP 1267 EP 1268 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UJ054 UT WOS:A1996UJ05400015 ER PT J AU Hurley, JH Chen, RD Dean, AM AF Hurley, JH Chen, RD Dean, AM TI Determinants of cofactor specificity in isocitrate dehydrogenase: Structure of an engineered NADP(+)->NAD(+) specificity-reversal mutant SO BIOCHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; 3-ISOPROPYLMALATE DEHYDROGENASE; THERMUS-THERMOPHILUS; COENZYME SPECIFICITY; GENE; PHOSPHORYLATION; ENZYME; MUTAGENESIS; DISRUPTION AB The 7-fold mutation Cys201Met/Cys332Tyr/Lys344Asp/Tyr345Ile/Val351Ala/Tyr391Lys/Arg395Ser converts the cofactor specificity of Escherichia coli isocitrate dehydrogenase from a 7000-fold preference for NADP(+) to a 200-fold preference for NAD(+), with overall activity comparable to that of wild-type NAD(+)-dependent isocitrate dehydrogenases. The structure of the NAD(+)-dependent mutant has been determined and refined to a working R-factor of 0.186 at 1.9 Angstrom resolution. The structure shows that NADP(+) affinity is destroyed by removing favorable interactions between the 2'-phosphate and Tyr345, Tyr391, and Arg395 and by adding a repulsive interaction with Asp344. NAD(+) affinity is enhanced by adding hydrogen bonds between Asp344 and the free 2'-hydroxyl. The favorable Asp344-2'-OH interaction requires a change in the pucker of the ribose to C2' endo and a shift in the adenine ring, The ring shift is made possible by a series of changes in steric packing interactions. The linchpin for repacking in the adenosine binding site is residue 351, The side chain of this ''second layer'' residue dictates packing of the surrounding ''first layer'' residues which interact with the 2' moiety and, in turn, directly determine specificity. C1 CHICAGO MED SCH,DEPT BIOL CHEM,N CHICAGO,IL 60064. RP Hurley, JH (reprint author), NIDDKD,MOLEC BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [1RO1-GM-48735] NR 41 TC 77 Z9 78 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 7 PY 1996 VL 35 IS 18 BP 5670 EP 5678 DI 10.1021/bi953001q PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK015 UT WOS:A1996UK01500009 PM 8639526 ER PT J AU Gowda, DC Jackson, CM Kurzban, GP McPhie, P Davidson, EA AF Gowda, DC Jackson, CM Kurzban, GP McPhie, P Davidson, EA TI Core sugar residues of the N-linked oligosaccharides of Russell's viper venom factor X-activator maintain functionally active polypeptide structure SO BIOCHEMISTRY LA English DT Article ID COAGULATION; PROTEIN; ENZYME AB We previously showed that the factor X activator of Russell's viper venom (RVV-X) contains six N-linked oligosaccharide chains: four in the heavy chain and one in each of the two light chains [Gowda, D. C., Jackson, C. M., Hensley, P., & Davidson, E. A. (1994) J. Biol. Chem. 269, 10644-10650).] In the present study, we have investigated the role of the carbohydrate moieties in the structure and functional activity of RVV-X. Sequential removal of sugar residues from the terminal ends by exoglycosidases, up to 50% of total carbohydrates, did not significantly alter the activity of RVV-X, demonstrating that the peripheral carbohydrate moieties are not involved in interactions with factor X. However, removal of whole oligosaccharide chains by N-glycanase caused an almost total loss of the ability of RVV-X to activate factor X to factor X(a). In parallel with these observations, circular dichroism spectroscopy showed that complete deglycosylation, but not the removal of peripheral sugars, caused a significant change in the secondary structure. Together, these data demonstrate that the oligosaccharide chains are necessary for the functional activity, and that the trimannosylchitobiose core residues are sufficient for the maintenance of the native polypeptide structure. C1 AMER RED CROSS,DETROIT,MI 48232. NIDDK,NATL INST HLTH,BETHESDA,MD. RP Gowda, DC (reprint author), GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. OI Jackson, Craig/0000-0001-9484-4420 NR 20 TC 14 Z9 16 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 7 PY 1996 VL 35 IS 18 BP 5833 EP 5837 DI 10.1021/bi953043e PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK015 UT WOS:A1996UK01500027 PM 8639544 ER PT J AU Wolff, J Knipling, L Sackett, DL AF Wolff, J Knipling, L Sackett, DL TI Charge-shielding and the ''paradoxical'' stimulation of tubulin polymerization by guanidine hydrochloride SO BIOCHEMISTRY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEINS; ESCHERICHIA-COLI; BETA-LACTOGLOBULIN; CHLORIDE; DENATURATION; DEHYDROGENASE; DISSOCIATION; AGGREGATION; SYSTEMS; SUBUNIT AB Low concentrations of guanidine hydrochloride (GuHCl) increase the rate (and to a lesser degree, the extent) of tubulin polymerization as assessed by light scattering. Maximum enhancement occurs at 120-160 mM GuHCl followed by decreases at higher GuHCl. The latent period is decreased, and there is a 3-4-fold reduction in the critical concentration for polymerization. Electronmicrographs reveal microtubules in the controls and an increasing fraction of total polymers present as aberrant microtubules as the GuHCl concentration is increased from 20 to 100 mM. The GuHCl effect is markedly reduced, but not abolished, in tubulin S (in which the anionic C termini of both monomers have been removed). The GuHCl-induced polymerization has an absolute requirement for GTP and taxol or DMSO, is very sensitive to podophyllotoxin inhibition, and can overcome urea-mediated inhibition of polymerization. Guanidinium analogues mimic the GuHCl effect roughly as a function of the number of potential cation effect according to the lyotropic series. At higher GuHCl concentrations (peak effect 500-700 mM), a different polymer (type II) is formed that is GTP and taxol independent. but whose polymerization is retarded but not prevented by podophyllotoxin. Its structure resembles the fibrillar network seen in unfolding intermediates of other proteins. We conclude that both charge and hydrogen-bonding ability are major contributors to the GuHCl-induced promotion of tubulin polymerization, and that charge-shielding is likely to be the basis for this effect. RP Wolff, J (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 60 TC 23 Z9 23 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 7 PY 1996 VL 35 IS 18 BP 5910 EP 5920 DI 10.1021/bi9527395 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK015 UT WOS:A1996UK01500036 PM 8639553 ER PT J AU Bastien, NR Ciuffo, GM Saavedra, JM Lambert, C AF Bastien, NR Ciuffo, GM Saavedra, JM Lambert, C TI Angiotensin II receptor expression in the conduction system and arterial duct of neonatal and adult rat hearts SO REGULATORY PEPTIDES LA English DT Article DE angiotensin II receptor; heart conduction system; arterial duct; neonatal and adult tissue; quantitative autoradiography ID SUBTYPES; RENIN; BRAIN; AUTORADIOGRAPHY; SITES; FETUS AB Paralleling the classic circulating system, recent evidence has demonstrated the presence of a cardiac renin-angiotensin system, as well as the synthesis of angiotensin II in the heart. Two receptors for angiotensin II have been identified and classified as AT(1) and AT(2). The proportions of these receptor subtypes vary with the tissues, species and stage of development, From the results of other studies, it might be generalized that the expression of angiotensin II receptors and the proportion of AT(2) receptor subtype are much higher in fetal and neonatal tissues than in the same tissues from an adult, The aim of this study was to specifically evaluate the AT(1)/AT(2) ratio in the neonatal and adult conduction systems of rat hearts by means of quantitative autoradiography, In the neonatal hearts, angiotensin II binding sites were highly concentrated in the vasculature, arterial duct, and conduction system, whereas their concentrations were barely detectable in the myocardium, Incubation with selective angiotensin II receptor ligands (losartan and CGP 42112) revealed that AT(2) was the major subtype in vasculature (86 +/- 3%) and conduction system (73 +/- 4%), In the adult conduction system, the total expression of angiotensin II receptors was greatly reduced meanwhile the AT(1) receptors represented the major proportion of the binding sites (80 +/- 3%). Our results demonstrated that the pattern of angiotensin II receptor expression in the conduction system of the rat heart is developmentally regulated. We suggest, as others have already, that the renin-angiotensin system plays a role during the early stage of cardiac development. C1 UNIV MONTREAL,FAC MED,DEPT PHARMACOL,MONTREAL,PQ H3C 3J7,CANADA. NIMH,PHARMACOL SECT,CLIN SCI LAB,BETHESDA,MD 20892. NR 29 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD MAY 7 PY 1996 VL 63 IS 1 BP 9 EP 16 DI 10.1016/0167-0115(96)00012-2 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA UR477 UT WOS:A1996UR47700002 PM 8795083 ER PT J AU Kao, CY Factor, VM Thorgeirsson, SS AF Kao, CY Factor, VM Thorgeirsson, SS TI Reduced growth capacity of hepatocytes from c-myc and c-myc/TGF-alpha transgenic mice in primary culture SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID REPLICATIVE SENESCENCE; HUMAN FIBROBLAST; RAT HEPATOCYTES; DNA-SYNTHESIS; CELLS; LIVER; MITOSIS AB We have previously shown that coexpression of c-myc and TGF-alpha in the liver results in accelerated replicative senescence and promotes tumor development in young adult transgenic mice. Here we describe the characteristics of hepatocyte proliferation in primary cultures established from 10-week-old control, c-mpc and c-myc/TGF-alpha transgenic mice. A variety of cellular and functional changes occurred in the transgenic Livers at this age including enhanced polypoidization and impairment of hepatic functions. Control mouse hepatocytes demonstrated a high level of DNA synthesis in serum-free medium with a maximum at day three in culture at which time 70% of the cells were in S phase. In contrast, DNA synthesis peaked one day later and was reduced by 50% in the cultured c-myc and c-myc/TGF-alpha hepatocytes. Also, higher frequency of apoptosis was observed in the transgenic hepatocytes. However, in hepatocytes isolated from c-myc/TGF-alpha mice, which show early appearance of preneoplastic lesions in vivo, the DNA synthesis continued for 6 days in culture in contrast to a sharp decrease in the labeling index of control and c-myc hepatocytes after 3-4 days in culture. The results suggest that proliferative features of the transgenic hepatocytes in vitro reflect tile general properties of these cells in vivo and thus may provide a model for studies on senescence and transformation of hepatocytes. (C) 1996 Academic Press, Inc. RP Kao, CY (reprint author), NCI,DIV BASIC SCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 25 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 6 PY 1996 VL 222 IS 1 BP 64 EP 70 DI 10.1006/bbrc.1996.0698 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UJ625 UT WOS:A1996UJ62500011 PM 8630075 ER PT J AU Mason, RP Estermyer, JD Kelly, JF Mason, PE AF Mason, RP Estermyer, JD Kelly, JF Mason, PE TI Alzheimer's disease amyloid beta peptide 25-35 is localized in the membrane hydrocarbon core: X-ray diffraction analysis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SUBSTANCE-P; PROTEIN AB Alzheimer's disease (AD) neuropathology is characterized by neuritic plaques composed primarily of amyloid beta peptide (A beta). An elevation in A beta in the cerebral cortex has been implicated in the pathophysiology of AD but its mechanism of action is unknown. The addition of A beta protein to neuronal cell cultures produces changes in the activity of various membrane proteins, including ion channels and receptors, potentially as a result of intercalating into the membrane bilayer. In this study, the interactions of the A beta fragment 25-35 [A beta(25-35)] with liposomes were directly examined by small angle x-ray diffraction approaches. One-dimensional electron density profiles generated from the diffraction data demonstrated that the addition of A beta(25-35) produced a discrete increase in electron density 0-12 Angstrom from the center of the lipid bilayer. Under these conditions, the membrane concentration of A beta(25-35) was 860-fold higher than in the aqueous buffer. These findings indicate that this peptide is highly lipophilic and inserts into the membrane hydrocarbon core. Following the intercalation of A beta(25-35) to this location in the membrane, the protein fragment may interact with regulatory membrane proteins. (C) 1996 Academic Press, Inc. C1 NIA, GERONTOL RES CTR, MOLEC PHYSIOL & GENET SECT, BALTIMORE, MD 21224 USA. RP MED COLL PENN & HAHNEMANN UNIV, NEUROSCI RES CTR, ALLEGHENY CAMPUS, PITTSBURGH, PA 15212 USA. NR 22 TC 82 Z9 85 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 EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 6 PY 1996 VL 222 IS 1 BP 78 EP 82 DI 10.1006/bbrc.1996.0699 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UJ625 UT WOS:A1996UJ62500013 PM 8630078 ER PT J AU Mannen, H Tseng, HM Cho, CL Li, SSL AF Mannen, H Tseng, HM Cho, CL Li, SSL TI Cloning and expression of human homolog HSMT3 to yeast SMT3 suppressor of MIF2 mutations in a centromere protein gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID KINETOCHORE AB A human HSMT3 cDNA encoding a homolog of the yeast SMT3, a suppressor of MIF2 mutations in a centromere protein gene, was identified and sequenced. The sequence of 95 amino acids deduced from the human HSMT3 cDNA exhibited 51.1% identity and 69.6% similarity to the yrast Smt3p sequence. The HSMT3 transcripts of 1.35Kb were found to be abundantly expressed in various human tissues. (C) 1996 Academic Press, Inc. C1 NIEHS,NIH,GENET MOLEC LAB,RES TRIANGLE PK,NC 27709. NATL SUN YAT SEN UNIV,INST LIFE SCI,KAOHSIUNG 80424,TAIWAN. NR 6 TC 48 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 6 PY 1996 VL 222 IS 1 BP 178 EP 180 DI 10.1006/bbrc.1996.0717 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UJ625 UT WOS:A1996UJ62500030 PM 8630065 ER PT J AU Smith, MR Liu, YL Kim, SR Bae, YS Kim, CG Kwon, KS Rhee, SG Kung, HF AF Smith, MR Liu, YL Kim, SR Bae, YS Kim, CG Kwon, KS Rhee, SG Kung, HF TI PLC gamma 1 Src homology domain induces mitogenesis in quiescent NIH 3T3 fibroblasts SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHOLIPASE-C; SH3 DOMAINS; GROWTH-FACTOR; TYROSINE; PHOSPHORYLATION; MICROINJECTION; ANTIBODIES; RECEPTORS; PROTEINS; CELLS AB Previously, we demonstrated that microinjection of phosphoinositide-specific phospholipase C gamma l (PLC gamma l) and lipase-defective mutants of PLC gamma l induced G(o) growth arrested NIH 3T3 fibroblasts to enter S phase of the cell cycle. These experiments suggested that regions other than the catalytic domain of PLCyl may be responsible for inducing mitogenesis. To test other regions of PLC gamma l for DNA synthesis inducing activity, cDNA fragments encoding Src homology (SH) and pleckstrin homology (PH) domains were subcloned into the bacterial expression plasmid pGEX-2TK, and the GST fusion proteins were purified. The complete PLC gamma l SH domain peptide was found to induce DNA synthesis after microinjection into growth arrested fibroblasts. Peptides containing a single SH3 domain or two SH2 domains induced a partial response that was restored to full activity if they were co-injected. The PH domain peptide did not induce DNA synthesis. Thus, both SH3 and SH2 activity combine to give maximum DNA synthesis induction, demonstrating that non-catalytic structural domains of PLC gamma l have pronounced effects on mitogenic signaling pathways. (C) 1996 Academic Press, Inc. C1 NHLBI,NIH,BIOCHEM LAB,BETHESDA,MD 20892. KOREA ADV INST SCI & TECHNOL,KIBB,PROT ENGN GRP,TAEJON 305333,SOUTH KOREA. RP Smith, MR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702, USA. NR 24 TC 33 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 6 PY 1996 VL 222 IS 1 BP 186 EP 193 DI 10.1006/bbrc.1996.0719 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UJ625 UT WOS:A1996UJ62500032 PM 8630067 ER PT J AU Fukuyama, R Rapoport, SI AF Fukuyama, R Rapoport, SI TI Isolation of a monoclonal antibody reactive to brain microsome-associated antigen, lap-1, and its preferential localization in limbic system of rat brain SO BRAIN RESEARCH LA English DT Article DE limbic system; monoclonal antibody; regional specificity; immunohistochemistry; western blot; synapse; hippocampus ID ENTORHINAL CORTEX; TISSUE DISTRIBUTION; MEMBRANE-PROTEIN; HIPPOCAMPUS; NEURONS; COMPLEX; CELL AB The distribution and subcellular localization of AH9 antigen, recognized by a monoclonal antibody AH9, were examined in rat brain. Highest expression was observed in the lamina lucidum of the dentate gyrus of the rat hippocampus. Synaptic subfields of other limbic areas also expressed AH9 antigen at a substantial level. The molecular size of the AH9 antigen is 15 kDa and it was found in the microsomal fraction of brain but not of heart or kidney. These results indicate that AH9 antigen is a novel synaptosomal protein that is relatively specific to the Limbic system, at least in the rat brain. We designated AH9 antigen as a limbic system associated protein-1, lap-1. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 6 PY 1996 VL 719 IS 1-2 BP 194 EP 197 DI 10.1016/0006-8993(95)01344-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA UP705 UT WOS:A1996UP70500025 PM 8782880 ER PT J AU Khan, MA Shoaib, M AF Khan, MA Shoaib, M TI Neuroanatomical localization of the effects of (+)-HA966 on locomotor activity after cocaine injections to the nucleus accumbens of rats SO BRAIN RESEARCH LA English DT Article DE nucleus accumbens; NMDA receptor/glycine site; cocaine; locomotor activity; sensitization ID NMDA RECEPTOR ANTAGONIST; BEHAVIORAL SENSITIZATION; SYSTEM; ACTIVATION; PROJECTION; R-(+)-HA-966; PHARMACOLOGY; ANTEROGRADE; BLOCKS AB Current research has shown that manipulation at the glycine site of the NMDA receptor by various compounds can modulate NMDA receptor function and its behavioural consequences. The present study was conducted in order to neuroanatomically localize the effects of (+)-HA966 upon the acute and chronic effects of cocaine. Locomotor activity of Sprague-Dawley rats pretreated with (+)-HA966 (60 mu g) into the nucleus accumbens five min prior to receiving cocaine (20 mg/kg i.p.) was significantly less than locomotor activity of the vehicle pretreated rats. Repeated treatment with cocaine resulted in sensitization to the locomotor stimulant effects of cocaine. Go-administration of (+)-HA966 with cocaine prevented the sensitization to a subsequent cocaine challenge, in which activity was comparable to levels of naive individuals given an acute injection of cocaine. These results suggest that the glycine site on NMDA ao receptors in the nucleus accumbens plays an important role in both the acute and sensitized responses to cocaine on locomotor activity. C1 NIDA,PRECLIN PHARMACOL RES BRANCH,ADDICT RES CTR,DIR,NIH,BALTIMORE,MD 21224. NIDA,NEUROSCI BRANCH,ADDICT RES CTR,DIR,NIH,BALTIMORE,MD 21224. NR 24 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 6 PY 1996 VL 719 IS 1-2 BP 198 EP 202 DI 10.1016/0006-8993(96)00028-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA UP705 UT WOS:A1996UP70500026 PM 8782881 ER EF