FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Arnhold, IJP Latronico, AC Batista, MC Carvalho, FM Chrousos, GP Mendonca, BB AF Arnhold, IJP Latronico, AC Batista, MC Carvalho, FM Chrousos, GP Mendonca, BB TI Ovarian resistance to luteinizing hormone: A novel cause of amenorrhea and infertility SO FERTILITY AND STERILITY LA English DT Article DE amenorrhea; luteinizing hormone receptor; infertility; polycystic evades; gonadotropins; ovarian physiology AB Objective: To report the clinical, hormonal, and histopathological features of Design: Clinical study. Setting: University hospital. Patient(s): A woman with amenorrhea, sister of a patient with male pseudohermaphroditism due to Leydig cell hypoplasia. Intervention(s): Blood drawing before and after GnRH stimulation and also after dexamethasone and hCG administration, pelvic ultrasound, and ovarian biopsy. Main Outcome Measure(s): Karyotype, gonadotropin and steroid measurements, follicular diameter, ovarian histology, and sequencing of the LH receptor gene. Result(s): Patient had normal female external genitalia, normal breast development at puberty, rare episodes of vaginal bleeding, and infertility. The karyotype was 46,XX. She had elevated serum LH levels, whereas E(2) and P concentrations were in the range seen in the early follicular phase. Pelvic ultrasound revealed a slightly hypoplastic uterus and enlarged polycystic ovaries. A normal follicular reserve for age, antral follicles, and absence of corpora lutea or albicans were observed on ovarian biopsy. Exon 11 of the LH receptor gene had a normal sequence. Conclusion(s): In our patient with ovarian resistance to LH, FSH stimulated follicular development until the preovulatory stage, but E(2) levels remained in the early follicular phase range, still sufficient for normal pubertal feminization. Apparently, LH is necessary for ovulation and corpus luteum formation. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV SAO PAULO, HOSP CLIN, SCH MED, DIV PATHOL LIM14, BR-05403000 SAO PAULO, BRAZIL. RP Arnhold, IJP (reprint author), UNIV SAO PAULO, HOSP CLIN,DIV ENDOCRINOL,SCH MED,PAMB, 8 ANDAR, AV ENEAS CARVALHO AGUIAR 255, BR-05403000 SAO PAULO, BRAZIL. RI Mendonca, Berenice/C-2827-2012; ARNHOLD, IVO/D-2672-2012; OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X; Carvalho, Filomena/0000-0002-5838-3636 NR 6 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 1997 VL 67 IS 2 BP 394 EP 397 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WE507 UT WOS:A1997WE50700030 PM 9022621 ER PT J AU Chapin, RE Ku, WW Kenney, MA McCoy, H Gladen, B Wine, RN Wilson, R Elwell, MR AF Chapin, RE Ku, WW Kenney, MA McCoy, H Gladen, B Wine, RN Wilson, R Elwell, MR TI The effects of dietary boron on bone strength in rats SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID MAGNESIUM; METABOLISM; CALCIUM; GROWTH AB Previous studies from our laboratory found that when boric acid (BA) was administered in the diet to rats, boron levels in bone were approximately fourfold greater than serum levels. The current studies were undertaken to determine if these elevations produced adverse effects on several bone-related measures, including serum electrolyte levels, bone structure, and bone strength. Data from two studies are presented: in the first study, young adult male rats consumed a powdered diet containing 0, 3000, 4500, 6000, or 9000 ppm BA for 9 weeks. Endpoints were serum calcium, phosphorous, potassium, and chloride, as well as blood and bone boron concentrations ([B]) measured weekly during the 9-week exposure period, and at 8, 16, 24, and 32 weeks after the end of exposure. In the second study, the male and female young adult rats diet contained 0, 200, 1000, 3000, or 9000 ppm BA for 12 weeks; endpoints measured weekly were serum levels of calcium, phosphorous, and magnesium, bone [B], and bone structure (humerus) and strength (tibia, femur, and lumbar vertebrae). In treated rats, calcium was reduced in the first study but not the second. Serum phosphorous was reduced in both studies; potassium was unchanged, chloride was increased by 1%, and magnesium was reduced in all BA-exposed groups in the second study, to a maximal 19% reduction. Bone [B] was consistently increased in all treated groups, to concentrations approximately fourfold those of serum. After cessation of exposure, serum and urinary boron concentrations dropped to within control values within a week. However, even 32 weeks after the end of exposure, bone [B] remained threefold greater than controls. Male tibia and femur resistance to bending was unchanged. However, vertebral strength in compression was significantly increased by 5-10% in all dose groups (200 to 9000 ppm). The pattern was substantially similar in females. Only the humerus was examined by light microscopy and was found to be unchanged at any level of BA consumption. These data show that, despite a reduction in some serum electrolyte levels, BA consumption increased vertebral resistance to crush force, without detectably altering the microscopic structure of the humerus or the resistance of femur and tibia to a bending load. This increase in compression resistance occurred at exposure levels substantially below those that were previously reported to be reproductively toxic. C1 NIEHS,BIOMATH GRP,RES TRIANGLE PK,NC 27709. NIEHS,EXPT PATHOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,PATHOL SECT,RES TRIANGLE PK,NC 27709. UNIV ARKANSAS,AGR EXPT STN,FAYETTEVILLE,AR 72701. RP Chapin, RE (reprint author), NIEHS,REPROD TOXICOL GRP,MAIL DROP A2-02,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 NR 34 TC 39 Z9 40 U1 0 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD FEB PY 1997 VL 35 IS 2 BP 205 EP 215 DI 10.1006/faat.1996.2275 PG 11 WC Toxicology SC Toxicology GA WK146 UT WOS:A1997WK14600008 PM 9038242 ER PT J AU Termanini, B Gibril, F Reynolds, JC Doppman, JL Chen, CC Stewart, CA Sutliff, VE Jensen, RT AF Termanini, B Gibril, F Reynolds, JC Doppman, JL Chen, CC Stewart, CA Sutliff, VE Jensen, RT TI Value of somatostatin receptor scintigraphy: A prospective study in gastrinoma of its effect on clinical management SO GASTROENTEROLOGY LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; ISLET-CELL TUMORS; GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS; RADIOLABELED SOMATOSTATIN; MALIGNANT GASTRINOMA; LONG-TERM; LOCALIZATION; RESECTION; CHEMOTHERAPY AB Background & Aims: Recently [In-111-DTPA-D-Phe(1)]-octreotide was approved for somatostatin receptor scintigraphy (SRS) of gastroenteropancreatic tumors. SRS and other tumor localization methods can be time consuming, expensive, and involve patient inconvenience. The role of SRS in comparison to other tumor localization modalities remains undefined because the relative effects of these methods on management have not been studied. The aim of this study was to determine whether SRS alters clinical management in Zollinger-Ellison syndrome. Methods: One hundred twenty-two consecutive patients were studied prospectively. Each patient was assigned to one of five different clinical categories. Conventional imaging studies (ultrasonography, computerized tomography, magnetic resonance image, angiography, and bone scan) were performed, and the management was proposed. SRS was then performed. Clinical management was reassessed, and whether SRS altered management was determined based on six criteria. Results: SRS was superior to any single imaging study. SRS altered management in 47% overall and in 22%-60% of patients in the five different clinical categories. Primary tumor localization and clarification of equivocal localization results from conventional studies were the principal reasons for altering management. SRS was equally useful in patients with or without metastatic liver disease. Conclusions: Because of the ability of SRS to alter clinical management combined with its superior sensitivity, high specificity, simplicity, and cost-effectiveness, SRS should be the initial imaging modality for patients with gastrinomas. C1 NIDDKD,DIGEST DIS BRANCH,NIH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. NR 66 TC 143 Z9 148 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1997 VL 112 IS 2 BP 335 EP 347 DI 10.1053/gast.1997.v112.pm9024287 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WF185 UT WOS:A1997WF18500007 PM 9024287 ER PT J AU Gibril, F Curtis, LT Termanini, B Fritsch, MK Lubensky, IA Doppman, JL Jensen, RT AF Gibril, F Curtis, LT Termanini, B Fritsch, MK Lubensky, IA Doppman, JL Jensen, RT TI Primary cardiac gastrinoma causing Zollinger-Ellison syndrome SO GASTROENTEROLOGY LA English DT Article ID SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; PANCREATIC ENDOCRINE TUMORS; DUODENAL GASTRINOMAS; LOCALIZE GASTRINOMAS; PROVOCATIVE TESTS; CELL TUMORS; HEART; PHEOCHROMOCYTOMA; METASTASES; SECRETIN AB Primary cardiac tumors are rare, and there are no reports of patients with a functional gastroenteropancreatic tumor syndrome caused by such a tumor, This case report describes a patient with a cardiac gastrinoma causing Zollinger-Ellison syndrome. Evidence is presented that this tumor represents a primary cardiac tumor. The exact identification of this gastrinoma in an extra-abdominal site was facilitated by the use of [In-111-DTPA-DPhe(1)]octreotide scanning for somatostatin receptors, which these tumors characteristically possess in high numbers, The recent availability of this novel localization method may facilitate identification of extra-abdominal sites in an increasing proportion of patients with gastrinomas and related neuroendocrine functional tumors in which no intra-abdominal primary tumor is currently found. C1 NIDDK,DDB,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. TETON VALLEY MED CTR,DRIGGS,ID. NR 50 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1997 VL 112 IS 2 BP 567 EP 574 DI 10.1053/gast.1997.v112.pm9024311 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WF185 UT WOS:A1997WF18500031 PM 9024311 ER PT J AU ChenevixTrench, G Kerr, J Hurst, T Shih, YC Purdie, D Bergman, L Friedlander, M Sanderson, B Zournazi, A Coombs, T Leary, JA Crawford, E Shelling, AN Cooke, I Ganesan, TS Searle, J Choi, C Barrett, JC Khoo, SK Ward, B AF ChenevixTrench, G Kerr, J Hurst, T Shih, YC Purdie, D Bergman, L Friedlander, M Sanderson, B Zournazi, A Coombs, T Leary, JA Crawford, E Shelling, AN Cooke, I Ganesan, TS Searle, J Choi, C Barrett, JC Khoo, SK Ward, B TI Analysis of loss of heterozygosity and KRAS2 mutations in ovarian neoplasms: Clinicopathological correlations SO GENES CHROMOSOMES & CANCER LA English DT Article ID CHROMOSOME 6Q; FREQUENT LOSS; ALLELIC LOSS; BRCA1 GENE; LATE EVENT; TUMORS; CANCER; CARCINOMA; P53; LOCUS AB The molecular events that give rise to ovarian epithelial neoplasms are not well understood. In particular, it is not known whether adenocarcinomas arise from benign or low malignant potential (LMP) precursors. We have examined a large series of benign (25) and LMP (31) ovarian tumors for loss of heterozygosity (LOH) at multiple loci on 17 chromosomes. LOH was observed in benign tumors on chromosomes 6 (14%) and 9 (5%) and on the X chromosome (33%) only. LOH on these chromosomes was also detected in a small number of LMP neoplasms, suggesting that these may derive sometimes from benign precursors. In addition, we examined LOH in 93 adenocarcinomas. Analysis of associations between LOH events showed that LOH on chromosomes 5 and 17 (P = 0.0002) and on chromosomes 17 and 18 (P = 0.00007) were associated significantly with each other, which suggests that these may represent cooperative, progressive events. No novel significant associations were identified between LOH events and stage, grade, or histology, which would indicate the existence of genetic heterogeneity in ovarian neoplasms. KRAS2 mutations were detected more often in LMP neoplasms than in malignant tumors (P = 0.004) and were detected more often in Stage I/II malignant tumors than in Stage III/IV malignant tumors (P = 0.033), suggesting that LMP tumors with KRAS2 mutations are unlikely to progress to frank malignancy. Univariate (but not multivariate) survival analysis showed that LOH of chromosomes II (P = 0.039) and 17 (P = 0.04) was associated with a significantly worse prognosis. Replication of these novel findings is necessary, and the identification, isolation, and characterization of the critical genes affected by LOH will determine their importance in the pathogenesis of ovarian malignancies. (C) 1997 Wiley-Liss, Inc. C1 UNIV QUEENSLAND,ROYAL BRISBANE HOSP,DEPT OBSTET & GYNECOL,BRISBANE,QLD,AUSTRALIA. PRINCE WALES HOSP,DEPT MED ONCOL,RANDWICK,NSW 2031,AUSTRALIA. UNIV SYDNEY,WESTMEAD HOSP,DEPT MED ONCOL,SYDNEY,NSW 2006,AUSTRALIA. UNIV SYDNEY,WESTMEAD HOSP,DEPT OBSTET & GYNECOL,SYDNEY,NSW 2006,AUSTRALIA. UNIV ALABAMA,MED GENET LAB,BIRMINGHAM,AL 35294. JOHN RADCLIFFE HOSP,INST MOL MED,IMPERIAL CANC RES FUND,OXFORD OX3 9DU,ENGLAND. ROYAL BRISBANE HOSP,DEPT PATHOL,BRISBANE,QLD 4029,AUSTRALIA. NIEHS,MOL CARCINOGENESIS LAB,RALEIGH,NC. RP ChenevixTrench, G (reprint author), QUEENSLAND INST MED RES,ROYAL BRISBANE HOSP PO,HERSTON,QLD 4029,AUSTRALIA. RI Shelling, Andrew/E-7496-2010; OI Shelling, Andrew/0000-0002-5300-1934 NR 50 TC 45 Z9 45 U1 0 U2 1 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 FEB PY 1997 VL 18 IS 2 BP 75 EP 83 DI 10.1002/(SICI)1098-2264(199702)18:2<75::AID-GCC1>3.0.CO;2-Y PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WG498 UT WOS:A1997WG49800001 PM 9115967 ER PT J AU Kuukasjarvi, T Tanner, M Pennanen, S Karhu, R Visakorpi, T Isola, J AF Kuukasjarvi, T Tanner, M Pennanen, S Karhu, R Visakorpi, T Isola, J TI Optimizing DOP-PCR for universal amplification of small DNA samples in comparative genomic hybridization SO GENES CHROMOSOMES & CANCER LA English DT Article ID MOLECULAR CYTOGENETIC ANALYSIS; SEQUENCE COPY NUMBER; CARCINOMA IN-SITU; CHROMOSOME MICRODISSECTION; BREAST-CANCER; SOLID TUMORS; GENETIC ALTERATIONS; LOSSES; GAINS; IDENTIFICATION AB The standard comparative genomic hybridization (CGH) protocol relies on availability of macroscopic tumor samples, which do not contain too much interfering normal cells. Recently, CGH after universal amplification of genomic DNA with degenerate oligonucleotide primed PCR (DOP-PCR) has been used to detect genetic aberrations in microdissected tumor specimens, However, owing to the technical difficulties, CGH results of only few microdissected samples have so far been published. We have developed an improved protocol for DOP-PCR, which includes direct incorporation of fluorochrome-conjugated nucleotides into the PCR product. Among the four polymerase enzymes tested, ThermoSequenase gave the best yield, with PCR products ranging from 100-4,000 bp. A two-step PCR-procedure was used, consisting of a preamplification with low stringency conditions followed by amplification in more stringent conditions. The method was first validated by hybridizing DOP-PCR-amplified normal DNA against nick-translated reference DNA, which showed uniform amd even hybridization result for all chromosomes. Comparison of DOP-PCR CGH to conventional CGH in MCF-7 breast cancer cell line further indicated that genetic aberrations can be reliable detected after DOP-PCR amplification. The sensitivity of the DOP-PCR-CCH was tested by serial dilution of MCF-7 DNA. Fifty picograms of sample DNA (corresponding roughly to two MCF-7 cells) was sufficient for high quality CGH. Experiments with cells microdissected from intraductal breast cancer demonstrated that carcinoma cells from 1 to 2 ducts were sufficient for a successful DOP-PCR CGH analysis. We conclude that the improved DOP-PCR-CGH protocol provides a powerful cool to study genetic aberrations in different histological subpopulations of malignant as well as precancerous lesions. DOP-PCR also improves the success rate of conventional paraffin-block CGH, because a poor quality or a too low yield of extracted DNA can be compensated by universal DNA amplification by DOP-PCR. (C) 1997 Wiley-Liss, Inc. C1 TAMPERE UNIV HOSP,CANC GENET LAB,FIN-33521 TAMPERE,FINLAND. TAMPERE UNIV HOSP,DEPT PATHOL,TAMPERE,FINLAND. TAMPERE UNIV,FIN-33101 TAMPERE,FINLAND. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 26 TC 112 Z9 114 U1 2 U2 4 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 FEB PY 1997 VL 18 IS 2 BP 94 EP 101 DI 10.1002/(SICI)1098-2264(199702)18:2<94::AID-GCC3>3.3.CO;2-5 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WG498 UT WOS:A1997WG49800003 PM 9115969 ER PT J AU Sonoda, G duManoir, S Godwin, AK Bell, DW Liu, ZM Hogan, M Yakushiji, M Testa, JR AF Sonoda, G duManoir, S Godwin, AK Bell, DW Liu, ZM Hogan, M Yakushiji, M Testa, JR TI Detection of DNA gains and losses in primary endometrial carcinomas by comparative genomic hybridization SO GENES CHROMOSOMES & CANCER LA English DT Article ID IN-SITU HYBRIDIZATION; MICROSATELLITE INSTABILITY; PROSTATE-CANCER; LONG ARM; CHROMOSOMAL GAINS; SOLID TUMORS; ADENOCARCINOMA; SEQUENCES; CHARACTERIZE; ABNORMALITY AB Comparative genomic hybridization (CGH) was used in a retrospective analysis of chromosomal imbalances in frozen primary tumor specimens from 14 endometrial carcinoma patients. Chromosome changes were detected in nine cases (64%), and tumor stage and grade tended to parallel the degree of genomic imbalances. Gain of the entire long arm of chromosome 1 was observed in six cases (43%), three of which displayed only this chromosome change. Other common sites of copy number increases included 8q21 --> qter (4 cases), 10p15 (4 cases), 10q11 --> q24 (3 cases), and 13q21 --> qter (3 cases, each with stage III disease). Two of the tumors with gains of chromosome 10 involved the whole chromosome, and this was the sole abnormality in one case. DNA amplification at 5p14 --> p15 was identified in one specimen, a stage III tumor having numerous imbalances. DNA microsatellite analysis revealed multiple replication errors (RER), indicative of the RER(+) phenotype, in four of 13 (31%) cases evaluated. The RER(+) phenotype was observed in four of six stage 1a tumors but in none of seven stage 1b or stage III tumors. Multiple genomic imbalances detected by CGH were not observed in RER(+) tumors but were detected in five of nine tumors without the RER(+) phenotype. These investigations demonstrate the feasibility of CGH for the retrospective assessment of chromosomal changes in endometrial carcinoma specimens. Moreover, these data suggest that the etiologies in tumors with and without the RER(+) phenotype may differ. (C) 1997 Wiley-Liss, Inc. C1 FOX CHASE CANC CTR,SECT MOL CYTOGENET,DEPT MED ONCOL,PHILADELPHIA,PA 19111. FOX CHASE CANC CTR,DEPT SURG ONCOL,PHILADELPHIA,PA 19111. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. KURUME UNIV,SCH MED,DEPT OBSTET & GYNECOL,FUKUOKA,JAPAN. NR 47 TC 62 Z9 62 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 1997 VL 18 IS 2 BP 115 EP 125 DI 10.1002/(SICI)1098-2264(199702)18:2<115::AID-GCC6>3.0.CO;2-5 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WG498 UT WOS:A1997WG49800006 PM 9115961 ER PT J AU Taylor, AC Graves, JM Murray, ND OBrien, SJ Yuhki, N Sherwin, B AF Taylor, AC Graves, JM Murray, ND OBrien, SJ Yuhki, N Sherwin, B TI Conservation genetics of the koala (Phascolarctos cinereus), low mitochondrial DNA variation amongst southern Australian populations SO GENETICAL RESEARCH LA English DT Article ID HAIRY-NOSED WOMBAT; EVOLUTION; SYSTEMATICS; VARIABILITY; HISTORY; NUMBER; MODEL AB Koala (Phascolarctos cinereus) populations in southern Australia have a history of bottlenecks earlier this century the species became extinct in South Australia, and almost so in Victoria. Subsequently large numbers of animals from island populations (founded from very few animals) have been translocated back to mainland sites and to other islands in the region. As part of a larger study of the genetic structure of koala populations in southern Australia, we have undertaken a survey of mitochondrial DNA restriction fragment length polymorphism (mtDNA-RFLP) variability. Genomic DNA from 91 koalas from five populations was examined using 23 restriction enzymes, and mtDNA fragments were detected using a domestic cat full-length mtDNA clone. Only one of the enzymes, TaqI, revealed polymorphism - a relatively low amount of variation compared with other mammals, although low mtDNA-RFLP variation has also been reported in Queensland koalas. French Island and populations established predominantly from French Island immigrant koalas, either directly or via other island populations, were indistinguishable by haplotype frequencies. The mtDNA data are thus consistent with the interpretation that the koala translocation programme has homogenized gene frequencies amongst those populations involved. South Gippsland is not recorded as having received translocated koalas directly, and has significantly different mtDNA-RFLP haplotype frequencies from all other populations examined. The fact that this distinction was not previously observed in nuclear gene frequencies may reflect predominantly male-mediated dispersal in koalas. C1 NIH,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Sherwin, William B/C-3432-2008; Taylor, Andrea/B-5795-2009 OI Sherwin, William B/0000-0002-1578-8473; NR 43 TC 21 Z9 21 U1 3 U2 19 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0016-6723 J9 GENET RES JI Genet. Res. PD FEB PY 1997 VL 69 IS 1 BP 25 EP 33 DI 10.1017/S0016672397002607 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XA890 UT WOS:A1997XA89000004 PM 9164173 ER PT J AU Gracia, E Ray, ME Polymeropoulos, MH Dehejia, A Meltzer, PS Trent, JM AF Gracia, E Ray, ME Polymeropoulos, MH Dehejia, A Meltzer, PS Trent, JM TI Isolation of chromosome-specific ESTs by microdissection-mediated cDNA capture SO GENOME RESEARCH LA English DT Article ID MOLECULAR CYTOGENETIC CHARACTERIZATION; IN-SITU HYBRIDIZATION; REGION; GENERATION; SELECTION; SEQUENCES; CLONING AB Despite dramatic advances in the identification of human expressed sequence tags (ESTs), techniques that facilitate isolation of chromosome or chromosome band-specific ESTs would be of considerable value. This report demonstrates the feasibility of identifying chromosome-specific ESTs following microdissection of a single-copy chromosome region. For this study, a reduced complexity cDNA library was linkered and chromosome 6 (6q) was microdissected. Following PCR amplification using linker-specific primers, captured cDNAs were subcloned and 187 individual clones picked at random. These 187 clones were then sorted by filter cross-hybridization into 34 unique groups. Of these 34 groups, 19 (56%) mapped to chromosome 6 by Southern blot. We identified three previously known genes, human cytovillin (ezrin) mapped previously to 6q25-26, human cardiac gap junction protein (connexin 43) mapped previously to 6q21-23.2 and prolyloligopeptidase, which had not been mapped previously. BLASTN identified three clone groups with homology to known ESTs and 12 representing novel cDNA sequences. Six of the groups were sublocalized to specific band regions of 6q using a chromosome 6 hybrid mapping panel, five representative clones were tested on Northern analysis to verify their expression, and Finally, nine clones were mapped against the Gene bridge 4 reduction hybrid panel to confirm their genetic map location on 6q. These results demonstrate that microdissection of single-copy sequences has sufficient specificity for isolation of chromosome-specific cDNAs. C1 NIH,CANC GENET LAB,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT HUMAN GENET,SCH MED,ANN ARBOR,MI 48109. NR 19 TC 6 Z9 6 U1 0 U2 0 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 FEB PY 1997 VL 7 IS 2 BP 100 EP 107 DI 10.1101/gr.7.2.100 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WH936 UT WOS:A1997WH93600003 PM 9049628 ER PT J AU Zimmerman, JE Bui, QT Steingrimsson, E Nagle, DL Fu, WL Genin, A Spinner, NB Copeland, NG Jenkins, NA Bucan, M Bonini, NM AF Zimmerman, JE Bui, QT Steingrimsson, E Nagle, DL Fu, WL Genin, A Spinner, NB Copeland, NG Jenkins, NA Bucan, M Bonini, NM TI Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene SO GENOME RESEARCH LA English DT Article ID HOMEOBOX-CONTAINING GENE; HUMAN PAX6 GENE; INTERSPECIFIC BACKCROSS; CHROMOSOMAL LOCATION; MOUSE CHROMOSOME-2; VISUAL-SYSTEM; BLIND-STERILE; EYELESS GENE; SINE OCULIS; SEQUENCES AB The Drosophila eyes absent [eya] gene plays an essential role in the events that lead to proper development of the fly eye and embryo. Here we report the analysis of two human and two mouse homologs of the Fly eya gene. Sequence comparison reveals a larger domain of similar to 270 amino acids in the carboxyl terminus of the predicted mammalian proteins that shows 53% identity between the fly sequence and all of the vertebrate homologs. This Eya-homology domain is of novel sequence, with no previously identified motifs. RNA hybridization studies indicate that the mouse genes are expressed during embryogenesis and in select tissues of the adult. Both mouse Eya genes are expressed in the eye, suggesting that these genes may Function in eye development in vertebrates as eya does in the fly. The mouse Eya2 gene maps to chromosome 2 in the region syntenic with human chromosome 20q13, and the mouse Eya3 gene maps to chromosome 4 in the region syntenic with human chromosome 1p36. Our findings support the notion that several families of genes (Pax-d/eyeless, Six-3/sine oculis, and Eya) play related and critical roles in the eye for both flies and vertebrates. C1 UNIV PENN,DEPT BIOL,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NICHD NIH HHS [HD 28410]; NIDA NIH HHS [T32-DA07241] NR 49 TC 72 Z9 78 U1 0 U2 5 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 FEB PY 1997 VL 7 IS 2 BP 128 EP 141 DI 10.1101/gr.7.2.128 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WH936 UT WOS:A1997WH93600006 PM 9049631 ER PT J AU Steeman, S Moskow, JJ Druck, T Montgomery, JC Huebner, K Daar, IO Buchberg, AM AF Steeman, S Moskow, JJ Druck, T Montgomery, JC Huebner, K Daar, IO Buchberg, AM TI Identification of a conserved family of Meis1-related homeobox gene SO GENOME RESEARCH LA English DT Letter ID MYELOID-LEUKEMIA; TRANSLOCATION PROTEIN; PRE-B; HOMEODOMAIN; SEQUENCE; CHROMOSOME; DOMAIN; MICE; ABNORMALITIES; DROSOPHILA AB The Meis1 locus was isolated as a common site of viral integration involved in myeloid leukemia in BXH-2 mice. Meis1 encodes a novel homeobox protein belonging to the TALE (three amino acid loop extension) family of homeodomain-containing proteins. The homeodomain of Meis1 is the only known motif within die entire 390-amino-acid protein. Southern blot analyses using the Meis1 homeodomain as a probe revealed the existence of a family of Meis1-related genes (Mrgs] in several diverged species. In addition, the 3' untranslated region (UTR) of Meis1 was remarkably conserved in evolution. To gain a Further understanding of the role Meis1 plays in leukemia and development, as well as to identify conserved regions of the protein that might reveal function, we cloned and characterized Mrgs from the mouse and human genomes. We report the sequence of Mrg1 and Mrg2 as well as their chromosomal locations in murine and human genomes. Both Mrgs share a high degree of sequence identity with the protein coding region of Meis1. We have also cloned the Xenopus laevis ortholog of Meis1 (XMeis1). Sequence comparison of the murine and Xenopus clones reveals that Meis1 is highly conserved its coding sequence as well as the 3' UTR. Finally, comparison of Meis1 and the closely related Mrgs homeoproteins Meis1 represents a new subfamily of TALE homeobox genes. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,KIMMEL CANC CTR,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES & SUPPORT PROGRAM,SCI APPLICAT INT CORP,FREDERICK,MD 21702. FU NCI NIH HHS [CA 21124, CA 58586]; PHS HHS [T32 H107780] NR 36 TC 37 Z9 40 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 FEB PY 1997 VL 7 IS 2 BP 142 EP 156 DI 10.1101/gr.7.2.142 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WH936 UT WOS:A1997WH93600007 PM 9049632 ER PT J AU DeSilva, U DArcangelo, G Braden, VV Miao, GG Curran, T Green, ED AF DeSilva, U DArcangelo, G Braden, VV Miao, GG Curran, T Green, ED TI The human reelin gene: Isolation, sequencing, and mapping on chromosome 7 SO GENOME RESEARCH LA English DT Letter ID NEURAL CELL-ADHESION; KALLMANN SYNDROME; CLEAVAGE SITES; MOLECULES; PROTEIN; HUMAN-CHROMOSOME-7; PATTERNS; ENCODES; MAPS AB The mouse reelin gene (Rein) encodes a novel protein that, when mutated, results in the characteristic reeler phenotype. A key component of this phenotype is the extensive disruption of the organization of many brain structures. Reelin is believed to be an extracellular protein that controls neural cell positioning during brain development. The reelin gene is conserved in many vertebrate species, including humans. To study the role of the reelin homolog in human brain development, we have isolated and characterized the human gene (RELN). Like its murine counterpart, RELN is large, encoding an mRNA of similar to 12 kb. Overlapping cDNA clones containing the entire open reading frame were isolated and sequenced, revealing that the predicted mouse and human proteins are similar in size (388 kD) and that the amino acid and nucleotide sequences are 94.2% and 87.2% identical, respectively. Northern hybridization analyses revealed that RELN is expressed in fetal and postnatal brain as well as liver. The expression of RELN in postnatal human brain was high in the cerebellum. RELN was mapped to human chromosome 7q22, based on both fluorescence in situ hybridization studies and localization within a well-position yeast artificial chromosome (YAC) contig. The YAC contig also contains a number of genetic markers. Together, these studies provide the sequence information and genetic tools for performing more detailed analyses of RELN in an attempt to define its role in human brain development and possibly in human disease. C1 NIH, GENOME TECHNOL BRANCH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT DEV NEUROBIOL, MEMPHIS, TN 38105 USA. RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011 OI Curran, Tom/0000-0003-1444-7551; FU NCI NIH HHS [P30-CA21765]; NINDS NIH HHS [NS09698] NR 26 TC 90 Z9 101 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 1997 VL 7 IS 2 BP 157 EP 164 DI 10.1101/gr.7.2.157 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WH936 UT WOS:A1997WH93600008 PM 9049633 ER PT J AU Ghosh, S Karanjawala, ZE Hauser, ER Ally, D Knapp, JI Rayman, JB Musick, A Tannenbaum, J Te, C Shapiro, S Eldridge, W Musick, T Martin, C Smith, JR Carpten, JD Brownstein, MJ Powell, JI Whiten, R Chines, P Nylund, SJ Magnuson, VL Boehnke, M Collins, FS AF Ghosh, S Karanjawala, ZE Hauser, ER Ally, D Knapp, JI Rayman, JB Musick, A Tannenbaum, J Te, C Shapiro, S Eldridge, W Musick, T Martin, C Smith, JR Carpten, JD Brownstein, MJ Powell, JI Whiten, R Chines, P Nylund, SJ Magnuson, VL Boehnke, M Collins, FS TI Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME; MICROSATELLITE MARKERS; LINKAGE; TRINUCLEOTIDE; SETS AB Large-scale genotyping is required to generate dense identity-by-descent maps to map genes for human complex disease. In some studies the number of genotypes needed can approach or even exceed million. Generally, linkage and linkage disequilibrium analyses depend on clear allele identification and subsequent allele frequency estimation. Accurate grouping or categorization of each allele in the sample [allele calling or binning) is therefore an absolute requirement. Hence,a genotyping system that can reliably achieve this is necessary. In the case of affected sib-pair analysis without parents, the need for accurate allele calling is even more critical. We describe methods that permit precise sizing of alleles across multiple gels using the fluorescence-based, Applied Biosystems (ABI] genotyping technology and discuss ways to reduce genotyping error rates. Using database utilities, we show how to minimize intergrel allele size variation, to combine data effectively from different models of ABI sequencing machines, and automatically bin alleles. The final data can then be converted into a format ready for analysis by statistical genetic packages such as MENDEL. C1 NIH,COMPUTAT BIOSCI & ENGN LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NIMH,NIH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI 48109. NATL PUBL HLTH INST,DEPT EPIDEMIOL & HLTH PROMOT,DIABET & GENET EPIDEMIOL UNIT,HELSINKI,FINLAND. RP Ghosh, S (reprint author), NIH,POSIT CLONING SECT,LAB GENE TRANSFER,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. RI Addington, Anjene/C-3460-2008; Brownstein, Michael/B-8609-2009; Smith, Jeff/C-3484-2012 NR 25 TC 87 Z9 92 U1 0 U2 8 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 FEB PY 1997 VL 7 IS 2 BP 165 EP 178 DI 10.1101/gr.7.2.165 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WH936 UT WOS:A1997WH93600009 PM 9049634 ER PT J AU Birrer, MJ AF Birrer, MJ TI Discoveries in the cell cycle and ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID GENE; EXPRESSION; NEOPLASMS; MUTATIONS; P53 RP Birrer, MJ (reprint author), NCI,MOL MECHANISMS SECT,MED BRANCH,DIV CLIN SCI,KEY W RES CTR,9610 MED CTR DR,ROCKVILLE,MD 20850, USA. NR 16 TC 4 Z9 4 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 1997 VL 64 IS 2 BP 187 EP 188 DI 10.1006/gyno.1997.4611 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA WK990 UT WOS:A1997WK99000001 PM 9038262 ER PT J AU Parker, MF Arroyo, GF Geradts, J Sabichi, AL Park, RC Taylor, RR Birrer, MJ AF Parker, MF Arroyo, GF Geradts, J Sabichi, AL Park, RC Taylor, RR Birrer, MJ TI Molecular characterization of adenocarcinoma of the cervix SO GYNECOLOGIC ONCOLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS DNA; SQUAMOUS-CELL CARCINOMA; RAS GENE-MUTATIONS; UTERINE CERVIX; ENDOMETRIAL CARCINOMA; P53 MUTATIONS; LOW-FREQUENCY; RB GENE; CANCER; EXPRESSION AB In an attempt to characterize the molecular alterations of cervical adenocarcinoma, we analyzed 32 paraffin-embedded specimens for the presence of K-ras mutations, p53 overexpression, p16 and Rb protein expression, and the presence of HPV 16 and 18 DNA, Overall 25/32 (78%) of the tumors displayed an abnormality in at least one of these analyses. K-ras mutations were detected by PCR amplification and RFLP analysis in 3 tumors, including 2 at codon 12 and 1 at codon 61. p53 overexpression determined by immunohistochemistry was demonstrated with >80% of tumor nuclei staining in 4 cases, 10-15% of nuclei staining in 3 cases, and <1% of nuclei staining in 5 cases. The pattern of staining was diffuse in 6 cases, focal in 1 case, and scattered in 5 cases, Analysis of p16 protein expression in 23 specimens revealed 1 tumor with abnormal staining, while Rb protein expression was determined to be normal in all 25 tumors tested. HPV DNA, detected by PCR with type-specific primers, was found in 16 tumors (50%), including 7 (22%) with HPV 16 and 9 (28%) with HPV 18, There was no correlation among these abnormalities except that the presence of HPV and strong p53 overexpression (>80% tumor nuclei staining) were mutually exclusive events. Clinical correlation demonstrated that p53 overexpression involving the majority of tumor cell nuclei is characteristic of advanced stage disease, while HPV positivity and activated ras genes are associated with early stage disease. (C) 1997 Academic Press. C1 NCI,PREVENT RES BRANCH,DIV CLIN SCI,ROCKVILLE,MD 20850. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514. RP Parker, MF (reprint author), WALTER REED ARMY MED CTR,DEPT OBSTET & GYNECOL GYNECOL ONCOL,WASHINGTON,DC 20307, USA. NR 39 TC 48 Z9 51 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 FEB PY 1997 VL 64 IS 2 BP 242 EP 251 DI 10.1006/gyno.1996.4580 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA WK990 UT WOS:A1997WK99000009 PM 9038270 ER PT J AU Tedeschi, V Akatsuka, T Shih, JWK Battegay, M Feinstone, SM AF Tedeschi, V Akatsuka, T Shih, JWK Battegay, M Feinstone, SM TI A specific antibody response to HCV E2 elicited in mice by intramuscular inoculation of plasmid DNA containing coding sequences for E2 SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; HYPERVARIABLE REGION; PROTECTIVE IMMUNITY; GLYCOPROTEIN; ENVELOPE; INFECTION; PROTEINS; VACCINATION; CHIMPANZEES; EPITOPES AB As the chimpanzee, the only reliable animal model for hepatitis C virus (HCV) infection, is impractical for early stage testing of HCV vaccine candidates, we have evaluated the immune response in mice to an experimental plasmid based HCV vaccine, We used this system because DNA vaccines can be rapidly constructed without the necessity of large scale protein production and purification, In this preliminary study we tested the immune response in mice to HCV envelope glycoprotein, E2, induced by a eukaryotic expression plasmid, Protein expression was monitored by immunofluorescence in transfected tissue culture cells, Each mouse was inoculated intramuscular with 100 mu g plasmid DNA and some mice were boosted after 5 weeks, Among 12 BALB/C mice inoculated, 10 developed antibody to E2 by the second week, The antibody levels increased steadily before reaching a plateau in mice receiving the booster, but in the nonboosted mice the antibody declined over time, The serum from one mouse was tested against a series of overlapping peptides covering most of E2. This serum contained antibodies recognizing two distinct epitopes beginning at amino acid 57 and amino acid 113 but no antibody was directed against peptides representing the hypervariable region of E2, antibody to which is thought to be important in HCV neutralization, We have shown that the use of plasmid based vaccines can induce a specific immune response in mice against HCV antigens, This system should be useful as the first step in vaccine development. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,HEPATITIS VIRUSES LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NR 29 TC 33 Z9 34 U1 0 U2 0 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 FEB PY 1997 VL 25 IS 2 BP 459 EP 462 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WG103 UT WOS:A1997WG10300034 PM 9021964 ER PT J AU Zern, MA Kresina, TF AF Zern, MA Kresina, TF TI Hepatic drug delivery and gene therapy SO HEPATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; CYTOSINE DEAMINASE GENE; RNA TUMOR-VIRUSES; B VIRUS; RETROVIRAL VECTORS; ADOPTIVE TRANSFER; HUMAN-SERUM; IN-VIVO; PHARMACOKINETIC ANALYSIS; MAMMALIAN-CELLS AB On September 21-22, 1995, an international meeting entitled ''Targeting of Novel Therapeutics to the Liver and GI Tract'' was held at the Natcher Conference Center on the campus of the National Institutes of Health. The conference was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases through the Division of Digestive Diseases and Nutrition and Digestive Diseases Interagency Coordinating Committee (DDICC). Section 440A of Public Law 94-562 in 1976 created the DDICC for the purpose of coordinating the digestive disease-related research activities of relevant federal health agencies into a coordinated program aimed at combating digestive diseases. As part of this federal effort, an assessment of the ''state of the art'' for targeted drug therapeutics to the liver and gene therapy was undertaken through the conference, cochaired by Dr, Mark Zern (Thomas Jefferson Medical College) and Dr. Flossie Wong-Staal (University of California, San Diego, CA). The conference was divided into four sessions: Session I was Vectors and Techniques; Session II was Liver and Metabolic Diseases; Session III was Hepatitis and GI Disease; and Session IV was Approaches for HIV infection, This summary focuses on the new technologies and the studies directly pertaining to liver disease, Table 1 lists the techniques and their applications. Table 2 describes viral vectors that have been employed for the purpose of hepatic gene therapy, Table 3 summarizes the studies presented as posters at the conference. C1 NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892. RP Zern, MA (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,1025 WALNUT ST,ROOM 901,PHILADELPHIA,PA 19107, USA. NR 71 TC 11 Z9 11 U1 0 U2 1 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 FEB PY 1997 VL 25 IS 2 BP 484 EP 491 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WG103 UT WOS:A1997WG10300038 PM 9021968 ER PT J AU Nussbaum, RL Orrison, BM Janne, PA Charnas, L Chinault, AC AF Nussbaum, RL Orrison, BM Janne, PA Charnas, L Chinault, AC TI Physical mapping and genomic structure of the Lowe syndrome gene OCRL1 SO HUMAN GENETICS LA English DT Article ID OCULOCEREBRORENAL SYNDROME; MARKERS AB The oculocerebrorenal syndrome of Lowe (OCRL; McKusick 309000) is a rare X-linked disorder characterized by mental retardation, congenital cataracts, and Fanconi syndrome of the proximal renal tubules. We have carried out physical mapping of the OCRL1 gene and determined that it contains 24 exons occupying 58 kb. The gene, located in Xq25-26, is transcribed in a centromeric to telomeric direction. Primers have been developed that allow all coding exons and their intron/exon boundaries to be amplified from genomic DNA for mutation detection. Two tetranucleotide tandem repeat polymorphisms were characterized that immediately flank the OCRL1 gene and, together, are informative in over 90% of females. Variable splicing was seen in the OCRL1 transcript, involving a small 24-bp exon. These results should prove useful to medical and molecular geneticists studying mutations and providing DNA diagnostic services to families dealing with Lowe syndrome as well as to cell biologists interested in structure-function relationships for the OCRL1 protein. C1 UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,MOL BIOL GRAD GRP,PHILADELPHIA,PA 19104. NICHHD,HEREDITARY DISORDERS BRANCH,BETHESDA,MD. BAYLOR COLL MED,DEPT MOL GENET,HOUSTON,TX 77030. RP Nussbaum, RL (reprint author), NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BLDG 49 ROOM 4A72,49 CONVENT DR,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [HG-00210]; NICHD NIH HHS [R01-HD23245]; NIGMS NIH HHS [T32-GM07170] NR 9 TC 55 Z9 60 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 1997 VL 99 IS 2 BP 145 EP 150 DI 10.1007/s004390050329 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WH788 UT WOS:A1997WH78800001 PM 9048911 ER PT J AU Hunziker, RD Lynch, F Shevach, EM Margulies, DH AF Hunziker, RD Lynch, F Shevach, EM Margulies, DH TI Split tolerance to the MHC class I molecule H-2D(d) in animals transgenic for its soluble analog SO HUMAN IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; TOXIC LYMPHOCYTES-T; SELF-TOLERANCE; MONOCLONAL-ANTIBODIES; TRANSPLANTATION ANTIGEN; PERIPHERAL TOLERANCE; POSITIVE SELECTION; NEGATIVE SELECTION; B-CELLS; MICE AB To determine whether the function of MHC molecules in tolerance and education is related to fell surface expression, we have produced two strains of transgenic mite in the C57B1/6 background that express soluble analogs of the H-2D(d) class I protein. The transgenes were stably integrated and genetically transmitted in a Mendelian fashion. Messenger RNA for the hybrid genes was detected in all tissues analyzed in a class I-like pattern of expression, with the highest levels in lymphoid tissues. All mice bearing the transgenes expressed relatively high levers (0.1 mg/ml) of the encoded protein in their serum as assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Gel filtration chromatography showed thar the soluble H-2D(d) protein exists as a heterodimer with beta 2-microglobulin and as higher order multimers in serum. Lymphoid cells From the transgenic mice showed no cell surface expression of the soluble class I protein in indirect immunofluorescence assays. Splenocytes from two independently derived transgenic lines generated primary cytotoxic and proliferative responses directed against membrane H-2D(d) antigens, Mice of both strains rejected tail skin from donors that differed from the BG background at the H-2D(d) locus only, but with delayed kinetics compared to nontransgenic littermate controls, Mice expressing the transgenic protein on immunization did not produce antibodies that recognized soluble H-2D(d) in ELISA, whereas B6 mice generated strong antibody responses to challenge with splenocytes bearing cell. surface H-2D(d). Thus, transgenic mice expressing soluble H-2D(d) were partially tolerant to stimulation by membrane-bound H-2D(d). As with the activation of T-cells, the induction and maintenance of immunologic tolerance apparently displayed different requirements depending upon the T-cell subpopulation involved. Published by Elsevier Science Inc. C1 NIAID,IMMUNOL LAB,NIH,MOL BIOL SECT,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,NIH,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 67 TC 10 Z9 10 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 FEB PY 1997 VL 52 IS 2 BP 82 EP 94 DI 10.1016/S0198-8859(96)00287-X PG 13 WC Immunology SC Immunology GA WQ242 UT WOS:A1997WQ24200003 PM 9077557 ER PT J AU Chong, SS Pack, SD Roschke, AV Tanigami, A Carrozzo, R Smith, ACM Dobyns, WB Ledbetter, DH AF Chong, SS Pack, SD Roschke, AV Tanigami, A Carrozzo, R Smith, ACM Dobyns, WB Ledbetter, DH TI A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3 SO HUMAN MOLECULAR GENETICS LA English DT Article ID INSITU HYBRIDIZATION; GENE; SUBUNIT AB Miller-Dieker syndrome (MDS) is a multiple malformation syndrome characterized by classical lissencephaly and a characteristic facies, It is associated with visible or submicroscopic deletions within chromosome band 17p13.3. Lissencephaly without facial dysmorphism has also been observed and is referred to as isolated lissencephaly sequence (ILS). Apparently partial and non-overlapping deletions of the 5' or 3' end of a candidate gene LIS1 in one ILS and one MDS patient had suggested that MDS was a single gene disorder, and that LIS1 spans in excess of 400 kb, However, the originally presumed 5' end of LIS1 was found to belong to the 14-3-3 epsilon gene residing more distally on 17p13.3. We have now isolated the correct 5' end of LIS1, constructed a similar to 500 kb genomic contig encompassing LIS1, and estimated its gene extent to be similar to 80 kb, Fluorescence in site hybridization analysis of an ILS patient with a de novo balanced translocation, as well as analysis of several other key MDS and ILS deletion patients, localizes the lissencephaly critical region within the LIS1 gene, Therefore, LIS1 remains the strongest candidate gene for the lissencephaly phenotype in ILS and MDS, Our analyses also suggest that additional genes distal to LIS1 may be responsible for the facial dysmorphology and other abnormalities seen in MDS but not in ILS patients, supporting our original concept of MDS as a contiguous gene deletion syndrome. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,INST MOL & HUMAN GENET,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. UNIV MILAN,OSPED SAN RAFFAELE,SERV GENET MED,I-20127 MILAN,ITALY. UNIV MINNESOTA,SCH MED,DEPT NEUROL,DIV PEDIAT NEUROL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT PEDIAT,MINNEAPOLIS,MN 55455. RI Pack, Svetlana/C-2020-2014; Chong, Samuel/D-8098-2015; OI Dobyns, William/0000-0002-7681-2844 NR 14 TC 126 Z9 128 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1997 VL 6 IS 2 BP 147 EP 155 DI 10.1093/hmg/6.2.147 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WH789 UT WOS:A1997WH78900001 PM 9063734 ER PT J AU LoNigro, C Chong, SS Smith, ACM Dobyns, WB Carrozzo, R Ledbetter, DH AF LoNigro, C Chong, SS Smith, ACM Dobyns, WB Carrozzo, R Ledbetter, DH TI Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID PLATELET-ACTIVATING-FACTOR; PRE-MESSENGER RNA; EXON; IDENTIFICATION; HETEROGENEITY; SUBUNIT; SITE AB Classical lissencephaly (smooth brain) or generalized agyria-pachygyria is a severe brain malformation which results from an arrest of neuronal migration at 9-13 weeks gestation, It has been observed in several malformation syndromes including Miller-Dieker syndrome (MDS) and isolated lissencephaly sequence (ILS), A gene containing P-transducin like repeats, now known as LIS1, was previously mapped to the ILS/MDS chromosome region on 17p13.3. We recently localized the classical lissencephaly critical region to the LISI gene locus by molecular analysis of key ILS and MDS patients, We have now characterized the structure of LISI, which consists of 11 exons, and have searched for the presence of subtle mutations in 19 ILS patients who showed no gross rearrangements of LISI, Single strand conformational polymorphism (SSCP) analysis revealed band-shifts for three patients, each involving a different coding exon, which were not observed in their respective parental DNAs. Sequence analysis identified these de novo mutations as a dA-->dG transition in exon VI at nucleotide 446, a dC-->dT transition in exon VIII at nucleotide 817, and a 22 bp deletion at the exon IX-intron 9 junction from nucleotide 988 to 1002+7, which causes skipping of exon IX in the mature LIS1 transcript, These changes are predicted to result in an H149R amino acid substitution, an R273X premature translation termination, and abolition of amino acids 301-334, in the respective LIS1 proteins. These data thus confirm LIS1 as the gene responsible for classical lissencephaly in ILS and MDS. C1 HOSP SAN RAFFAELE,MOL GENET LAB,I-20132 MILAN,ITALY. HOSP SAN RAFFAELE,SERV GENET MED,I-20132 MILAN,ITALY. TELETHON INST GENET & MED,MILAN,ITALY. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. UNIV MINNESOTA,SCH MED,DEPT NEUROL,DIV PEDIAT NEUROL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT PEDIAT,MINNEAPOLIS,MN 55455. RI Chong, Samuel/D-8098-2015; OI Dobyns, William/0000-0002-7681-2844 FU Telethon [E.0148] NR 29 TC 157 Z9 160 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1997 VL 6 IS 2 BP 157 EP 164 DI 10.1093/hmg/6.2.157 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WH789 UT WOS:A1997WH78900002 PM 9063735 ER PT J AU Chong, SS Almqvist, E Telenius, H LaTray, L Nichol, K BourdelatParks, B Goldberg, YP Haddad, BR Richards, F Sillence, D Greenberg, CR Ives, E VandenEngh, G Hughes, MR Hayden, MR AF Chong, SS Almqvist, E Telenius, H LaTray, L Nichol, K BourdelatParks, B Goldberg, YP Haddad, BR Richards, F Sillence, D Greenberg, CR Ives, E VandenEngh, G Hughes, MR Hayden, MR TI Contribution of DNA sequence and CAG size to mutation frequencies of intermediate alleles for Huntington disease: Evidence from single sperm analyses SO HUMAN MOLECULAR GENETICS LA English DT Article ID REPEAT INSTABILITY; FLOW-CYTOMETRY; GENE; EXPANSION; MECHANISMS; POLYMORPHISM; CHROMOSOMES; SEX AB New mutations for Huntington disease (HD) arise from intermediate alleles (IAs) with between 29 and 35 CAG repeats that expand on transmission through the paternal germline to 36 CAGs or greater. Using single sperm analysis, we have assessed CAG mutation frequencies for four IAs in families with sporadic HD (IA(NM)) and IAs ascertained from the general population (IA(GP)) by analyzing 1161 single sperm from three persons. We show that IA(NM) are more unstable than IA(GP) with identical size and sequence. Furthermore, comparison of different sized IAs and IAs with different sequences between the CAG and the adjacent CCG tracts indicates that DNA sequence is a major influence on CAG stability. These studies provide estimates of the likelihood of expansion of IA(NM) and IA(GP) to greater than or equal to 36 CAG repeats for these individuals. For an IA with a CAG of 35 in this family with sporadic HD, the likelihood for siblings to inherit a recurrent mutation greater than or equal to 36 CAG is similar to 10%. For IA(GP) Of a similar size, the risk of inheriting an expanded allele of greater than or equal to 36 CAG through the paternal germline is similar to 6%. These risk estimates are higher than previously reported and provide additional information for counselling in these families. Further studies on persons with IAs will be needed to determine whether these results can be generalized to other families. C1 UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC V6T 1Z4,CANADA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. KAROLINSKA INST,DEPT CLIN NEUROSCI,DIV GERIATR MED,S-17177 STOCKHOLM,SWEDEN. KAROLINSKA INST,DEPT MOL MED,S-17177 STOCKHOLM,SWEDEN. UNIV WASHINGTON,DEPT MOL BIOTECHNOL,SEATTLE,WA 98195. CHILDRENS HOSP,HLTH SCI CTR,SECT GENET & METAB,WINNIPEG,MB R3A 1S1,CANADA. MEM UNIV NEWFOUNDLAND,FAC MED,HLTH SCI CTR,DIV COMMUNITY MED,ST JOHNS,NF A1B 3V6,CANADA. NEW CHILDRENS HOSP,DEPT CLIN GENET,PARRAMATTA,NSW 2124,AUSTRALIA. GEORGETOWN UNIV,MED CTR,INST MOL & HUMAN GENET,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. RI Chong, Samuel/D-8098-2015; Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 NR 26 TC 71 Z9 72 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1997 VL 6 IS 2 BP 301 EP 309 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WH789 UT WOS:A1997WH78900018 PM 9063751 ER PT J AU Weinberg, CR Baird, DD Wilcox, AJ AF Weinberg, CR Baird, DD Wilcox, AJ TI Follicular phase length, time of insemination, mean cycle length, season of mother's birth and sex ratio of offspring SO HUMAN REPRODUCTION LA English DT Letter ID CONCEPTION; BABY RP Weinberg, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 1997 VL 12 IS 2 BP 398 EP 399 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA WN639 UT WOS:A1997WN63900048 ER PT J AU Lazarus, JM Bourgoignie, JJ Buckalew, VM Greene, T Levey, AS Milas, NC Paranandi, L Peterson, JC Porush, JG Rauch, S Soucie, JM Stollar, C AF Lazarus, JM Bourgoignie, JJ Buckalew, VM Greene, T Levey, AS Milas, NC Paranandi, L Peterson, JC Porush, JG Rauch, S Soucie, JM Stollar, C TI Achievement and safety of a low blood pressure goal in chronic renal disease - The Modification of Diet in Renal Disease Study Group SO HYPERTENSION LA English DT Article DE drugs, antihypertensive; blood pressure; renal disease; safety ID DIABETIC NEPHROPATHY; PROGRESSION; FAILURE; PROTEINURIA; ENALAPRIL; INSUFFICIENCY; HYPERTENSION; INHIBITION; VERAPAMIL; CAPTOPRIL AB The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m(2) (0.22 to 0.92 mL/s per 1.73 m(2)) were randomly assigned to either a usual or low BP goal (mean arterial pressure less than or equal to 107 or less than or equal to 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/-SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0+/-7.3 and 97.7+/-7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure >92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion >1 g/d, age greater than or equal to 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens mens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion >1 g/d, target BP should be a mean arterial pressure of less than or equal to 92 mm Hg, equivalent to 125/75 mm Hg. C1 NIDDKD, NIH, BETHESDA, MD 20892 USA. NR 41 TC 167 Z9 172 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD FEB PY 1997 VL 29 IS 2 BP 641 EP 650 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WH718 UT WOS:A1997WH71800018 PM 9040451 ER PT J AU Goldstein, SR DaubeWitherspoon, ME Green, MV Eidsath, A AF Goldstein, SR DaubeWitherspoon, ME Green, MV Eidsath, A TI A head motion measurement system suitable for emission computed tomography SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE brain imaging; motion correction; PET; SPECT ID PATIENT MOTION; PET; IMAGES AB Subject motion during brain imaging studies can adversely affect the images through loss of resolution and other artifacts related to movement, We have developed and tested a device to measure head motion externally in real-time during emission computed tomographic (ECT) brain imaging studies, to be used eventually to correct ECT data for that motion, The system is based on optical triangulation of three miniature lights affixed to the patient's head and viewed by two position-sensitive detectors, The computer-controlled device converts the three sets of lamp positions into rotational and translational coordinates every 0.7 seconds, When compared against a mechanical test fixture, the optical system was found to be linear and accurate with minimal crosstalk between the coordinates, In a study of two subjects, comparing the angular motions measured by the optical device and a commercially available electromagnetic motion detector, the two systems agreed well, with an root mean square (rms) difference of less than 0.6 degrees for all rotations. C1 NIH,CTR CLIN,POSITRON EMISS TOMOG DEPT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. RP Goldstein, SR (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,RM 3W13,BETHESDA,MD 20892, USA. NR 11 TC 41 Z9 42 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD FEB PY 1997 VL 16 IS 1 BP 17 EP 27 DI 10.1109/42.552052 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA WF023 UT WOS:A1997WF02300003 PM 9050405 ER PT J AU Sarin, A Williams, MS AlexanderMiller, MA Berzofsky, JA Zacharchuk, CM Henkart, PA AF Sarin, A Williams, MS AlexanderMiller, MA Berzofsky, JA Zacharchuk, CM Henkart, PA TI Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases SO IMMUNITY LA English DT Article ID REQUIRE GRANZYME-B; INTERLEUKIN-1-BETA-CONVERTING ENZYME; MEDIATED CYTOTOXICITY; DNA FRAGMENTATION; RAPID INDUCTION; APOPTOSIS; INHIBITION; DEATH; ACTIVATION; PROTEIN AB Activation of ICE/Ced-3 family proteases (caspases) has been proposed to mediate both the granule exocytosis and Fas-Fas ligand pathways of rapid target cell death by cytotoxic T lymphocytes. In agreement with this model, two peptide fluoromethyl ketone caspase inhibitors and baculovirus p35 blocked apoptotic nuclear damage and target cell lysis by the CTL-mediated Fas-Fas ligand pathway. The peptide caspase inhibitors also blocked drug-induced apoptotic cell death in tumor cells. In contrast, the caspase inhibitors blocked CTL granule exocytosis-induced target apoptotic nuclear damage, but did not inhibit target lysis. These results are consistent with recent demonstrations that granzyme B can activate caspases leading to apoptotic nuclear damage, but show that target cell lysis by CTL granule exocytosis occurs by a caspase-independent pathway. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NCI,IMMUNE CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 40 TC 185 Z9 186 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1997 VL 6 IS 2 BP 209 EP 215 DI 10.1016/S1074-7613(00)80427-6 PG 7 WC Immunology SC Immunology GA XC616 UT WOS:A1997XC61600010 PM 9047242 ER PT J AU Long, EO Burshtyn, DN Clark, WP Peruzzi, M Rajagopalan, S Rojo, S Wagtmann, N Winter, CC AF Long, EO Burshtyn, DN Clark, WP Peruzzi, M Rajagopalan, S Rojo, S Wagtmann, N Winter, CC TI Killer cell inhibitory receptors: Diversity, specificity, and function SO IMMUNOLOGICAL REVIEWS LA English DT Review ID MHC CLASS-I; HLA-B MOLECULES; IMMUNOGLOBULIN-SUPERFAMILY; NK CLONES; SURFACE-ANTIGEN; GENE FAMILIES; TARGET-CELLS; RECOGNITION; P58; CLONING AB NK cells selectively kill target cells that fail to express self-MHC class I molecules. This selective killing results from a balance between inhibitory NK receptors specific for MHC class I molecules and activating receptors that are still largely unknown. Isolation of molecular clones for the human killer cell inhibitory receptors (KIR) revealed that FIR consist of a family of molecules with Ig ectodomains and cytoplasmic tails of varying length. Soluble complexes of KIR and HLA-C molecules established that KIR recognizes and binds to its ligand as an autonomous receptor A functional expression system in human NK clones demonstrated that a single KIR can provide both recognition of MHC class I and delivery of a dominant negative signal to the NK cell. Functional evidence has been obtained for a role of the tyrosine phosphatase SHP-1 in KIR-mediated inhibition. The presence of a conserved motif used to recruit and activate SHP-1 in the cytoplasmic tail of KIR and of the mouse Ly-49 inhibitory receptor (otherwise structurally unrelated to KIR) represents an interesting case of evolutionary convergence. Furthermore, the motified to the identification of other receptors with inhibitory potential, including a type I Ig-like receptor shared by mouse mast cells and NK cells. RP Long, EO (reprint author), NIAID,IMMUNOGENET LAB,NIH,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 53 TC 179 Z9 181 U1 0 U2 1 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 FEB PY 1997 VL 155 BP 135 EP 144 DI 10.1111/j.1600-065X.1997.tb00946.x PG 10 WC Immunology SC Immunology GA WH029 UT WOS:A1997WH02900012 PM 9059889 ER PT J AU Nihrane, A Silver, J AF Nihrane, A Silver, J TI Spontaneous priming for anti-viral envelope cytotoxic T lymphocytes in mice transgenic for a murine leukaemia virus envelope gene (Fv4) SO IMMUNOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; FV-4 RESISTANCE GENE; FOCUS-FORMING VIRUS; LEUKEMIA-VIRUS; FRIEND-VIRUS; IN-VIVO; INFECTION; GLYCOPROTEIN; CELLS; TOLERANCE AB Compared with non-transgenic controls, mice bearing an Fv4 murine retroviral env transgene resist infection and do not become immunosuppressed when inoculated with Friend virus (FV). When immunized with FV antigens in the absence of infectious virus, they make antibodies and cytotoxic lymphocytes (CTL) to FV comparably to non-transgenic controls. Unimmunized transgenic mice were found to have CTL precursors, which could be activated by in vitro stimulation, specific for viral (and self) envelope protein (Env). This 'spontaneous priming' for antiviral CTL is surprising because the transgene Env is present on the surface of thymocytes and in serum from before birth. Our experiments demonstrate that T cells reactive with self-thymic and serum antigens sometimes avoid clonal elimination or inactivation. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 48 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD FEB PY 1997 VL 90 IS 2 BP 219 EP 228 DI 10.1046/j.1365-2567.1997.00157.x PG 10 WC Immunology SC Immunology GA WG060 UT WOS:A1997WG06000010 PM 9135550 ER PT J AU Strober, W Kelsall, B Fuss, I Marth, T Ludviksson, B Ehrhardt, R Neurath, M AF Strober, W Kelsall, B Fuss, I Marth, T Ludviksson, B Ehrhardt, R Neurath, M TI Reciprocal IFN-gamma and TGF-beta responses regulate the occurrence of mucosal inflammation SO IMMUNOLOGY TODAY LA English DT Article ID ORAL TOLERANCE; INDUCTION; CELLS; MICE AB Recent studies of oral tolerance and experimental colitis indicate that the occurrence of gastrointestinal inflammation is determined by a balance between proinflammatory interferon gamma responses and anti-inflammatory transforming growth factor beta responses. Here, Warren Strober and colleagues discuss the new findings. C1 UNIV MAINZ,MED KLIN 1,D-55516 MAINZ,GERMANY. RP Strober, W (reprint author), NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892, USA. OI Ludviksson, Bjorn/0000-0002-6445-148X NR 11 TC 326 Z9 330 U1 0 U2 3 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 FEB PY 1997 VL 18 IS 2 BP 61 EP 64 DI 10.1016/S0167-5699(97)01000-1 PG 4 WC Immunology SC Immunology GA WJ203 UT WOS:A1997WJ20300004 PM 9057354 ER PT J AU Kole, HK Liotta, AS Garant, MJ Kole, S Bernier, M AF Kole, HK Liotta, AS Garant, MJ Kole, S Bernier, M TI Specific inhibition of insulin receptor dephosphorylation by a synthetic dodecapeptide containing sulfotyrosyl residues as phosphotyrosyl mimetic SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article; Proceedings Paper CT 4th International Symposium on Biochemical Role of Eukaryotic Cell Surface Macromolecules CY JAN 06-10, 1996 CL NEW DELHI, INDIA SP Natl Inst Immunol, Univ Delhi S Campus, New Delhi, India, Council Sci & Ind Res (CSIR), Dept Biotechnol (DBT), Govt India ID PROTEIN-TYROSINE-PHOSPHATASE; LAR AB We have synthesized a tris-sulfotyrosyl dodecapeptide (3S-peptide-I) that corresponds to the major autophosphorylation domain within the insulin receptor beta-subunit and showed that it potently inhibited insulin receptor dephosphorylation by protein tyrosine phosphatases (PTPases) in vitro. 3S-peptide-I also inhibited tyrosine dephosphorylation of a synthetic peptide by the recombinant PTPase PTP-1B, indicating that 3S-peptide-I interacts directly with PTPase, causing its inactivation. The peptide had no effect on the activity of serine/threonine phosphatases, PP-1 and PP-2A, or alkaline phosphatase. Furthermore, we found that the introduction of a N-stearyl derivative of 3S-peptide-I in CHO/HIRc cells caused a significant increase in insulin-stimulated phosphorylation of the insulin receptor. In contrast, ligand-stimulated phosphorylation of epidermal growth factor (EGF) receptor in CHO cells overexpressing EGF receptors was not affected by the presence of N-stearyl-3S-peptide-I. These data suggest that by inhibiting dephosphorylation of the insulin receptor in intact cells, 3S-peptide-I may specifically enhance insulin signalling. RP Kole, HK (reprint author), NIA,GERONTOL RES CTR,DIABET UNIT,LAB CLIN PHYSIOL,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Bernier, Michel/0000-0002-5948-368X NR 14 TC 1 Z9 1 U1 0 U2 0 PU COUNCIL SCIENTIFIC INDUSTRIAL RESEARCH PI NEW DELHI PA PUBL & INFO DIRECTORATE, NEW DELHI 110012, INDIA SN 0301-1208 J9 INDIAN J BIOCHEM BIO JI Indian J. Biochem. Biophys. PD FEB-APR PY 1997 VL 34 IS 1-2 BP 50 EP 55 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XH906 UT WOS:A1997XH90600010 PM 9343928 ER PT J AU Ma, J Saito, H Oka, T Vijay, IK AF Ma, J Saito, H Oka, T Vijay, IK TI Further characterization of negative regulatory element involved in the hormonal regulation of GlcNAc-1-P transferase gene in mouse mammary gland SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article; Proceedings Paper CT 4th International Symposium on Biochemical Role of Eukaryotic Cell Surface Macromolecules CY JAN 06-10, 1996 CL NEW DELHI, INDIA SP Natl Inst Immunol, Univ Delhi S Campus, New Delhi, India, Council Sci & Ind Res (CSIR), Dept Biotechnol (DBT), Govt India ID ASPARAGINE-LINKED GLYCOPROTEINS; ACETYL-D-GLUCOSAMINE; N-ACETYLGLUCOSAMINE-1-PHOSPHATE TRANSFERASE; NUCLEAR FACTOR; BETA-CASEIN; UDP-GLCNAC; TRANSCRIPTION; BIOSYNTHESIS; INITIATION; FAMILY 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. Earlier, we demonstrated that a distal negative regulatory element in mouse GPT (mGPT) promoter plays an important role in developmental and hormonal control of mGPT gene expression in mammary gland (Ma J, Saito H, Oka T and Vijay I K (1996) J Biol Chem, in press). In this report, a tissue distribution of the repressor that binds the negative regulatory element was examined; a comparison of the negative regulatory element to other consensus sequences for known transcription factors is discussed. C1 UNIV MARYLAND,DEPT ANIM SCI,COLLEGE PK,MD 20742. NIDDKD,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK19682] NR 23 TC 1 Z9 1 U1 0 U2 1 PU COUNCIL SCIENTIFIC INDUSTRIAL RESEARCH PI NEW DELHI PA PUBL & INFO DIRECTORATE, NEW DELHI 110012, INDIA SN 0301-1208 J9 INDIAN J BIOCHEM BIO JI Indian J. Biochem. Biophys. PD FEB-APR PY 1997 VL 34 IS 1-2 BP 110 EP 117 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XH906 UT WOS:A1997XH90600020 PM 9343938 ER PT J AU Lands, WEM AF Lands, WEM TI Alcohol's impact upon glycobiology SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article; Proceedings Paper CT 4th International Symposium on Biochemical Role of Eukaryotic Cell Surface Macromolecules CY JAN 06-10, 1996 CL NEW DELHI, INDIA SP Natl Inst Immunol, Univ Delhi S Campus, New Delhi, India, Council Sci & Ind Res (CSIR), Dept Biotechnol (DBT), Govt India ID GAMMA-GLUTAMYL-TRANSFERASE; ETHANOL INTOXICATION; LIVER-INJURY; MARKER; SERUM; GM1; DESIALYLATION; SIALYLATION; RECEPTOR; DRINKING AB This report reviews and illustrates ways in which some of the problems linked to excessive alcohol intake may develop from alcohol-induced alterations of eukaryotic cell surface molecules, Alcohol is the number one drug of abuse in the US, affecting at least 15 million Americans and causing annual losses of more than $80 billion and 100,000 lives. An estimated 20-40% of all persons admitted to general hospitals have alcohol-related problems and are often undiagnosed alcoholics being treated for the consequences of their drinking. Chronic alcohol-related cirrhosis of the liver is the ninth leading cause of death in the US, with over 28,000 deaths annually. Alcohol has harmful effects on almost every organ system in the body, producing cardiovascular disorders, liver disease, neuropathological illness and fetal injury. The etiologic mechanisms for these effects of alcohol is a research area of considerable importance to the National Institute for Alcohol Abuse and Alcohlism. RP Lands, WEM (reprint author), NIAAA,DIV BASIC RES,NIH,6000 EXECUT BLVD MSC 7003,BETHESDA,MD 20892, USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU COUNCIL SCIENTIFIC INDUSTRIAL RESEARCH PI NEW DELHI PA PUBL & INFO DIRECTORATE, NEW DELHI 110012, INDIA SN 0301-1208 J9 INDIAN J BIOCHEM BIO JI Indian J. Biochem. Biophys. PD FEB-APR PY 1997 VL 34 IS 1-2 BP 212 EP 213 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XH906 UT WOS:A1997XH90600035 PM 9343953 ER PT J AU Bos, MP Hogan, D Belland, RJ AF Bos, MP Hogan, D Belland, RJ TI Selection of Opa(+) Neisseria gonorrhoeae by limited availability of normal human serum SO INFECTION AND IMMUNITY LA English DT Article ID COMPLEMENT; LIPOOLIGOSACCHARIDE; SIALYLATION; RESISTANCE; GONOCOCCI; OPACITY; LIPOPOLYSACCHARIDE; PATHOGENESIS; ANTIBODIES; EXPRESSION AB Experimental infections of human male volunteers with Neisseria gonorrhoeae have provided valuable insights into the early stages of gonorrheal disease. Bacterial variants expressing outer membrane opacity (Opa) proteins appear to be selected from the inoculum during a period in which total recoverable numbers of bacteria decrease rapidly. This apparent survival advantage occurs simultaneously with the onset of an inflammatory response, characterized by local production of interleukin 6 (IL-6) and IL-8 and the appearance of leukocytes in urine. Since the inflammatory response may also result in the presence of serum factors on the mucosal surface, we investigated the possibility that killing in normal human serum (NHS) leads to the selection of Opa(+) variants. We therefore studied killing of separate populations and mixtures of Opa(-) and Opa(+) N. gonorrhoeae MS11mk in NHS. Expression of an Opa protein conferred a survival advantage upon the organism; i.e., the Opa(+) variants were more serum resistant than their isogenic Opa(-) counterparts, resulting in a selection for Opa(+) phenotypes when a mixture of Opa(+) and Opa(-) gonococci (GC) was exposed to submaximal doses of NHS. This selection was observed in three different lipooligosaccharide (LOS) backgrounds, indicating that it was not due to a difference in LOS expression between Opa(-) and Opa(+) phenotypes. Incubation in NHS of sialylated GC resulted in a similar selection for Opa(+) variants. The presence of normal human urine during the serum killing assay had no effect on the selection phenomenon but drastically depleted NHS of bactericidal activity, which was found to be at least partly due to complement inhibition. The results suggest that serum killing may contribute to the transition from Opa(-) to Opa(+) phenotypes during the early stages of infection of the male urethra. RP Bos, MP (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 31 TC 15 Z9 15 U1 1 U2 3 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 FEB PY 1997 VL 65 IS 2 BP 645 EP 650 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WE900 UT WOS:A1997WE90000045 PM 9009326 ER PT J AU Ramakrishnan, L Valdivia, RH McKerrow, JH Falkow, S AF Ramakrishnan, L Valdivia, RH McKerrow, JH Falkow, S TI Mycobacterium marinum causes both long-term subclinical infection and acute disease in the leopard frog (Rana pipiens) SO INFECTION AND IMMUNITY LA English DT Article ID TUBERCULOSIS AB Mycobacterium marinum grows at an optimal temperature of 33 degrees C, far lower than that for M. tuberculosis. Consequently, M. marinum infection of mammals is restricted largely to the cooler surfaces of the body, such as the extremities, but it causes a systemic infection in a large number of poikilothermic animals, Here, we describe a laboratory animal model for M. marinum disease in the leopard frog (Rana pipiens), a natural host species. M. marinum causes a chronic granulomatous, nonlethal disease in immunocompetent frogs. Immunosuppression of the frogs with hydrocortisone results in an acute, fulminant, lethal disease, This animal model, in which a spectrum of tuberculosis-like disease can be produced, will be useful for the dissection of the genetic basis of mycobacterial pathogenesis. C1 UNIV CALIF SAN FRANCISCO, DEPT PATHOL, SAN FRANCISCO, CA 94143 USA. UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA. VET ADM MED CTR, SAN FRANCISCO, CA 94121 USA. NIAID, ROCKY MT LABS, NIH, HAMILTON, MT 59840 USA. RP STANFORD UNIV, DEPT MICROBIOL & IMMUNOL, SCH MED, FAIRCHILD D309B, STANFORD, CA 94305 USA. FU NIAID NIH HHS [AI36396] NR 24 TC 79 Z9 79 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1997 VL 65 IS 2 BP 767 EP 773 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WE900 UT WOS:A1997WE90000059 PM 9009340 ER PT J AU Moore, DF Rosenfeld, MR Gribbon, PM Winlove, CP Tsai, CM AF Moore, DF Rosenfeld, MR Gribbon, PM Winlove, CP Tsai, CM TI Alpha-1-acid (AAG, orosomucoid) glycoprotein: Interaction with bacterial lipopolysaccharide and protection from sepsis SO INFLAMMATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; ENDOTOXIN; TOXICITY; SEQUENCE; BINDING AB In the acute phase response to a variety of insults a rise in the levels of the acute phase proteins, including elevations of serum cui acid glycoprotein (AAG) occurs. The physiological role of AAG is unknown, however, the time course of AAG production in the acute phase response together with its strong affinity for basic compounds suggests that AAG may function as an immune modulator to bind both exogenous and endogenous inflammatory mediators. Using E. coli lipopolysaccharide (LPS), an initiator of the acute inflammatory response associated with septic shock, we demonstrate that AAG-LPS complexes can activate mouse macrophages in vitro. In a mouse animal model of sepsis, AAG was shown to protect against meningococcal endotoxin. To pursue the mechanism of AAG action we demonstrated that AAG interacts directly with LPS using dynamic light scattering particle sizing and particle mobility. We also determined the enthalpy of interaction of AAG and LPS and showed that AAG leads to agglutination of LPS impregnated rabbit red blood cells. These studies suggest that AAG may function as an immune-modulator in the acute phase response, possibly by counter-regulating the activity of macrophage proinflammatory cytokines. C1 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,COTZIAS LAB NEUROONCOL,NEW YORK,NY 10021. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,CTR BIOL & MED SYST,PHYSIOL FLOW STUDIES GRP,LONDON SW7 2BX,ENGLAND. NIH,CTR BIOL EVALUAT & RES,LAB BACTERIAL POLYSACCHARIDES,BETHESDA,MD 20892. RP Moore, DF (reprint author), CORNELL UNIV,MED CTR,DEPT NEUROL,NEW YORK,NY 10021, USA. NR 28 TC 43 Z9 46 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-3997 J9 INFLAMMATION JI Inflammation PD FEB PY 1997 VL 21 IS 1 BP 69 EP 82 DI 10.1023/A:1027342909423 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA XC494 UT WOS:A1997XC49400007 PM 9179623 ER PT J AU Andrews, L Laughinghouse, A Sina, BJ AF Andrews, L Laughinghouse, A Sina, BJ TI Lectin binding characteristics of male and female salivary gland proteins of Anopheles gambiae: Identification and characterization of female specific glycoproteins SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Anopheles gambiae; mosquito; vector; salivary glands; saliva; glycoprotein lectins ID CELL-MEMBRANE GLYCOPROTEINS; MOSQUITO AEDES-AEGYPTI; ELECTRON-MICROSCOPE; PROBING TIME; APYRASE; SPOROZOITES; STEPHENSI AB Male and female salivary gland proteins of Anopheles gambiae were analyzed on blots of SDS gels by lectin binding in order to identify female specific glycoproteins. At least six major and several minor protein bands were identifiable in the total female gland proteins which were not visible in the male glands. The proximal lateral region of the female gland contained minor proteins which were similar in electrophoretic pattern to male salivary gland proteins. The distal lateral region and the median lobe each contained four different predominant protein bands. Western blot analysis with seven biotinylated lectins showed a distinct pattern of glycosylation between male and female salivary glands. Concanavalin agglutinin (Con A) and Dolichos biflorus agglutinin (DBA) bound to the highest number of male and female salivary gland glycoproteins while Ricinus communis agglutinin (RCA) and wheat germ agglutinin (WGA) showed the least binding, recognizing at least five female specific salivary gland glycoproteins. Soybean agglutinin (SEA) and peanut agglutinin (PNA) displayed a similarity in their binding pattern and distinguished the most female specific glycoproteins. Con A binding of the different morphological regions of the female salivary gland detected seven glycoproteins in the distal lateral region and four in the median lobe with trace amounts of glycoproteins in the proximal regions, In contrast, SEA detected glycoproteins mostly in the median lobe including eight female specific glycoproteins. Four out of the eight female specific glycoproteins were also found in the distal lateral region, Enzymatic deglycosylation followed by lectin binding showed that salivary gland glycoproteins are predominantly asparagine linked N-glycans with some possible O-linked glycans. (C) 1997 Elsevier Science Ltd. C1 UNIV MARYLAND,DEPT ENTOMOL,COLLEGE PK,MD 20742. NIH,MALARIA RES LAB,BETHESDA,MD 20505. NR 37 TC 7 Z9 7 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD FEB PY 1997 VL 27 IS 2 BP 159 EP 166 DI 10.1016/S0965-1748(96)00081-1 PG 8 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA WL614 UT WOS:A1997WL61400007 ER PT J AU Ichijo, T Nakatsuji, Y Tanaka, E Alter, HJ Yoshizawa, K Imai, H Sodeyama, T Kiyosawa, K AF Ichijo, T Nakatsuji, Y Tanaka, E Alter, HJ Yoshizawa, K Imai, H Sodeyama, T Kiyosawa, K TI Autoimmune hepatitis type 1 without evidence of hepatitis G virus infection SO INTERNATIONAL HEPATOLOGY COMMUNICATIONS LA English DT Article DE autoimmune hepatitis; hepatitis G virus; HGV RNA; HGV infection ID CHRONIC ACTIVE HEPATITIS; JAPANESE PATIENTS; IDENTIFICATION AB Hepatitis G virus (HGV) RNA was measured in sera from 60 patients satisfying the international diagnostic criteria of definite autoimmune hepatitis type 1 using a reverse transcription and polymerase chain reaction with primers of the putative NS5 region of the HGV genome. Five patients had a history of blood transfusion. Of the 60 patients, 55 (92%) were confirmed as having human leukocyte antigen (HLA) DR4 or DR2 which are genetic markers for susceptibility to autoimmune hepatitis in Japanese. None of the 60 patients had any serum markers suggesting hepatitis B virus infection and 5 (8%) had evidence of on-going hepatitis C virus infection. No patients had HGV RNA in serum. The absence of active HGV infection in this cohort suggests that HGV does not play a casual role in the development of autoimmune hepatitis in Japan. (C) 1997 Elsevier Science Ireland Ltd. C1 SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 2,MATSUMOTO,NAGANO 390,JAPAN. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 20 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0928-4346 J9 INT HEPATOL COMMUN JI Int. Hepatol. Commun. PD FEB PY 1997 VL 6 IS 5 BP 219 EP 224 DI 10.1016/S0928-4346(96)00349-0 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WR983 UT WOS:A1997WR98300002 ER PT J AU Kaslow, DC AF Kaslow, DC TI Transmission-blocking vaccines: Uses and current status of development SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article; Proceedings Paper CT Australian and New Zealand Societies for Parasitology Scientific Meeting CY SEP 27-30, 1995 CL ADELAIDE, AUSTRALIA DE Plasmodium falciparum; transmission-blocking; malaria vaccines; sexual stages; gametocytes; gametes; zygotes; ookinetes; oocysts; mosquitoes ID GAMETE SURFACE PROTEIN; PLASMODIUM-FALCIPARUM; SEXUAL STAGES; PERITROPHIC MEMBRANE; PARASITE CHITINASE; MALARIA PARASITE; TARGET ANTIGEN; PFS25 PROTEIN; ANTIBODIES; GENE AB Malaria continues to cause incomprehensible human suffering throughout most of the tropics and subtropics: in sub-Saharan Africa it is estimated that 2 million children die each year as a direct cause of infection with Plasmodium. Vector control and malaria chemotherapy that were previously effective in controlling and treating malaria are now largely ineffective due to insecticide-resistant mosquitoes and drug-resistant parasites. As alternatives to these mainstays of control, an intensive effort to develop subunit vaccines targeted at various stages of the life has been undertaken. One such vaccine, directed against the sexual and sporogonic stages and referred to as a transmission-blocking vaccine, offers the hope of controlling malaria in geographically isolated areas, preventing re-introduction of the parasite in malaria-free zones, blocking the spread of drug-resistant or vaccine escape mutants, and reducing exposure to ''virulent'' strains of parasites. A series of potential transmission-blocking vaccine candidates have identified and the genes encoding these surface proteins have now been isolated and sequenced. One such vaccine candidate, Pfs25, is now being tested in human Phase I safety and immunogenicity studies. Here the use and status of transmission-blocking vaccines are reviewed. Published by Elsevier Science Ltd. RP Kaslow, DC (reprint author), NIAID,PARASIT DIS LAB,MALARIA VACCINES SECT,NIH,BETHESDA,MD 20892, USA. NR 44 TC 74 Z9 75 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD FEB PY 1997 VL 27 IS 2 BP 183 EP 189 DI 10.1016/S0020-7519(96)00148-8 PG 7 WC Parasitology SC Parasitology GA WN333 UT WOS:A1997WN33300008 PM 9088989 ER PT J AU Fracasso, MP Lamb, ME Scholmerich, A Leyendecker, B AF Fracasso, MP Lamb, ME Scholmerich, A Leyendecker, B TI The ecology of mother-infant interaction in Euro-American and immigrant central American families living in the United States SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article AB In an attempt to explore cultural and subcultural similarities and variations in the patterns of child care, two culturally and economically distinct groups were studied. Twenty-one 3-month-old infants had well-educated Euro-American mothers and another 17 had recently migrated Central American mothers. Observations of parent-infant interaction and behaviour were conducted at home throughout the day to ensure coverage of complete 12-hour cycles. Descriptive analyses revealed remarkable similarities and few differences in the everyday experiences of infants in these two diverse groups. Both groups of mothers spent most of their time playing with, feeding, or caring for their infants. Fathers spent little time with their infants during the day but their presence affected the amount of time spent in various contexts, with significantly less object play occurring when the fathers were present. Mother and infant vocalisations and mutual attention occurred more frequently during social interaction and caretaking than in bouts of feeding. These descriptive profiles expand our basic understanding of infants' everyday experiences in diverse subcultural groups. RP Fracasso, MP (reprint author), NICHHD,SECT SOCIAL & EMOT DEV,9190 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 17 TC 13 Z9 13 U1 1 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD FEB PY 1997 VL 20 IS 2 BP 207 EP 217 PG 11 WC Psychology, Developmental SC Psychology GA WR310 UT WOS:A1997WR31000002 ER PT J AU Katagiri, C Maeda, R Yamashika, C Mita, K Sargent, TD Yasumasu, S AF Katagiri, C Maeda, R Yamashika, C Mita, K Sargent, TD Yasumasu, S TI Molecular cloning of Xenopus hatching enzyme and its specific expression in hatching gland cells SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE hatching enzyme; gene expression; hatching gland cells; metalloprotease; Xenopus laevis ID LAEVIS; PROTEINS; CLEAVAGE; EVENTS; HEAD AB UVS.2 has been known as a cloned cDNA expressed selectively in the hatching gland cells of Xenopus laevis. To determine the molecular identity and function of UVS.2-encoded proteins, antibodies were raised against a bacterially-expressed fusion protein comprising glutathione-S-transferase (GST) and UVS.2. Anti-GST-UVS.2 antibodies inhibited the vitelline envelope digesting activity of the medium (hatching medium) in which dejellied prehatching embryos were cultured. On Western blotting, hatching medium contained 60 kDa and 40 kDa molecules reactive with these antibodies. Whole-mount immunostaining showed a specific localization of UVS.2 protein in the hatching gland cells which appeared first at stage 20, increased in number and intensity to stage 31 then decreased gradually thereafter. Immunoelectron microscopy revealed that UVS.2 protein is localized exclusively in the secretory granules in the hatching gland cells. A cDNA library from the dorsoanterior portion of stage 25 embryos was screened with UVS.2, and a 1.8 kb insert thus cloned contained additional 619bp and 204bp at the 5' and 3' ends of UVS.2, respectively. This clone, designated XHE, contained an open reading frame encoding 514 amino acids including both signal and propeptide sequences. The predicted mature enzyme comprising 425 amino acids consists of about 200 amino acid-long metalloprotease sequence of astacin family at the hi-terminus, followed by two repeats of CUB domain each 110 amino acid-length. We conclude that UVS.2 represents an approximately 3/4 C-terminal portion of the hatching enzyme. C1 NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. SOPHIA UNIV,INST LIFE SCI,CHIYODA KU,TOKYO 102,JAPAN. RP Katagiri, C (reprint author), HOKKAIDO UNIV,GRAD SCH SCI,DIV BIOL SCI,SAPPORO,HOKKAIDO 060,JAPAN. NR 24 TC 52 Z9 55 U1 1 U2 3 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD FEB PY 1997 VL 41 IS 1 BP 19 EP 25 PG 7 WC Developmental Biology SC Developmental Biology GA WK284 UT WOS:A1997WK28400002 PM 9074934 ER PT J AU ZeichnerDavid, M Vo, H Tan, H Diekwisch, T Berman, B Thiemann, F Alcocer, MD Hsu, P Wang, T Eyna, J Caton, J Slavkin, HC MacDougall, M AF ZeichnerDavid, M Vo, H Tan, H Diekwisch, T Berman, B Thiemann, F Alcocer, MD Hsu, P Wang, T Eyna, J Caton, J Slavkin, HC MacDougall, M TI Timing of the expression of enamel gene products during mouse tooth development SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE tooth development; amelogenesis; tuftelin; amelogenin; ameloblastin; mouse ID EPITHELIAL-MESENCHYMAL INTERACTIONS; DEVELOPING BOVINE ENAMEL; IMMUNOHISTOCHEMICAL LOCALIZATION; MOLAR DEVELOPMENT; MATRIX PROTEINS; SERUM-PROTEINS; AMELOGENIN; GROWTH; ORGANOGENESIS; DENTIN AB In order to understand the mechanisms involved in tooth development it is important to define the timing for tissue-specific gene expression. A consequence of ameloblast cell differentiation is the sequential expression of tissue-specific genes whose products form the enamel extracellular matrix. The ameloblast phenotype has been characterized as consisting of two major classes of proteins: amelogenins and non-amelogenin proteins such as anionic enamel proteins (enamelins, tuft proteins, tuftelin, sulfated proteins) and enamel proteases. The postulated functions for the anionic enamel proteins are as nucleators for hydroxyapatite crystal formation while amelogenins control the crystal size, growth and orientation. While the amelogenins have been well characterized, detailed knowledge for anionic enamel proteins has been sparse. In the present study, we designed experiments to characterize one of the anionic enamel proteins from mouse molars, tuftelin, and to determine the timing of expression of this protein during molar tooth development. Our results showed the initial detection of tuftelin transcripts within proliferating inner enamel epithelial cells at very early stages of tooth development (13 days of embryonic development equivalent to the bud stage of tooth development). These data provide direct evidence that invalidates previous dogmas that enamel proteins were synthesized by polarized, non-dividing, fully differentiated ameloblast cells. In addition, tuftelin was found to be synthesized also by dental papilla mesenchyme cells suggesting that this protein is not enamel-specific. These data taken together open the possibility that the tuftelin present in the dentino-enamel junction could be secreted by both, preodontoblast cells and preameloblast cells. It might also suggest a possible different role for tuftelin than nucleator of hydroxyapatite crystals. C1 UNIV TEXAS, SCH DENT, DALLAS, TX 75230 USA. NIAMSD, CRANIOFACIAL DEV SECT, NIH, BETHESDA, MD USA. UNIV TEXAS, HLTH SCI CTR, SCH DENT, SAN ANTONIO, TX 78284 USA. RP ZeichnerDavid, M (reprint author), UNIV SO CALIF, SCH DENT, CTR CRANIOFACIAL MOL BIOL, 2250 ALCAZAR ST, CSA 106, LOS ANGELES, CA 90033 USA. RI Zeichner-David, Margarita/A-6567-2008; Thiemann, Flavia/E-5569-2012 OI Thiemann, Flavia/0000-0003-3199-5832 FU NIDCR NIH HHS [DE 11172, DE-02848] NR 63 TC 63 Z9 64 U1 2 U2 2 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD FEB PY 1997 VL 41 IS 1 BP 27 EP 38 PG 12 WC Developmental Biology SC Developmental Biology GA WK284 UT WOS:A1997WK28400003 PM 9074935 ER PT J AU CorreaSales, C Tosta, CE Rizzo, LV AF CorreaSales, C Tosta, CE Rizzo, LV TI The effects of anesthesia with thiopental on T lymphocyte responses to antigen and mitogens in vivo and in vitro SO INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY LA English DT Article DE anesthesia; interleukin-2; interleukin-4; lymphocyte; thiopental ID KILLER-CELL CYTOTOXICITY; NATURAL-KILLER; HALOTHANE ANESTHESIA; GENERAL-ANESTHESIA; SURGICAL STRESS; MICE; SURGERY; INTERFERON; INDUCTION; HELPER AB In this study we show that antigen-specific lymphocyte proliferation and interleukin (IL)-2 production by peripheral blood lymphocytes from patients under thiopental anesthesia are significantly depressed. In contrast, mitogen-induced lymphocyte proliferation and IL-2 secretion are not depressed. We have also shown that tetanus toroid (TT) specific CD4+ T cell clones, with a known cytokine production profile, were sensitive to the inhibitory effects of thiopental and exhibited decreased proliferation to TT as well as decreased secretion of IL-2. We observed no difference regarding IL-4 production by these clones. The data suggest that the immunosuppressive effect of thiopental is confined to antigen-specific responses. In addition, we have shown that whereas IL-2 and interferon-gamma production is dramatically impaired by the drug, IL-4 production is not significantly altered. This last finding has important implications regarding the type of immune response that is most affected by this anesthetic agent. In spite of the transient decrease in antigen-driven IL-2 synthesis, no clinical evidence of infection was noted in any healthy patient. (C) 1997 International Society for Immunopharmacology. C1 NEI,CLIN IMMUNOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. UNIV BRASILIA,FAC CIENCIAS SAUDE,HOSP UNIV BRASILIA,ANESTHESIOL UNIT,BRASILIA,DF,BRAZIL. UNIV BRASILIA,FAC CIENCIAS SAUDE,DEPT PATHOL,IMMUNOL SECT,BRASILIA,DF,BRAZIL. RI Rizzo, Luiz Vicente/B-4458-2009 NR 46 TC 32 Z9 32 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0192-0561 J9 INT J IMMUNOPHARMACO JI Int. J. Immunopharmacol. PD FEB PY 1997 VL 19 IS 2 BP 117 EP 128 DI 10.1016/S0192-0561(97)00003-9 PG 12 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA XP902 UT WOS:A1997XP90200008 PM 9278182 ER PT J AU Westergaard, GC Lundquist, AL Kuhn, HE Suomi, SJ AF Westergaard, GC Lundquist, AL Kuhn, HE Suomi, SJ TI Ant-gathering with tools by captive tufted capuchins (Cebus apella) SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE ants; capuchin; Cebus apella; Pan troglodytes; tool use ID MONKEYS; CHIMPANZEES; MANIPULATION; TECHNOLOGY; SET AB We examined ant-gathering with tools by captive tufted capuchins (Cebus apella) via two experiments. In Experiment 1, we provided groups of subjects with sticks and small branches and an apparatus that accommodated the use of tools to gather ants. In Experiment 2, we sealed the apparatus with acetate and provided the same subjects with sticks and stones. Seven of 14 subjects used sticks and leaves as probes to extract ants from the apparatus. Six of them modified probes by detaching sticks from larger branches, breaking sticks into two or more pieces, and subtracting leaves and bark. Three subjects later used a stone and stick tool-set to penetrate acetate barriers and to extract ants. These results demonstrate the use of tools by Cebus to capture moving prey and are consistent with the idea that sensorimotor skills associated with the production and use of tools in primates evolved convergently in capuchins and great apes. C1 NICHHD,LAB COMARAT ETHOL,POOLESVILLE,MD 20837. RP Westergaard, GC (reprint author), NIH,ANIM CTR,POB 529,POOLESVILLE,MD 20837, USA. NR 20 TC 12 Z9 13 U1 2 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD FEB PY 1997 VL 18 IS 1 BP 95 EP 103 DI 10.1023/A:1026345307953 PG 9 WC Zoology SC Zoology GA WQ882 UT WOS:A1997WQ88200006 ER PT J AU Goodman, SH Lahey, BB Fielding, B Dulcan, M Narrow, W Regier, D AF Goodman, SH Lahey, BB Fielding, B Dulcan, M Narrow, W Regier, D TI Representativeness of clinical samples of youths with mental disorders: A preliminary population-based study SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID PSYCHIATRIC-DISORDERS; EMOTIONAL-PROBLEMS; CHILDHOOD PSYCHOPATHOLOGY; DYADIC ADJUSTMENT; PUBERTAL STATUS; HELP-SEEKING; RISK-FACTORS; DRUG-USE; CHILDREN; FAMILY AB In a household community sample of 1,285, 9-17 year-olds with mental disorders who had received outpatient specialty mental health services in the past year were compared with youths with mental disorders who had not received those services to determine if samples drawn from clinical settings are representative of youths with mental disorders in the general population. Those who had used services were more impaired, less competent, more likely to have comorbid disorders, more likely to belong to non-Hispanic White relative to other ethnic groups, and less likely to be prepubertal girls. Their parents were more educated, but less satisfied with family life, engaged in less monitoring of their children, and more likely to have used mental health services themselves. These findings suggest the hypothesis that samples of youths with mental disorders drawn from outpatient clinical settings are not representative of all youths with mental disorders. If confirmed, this would indicate the importance of population-based samples for the study of psychopathology in youths. C1 UNIV CHICAGO,DEPT CHILD PSYCHIAT,CHICAGO,IL 60637. EMORY UNIV,SCH PUBL HLTH,ATLANTA,GA. NORTHWESTERN UNIV,SCH MED,DEPT CHILD PSYCHIAT,EVANSTON,IL 60208. NIMH,DIV CLIN RES,EPIDEMIOL & PSYCHOPATHOL RES BRANCH,ROCKVILLE,MD 20857. RP Goodman, SH (reprint author), EMORY UNIV,DEPT PSYCHOL,532 KILGO CIRCLE,ATLANTA,GA 30322, USA. FU NIMH NIH HHS [UO1 MH46725, UO1 MH46717, UO1 MH46718] NR 66 TC 130 Z9 130 U1 7 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 1997 VL 106 IS 1 BP 3 EP 14 DI 10.1037/0021-843X.106.1.3 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA WF064 UT WOS:A1997WF06400001 PM 9103713 ER PT J AU Barchi, JJ Jeong, LS Siddiqui, MA Marquez, VE AF Barchi, JJ Jeong, LS Siddiqui, MA Marquez, VE TI Conformational analysis of the complete series of 2' and 3' monofluorinated dideoxyuridines SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE conformational analysis; uridine 2',3'-dideoxynucleosides; nuclear magnetic resonance spectroscopy; pseudorotational analysis ID NMR COUPLING-CONSTANTS; SUBSTITUENT ELECTRONEGATIVITIES; KARPLUS EQUATION; BIOLOGICAL-ACTIVITY; SUGAR RING; NUCLEOSIDES; ANALOGS; SPECTROSCOPY; PSEUDOROTATION; NUCLEOTIDES AB The solution conformations of a set of uridine 2',3'-dideoxynucleosides, where each of the hydrogens at the 2'- and 3'-positions of the sugar ring were individually replaced with a fluorine atom, were studied by nuclear magnetic resonance spectroscopy and pseudorotational analysis. The distribution of the north/south (N/S) puckering equilibrium for each compound was calculated by coupling constant analysis aided by the program PSEUROT. The data confirmed that the pseudorotational equilibrium of the fluorinated glycones is governed by the position of the fluorine atom. The preferred rotamer populations about the C4'-C5' (gamma) and C1'-N1' (chi) bonds calculated from coupling constant and NOE analysis, respectively, were also influenced by the presence of fluorine. Proton coupling to the fluorine atom was also used to qualitatively estimate the N/S equilibrium population. Through space, long range H-1-F-19 coupling constants were observed in compounds where the fluorine atom was above the plane of the ring ('up'). The pseudorotational parameters of the compounds described were tempered by the anomeric effect which drives the pseudorotational equilibrium towards the 2'-exo/3'-endo (northern) pucker. Ab initio calculations using the 3-21 G* basis set yielded a measure of the energy differences between the N and S local minima in each compound. These results agree with previous conformational studies of other fluorinated nucleoside analogues and prove that the furanose ring pucker is governed by the highly electronegative fluorine atom. However, the competing anomeric effect plays a major role in determining the mole fraction of the minor conformer of these compounds in solution. (C) 1997 Elsevier Science B.V. C1 NCI, DIV BASIC RES, MED CHEM LAB, NIH, BETHESDA, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 37 TC 37 Z9 37 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD FEB 1 PY 1997 VL 34 IS 1 BP 11 EP 29 DI 10.1016/S0165-022X(96)00032-2 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP422 UT WOS:A1997WP42200002 PM 9089381 ER PT J AU Hansford, RG Hogue, BA Mildaziene, V AF Hansford, RG Hogue, BA Mildaziene, V TI Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE respiratory chain; reactive oxygen species ID HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE; GENERATION; DNA; RADICALS; COMPLEX; OXYGEN AB We have examined the substrate specificity and inhibitor sensitivity of H2O2 formation by rat heart mitochondria. Active H2O2 production requires both a high fractional reduction of Complex I (indexed by NADH/NAD(+) + NADH ratio) and a high membrane potential, Delta psi. These conditions are achieved with supraphysiological concentrations of succinate. With physiological concentrations of NAD-linked substrates, rates of H2O2 formation are much lower (less than 0.1% of respiratory chain electron flux) but may be stimulated by the Complex III inhibitor antimycin A, but not by myxothiazol. Addition of Mn2+ to give 10 nmol/mg of mitochondrial protein enhances H2O2 production with all substrate combinations, possibly by repleting mitochondrial superoxide dismutase with this cation. Contrary to previously published work, no increased activity of H2O2 production was found with heart mitochondria from senescent (24 month) rats, relative to young adults (6 month). C1 KAUNAS MED ACAD,INST BIOMED RES,LT-3007 KAUNAS,LITHUANIA. RP Hansford, RG (reprint author), NIA,BALTIMORE,MD 21224, USA. NR 27 TC 306 Z9 313 U1 1 U2 10 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 1997 VL 29 IS 1 BP 89 EP 95 DI 10.1023/A:1022420007908 PG 7 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA WM241 UT WOS:A1997WM24100011 PM 9067806 ER PT J AU Varmus, H AF Varmus, H TI Foreword to National Sleep Disorders Research Plan, National Institutes of Health, March 1996 SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Editorial Material RP Varmus, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD FEB PY 1997 VL 12 IS 1 BP 4 EP 4 DI 10.1177/074873049701200102 PG 1 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA WG645 UT WOS:A1997WG64500002 ER PT J AU Grzesiek, S Bax, A AF Grzesiek, S Bax, A TI A three-dimensional NMR experiment with improved sensitivity for carbonyl-carbonyl J correlation in proteins SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE carbon-carbon J coupling; HOHAHA; TOCSY; relaxation; phi angle; HIV-1 Nef; ubiquitin ID COUPLING-CONSTANTS; COHERENCE TRANSFER; SPECTROSCOPY; H2O AB Recently, a quantitative J correlation technique has been presented that permits measurement of (3)J(C'C') in proteins isotopically enriched with C-13 [HU, J.-S. and Bar, A. (1996) J. Am. Chem. Soc, 118, 8170-8171]. Here, we describe an analogous experiment that is less sensitive to transverse C-13' relaxation, which is the principal limiting factor in all C-13-C-13 long-range correlation experiments on macromolecules. The new scheme utilizes homonuclear Hartmann-Hahn cross polarization (TOCSY) instead of a COSY-type transfer to accomplish magnetization transfer; a description of the relevant relaxation terms is presented. The experiment is demonstrated for ubiquitin and HIV-I Nef The results show excellent agreement between (3)J(C'C') values measured for ubiquitin with the new scheme and those reported previously. The experiment is particularly useful for distinguishing backbone phi angles that are smaller than -120 degrees from those larger than -120 degrees. RP Grzesiek, S (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 16 TC 24 Z9 25 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD FEB PY 1997 VL 9 IS 2 BP 207 EP 211 DI 10.1023/A:1018614505948 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA WP114 UT WOS:A1997WP11400008 PM 9090134 ER PT J AU Evans, LL Hammer, J Bridgman, PC AF Evans, LL Hammer, J Bridgman, PC TI Subcellular localization of myosin V in nerve growth cones and outgrowth from dilute-lethal neurons SO JOURNAL OF CELL SCIENCE LA English DT Article DE myosin V; growth cone; cytoskeleton ID UNCONVENTIONAL MYOSIN; SACCHAROMYCES-CEREVISIAE; ACTIN-FILAMENTS; SQUID AXOPLASM; MOTOR-ACTIVITY; IDENTIFICATION; GENE; TRANSPORT; BRAIN; YEAST AB Myosin V-null mice (dilute-lethal mutants) exhibit apparent neurological defects that worsen from birth until death in the third postnatal week, Although myosin V is enriched in brain, the neuronal function of myosin V is unclear and the underlying cause of the neurological defects in these mice is unknown, To aide in understanding myosin V function, we examined the distribution of myosin V in the rodent superior cervical ganglion (SCG) growth cone, a well characterized neuronal structure in which myosin V is concentrated, Using affinity purified, myosin V-specific antibodies in immunofluorescence and immunoelectron microscopy, we observed that myosin V is concentrated in organelle-rich regions of the growth cone, Myosin V is present on a distinct population of small (50-100 nm) organelles, and on actin filaments and the plasma membrane, Myosin V-associated organelles are present on both microtubules and actin filaments, These results indicate that myosin V may be carried as a passenger on organelles that are transported along microtubules, and that these organelles may also be capable of movement along actin filaments, In addition, we found no abnormalities in outgrowth, morphology, or cytoskeletal organization of SCG growth cones from dilute-lethal mice, These results indicate that myosin V is not necessary for the traction force needed for growth cone locomotion, for organization of the actin cytoskeleton, or for filopodial dynamics. C1 NIH,CELL BIOL LAB,BETHESDA,MD 20892. RP Evans, LL (reprint author), WASHINGTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,ST LOUIS,MO 63110, USA. FU NINDS NIH HHS [NS35162] NR 31 TC 90 Z9 90 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 FEB PY 1997 VL 110 BP 439 EP 449 PN 4 PG 11 WC Cell Biology SC Cell Biology GA WL460 UT WOS:A1997WL46000005 PM 9067596 ER PT J AU Clarke, HJ Bustin, M Oblin, C AF Clarke, HJ Bustin, M Oblin, C TI Chromatin modifications during oogenesis in the mouse: Removal of somatic subtypes of histone H1 from oocyte chromatin occurs post-natally through a post-transcriptional mechanism SO JOURNAL OF CELL SCIENCE LA English DT Article DE histone H1; histone H1(0); mouse; oogenesis; gene expression ID MATERNAL MESSENGER-RNA; GENE-EXPRESSION; DEVELOPMENTAL REGULATION; FUNCTIONAL-ANALYSIS; DROSOPHILA EMBRYOS; LINKER HISTONE; XENOPUS-LAEVIS; CELL-CYCLE; IN-VIVO; PROTEIN AB We examined the distribution of the somatic subtypes of histone H1 and the variant subtype, H1(0), and their encoding mRNAs during oogenesis and early embryogenesis in the mouse, As detected using immunocytochemistry, somatic H1 was present in the nuclei of oocytes of 18-day embryos. Following birth, however, somatic H1 became less abundant in both growing and non-growing oocytes, beginning as early as 4 days of age in the growing oocytes, and was scarcely detectable by 19 days, Together with previous results, this defines a period of time when somatic H1 is depleted in oocytes, namely, from shortly after birth when the oocytes are at prophase I until the 4-cell stage following fertilization, At the stages when somatic H1 was undetectable, oocyte nuclei could be stained using an antibody raised against histone H1(0), which suggests that this may be a major linker histone in these cells, In contrast to the post-natal loss of somatic H1 protein, mRNAs encoding four (H1a, H1b, H1d, H1e) of the five somatic subtypes were present, as detected using RT-PCR in growing oocytes of 9-day pups, and all five subtypes including H1c were present in fully grown oocytes of adults, All five subtypes were also present in embryos, both before and after activation of the embryonic genome, mRNA encoding H1(0) was also detected in oocytes and early embryos, Whole-mount in situ hybridization using cloned H1c and H1e cDNAs revealed that the mRNAs were present in the cytoplasm of oocytes and 1-cell embryos, in contrast to the sea urchin early embryo where they are sequestered in the cell nucleus, We suggest that, as in many somatic cell types, the chromatin of mouse oocytes becomes depleted of somatic H1 and relatively enriched in histone H1(0) postnatally, and that somatic H1 is reassembled onto chromatin in cleavage-stage embryos, The post-natal loss of somatic H1 appears to be regulated post-transcriptionally by a mechanism not involving nuclear localization. C1 MCGILL UNIV,DEPT BIOL,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT MED,MONTREAL,PQ,CANADA. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Clarke, HJ (reprint author), ROYAL VICTORIA HOSP,DEPT OBSTET & GYNECOL,ROOM F3-50,687 PINE AVE W,MONTREAL,PQ H3A 1A1,CANADA. RI Bustin, Michael/G-6155-2015 NR 66 TC 29 Z9 30 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 FEB PY 1997 VL 110 BP 477 EP 487 PN 4 PG 11 WC Cell Biology SC Cell Biology GA WL460 UT WOS:A1997WL46000008 PM 9067599 ER PT J AU Gordeladze, JO Hovik, KE Merendino, JJ Hermouet, S Gutkind, S Accili, D AF Gordeladze, JO Hovik, KE Merendino, JJ Hermouet, S Gutkind, S Accili, D TI Effect of activating and inactivating mutations of G(s)- and G(i2)-alpha protein subunits on growth and differentiation of 3T3-L1 preadipocytes SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE GTP-binding proteins; site-directed mutagenesis; stable transfection; adenylate cyclase; glucose uptake; hormone sensitive lipase; cell growth; cell differentiation ID NUCLEOTIDE-BINDING PROTEINS; CYCLIC-AMP ACCUMULATION; NB2 LYMPHOMA-CELLS; ADENYLATE-CYCLASE; ALPHA-SUBUNIT; PERTUSSIS TOXIN; ADIPOCYTE DIFFERENTIATION; POSSIBLE INVOLVEMENT; SIGNAL-TRANSDUCTION; GS-ALPHA AB Previous investigations have demonstrated that both G(s) - and the G(i)-family of GTP-binding proteins are implicated in differentiation of the 3T3-L1 preadipocyte. In order to further analyze the role of G(s) alpha vs. G(i2)alpha, which are both involved in adenylate cyclase modulation, we transfected undifferentiated 3T3-L1 cells with two sets of G-protein cDNA: the pZEM vector with either wild type, the activating (i.e., GTP-ase inhibiting) R201C-G(s) alpha or the inactivating G226A(H21a)-G(s) alpha point mutations, or the pZIPNeoSV(X) retroviral vector constructs containing the G(i2)alpha wild type or the missense mutations R179E-G(i2)alpha, Q205L-G(i2)alpha, and G204A(H21a)-G(i2)alpha. The activating [R201C]G alpha-mutant did not significantly affect the differentiation process, i.e., increase in the steady-state levels of G-protein subunits, gross appearance, or insulin-elicited deoxy-glucose uptake into 3T3-L1 adipocytes, despite a marked initial increase in hormone-elicited adenylate cyclase activity. The [H21a]G alpha-mutant, on the other hand, enhanced the degree of differentiation slightly as evidenced by an augmented production of lipid vesicles and insulin-stimulated deoxy-gtucose uptake. However, an expected increase in mRNA for hormone-sensitive lipase was not seen. Secondly, it appeared that both activating [R179E]G(i2)alpha or [Q205L]G(i2)alpha mutants reduced cell doubling time in nonconfluent 3T3-L1 cell cultures, while [H21a]G(i2)alpha slowed proliferation rate. Furthermore, it seemed that cell proliferation, as evidenced by thymidine incorporation, ceased at a much earlier stage prior to cell confluency when cultures were transfected with the [R179E]G(i2)alpha or [Q205L]G(i2)alpha mutants. Upon differentiation with insulin, dexamethasone, and iBuMeXan, the following cell characteristics emerged: the [R179E]G(i2)alpha and [Q205L]G(i2)alpha mutants consistently enhanced adenylate cyclase activation and cAMP accumulation stimulated by isoproterenol and corticotropin over controls. Deoxy-glucose uptake was also super-activated by the [R179E]G(i2)alpha and [Q205L]G(i2)alpha mutants. Finally, steady-state levels of hormone sensitive lipase mRNA were dramatically increased by [R179E]G(i2)alpha and [Q205L]G(i2)alpha over differentiated controls. The inactivating [H21a]G(i2)alpha-mutant obliterated all signs of preadipocyte differentiation. It is concluded that G(i2) plays a positive and much more important role than G(s) in 3T3-L1 preadipocyte differentiation. Cyclic AMP appears to play no role in this process. J. Cell. Biochem. 64:242-257. (C) 1997 Wiley-Liss, Inc. C1 NIDDK,MOL PATHOPHYSIOL BRANCH,NIH,BETHESDA,MD. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD. NIDR,CELL DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. RP Gordeladze, JO (reprint author), UNIV OSLO,INST MED BIOCHEM,POB 1112,N-0317 OSLO,NORWAY. RI Gutkind, J. Silvio/A-1053-2009 NR 49 TC 13 Z9 13 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB PY 1997 VL 64 IS 2 BP 242 EP 257 DI 10.1002/(SICI)1097-4644(199702)64:2<242::AID-JCB8>3.0.CO;2-X PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WF028 UT WOS:A1997WF02800008 PM 9027585 ER PT J AU Nawashiro, H Martin, D Hallenbeck, JM AF Nawashiro, H Martin, D Hallenbeck, JM TI Inhibition of tumor necrosis factor and amelioration of brain infarction in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE tumor necrosis factor; soluble receptor; brain infarction; mice ID CEREBRAL-ARTERY OCCLUSION; FACTOR-ALPHA; ISCHEMIA; RATS; INTERLEUKIN-1; NEURONS; INVOLVEMENT; EXPRESSION; VOLUME; DAMAGE AB Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic brain; however, its precise role is not fully understood. We studied the effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or intraperitoneally. TNFbp binds and inhibits TNF-alpha. The volume of cortical ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24 h after MCAO. TNFbp produced a significant reduction in the cortical infarct volume of vehicle-treated animals (p < 0.001). The reduction in the volume of brain damage was 26% in animals that received 3 mg/kg of TNFbp topically. Further analysis of TNF-alpha inhibition following acute brain ischemia is indicated. C1 AMGEN INC,DEPT PHARMACOL,BOULDER,CO. RP Nawashiro, H (reprint author), NINCDS,STROKE BRANCH,NIH,BLDG 36,RM 4A03,36 CONVENT DR MSC4128,BETHESDA,MD 20892, USA. NR 17 TC 143 Z9 147 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 1997 VL 17 IS 2 BP 229 EP 232 PG 4 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA WH707 UT WOS:A1997WH70700013 PM 9040503 ER PT J AU Williams, KS Hankerson, JG Ernst, M Zametkin, A AF Williams, KS Hankerson, JG Ernst, M Zametkin, A TI Use of propofol anesthesia during outpatient radiographic imaging studies in patients with Lesch-Nyhan syndrome SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE anesthesia, ambulatory; Lesch-Nyhan syndrome; propofol AB Lesch-Nyhan syndrome is a rare, x-linked, recessive disorder of purine metabolism resulting in hyperuricemia, spasticity, choreoathetosis, dystonia, self-injurious behavior, and aggression, without significant cognitive impairment. Anesthetic management of inpatients who demonstrate classic manifestations of Lesch-Nyhan syndrome and require surgical interventions have been described. There are no guidelines in the literature addressing the anesthetic management of the outpatient with Lesch-Nyhan syndrome. Specifically, sudden, unexplained death, abnormalities in respiration, apnea, severe bradycardia, and an increased incidence of vomiting and chronic pulmonary aspiration may preclude this patient population from receiving anesthesia for outpatient procedures. General anesthesia with spontaneous ventilation was performed for diagnostic, radiographic imaging in 11 outpatients with Lesch-Nyhan syndrome using intravenous propofol. A bolus dose of 1.5 to 2.0 mg/kg propofol was followed by maintenance doses of 60 to 160 mcg/hg/min. Results during and following sedation indicated end-tidal carbon dioxide ranges between 34 mmHg and 59 mmHg. Respiratory rates were never below 10 breaths/min and no partial/complete airway obstruction or labored breathing was clinically evident. Hemodynamics were within 30% of presedation values. No patient demonstrated nausea, vomiting, or pulmonary aspiration. Baseline neuropsychologic status was achieved following sedation, and patients were discharged from the hospital 35 to 90 minutes after sedation was completed. Potential risks and benefits of using propofol in this patient population are discussed. (C) 1997 Elsevier Science Inc. RP Williams, KS (reprint author), GEORGETOWN UNIV,DEPT ANESTHESIOL,NIH,GEORGETOWN ANESTHESIOL CONTRACT SERV,10 CTR DR,MSC 1512,BETHESDA,MD 20892, USA. NR 17 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 1997 VL 9 IS 1 BP 61 EP 65 DI 10.1016/S0952-8180(96)00177-8 PG 5 WC Anesthesiology SC Anesthesiology GA WJ715 UT WOS:A1997WJ71500012 PM 9051548 ER PT J AU MercadoAsis, LB Yanovski, JA Tracer, HL Chik, CL Cutler, GB AF MercadoAsis, LB Yanovski, JA Tracer, HL Chik, CL Cutler, GB TI Acute effects of bromocriptine, cyproheptadine, and valproic acid on plasma adrenocorticotropin secretion in Nelson's syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; CUSHINGS-DISEASE; SODIUM VALPROATE; ALPHA-MSH; ACTH; ADRENALECTOMY; MANAGEMENT; PROGNOSIS; NALOXONE; HORMONE AB Previous studies have found that bromocriptine, cyproheptadine, and valproic acid can reduce ACTH secretion in Nelson's syndrome, but none of these agents has achieved widespread use due to their failure to normalize ACTH in most patients. The current study was undertaken to determine whether these three agents, which act through different mechanisms, decrease plasma ACTH synergistically when administered together. Six adult female patients (mean age, 41 yr) with Nelson's syndrome were studied. ACTH was measured every 20 min for 8 h, 2 h before and 6 h after each of the following six treatments: placebo, bromocriptine (2.5 mg), cyproheptadine (8 mg), valproic acid (1 g), cyproheptadine plus valproic acid, and the combination of all three drugs. The sequence of treatments was determined randomly, and there was an interval of at least 2 days between each treatment. The hourly ACTH values were averaged, and the percent maximal suppression of plasma ACTH, relative to the baseline values before drug administration, was compared among the six treatments. Basal plasma ACTH levels in the six patients ranged from 40-3324 pmol/L (normal range, 1-8). The percent maximal suppression of ACTH after administration of placebo (6+/-11%), cyproheptadine (17+/-15%), valproic acid (37+/-10%), or the combination of cyproheptadine and valproic acid (19+/-14%) did not achieve statistical significance. Bromocriptine, bn the other hand, caused a significant decrease in plasma ACTH (52+/-8%; P <0.05), as did the combination of bromocriptine, cyproheptadine, and valproic acid (58+/-1245; P <0.05). However, the combined effect of the three drugs did not significantly exceed the effect of bromocriptine alone. We conclude that at the doses studied, bromocriptine had the greatest acute effect in suppressing ACTH secretion in Nelson's syndrome, and that combined administration with valproic acid and cyproheptadine did not further increase this acute ACTH-suppressive effect. C1 NICHHD, DEV ENDOCRINOL BRANCH, SECT DEV ENDOCRINOL, BETHESDA, MD 20892 USA. NIH, WARREN GRANT MAGNUSON CLIN CTR, OFF DIRECTOR, BETHESDA, MD 20892 USA. NR 39 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 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1997 VL 82 IS 2 BP 514 EP 517 DI 10.1210/jc.82.2.514 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WG065 UT WOS:A1997WG06500039 PM 9024246 ER PT J AU Cizza, G Gold, PW Chrousos, GP AF Cizza, G Gold, PW Chrousos, GP TI High-dose transdermal estrogen, corticotropin-releasing hormone, and postnatal depression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID STRESS RP Cizza, G (reprint author), NICHHD, NIH, BLDG 10, ROOM 10N-262, 10 CTR DR, BETHESDA, MD 20892 USA. NR 7 TC 12 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1997 VL 82 IS 2 BP 704 EP 704 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WG065 UT WOS:A1997WG06500077 PM 9024283 ER PT J AU Marchionni, N Ferrucci, L Baldasseroni, S Fumagalli, S Guralnik, JM Bonazinga, M Cecchi, F Masotti, G AF Marchionni, N Ferrucci, L Baldasseroni, S Fumagalli, S Guralnik, JM Bonazinga, M Cecchi, F Masotti, G TI Item re-scaling of an Italian version of the Sickness Impact Profile: Effect of age and profession of the observers SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE SIP; quality of life; psychometric methods; geriatric medicine; multidimensional assessment; disability ID QUALITY-OF-LIFE; HEALTH-STATUS MEASURE; VALIDATION; ILLNESS; FRENCH AB An Italian version of the Sickness Impact Profile (SIP) obtained by professional and nonprofessional translators was checked for cross-cultural equivalence using a back-translation method followed by two scaling studies. The first scaling study involved 30 health professionals who ranked the items within each category for severity of dysfunction. By comparing Italian and US average ranks, 14 highly discordant items were identified. A revised translation was evaluated in a new study involving 120 observers stratified by age (<65 versus greater than or equal to 65 years) and profession (health versus non health professionals) into 4 groups of the same size. The Italian and American item rank orders were almost equivalent, independently of the age and profession of the observers (93% of the ranks showing differences <2), suggesting that this Italian version of SIP is cross-culturally unbiased. However, older age was associated with higher variability in the rank orders, and some caution is required for use in the geriatric population. Copyright (C) 1997 Elsevier Science Inc. C1 INRCA FLORENCE,DEPT GERIATR MED,I-50139 FLORENCE,ITALY. NIA,BETHESDA,MD 20892. RP Marchionni, N (reprint author), UNIV FLORENCE,DEPT GERONTOL & GERIATR MED,VIA OBLATE 4,I-50141 FLORENCE,ITALY. NR 24 TC 9 Z9 9 U1 0 U2 0 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 FEB PY 1997 VL 50 IS 2 BP 195 EP 201 DI 10.1016/S0895-4356(96)00318-6 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA WJ832 UT WOS:A1997WJ83200010 PM 9120513 ER PT J AU Rothe, H Jenkins, NA Copeland, NG Kolb, H AF Rothe, H Jenkins, NA Copeland, NG Kolb, H TI Active stage of autoimmune diabetes is associated with the expression of a novel cytokine, IGIF, which is located near Idd2 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE macrophages; NOD mouse; genomic mapping; IFN-gamma; Th1/Th2-balance ID INTERFERON-GAMMA; NOD MICE; MOUSE; CELLS AB Recently, interferon-gamma-inducing-factor (IGIF) has been described as a novel monokine that is a more potent interferon-gamma (IFN-gamma) inducer than IL-12. By cloning IGIF from affected tissue and studying IGIF gene expression, we describe for the first time a close association of this cytokine with an autoimmune disease. The non-obese diabetic (NOD) mouse spontaneously develops autoimmune insulitis and diabetes which can be accelerated and synchronized by a single injection of cyclo-phosphamide. IGIF mRNA was demonstrated by reverse transcriptase PCR in NOD mouse pancreas during early stages of insulitis. Levels of IGIF mRNA increased rapidly after cyclophosphamide treatment and preceded a rise in IFN-gamma mRNA, and subsequently diabetes. Interestingly, these kinetics mimick that of IL-12p40 mRNA, resulting in a close correlation of individual mRNA levels. Cloning of the IGIF cDNA from pancreas RNA followed by sequencing revealed identity with the IGIF sequence cloned from Kupffer cells and in vivo preactivated macrophages. When extending our study to macrophages of the spleen we observed that NOD mouse macrophages responded to cyclophosphamide with IGIF gene expression while macrophages from Balb/c mice treated in parallel did not. The IGIF gene position is located within the Idd2 interval on mouse chromosome 9 and therefore it is a candidate for the Idd2 susceptible gene. We conclude that IGIF expression is abnormally regulated in autoimmune NOD mice and closely associated with diabetes development. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Rothe, H (reprint author), UNIV DUSSELDORF,DIABET RES INST,HENNEKAMP 65,D-40225 DUSSELDORF,GERMANY. NR 22 TC 141 Z9 154 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1997 VL 99 IS 3 BP 469 EP 474 DI 10.1172/JCI119181 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WH021 UT WOS:A1997WH02100016 PM 9022080 ER PT J AU Funakoshi, S Taub, DD Anver, MR Raziuddin, A Asai, O Reddy, V Rager, H Fanslow, WC Longo, DL Murphy, WJ AF Funakoshi, S Taub, DD Anver, MR Raziuddin, A Asai, O Reddy, V Rager, H Fanslow, WC Longo, DL Murphy, WJ TI Immunologic and hematopoietic effects of CD40 stimulation after syngeneic bone marrow transplantation in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE bone marrow transplantation; CD40; immune; hematopoietic; engraftment ID VIVO CD40-GP39 INTERACTIONS; DEPENDENT HUMORAL IMMUNITY; B-CELL PROLIFERATION; ANTIBODY-PRODUCTION; FACTOR RECEPTOR; T-CELLS; LIGAND; CYTOKINES; ACTIVATION; GROWTH AB CD40 is a molecule present on multiple cell types including B lymphocyte lineage cells. CD40 has been shown to play an important role in B cell differentiation and activation in vitro, although little is known concerning the effects of CD40 stimulation in vivo. We therefore examined the effects of CD40 stimulation in mice using a syngeneic bone marrow transplantation (BMT) model in an effort to augment B cell recovery after high dose therapy with hematopoietic reconstitution. After the BMT, mice were treated with or without 2-6 mu g of a soluble recombinant murine CD40 ligand (srmCD40L) given intraperitoneally twice a week. A significant increase in B cell progenitors (B220(+)/ surface IgM(-)) was observed in the bone marrow of mice receiving the srmCD40L. The treated recipients also demonstrated improved B-cell function with increases in total serum immunoglobulin and increased splenic mitogen responsiveness to LPS being noted. Additionally, srmCD40L treatment promoted secondary lymphoid organ repopulation, accelerating germinal center formation in the lymph nodes. Total B cell numbers in the periphery were not significantly affected even with continuous srmCD40L administration. Lymphocytes obtained from mice treated with the ligand also had increases in T cell mitogen and anti-CDS mAb responsiveness and acquired the capability to produce IL-4. Surprisingly, treatment with srmCD40L also produced hematopoietic effects in mice, resulting in an increase of BM and splenic hematopoietic progenitor cells in the mice after BMT. Treatment with srmCD40L significantly increased granulocyte and platelet recovery in the peripheral blood. Incubation of BMC with srmCD40L in vitro also resulted in increased progenitor proliferation, demonstrating that the hematopoietic effects of the ligand may be direct. Thus, stimulation of CD40 by its ligand may be beneficial in accelerating both immune and hematopoietic recovery in the setting of bone marrow transplantation. C1 NCI,IRSP,SAIC FREDERICK,FCRDC,CLIN SCI PROGRAM,FREDERICK,MD 21702. NCI,LAB ANIM SCI PROGRAMS,SCI APPLICAT INT CORP,FCRDC,FREDERICK,MD 21702. IMMUNEX CORP,SEATTLE,WA 98101. NCI,LAB LEUKOCYTE BIOL,BIOL RESPONSE MODIFIERS PROGRAM,DIV CANC TREATEMENT,FREDERICK,MD 21702. NR 31 TC 19 Z9 23 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1997 VL 99 IS 3 BP 484 EP 491 DI 10.1172/JCI119183 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WH021 UT WOS:A1997WH02100018 PM 9022082 ER PT J AU Sorensen, JM Vena, DA Fallavollita, A Chun, HG Cheson, BD AF Sorensen, JM Vena, DA Fallavollita, A Chun, HG Cheson, BD TI Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: Five-year follow-up report SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-I; RIBONUCLEOTIDE REDUCTASE; DNA-POLYMERASES; 9-BETA-D-ARABINOFURANOSYL-2-FLUOROADENINE; ANALOGS; CELLS; COMBINATION; METABOLISM; TOXICITY; EFFICACY AB Purpose: To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. Patients and Methods: This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. Results: Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response, The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 74% patients and correlated with age. Conclusion: This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% pal high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment, Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease. C1 NCI,CANC THERAPY EVALUAT PROGRAM,DIV CANC TREATMENT DIAGNOSIS & CTR,NIH,BETHESDA,MD 20892. EMMES CORP,POTOMAC,MD. NR 39 TC 80 Z9 80 U1 0 U2 1 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 FEB PY 1997 VL 15 IS 2 BP 458 EP 465 PG 8 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800008 PM 9053466 ER PT J AU Zeltzer, LK Chen, E Weiss, R Guo, MD Robison, LL Meadows, AT Mills, JL Nicholson, HS Byrne, J AF Zeltzer, LK Chen, E Weiss, R Guo, MD Robison, LL Meadows, AT Mills, JL Nicholson, HS Byrne, J TI Comparison of psychologic outcome in adult survivors of childhood acute lymphoblastic leukemia versus sibling controls: A cooperative Children's Cancer Group and National Institutes of Health study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; ADOLESCENT CANCER; ADJUSTMENT; ADAPTATION; LIFE AB Purpose: To determine psychologic outcome, with the focus on emotional or mood state, of young adult survivors of childhood acute lymphoblastic leukemia (ALL) compared with sibling controls and to identify vulnerable subgroups at highest risk for negative mood. Patients and Methods: Adult survivors (n = 580), aged greater than or equal to 18 years, who were created before age 20 years on Children's Cancer Group (CCG) protocols for ALL and 396 sibling controls were administered a structured telephone interview and the Profile of Moods State (POMS), a standardized measure of affective state. Results: Survivors had higher total mood scores (which indicates greater negative mood) than sibling controls (P < .01) and reported more tension (P < .01), depression (P < .01), anger (P < .01), and confusion (P < .01), but not more fatigue or less vigor, Female, minority, and unemployed survivors reported the highest total time (P < .01) compared with controls. Conclusion: This large, sibling-controlled, multisite study of young adult survivors of childhood ALL treated on CCG protocols after 1970 found significant increased negative mood in survivors, not accounted for by reported energy level differences, which suggests that these emotional effects are not likely the result of current illness. Survivors are less likely to be fully employed. Female, minority, and unemployed survivors are at greatest risk for emotional sequelae, a finding that indicates the need for targeted, preventive intervention. (C) 1997 by American Society of Clinical Oncology. C1 UNIV CALIF LOS ANGELES,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT BIOSTAT,LOS ANGELES,CA 90024. UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN 55455. CHILDRENS HOSP PHILADELPHIA,DIV ONCOL,PHILADELPHIA,PA 19104. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. NR 31 TC 97 Z9 97 U1 2 U2 5 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 FEB PY 1997 VL 15 IS 2 BP 547 EP 556 PG 10 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800018 PM 9053476 ER PT J AU Georgiadis, MS Schuler, BS Brown, JE Kieffer, LV Steinberg, SM Wilson, WH Takimoto, CH Kelley, MJ Johnson, BE AF Georgiadis, MS Schuler, BS Brown, JE Kieffer, LV Steinberg, SM Wilson, WH Takimoto, CH Kelley, MJ Johnson, BE TI Paclitaxel by 96-hour continuous infusion in combination with cisplatin: A phase I trial in patients with advanced lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 1995 CL LOS ANGELES, CA SP Amer Soc Clin Oncol ID COOPERATIVE-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; RANDOMIZED TRIAL; OVARIAN-CANCER; BREAST-CANCER; DRUG-THERAPY; CHEMOTHERAPY; TAXOL; ETOPOSIDE; VINDESINE AB Purpose: To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 96-hour continuous infusion in combination with cisplatin, to determine if the addition of granulocyte colony-stimulating factor (G-CSF) permits significant paclitaxel dose escalation, and to assess the toxicity and preliminary activity of this combination in patients with advanced lung cancer. Patients and Methods: Fifty patients with untreated lung cancer were enrolled: 42 had advanced non-small-cell lung cancer (NSCLC) and eight had extensive-stage small-cell lung cancer (SCLC). patients received paclitaxel doses of 100 to 180 mg/m(2)/96 hours and cisplatin doses of 60 to 80 mg/m(2) as a single 30-minute bolus injection at the end of the paclitaxel infusion. Results: Two of six patients experienced dose-limiting neutropenia at a dose of paclitaxel 140 mg/m(2)/96 hours and cisplatin 80 mg/m(2). With G-CSF support, one of three patients experienced both dose-limiting mucositis and fatal neutropenic sepsis at a dose of paclitaxel 180 mg/m(2)/96 hours and cisplatin 80 mg/m(2). Significant peripheral neuropathy developed in five patients and occurred after six or more cycles of therapy. Thirty-three of 42 patients with NSCLC had measurable disease; the objective response rate was 55%, with two complete responses and 16 partial responses. For all 42 patients with NSCLC, the median time to progression and median survival duration were 5 months and 10 months, respectively. The actuarial 1-year survival rate was 41%. Of eight SCLC patients, four responded to therapy, and the median survival duration for all SCLC patients was 11 months. Conclusion: The MTD without G-CSF is paclitaxel 120 mg/m(2)/96 hours and cisplatin 80 mg/m(2), and the MTD with G-CSF is paclitaxel 160 mg/m(2)/96 hours and cisplatin 80 mg/m(2). Infusional paclitaxel with cisplatin is well tolerated and active in patients with advanced NSCLC. (C) 1997 by Society of Clinical Oncology. C1 NCI, USN, MED ONCOL BRANCH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT MED, DIV PULM MED, BETHESDA, MD 20889 USA. NCI, MED BRANCH, BETHESDA, MD 20892 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, DIV CLIN SCI, BETHESDA, MD 20892 USA. RP Georgiadis, MS (reprint author), NATL NAVAL MED CTR, DEPT MED, DIV ONCOL, BETHESDA, MD 20889 USA. OI Kelley, Michael/0000-0001-9523-6080 NR 32 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1997 VL 15 IS 2 BP 735 EP 743 PG 9 WC Oncology SC Oncology GA WG098 UT WOS:A1997WG09800041 PM 9053499 ER PT J AU Korrapati, MR Sorkin, JD Andres, R Muller, DC Loi, CM Vesell, ES Vestal, RE AF Korrapati, MR Sorkin, JD Andres, R Muller, DC Loi, CM Vesell, ES Vestal, RE TI Acetylator phenotype in relation to age and gender in the Baltimore longitudinal study of aging SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID ARYLAMINE N-ACETYLTRANSFERASE; BLADDER-CANCER; DAPSONE; POLYMORPHISM; POPULATION; OXIDATION; CAFFEINE; SEX; SULFADIMIDINE; INDIVIDUALS AB This study investigated in healthy Caucasians the possible occurrence of age and gender-associated differences in NAT2 acetylator phenotype. Acetylator phenotype was determined after a single oral dose of 100 mg dapsone during testing of oral glucose tolerance in 510 Caucasian volunteers aged from 19 to 93 years, 339 men and 171 women, from the Baltimore Longitudinal Study of Aging. Participants were classified as slow or rapid acetylators according to the ratio of monoacetyldapsone to dapsone concentration in plasma. The ratio dividing the two groups, 0.30, was chosen after inspection of a probit plot and histogram of the monoacetyldapsone/dapsone ratios. Fifty-one percent of the participants were slow acetylators and 49% were rapid acetylators. Because there was no significant difference between the sexes in the monoacetyldapsone/dapsone ratios, all 510 participants were pooled into a single group for further analysis. In the combined analysis, there was a small decline in the prevalence of the slow acetylator phenotype with age, but this age effect accounted for less than 1% of the total variance in the monoacetyldapsone/dapsone ratio (r(2) = 0.009). Also, it was shown in a group of 20 participants that administration of glucose with dapsone does not influence the determination of acetylator phenotype. In a large healthy Caucasian-American population, there was no biologically important effect of age or sex on the distribution of NAT2 acetylator phenotype. C1 VET ADM MED CTR,RES SERV 151,CLIN PHARMACOL & GERONTOL RES UNIT,BOISE,ID 83702. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. IDAHO STATE UNIV,COLL PHARM,POCATELLO,ID 83209. PENN STATE UNIV,COLL MED,HERSHEY,PA. MT STATES MED RES INST,BOISE,ID. NR 41 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD FEB PY 1997 VL 37 IS 2 BP 83 EP 91 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WK569 UT WOS:A1997WK56900001 PM 9055133 ER PT J AU Lush, RM Meadows, B Fojo, AT Kalafsky, G Smith, HT Bates, S Figg, WD AF Lush, RM Meadows, B Fojo, AT Kalafsky, G Smith, HT Bates, S Figg, WD TI Initial pharmacokinetics and bioavailability of PSC 833, a P-glycoprotein antagonist SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; HUMAN-LEUKEMIC LYMPHOBLASTS; SDZ PSC-833; CYCLOSPORINE-A; RENAL-TRANSPLANTATION; CELL-LINES; IN-VITRO; DRUGS; PERMEABILITY; MECHANISM AB Resistant cancer cells have been shown to overexpress a 170-kd membrane glycoprotein called P-glycoprotein. P-glycoprotein, a product of the multidrug resistance 1 gene, functions as an energy-dependent efflux pump that decreases intracellular drug concentrations. A variety of nonchemotherapeutic agents have been shown to inhibit P-glycoprotein-dependent drug efflux including cyclosporin. PSC 833 is a nonimmunosuppressive derivative of cyclosporin D with the ability to reverse multidrug resistance because of P-glycoprotein overexpression in vitro. As part of early clinical development of PSC 833, the authors investigated the bioavailability of an oral formulation of PCS 833. PSC 833 (3 mg/kg) was administered as a 2-hour intravenous infusion on day 1 of the treatment cycle. Serial blood samples for the determination of PSC 833 whole blood concentrations were obtained after both the intravenous and oral doses. On day 5 of the study, patients received a single oral dose (9 mg/kg) of PSC 833. A total of 14 patients were treated. The intravenous data were best described by a two-compartment open model. The oral data also were described using a two-compartment model, with oral absorption incorporating a lag time to account for possible delays in absorption. There was large intra- and interpatient variability in the pharmacokinetics of PSC 833 in these patients. The absolute bioavailability of PSC 833 was 34% but ranged from 3% to 58% of the administered dose. The clearance (Cl) of PSC 833, in general, was consistent between the two dose forms administered. The pharmacokinetic behavior of PSC 833 appears to be similar to that of cyclosporine. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,DIV CLIN SCI,BETHESDA,MD 20892. SANDOZ PHARMACEUT CORP,E HANOVER,NJ. RI Figg Sr, William/M-2411-2016 NR 29 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD FEB PY 1997 VL 37 IS 2 BP 123 EP 128 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WK569 UT WOS:A1997WK56900006 PM 9055138 ER PT J AU FeldmanNaim, S Turner, EH Leibenluft, E AF FeldmanNaim, S Turner, EH Leibenluft, E TI Diurnal variation in the direction of mood switches in patients with rapid-cycling bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SLEEP-DEPRIVATION; DEPRESSION; CYCLES; PREDICTION; BRIGHT; LIGHT; MANIA AB Background: We assessed diurnal variation in the direction of mood switches in a sample of outpatients with rapid-cycling bipolar disorder who were on stable medication regimens. We predicted that patients would be more likely to switch from depression into mania or hypomania during the daytime hours and from mania/hypomania into depression overnight. Method: Fifteen patients with rapid-cycling bipolar disorder completed self-rated mood scales twice a day: once shortly after awakening and once at bedtime. Using 3 months of data for each patient, we performed categorical analyses (McNemar chi-square) to study the direction of mood switches between each day's morning and evening rating and between each evening rating and the subsequent morning rating. Results: As predicted, switches that occurred between the morning and evening ratings were more likely to be from depression into mania/hypomania or euthymia (64.3%) than in the opposite direction (35.6%; p < .0001). Similarly, switches that occurred between the evening rating and the next morning's ratings were more likely to be from mania/hypomania or euthymia into depression (64.8%) than in the opposite direction (35.2%; p < .0001). Conclusion: Extended wakefulness, exposure to light, increased activity, and/or endogenous rhythms could contribute to the elevation of mood during the course of the day. Sleep, darkness, reduced activity, and/or endogenous rhythms could contribute to the tendency to switch into depression overnight. Clinicians should attend to the time of day that clinical assessments are performed in patients with rapid-cycling bipolar disorder. Potential therapeutic implications include the use of light or activity during depression and use of induced sleep or exposure to darkness during mania/hypomania. RP FeldmanNaim, S (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,10-4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 27 TC 32 Z9 32 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 1997 VL 58 IS 2 BP 79 EP 84 DI 10.4088/JCP.v58n0205 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA WM261 UT WOS:A1997WM26100005 PM 9062377 ER PT J AU Slavkin, H AF Slavkin, H TI Craniofacial-oral-dental research in the 21st century SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material RP Slavkin, H (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1997 VL 76 IS 2 BP 628 EP 630 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WL793 UT WOS:A1997WL79300001 PM 9062554 ER PT J AU Baum, BJ Fox, PC Tabak, LA AF Baum, BJ Fox, PC Tabak, LA TI Columbia, salivary research, plus Irwin Mandel equal a special combination for dentistry SO JOURNAL OF DENTAL RESEARCH LA English DT Item About an Individual C1 UNIV ROCHESTER,DEPT DENT RES,ROCHESTER,NY 14642. RP Baum, BJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,10 CTR DR,MSC 1190,BLDG 10,ROOM 1N113,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1997 VL 76 IS 2 BP 631 EP 633 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WL793 UT WOS:A1997WL79300002 PM 9062555 ER PT J AU Alison, M Golding, M ElNasir, L Nagy, P Thorgeirsson, S Sarraf, C AF Alison, M Golding, M ElNasir, L Nagy, P Thorgeirsson, S Sarraf, C TI Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells SO JOURNAL OF HEPATOLOGY LA English DT Article DE acetylaminofluorene; albumin; cytokeratins; alpha-foetoprotein; liver regeneration; oval cells; vimentin ID ALPHA-FETOPROTEIN EXPRESSION; CHOLINE-DEFICIENT DIET; CAUDATE LIVER LOBES; FURAN-TREATED RATS; EPITHELIAL-CELLS; FEEDING N-2-FLUORENYLACETAMIDE; D-GALACTOSAMINE; DEVOID DIET; EARLY STAGE; ADULT-RAT AB Background/Aims: Biliary epithelial cells (ductular oval cells) migrate into the periportal and midzonal parenchyma when hepatocyte regeneration after injury is significantly impeded, The potential of oval cells to differentiate into hepatocytes has been questioned. We have sought to resolve this issue using the modified Solt-Farber procedure in which 2-acetylaminofluorene is used to block hepatocyte regeneration in partially hepatectomized rats. Methods: Rats received 2-acetylaminofluorene by oral gavage for 6 days before and up to 7 days after a two-thirds hepatectomy. The cellular reaction was visualized by the immunohistochemical localization of intermediate filaments cytokeratins 8 and 19 and vimentin, cytochrome P450 enzymatic proteins and alpha-foetoprotein. Expression of albumin and alpha-foetoprotein mRNA transcripts were observed in situ using antisense riboprobes. Results: During the first 9 days after partial hepatectomy long strings of ductular cells spread outwards from the portal areas. These cells exhibited strong diffuse cytoplasmic staining with the anticytokeratin 8 and 19 antibodies, like authentic bile ducts, but in addition also expressed vimentin and alpha-foetoprotein (protein and mRNA) - collectively termed the ''oval cell phenotype''. Thereafter, these ducts rapidly vanished to be replaced by basophilic hepatocytes which lacked the oval cell phenotype, but which acquired strong expression of albumin mRNA. At 14 days after partial hepatectomy the oval cell phenotype was restricted to the peripheral margins of the newborn periportal hepatocytes, the distal tips of the oval cell ducts, and these too had disappeared within another 7 days. Conclusions: Ductular oval cells will differentiate into hepatocytes under appropriate experimental conditions. C1 NATL CANC INST,EXPT CARCINOGENESIS LAB,BETHESDA,MD. RP Alison, M (reprint author), ROYAL POSTGRAD MED SCH,DEPT HISTOPATHOL,DU CANE RD,LONDON W12 0NN,ENGLAND. NR 52 TC 86 Z9 92 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD FEB PY 1997 VL 26 IS 2 BP 343 EP 352 DI 10.1016/S0168-8278(97)80051-7 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WH835 UT WOS:A1997WH83500018 PM 9059956 ER PT J AU Martinez, A Miller, MJ Catt, KJ Cuttitta, F AF Martinez, A Miller, MJ Catt, KJ Cuttitta, F TI Adrenomedullin receptor expression in human lung and in pulmonary tumors SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE human lung; lung tumors; adrenomedullin receptor; growth regulation; in situ hybridization ID SMOOTH-MUSCLE CELLS; IMMUNOREACTIVE ADRENOMEDULLIN; HYPOTENSIVE PEPTIDE; CLONING; PLASMA; GENE AB Adrenomedullin (AM) is a multifunctional regulatory peptide that stimulates cyclic AMP production in many target tissues and is highly expressed in the lung. Analysis of the distribution of the recently cloned AM receptor (AM-R) by non-radioactive in situ hybridization revealed abundant expression in the basal cells of the airway epithelium and Type II pneumocytes. The expression of AM-R in the two cell types involved in epithelial regeneration of the lung suggests that AM may be relevant in such functions as organ development, wound repair, and epithelial turnover. AM-Rs are also synthesized in vivo and in vitro by a variety of tumor cells that also express the ligand, suggesting the existence of an autocrine loop that may be involved in tumor growth stimulation. The present findings suggest that the AM/AM-R regulatory system plays a major role in respiratory physiology and lung carcinogenesis and that new functions for AM remain to be identified. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD. RP Martinez, A (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,NIH,9610 MED CTR DR,RM 300,ROCKVILLE,MD 20850, USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 28 TC 36 Z9 37 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 1997 VL 45 IS 2 BP 159 EP 164 PG 6 WC Cell Biology SC Cell Biology GA WM757 UT WOS:A1997WM75700002 PM 9016306 ER PT J AU Wang, HY Zamorano, J Yoerkie, JL Paul, WE Keegan, AD AF Wang, HY Zamorano, J Yoerkie, JL Paul, WE Keegan, AD TI The IL-4-induced tyrosine phosphorylation of the insulin receptor substrate is dependent on JAK1 expression in human fibrosarcoma cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA SIGNAL-TRANSDUCTION; INTERLEUKIN-4 RECEPTOR; INTERFERON-ALPHA/BETA; HEMATOPOIETIC-CELLS; JANUS KINASE; ACTIVATION; PROTEIN; PATHWAYS; IL-4; MITOGENESIS AB It has been shown that IL-4 induces the tyrosine phosphorylation of JAK1 and JAK3 in the majority of hemopoietic cell types, and JAK2 and TYK2 in several other types. However, the significance of this tyrosine phosphorylation in regulating IL-4 signaling has not been shown. To determine whether JAKs play a role in activating a signal transduction pathway different from the classical JAK/STAT pathway, we analyzed the ability of huIL-4 to stimulate the tyrosine phosphorylation of one of its major cellular substrates, the insulin receptor substrate (IRS), Using human fibrosarcoma cell lines with mutations in JAK1, JAK2, and TYK2, we found that expression of functional JAK1, but not TYK2 or JAK2, is essential for IL-4-induced tyrosine phosphorylation of IRS, We also provide evidence that the IRS pathway is independent of STAT-6, showing that JAK1 is essential for activating a STAT-independent pathway. C1 AMER RED CROSS,JEROME H HOLLAND LABS,DEPT IMMUNOL,ROCKVILLE,MD 20855. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-38985] NR 35 TC 18 Z9 18 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 FEB 1 PY 1997 VL 158 IS 3 BP 1037 EP 1040 PG 4 WC Immunology SC Immunology GA WE020 UT WOS:A1997WE02000002 PM 9013940 ER PT J AU Epstein, SL Lo, CY Misplon, JA Lawson, CM Hendrickson, BA Max, EE Subbarao, K AF Epstein, SL Lo, CY Misplon, JA Lawson, CM Hendrickson, BA Max, EE Subbarao, K TI Mechanisms of heterosubtypic immunity to lethal influenza A virus infection in fully immunocompetent, T cell-depleted, beta(2)-microglobulin-deficient, and J chain-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID A VIRUS; IMMUNOGLOBULIN-A; VACCINIA VIRUS; MONOCLONAL-ANTIBODIES; INTRACELLULAR NEUTRALIZATION; HETEROTYPIC IMMUNITY; MURINE INFLUENZA; EPITHELIAL-CELLS; INTERFERON-GAMMA; NUCLEOPROTEIN AB Immunity that is cross-protective between different influenza A virus subtypes (termed heterosubtypic immunity) can be demonstrated readily in some animals but only rarely in humans. Induction of heterosubtypic immunity in humans by vaccines would provide public health benefit, perhaps offering some protection against pandemics or other new influenza A strains. Therefore, we studied mechanisms mediating heterosubtypic immunity in mice. Immunization with either A/H1N1 or A/H3N2 virus protected mice against mortality following heterosubtypic challenge while providing modest reductions in lung virus titers. No cross-protection was seen with distantly related type B influenza virus. Depletion of CD4(+) or CD8(+) T cells or both around the time of challenge had no significant effect on survival, indicating that these cells are not required at the effector stage. beta(2)-microglobulin knockout mice could be protected readily against heterosubtypic challenge, confirming that class I-restricted T cells are not required. In beta(2)-microglobulin -/- mice, depletion of CD4(+) T cells partially abrogated heterosubtypic immunity, showing that they play a role in these mice. Passive transfer of Abs to naive recipients protected against subsequent challenge with homologous but not heterosubtypic virus. Because a role for secretory Abs has been suggested, we studied dependence on the I chain, which is required for polymeric Ig receptor-mediated IgA transport. I chain knockout mice were readily protected by heterosubtypic immunity, indicating that polymeric Ig receptor-mediated transport is not required. Better understanding of heterosubtypic immunity should be valuable in analyzing new vaccines, including peptide and DNA vaccines, intended to induce broadly cross-reactive immunity. C1 US FDA, CTR BIOL EVALUAT & RES, DIV CELLULAR & GENE THERAPIES, MOL IMMUNOL LAB, BETHESDA, MD 20892 USA. NIAID, INFECT DIS LAB, NIH, BETHESDA, MD 20892 USA. UNIV CHICAGO, WYLER CHILDRENS HOSP, SECT PEDIAT INFECT DIS, CHICAGO, IL 60637 USA. US FDA, CTR BIOL EVALUAT & RES, DIV HEMATOL PROD, BETHESDA, MD 20892 USA. NR 60 TC 109 Z9 114 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1997 VL 158 IS 3 BP 1222 EP 1230 PG 9 WC Immunology SC Immunology GA WE020 UT WOS:A1997WE02000025 PM 9013963 ER PT J AU Ortaldo, JR Mason, AT Mason, LH WinklerPickett, RT Gosselin, P Anderson, SK AF Ortaldo, JR Mason, AT Mason, LH WinklerPickett, RT Gosselin, P Anderson, SK TI Selective inhibition of human and mouse natural killer tumor recognition using retroviral antisense in primary natural killer cells - Involvement with MHC class I killer cell inhibitory receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; GENE-TRANSFER; HLA-C; CYTOTOXICITY; EXPRESSION; LINES; SAFE AB The natural killer tumor recognition (NK-TR) protein has been shown to be a necessary component for the killing of NK-sensitive and virus-infected targets by the rat RNK-16 cell line. Class I-recognizing killer cell inhibitory receptors (KIR) have been found in the human (p58; NKAT family) and mouse (Ly-49 family). The principal functional characteristic of these receptors is their ability to block NK cell lysis by recognition of selected class I molecules on target cells. In the present study, we examined whether abrogation of NK-TR expression by retroviral infection of primary human or mouse NK cells with virus-producing antisense NK-TR also would demonstrate loss of non-MHC-restricted killing and whether the NK-TR was associated with KIR function in humans or with Ly-49 in the mouse. Using short term culture of fresh human or mouse NK cells, antisense NK-TR-treated NK cells demonstrated strong selective reduction of NK cytotoxicity, NK-TR was necessary for lytic activity even when KIR function was blocked by Ab in experiments involving NK3.3 lysis of HLA.cw3-expressing targets or killing of D-d targets by Ly-49A(+) or Ly-49G2(+) mouse NK cells. These studies extend our previous studies in rat NK cell lines to demonstrate that primary mouse and human NK cells require NK-TR for non-MHC-restrided lysis of tumor and virus-infected targets. In addition, the reversal of KIR or Ly-49 inhibition of NK cell lysis requires NK-TR expression for cellular killing in both human and mouse. C1 NCI,LAB EXPT IMMUOL,DIV BASIC SCI,FREDERICK,MD 21702. SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. RP Ortaldo, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,560 CHANDLER ST,ROOM 31-93,FREDERICK,MD 21702, USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 NR 21 TC 4 Z9 4 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 FEB 1 PY 1997 VL 158 IS 3 BP 1262 EP 1267 PG 6 WC Immunology SC Immunology GA WE020 UT WOS:A1997WE02000030 PM 9013968 ER PT J AU Rumsaeng, V Vliagoftis, H Oh, CK Metcalfe, DD AF Rumsaeng, V Vliagoftis, H Oh, CK Metcalfe, DD TI Lymphotactin gene expression in mast cells following Fc epsilon receptor I aggregation - Modulation by TGF-beta, IL-4, dexamethasone, and cyclosporin A SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN ANTIGENIC DETERMINANTS; CYTOKINE MESSENGER-RNA; CHRONIC SEVERE ASTHMA; CD4+ T-CELLS; BRONCHOALVEOLAR LAVAGE; ATOPIC ASTHMA; TNF-ALPHA; MOLECULAR-CLONING; ALLERGEN; CHEMOKINE AB Recruitment of lymphocytes is a prominent feature of allergic inflammation. However, the mechanisms by which lymphocytes are attracted to such sites are not understood. Recently, cDNAs encoding a lymphocyte-specific chemokine, lymphotactin (Ltn), were isolated from mouse pro-T cell and human CD8(+) T cell libraries, leading us to hypothesize that mast cells might also produce Ltn. Using the reverse transcriptase-PCR and Northern blot analysis, we found that the Ltn gene is inducible in C1.MC/C57.1 and murine bone marrow-cultured mast cells (BMCMC) by Fc epsilon RI aggregation. Activation of a human mast cell (HMC-1) or basophil cell line (KU812) similarly led to transcription of Ltn. Fc epsilon RI aggregation-dependent Ltn mRNA expression was detected by 1 to 2 h, maximal at 6 h, independent of de novo protein synthesis, and was inhibited by cyclosporin A and dexamethasone. Compared with macrophage inflammatory protein alpha (MIP-1 alpha), Fc epsilon RI-dependent Ltn and MIP-1 alpha mRNA levels were up-regulated by IL-4, but not IFN-gamma, although higher levels of IL-4 (100 and 1000 U/ml) inhibited Ltn expression only; and TCF-beta preferentially enhanced Fc epsilon RI-dependent Ltn mRNA levels, suggesting that Ltn and MIP-1 alpha have shared and unique regulatory mechanisms. A rabbit polyclonal Ab against a synthetic peptide was developed for use in immunoblot analysis and detected a 15-kDa Ltn protein within mast cell pellets and in the supernatants of mast cells following Fc epsilon RI aggregation. Ltn is thus expressed in mast cells and may contribute to the recruitment of lymphocytes to areas of allergic inflammation. C1 HARBOR UCLA MED CTR,DEPT PEDIAT,TORRANCE,CA 90509. RP Rumsaeng, V (reprint author), NIAID,NATL INST HLTH,LAD,BLDG 10,ROOM 11C206,10 CTR DR,BETHESDA,MD 20892, USA. RI Vliagoftis, Harissios/C-6480-2013 NR 59 TC 53 Z9 53 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 FEB 1 PY 1997 VL 158 IS 3 BP 1353 EP 1360 PG 8 WC Immunology SC Immunology GA WE020 UT WOS:A1997WE02000041 PM 9013979 ER PT J AU Lambert, JS Mofenson, LM Fletcher, CV Moye, J Stiehm, ER Meyer, WA Nemo, GJ Mathieson, BJ Hirsch, G Sapan, CV Cummins, LM Jimenez, E ONeill, E Kovacs, A Stek, A AF Lambert, JS Mofenson, LM Fletcher, CV Moye, J Stiehm, ER Meyer, WA Nemo, GJ Mathieson, BJ Hirsch, G Sapan, CV Cummins, LM Jimenez, E ONeill, E Kovacs, A Stek, A TI Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 35th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 17-22, 1995 CL SAN FRANCISCO, CA SP Amer Soc Microbiol ID VERTICAL TRANSMISSION; MATERNAL ANTIBODIES; INFANT TRANSMISSION; CHILD TRANSMISSION; TYPE-1; PLASMA; GP120; MOTHERS; IMMUNOTHERAPY; REACTIVITY AB The pharmacokinetics and safety of hyperimmune anti-human immunodeficiency virus (HIV) intravenous immunoglobulin (HMG) were evaluated in the first 28 maternal-infant pairs enrolled in a randomized, intravenous immunoglobulin (IVIG)-controlled trial of HIVIG maternal-infant HIV transmission prophylaxis. Using 200 mg/kg, mean half-life and volume of distribution (V-d) in women were 15 days and 72 mL/kg, respectively, after one and 32 days and 154 mL/kg after three monthly infusions, with stable 4 mL/kg/day clearance. Transplacental passage occurred. Newborn single-dose half-life, V-d, and clearance were 30 days, 143 mL/kg, and 4 mL/kg/day, respectively. HIVIG rapidly cleared maternal serum immune complex-dissociated p24 antigen, and plasma HIV-1 RNA levels were stable. Mild to moderate adverse clinical effects occurred in 2 of 103 maternal and 2 of 25 infant infusions. No adverse hematologic, blood chemistry, or immunologic effects were seen, HIVIG is well-tolerated in HIV-infected pregnant women and their newborns, clears antigenemia, crosses the placenta, and exhibits pharmacokinetics similar to those of other immunoglobulin preparations. C1 CORNING CLIN LABS,BALTIMORE,MD. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,DIV BLOOD DIS & RESOURCES,NHLBI,BETHESDA,MD 20892. NIAID,VACCINE RES & DEV BRANCH,DIV AIDS,NATL INST HLTH,BETHESDA,MD 20892. WESTAT CORP,ROCKVILLE,MD. BAYLOR PEDIAT PHARMACOL LAB,MINNEAPOLIS,MN. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV CALIF LOS ANGELES,CTR MED,LOS ANGELES,CA 90024. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. NABI,BOCA RATON,FL. SAN JUAN CITY HOSP,SAN JUAN,PR. RP Lambert, JS (reprint author), UNIV MARYLAND,CTR MED BIOTECHNOL,INST HUMAN VIROL,725 W LOMBARD ST,5TH FLOOR,BALTIMORE,MD 21201, USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NHLBI NIH HHS [HL-57128]; NIAID NIH HHS [AI-27565]; NICHD NIH HHS [HD-33162] NR 34 TC 56 Z9 56 U1 0 U2 1 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 FEB PY 1997 VL 175 IS 2 BP 283 EP 291 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WF063 UT WOS:A1997WF06300007 PM 9203648 ER PT J AU Feng, NG Vo, PT Chung, D Vo, TVP Hoshino, Y Greenberg, HB AF Feng, NG Vo, PT Chung, D Vo, TVP Hoshino, Y Greenberg, HB TI Heterotypic protection following oral immunization with live heterologous rotaviruses in a mouse model SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RHESUS-ROTAVIRUS; VACCINE CANDIDATES; MURINE ROTAVIRUS; MICE; NEUTRALIZATION; ANTIGENICITY; INFECTION; INFANTS; VP7; IMMUNOGENICITY AB A Jennerian approach using live animal viruses to immunize humans is the current lead strategy for developing rotavirus vaccines. This strategy has been modified by incorporating human rotavirus VP7 genes into vaccine strains to induce serotype-specific neutralizing antibodies to human strains. However, the role of homotypic versus heterotypic immunity in protection is unclear, To investigate the importance of serotype-specific immunity in a mouse model, mice were immunized with rhesus rotavirus (RRV: G3, P5[3]), RRV-based modified Jennerian vaccine strains DxRRV (G1, P5[3]), DS1xRRV (G2, P5[3]), or ST3xRRV (G4, P5[3]), or bovine rotavirus NCDV (G6, PG[1]) and challenged with murine rotavirus EC(W) (G3, P[16]), Mice immunized with modified Jennerian vaccines exhibited complete to near-complete protection from challenge. NCDV-immunized mice also showed partial protection, The protection was correlated with fecal IgA levels to VP6, not serum IgG responses. Modified Jennerian vaccines induce both heterotypic and homotypic immunity in mice. C1 STANFORD UNIV,SCH MED,LAB SURGE,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. VA PALO ALTO HLTH CARE SYST,PALO ALTO,CA. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP Feng, NG (reprint author), STANFORD UNIV,SCH MED,LAB SURGE,DEPT MED,P304,MAIL CODE 5487,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI-21632]; NIDDK NIH HHS [DK-38707, DK-07056] NR 33 TC 29 Z9 29 U1 1 U2 1 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 FEB PY 1997 VL 175 IS 2 BP 330 EP 341 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WF063 UT WOS:A1997WF06300013 PM 9203654 ER PT J AU Brown, KE Wong, S Buu, M Binh, TV Be, TV Young, NS AF Brown, KE Wong, S Buu, M Binh, TV Be, TV Young, NS TI High prevalence of GB virus C hepatitis G virus in healthy persons in Ho Chi Minh City, Vietnam SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Hematology CY DEC 01-05, 1995 CL SEATTLE, WA SP Amer Soc Hematol ID AGENT AB GB virus C or hepatitis G virus (GBV-C/HGV), a novel Flavivirus, is detected in 1.5% of US blood donors, The prevalence is higher in multiply transfused patients and in persons with liver disease, Because of the increased incidence of hepatitis in Asia, sera from healthy Vietnamese were tested for the presence of GBV-C/HGV RNA by the reverse transcription polymerase chain reaction, Viral RNA was detected in 5.7% of those tested; 6 of 81 volunteer blood donors had positive samples as did 5 of 97 army recruits and 2 of 50 postpartum women, When the 188-bp product from 6 subjects was sequenced, there was 75%-85% homology at the nucleotide level compared with published sequences, indicating a high degree of genotypic variation, even within a putatively well-conserved region of the viral genome, Viremia with this non-cell-associated novel virus appears to be common among normal persons in Vietnam. C1 NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA. BLOOD TRANSFUS & HEMATOL CTR, Ho Chi Minh City, VIETNAM. NR 15 TC 30 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1997 VL 175 IS 2 BP 450 EP 453 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WF063 UT WOS:A1997WF06300030 PM 9203671 ER PT J AU Dille, BJ Surowy, TK Gutierrez, RA Coleman, PF Knigge, MF Carrick, RJ Aach, RD Hollinger, FB Stevens, CE Barbosa, LH Nemo, GJ Mosley, JW Dawson, GJ Mushahwar, IK AF Dille, BJ Surowy, TK Gutierrez, RA Coleman, PF Knigge, MF Carrick, RJ Aach, RD Hollinger, FB Stevens, CE Barbosa, LH Nemo, GJ Mosley, JW Dawson, GJ Mushahwar, IK TI An ELISA for detection of antibodies to the E2 protein of GB virus C SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HEPATITIS; INFECTION AB An ELISA was developed for detection of antibodies to GB virus C (GBV-C) using a recombinant E2 protein expressed in CHO cells, Seroconversion to anti-E2 positivity was noted among several persons infected with GBV-C RNA-positive blood through transfusion, Of 6 blood recipients infected by GBV-C RNA-positive donors, 4 (67%) became anti-E2 positive and cleared their viremia. Thus, anti-E2 seroconversion is associated with viral clearance, The prevalence of antibodies to E2 was relatively low (3.0%-8.1%) in volunteer blood donors but was higher in several other groups, including plasmapheresis donors (34.0%), intravenous drug users (85.2%);and West African subjects (13.3%), all of whom tested negative by GBV-C reverse-transcription polymerase chain reaction (RT-PCR), These data demonstrate that testing for anti-E2 should greatly extend the ability of RT-PCR to define the epidemiology and clinical significance of GBV-C. C1 MT SINAI MED CTR,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NEW YORK BLOOD CTR,NEW YORK,NY 10021. BAYLOR COLL MED,HOUSTON,TX 77030. NHLBI,DIV BLOOD DIS & RESOURCES,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. RP Dille, BJ (reprint author), ABBOTT LABS,VIRAL DISCOVERY GRP,EXPT BIOL RES,ABBOTT DIAGNOST DIV,D-90D NC L3,1401 SHERIDAN RD,N CHICAGO,IL 60064, USA. NR 17 TC 159 Z9 161 U1 0 U2 1 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 FEB PY 1997 VL 175 IS 2 BP 458 EP 461 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WF063 UT WOS:A1997WF06300032 PM 9203673 ER PT J AU Fujimoto, W Nakanishi, G Arata, J Jetten, AM AF Fujimoto, W Nakanishi, G Arata, J Jetten, AM TI Differential expression of human cornifin alpha and beta in squamous differentiating epithelial tissues and several skin lesions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cornifin; SPRR; involucrin; keratinocyte; cornified envelope ID HUMAN EPIDERMAL-KERATINOCYTES; HUMAN INVOLUCRIN GENE; RETINOIC ACID; CELL-ENVELOPE; HUMAN-HAIR; PRECURSOR; LORICRIN; TRANSGLUTAMINASE; PROTEINS AB Cornifins/small proline-rich proteins (SPRRs) belong to a family of proline-rich proteins that function as cornified envelope precursors, We report here an immunohistochemical analysis of human cornifin-alpha and -beta expression in several stratified squamous epithelia. In normal human skin, cornifin-alpha was expressed in the granular layer of the epidermis of palmoplantar skin, in the inner lining cells of the follicular infundibulum, and in the inner root sheath of the hair follicle. It was also expressed in the upper squamous layers of the oral, esophageal, and vaginal epithelia, Cornifin-beta was detected in oral, esophageal, and vaginal epithelia, but not in normal skin, Immunoblot analysis revealed quantitative differ; ences in cornifin-alpha expression in skin from different regions, Studies of specimens from various skin diseases showed that (i) cornifin-alpha was upregulated in inflammatory skin diseases, hyperplastic lesions, and in well-differentiated squamous cell carcinomas (SCCs), (ii) the expression of cornifin-beta was absent in inflammatory skin but was detected in highly differentiated keratinocytes in well-differentiated SCCs of the skin and some other hyperproliferative skin lesions, and in SCCs of the oral mucosa and esophagus. Northern blot analysis revealed that cornifin-alpha mRNA was present in all the squamous epithelial tissues studied, whereas cornifin-beta mRNA was expressed in oral mucosal epithelia and verrucous carcinoma of the skin but neither in normal nor in psoriatic skin, These results indicate that (i) the amount of cornifin alpha/SPRR1 expression in normal human skin depends on the body region, (ii) cornifin-alpha/SPRR1, but not cornifin-beta, contributes to the integrity of the hair follicle, and (iii) the expression of cornifin-beta is induced in some hyperplastic skin diseases only when the keratinocytes undergo extensive squamous differentiation. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,NIH,RES TRIANGLE PK,NC 27709. RP Fujimoto, W (reprint author), OKAYAMA UNIV,SCH MED,DEPT DERMATOL,2-5-1 SHIKATO CHO,OKAYAMA 700,JAPAN. OI Jetten, Anton/0000-0003-0954-4445 NR 27 TC 44 Z9 44 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1997 VL 108 IS 2 BP 200 EP 204 DI 10.1111/1523-1747.ep12334240 PG 5 WC Dermatology SC Dermatology GA WE836 UT WOS:A1997WE83600013 PM 9008234 ER PT J AU Pericle, F EplingBurnette, PK Podack, ER Wei, S Djeu, JY AF Pericle, F EplingBurnette, PK Podack, ER Wei, S Djeu, JY TI CD40-CD40L interactions provide ''third-party'' costimulation for T cell response against B7-1-transfected human breast tumor cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE gp39; CD80; cytotoxic T lymphocytes; transfection ID HUMAN B-CELLS; LYMPHOCYTES-T; ANTITUMOR IMMUNITY; HUMAN-MELANOMA; CD28 RECEPTOR; ANTIGEN; LIGAND; CD40; ACTIVATION; MOLECULES AB In this study we provide evidence that a human breast carcinoma cell line, MDA-MB-231 (MDA), can be made immunogenic following B7 transfection and that full T cell activation is obtained through cooperation of T-B lymphocytes via CD40-CD40L interactions, Tumor cells transfected with either B7 gene (MDAB7), neomycin-resistant gene only (MDAneo), or untransfected (MDA) were used in an allogeneic mixed lymphocyte tumor culture (MLTC) to investigate their ability to stimulate T cell proliferation and generate cytotoxic T lymphocytes (CTL), MDAB7 induced moderate T cell proliferation while MDAneo or MDA did not. Substantial T cell proliferation and de novo generation of cytolytic T cells was obtained only in response to MDAB7 when B cells were present during the MLTC, CD8(+)-purified T + B cells proliferated to a greater extent than whole T cell populations + B or CD4(+) + B in response to MDAB7. Addition of alpha-B7-1 or alpha-CD40 in the MLTC inhibited T cell proliferation by 65 and 40%, respectively, whereas T cell proliferation and generation of CTL was completely abrogated when MLTC was performed in the presence of both antibodies. These data suggest that the engagement of CD40L on T cells with CD40 on B cells provides a costimulatory signal which, in synergism with TCR-dependent MDAB7-T cell recognition (signal 1) and B7/CD28 interactions (signal 2), leads to full T cell activation. C1 UNIV S FLORIDA,H LEE MOFFITT CANC CTR,PROGRAM IMMUNOL,TAMPA,FL 33682. UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOL,MIAMI,FL. RP Pericle, F (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. NR 43 TC 8 Z9 9 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 FEB PY 1997 VL 61 IS 2 BP 201 EP 208 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA WG207 UT WOS:A1997WG20700011 PM 9021926 ER PT J AU Ortaldo, JR WinklerPickett, RT Nagata, S Ware, CF AF Ortaldo, JR WinklerPickett, RT Nagata, S Ware, CF TI Fas involvement in human NK cell apoptosis: Lack of a requirement for CD16-mediated events SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytokines; cross-linking; Fc gamma RIII receptor ID NATURAL-KILLER-CELLS; LARGE GRANULAR LYMPHOCYTES; T-LYMPHOCYTES; PERIPHERAL-BLOOD; TRIGGERING MOLECULE; DEATH FACTOR; ANTIGEN; EXPRESSION; LIGAND; ACTIVATION AB Propriocidal regulation of T cells refers to apoptosis induced by interleukin-2 (IL-2) activation with subsequent antigen receptor stimulation, We previously reported that natural killer (NK) cells also exhibit propriocidal death. Cell death can be induced following occupancy of the Fc gamma RIII (CD16) receptor when NK cells were pretreated with IL-2, IL-12, or IL-15, Here we show other triggering receptors on NK cells such as CD44, anti-NK-receptor antibodies, and pharmacological activation can result in the cell death signal. Requirement for cell interactions indicated that cell contact was required; however, unlike cell-mediated lysis, extracellular calcium was not required. Like T cells, the process of cell death for NK cells was receptor-induced apoptosis. Activation-induced apoptosis of T cells is mediated by members of the tumor necrosis factor (TNF) cytokine superfamily. We examined the involvement of TNF receptor family members or Fas in this rapid cell death, Antibody directed against Fas, TNFR(60), TNFR(80), LTBR, and LT alpha failed to inhibit receptor-induced death. Therefore, NK cells appear to demonstrate a rapid apoptotic episode when CD16 is cross-linked, but the mechanism of this apoptosis is quite different than was observed in T cells with CD3. The direct examination of the Fas pathway on activated NK cells revealed that susceptibility required longer treatment times and IL-2 activation. This susceptibility was paralleled by increased Fas-ligand expression. Therefore, NK cells can demonstrate an apoptotic response to CD16, CD44, NK receptors, and Fas. The enumeration of ligands capable of eliciting NK cell death and the in vivo relevance of this observation require further study. C1 UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521. OSAKA BIOSCI INST,OSAKA,JAPAN. RP Ortaldo, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LEI,DIV BASIC SCI,BLDG 560,RM 31-93,FREDERICK,MD 21702, USA. NR 37 TC 22 Z9 22 U1 0 U2 1 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 FEB PY 1997 VL 61 IS 2 BP 209 EP 215 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA WG207 UT WOS:A1997WG20700012 PM 9021927 ER PT J AU Chang, MCJ Grange, E Rabin, O Bell, JM AF Chang, MCJ Grange, E Rabin, O Bell, JM TI Incorporation of [U-C-14]palmitate into rat brain: Effect of an inhibitor of beta-oxidation SO JOURNAL OF LIPID RESEARCH LA English DT Article DE methyl palmoxirate; palmitate; fatty acids; phospholipids; brain; rat; in vivo imaging; beta-oxidation ID FATTY-ACID OXIDATION; CEREBRAL PALMITATE INCORPORATION; 2-TETRADECYLGLYCIDIC ACID; CARNITINE DEFICIENCY; UNANESTHETIZED RATS; METHYL 2-TETRADECYLGLYCIDATE; HYPOGLYCEMIC AGENT; LIVER MITOCHONDRIA; PLASMA PALMITATE; SKELETAL-MUSCLE AB We examined the effect of a clinically therapeutic dose of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate, MEP) (2.5 mg/kg), an inhibitor of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-C-14]PAM) from plasma into brain lipids of awake rats. Four hour pretreatment with 2.5 mg/kg MEP significantly increased the incorporation of [U-C-14]PAM into brain lipids and substantially decreased aqueous radiolabeled metabolites in brain that can constitute unwanted background signal when analyzed by quantitative autoradiography. MEP treatment increased the lipid to aqueous background radioactivity from 0.8 to 3.0. Net rate of incorporation, k*, was significantly increased (60%) by MEP and was attributed to incorporation of [U-C-14]PAM into phospholipid and triglyceride brain compartments. MEP treatment did not affect the size of the fatty acyl-CoA pool or the distribution of the Various molecular acyl-CoA species. These results indicate that MEP, at a dose of 2.5 mg/kg (per os), can be used to increase incorporation of [1-C-11]PAM for studying brain lipid metabolism in humans by positron emission tomography (PET). RP Chang, MCJ (reprint author), NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892, USA. NR 32 TC 12 Z9 12 U1 0 U2 2 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 FEB PY 1997 VL 38 IS 2 BP 295 EP 300 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM242 UT WOS:A1997WM24200010 PM 9162749 ER PT J AU Tjandra, N Bax, A AF Tjandra, N Bax, A TI Measurement of dipolar contributions to (1)J(CH) splittings from magnetic-field dependence of J modulation in two-dimensional NMR spectra SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID PROTEIN BACKBONE CONFORMATION; RESOLUTION; SPECTROSCOPY RP Tjandra, N (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 2,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [1F32DK09143-01] NR 21 TC 117 Z9 119 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD FEB PY 1997 VL 124 IS 2 BP 512 EP 515 DI 10.1006/jmre.1996.1088 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA WP821 UT WOS:A1997WP82100029 PM 9169226 ER PT J AU Lamb, ME AF Lamb, ME TI The book of David: How preserving families can cost children's lives - Gelles,R SO JOURNAL OF MARRIAGE AND THE FAMILY LA English DT Book Review RP Lamb, ME (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU NATL COUNCIL FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0022-2445 J9 J MARRIAGE FAM JI J. Marriage Fam. PD FEB PY 1997 VL 59 IS 1 BP 235 EP 236 DI 10.2307/353677 PG 2 WC Family Studies; Sociology SC Family Studies; Sociology GA WL628 UT WOS:A1997WL62800020 ER PT J AU Malinchik, S Cuda, G Podolsky, RJ Horowits, R AF Malinchik, S Cuda, G Podolsky, RJ Horowits, R TI Isometric tension and mutant myosin heavy chain content in single skeletal myofibers from hypertrophic cardiomyopathy patients SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE hypertrophic cardiomyopathy; muscle contraction; myosin; mutation; molecular genetics ID BETA-CARDIAC MYOSIN; VENTRICULAR ALPHA-MYOSIN; PROTEIN-C GENE; MISSENSE MUTATION; MUSCLE-FIBERS; MESSENGER-RNA; PROGNOSTIC IMPLICATIONS; SARCOMERE-LENGTH; SUDDEN-DEATH; EXPRESSION AB Several mutations in the beta-myosin heavy chain (beta-MHC) gene have been linked to hypertrophic cardiomyopathy (HCM). Because this gene is also expressed in slow-twitch fibers of skeletal muscle, we have been able to study the mutant beta-myosin content and mechanical properties associated with these myosin mutations in single skinned skeletal muscle fibers obtained from HCM patients. We found that in patients carrying the 403(Arg-->Gla) mutation, the mutant beta-MHC comprises 47.3 +/- 9.1% of the total beta-MHC present in single slow-twitch fibers. Therefore, both alleles of the beta-MHC gene are on average equally expressed. Isometric tension was decreased by 18% in slow fibers from HCM patients with the 403(Arg-->Gla) mutation, but was unchanged in slow fibers from patients with two other beta-MHC gene mutations. Taken together with the previous demonstration of reduced velocities generated by these myosins in an in vitro assay, our results suggest that the mutant beta-myosins are functional molecular meters that are able to generate tension and movement, but with abnormal kinetics. (C) 1997 Academic Press Limited. C1 NIAMS, LPB, BETHESDA, MD 20892 USA. NHLBI, NIH, BETHESDA, MD 20892 USA. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 59 TC 18 Z9 19 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD FEB PY 1997 VL 29 IS 2 BP 667 EP 676 DI 10.1006/jmcc.1996.0309 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA WU808 UT WOS:A1997WU80800022 PM 9140824 ER PT J AU Quarles, RH AF Quarles, RH TI Glycoproteins of myelin sheaths SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Review DE adhesion; carbohydrate; cell-cell interactions; glycoprotein; HNK-1; myelin; oligodendrocyte; oligosaccharide; P0 protein; Schwann cell ID PERIPHERAL NERVOUS-SYSTEM; LINKED OLIGOSACCHARIDE STRUCTURES; CELL-ADHESION MOLECULES; OLIGODENDROCYTE GLYCOPROTEIN; SCHWANN-CELLS; L2/HNK-1 CARBOHYDRATE; MULTIPLE-SCLEROSIS; IMMUNOGLOBULIN SUPERFAMILY; NEURAL ADHESION; PO PROTEIN AB A growing number of glycoproteins have been identified and characterized in myelin and myelin-forming cells. Ln addition to the major PO glycoprotein of compact PNS myelin and the myelin-associated glycoprotein (MAG) in the periaxonal membranes of myelin-forming oligodendrocytes and Schwann cells, the list now includes peripheral myelin protein-22 (PMP-22), a 170 kDa glycoprotein associated with PNS myelin and Schwann cells (P170k/SAG), Schwann cell myelin protein (SMP), myelin/oligodendrocyte glycoprotein (MOG), and oligodendrocyte-myelin glycoprotein (OMgp). Many of these glycoproteins are members of tho immunoglobulin superfamily and express the adhesion-related HNK-1 carbohydrate epitope. This review summarizes recent findings concerning the structure and function of these glycoproteins of myelin sheaths with emphasis on the physiological roles of oligosaccharide moieties. RP Quarles, RH (reprint author), NINCDS,MYELIN & BRAIN DEV SECT,CELLULAR & MOL NEUROBIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 95 TC 66 Z9 66 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD FEB PY 1997 VL 8 IS 1 BP 1 EP 12 DI 10.1007/BF02736858 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WK425 UT WOS:A1997WK42500001 PM 9061610 ER PT J AU Olde, B McCombie, WR AF Olde, B McCombie, WR TI Molecular cloning and functional expression of a serotonin receptor from Caenorhabditis elegans SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE 5HT receptor; Caenorhabditis elegans; cloning; expression ID ADENYLATE-CYCLASE; NERVOUS-SYSTEM; SEQUENCE TAGS; BINDING; FAMILY; GENE; DNA; 5-HYDROXYTRYPTAMINE; LOCALIZATION; SUBTYPE AB A cDNA encoding a serotonin receptor has been isolated from a Caenorhabditis elegans mixed stage cDNA library. The nematode serotonin receptor, designated 5HT-Ce, was permanently expressed in murine Ltk- cells, where it mediates adenylate cyclase attenuation. Sequence analysis and the pharmacological profiles demonstrate its relatedness not only to Drosophila and Lymnae 5HT receptors but also to mammalian 5HT1a receptors. The 5HT-Ce gene does not map close to the position of any known serotonergic mutations. C1 NINCDS,NEUROGENET SECT,NIH,BETHESDA,MD 20892. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. OI McCombie, W. Richard/0000-0003-1899-0682 NR 43 TC 62 Z9 68 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD FEB PY 1997 VL 8 IS 1 BP 53 EP 62 DI 10.1007/BF02736863 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WK425 UT WOS:A1997WK42500006 PM 9061615 ER PT J AU Groweiss, A Cardellina, JH Pannell, LK Uyakul, D Kashman, Y Boyd, MR AF Groweiss, A Cardellina, JH Pannell, LK Uyakul, D Kashman, Y Boyd, MR TI Novel cytotoxic, alkylated hydroquinones from Lannea welwitschii SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB Two novel natural products, lanneaquinol(1) and 2'(R)-hydroxylanneaquinol (2), were isolated from the organic extract of the plant Lannea welwitschii (Hiern) Engl. Their structures were solved by spectroanalytical methods and confirmed by comparison to synthetic models. The absolute configuration of 2 was determined by the modified Mosher method. Both compounds exhibited modest cytotoxicity against the NCI panel of 60 human tumor cell lines. The structures of two isomeric 4,5-dihydroxy-5-alkyl-2-cyclohexenones (7 and 8), which appear to be biogenetic precursors of 1 and 2, were also elucidated. C1 NCI, FREDERICK CANC RES & DEV CTR, DIV CANC TREATMENT, LAB DRUG DISCOVERY RES & DEV, FREDERICK, MD 21702 USA. NIDDKD, ANALYT CHEM LAB, BETHESDA, MD 20892 USA. NR 11 TC 18 Z9 18 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 1997 VL 60 IS 2 BP 116 EP 121 DI 10.1021/np960435t PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA WK283 UT WOS:A1997WK28300011 PM 9051911 ER PT J AU Pettit, GR McNulty, J Herald, DL Doubek, DL Chapuis, JC Schmidt, JM Tackett, LP Boyd, MR AF Pettit, GR McNulty, J Herald, DL Doubek, DL Chapuis, JC Schmidt, JM Tackett, LP Boyd, MR TI Antineoplastic agents .362. Isolation and X-ray crystal structure of dibromophakellstatin from the Indian ocean sponge Phakellia mauritiana SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID VANDERWAALS ATOMIC RADII; MARINE SPONGE; MOLECULAR-CRYSTALS; NATURAL-PRODUCTS; ALKALOIDS; PEPTIDES; REVISION; CARBON; SCREEN; ACIDS AB Bioassay-guided isolation procedures using human tumor cell lines led to isolation of dibromophakellstatin (4) from the Republic of Seychelles sponge Phakellia mauritiana. The isolation, X-ray crystal structure elucidation, absolute stereochemistry, and antineoplastic activity have been summarized. P. mauritiana was also found to contain dibromophakellin (1), debromohymenialosine (2), thymidine, deoxyuridine, and thymine. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DTP,DCTDC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Pettit, GR (reprint author), ARIZONA STATE UNIV,DEPT CHEM,CANC RES INST,TEMPE,AZ 85287, USA. RI McNulty, James/E-7871-2011 FU NCI NIH HHS [CA-16049-05-12, CA-44344-01A1-08] NR 42 TC 73 Z9 73 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 1997 VL 60 IS 2 BP 180 EP 183 DI 10.1021/np9606106 PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA WK283 UT WOS:A1997WK28300028 PM 9051914 ER PT J AU Powell, SK Rivas, RJ RodriguezBoulan, E Hatten, ME AF Powell, SK Rivas, RJ RodriguezBoulan, E Hatten, ME TI Development of polarity in cerebellar granule neurons SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE neuronal polarity; GPI-anchor; cerebellar granule neurons; protein sorting ID RAT SYMPATHETIC NEURONS; MICROTUBULE-ASSOCIATED PROTEIN-2; NEURITE-ASSOCIATED PROTEINS; HIPPOCAMPAL-NEURONS; ADHESION MOLECULES; MORPHOLOGICAL-DIFFERENTIATION; IMMUNOGLOBULIN SUPERFAMILY; POSTNATAL-DEVELOPMENT; EPITHELIAL-CELLS; PURKINJE-CELLS AB Axon formation in developing cerebellar granule neurons irt situ is spatially and temporally segregated from subsequent neuronal migration and dendrite formation. To examine the role of local environmental cues on early steps in granule cell differentiation, the sequence of morphologic development and polarized distribution of membrane proteins was determined in granule cells isolated from contact with other cerebellar cell types. Granule cells cultured at low density developed their characteristic axonal and dendritic morphologies in a series of discrete temporal steps highly similar to those observed in situ, first extending a unipolar process, then long, thin bipolar axons, and finally becoming multipolar, forming short dendrites around the cell body. Axonal- and dendritic-specific cytoskeletal markers were segregated to the morphologically distinct domains. The cell surface distribution of a specific class of endogenous glycoproteins, those linked to the membrane by a glycosylphosphatidyl inositol (GPI) anchor, was also examined. The GPI-anchored protein, TAG-1, which is segregated to the parallel fiber axons in situ, was found exclusively on granule cell axons in vitro; however, two other endogenous GPI-anchored proteins were found on both the axonal and somatodendritic domains. These results demonstrate that granule cells develop polarity in a cell type-specific manner in the absence of the spatial cues of the developing cerebellar cortex. (C) 1997 John Wiley & Sons, Inc. C1 ROCKEFELLER UNIV,DEV NEUROBIOL LAB,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,DEPT CELL BIOL,NEW YORK,NY 10021. RP Powell, SK (reprint author), NIDR,DEV BIOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [R01 GM034107]; NINDS NIH HHS [NS 15429, NS 30532] NR 53 TC 77 Z9 77 U1 0 U2 1 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 FEB PY 1997 VL 32 IS 2 BP 223 EP 236 DI 10.1002/(SICI)1097-4695(199702)32:2<223::AID-NEU7>3.0.CO;2-A PG 14 WC Neurosciences SC Neurosciences & Neurology GA WG093 UT WOS:A1997WG09300007 PM 9032664 ER PT J AU Farrer, RG Quarles, RH AF Farrer, RG Quarles, RH TI Expression of sulfated gangliosides in the central nervous system SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE sulfated gangliosides; CNS; oligodendrocytes; gangliosides; glycolipid ID MYELIN-ASSOCIATED GLYCOPROTEIN; BOVINE GASTRIC-MUCOSA; GLIAL-CELL LINE; SULFOGLUCURONYL GLYCOLIPIDS; OLIGODENDROCYTES; RECOGNITION; NEUROPATHY; CULTURES; BRAIN; CG-4 AB Several sulfated lipids were detected in the ganglioside fraction isolated from a cell line of oligodendrocyte progenitors that had been metabolically labeled with [S-35]sulfate. Separation of the ganglioside fraction by two-dimensional TLC showed that, except for galactosylceramide-sulfate, none of the sulfate-labeled lipids comigrated with those glycosphingolipids visualized by orcinol staining, indicating that these sulfolipids were quantitatively minor components. At least eight sulfate-labeled lipid bands were susceptible to desialylation by Arthrobacter ureafaciens neuraminidase, which resulted in the formation of three new bands that retained the labeled sulfate. Six of the sulfate-labeled lipid bands containing sialic acid were also susceptible to Vibrio cholerae neuraminidase, which generated two labeled bands that appeared identical to the two major products formed after treatment with A. ureafaciens neuraminidase. In vivo labeling of lipids from 14-day-old rat brain with [S-35]sulfate demonstrated that the synthesis of sulfated lipids containing sialic acid also occurred in intact brain tissue. These results show that sulfated gangliosides are synthesized in the CNS and that oligodendrocytes are one cell type that contributes to this synthesis. RP Farrer, RG (reprint author), NINCDS,MYELAIN & BRAIN DEV SECT,MOL & CELLULAR NEUROBIOL LAB,NIH,BLDG 49,ROOM 2A28,BETHESDA,MD 20892, USA. NR 22 TC 6 Z9 6 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 FEB PY 1997 VL 68 IS 2 BP 878 EP 881 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WD079 UT WOS:A1997WD07900053 PM 9003081 ER PT J AU Coling, DE Espreafico, EM Kachar, B AF Coling, DE Espreafico, EM Kachar, B TI Cellular distribution of myosin-V in the guinea pig cochlea SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID UNCONVENTIONAL MYOSIN; GENE ENCODES; PROTEINS AB The importance of unconventional myosins to hearing has recently been revealed by the identification of myosins-VI and -VII as the defective genes in mouse mutations and in a human syndrome which lead to profound hearing loss. Another class of novel myosins (V) has been implicated in the trafficking of intracellular vesicles in neurons and other secretory cells. We used affinity-purified antibodies to determine the localization of myosin-V in the guinea pig inner ear. In the sensory epithelium of the cochlea, myosin-V epitopes were recognized in neuronal and supporting cells. Neuronal labelling was most intense in the afferent innervation of inner and outer hair cells. Supporting cells labelled were cells of Hensen and Deiters, and inner border, inner phalangeal, inner sulcus and interdental cells. In the vascular tissue of the cochlea, we observed staining of intermediate cells of the stria vascularis and of border cells between the stria and the spiral prominence. Staining of afferent chalice nerve endings was observed on type I vestibular hair cells. The results suggest that, like myosins VI and VIII, myosin-V is localized in positions that may be critical to auditory function. C1 NIDCD,LAB CELLULAR BIOL,SECT STRUCT CELL BIOL,NIH,ROCKVILLE,MD 20850. UNIV SAO PAULO,FAC MED RIBEIRAO PRETO,DEPT MORPHOL,RIBEIRAO PRET,SP,BRAZIL. RI Espreafico, Enilza/O-3053-2016; OI Coling, Donald/0000-0001-6285-5336 NR 16 TC 14 Z9 15 U1 1 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD FEB PY 1997 VL 26 IS 2 BP 113 EP 120 DI 10.1023/A:1018523827852 PG 8 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA XA410 UT WOS:A1997XA41000005 PM 9181485 ER PT J AU Buckley, MJ Gaffan, D Murray, EA AF Buckley, MJ Gaffan, D Murray, EA TI Functional double dissociation between two inferior temporal cortical areas: Perirhinal cortex versus middle temporal gyrus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID FORNIX TRANSECTION; VISUAL RECOGNITION; ENTORHINAL CORTEX; RHESUS-MONKEYS; MEMORY; CONNECTIONS; ORGANIZATION; ABLATIONS; COLD; AMYGDALECTOMY AB There is both anatomic and cytoarchitectural evidence for dorsal-ventral subdivisions of the inferior temporal cortex. Despite this, there has been only limited evidence of corresponding functional subdivisions and no evidence that two adjacent cortical areas within the inferior temporal cortex, namely area TE and the perirhinal cortex, have distinctly different roles in vision and memory. We assessed the color discrimination abilities of cynomolgus monkeys with either bilateral ablation of the perirhinal cortex or bilateral ablation of the middle temporal gyrus. The stimuli were isoluminant colored squares presented on a touch screen. Ln each trial the subject had to learn to discriminate and select the correct choice (green) from among a maximum of eight other foils, each varying in either hue or saturation. Relative to unoperated controls, monkeys with middle temporal gyrus lesions were severely impaired in the color discrimination task, whereas monkeys with perirhinal lesions were unimpaired on this task. We also assessed the visual recognition abilities, as measured by a basic delayed nonmatching-to-sample task with trial-unique objects presented in a Wisconsin General Test Apparatus, of rhesus monkeys with bilateral middle temporal gyrus lesions. We then tested the monkeys' postoperative performance on a delayed nonmatching-to-sample task with delays and extended list lengths. The results from this experiment were compared with those from two other groups of rhesus monkeys, an unoperated control group and a group with bilateral perirhinal cortex lesions, both of which had performed the identical tasks in a previous experiment. Relative to unoperated controls, monkeys with perirhinal cortex lesions were severely impaired both in relearning the basic delayed nonmatching-to-sample task and on the postoperative performance test. In contrast, monkeys with middle temporal gyrus lesions were only mildly affected in relearning the basic nonmatching task and were unimpaired on the postoperative performance test. Thus our data demonstrate a clear functional double dissociation between the perirhinal cortex and the middle temporal gyrus. This result gives strong support to the hypothesis that the perirhinal cortex and the adjacent area TE have distinctly different roles in visual learning and memory. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP Buckley, MJ (reprint author), UNIV OXFORD,DEPT EXPT PSYCHOL,S PARKS RD,OXFORD OX1 3UD,ENGLAND. OI Murray, Elisabeth/0000-0003-1450-1642 NR 30 TC 128 Z9 128 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1997 VL 77 IS 2 BP 587 EP 598 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WK036 UT WOS:A1997WK03600007 PM 9065832 ER PT J AU Duffy, CJ Wurtz, RH AF Duffy, CJ Wurtz, RH TI Planar directional contributions to optic flow responses in MST neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPERIOR TEMPORAL AREA; MACAQUE MONKEY; EXPANSION CONTRACTION; NEURAL NETWORK; ROTATION CELLS; VISUAL-CORTEX; FIELD STIMULI; DORSAL PART; MOTION; SENSITIVITY AB Many neurons in the dorsal region of the medial superior temporal area (MSTd) of monkey cerebral cortex respond to optic flow stimuli in which the center of motion is shifted off the center of the visual field. Each shifted-center-of-motion stimulus presents both different directions of planar motion throughout the visual field and a unique pattern of global motion across the visual field. We investigated the contribution of planar motion to the responses of these neurons in two experiments. In the first, we compared the responses of 243 neurons to planar motion and to shifted-center-of-motion stimuli created by Vector summation of planar motion and radial or circular motion. We found that many neurons preferred the same directions of motion in the combined stimuli as in the planar stimuli, but other neurons did not. When we divided our sample into one group with stronger directionality to both planar and vector combination stimuli and one group with weaker directionality, we found that the neurons with the stronger directionality were those that showed the greatest similarity in the preferred direction of motion for both the planar and combined stimuli. In a second set of experiments, we overlapped planar motion and radial or circular motion to create transparent stimuli with the same motion components as the vector combination stimuli, but without the shifted centers of motion. We found that the neurons that responded most strongly to the planar motion when it was combined with radial or circular motion also responded best when the planar motion was overlapped by a transparent motion stimulus. We conclude that the responses of those neurons with stronger directional responses to both the motion of planar and vector combination stimuli are most readily understood as responding to the total planar motion in the stimulus, a planar motion mechanism. Other neurons that had weaker directional responses showed no such similarity in the preferred directions of planar motion in the vector combination and the transparent overlap stimuli and fit best with a mechanism dependent on the global motion pattern. We also found that neurons having significant responses to both radial and circular motion also responded to the spiral stimuli that result from a vector combination of radial and circular motion. The preferred planar-spiral vector combination stimulus was frequently the one containing that neurons' preferred direction of planar motion, which makes them similar to other MSTd neurons. C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. UNIV ROCHESTER,MED CTR,DEPT NEUROL NEUROBIOL & ANAT,NEW YORK,NY 14642. UNIV ROCHESTER,MED CTR,DEPT OPHTHALMOL,NEW YORK,NY 14642. UNIV ROCHESTER,MED CTR,CTR VISUAL SCI,NEW YORK,NY 14642. FU NEI NIH HHS [EY-10287] NR 27 TC 49 Z9 50 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 FEB PY 1997 VL 77 IS 2 BP 782 EP 796 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WK036 UT WOS:A1997WK03600025 PM 9065850 ER PT J AU Granholm, ACE Srivastava, N Mott, JL Henry, M Westphal, H Pichel, JG Shen, LY Hoffer, BJ AF Granholm, ACE Srivastava, N Mott, JL Henry, M Westphal, H Pichel, JG Shen, LY Hoffer, BJ TI Morphological alterations in the peripheral and central nervous systems of mice lacking glial cell line-derived neurotrophic factor (GDNF): Immunohistochemical studies SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glial cell line-derived neurotrophic factor; aminergic neurons; substantia nigra; locus coeruleus; gastrointestinal innervation; tooth development; basal forebrain ID MIDBRAIN DOPAMINERGIC-NEURONS; IN-VIVO; MESSENGER-RNA; GROWTH-FACTOR; CHOLINERGIC NEURONS; BASAL FOREBRAIN; SURVIVAL FACTOR; MOTOR-NEURONS; EXPRESSION; RAT AB Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with neurotrophic activity on midbrain dopaminergic neurons and on developing and mature motoneurons of the brainstem and spinal cord. To investigate the extent of GDNF dependency of central and peripheral nervous structures during development, we have performed an immunohistochemical analysis of sections from the whole head including brain, peripheral ganglia, developing teeth and tongue, as well as intestines, in mutant mice lacking a part of the third exon that encodes the GDNF protein. As described previously, these null-mutated mice lack most of the enteric nerve plexus and are subject to agenesis or severe dysgenesis of the kidneys. In the present communication, we examined the development of vibrissae and incisor and molar teeth, as well as the innervation of these structures, and found no differences between null-mutated and control mice. A decrease in the immunohistochemical labeling intensity with tyrosine hydroxylase was observed in the superior cervical ganglion (SCG), as well as in the pontine nucleus locus coeruleus, and the sympathetic innervation of blood vessels and glands in the head was significantly decreased. None of the brain nuclei studied exhibited any significant decreases in the total number of neurons, but the packing density of neurons in the nucleus locus coeruleus was decreased. These data indicate that GDNF might be one neurotrophic factor that contributes to the development of central and peripheral noradrenergic neurons. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,NEUROSCI TRAINING PROGRAM,DENVER,CO 80262. NICHHD,LMGD,NIH,BETHESDA,MD 20892. RP Granholm, ACE (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT BASIC SCI,4200 E 9TH AVE,POB C286,DENVER,CO 80262, USA. FU NIA NIH HHS [AG04418]; NIMH NIH HHS [MH49661]; NINDS NIH HHS [NS09199] NR 45 TC 57 Z9 59 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 1 PY 1997 VL 17 IS 3 BP 1168 EP 1178 PG 11 WC Neurosciences SC Neurosciences & Neurology GA WJ678 UT WOS:A1997WJ67800028 PM 8994069 ER PT J AU Zhao, B Chrest, FJ Horton, WE Sisodia, SS Kusiak, JW AF Zhao, B Chrest, FJ Horton, WE Sisodia, SS Kusiak, JW TI Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer disease (AD); amyloid precursor protein (APP); mutation; neurodegeneration; pheochromocytoma (PC12) cells ID FAMILIAL ALZHEIMERS-DISEASE; BETA-PROTEIN; CEREBRAL-HEMORRHAGE; TRANSGENIC MICE; RAT-BRAIN; NEUROTOXICITY; MUTATION; GENE; DEATH; FRAGMENT AB The cause of neuronal loss in Alzheimer disease is unknown, We investigated the effects on survival of PC12 cells expressing A692G, E693Q, and V717F mutant amyloid precursor proteins (APP), Differentiated cells expressing mutant APPs exhibited somal shrinkage, followed by cell detachment from the plates, Increased levels of oligonucleosome-sized DNA ladders and TUNEL-positive nuclei were observed, and electron microscopy revealed extensive plasma membrane blebbing, margination of condensed chromatin, and well-preserved organelles in these transfectants, The levels of TUNEL-positive cells, analyzed by a flow-cytometric method, were increased by four- to sevenfold in mutant APP transfectants, but less than twofold in wild-type APP transfectants relative to untransfected cells, Our results provide evidence that expression of mutant APPs in differentiated PC12 cells induces cell death via an apoptotic pathway. (C) 1997 Wiley-Liss, Inc. C1 NIA, GERONTOL RES CTR, CLIN IMMUNOL SECT, LCP, BALTIMORE, MD 21224 USA. NIA, GERONTOL RES CTR, CELL BIOL UNIT, LBC, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, DEPT PATHOL, BALTIMORE, MD USA. JOHNS HOPKINS UNIV, NEUROPATHOL LAB, BALTIMORE, MD USA. RP Zhao, B (reprint author), NIA, CTR GERONTOL RES, MOL NEUROBIOL UNIT, LBC, BALTIMORE, MD 21224 USA. NR 43 TC 58 Z9 58 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 1997 VL 47 IS 3 BP 253 EP 263 PG 11 WC Neurosciences SC Neurosciences & Neurology GA WG306 UT WOS:A1997WG30600003 PM 9039647 ER PT J AU Dickens, G Lavarreda, M Zheng, WH Guroff, G AF Dickens, G Lavarreda, M Zheng, WH Guroff, G TI Involvement of protein kinase C in nerve growth factor- and K-252a-stimulated calcium uptake into PC12 cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE PMA; ATP; thymeleatoxin ID PHEOCHROMOCYTOMA CELLS; NEURITE OUTGROWTH; PHORBOL ESTERS; NEURONAL DEATH; INCREASE; PHOSPHORYLATION; PC12-CELLS; K-252A; DIFFERENTIATION; TRANSLOCATION AB Both nerve growth factor (NGF) and K-252a stimulate the uptake of calcium into PC12 cells, Stimulation by either is prevented by pretreatment of the cells with the tumor promoter phorbol 12-myristate 13-acetate (PMA), suggesting an involvement of protein kinase C in the stimulation, The effect of PMA is specific in that the calcium uptake stimulated by either the L-type channel agonist BAY K 8644 or by ATP is not altered in PMA-pretreated cells, An involvement of kinase C is also suggested by the inhibition of NGF- or K-252a-stimulated calcium uptake by the kinase C inhibitors staurosporine and calphostin C, Inhibition by the isoform-specific agents GO 6976 and thymeleatoxin implicates one of the classic calcium-sensitive isoforms of kinase C, The close similarity in the profiles of inhibition of NGF-stimulated and K-252a-stimulated calcium uptake by the various effecters suggests that NGF and K-252a act on calcium uptake through some of the same signaling elements. (C) 1997 Wiley-Liss, Inc. C1 NICHHD, GROWTH FACTORS SECT, NIH, BETHESDA, MD 20892 USA. NR 33 TC 5 Z9 5 U1 0 U2 1 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 1997 VL 47 IS 3 BP 271 EP 276 DI 10.1002/(SICI)1097-4547(19970201)47:3<271::AID-JNR5>3.0.CO;2-F PG 6 WC Neurosciences SC Neurosciences & Neurology GA WG306 UT WOS:A1997WG30600005 PM 9039649 ER PT J AU Blight, AR Leroy, EC Heyes, MP AF Blight, AR Leroy, EC Heyes, MP TI Quinolinic acid accumulation in injured spinal cord: Time course, distribution, and species differences between rat and guinea pig SO JOURNAL OF NEUROTRAUMA LA English DT Article DE inflammation; macrophage; quinolinate; spinal trauma; somatosensory evoked potentials ID IMPROVES NEUROLOGIC RECOVERY; L-TRYPTOPHAN; MORPHOMETRIC ANALYSIS; BRAIN; METHYLPREDNISOLONE; MACROPHAGES; NALOXONE; TRAUMA; QUANTIFICATION; IMPAIRMENT AB Experimental compression injury of the spinal cord in guinea pigs results in delayed neurologic deficits that continue to increase in severity for several days following trauma, coincident with inflammatory responses, including invasion of the lesion by mononuclear phagocytes and increased levels of the neurotoxin quinolinic acid (QUIN). Inflammatory responses and QUIN elevation also occur following spinal cord contusion in rats, but maximal neurologic deficits develop immediately. In this study, somatosensory evoked potentials (SEP) and tissue, serum, and cerebrospinal fluid levels of QUIN were measured in guinea pigs and rats following similar compression injuries of the thoracic spinal cord. SEP changes differed between the species, consistent with other neurological changes. In guinea pigs, increases in QUIN levels at the lesion site began at 1 day postinjury, achieved maximal elevation (100-fold) by 12 days, then declined, but remained above serum levels at 25 days postinjury. A similar increase occurred in adjacent areas of the spinal cord, with lower peak levels. In rats, tissue QUIN at the center of the lesion remained below serum levels at all times, increasing moderately (<10-fold) up to 7 days, then decreasing between 7 and 25 days. These data demonstrate differences in the time course and magnitude of QUIN accumulation and neurological deficit between guinea pig and rat, which may relate to differences in secondary pathological mechanisms. Such profound differences may affect the use of these species for evaluation of experimental therapy in this and other inflammatory conditions of the central nervous system. C1 NIMH,LAB NEUROTOXICOL,BETHESDA,MD 20892. RP Blight, AR (reprint author), UNIV N CAROLINA,DIV NEUROSURG,CB 7060,CHAPEL HILL,NC 27599, USA. FU NINDS NIH HHS [NS-21122] NR 41 TC 31 Z9 34 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD FEB PY 1997 VL 14 IS 2 BP 89 EP 98 DI 10.1089/neu.1997.14.89 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA WN400 UT WOS:A1997WN40000003 PM 9069440 ER PT J AU Ressetar, HG Webster, HD Stoner, GL AF Ressetar, HG Webster, HD Stoner, GL TI Persistence of neurotropic JC virus DNA in hamster tissues six months after intracerebral inoculation SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE JC virus; hamster; latency; polymerase chain reaction ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; TRANSGENIC MICE; BRAIN TUMORS; T-ANTIGEN; BK VIRUS; PAPOVAVIRUS; EXPRESSION; PROTEIN; AIDS AB Immunostaining and polymerase chain reaction (PCR) methods were used to examine tissues from 18 6-month-old hamsters intracerebrally inoculated with JC virus (JCV) as newborns. JCV DNA was detected in all hamster brains and urinary bladders, as well as in most kidney, adrenal gland and pancreas samples. While results from reverse transcription PCR (RNA PCR) and immunostaining suggest that T antigen transcription and protein expression were restricted to the brain, the DNA evidence suggests that intracerebrally inoculated JCV enters the systemic circulation and latently infects organs in a tissue specific manner. RP Ressetar, HG (reprint author), NINCDS,EXPT NEUROPATHOL LAB,NIH,BETHESDA,MD 20892, USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 1997 VL 3 IS 1 BP 66 EP 70 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA WJ820 UT WOS:A1997WJ82000008 PM 9147823 ER PT J AU Yoo, TM Chang, HK Choi, CW Webber, KO Le, N Kim, IS Eckelman, WC Pastan, I Carrasquillo, JA Paik, CH AF Yoo, TM Chang, HK Choi, CW Webber, KO Le, N Kim, IS Eckelman, WC Pastan, I Carrasquillo, JA Paik, CH TI Technetium-99m labeling and biodistribution of anti-Tac disulfide-stabilized Fv fragment SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE technetium-99m; Fv fragment; monoclonal antibody; radioimmunodetection; athymic mice ID SINGLE-CHAIN-FV; MONOCLONAL-ANTIBODY; IMMUNOGLOBULIN FRAGMENTS; TUMOR XENOGRAFTS; NUDE-MICE; BINDING; TC-99M; PROTEIN; IN-111; FORMS AB We used a preformed Tc-99m chelate approach to label a genetically engineered disulfide-bonded Fv fragment of anti-Tac monoclonal antibody (dsFv). The biodistribution of this Tc-99m-labeled dsFv was evaluated in athymic mice with IL-2 alpha-receptor-positive ATAC4 tumor xenografts. Methods: Benzoylmercaptoacetyl-triglycine (Bz-MAG3) was first labeled with Tc-99m, and the carboxy group of Tc-99m-MAG3 was then activated to the corresponding tetrafluorophenyl ester. This activated ester was purified with a Sep-Pak C-18 column and conjugated to dsFv, The resulting Tc-99m-MAG3-dsFv was purified with PD-10 size-exclusion chromatography. The immunoreactivity of Tc-99m-MAG3-dsFv was 76% +/- 9%. When incubated in serum at 37 degrees C for 24 hr, there was no appreciable dissociation of Tc-99m. The mice were co-injected with I-125-dsFV labeled by the Iodo-Gen method as a control. The mice were killed at 15 to 720 min far analysis of biodistribution and radiocatabolites. Results: The tumor uptake of Tc-99m-MAG3-dsFv was similar to that of I-125-dsFv. The tumor uptake of Tc-99m-MAG3-dsFv was rapid with a tumor-to-blood or tumor-to-organ ratio higher than 1 for all organs except the kidneys. The peak tumor value of 5.1% injected dose per gram was obtained at 45 min, and the tumor-to-organ ratios increased steadily over time; a ratio of 15, 11, 7, 95 and 0.10 resulted at 6 hr for blood, liver, stomach, muscle and kidney. The radioactivity was primarily excreted through kidneys. Conclusion: The rapid achievement of high tumor-to-blood and -tissue ratios makes Tc-99m-MAG3-dsFv a promising agent for scintigraphic detection of various hematological malignancies that express IL-2 alpha receptors. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,POSTIRON EMISS TOMOG DEPT,BETHESDA,MD 20892. NCI,MOL BIOL LAB,DIV CANC BIOL DIAG & CTR,NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 39 TC 21 Z9 21 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 1997 VL 38 IS 2 BP 294 EP 300 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WF888 UT WOS:A1997WF88800039 PM 9025758 ER PT J AU Buvat, I Bartlett, ML Kitsiou, AN Dilsizian, V Bacharach, SL AF Buvat, I Bartlett, ML Kitsiou, AN Dilsizian, V Bacharach, SL TI A ''hybrid'' method for measuring myocardial wall thickening from gated PET/SPECT images SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE myocardial wall thickening; heart; receiver operating characteristic curve ID POSITRON EMISSION TOMOGRAPHY; LEFT-VENTRICULAR FUNCTION; COMPUTED-TOMOGRAPHY; QUANTITATION; METABOLISM; VALIDATION; PERFUSION; PARAMETER AB We introduce a hybrid index, HYB, which combines counts with geometric information to measure wall thickening from PET/SPECT gated images, Its accuracy is compared with that of a count-based index (MAX) and a geometric index (FWHM). Methods: For each index, the index values versus thickness and the estimated thickening values versus true thickening were investigated using theoretical analyses, realistic simulated data obtained from clinical gated NIR scans, phantom measurements and preliminary gated MRI and PET patient studies, Each index was studied for different spatial resolutions and noise and background conditions, The performance of each index was quantified using a parameter ''Q'' reflecting bias and variability of thickening estimates, Results: HYB varied more linearly with thickness than MAX and FWHM, resulting in a better Q value than with MAX and FWHM for all noise, background and spatial resolutions, ROC analysis confirmed that HYB significantly increases the sensitivity and specificity for detection of wall thickening abnormalities (sensitivity = 100%; specificity = 85% for HYB, 95% and 50% for MAX and 100% and 0% for FWHM, respectively), Conclusion: Use of the hybrid index instead of conventional count-based or geometric indices should improve the classification of normal/abnormal wall thickening values in gated SPECT and PET. C1 NIH, DEPT NUCL MED, CARDIOL BRANCH, BETHESDA, MD 20892 USA. U66 INSERM CNRS, PARIS, FRANCE. NR 14 TC 35 Z9 35 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 1997 VL 38 IS 2 BP 324 EP 329 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WF888 UT WOS:A1997WF88800044 PM 9025763 ER PT J AU Costa, PT McCrae, RR AF Costa, PT McCrae, RR TI Stability and change in personality assessment: The Revised NEO Personality Inventory in the year 2000 SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID SOCIAL DESIRABILITY SCALES; 5-FACTOR MODEL; VALIDITY; PROFILES AB The Revised NEO Personality Inventory (NEO-PI-R) consists of 30 facet scales that define the broad domains of the Five-Factor Model of personality. No major revisions of the basic model are anticipated in the near future. Despite their popularity, social desirability and inconsistency scales will not be added to the NEO-PI-R because their validity and utility have not yet been demonstrated. Among possible changes are minor modifications in wording and more extensive adaptations for adolescents and for populations with low reading levels. Contextualized (e.g., work-related) versions of the instrument will be further explored. Many changes are more easily implemented on the computer than the print version of the instrument. RP Costa, PT (reprint author), NIA,GERONTOL RES CTR,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712 NR 26 TC 179 Z9 183 U1 2 U2 51 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 1997 VL 68 IS 1 BP 86 EP 94 DI 10.1207/s15327752jpa6801_7 PG 9 WC Psychology, Clinical; Psychology, Social SC Psychology GA WD977 UT WOS:A1997WD97700008 PM 9018844 ER PT J AU Chulada, PC Langenbach, R AF Chulada, PC Langenbach, R TI Differential inhibition of murine prostaglandin synthase-1 and -2 by nonsteroidal anti-inflammatory drugs using exogenous and endogenous sources of arachidonic acid SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ENDOPEROXIDE-H SYNTHASE-1; ASPIRIN-LIKE DRUGS; ANTIINFLAMMATORY DRUGS; SELECTIVE-INHIBITION; G/H SYNTHASE; CYCLOOXYGENASE COX-2; MESSENGER-RNA; CELLS; BIOSYNTHESIS; EXPRESSION AB Mouse embryonic fibroblasts (10T1/2) and Chinese hamster ovary (AS52) cell lines that stably express murine prostaglandin G/H synthase (PGHS)-1 or -2 were used to compare the effects of exogenous and endogenous arachidonic acid (AA) on isozyme-selective inhibition by acetylsalicylic acid, indomethacin, and N-[2-cyclohexyloxyl-4-nitrophenyl] methanesulfonamide (NS-398). The rationale for developing in vitro systems that identify PGHS-2-selective inhibitors is the belief that inhibition of this isoform accounts for the therapeutic benefits of nonsteroidal anti-inflammatory drugs (NSAIDs). Conversely, inhibition of PGHS-1 is believed to cause the toxic effects of NSAIDs, such as gastric and renal damage. When exogenous AA was used, acetylsalicylic acid was a 5- to 10-fold more potent inhibitor of PGHS-1, whereas indomethacin was a 4- to 5-fold more potent inhibitor of PGHS-2. Within the dose range tested (1 x 10(-6) mu M to 100 mu M), NS-398 was highly selective for PGHS-2. When calcium ionophore A23187 was used to mobilize endogenous AA, acetylsalicylic acid and indomethacin equipotently inhibited both PGHS-1 and PGHS-2 isozymes. NS-398 remained highly selective for PGHS-2 in 10T1/2 and AS52 cells but also effectively (100%) inhibited PGHS-1 in AS52 cells. Pharmacological data derived using endogenous AA correlated better with the anti-inflammatory efficacy of these NSAIDs in laboratory animals and with the therapeutic/toxic activities of these NSAIDs in rheumatoid arthritic patients. Therefore, screening for PGHS-selective NSAIDs may best be conducted in intact cells that express high levels of each isozyme using endogenous sources of AA. RP Chulada, PC (reprint author), NIEHS, LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 43 TC 18 Z9 18 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 FEB PY 1997 VL 280 IS 2 BP 606 EP 613 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WG580 UT WOS:A1997WG58000012 PM 9023270 ER PT J AU Kari, FW Weaver, R Neville, MC AF Kari, FW Weaver, R Neville, MC TI Active transport of nitrofurantoin across the mammary epithelium in vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BREAST-MILK; LACTATING RABBIT; P-GLYCOPROTEIN; EXCRETION; CIMETIDINE; RESISTANCE; PHARMACOKINETICS; PROTEIN; MODEL AB Nitrofurantoin is a commonly used urinary tract antibiotic that has been found at high concentrations in human milk. In vivo studies in rats were carried out to determine the mechanism by which this drug crosses the mammary epithelium. Lactating rats were gavage-fed with nitrofurantoin, and their milk and plasma levels of the antibiotic were measured at intervals up to 8 hr. The average milk-to-plasma (M/P) ratio, calculated from the areas under the milk and plasma curves, respectively, was 23 compared with a ratio predicted to be about 0.3 on the basis of lipid partitioning and protein binding determinations. M/P ratios for two nitrofurantoin congeners were also calculated. The neutral compound furazolidone had a M/P ratio of about 1, as predicted, whereas the basic compound furaltadone had a M/P ratio of 3.49 compared with a predicted ratio of 1.4. These data suggest that nitrofurantoin and, to a lesser extent, furaltadone are actively transported across the mammary epithelium into milk. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHYSIOL,DENVER,CO 80262. RP Kari, FW (reprint author), NIEHS,POB 12233,MAIL DROP B3-09,RES TRIANGLE PK,NC 27709, USA. NR 28 TC 27 Z9 28 U1 0 U2 2 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 FEB PY 1997 VL 280 IS 2 BP 664 EP 668 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WG580 UT WOS:A1997WG58000019 PM 9023277 ER PT J AU Toddywalla, VS Kari, FW Neville, MC AF Toddywalla, VS Kari, FW Neville, MC TI Active transport of nitrofurantoin across a mouse mammary epithelial monolayer SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INVIVO; MILK AB The antibiotic nitrofurantoin is transported against an electrochemical gradient into milk.A monolayer of CIT3 cells, a subline of the Comma 1D normal mouse mammary epithelial cell line, transports [C-14]-nitrofurantoin against a concentration gradient from the basal to the apical solution when grown on membrane filters. In a side-by-side diffusion chamber with well-stirred solutions on both sides, the transfer rate is 50% higher in the basal-to-apical than in the apical-to-basal direction. Nonlabeled nitrofurantoin (500 mu M) in the basal chamber equalized the transport in both directions, suggesting that a specific transporter is responsible for the basal-to-apical increment in flux. From inhibition studies, the apparent affinity of this transporter for nitrofurantoin is 50 mu M. Changes in pH between 6.4 and 7.8 had no effect on the active transport component of the flux but did affect the passive flux component. Passive flux of the nonionized molecule was 2.6 times faster than that of the ionized molecule, but the ionized molecule did appear to cross the membrane passively. Our findings show that nitrofurantoin is actively transported across a mammary epithelial cell monolayer by a transporter whose affinity for nitrofurantoin does not depend on the anionic charge on nitrofurantoin. The pH dependence of a parallel passive pathway suggests that both nonionized and ionized forms of nitrofurantoin cross the membranes of the mammary epithelial cell by passive diffusion. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHYSIOL,DENVER,CO 80262. INDIAN COUNCIL MED RES,INST RES REPROD,BOMBAY 400012,MAHARASHTRA,INDIA. NIEHS,RES TRIANGLE PK,NC 27709. FU NICHD NIH HHS [HD 19547] NR 10 TC 28 Z9 28 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 FEB PY 1997 VL 280 IS 2 BP 669 EP 676 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WG580 UT WOS:A1997WG58000020 PM 9023278 ER PT J AU Marples, D Monster, B Frokiaer, J Knepper, MA Nielsen, S AF Marples, D Monster, B Frokiaer, J Knepper, MA Nielsen, S TI Thirsting reverses both the diuresis and decreases in aquaporin-2 (AQP2) expression in rat kidney inner medulla produced by the specific V-2 receptor antagonist OPC31260 SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract ID COLLECTING DUCT; VASOPRESSIN C1 UNIV LEEDS,DEPT PHYSIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. AARHUS UNIV,DEPT CELL BIOL,DK-8000 AARHUS,DENMARK. AARHUS UNIV,DEPT CLIN PHYSIOL,DK-8000 AARHUS,DENMARK. NHLBI,NIH,BETHESDA,MD 20892. NR 3 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB PY 1997 VL 499P SI SI BP P57 EP P57 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WU054 UT WOS:A1997WU05400086 ER PT J AU Kafadar, K Prorok, PC AF Kafadar, K Prorok, PC TI Estimating the difference in location parameters of two survival curves, with applications to cancer screening SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE influence function; lead time; benefit time; randomized screening trial; simulation ID TRIALS AB In randomized screening trials, the survival time of a screened participant involves three components: (1) the lead time, or time by which diagnosis is advanced simply by virtue of the screen, (2) the survival time in the absence of screening, and (3) the benefit time, or time by which survival is truly extended due to screening, if any. When the effect of benefit time on survival is additive and survival is measured from time of start of study, the difference in the location parameters of the two survival curves (control and screened arms) is equal to the average benefit time. Similarly, when the effect of lead time on survival is additive, but when survival is measured from time of diagnosis, the difference in location parameters is equal to the sum of the average lead time and average benefit time. Using influence functions, it can be shown that the previously proposed estimators of average lead time and average benefit time are asymptotically equivalent to classical sample means. This result suggests a method for obtaining standard errors via asymptotic variances as well as generalizations which may be more robust to assumptions of duration of preclinical disease. However, this method depends upon the assumption that the case groups used for the analysis are comparable in terms of natural history of disease in the absence of screening. Approaches have been proposed for identifying comparable case groups; any such approach adds variability to the estimators. We investigate the effect of this source of variation and propose one way of reducing it so as to obtain approximately valid confidence intervals for average lead time and average benefit time. C1 UNIV COLORADO,DEPT MATH,DENVER,CO 80217. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD FEB 1 PY 1997 VL 57 IS 2 BP 165 EP 179 DI 10.1016/S0378-3758(96)00042-0 PG 15 WC Statistics & Probability SC Mathematics GA WH851 UT WOS:A1997WH85100001 ER PT J AU Orchinik, M Hastings, N Witt, D McEwen, BS AF Orchinik, M Hastings, N Witt, D McEwen, BS TI High affinity binding of corticosterone to mammalian neuronal membranes: Possible role of corticosteroid binding globulin SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN CEREBROSPINAL-FLUID; SYNAPTIC PLASMA-MEMBRANE; STEROID-HORMONE BINDING; RAT-BRAIN; CELL-MEMBRANES; RECEPTOR; PROTEIN; SITES; PROGESTERONE; SULFATE AB The signal transduction mechanisms mediating rapid steroid actions are poorly understood. To characterize corticosteroid interaction with neuronal membranes in a species with rapid behavioral responses to corticosterone, we examined [H-3]corticosterone binding to membranes prepared from prairie vole brains. At 22 degrees C, the rates of association and dissociation of [H-3]corticosterone with well-washed synaptosomal membranes were very rapid. Specific binding was characterized by high affinity (K-d = 6.01 nM) and low density (B-max = 63.1 fmol/mg protein). The binding sites were highly specific for naturally occurring glucocorticoids and the density of binding sites appeared to vary by neuroanatomical region. Unlike most G-protein-coupled receptors, the high-affinity binding of [H-3]corticosterone to vole brain membranes was unaffected by the addition of Mg2+ or guanyl nucleotides. Surprisingly, saline perfusion of vole brains before tissue homogenization greatly reduced high-affinity binding. In addition, the affinity and specificity of corticosteroid binding sites were similar in vole neuronal membranes and vole plasma. These data suggest that corticosteroid binding globulins may facilitate [H-3]corticosterone binding to neuronal membranes. However, the addition of blood to perfused brains before homogenization did not restore high-affinity binding, so the role of plasma binding globulins is unclear. Whether these binding phenomena represent a technical artifact or a regulatory mechanism for corticosteroid action has yet to be determined. (C) 1997 Elsevier Science Ltd. C1 ROCKEFELLER UNIV,NEUROENDOCRINOL LAB,NEW YORK,NY 10021. NIH,NEUROCHEM LAB,BETHESDA,MD 20892. RP Orchinik, M (reprint author), ARIZONA STATE UNIV,DEPT ZOOL,BOX 871501,TEMPE,AZ 85287, USA. FU NIMH NIH HHS [MH41256]; NINDS NIH HHS [NS07080, NS09129] NR 30 TC 31 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD FEB PY 1997 VL 60 IS 3-4 BP 229 EP 236 DI 10.1016/S0960-0760(96)00191-4 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA XD637 UT WOS:A1997XD63700009 PM 9191981 ER PT J AU Kocsis, E Greenstone, HL Locke, EG Kessel, M Steven, AC AF Kocsis, E Greenstone, HL Locke, EG Kessel, M Steven, AC TI Multiple conformational states of the bacteriophage T4 capsid surface lattice induced when expansion occurs without prior cleavage SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID MAJOR HEAD PROTEIN; STRUCTURAL TRANSITIONS; MATURATION; POLYHEADS; TRANSFORMATION; FRAGMENT; VIRUS; HEMAGGLUTININ; PATHWAY; IMAGES AB The maturation pathway of bacteriophage T4 capsid provides a model system for the study of large-scale conformational changes, in that the precursor capsid progresses through four long-lived and widely differing states. The surface lattice first assembled (uncleaved/unexpanded state: hexagonal lattice constant, a = 11.8 nm) undergoes proteolytic cleavage (cleaved/unexpanded state), then expands (cleaved/expanded state: a = 14.0 nm), and then binds accessory proteins. The most profound change, expansion, normally follows cleavage of the major capsid protein gp23 to gp23* (the 65-residue N-terminal ''Delta-domain'' is removed), but can be induced in vitro in the absence of cleavage by treatment with 0.25 M guanidine-HCl (uncleaved/expanded state). We have studied this alternative pathway by negative staining electron microscopy of polyheads (tubular capsid variants). We find that uncleaved/expanded polyheads encompass four discrete states, called G1-G4, distinguished by their lattice constants of 12.6 nm (G1), 13.4 nm (G2), and 14.0 nm (G3, G4) and by the structures of their hexameric capsomers. Viewed in projection, the G4 capsomer differs from the cleaved/expanded capsomer only in the presence of additional mass at one site per protomer. This mass correlates with the presence of the Delta-domain, which translocates from the inner to the outer surface when the uncleaved lattice expands. Based on proximity of resemblance among these capsomers, we suggest that G1 to G4 represent a sequence of transitional states whose endpoint is G4. G1, G2, and G3 may correspond to intermediates that are too short-lived to be observed when the cleaved lattice expands, but are trapped by the retention of Delta-domains at the interfaces between subunits in the uncleaved lattice. (C) 1997 Academic Press. C1 NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NR 47 TC 8 Z9 8 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD FEB PY 1997 VL 118 IS 1 BP 73 EP 82 DI 10.1006/jsbi.1996.3833 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WN413 UT WOS:A1997WN41300007 PM 9087916 ER PT J AU Blauvelt, A AF Blauvelt, A TI The role of Langerhans cells in the immunopathogenesis of HIV disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article RP Blauvelt, A (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,10 CTR DR,MSC 1908,BETHESDA,MD 20892, USA. NR 0 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 1997 VL 36 IS 2 BP 270 EP 271 PN 1 PG 2 WC Dermatology SC Dermatology GA WH016 UT WOS:A1997WH01600028 ER PT J AU Panza, JA Laurienzo, JM Curiel, RV Unger, EF Quyyumi, AA Dilsizian, V Cannon, RO AF Panza, JA Laurienzo, JM Curiel, RV Unger, EF Quyyumi, AA Dilsizian, V Cannon, RO TI Investigation of the mechanism of chest pain in patients with angiographically normal coronary arteries using transesophageal dobutamine stress echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SYNDROME-X; ANGINA-PECTORIS; DIPYRIDAMOLE-ECHOCARDIOGRAPHY; ENDOTHELIAL DYSFUNCTION; VENTRICULAR-FUNCTION; VASODILATOR RESERVE; FLOW RESERVE; DISEASE; EXERCISE; ARTERIOGRAMS AB Objectives. The present study sought to determine whether myocardial contractile abnormalities accompany the development of chest pain in patients with normal coronary angiograms. Background. The mechanism of chest pain in patients with angina despite a normal coronary arteriogram is controversial. Although previous studies postulated the existence of coronary microvascular dysfunction, others failed to find evidence of myocardial ischemia, and recent studies have demonstrated abnormal cardiac sensitivity in these patients that can lead to chest pain on a nonischemic basis. Methods. Seventy patients (26 men and 44 women, mean age 49 +/- 10 years) with angina-like chest pain and angiographically normal coronary arteries underwent exercise treadmill testing, radionuclide angiography at rest and during exercise, thallium stress testing and transesophageal dobutamine stress echocardiography, The results of exercise treadmill testing and stress echocardiography were compared with those obtained in 26 normal control subjects (19 men and 7 women, mean age 56 +/- 7 years). Results. Abnormalities consistent with myocardial ischemia were noted in 31% of the patients during exercise treadmill testing, in 16% during exercise radionuclide angiography and in 18% during thallium stress testing. The findings of the radionuclide studies were not concordant with one another and were not related to the presence of repolarization changes during exercise testing. During infusion of dobutamine, chest pain developed in 59 patients (84%) and in none of the control subjects (p < 0.0001); repolarization changes occurred in 22 patients (34%) and in 2 control subjects (8%) (p < 0.04). None of the patients or the control subjects developed regional mall motion abnormalities with dobutamine. The quantitative myocardial contractile response to dobutamine was similar in patients and control subjects, with an 80% power to detect a 25% difference in systolic mall thickening at the maximal dose of dobutamine. Conclusions. There was no agreement in the results of noninvasive tests in our patients. Despite the frequent provocation of chest pain and electrocardiographic abnormalities with dobutamine, the patients demonstrated a quantitatively normal myocardial contractile response without development of wall motion abnormalities, These observations strongly suggest that myocardial ischemia is not the cause of chest pain in patients with a normal coronary arteriogram. (C) 1997 by the American College of Cardiology. RP Panza, JA (reprint author), NHLBI,NIH,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 55 TC 86 Z9 92 U1 0 U2 1 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 FEB PY 1997 VL 29 IS 2 BP 293 EP 301 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WE838 UT WOS:A1997WE83800010 PM 9014980 ER PT J AU Quyyumi, AA Dakak, N Mulcahy, D Andrews, NP Husain, S Panza, JA Cannon, RO AF Quyyumi, AA Dakak, N Mulcahy, D Andrews, NP Husain, S Panza, JA Cannon, RO TI Nitric oxide activity in the atherosclerotic human coronary circulation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ENDOTHELIUM-DEPENDENT VASODILATION; VASOMOTOR RESPONSE; SMOOTH-MUSCLE; RISK-FACTORS; BLOOD-FLOW; L-ARGININE; ARACHIDONIC-ACID; ARTERIES; ACETYLCHOLINE; RELAXATION AB Objectives. We determined the activity of nitric oxide at rest and after acetylcholine in the atherosclerotic human coronary circulation. Background. Although responses to acetylcholine, an endothelium dependent vasodilator, are abnormal in patients with coronary atherosclerosis, whether this reflects abnormal nitric oxide activity in humans in vivo has not been investigated previously. Methods. We investigated the effects of intracoronary L-N-G-monomethyl arginine (L-NMMA), a specific antagonist of nitric oxide synthesis, on coronary vascular resistance and epicardial coronary artery diameter at rest and after acetylcholine in 24 patients with coronary artery disease and in 12 subjects with angiographically normal coronary arteries who were free from atherosclerotic risk factors. Results. With L-NMMA, the 13 +/- 4% (mean +/- SEM) increase in coronary vascular resistance and the 4 +/- 1% lumen diameter narrowing in atherosclerotic patients were lower than the 38 +/- 9% increase in resistance and the 15 +/- 2% decrease in diameter (both p < 0.01) observed in normal control subjects, indicating reduced basal nitric oxide activity in atherosclerosis. The degree of angiographic atherosclerotic narrowing did not correlate with the magnitude of diameter reduction, Acetylcholine induced coronary epicardial and microvascular dilation was also depressed in atherosclerotic patients (32.2 +/- 9% reduction in coronary vascular resistance with 10(-6) mol/liter acetylcholine) compared with normal control subjects (65.5 +/- 2% decrease, p < 0.01), L-NMMA inhibited acetylcholine induced epicardial and microvascular vasodilation in both patient groups, but the inhibition was greater in normal control subjects than in atherosclerotic patients, indicating that stimulation of nitric oxide activity by acetylcholine is reduced in atherosclerotic patients compared with normal control subjects. Coronary vascular dilation with sodium nitroprusside was similar in both groups and was not suppressed by L-NMMA. Furthermore, L-arginine reversed the constrictor effects of L-NMMA, indicating that the action of L-NMMA is specifically caused by inhibition of nitric oxide production from L-arginine. Conclusions. These findings indicate that 1) there is a reduced basal activity of nitric oxide in the human atherosclerotic epicardial and microvascular coronary circulation; and 2) acetylcholine induced coronary vascular dilation is at least partly due to stimulation of the activity of nitric oxide, and the reduced response to acetylcholine is due to attenuation in the stimulated activity of nitric oxide in patients with atherosclerosis. (C) 1997 by the American College of Cardiology. RP Quyyumi, AA (reprint author), NHLBI,NIH,CARDIOL BRANCH,BLDG 10,ROOM 7B15,10 CTR DR,MSC 1650,BETHESDA,MD 20892, USA. NR 45 TC 116 Z9 119 U1 0 U2 1 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 FEB PY 1997 VL 29 IS 2 BP 308 EP 317 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WE838 UT WOS:A1997WE83800012 PM 9014982 ER PT J AU Taylor, HA Mickel, MC Chaitman, BR Sopko, G Cutter, GR Rogers, WJ AF Taylor, HA Mickel, MC Chaitman, BR Sopko, G Cutter, GR Rogers, WJ TI Long-term survival of African Americans in the coronary artery surgery study (CASS) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RACIAL-DIFFERENCES; HEART-DISEASE; MYOCARDIAL-INFARCTION; BLACK POPULATIONS; MORTALITY-RATES; RACE; REVASCULARIZATION AB Objectives. This study sought to determine the long term (>15 years) outcome of a clinically well characterized cohort of African Americans with known or suspected coronary artery disease (CAD). Background. The mortality rate from CAD is higher in African Americans than in whites, An earlier analysis of data from the Coronary Artery Surgery Study (CASS) registry suggested that African American and white patients treated surgically had equal 5-year survival rates. Methods. Survival data from the CASS registry were analyzed to determine whether 1) African American race is an independent predictor of mortality; and 2) initial therapy is predictive of mortality among African American patients. Results. Overall, 60% of white and 52% of African American patients survived 16 years (p < 0.00001), Multivariate Cox models confirmed that African American race was independently associated with higher mortality in both the medical group (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.11 to 1.63) and the surgical group (HR 1.63, 95% CI 1.13 to 2.23), Initial therapy was not predictive of survival among African American patients (p = 0.81), However, smoking status significantly influenced survival: African Americans who did not smoke experienced significantly improved survival (60% vs. 48% for smokers), which equaled survival for white nonsmokers (61%, p = NS). Conclusions. In contrast to results from shorter term studies, African Americans experienced higher overall mortality rates than whites over the long term, regardless of the type of initial treatment, Survival among nonsmoking African Americans at 16 years equaled survival among nonsmoking whites. (C) 1997 by the American College of Cardiology. C1 UNIV WASHINGTON,SEATTLE,WA 98195. ST LOUIS UNIV,DEPT MED,DIV CARDIOVASC,ST LOUIS,MO 63103. NHLBI,NATL INST HLTH,BETHESDA,MD 20892. PYTHAGORAS INC,BIRMINGHAM,AL. RP Taylor, HA (reprint author), UNIV ALABAMA,DEPT MED,DIV CARDIOVASC DIS,318 LHRB,701 S 19TH ST,UAB STN,BIRMINGHAM,AL 35294, USA. NR 18 TC 27 Z9 27 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 FEB PY 1997 VL 29 IS 2 BP 358 EP 364 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WE838 UT WOS:A1997WE83800019 PM 9014989 ER PT J AU Zhou, YF Shou, M Harrell, RL Unger, EF Finkel, T Epstein, SE AF Zhou, YF Shou, M Harrell, RL Unger, EF Finkel, T Epstein, SE TI Effect of latent cytomegalovirus infection of rats on the neointimal response to vascular balloon injury SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 1997 VL 29 IS 2 SU A BP 3994 EP 3994 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101796 ER PT J AU Devereux, RB Roman, MJ Ilercil, A Paranicas, M OGrady, MJ Welty, TK Fabsitz, RR Howard, BV Lee, ET AF Devereux, RB Roman, MJ Ilercil, A Paranicas, M OGrady, MJ Welty, TK Fabsitz, RR Howard, BV Lee, ET TI Impact of diabetes on cardiac structure and function in American Indians: The strong heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 CORNELL MED CTR,NEW YORK,NY. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73190. NHLBI,BETHESDA,MD 20892. MEDLANT RES INST,WASHINGTON,DC. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 5410 EP 5410 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101920 ER PT J AU Baek, SH Keefer, LK Mehdi, K March, KL AF Baek, SH Keefer, LK Mehdi, K March, KL TI Intrapericardial nitric oxide donor reduces neointimal and adventitial thickening following porcine coronary overstretch SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,KRANNERT INST CARDIOL,RICHARD L ROUDEBUSH VET ADM MED CTR,INDIANAPOLIS,IN 46202. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 1997 VL 29 IS 2 SU A BP 7011 EP 7011 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100204 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Reduced nitric oxide-dependent forearm vasodilation in normotensive blacks compared to whites SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7062 EP 7062 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100235 ER PT J AU Koh, KK Mincemoyer, R Bui, MN Guetta, V Cannon, RO AF Koh, KK Mincemoyer, R Bui, MN Guetta, V Cannon, RO TI Different effects of hormone therapies on low-density lipoprotein oxidation in postmenopausal women SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7254 EP 7254 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100351 ER PT J AU Becker, J Adams, E Plotz, P Raben, N AF Becker, J Adams, E Plotz, P Raben, N TI The African origin of the common mutation in African American patients with glycogen storage disease type II (GSD II) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIAMS,ARB,NIH,BETHESDA,MD. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7266 EP 7266 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100359 ER PT J AU Li, X Jones, M Shiota, T Delabays, A Yamada, I Pandian, NG Sahn, DJ AF Li, X Jones, M Shiota, T Delabays, A Yamada, I Pandian, NG Sahn, DJ TI Direct calculation of 3D flow convergence surface area from 3D color Doppler flow maps for computing aortic regurgitant flows: A chronic animal study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,LAMS,BETHESDA,MD 20892. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7306 EP 7306 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100738 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Increased contribution of endogenous endothelin to the regulation of vascular tone in essential hypertension SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7411 EP 7411 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100799 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI A localized defect in the phosphoinositol pathway may explain the impaired endothelial nitric oxide activity in hypertensive patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7416 EP 7416 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100804 ER PT J AU Prasad, A Husain, S Mincemoyer, R Hathaway, L Quyyumi, AA AF Prasad, A Husain, S Mincemoyer, R Hathaway, L Quyyumi, AA TI Converting enzyme inhibition improves endothelial dysfunction in humans by increasing nitric oxide activity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7432 EP 7432 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100812 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Racial differences in nitric oxide-mediated response to mental stress in the forearm circulation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7433 EP 7433 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100813 ER PT J AU Kumar, A Zhang, J Ferrans, VJ Horiba, K Fricker, FJ Wallace, MR AF Kumar, A Zhang, J Ferrans, VJ Horiba, K Fricker, FJ Wallace, MR TI Desmin related familial restrictive cardiomyopathy: Clinical observations in a large kindred SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. UNIV FLORIDA,GAINESVILLE,FL. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 1997 VL 29 IS 2 SU A BP 7441 EP 7441 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100817 ER PT J AU Shandas, R Jones, M Chikada, M Kwon, J Knudson, O ValdesCruz, L AF Shandas, R Jones, M Chikada, M Kwon, J Knudson, O ValdesCruz, L TI Three dimensional flow reconstruction of irregular stenotic mitral bioprostheses: In vitro and animal studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 CHILDRENS HOSP,DENVER,CO 80218. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7841 EP 7841 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101585 ER PT J AU Koh, KK Mincemoyer, R Bui, M Csako, G Pucino, F Cannon, RO AF Koh, KK Mincemoyer, R Bui, M Csako, G Pucino, F Cannon, RO TI Improved fibrinolytic profile by estrogen in postmenopausal women: Endothelium versus liver SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7851 EP 7851 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101591 ER PT J AU Guetta, V Quyyumi, AA Prasad, A Panza, JA Cannon, RO AF Guetta, V Quyyumi, AA Prasad, A Panza, JA Cannon, RO TI Contribution of nitric oxide to coronary vasodilation by estrogen in postmenopausal women SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 7853 EP 7853 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101593 ER PT J AU AbdulNour, K Srinivasan, G Davis, CM Bacharach, SL Quyyumi, AA Dilsizian, V AF AbdulNour, K Srinivasan, G Davis, CM Bacharach, SL Quyyumi, AA Dilsizian, V TI Relation between regional contraction and perfusion during stress and 15 to 45 minutes after stress in ischemic and nonischemic myocardial regions SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 26113 EP 26113 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101469 ER PT J AU Lazarous, DF Shou, M Stiber, JA Thirumurti, V Hodge, E Unger, EF AF Lazarous, DF Shou, M Stiber, JA Thirumurti, V Hodge, E Unger, EF TI Adenoviral-mediated gene therapy induces sustained intrapericardial vascular endothelial growth factor expression in dogs: Effect on myocardial angiogenesis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 41148 EP 41148 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100514 ER PT J AU Srinivasan, G Bacharach, SL Kitsiou, AN Nour, KA Davis, CM Dilsizian, V AF Srinivasan, G Bacharach, SL Kitsiou, AN Nour, KA Davis, CM Dilsizian, V TI Delayed FDG imaging improves myocardial/blood pool contrast SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 47146 EP 47146 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101869 ER PT J AU Kitsiou, AN Bacharach, SL Davis, CM Srinivasan, G Nour, KA Quyyumi, AA Dilsizian, V AF Kitsiou, AN Bacharach, SL Davis, CM Srinivasan, G Nour, KA Quyyumi, AA Dilsizian, V TI Myocardial blood flow changes during low dose dobutamine infusion: Relation to F-18 deoxyglucose uptake SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 47148 EP 47148 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101871 ER PT J AU Andrews, NP Husain, S Prasad, A Husain, M Mincemoyer, R Panza, JA Cannon, RO Quyyumi, AA AF Andrews, NP Husain, S Prasad, A Husain, M Mincemoyer, R Panza, JA Cannon, RO Quyyumi, AA TI N-acetylcysteine improves coronary vascular endothelial dysfunction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 52133 EP 52133 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101903 ER PT J AU Shou, M Lazarous, DF Stiber, JA Thirumurti, V Hodge, E Unger, EF AF Shou, M Lazarous, DF Stiber, JA Thirumurti, V Hodge, E Unger, EF TI The pericardium as a repository for an angiogenic growth factor: Effect of intrapericardial basic fibroblast growth factor on myocardial collateral development SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 61116 EP 61116 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100650 ER PT J AU Fleg, JL OConnor, FC Becker, LC Gerstenblith, G Lakatta, EG AF Fleg, JL OConnor, FC Becker, LC Gerstenblith, G Lakatta, EG TI Cardiac versus peripheral contributions to the age-associated decline in aerobic capacity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 1997 VL 29 IS 2 SU A BP 89104 EP 89104 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101145 ER PT J AU Koh, KK Mincemoyer, R Bui, MN Csako, G Pucino, F Cannon, RO AF Koh, KK Mincemoyer, R Bui, MN Csako, G Pucino, F Cannon, RO TI Effects of hormone therapy on fibrinolytic potential in postmenopausal women SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 91965 EP 91965 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100167 ER PT J AU Lazarous, DF Shou, M Stiber, JA Dadhania, D Thirumurti, V Hodge, E Unger, EF AF Lazarous, DF Shou, M Stiber, JA Dadhania, D Thirumurti, V Hodge, E Unger, EF TI Pharmacodynamics of basic fibroblast growth factor: Effect of route of administration on regional distribution SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 95946 EP 95946 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100639 ER PT J AU Vossoughi, J Hong, MK Mintz, GS Kauffman, RD Hoyt, RF Leon, MB Hoeg, JM AF Vossoughi, J Hong, MK Mintz, GS Kauffman, RD Hoyt, RF Leon, MB Hoeg, JM TI Aortic cholesterol content in LDL-receptor deficiency rabbits correlates with vascular biomechanical parameters ex vivo prior to detectable change in vivo SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 WASHINGTON HOSP CTR,WASHINGTON,DC 20010. NIH,BETHESDA,MD 20892. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1997 VL 29 IS 2 SU A BP 96486 EP 96486 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76100675 ER PT J AU Nagai, Y Metter, EJ Earley, CJ Kemper, MK Lakatta, EG Fleg, JL AF Nagai, Y Metter, EJ Earley, CJ Kemper, MK Lakatta, EG Fleg, JL TI Increased intimal-medial thickness (IMT) of the common carotid artery (CCA) in asymptomatic volunteers with a positive exercise ECG SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 1997 VL 29 IS 2 SU A BP 99762 EP 99762 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF761 UT WOS:A1997WF76101229 ER PT J AU Slavkin, HC AF Slavkin, HC TI Charles Darwin and the foundations of clinical genetics in dentistry 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 2 Z9 2 U1 0 U2 2 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 FEB PY 1997 VL 128 IS 2 BP 241 EP 245 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WG316 UT WOS:A1997WG31600031 PM 9037982 ER PT J AU Harris, TB Kiel, D Roubenoff, R Langlois, J Hannan, M Havlik, R Wilson, P AF Harris, TB Kiel, D Roubenoff, R Langlois, J Hannan, M Havlik, R Wilson, P TI Association of insulin-like growth factor-I with body composition, weight history, and past health behaviors in the very old: The framingham heart study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID SOMATOMEDIN-C; PHYSICAL-ACTIVITY; HORMONE; MEN; AGE; POPULATION; INDICATOR AB OBJECTIVES: We examined correlates of insulin-like growth factor-I (IGF-I), an indicator of growth hormone levels, to identify factors associated with higher levels of IGF-I in old age. DESIGN: Nested study of cross-sectional correlates and early-life predictors of IGF-I level. SETTING: A longitudinal cohort study, the Framingham Heart Study. PARTICIPANTS: A total of 790 men and women (mean age 78.5, range 72-94), who had weight, waist and hip circumferences measured at the time of IGF-I measurement. MEASUREMENTS: Association of IGF-I with weight, fat distribution, functional status, nutritional indicators, and past health behaviors was assessed. We also examined IGF-I in relation to body composition derived from dual energy X-ray absorptiometry. RESULTS: ICE-I levels declined with age in both men and women. However, low IGF-I did not show expected associations with low lean mass and increased body fat. Current functional status and grip strength were not associated with IGF-I. Low IGF-I was associated with weight loss in men; the strongest associations were with indicators of poorer nutritional status in both men and women. Levels of IGF-I in old age did not vary by past health behaviors. CONCLUSION: Although IGF-I declined with age, these data from the Framingham Heart Study did not show expected cross-sectional associations of weight, body fat, and lean mass. The strongest associations were between IGF-I and nutritional indicators. These results suggest caution may be warranted with regard to use of IGF-I as an indicator of growth hormone. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HEBREW REHABIL CTR AGED,RES & TRAINING INST,BOSTON,MA 02131. TUFTS UNIV,SCH MED,USDA,HUMAN NUTR CTR AGING,BOSTON,MA 02111. BOSTON UNIV,SCH MED,BOSTON,MA 02118. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. RP Harris, TB (reprint author), NIA,DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,ROOM 3C-309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. OI Hannan, Marian/0000-0002-9586-6928; Kiel, Douglas/0000-0001-8474-0310 NR 25 TC 62 Z9 62 U1 0 U2 3 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 FEB PY 1997 VL 45 IS 2 BP 133 EP 139 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WG194 UT WOS:A1997WG19400001 PM 9033509 ER PT J AU Toto, RD Kirk, KA Coresh, J Jones, C Appel, L Wright, J Campese, V Olutade, B Agodoa, L AF Toto, RD Kirk, KA Coresh, J Jones, C Appel, L Wright, J Campese, V Olutade, B Agodoa, L TI Evaluation of serum creatinine for estimating glomerular filtration rate in African Americans with hypertensive nephrosclerosis: Results from the African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; RACIAL-DIFFERENCES; CLEARANCE; PREDICTION; FAILURE; ESRD AB Measurement of GFR is considered the standard for estimating renal function. However, standardized accurate GFR methodology is expensive and cumbersome; therefore, estimates of GFR based on serum creatinine concentration have been employed. The purpose of the study presented here was to assess the accuracy and precision of using serum creatinine measurements to estimate GFR in the screenee cohort of The African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study. GFR was estimated by four methods: 100/serum creatinine, Cockcroft-Gault equation, creatinine clearance from 24-h urine collection, and a new regression equation derived from the pilot study data. These methods were compared with renal clearance of I-125-iothalamate GFR (GFR1) in 193 hypertensive (diastolic blood pressure greater than or equal to 95 mm Hg) African-American screenees (142 men, 51 women). A second GFR (GFR2) was performed in 98 screenees who were eligible (GFR1 25-70 mL/min per 1.73 m(2)) for the pilot study. Accuracy was assessed by the difference of I-125-iothalamate GFR-estimated GFR (Delta GFR), and precision was estimated from the combined root mean squared error (CRMSE) and the coefficient of determination (r(2)) The results for accuracy (+/- SD) and precision were as follows: (1)100/Scr, Delta GFR = -0.76 +/- 16.5, CRMSE = 16.5, r(2) = 0.69; (2) Cockcroft- Gault, Delta GFR = 9.56 +/- 14.9, CRMSE = 17.7, r(2) = 0.66; 3) 24-h creatinine clearance, Delta GFR = 0.79 +/-i 20.7, CRMSE = 20.7, r(2) = 0.49; 4) New equation Delta GFR = -0.08 +/- 12.8, CRMSE 12.7, r(2) = 0.75. In comparison, a second GFR (GFR2, N = 98) had Delta GFR = 1.36 +/- 8.48, CRMSE 8.6, r(2) = 0.75. Estimates based on 100/SCr and the new equation were the most precise. It was concluded that GFR estimated by serum creatinine is superior to outpatient 24-h urine creatinine clearance in this population. Serum creatinine values can be used to provide a reasonably accurate estimate of GFR in hypertensive African Americans. C1 UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. JOHNS HOPKINS UNIV,SCH MED,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV SO CALIF,MED CTR,LOS ANGELES,CA. EMORY UNIV,ATLANTA,GA 30322. NIDDK,BETHESDA,MD. RP Toto, RD (reprint author), UNIV TEXAS,SW MED CTR,DEPT MED,DALLAS,TX 75235, USA. FU NCRR NIH HHS [M01-RR00633]; NIDDK NIH HHS [DK45386-02] NR 30 TC 64 Z9 69 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1997 VL 8 IS 2 BP 279 EP 287 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA WJ553 UT WOS:A1997WJ55300013 PM 9048347 ER PT J AU Lidl, GM Jernigan, AD Haibel, GK AF Lidl, GM Jernigan, AD Haibel, GK TI Selected pharmacokinetics of theophylline ethylenediamine in pre-term and term goat kids SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID DRUG-METABOLIZING-ENZYMES; MATURATIONAL DEVELOPMENT C1 OHIO STATE UNIV,COLL VET MED,DEPT PHYSIOL & PHARMACOL,COLUMBUS,OH 43210. OHIO STATE UNIV,COLL VET MED,DEPT CLIN SCI,COLUMBUS,OH 43210. RP Lidl, GM (reprint author), NCI,OFF LAB ANIM SCI,NIH,BETHESDA,MD 20892, USA. NR 15 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD FEB PY 1997 VL 20 IS 1 BP 69 EP 72 DI 10.1046/j.1365-2885.1997.00805.x PG 4 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA WG578 UT WOS:A1997WG57800010 PM 9049952 ER PT J AU Mahieux, R Ibrahim, F Mauclere, P Herve, V Michel, P Tekaia, F Chappey, C Garin, B VanderRyst, E Guillemain, B Ledru, E Delaporte, E DeThe, G Gessain, A AF Mahieux, R Ibrahim, F Mauclere, P Herve, V Michel, P Tekaia, F Chappey, C Garin, B VanderRyst, E Guillemain, B Ledru, E Delaporte, E DeThe, G Gessain, A TI Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV-1) strains: Identification of a new and distinct HTLV-1 molecular subtype in central Africa and in pygmies SO JOURNAL OF VIROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; COMPLETE NUCLEOTIDE-SEQUENCE; PAPUA-NEW-GUINEA; LONG TERMINAL REPEAT; OPEN READING FRAME; LYMPHOTROPIC VIRUS; PHYLOGENETIC ANALYSES; I INFECTION; GEOGRAPHICAL SUBTYPES; HUMAN-POPULATIONS AB To gain new insights on the origin, evolution, and modes of dissemination of human T-cell leukemia virus type 1 (HTLV-1), we performed a molecular analysis of 58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4 from South Africa) originating from 13 countries. Of particular interest were eight strains from Pygmies of remote areas of Cameroon and the Central African Republic (CAR), considered to be the oldest inhabitants of these regions. Eight long-term activated T-cell lines producing HTLV-1 gag and env antigens were established from peripheral blood mononuclear cell cultures of HTLV-1 seropositive individuals, including three from Pygmies. A fragment of the env gene encompassing most of the gp21 transmembrane legion was sequenced for the 58 new strains, while the complete long terminal repeat (LTR) region was sequenced for 9 strains, including 4 from Pygmies. Comparative sequence analyses and phylogenetic studies performed on both the env and LTR regions by the neighbor-joining and DNA parsimony methods demonstrated that all 22 strains from West and South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1 subtype A). Within or alongside the previously described Zairian cluster (HTLV-1 subtype B), we discovered a number of new HTLV-1 variants forming different subgroups corresponding mainly to the geographical origins of the infected persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy strains clustered together within this Central African subtype, suggesting a common origin. Furthermore, three new strains (two originating from Pygmies from Cameroon and the CAR, respectively, and one from a Gabonese individual) were particularly divergent and formed a distinct new phylogenetic cluster, characterized by specific mutations and occupying in most analyses a unique phylogenetic position between the large Central African genotype (HTLV 1 subtype B) and the Melanesian subtype (HTLV-1 subtype C). We have tentatively named this new HTLV 1 genotype HTLV-1 subtype D. While the HTLV-1 subtype D strains were not closely related to any known African strain of simian T-cell leukemia virus type 1 (STLV-1), other Pygmy strains and some of the new Cameroonian and Gabonese HTLV-1 strains were very similar (>98% nucleotide identity) to chimpanzee STLV-1 strains, reinforcing the hypothesis of interspecies transmission between humans and monkeys in Central Africa. C1 INST PASTEUR,UNITE EPIDEMIOL VIRUS ONCOGENES,F-75724 PARIS 15,FRANCE. INST PASTEUR,UNITE GENET MOL LEVURES,PARIS,FRANCE. HOP CLAUDE BERNARD,INSERM,U13,PARIS,FRANCE. INSERM,U328,BORDEAUX,FRANCE. CTR PASTEUR CAMEROUN,YAOUNDE,CAMEROON. INST PASTEUR,BANGUI,CENT AFR REPUBL. INST PASTEUR,DAKAR,SENEGAL. NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. UNIV ORANGE FREE STATE,DEPT MED VIROL,BLOEMFONTEIN,SOUTH AFRICA. CTR MURAZ,BOBO DIOULASSO,BURKINA FASO. RI Tekaia, Fredj/H-4553-2012 NR 87 TC 105 Z9 108 U1 0 U2 3 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 FEB PY 1997 VL 71 IS 2 BP 1317 EP 1333 PG 17 WC Virology SC Virology GA WC305 UT WOS:A1997WC30500056 PM 8995656 ER PT J AU Williams, RK Straus, SE AF Williams, RK Straus, SE TI Specificity and affinity of binding of herpes simplex virus type 2 glycoprotein B to glycosaminoglycans SO JOURNAL OF VIROLOGY LA English DT Article ID SURFACE-PLASMON RESONANCE; HEPARAN-SULFATE; CELLULAR RECEPTOR; INITIAL INTERACTION; CELLS; ADSORPTION; IDENTIFICATION; INFECTION; GB; PROTEOGLYCANS AB Herpes simplex virus type 2 (HSV-2) interacts with cell surface glycosaminoglycans during virus attachment. Glycoprotein B of HSV-2 can potentially mediate the interaction between the virion and cell surface glycosaminoglycans. To determine the specificity, kinetics, and affinity of these interactions, we used plasmon resonance-based biosensor technology to measure HSV-2 glycoprotein binding to glycosaminoglycans in real time. The recombinant soluble ectodomain of HSV-2 gB (gB2) but not the soluble ectodomain of HSV-2 gD bound readily to biosensor surfaces coated with heparin. The affinity constants (K(d)s) were determined for gB2 (K-d = 7.7 x 10(-7) M) and for gB2 Delta TM (K-d = 9.9 x 10(-7) M), a recombinant soluble form of HSV-2 gB in which only its transmembrane domain has been deleted. gB2 binding to the heparin surface was competitively inhibited by low concentrations of heparin (50% effective dose [ED(50)] = 0.08 mu g/ml). Heparan sulfate and dermatan sulfate glycosaminoglycans have each been suggested as cell surface receptors for HSV. Our biosensor analyses showed that both heparan sulfate and dermatan sulfate inhibited gB2 binding (ED(50) = 1 to 5 mu g/ml), indicating that gB2 interacts with both heparin-like and dermatan sulfate glycosaminoglycans. Chondroitin sulfate A, in contrast, inhibited gB2 binding to heparin only at high levels (ED(50) = 65 mu g/ml). The affinity and specificity of gB2 binding to glycosaminoglycans demonstrated in these studies support its role in the initial binding of HSV-2 to cells bearing heparan sulfate or dermatan sulfate glycosaminoglycans. RP Williams, RK (reprint author), NIAID,MED VIROL SECT,CLIN INVEST LAB,NIH,9000 ROCKVILLE PIKE,BLDG 10,RM 11N228,MSC 1888,BETHESDA,MD 20892, USA. NR 31 TC 43 Z9 43 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 FEB PY 1997 VL 71 IS 2 BP 1375 EP 1380 PG 6 WC Virology SC Virology GA WC305 UT WOS:A1997WC30500062 PM 8995662 ER PT J AU Hirsch, V AdgerJohnson, D Campbell, B Goldstein, S Brown, C Elkins, WR Montefiori, DC AF Hirsch, V AdgerJohnson, D Campbell, B Goldstein, S Brown, C Elkins, WR Montefiori, DC TI A molecularly cloned, pathogenic, neutralization-resistant simian immunodeficiency virus, SIVsmE543-3 SO JOURNAL OF VIROLOGY LA English DT Article ID MACROPHAGE-TROPIC VARIANTS; RHESUS-MONKEYS; MONOCLONAL-ANTIBODIES; SYNCYTIUM FORMATION; SEQUENCE VARIATION; TYPE-1 CLONES; CELL TROPISM; SOLUBLE CD4; INFECTION; AIDS AB An infectious molecular clone of simian immunodeficiency virus SIVsm was derived from a biological isolate obtained late in disease from an immunodeficient rhesus macaque (E543) with SIV-induced encephalitis. The molecularly cloned virus, SIVsmE543-3, replicated well in macaque peripheral blood mononuclear cells and monocyte-derived macrophages and resisted neutralization by heterologous sera which broadly neutralized genetically diverse SIV variants in vitro. SIVsmE543-3 was infectious and induced AIDS when inoculated intravenously into pig tailed macaques (Macaca nemestrina). Two of four infected macaques developed no measurable SIV-specific antibody and succumbed to a wasting syndrome and SIV-induced meningoencephalitis by 14 and 33 weeks postinfection. The other two macaques developed antibodies reactive in Western blot and virus neutralization assays. One macaque was sacrificed at 1 year postinoculation, and the survivor has evidence of immunodeficiency, characterized by persistently low CD4 lymphocyte subsets in the peripheral blood. Plasma samples from these latter animals neutralized SIVsmE543-3 but with much lower efficiency than neutralization of other related SIV strains, confirming the difficulty by which this molecularly cloned virus is neutralized in vitro. SIVsmE543-3 will provide a valuable reagent for studying SIV-induced encephalitis, mapping determinants of neutralization, and determining the in vivo significance of resistance to neutralization in vitro. C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. RP Hirsch, V (reprint author), NIAID,IMMUNODEFICIENCY VIRUSES SECT,INFECT DIS LAB,TWINBROOK FACIL 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. FU NCPDCID CDC HHS [NCI-6S-1649] NR 68 TC 103 Z9 103 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 FEB PY 1997 VL 71 IS 2 BP 1608 EP 1620 PG 13 WC Virology SC Virology GA WC305 UT WOS:A1997WC30500088 PM 8995688 ER PT J AU Ellenberg, SS Rida, WN AF Ellenberg, SS Rida, WN TI HIV vaccines SO LANCET LA English DT Letter C1 NIAID,DIV AIDS,BETHESDA,MD 20892. RP Ellenberg, SS (reprint author), US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852, USA. NR 2 TC 0 Z9 0 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 FEB 1 PY 1997 VL 349 IS 9048 BP 361 EP 361 DI 10.1016/S0140-6736(05)62865-6 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WF794 UT WOS:A1997WF79400063 PM 9024406 ER PT J AU Ye, FQ Mattay, VS Jezzard, P Frank, JA Weinberger, DR McLaughlin, AC AF Ye, FQ Mattay, VS Jezzard, P Frank, JA Weinberger, DR McLaughlin, AC TI Correction for vascular artifacts in cerebral blood flow values measured by using arterial spin tagging techniques SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood flow; perfusion; human; magnetic resonance imaging (MRI) ID POSITRON EMISSION TOMOGRAPHY; BRAIN PERFUSION; WATER; SATURATION; INVERSION; O-15 AB ''Vascular'' artifacts can have substantial effects on human cerebral blood flow values calculated by using arterial spin tagging approaches. One vascular artifact arises from the contribution of ''tagged'' arterial water spins to the observed change in brain water MR signal. This artifact can be reduced a large bipolar gradients are used to ''crush'' the MR signal from moving arterial water spins. A second vascular artifact arises from relaxation of ''tagged'' arterial blood during transit from the tagging plane to the capillary exchange site in the imaging slice. This artifact can be corrected if the arterial transit times are measured by using ''dynamic'' spin tagging approaches. The mean transit time from the tagging plane to capillary exchange sites in a gray matter region of interest was calculated to be similar to 0.94 s. Cerebral blood flow values calculated for seven normal volunteers agree reasonably well with values calculated by using radioactive tracer approaches. C1 NIMH, CLIN BRAIN DISORDERS BRANCH, NIH, BETHESDA, MD 20892 USA. NIMH, PSYCHOL & PSYCHOPATHOL LAB, NIH, BETHESDA, MD 20892 USA. NIH, OIR, LAB DIAGNOST RADIOL RES, BETHESDA, MD 20892 USA. OI Jezzard, Peter/0000-0001-7912-2251 NR 29 TC 216 Z9 218 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 1997 VL 37 IS 2 BP 226 EP 235 DI 10.1002/mrm.1910370215 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD272 UT WOS:A1997WD27200011 PM 9001147 ER PT J AU Mattiello, J Basser, PJ LeBihan, D AF Mattiello, J Basser, PJ LeBihan, D TI The b matrix in diffusion tensor echo-planar imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; b matrix; EPI; diffusion tensor ID SPIN-ECHO; NMR; COEFFICIENTS; SPECTROSCOPY; WATER AB In diffusion tensor imaging (DTI) an effective diffusion tensor in each voxel is measured by using a set of diffusion-weighted images (DWIs) in which diffusion gradients are applied in a multiplicity of oblique directions. However, to estimate the diffusion tensor accurately, one must account for the effects of all imaging and diffusion gradient pulses on each signal echo, which are embodied in the b matrix. For DTI to be practical clinically, one must also acquire DWIs rapidly and free of motion artifacts, which is now possible with diffusion-weighted echo-planar imaging (DW-EPI). An analytical expression for the b matrix of a general DW-EPI pulse sequence is presented and then validated experimentally by measuring the diffusion tensor in an isotropic phantom whose diffusivity is already known. The b matrix is written in a convenient tabular form as a sum of individual pair-wise contributions arising from gradient pulses applied along parallel and perpendicular directions. While the contributions from readout and phase-encode gradient pulse trains are predicted to have a negligible effect on the echo, the contributions from other imaging and diffusion gradient pulses applied in both parallel and orthogonal directions are shown to be significant in our sequence. in general, one must understand and account for the multiplicity of interactions between gradient pulses and the echo signal to ensure that diffusion tensor imaging is quantitative. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RI Basser, Peter/H-5477-2011 NR 32 TC 145 Z9 148 U1 2 U2 25 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1997 VL 37 IS 2 BP 292 EP 300 DI 10.1002/mrm.1910370226 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD272 UT WOS:A1997WD27200021 PM 9001155 ER PT J AU Pratt, RG Zheng, J Stewart, BK Shiferaw, Y McGoron, AJ Samaratunga, RC Thomas, SR AF Pratt, RG Zheng, J Stewart, BK Shiferaw, Y McGoron, AJ Samaratunga, RC Thomas, SR TI Application of a 3D volume F-19 MR imaging protocol for mapping oxygen tension (pO(2)) in perfluorocarbons at low field SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fluorine-19 magnetic resonance imaging; volume acquisition; oxygen imaging; spectral deconvolution ID MAGNETIC-RESONANCE SPECTROSCOPY; CHEMICAL-SHIFT; NMR; RELAXATION; TISSUES; BLOOD AB A limited flip angle gradient-echo 3D volume acquisition imaging protocol for mapping partial pressure of oxygen (pO(2)) in perfluorocarbon compounds (PFCs) at tow field (0.14 T) is presented. The pO(2) measurement method is based on the paramagnetic effect of dissolved molecular oxygen (O-2) which reduces the PFC F-19 T-1. Specific objectives related to imaging of PFCs through use of the protocol include improved image signal-to-noise characteristics and elimination of F-19 chemical shift artifacts. A parametric Wiener deconvolution filtering algorithm is used for suppression of F-19 chemical shift artifacts. Application of the protocol is illustrated in a series of calculated pO(2) maps of a gas equilibrated, multi-chamber phantom containing perfluorotributylamine (FC-43). The utility of the protocol is demonstrated in vivo through images of a commercially available perfluorocarbon based blood substitute emulsion containing FC-43 sequestered in the liver and spleen of a rat. C1 UNIV IOWA HOSP & CLIN,DEPT RADIOL,IOWA CITY,IA 52242. UNIV WASHINGTON,DEPT RADIOL,SEATTLE,WA 98195. NIH,IN VITRO NMR RES CTR,CINCINNATI,OH. RP Pratt, RG (reprint author), UNIV CINCINNATI,MED CTR,DEPT RADIOL,DIV MED PHYS,231 BETHESDA AVE,ROOM E560,POB 670579,CINCINNATI,OH 45267, USA. RI McGoron, Anthony/M-4642-2016 OI McGoron, Anthony/0000-0003-3714-4676 FU NHLBI NIH HHS [R01 HL45243] NR 25 TC 11 Z9 11 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1997 VL 37 IS 2 BP 307 EP 313 DI 10.1002/mrm.1910370229 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD272 UT WOS:A1997WD27200023 PM 9001157 ER PT J AU Deng, XN Moran, J Copeland, NG Gilbert, DJ Jenkins, NA Primakoff, P MartinDeLeon, PA AF Deng, XN Moran, J Copeland, NG Gilbert, DJ Jenkins, NA Primakoff, P MartinDeLeon, PA TI The mouse Spam1 maps to proximal chromosome 6 and is a candidate for the sperm dysfunction in Rb(6.16)24Lub and Rb(6.15)1Ald heterozygotes SO MAMMALIAN GENOME LA English DT Article ID GENE; TRANSLOCATION; PROTEIN; PH-20; HYALURONIDASE; SEGREGANTS; SEQUENCES; ADHESION; REGION; EGG AB We have determined the chromosomal localization of the murine gene encoding the 68-kDa sperm adhesion molecule 1, Spam1 or Ph-20. Using two independent approaches, fluorescence in situ hybridization (FISH) and interspecific backcross analysis, we show that Spam1 maps to proximal mouse Chromosome (Chr) 6. This map position is within the conserved linkage group corresponding to human Chr 7q, where the human homolog, SPAM1, has been shown to map previously. Genetic mapping shows the gene to be very closely linked to Met, one of the most proximal loci on MMU 6. It thus places the gene near the centromere and the junction of the Rb(6.16)24Lub and Rb(6.15)1Ald translocations. The essential role of the Spam1 sperm antigen in mouse sperm-egg interactions and its gene location provide strong support for its candidacy as the gene involved in the dysfunction of mouse sperm bearing the Rb(6.16)24Lub or Rb(6.15)1Ald translocation. C1 UNIV DELAWARE,DEPT BIOL,NEWARK,DE 19716. PRINCETON UNIV,DEPT MOL BIOL,PRINCETON,NJ 08544. FREDERICK CANC RES CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD. LAWRENCE LIVERMORE NATL LAB,SECT MOL & CELL BIOL,DAVIS,CA 95616. NR 26 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1997 VL 8 IS 2 BP 94 EP 97 DI 10.1007/s003359900365 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WJ659 UT WOS:A1997WJ65900004 PM 9060406 ER PT J AU Dey, A Ozato, K AF Dey, A Ozato, K TI Genomic footprinting of retinoic acid regulated promoters in embryonal carcinoma cells SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID THYROID-HORMONE RECEPTOR; TRANSCRIPTION FACTOR; RESPONSE ELEMENT; DEPENDENT TRANSACTIVATION; GENE-EXPRESSION; STEM-CELLS; POU-DOMAIN; RXR-BETA; ACTIVATION; BINDING AB Retinoic acid (RA) treatment of embryonal carcinoma (EO) cells initiates a cascade of alterations in gene regulation, leading to their differentiation into various cell types. In P19 EC cells RA treatment stimulates induction of the RAR beta gene, while it represses Oct3/4 gene expression. Here we present dimethyl-sulfate-based genomic footprinting analyses of these,two genes. We found that the RAR beta promoter is not occupied prior to RA treatment, but following RA treatment all regulatory elements in this promoter become occupied. On the other hand, the Oct 3/4 promoter is occupied at all three known elements before RA treatment, but this occupancy is coordinately lost following the treatment. Thus, factor occupancy coincides with expression of the genes. It is likely that the presence of factor binding or its absence revealed here represents a mechanism of the regulated expression of these genes in vivo. Our results demonstrate the power of genomic footprinting for studying regulatory events for transcription in vivo. In contrast, with in vitro protein-DNA binding assay, factors for both promoters are present in these cells regardless of RA treatment. It has been shown that RA receptor (RAR) and retinoid X receptor (RXR), by heterodimerization, mediate the RA action in EC cells. To elucidate the role of RAR/RXR heterodimers in the RAR beta promoter occupancy in vivo, genomic footprinting has been performed in P19 cells stably expressing dominant negative mutants of RXR. Two such mutants, lacking either the DNA binding domain or the C-terminal activation domain, inhibit RA induction of the RAR beta gene in these cells. RA-induced factor occupancy is also markedly inhibited at all elements in the RAR beta promoter in these cells. Our results show that binding of liganded RAR/RXR heterodimers to RARE is required for other factors to gain access to their respective elements in the promoter. (C) 1997 Academic Press. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NR 50 TC 10 Z9 10 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 1046-2023 J9 METHODS JI Methods PD FEB PY 1997 VL 11 IS 2 BP 197 EP 204 DI 10.1006/meth.1996.0406 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT376 UT WOS:A1997XT37600007 PM 8993032 ER PT J AU Fragoso, G Hager, GL AF Fragoso, G Hager, GL TI Analysis of in vivo nucleosome positions by determination of nucleosome-linker boundaries in crosslinked chromatin SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID CORE PARTICLE; IN-VITRO; DNA; FORMALDEHYDE; HISTONE; INVIVO; GENE; ORGANIZATION; POLYMERASE; DIGESTION AB We describe a procedure for the determination of nucleosome boundaries that utilizes single-stranded mononucleosomal DNA obtained from fixed cells as the template in a primer extension assay. The procedure entails treatment of cells with formalde-hyde, a reversible protein-DNA crosslinking agent used with the object of fixing the histone octamers to DNA in vivo, followed by preparation of nucleosomal DNA with micrococcal nuclease, reversal of the crosslinks, and isolation of the mononucleosomal material. Full-length single-stranded mononucleosomal DNA is then prepared and used as a template in a linear amplification primer extension assay. The use of single-stranded DNA templates eliminates interference from nicked DNA present in double-stranded preparations. Because of its reversibility, the use of formaldehyde permits the preparation of DNA suitable as a template in DNA synthesis. We present evidence demonstrating the efficiency of histone-DNA crosslinking and the reversibility of the crosslinking reaction as applied to the regeneration of native DNA, active in DNA synthesis. Use of this methodology removes the impact that mobility of the histone octamer and the presence of nicks on nucleosomal DNA have on the determination of nucleosome boundaries. (C) 1997 Academic Press. C1 NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NR 29 TC 34 Z9 34 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 1046-2023 J9 METHODS JI Methods PD FEB PY 1997 VL 11 IS 2 BP 246 EP 252 DI 10.1006/meth.1996.0411 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT376 UT WOS:A1997XT37600012 PM 8993037 ER PT J AU Cormack, BP Bertram, G Egerton, M Gow, NAR Falkow, S Brown, AJP AF Cormack, BP Bertram, G Egerton, M Gow, NAR Falkow, S Brown, AJP TI Yeast-enhanced green fluorescent protein (yEGFP): A reporter of gene expression in Candida albicans SO MICROBIOLOGY-UK LA English DT Article DE enhanced GFP; green fluorescent protein; Candida albicans; Saccharomyces cerevisiae ID MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; IN-VIVO; CODON; TRANSFORMATION; LOCALIZATION; LEUCINE; CELLS; DNA; VIRULENCE AB The green fluorescent protein (GFP) of Aequorea victoria has been developed here as a reporter for gene expression and protein localization in Candida albicans. When wild-type (wt) GFP was expressed in C. albicans, it was not possible to detect fluorescence or a translation product for the wt protein. Since this was probably due in part to the presence of the non-canonical CTG serine codon in the Aequorea sequence, this codon was changed to the leucine codon TTG. C. albicans cells expressing this construct contained GFP mRNA but were non-fluorescent and contained no detectable translation product. Hence a codon-optimized GFP gene was constructed in which all of the 239 amino acids are encoded by optimal codons for C. albicans. In this gene were also incorporated two previously identified mutations in the chromophore that increase GFP fluorescence. C. albicans cells expressing this yeast-enhanced GFP gene (yEGFP3) are fluorescent and contain GFP protein. yEGFP3 can be used as a versatile reporter of gene expression in C. albicans and Saccharomyces cerevisiae and the optimized GFP described here should have broad applications in these and other fungal species. C1 UNIV ABERDEEN,INST MED SCI,ABERDEEN AB25 2ZD,SCOTLAND. ZENECA PHARMACEUT,MACCLESFIELD SK10 4TG,CHESHIRE,ENGLAND. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RP Cormack, BP (reprint author), STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305, USA. RI Brown , Alistair /B-6627-2014 NR 42 TC 374 Z9 392 U1 1 U2 20 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD FEB PY 1997 VL 143 BP 303 EP 311 PN 2 PG 9 WC Microbiology SC Microbiology GA WH225 UT WOS:A1997WH22500005 PM 9043107 ER PT J AU Samuels, DS Garon, CF AF Samuels, DS Garon, CF TI Oligonucleotide-mediated genetic transformation of Borrelia burgdorferi SO MICROBIOLOGY-UK LA English DT Article DE Lyme disease; Borrelia burgdorferi; oligonucleotide; genetic transformation; electroporation; gyrB ID LYME-DISEASE AGENT; SYNTHETIC OLIGONUCLEOTIDES; PLASMIDS; YEAST; GYRB AB We have used short oligonucleotides to genetically transform the Lyme disease spirochaete Borrelia burgdorferi. The oligonucleotides are derived from the sequence of an Arg-133 to lie mutant gyrB (chromosomal) gene that confers resistance to the antibiotic coumermycin A(1). Oligonucleotides were about 10000-fold less efficient at transformation, on a molar basis, than longer PCR-generated substrates. All of the transformants tested contained the predicted site-directed silent mutation in their gyrB genes. Antisense oligonucleotides were more efficient at transformation than either sense or double-stranded oligonucleotides. This is the first demonstration of oligonucleotides used to introduce site-directed mutations directly into the genome of a bacterium. C1 NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,BACTERIAL PATHOGENESIS SECT,HAMILTON,MT 59840. RP Samuels, DS (reprint author), UNIV MONTANA,DIV BIOL SCI,MISSOULA,MT 59812, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 NR 17 TC 10 Z9 10 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD FEB PY 1997 VL 143 BP 519 EP 522 PN 2 PG 4 WC Microbiology SC Microbiology GA WH225 UT WOS:A1997WH22500029 PM 9043127 ER PT J AU HernandezRivas, R Mattei, D Sterkers, Y Peterson, DS Wellems, TE Scherf, A AF HernandezRivas, R Mattei, D Sterkers, Y Peterson, DS Wellems, TE Scherf, A TI Expressed var genes are found in Plasmodium falciparum subtelomeric regions SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMOSOME SIZE POLYMORPHISMS; INFECTED ERYTHROCYTES; ANTIGENIC VARIATION; AFRICAN TRYPANOSOMES; CONSERVED DOMAINS; SAIMIRI-SCIUREUS; SQUIRREL-MONKEY; MALARIA; DNA; PARASITE AB The antigenic variation and cytoadherence of Plasmodium falciparum-infected erythrocytes are modulated by a family of variant surface proteins encoded by the var multigene family. The var genes occur on multiple chromosomes, often in clusters, and 50 to 150 genes are estimated to be present in the haploid parasite genome. Transcripts from var genes have been previously mapped to internal chromosome positions, but the generality of such assignments and the expression sites and mechanisms that control switches of var gene expression are still in early stages of investigation. Here we describe investigations of closely related var genes that occur in association with repetitive elements near the telomeres of P. falciparum chromosomes. DNA sequence analysis of one of these genes (FCR3-varT11-1) shows the characteristic two-exon structure encoding expected var features, including three variable Duffy binding-like (DBL) domains, a transmembrane sequence, and a carboxy-terminal segment thought to anchor the protein product in knobs at the surface of the parasitized erythrocyte. FCR3-varT11-1 cross-hybridizes with var genes located close to the telomeres of many other P. falciparum chromosomes, including a transcribed gene (FCR3-varT3-1) in chromosome 3 of the P. falciparum FCR3 line. The relatively high level transcription from this gene shows that the polymorphic chromosome ends of P. falciparum, which have been proposed to be transcriptionally silent, can be active expression sites for var genes. The pattern of the FCR3-varT11-1 and FCR3-varT3-1 genes are variable between different P. falciparum lines, presumably due to DNA rearrangements. Thus, recombination events in subtelomeric DNA may have a role in the expression of novel var forms. C1 INST PASTEUR,UNITE PARASITOL EXPT,CNRS URA 1960,F-75724 PARIS,FRANCE. NIH,MALARIA RES LAB,BETHESDA,MD 20892. RI Scherf, Artur/A-9674-2014; Mattei, Denise/B-1088-2014 NR 48 TC 79 Z9 81 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 FEB PY 1997 VL 17 IS 2 BP 604 EP 611 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC879 UT WOS:A1997WC87900009 PM 9001213 ER PT J AU Minucci, S Leid, M Toyama, R SaintJeannet, JP Peterson, VJ Horn, V Ishmael, JE Bhattacharyya, N Dey, A Dawid, IB Ozato, K AF Minucci, S Leid, M Toyama, R SaintJeannet, JP Peterson, VJ Horn, V Ishmael, JE Bhattacharyya, N Dey, A Dawid, IB Ozato, K TI Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYROID-HORMONE RECEPTOR; NUCLEAR RECEPTOR; CONFORMATIONAL-CHANGES; RESPONSE ELEMENT; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; CO-REPRESSOR; BETA-GENE; ACTIVATION; DOMAIN AB Retinoic acid receptor (RAR) and retinoid X receptor (RXR) form heterodimers and regulate retinoid-mediated gene expression. We studied binding of RXR- and RAR-selective ligands to the RXR-RAR hetero dimer and subsequent transcription. In limiter! proteolysis analyses, both RXR and RAR in the heterodimer bound their respective ligands and underwent a conformational change in the presence of a retinoic acid-responsive element. In reporter analyses, the RAR ligand (but not the RXR ligand), when added singly, activated transcription, but coaddition of the two ligands led to synergistic activation of transcription. This activation required the AF-2 domain of both RXR and RAR. Genomic footprinting analysis was performed with P19 embryonal carcinoma cells, in which transcription of the RAR beta gene is induced upon retinoid addition. Paralleling the reporter activation data, only the RAR ligand induced in vivo occupancy of the RAR beta 2 promoter when added singly. However, at suboptimal concentrations of RAR ligand, coaddition of the RXR ligand increased the stability of promoter occupancy. Thus, liganded RXR and RAR both participate in transcription. Finally, when these ligands were tested for teratogenic effects on zebra fish and Xenopus embryos, we found that coadministration of the RXR and RAR ligands caused more severe abnormalities in these embryos than either ligand alone, providing biological support for the synergistic action of the two ligands. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. OREGON STATE UNIV,COLL PHARM,CORVALLIS,OR 97331. RI Minucci, Saverio/J-9669-2012 NR 67 TC 127 Z9 129 U1 0 U2 5 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 FEB PY 1997 VL 17 IS 2 BP 644 EP 655 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC879 UT WOS:A1997WC87900014 PM 9001218 ER PT J AU Jeffers, M Taylor, GA Weidner, KM Omura, S VandeWoude, GF AF Jeffers, M Taylor, GA Weidner, KM Omura, S VandeWoude, GF TI Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; FACTOR BETA-RECEPTOR; LIGAND-INDUCED POLYUBIQUITINATION; C-MET; PROTOONCOGENE PRODUCT; EPITHELIAL-CELLS; FACTOR/SCATTER FACTOR; EXTRACELLULAR DOMAIN; PROTEOLYTIC CLEAVAGE AB The Met tyrosine kinase receptor is a widely expressed molecule which mediates pleiotropic cellular responses following activation by its ligand, hepatocyte growth factor/scatter factor (HGF/SF). In this communication we demonstrate that significant Met degradation is induced by HGF/SF and that this degradation can be blocked by lactacystin, an inhibitor of proteasome activity. We also show that Met is rapidly polyubiquitinated in response to ligand and that polyubiquitinated Met molecules, which are normally unstable, are stabilized by lactacystin. Both HGF/SF-induced degradation and polyubiquitination of Met were shown to be dependent on the receptor possessing intact tyrosine kinase activity. Finally, we found that a normally highly labile 55-kDa fragment of the Met receptor is stabilized by lactacystin and demonstrate that it represents a cell-associated remnant that is generated following the ligand-independent proteolytic cleavage of the Met receptor in its extracellular domain. This truncated Met molecule encompasses the kinase domain of the receptor and is itself tyrosine phosphorylated. We conclude that the ubiquitin-proteasome pathway plays a significant role in the degradation of the Met tyrosine kinase receptor as directed by ligand-dependent and -independent signals. We propose that this proteolytic pathway may be important for averting cellular transformation by desensitizing Met signaling following ligand stimulation and by eliminating potentially oncogenic fragments generated via extracellular cleavage of the Met receptor. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. MAX DELBRUCK CTR MOL MED,D-13125 BERLIN,GERMANY. KITASATO INST,BIOL FUNCT RES CTR,TOKYO 108,JAPAN. NR 68 TC 172 Z9 172 U1 0 U2 0 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 FEB PY 1997 VL 17 IS 2 BP 799 EP 808 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC879 UT WOS:A1997WC87900030 PM 9001234 ER PT J AU Tran, H Degtyareva, N Gordenin, D Resnick, MA AF Tran, H Degtyareva, N Gordenin, D Resnick, MA TI Altered replication and inverted repeats induce mismatch repair-independent recombination between highly diverged DNAs in yeast SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSPOSON TN5 EXCISION; DOUBLE-STRAND BREAKS; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; HOMEOLOGOUS RECOMBINATION; COMPLEX HETERODUPLEXES; SALMONELLA-TYPHIMURIUM; MSH2 PROTEIN; RECA PROTEIN; JUNK DNA AB Replication, DNA organization, and mismatch repair (MMR) can influence recombination. We examined the effects of altered replication due to a mutation in the polymerase delta gene, long inverted repeats (LIRs) in motifs similar to those in higher eukaryotes, and MMR on intrachromosomal recombination between highly diverged (28%) truncated genes in Saccharomyces cerevisiae. A combination of altered replication and an LIR increased recombination up to 700-fold, while each alone led to a 3- to 20-fold increase. Homeologous recombination was not altered by pms1, msh2, and msh3 mismatch repair mutations. Similar to our previous observations for replication slippage-mediated deletions, there were greater than or equal to 5-bp identical runs at the recombination breakpoints. We propose that the dramatic increase in recombination results from enhancement of the effects of altered replication by the LIR, leading to recombinationally active initiating structures. Such interactions predict replication-related, MMR-independent genome changes. C1 NIEHS,MOL GENET LAB,NIH,RES TRIANGLE PK,NC 27709. ST PETERSBURG STATE UNIV,DEPT GENET,ST PETERSBURG 199034,RUSSIA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 59 TC 29 Z9 29 U1 0 U2 0 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 FEB PY 1997 VL 17 IS 2 BP 1027 EP 1036 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC879 UT WOS:A1997WC87900051 PM 9001255 ER PT J AU Howell, R Usdin, K AF Howell, R Usdin, K TI The ability to form intrastrand tetraplexes is an evolutionarily conserved feature of the 3' end of L1 retrotransposons SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE L1 retrotransposons; mammals; tetraplex; evolution ID HUMAN TRANSPOSABLE ELEMENT; DNA-SYNTHESIS; REVERSE TRANSCRIPTION; NUCLEOTIDE-SEQUENCES; RNA; INSERTION; GENE; REQUIREMENTS; MECHANISM; PROTEIN AB Mammalian genomes contain many thousands of members of a family of retrotransposons known as L1 (or LINE-I) elements. These elements lack long terminal repeats (LTRs), and an thought to use a retroposition mechanism that differs from that of retroviruses and other LTR-containing retroelements. In order to define those regions of the L1 element that may be important for L1 retroposition, we examined the 3' untranslated regions (UTRs) of LI elements from a diverse group of mammals. We show that while the 3' UTRs of LI elements from different species share little if any sequence homology, they all contain a G-rich polypurine tract of variable length and sequence which can form one or more intrastrand tetraplexes. This conservation over the 100 Myr since the mammalian radiation suggests that either the G-rich motif itself or a conserved structure such as the tetraplex that can be formed by this motif is a significant structural feature of L1 elements and may play a role in their propagation. C1 NIDDK,SECT GENOM STRUCT & FUNCT,MOL & CELLULAR BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 45 TC 28 Z9 28 U1 0 U2 0 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD FEB PY 1997 VL 14 IS 2 BP 144 EP 155 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA WG123 UT WOS:A1997WG12300003 PM 9029792 ER PT J AU Olafsson, P Soares, HD Herzog, KH Wang, T Morgan, JI Lu, B AF Olafsson, P Soares, HD Herzog, KH Wang, T Morgan, JI Lu, B TI The Ca2+ binding protein, frequenin is a nervous system-specific protein in mouse preferentially localized in neurites SO MOLECULAR BRAIN RESEARCH LA English DT Article DE frequenin; Ca2+-binding protein; hybridization, in situ; immunocytochemistry; synapse; astroglia ID GENE-EXPRESSION; CALCIUM; DROSOPHILA; RECOVERIN; BRAIN; CHICKEN; VISININ; BOVINE; NCS-1; VILIP AB Frequenin is a Ca2+-binding protein that has been implicated in the regulation of neurotransmitter release at the neuromuscular junction [15,16]. However, its cellular and subcellular localization in brain have not been determined. Therefore, we cloned mouse frequenin (Mfreq) and investigated its expression both in vivo and in vitro. The amino acid sequence of Mfreq is homologous to that of frequenins from other species. Northern and Western blot analyses indicated that the Mfreq mRNA is a single species of 4.2 kb, and that the protein has a mass of 24 kDa protein on SDS gel, respectively. Expression of Mfreq is nervous system specific. However, Mfreq mRNA and protein are widely distributed in the brain, spinal cord, and dorsal root ganglia. Mfreq is expressed in early embryonic brain and the levels of Mfreq remain high throughout development. In situ hybridization and immunocytochemistry demonstrated that Mfreq is expressed primarily in neurons and presumptive astrocytes. The Mfreq protein was preferentially localized in neurites (dendrites and axons). Double immunofluorescence microscopy established that Mfreq was co-localized with the dendritic marker, MAP-2 and the synapse marker, SV2 in cultured hippocampal neurons. The distribution and subcellular localization of Mfreq may help understand its cellular function. C1 NICHHD, NIH, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT DEV NEUROBIOL, MEMPHIS, TN 38105 USA. RI Lu, Bai/A-4018-2012 NR 20 TC 47 Z9 47 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 FEB PY 1997 VL 44 IS 1 BP 73 EP 82 DI 10.1016/S0169-328X(96)00188-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA WF402 UT WOS:A1997WF40200009 ER PT J AU Chandrasekaran, K Hatanpaa, K Rapoport, SI Brady, DR AF Chandrasekaran, K Hatanpaa, K Rapoport, SI Brady, DR TI Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex in Alzheimer disease SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Northern blot; mRNA; mitochondria; oxidative phosphorylation; energy metabolism; cerebral cortex; brain; Alzheimer disease ID CYTOCHROME-C-OXIDASE; DIFFERENTIAL EXPRESSION; NEUROFIBRILLARY TANGLES; DEMENTIA; SUBUNITS; REGIONS; BRAIN; IMPAIRMENT; BIOGENESIS; SEQUENCE AB We recently reported 50% decreases in mRNA levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunits I and III in Alzheimer disease (AD) brains. The decreases were observed in an association neocortical region (midtemporal cortex) affected in AD, but not in the primary motor cortex unaffected in AD. To investigate whether the decreases are specific to mtDNA-encoded mRNA, we extended this analysis to nuclear DNA (nDNA)-encoded subunits of mitochondrial enzymes of oxidative phosphorylation (OXPHOS). Brains from five AD patients showed 50-60% decreases in mRNA levels of nDNA-encoded subunit IV of COX and the beta-subunit of the F0F1-ATP synthase in midtemporal cortex compared with mRNA levels from midtemporal cortex of control brains. In contrast, these mRNAs were not reduced in primary motor cortices of the AD brains. The amount of nDNA-encoded beta-actin mRNA and the amount of 28S rRNA were not altered in either region of the AD brain. The results suggest that coordinated decreases in expression of mitochondrial and nuclear genes occur in association cortex of AD brains and are a consequence of reduced neuronal activity and downregulation of OXPHOS machinery. RP Chandrasekaran, K (reprint author), NIA,NIH,LNS,BLDG 10,RM 6C 103,BETHESDA,MD 20892, USA. NR 34 TC 40 Z9 40 U1 2 U2 3 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 FEB PY 1997 VL 44 IS 1 BP 99 EP 104 DI 10.1016/S0169-328X(96)00191-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA WF402 UT WOS:A1997WF40200012 ER PT J AU Chernak, JM Hoffman, PW Minowa, T Mouradian, MM Roth, GS AF Chernak, JM Hoffman, PW Minowa, T Mouradian, MM Roth, GS TI Interaction of nuclear factors from young and old rat brain regions with regulatory sequences of the D-2 dopamine receptor gene promoter SO MOLECULAR BRAIN RESEARCH LA English DT Article DE transcription; DNA-protein interaction; aging; neurodegenerative disease; Parkinson's; Huntington's; motor control; striatum ID MESSENGER-RNA; HUNTINGTONS-DISEASE; WISTAR RATS; BINDING; AGE; TRANSCRIPTION; RECOVERY; PROTEIN; MECHANISMS; STRIATUM AB Alterations in the number or functional state of D-2 dopamine receptors have been implicated in the decreased motor abilities associated with normal aging, Parkinson's disease and other neurodegenerative diseases. Previous work has demonstrated a substantial decrease in D-2 receptor-containing neurons, receptor proteins, steady-state mRNA levels, and the rate of mRNA synthesis with age in the rat striatum in particular and in mammalian brains in general. These observations suggest that one key area of regulatory control is at the level of transcriptional initiation and/or elongation. In the present study gel mobility shift experiments were used to assess the interaction of nuclear proteins from different rat brain regions with DNA containing putative DNA regulatory sites of the transcriptionally active rat D-2 receptor gene promoter. Oligonucleotides containing either of the two SP1 binding sites immediately upstream of the primary transcriptional start site were bound by proteins found in nuclear extracts obtained from rat striatum, hippocampus, cortex, and cerebellum. Extracts from striatum and hippocampus formed predominantly low molecular weight complexes which do not contain SP1, as well as a small amount of high molecular weight complexes which may contain SP1 or an SP1-related protein. Cerebellar extracts formed two similar sets of complexes, but they were formed in roughly equal amounts. Extracts from cortex produced a more involved pattern of complexes, but still formed both high molecular weight complexes which contain SP1 and low molecular weight complexes which do not contain SP1. There were differences in the gel mobility as well as the relative amounts of complexes formed with the two SP1-specific oligonucleotides among different brain regions. With respect to possible age-related changes in transcription of the D-2 dopamine receptor gene, there appeared to be no statistically significant difference in the DNA-protein complexes formed with striatal nuclear proteins from a population of young rats versus a population of old rats. C1 NINCDS,GENET PHARMACOL UNIT,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. RP Chernak, JM (reprint author), NIA,MOL PHYSIOL & GENET SECT,CELLULAR & MOL BIOL LAB,NIH,JOHNS HOPKINS BAYVIEW RES CAMPUS,BALTIMORE,MD 21224, USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 37 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1997 VL 44 IS 1 BP 113 EP 124 DI 10.1016/S0169-328X(96)00197-0 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WF402 UT WOS:A1997WF40200014 ER PT J AU Cardinali, M Kratochvil, FJ Ensley, JF Robbins, KC Yeudall, WA AF Cardinali, M Kratochvil, FJ Ensley, JF Robbins, KC Yeudall, WA TI Functional characterization in vivo of mutant p53 molecules derived from squamous cell carcinomas of the head and neck SO MOLECULAR CARCINOGENESIS LA English DT Article DE p53; squamous cell carcinoma; cell transformation; tumor suppressor; angiogenesis; metastasis ID WILD-TYPE P53; TUMOR-SUPPRESSOR GENE; DNA-BINDING; MUTATIONS; CANCER; PROTEIN; EXPRESSION; LINES; METASTASIS; TRANSFORMATION AB Loss of wild-type p53, either through deletion or mutation, has been demonstrated in most squamous cell carcinomas of the head and neck (HNSCC). Whether these mutant molecules contribute to tumor progression purely through loss of wild-type functions or by growth-promoting mechanisms, however, remains unclear. To begin to address these issues, we isolated a series of p53 cDNAs from HNSCC cell lines that contain missense or nonsense point mutations, insertions, or deletions. The ability of each of these molecules to transform NIH/3T3 cells to a malignant phenotype was assessed by stable transfection and expression under the control of a strong heterologous promoter. NIH/3T3 cells transfected with pLTR6p53, which harbors an H179L missense mutation, formed large tumors rapidly (in less than 4 wk) when transplanted to athymic mice, as did cells expressing pLTR13p53, which had undergone a V173F missense mutation and an in-frame deletion of 48 bp between codons 208 and 223. Cells transfected with pLTR17p53, predicted from the nucleotide sequence to encode a severely truncated p53 corresponding to the N-terminal 56 amino acids, also formed tumors. Cells transfected with pLTR15p53, which was predicted to encode a less severely truncated molecule, formed much smaller tumors and at lower frequencies. NIH/3T3 cells transfected with pLTR12p53 (exon 7 splice donor mutant), pLTRwtp53 (wild-type p53), or vector alone failed to form tumors for up to 2 mo after transplantation. pLTR6p53-transfected cells exhibited a highly malignant phenotype with invasion of regional lymph nodes, mediastinal and lung metastases, invasion of the abdominal wall, and dissemination throughout the peritoneal cavity. Histological asssessment of the tumors revealed intensely vascularized fibrosarcomas with numerous cellular atypia, including frequent and aberrant mitoses. Tumor explants were recultured, and northern blot analysis of cellular RNA confirmed that the expression of exogenous p53 was maintained in each case. These data indicate that different p53 mutants contribute to tumorigenesis by specific mechanisms. Furthermore, the results obtained by using the pLTR17p53 transfectants imply that some truncated molecules may overcome the effects of wild-type p53 to contribute to malignancy. (C) 1997 Wiley-Liss, Inc. C1 NIDR,MOL & CELLULAR BIOL SECT,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. NATL NAVAL DENT CTR,DEPT ORAL PATHOL,BETHESDA,MD. WAYNE STATE UNIV,DIV HEMATOL ONCOL,DETROIT,MI. NIDR,MOL CARCINOGENESIS GRP,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. NR 70 TC 19 Z9 19 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 FEB PY 1997 VL 18 IS 2 BP 78 EP 88 DI 10.1002/(SICI)1098-2744(199702)18:2<78::AID-MC3>3.0.CO;2-M PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA WL325 UT WOS:A1997WL32500003 PM 9049183 ER PT J AU Yeudall, WA Jakus, J Ensley, JF Robbins, KC AF Yeudall, WA Jakus, J Ensley, JF Robbins, KC TI Functional characterization of p53 molecules expressed in human squamous cell carcinomas of the head and neck SO MOLECULAR CARCINOGENESIS LA English DT Article DE p53; squamous cell carcinoma; oral cancer; gene mutation; transcription; transactivation ID WILD-TYPE P53; NASOPHARYNGEAL CARCINOMA; GENE-MUTATIONS; LINES; CANCER; MUTANTS; TUMORS; TRANSFORMATION; OVEREXPRESSION; TRANSCRIPTION AB Mutation of the p53 tumor suppressor gene has been demonstrated in a large proportion of human head and neck squamous cell carcinomas (HNSCCs) and has been assumed to play a role in the pathogenesis of these tumors, although no formal evidence of functional aberration has been demonstrated. In this study, we isolated cDNA clones encoding the entire p53 coding region from six human HNSCC cell lines that showed aberrant patterns of p53 expression in the parental cells, analyzed their nucleotide sequences, and characterized their function in vivo. cDNAs cloned from four cell lines harbored alterations within the p53 coding sequence (one missense mutation, one missense mutation plus in-frame deletion, one splice donor mutation, and a l-nt insertion). HN30 cells, which contained wild-type p53 nucleotide sequences, showed a high constitutive level of protein expression. HN26 cells contained wild-type coding sequences but did not express the 53-kDa protein, although the mRNA was transcribed and a molecule of increased molecular mass (70 kDa) was observed by western blotting. Functional studies revealed that none of the four proteins encoded by mutant cDNAs were able to transactivate expression of a reporter plasmid containing a wild-type p53 consensus binding site when cotransfected into p53-null cells, whereas molecules encoded by wild-type p53 cDNAs increased reporter gene expression about a hundredfold over uninduced levels. Co-expression of each mutant cDNA with wild-type p53 cDNA and a wild-type p53-responsive reporter gene demonstrated that each of the proteins encoded by mutant cDNAs harbored some degree of inhibitory activity that varied depending on the mutation present. Thus, aberrant p53 function as a result of mutation or altered expression characterizes oral squamous cell carcinomas. The inhibitory activity of these molecules may be a mechanism for deregulation of the function of co-expressed wild-type p53 that may be of importance during the early stages of tumor development. (C) 1997 Wiley-Liss, Inc. C1 NIDR,MOL & CELLULAR BIOL SECT,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. WAYNE STATE UNIV,DIV HEMATOL ONCOL,DETROIT,MI. RP Yeudall, WA (reprint author), NIDR,MOL CARCINOGENESIS GRP,CELLULAR DEV & ONCOL LAB,BLDG 30,ROOM B01,30 CONVENT DR,MSC 4330,BETHESDA,MD 20892, USA. NR 42 TC 35 Z9 35 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 1997 VL 18 IS 2 BP 89 EP 96 DI 10.1002/(SICI)1098-2744(199702)18:2<89::AID-MC4>3.0.CO;2-L PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA WL325 UT WOS:A1997WL32500004 PM 9049184 ER PT J AU Sun, XJ Pons, S Wang, LM Zhang, YT Yenush, L Burks, D Myers, MG Glasheen, E Copeland, NG Jenkins, NA Pierce, JH White, MF AF Sun, XJ Pons, S Wang, LM Zhang, YT Yenush, L Burks, D Myers, MG Glasheen, E Copeland, NG Jenkins, NA Pierce, JH White, MF TI The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHOSPHOTYROSINE-DEPENDENT INTERACTION; GROWTH-FACTOR-I; RECEPTOR SUBSTRATE-1; LINKAGE MAP; PHOSPHATIDYLINOSITOL 3'-KINASE; HEMATOPOIETIC-CELLS; MOUSE CHROMOSOME-8; TYROSINE KINASE; NPEY MOTIF; DOMAINS AB Signal transduction by insulin and IGF-1, several interleukins (IL-2, IL-4, IL-9, IL-13), interferons, GH, and other cytokines involves IRS proteins, which link the receptors for these factors to signaling molecules with Src homology-2 domains (SH2-proteins). We recently reported the amino acid sequence of murine IRS-2; in order to examine a potential genetic role for this molecule in disease, we isolated the murine IRS-2 gene and compared the expression pattern of IRS-2 against IRS-1. Like IRS-1, IRS-2 is encoded by a single exon. Whereas IRS-1 is located on murine chomosome 1, IRS-2 is located on murine chromosome 8 near the insulin receptor. IRS-2 is expressed together with IRS-1 in many cells and tissues; however, IRS-2 predominates in murine hematopoietic cells where it may be essential for cytokine signaling; IRS-1 predominates in adipocytes and differentiated 3T3-L1 cells where it contributes to the normal insulin response. In 32D cells, IRS-1 and IRS-2 undergo differential tyrosine phosphorylation during insulin or IL-4 stimulation, as assessed indirectly by interaction with various recombinant SH2 domains. Thus, signaling specificity through the IRS proteins may be accomplished by specific expression patterns and distinct phosphorylation patterns during interaction with various activated receptors. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02215 USA. NIH, LAB CELL & MOL BIOL, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RI Pons , Sebastian/K-7794-2014; Yenush, Lynne/J-8815-2014 OI Pons , Sebastian/0000-0003-1027-0621; Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK-43808, DK-38712] NR 53 TC 121 Z9 125 U1 0 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 FEB PY 1997 VL 11 IS 2 BP 251 EP 262 DI 10.1210/me.11.2.251 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WF111 UT WOS:A1997WF11100014 PM 9013772 ER PT J AU Stephan, V Seibt, A Dukanovic, D Skasa, M Swaim, WD Berenstein, EH Siraganian, RP Wahn, V AF Stephan, V Seibt, A Dukanovic, D Skasa, M Swaim, WD Berenstein, EH Siraganian, RP Wahn, V TI Anti-ganglioside monoclonal antibody AA4 selectively inhibits IgE-induced signal transduction pathways in rat basophilic leukemia cells SO MOLECULAR IMMUNOLOGY LA English DT Article DE rat basophilic leukemia cells; IgE receptor; gangliosides ID PROTEIN-TYROSINE PHOSPHORYLATION; ALPHA-GALACTOSYL DERIVATIVES; RBL-2H3 CELLS; FC-RECEPTORS; MAST-CELLS; ACTIVATION; BINDING AB In rat basophilic leukemia 2H3 (RBL-2H3) cells, mAb AA4 binds to two derivatives of ganglioside GD(1b) that associate with the Src family kinase p53/56(lym) and a serine kinase. Pre-incubation of cells with mAb AA4 blocks immunoglobulin E (IgE) mediated histamine release. In the present study we investigated the effect of incubation with mAb AA4 on signal transduction events. In addition to stimulation of the high affinity IgE receptor (FceRI), cells were also activated by the calcium ionophore A23187 and the acetylcholine agonist carbachol in RBL-2H3 cells transfected with the G protein-coupled m3 muscarinic receptor. Incubation of cells with mAb AA4 in a dose-dependent manner inhibited the following FcsRI-induced signal transduction events: the increase of intracellular free calcium, phosphoinositol breakdown, tyrosine phosphorylation of proteins including the beta- of FcERI and secretion. However, there was no inhibition of degranulation or of these biochemical events when cells were stimulated with calcium ionophore or activated via a G protein-coupled pathway. Our results demonstrate that mAb AA4 selectively blocks FcERI-induced cell activation at a very early step upstream of receptor tyrosine phosphorylation. As mAb AA4 has previously been found to bind to gangliosides associated with FcERI, inhibition of very early biochemical events may be due to interaction of mAb AA4 with the FcERI induced signal transduction cascade at the receptor level. (C) 1997 Elsevier Science Ltd. C1 NIDR, IMMUNOL LAB, RECEPTORS & SIGNAL TRANSDUCT SECT, NIH, BETHESDA, MD 20892 USA. RP Stephan, V (reprint author), UNIV DUSSELDORF, KINDERKLIN, MOORENSTR 5, D-40225 DUSSELDORF, GERMANY. NR 27 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 1997 VL 34 IS 3 BP 227 EP 235 DI 10.1016/S0161-5890(97)00026-6 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA XJ083 UT WOS:A1997XJ08300004 PM 9224965 ER PT J AU Brendler, TG Abeles, AL Reaves, LD Austin, SJ AF Brendler, TG Abeles, AL Reaves, LD Austin, SJ TI The iteron bases and spacers of the P1 replication origin contain information that specifies the formation of a complex structure involved in initiation SO MOLECULAR MICROBIOLOGY LA English DT Article ID RNA-DNA HYBRID; PLASMID REPLICATION; ESCHERICHIA-COLI; CHROMOSOMAL ORIGIN; HOST STRAINS; PROTEIN; REPA; BINDING; SEQUENCES; AFFINITY AB The origin of replication of the P1 plasmid contains five direct, imperfect repeats (iterons) of a 19 bp sequence that binds the P1-encoded RepA initiator protein, RepA binding to these iterons triggers origin initiation and represses transcription from the repA promoter that is nested within the iterons. The origin iterons were replaced with ligated oligonucleotides that insert five perfect 19 bp repeats with identical spacer sequences. This eliminates the natural variation in the iteron and spacer sequences and removes the repA promoter. The reconstructed origin is functional, showing that the repA promoter is not essential for origin function. The method used to make the reconstructed origin allows substitution of identical iterons with altered sequence or spacer length. Single changes of conserved iteron bases gave reduced or non-existent origin activity, as did an increase in spacer length. Like the wild type, most of these mutant arrays retain avid primary binding activity for the RepA protein. However, although the wild-type arrays readily form a mature complex in which all iterons are saturated, the most replication-defective mutants were completely unable to do this, even at very high RepA concentrations. It appears that iteron spacing and contacts involving at least three of the conserved iteron bases play an important role in the assembly of the mature structure in which all sites are occupied. A model is presented in which an allosteric interaction between the DNA site and protein is needed for the saturated, mature complex required for initiation. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,GENE REGULAT & CHROMOSOME BIOL LAB,FREDERICK,MD 21702. NR 30 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1997 VL 23 IS 3 BP 559 EP 567 DI 10.1046/j.1365-2958.1997.d01-1869.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WF231 UT WOS:A1997WF23100014 PM 9044289 ER PT J AU Hill, SA Samuels, DS Carlson, JH Wilson, J Hogan, D Lubke, L Belland, RJ AF Hill, SA Samuels, DS Carlson, JH Wilson, J Hogan, D Lubke, L Belland, RJ TI Integration host factor is a transcriptional cofactor of pilE in Neisseria gonorrhoeae SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; GENE-EXPRESSION; BETA-SUBUNIT; HIP GENE; PROTEIN; DNA; PROMOTER; BINDING; SITES; CONVERSION AB Integration host factor (IHF) is a small, heterodimeric DNA-binding protein with pleiotropic function. IHF was purified to apparent homogeneity from Neisseria gonorrhoeae. Gel-retardation assays demonstrated binding of IHF to the pilE promoter region. The IHF-binding site was identified by DNase I protection assays and mapped proximal to three previously defined pilE promoters. Removal of the putative IHF-binding domain from pilE promoter DNA negated retardation of the DNA fragment when assessed by gel-shift analysis. Kleinschmidt electron microscopy showed pronounced kinking of pilE promoter DNA following incubation with IHF. Isogenic N. gonorrhoeae strains were constructed that contained either a wild-type pilE locus or a deleted pilE locus where the IHF-binding domain was removed. Primer-extension analysis and Northern blotting of total gonococcal RNA showed that in the absence of IHF binding at the pilE promoter, transcription was reduced 10-fold. Together, these data indicate that IHF is a transcriptional co-activator of pilE. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,NIH,HAMILTON,MT 59840. RP Hill, SA (reprint author), NIAID,MICROBIAL STRUCT & FUNCT LAB,NIH,ROCKY MT LABS,HAMILTON,MT 59840, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 NR 30 TC 23 Z9 23 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1997 VL 23 IS 4 BP 649 EP 656 DI 10.1046/j.1365-2958.1997.2321612.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WH738 UT WOS:A1997WH73800003 PM 9157237 ER PT J AU Kyle, E Neckers, L Takimoto, C Curt, G Bergan, R AF Kyle, E Neckers, L Takimoto, C Curt, G Bergan, R TI Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity SO MOLECULAR PHARMACOLOGY LA English DT Article ID ANDROGEN-BINDING; GROWTH-FACTORS; INHIBITION; DIET; MEN; EXPRESSION; RESISTANCE; MICE AB Genistein (5,7,4'-trihydroxyisoflavone), an isoflavinoid found in soy beans, has been identified as potentially causal for the low incidence of metastatic prostate cancer (PCa) in certain countries. Although genistein-induced PCa cell adhesion has been identified as a possible causative mechanism, direct growth inhibition by genistein has been reported and also could be causal. If in vivo growth inhibition was significant, then growth inhibition should occur at concentrations attained with dietary consumption, the mechanism of growth inhibition should be relevant to PCa, and genistein (a broad-spectrum in vitro protein-tyrosine kinase inhibitor) should have relatively specific kinase inhibitory effects in vivo. These considerations were investigated by measuring growth inhibitory activity in a variety of PCa cell lines. Growth inhibitory effects were shown not to occur with concentrations below the low micromolar range (i.e., 3 logs above that attained in serum). In-depth mechanistic studies with the PC3-M metastatic variant cell line demonstrated that growth inhibition was independent of genistein's estrogenic effects. Genistein was shown to decrease the viability of nonadherent cells, suggesting a lack of dependence on cell adhesion for growth inhibition. However, important molecular and kinetic differences between genistein's effects on growth in adherent versus nonadherent cells were identified. Specific suppression of focal adhesion kinase activity (without global decreases in phosphotyrosine) was shown to precede induction of apoptosis, which was responsible for growth inhibition in adherent cells. These findings do not support an in vivo growth inhibitory role by genistein consumed in quantities associated with a soy-based diet. They do, however, identify genistein as a potential therapeutic agent for PCa and as a tool with which to study the control of apoptosis in PCa. C1 NCI,NIH,BETHESDA,MD 20892. USN,MED ONCOL BRANCH,CLIN PHARMACOL BRANCH,BETHESDA,MD 20084. NR 35 TC 146 Z9 150 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 FEB PY 1997 VL 51 IS 2 BP 193 EP 200 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WJ446 UT WOS:A1997WJ44600004 PM 9203623 ER PT J AU Steeg, PS Abrams, JS AF Steeg, PS Abrams, JS TI Cancer prognostics: Past, present and p27 SO NATURE MEDICINE LA English DT Editorial Material C1 NCI,CLIN INVEST BRANCH,BETHESDA,MD 20892. RP Steeg, PS (reprint author), NCI,WOMENS CANCERS SECT,BETHESDA,MD 20892, USA. NR 11 TC 99 Z9 99 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 FEB PY 1997 VL 3 IS 2 BP 152 EP 154 DI 10.1038/nm0297-152 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WF088 UT WOS:A1997WF08800030 PM 9018230 ER PT J AU Reinhart, TA Rogan, MJ Viglianti, GA Rausch, DM Eiden, LE Haase, AT AF Reinhart, TA Rogan, MJ Viglianti, GA Rausch, DM Eiden, LE Haase, AT TI A new approach to investigating the relationship between productive infection and cytopathicity in vivo SO NATURE MEDICINE LA English DT Article ID FOLLICULAR DENDRITIC CELLS; IMMUNODEFICIENCY SYNDROME AIDS; LYMPH-NODE; RHESUS-MONKEYS; VIRUS TYPE-1; HIV-1; MACROPHAGES; PROGRESSION; EXPRESSION; PARTICLES AB We describe a novel experimental approach to analyzing virus-host relationships and potential mechanisms of cytopathicity in vivo in simian immunodeficiency virus (SIV) infections. Progressive destruction of lymphoid tissue in the course of infection by SIV or human immunodeficiency virus (HIV) accompanies the loss of CD4(+) T lymphocytes and sets the stage for AIDS(1,2). Because one of the important early events in this pathological process is lysis of follicular dendritic cells(3) (FDCs), we investigated the controversial role of productive SIV infection in the destruction of FDCs. To differentiate productive infections from the known association of virus with FDCs as immune complexes trapped on cell surfaces(4-6), we used detection of spliced viral mRNAs in cells as evidence of productive infection. We found that spliced and unspliced viral RNAs could be detected by in situ hybridization (ISH) with specific antisense oligonucleotide probes in lymphocytes and macrophages with sensitivities of fewer than ten copies of spliced viral RNA per cell. We detected only unspliced RNA in germinal centers where FDCs reside. Thus, no productive infection of these cells can be detected in vivo by this assay, and their destruction likely occurs by indirect mechanisms that have yet to be determined. C1 UNIV MINNESOTA,SCH MED,DEPT MICROBIOL,MINNEAPOLIS,MN 55455. BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. NIMH,CELL BIOL LAB,BETHESDA,MD. OI Eiden, Lee/0000-0001-7524-944X NR 26 TC 30 Z9 31 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 FEB PY 1997 VL 3 IS 2 BP 218 EP 221 DI 10.1038/nm0297-218 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WF088 UT WOS:A1997WF08800042 PM 9018242 ER PT J AU Kidder, LH Kalasinsky, VF Luke, JL Levin, IW Lewis, EN AF Kidder, LH Kalasinsky, VF Luke, JL Levin, IW Lewis, EN TI Visualization of silicone gel in human breast tissue using new infrared imaging spectroscopy SO NATURE MEDICINE LA English DT Article ID IMPLANTS; MICROSPECTROSCOPY; SYMPTOMS; DISEASES; RISK AB Between 1 and 2 million women in the United States have silicone breast implants. Complications include capsular contracture and calcification and possibly connective tissue diseases such as scleroderma and rheumatoid arthritis, a subject of some controversy(1-7). In order to accurately assess the role of silicone in any histopathologic change, it is necessary to confirm its presence and to identify other foreign materials in the capsular tissue. Although light microscopy is used to visualize regions of tissue containing foreign inclusions, their chemical identity can only be determined using analytical techniques such as infrared or Raman microscopy. However, these conventional microprobe techniques record spectra only at single points and require an a priori knowledge of the locations of the inclusion to be probed. To significantly extend the capabilities of both infrared spectroscopy and optical microscopy, we have developed a new infrared imaging system that completely integrates these two methods. In this manuscript we highlight the ability of the technique to screen rapidly and to determine accurately the presence, size and chemical composition of silicone gel inclusions in human breast tissue. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT ENVIRONM & TOXICOL PATHOL,WASHINGTON,DC 20306. NR 18 TC 110 Z9 110 U1 1 U2 3 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 FEB PY 1997 VL 3 IS 2 BP 235 EP 237 DI 10.1038/nm0297-235 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WF088 UT WOS:A1997WF08800046 PM 9018246 ER PT J AU Ravussin, E Pratley, RE Maffei, M Wang, H Friedman, JM Bennett, PH Bogardus, C AF Ravussin, E Pratley, RE Maffei, M Wang, H Friedman, JM Bennett, PH Bogardus, C TI Relatively low plasma leptin concentrations precede weight gain in Pima Indians SO NATURE MEDICINE LA English DT Article ID OBESE GENE-PRODUCT; INSULIN-RESISTANCE; PROTEIN; MICE; RNA AB Leptin, the product of the ob gene(1), is a hormone, produced by adipose cells, that inhibits food intake(2-5) and increases energy expenditure(2,3) in rodents. In humans, plasma leptin concentrations correlate closely with the size of the adipose tissue depot; however, there is considerable variation in plasma leptin concentrations at any given degree of fatness(6,7). To investigate whether individuals prone to weight gain are hypoleptinemic, we measured fasting plasma leptin concentrations in two groups of weight-matched nondiabetic Pima Indians followed for approximately 3 years, 19 of whom subsequently gained weight and 17 of whom maintained their weight. After we adjusted for initial percent body fat, mean plasma leptin concentration was lower in those who gained weight than in those whose weight was stable. These data indicate that relatively low plasma leptin concentrations may play a role in the development of obesity in Pima Indians, a population prone to obesity. C1 ROCKEFELLER UNIV,GENET MOL LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10021. RP Ravussin, E (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 28 TC 215 Z9 217 U1 1 U2 4 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 FEB PY 1997 VL 3 IS 2 BP 238 EP 240 DI 10.1038/nm0297-238 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WF088 UT WOS:A1997WF08800047 PM 9018247 ER PT J AU Szilak, L Moitra, J Krylov, D Vinson, C AF Szilak, L Moitra, J Krylov, D Vinson, C TI Phosphorylation destabilizes alpha-helices SO NATURE STRUCTURAL BIOLOGY LA English DT Letter ID LEUCINE ZIPPER; DNA-BINDING; AMINO-ACIDS; PROTEIN; SPECIFICITY; PROPENSITIES; STABILITY; SUBUNIT; PEPTIDE; KINASE AB Phosphorylation of threonine destabilizes the leucine zipper of a bZIP protein by 4.6 kcal mol(-1) dimer(-1), which reduces DNA binding 100-fold. This decrease in stability reflects the low a-helix forming propensity of a phosphorylated threonine. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. OI Szilak, Laszlo/0000-0003-0334-272X NR 26 TC 59 Z9 61 U1 1 U2 1 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 FEB PY 1997 VL 4 IS 2 BP 112 EP 114 DI 10.1038/nsb0297-112 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WF961 UT WOS:A1997WF96100010 PM 9033589 ER PT J AU Omichinski, JG Pedone, PV Felsenfeld, G Gronenborn, AM Clore, GM AF Omichinski, JG Pedone, PV Felsenfeld, G Gronenborn, AM Clore, GM TI The solution structure of a specific GAGA factor-DNA complex reveals a modular binding mode SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; PROTEIN-STRUCTURE DETERMINATION; HEAT-SHOCK ELEMENTS; CRYSTAL-STRUCTURE; TRANSCRIPTION FACTOR; ZINC-FINGER; DIRECT REFINEMENT; GLOBULAR DOMAIN; HIGH-RESOLUTION; HISTONE H5 AB The structure of a complex between the DNA binding domain of the GAGA factor (GAGA-DBD) and an oligonucleotide containing its GAGAG consensus binding site has been determined by nuclear magnetic resonance spectroscopy. The GAGA-DBD comprises a single classical Cys(2)-His(2), zinc finger core, and an N-terminal extension containing two highly basic regions, BR1 and BR2. The zinc: finger core binds in the major groove and recognizes the first three GAG bases of the consensus in a manner similar to that seen in other classical zinc finger-DNA complexes. Unlike the tatter, which require tandem zinc finger repeats with a minimum of two units for high affinity binding, the GAGA-DBD makes use of only a single finger complemented by BR1 and BR2. BR2 forms a helix that interacts in the major groove recognizing the last G of the consensus, while BR1. wraps around the DNA in the minor groove and recognizes the A in the fourth position of the consensus. The implications of the structure of the GAGA-DBD-DNA complex for chromatin remodelling are discussed. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 63 TC 155 Z9 157 U1 0 U2 2 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 FEB PY 1997 VL 4 IS 2 BP 122 EP 132 DI 10.1038/nsb0297-122 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WF961 UT WOS:A1997WF96100014 PM 9033593 ER PT J AU Mentis, MJ Alexander, GE Grady, CL Horwitz, B Krasuski, J Pietrini, P Strassburger, T Hampel, H Schapiro, MB Rapoport, SI AF Mentis, MJ Alexander, GE Grady, CL Horwitz, B Krasuski, J Pietrini, P Strassburger, T Hampel, H Schapiro, MB Rapoport, SI TI Frequency variation of a pattern-flash visual stimulus during PET differentially activates brain from striate through frontal cortex SO NEUROIMAGE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; SELECTIVE ATTENTION; EVOKED-POTENTIALS; COLOR; FORM; DISCRIMINATION; ORGANIZATION; CHANNELS; MOTION AB We evaluated regional cerebral blood flow (rCBF) in 19 healthy elderly subjects, mean age 64 +/- 11 (SD, years), during a passive visual stimulus in which pattern-flash frequency was parametrically manipulated. Using goggles with a grid of red lights imbedded into each lens, we performed five positron emission tomography (PET) (H2O)-O-15 water scans on each subject at alternating (left to right eye) flash frequencies of 0, 1, 4, 7, and 14 Hz. We found a biphasic rising and falling rCBF response in the striate cortex (7 Hz peak) and left anterior cingulate (4 Hz peak), 1 Hz activation in left middle temporal gyrus (V5), monotonically increasing rCBF in posterior areas (lateral and inferior visual association areas, Brodmann 18 and 19), and monotonically decreasing rCBF in anterior areas (frontal, cingulate, and superior temporal) predominantly in right hemisphere. We suggest the striate rCBF changes at all frequencies primarily reflect lateral geniculate input, the middle temporal activation at 1 Hz reflects perception of apparent motion, and the posterior extrastriate rCBF monotonic increase represents a neural response to increasing luminance intensity and form and color complexity that occur as pattern-flash frequency increases. The anterior monotonic rCBF decrease may represent active cross-modal functional suppression of brain areas irrelevant for processing the passive visual stimulus. Pattern-flash rCBF responses were highly reproducible (no series effect), more so in posterior than in anterior brain regions. The reproducibility and systematically changing rCBF responses to this passive stimulus suggest that it could be successfully used as a disease probe to evaluate neural function and drug effects in cognitively impaired patients. (C) 1997 Academic Press. RP Mentis, MJ (reprint author), NIA, NEUROSCI LAB, NIH, BLDG 10, ROOM 6C 414, BETHESDA, MD 20892 USA. NR 49 TC 49 Z9 51 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1997 VL 5 IS 2 BP 116 EP 128 DI 10.1006/nimg.1997.0256 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA WT243 UT WOS:A1997WT24300003 PM 9345542 ER PT J AU Murphy, EL Fridey, J Smith, JW Engstrom, J Sacher, RA Miller, K Gibble, J Stevens, J Thomson, R Hansma, D Kaplan, J Khabbaz, R Nemo, G Williams, AE Nass, C Jackson, CM Ownby, H Kleinman, S Hutching, S Busch, MP Evans, C Gilcher, RO Schreiber, GB Sacher, R Luban, N Hollingsworth, CG Nemo, GJ AF Murphy, EL Fridey, J Smith, JW Engstrom, J Sacher, RA Miller, K Gibble, J Stevens, J Thomson, R Hansma, D Kaplan, J Khabbaz, R Nemo, G Williams, AE Nass, C Jackson, CM Ownby, H Kleinman, S Hutching, S Busch, MP Evans, C Gilcher, RO Schreiber, GB Sacher, R Luban, N Hollingsworth, CG Nemo, GJ TI HTLV-associated myelopathy in a cohort of HTLV-I and HTLV-II-infected blood donors SO NEUROLOGY LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; CHRONIC PROGRESSIVE MYELOPATHY; UNITED-STATES; DRUG-ABUSERS; ANTIBODIES; RISK; TRANSFUSION; ZAIRE; FLUID AB Objective: HTLV-I-associated myelopathy (HAM) is a slowly progressive spastic paraparesis caused by infection with human T-lymphotropic virus type I (HTLV-I). The prevalence of HAM among those infected with HTLV-I is poorly defined, and the association of a similar myelopathy with HTLV-II infection has not been confirmed. Design: Cross-sectional examination of HTLV-I, HTLV-II, and control subjects from the baseline visit of a cohort study. Setting/subjects: Persons testing HTLV seropositive at the time of blood donation at five U.S. blood centers, their seropositive sex partners, and a matched control group of HTLV seronegative blood donors. Measurements: HTLV-I and HTLV-II were differentiated by serology and/or polymerase chain reaction. All subjects received systematic neurologic screening examinations. Results: A diagnosis of myelopathy was confirmed in four of 166 HTLV-I subjects (2.4%, 95% confidence interval 0.7%, 6.1%) and in one of 404 HTLV-II subjects (0.25%, 95% confidence interval 0.0%, 0.6%). None of the 798 controls had a similar myelopathy, although one had longstanding typical multiple sclerosis. Conclusions: Our data also suggest that HAM occurs more frequently among HTLV-I-infected subjects than reported by previous studies, The HTLV-II infected myelopathy patient identified in this cohort, together with three other case reports in the literature, implies a pathogenic role for this human retrovirus. The diagnosis of HTLV-associated myelopathy should be considered in cases of spastic paraparesis or neurogenic bladder when risk factors for HTLV-I or HTLV-II infection are present. C1 BLOOD BANK,SAN BERNARDINO,CA. BLOOD BANK,RIVERSIDE,CA. OKLAHOMA BLOOD INST,OKLAHOMA CITY,OK. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. WESTAT CORP,ROCKVILLE,MD. AMER RED CROSS CHESAPEAKE & POTOMAC REG,BALTIMORE,MD. AMER RED CROSS SE MICHIGAN,DETROIT,MI. CTR DIS CONTROL & PREVENT,ATLANTA,GA. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. UNIV CALIF SAN FRANCISCO,IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA 94143. NHLBI,NIH,BETHESDA,MD. RP Murphy, EL (reprint author), UNIV CALIF SAN FRANCISCO,DEPT LAB MED,BOX 0884,SAN FRANCISCO,CA 94143, USA. FU NHLBI NIH HHS [N01-HB-97077, N01-HB-97078, N01-HB-97079] NR 36 TC 89 Z9 93 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1997 VL 48 IS 2 BP 315 EP 320 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA WH535 UT WOS:A1997WH53500004 PM 9040713 ER PT J AU Metman, LV Locatelli, ER Bravi, D Mouradian, MM Chase, TN AF Metman, LV Locatelli, ER Bravi, D Mouradian, MM Chase, TN TI Apomorphine responses in Parkinson's disease and the pathogenesis of motor complications SO NEUROLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Academy-of-Neurology CY MAY 11, 1995 CL SEATTLE, WA SP Amer Acad Neurol ID FLUCTUATIONS; LEVODOPA; MECHANISMS; DOPAMINE AB We studied the contribution of basal ganglia circuitry downstream from the nigrostriatal dopaminergic system to the pathogenesis of levodopa associated motor complications by means of an apomorphine dose-response paradigm in 28 parkinsonian patients grouped according to their clinical response to levodopa therapy, With progression from the dopa-naive to the severely fluctuating dyskinetic state, apomorphine response duration shortened, the dose-response slope steepened, and the therapeutic window narrowed. Because apomorphine acts independently of the integrity of presynaptic dopaminergic neurons, our results suggest that postsynaptic alterations account mainly for the appearance of response complications. The present findings support the possibility, raised by animal model studies, that motor response complications arise as a consequence of altered signal transduction mechanisms in striatal medium-sized neurons. C1 NINCDS, EXPT THERAPEUT BRANCH, NIH, BETHESDA, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 17 TC 38 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD FEB PY 1997 VL 48 IS 2 BP 369 EP 372 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA WH535 UT WOS:A1997WH53500014 ER PT J AU Bruijn, LI Becher, MW Lee, MK Anderson, KL Jenkins, NA Copeland, NG Sisodia, SS Rothstein, JD Borchelt, DR Price, DL Cleveland, DW AF Bruijn, LI Becher, MW Lee, MK Anderson, KL Jenkins, NA Copeland, NG Sisodia, SS Rothstein, JD Borchelt, DR Price, DL Cleveland, DW TI ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions SO NEURON LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE ACTIVITY; GLUTAMATE TRANSPORTER; NEUROTROPHIC FACTOR; TRANSGENIC MICE; ANIMAL-MODEL; RAT-BRAIN; WILD-TYPE; MUTATIONS; NEURONS AB High levels of familial Amyotrophic Lateral Sclerosis (ALS)-linked SOD1 mutants G93A and G37R were previously shown to mediate disease in mice through an acquired toxic property. We report here that even low levels of another mutant, G85R, cause motor neuron disease characterized by an extremely rapid clinical progression, without changes in SOD1 activity. Initial indicators of disease are astrocytic inclusions that stain intensely with SOD1 antibodies and ubiquitin and SOD1-containing aggregates in motor neurons, features common with some cases of SOD1 mutant-mediated ALS. Astrocytic inclusions escalate markedly as disease progresses, concomitant with a decrease in the glial glutamate transporter (GLT-1). Thus, the G85R SOD1 mutant mediates direct damage to astrocytes, which may promote the nearly synchronous degeneration of motor neurons. C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROPATHOL,BALTIMORE,MD 21205. NCI,MAMMALIAN GENET LAB,ADV BIOSCI LABS RES PROGRAM,FREDERICK,MD 21701. RP Bruijn, LI (reprint author), UNIV CALIF SAN DIEGO,LUDWIG INST CANC RES,LA JOLLA,CA 92093, USA. RI rothstein, jeffrey/C-9470-2013; Lee, Michael/D-9491-2013 OI Lee, Michael/0000-0001-5865-9682 FU NIA NIH HHS [AG 05146]; NINDS NIH HHS [NS 10580, NS 27036] NR 39 TC 843 Z9 854 U1 1 U2 39 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 1997 VL 18 IS 2 BP 327 EP 338 DI 10.1016/S0896-6273(00)80272-X PG 12 WC Neurosciences SC Neurosciences & Neurology GA WK822 UT WOS:A1997WK82200015 PM 9052802 ER PT J AU Ruchkin, DS Johnson, R Grafman, J Canoune, H Ritter, W AF Ruchkin, DS Johnson, R Grafman, J Canoune, H Ritter, W TI Multiple visuospatial working memory buffers: Evidence from spatiotemporal patterns of brain activity SO NEUROPSYCHOLOGIA LA English DT Article DE working memory; visuospatial; event-related potentials ID HUMAN EXTRASTRIATE CORTEX; EVENT-RELATED POTENTIALS; SHORT-TERM-MEMORY; POSITRON EMISSION TOMOGRAPHY; PREFRONTAL CORTEX; MENTAL-IMAGERY; SPATIAL VISION; OBJECT; DISSOCIATION; FACES AB Numerous studies have shown that the visual system involves different cortical pathways in the perception of object (ventral visual pathway) and spatial (dorsal visual pathway) information. The present study was concerned with whether human visuospatial working memory divides along similar lines. We used event-related brain potentials (ERPs) recorded from scalp of normal humans to show the existence of different buffering systems for the retention of object and spatial visual information. Subjects were presented with object or spatial stimuli to be retained for a 3.6-sec interval. The ERPs isolated brain activity associated with retention from earlier storage and later retrieval processes. The ERP scalp topographies indicated that the underlying patterns of brain activation were different during retention of object and spatial information. Copyright (C) 1996 Elsevier Science Ltd. C1 CUNY QUEENS COLL, DEPT PSYCHOL, FLUSHING, NY 11367 USA. NINCDS, MED NEUROL BRANCH, COGNIT NEUROSCI SECT, BETHESDA, MD 20892 USA. ALBERT EINSTEIN COLL MED, DEPT NEUROSCI, BRONX, NY 10467 USA. RP Ruchkin, DS (reprint author), UNIV MARYLAND, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21201 USA. FU NINDS NIH HHS [NS11199, NS30029] NR 54 TC 85 Z9 89 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD FEB PY 1997 VL 35 IS 2 BP 195 EP 209 PG 15 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA WC307 UT WOS:A1997WC30700009 PM 9025123 ER PT J AU Vodovotz, Y AF Vodovotz, Y TI Control of nitric oxide production by transforming growth factor-beta 1: Mechanistic insights and potential relevance to human disease SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Review ID SMOOTH-MUSCLE CELLS; SYNTHASE MESSENGER-RNA; PIGMENT EPITHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; HUMAN CUTANEOUS LEISHMANIASIS; INFLAMMATORY BOWEL-DISEASE; RENAL MESANGIAL CELLS; NF-KAPPA-B/REL; FACTOR-BETA; ALZHEIMERS-DISEASE AB Studies on the multifunctional nature of the transforming growth factor-beta (TGF-beta) family of cytokines and the enzyme nitric oxide synthase (NOS) have suggested that they mediate a wide variety of vital processes in evolutionarily divergent organisms. Numerous mechanistic studies have investigated the consequences of the regulation of NO by the TGF-beta's for mammalian physiology. Studies with several cell types in vitro indicate that TGF-beta 1 negatively controls the expression of the enzyme responsible for the prolonged production of large amounts NO, the inducible nitric oxide synthase (NOS2; iNOS), by reducing the expression and activity of NOS2 at multiple levels. Recent studies with TGF-beta 1 null mice or mice which overexpress TGF-1 beta suggest that this cytokine may be a primary negative regulator of NOS2 in vivo. The interaction between NOS2 and TGF-beta 1 may represent a central homeostatic mechanism in mammalian physiology with implications for a variety of human diseases. (C) 1997 Academic Press. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Vodovotz, Y (reprint author), NCI, Radiat Biol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. NR 168 TC 88 Z9 89 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 EI 1089-8611 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD FEB PY 1997 VL 1 IS 1 BP 3 EP 17 DI 10.1006/niox.1996.0105 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG180 UT WOS:000072975200002 PM 9701040 ER PT J AU Wink, DA Cook, JA Christodoulou, D Krishna, MC Pacelli, R Kim, S DeGraff, W Gamson, J Vodovotz, Y Russo, A Mitchell, JB AF Wink, DA Cook, JA Christodoulou, D Krishna, MC Pacelli, R Kim, S DeGraff, W Gamson, J Vodovotz, Y Russo, A Mitchell, JB TI Nitric oxide and some nitric oxide donor compounds enhance the cytotoxicity of cisplatin SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article ID DNA-REPAIR; IN-VIVO; MECHANISMS; PROTECTS; RELEASE; INHIBITION; COMPLEXES; BIOLOGY; AGENTS; DAMAGE AB A major emphasis in cancer therapy research is finding mechanisms to enhance the effectiveness of clinically used chemotherapeutic agents. In this report, we show the effects of direct NO exposure or NO delivery agents such as NONOate NO donors, DEA/NO ((C2H5)(2)N[N(O)NO]Na--(+)) and PAPA/ NO (NH2(C3H6)(N[N(O)NO]C3H7)), Or S-nitrosothiol NO donors (GSNO, S-nitrosoglutathione, and SNAP, S-nitroso-N-acetylpenicillamine) on the cytotoxicity of cisplatin with Chinese hamster V79 lung fibroblast cells. Cells pretreated with bolus NO or NO delivered from NONOate NO donors were markedly sensitized to subsequent cisplatin treatment, whereas S-nitrosothiol NO donors exerted little effect. The enhancement in cisplatin cytotoxicity from pretreatment with DEA/NO and PAPA/ NO persisted for similar to 180 and 240 min, respectively; thereafter cytotoxicity returned to a level consistent with cisplatin treatment alone. Pretreatment of cells with GSNO or SNAP did not enhance cisplatin cytotoxity. To discern why there were differential effects among the different NO donors, formation of NO over the time course of the experiment was assessed by the nitrosation of 2,3-diaminonaphthylene. Bolus NO, DEA/NO, and PAPA/NO produced more reactive nitrogen oxide species (RNOS) than did treatment with GSNO or SNAP. Previously reported electrochemical studies revealed that temporal NO concentrations measured from DEA/NO and PAPA/NO (1 mM) were greater than 5 mu M. It appears that the flux of NO, as well as the amount of RNOS, is important in the NO-mediated enhancement of cisplatin cytotoxicity. Our results demonstrate the importance of NO delivery systems in the enhancement of cisplatin cytotoxicity and may provide insights into strategies for participation of NO donors and nitric oxide synthase with cisplatin therapy. (C) 1997 Academic Press. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 23 TC 83 Z9 85 U1 1 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD FEB PY 1997 VL 1 IS 1 BP 88 EP 94 DI 10.1006/niox.1996.0108 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG180 UT WOS:000072975200010 PM 9701048 ER PT J AU Karakaya, A Jaruga, P Bohr, VA Grollman, AP Dizdaroglu, M AF Karakaya, A Jaruga, P Bohr, VA Grollman, AP Dizdaroglu, M TI Kinetics of excision of purine lesions from DNA by Escherichia coli Fpg protein SO NUCLEIC ACIDS RESEARCH LA English DT Article ID APURINIC APYRIMIDINIC SITES; GENERATED FREE-RADICALS; SUBSTRATE-SPECIFICITY; CATALYTIC MECHANISM; MAMMALIAN CHROMATIN; ENDONUCLEASE-III; IMIDAZOLE RINGS; N-GLYCOSYLASE; DAMAGED DNA; RADIATION AB The kinetics of excision of damaged purine bases from oxidatively damaged DNA by Escherichia coli Fpg protein were investigated. DNA substrates, prepared by treatment with H2O2/Fe(III)-EDTA or by gamma-irradiation under N2O or air, were incubated with Fpg protein, followed by precipitation of DNA. Precipitated DNA and supernatant fractions were analyzed by gas chromatography/isotope-dilution mass spectrometry. Kinetic studies revealed efficient excision of 8-hydroxyguanine (8-OH-Gua), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 4,6-diamino-5-formamidopyrimidine (FapyAde). Thirteen other modified bases in the oxidized DNA substrates, including 5-hydroxycytosine and 5-hydroxyuracil, were not excised. Excision was measured as a function of enzyme concentration, substrate concentration, time and temperature. The rate of release of modified purine bases from the three damaged DNA substrates varied significantly even though each DNA substrate contained similar levels of oxidative damage. Specificity constants (K-cat/K-M) for the excision reaction indicated similar preferences of Fpg protein for excision of 8-OH-Gua, FapyGua and FapyAde from each DNA substrate. These findings suggest that, in addition to 8-OH-Gua, FapyGua and FapyAde may be primary substrates for this enzyme in cells. C1 NIST,CHEM SCI & TECHNOL LAB,GAITHERSBURG,MD 20899. ANKARA UNIV,FAC PHARM,TR-06100 ANKARA,TURKEY. MED ACAD,DEPT CLIN BIOCHEM,PL-85094 BYDGOSZCZ,POLAND. NIA,GENET MOL LAB,NIH,BALTIMORE,MD 21224. SUNY STONY BROOK,DEPT PHARMACOL SCI,STONY BROOK,NY 11794. RI Jaruga, Pawel/M-4378-2015 FU NCI NIH HHS [CA17395] NR 41 TC 134 Z9 134 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 1 PY 1997 VL 25 IS 3 BP 474 EP 479 DI 10.1093/nar/25.3.474 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG771 UT WOS:A1997WG77100004 PM 9016584 ER PT J AU Cahill, GF Buskirk, ER Delahanty, LM Fajans, SS Field, JB Holverson, HE Hoover, JW Horwitz, RI Hentz, KI Lachin, JM Lockwood, DH Service, FJ Thompson, PD Wheeler, ML Eschwege, E Gorden, P Hubbard, VS PiSunyer, FX Rose, M Sherwin, R Silverman, RE Taylor, SI Tchobroutsky, G WylieRosett, J Bernstein, MJ Armstrong, C AF Cahill, GF Buskirk, ER Delahanty, LM Fajans, SS Field, JB Holverson, HE Hoover, JW Horwitz, RI Hentz, KI Lachin, JM Lockwood, DH Service, FJ Thompson, PD Wheeler, ML Eschwege, E Gorden, P Hubbard, VS PiSunyer, FX Rose, M Sherwin, R Silverman, RE Taylor, SI Tchobroutsky, G WylieRosett, J Bernstein, MJ Armstrong, C TI Diet and exercise in noninsulin-dependent diabetes mellitus SO NUTRITION LA English DT Editorial Material C1 PENN STATE UNIV,UNIVERSITY PK,PA 16802. MASSACHUSETTS GEN HOSP,DEPT DIETET,BOSTON,MA 02114. UNIV MICHIGAN,MED CTR,DIV ENDOCRINOL & METAB,ANN ARBOR,MI 48109. BAYLOR COLL MED,HOUSTON,TX 77030. UNITED SENIORS CONSUMER COOPERAT,CONSUMER HLTH INFORMAT,WASHINGTON,DC. YALE UNIV,SCH MED,NEW HAVEN,CT 06520. IACOCCA FDN,NEW YORK,NY. GEORGE WASHINGTON UNIV,DEPT STAT COMP & INFORMAT SYST,CTR BIOSTAT,WASHINGTON,DC 20052. UNIV ROCHESTER,MED CTR,ENDOCRINE METAB UNIT,ROCHESTER,NY 14627. MAYO CLIN,ROCHESTER,MN. MAYO CLIN & MAYO FDN,MAYO MED SCH,ROCHESTER,MN 55905. BROWN UNIV,MIRIAM HOSP,PROGRAM MED,PROVIDENCE,RI 02912. INDIANA UNIV,MED CTR,CTR DIABET RES & TRAINING,INDIANAPOLIS,IN. INSERM,UNITE RECH STAT,VILLEJUIF,FRANCE. NIDDKD,NUTRIENT METAB OBES EATING DISORDERS & ENERGY PRO,DIV DIGEST DIS & NUTR,NIH,BETHESDA,MD 20892. ST LUKES ROOSEVELT HOSP,DIV ENDOCRINOL & DIABET,NEW YORK,NY. COLUMBIA UNIV,NEW YORK,NY 10027. NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. YALE UNIV,SCH MED,NEW HAVEN,CT 06520. NIDDKD,DIABET PROGRAMS BRANCH,DIV DIABET ENDOCRINOL & MET DIS,NIH,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. HOP HOTEL DIEU,DEPT DIABETOL,F-75181 PARIS,FRANCE. UNIV PARIS 06,PARIS,FRANCE. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. RP Cahill, GF (reprint author), HOWARD HUGHES MED INST,BETHESDA,MD 20817, USA. OI Lachin, John/0000-0001-9838-2841 NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0899-9007 J9 NUTRITION JI Nutrition PD FEB PY 1997 VL 13 IS 2 BP 89 EP 94 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WT031 UT WOS:A1997WT03100001 ER PT J AU Meyer, GS AF Meyer, GS TI Making new markets in the British NHS SO NUTRITION LA English DT Article ID NATIONAL-HEALTH-SERVICE RP Meyer, GS (reprint author), NIH,DEPT MED,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0899-9007 J9 NUTRITION JI Nutrition PD FEB PY 1997 VL 13 IS 2 BP 171 EP 172 DI 10.1016/S0899-9007(96)00436-4 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WT031 UT WOS:A1997WT03100020 PM 9106802 ER PT J AU Fananapazir, L McAreavey, D AF Fananapazir, L McAreavey, D TI Hypertrophic cardiomyopathy: Evaluation and treatment of patients at high risk for sudden death SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cardiac Electrophysiology - The Duke Perspective CY APR 26-28, 1996 CL DURHAM, NC DE hypertrophic cardiomyopathy; systolic and diastolic dysfunction; sudden death ID HEAVY-CHAIN GENE; LEFT-VENTRICULAR HYPERTROPHY; BETA-CARDIAC MYOSIN; MYOCARDIAL PERFUSION ABNORMALITIES; SUB-AORTIC STENOSIS; OBSTRUCTIVE CARDIOMYOPATHY; ATRIAL-FIBRILLATION; OUTFLOW OBSTRUCTION; MISSENSE MUTATION; CLINICAL MANIFESTATIONS AB Hypertrophic cardiomyopathy (HCM) is a heritable disease characterized by LV hypertrophy with markedly variable clinical, morphological, and genetic manifestations. It is the most common cause of sudden death in otherwise healthy young individuals. HCM patients often have disabling symptoms and are prone to arrhythmias. Frequently, there is associated LV systolic and diastolic dysfunction, LV outflow obstruction, and myocardial ischemia. Over the past decade, progress has been made in identifying patients who are at high risk for sudden death, in elucidating potential mechanisms of sudden death, and in defining therapeutic algorithms that may improve prognosis. It has also been possible to determine the genetic defect in some of the patients and to correlate clinical findings with the molecular defects. An exciting development has been the use of the dual chamber pacemaker as an alternative to cardiac surgery to improve symptoms and relieve LV outflow obstruction. RP Fananapazir, L (reprint author), NHLBI,CARDIOL BRANCH,NIH,BLDG 10,ROOM 7B-14,10 CTR DR,MSC 1650,BETHESDA,MD 20892, USA. NR 133 TC 17 Z9 17 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD FEB PY 1997 VL 20 IS 2 BP 478 EP 501 DI 10.1111/j.1540-8159.1997.tb06206.x PN 2 PG 24 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA WK500 UT WOS:A1997WK50000011 PM 9058851 ER PT J AU Ravichandran, M Mahanty, S Kumaraswami, V Nutman, TB Jayaraman, K AF Ravichandran, M Mahanty, S Kumaraswami, V Nutman, TB Jayaraman, K TI Elevated IL-10 mRNA expression and downregulation of Th1-type cytokines in microfilaraemic individuals with Wuchereria bancrofti infection SO PARASITE IMMUNOLOGY LA English DT Article DE cytokine; filariasis; Wuchereria bancrofti; RT-PCR ID HUMAN LYMPHATIC FILARIASIS; T-CELL PROLIFERATION; PROTECTIVE IMMUNITY; CD28 RECEPTOR; RESPONSES; ANTIGEN; B7; ACTIVATION; UNRESPONSIVENESS; INTERLEUKIN-4 AB To understand the molecular basis of parasite-specific anergy in human lymphatic filariasis caused by the nematode Wuchereria bancrofti, parasite antigen-dependent cellular proliferation and cytokine gene expression were investigated. By reverse transcriptase polymerase chain reaction (RT-PCR), the levels of cytokine mRNA were determined in the peripheral blood mononuclear cells (PBMCs) of different clinical groups of filariasis patients. This includes individuals with circulating microfilariae (MF), patients with chronic lymphatic obstruction (CP), and exposed but uninfected individuals (EN). Those with CP exhibited both a Th2 and a Th1 parasite antigen-driven response. In PBMCs from those with MF, there was a marked downregulation of cellular response to parasite antigens, with lowered expression of Th1-specific cytokines (IFN-gamma and IL-2) and this was paralleled by increased IL-10 expression. The EN individuals had a purely TH1-type pattern with absence of IL-4 and IL-5 expression. Further, the mRNA expression of the costimulatory surface marker, CD80 (B7-1), was not associated with either disease status or IL-10 expression. There was a significant negative correlation between IL-10 mRNA expression and PBMC proliferation in the MF individuals, thus indicating the possible role of IL-10 in antigen-specific hyporesponsiveness. C1 ANNA UNIV,CTR BIOTECHNOL,MADRAS 600025,TAMIL NADU,INDIA. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. TB RES CTR,MADRAS 600030,TAMIL NADU,INDIA. RI Ravichandran, Manickam/A-7128-2011; OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 26 TC 51 Z9 53 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD FEB PY 1997 VL 19 IS 2 BP 69 EP 77 DI 10.1046/j.1365-3024.1997.d01-185.x PG 9 WC Immunology; Parasitology SC Immunology; Parasitology GA WM743 UT WOS:A1997WM74300003 PM 9076809 ER PT J AU Miller, LH Good, MF Kaslow, DC AF Miller, LH Good, MF Kaslow, DC TI The need for assays predictive of protection in development of malaria bloodstage vaccines SO PARASITOLOGY TODAY LA English DT Editorial Material ID PLASMODIUM-FALCIPARUM MALARIA; MEROZOITE SURFACE PROTEIN-1; AOTUS MONKEYS; IMMUNIZATION; EFFICACY; ANTIBODY; ANTIGEN; SPF66 C1 QUEENSLAND INST MED RES,COOPERAT RES CTR VACCINE TECHNOL,BRISBANE,QLD 4029,AUSTRALIA. RP Miller, LH (reprint author), NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892, USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD FEB PY 1997 VL 13 IS 2 BP 46 EP 47 DI 10.1016/S0169-4758(96)20063-8 PG 2 WC Parasitology SC Parasitology GA WF293 UT WOS:A1997WF29300003 PM 15275121 ER PT J AU Taranger, J Trollfors, B Lagergard, T Lind, L Sundh, V Zackrisson, G Bryla, DA Robbins, JB AF Taranger, J Trollfors, B Lagergard, T Lind, L Sundh, V Zackrisson, G Bryla, DA Robbins, JB TI Unchanged efficacy of a pertussis toxoid vaccine throughout the two years after the third vaccination of infants SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE pertussis; vaccine; efficacy ID SEROLOGY; TRIAL AB Background. In a previously reported double blind efficacy trial of a pertussis toroid vaccine, 3450 infants were randomized to receive diphtheria-tetanus toxoids with or without, pertussis toroid at 3, 5 and 12 months of age. Efficacy against pertussis as defined by the World Health Organization was 71% from 30 days after the third vaccination with an average follow-up of 17.5 months, We now report efficacy for an additional 6 months of open follow-up. Methods. Parents were contacted monthly by a nurse, If a participant or a family member coughed for greater than or equal to 7 days, a nasopharyngeal sample and paired sera mere obtained. Results. Efficacy during this open follow-up period was 77% (95% confidence intervals, 66 to 85%) based on 29 and 110 cases fulfilling the WHO definition of pertussis in vaccinated and control children, respectively. Efficacy against household exposure was 76% (95% confidence intervals, 51 to 91%), Pertussis in vaccinated children had a significantly shorter duration than pertussis in control children. Determination of pertussis toxin antibodies in paired sera with enzyme-linked immunosorbent assay had a lower diagnostic sensitivity in vaccinated (45%) than in control (92%) children, while determination of antibodies against filamentous hemagglutinin (not included in the vaccine) was highly sensitive for diagnosing pertussis in both groups (100 and 90%, respectively). Conclusions. A monocomponent pertussis toxoid vaccine induces significant protection against pertussis for at least 2 years after the third injection. To obtain an unbiased estimate of vaccine efficacy it is important to determine antibodies against an antigen that is not included in the vaccine. C1 GOTHENBURG UNIV,DEPT PEDIAT,S-41124 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT CLIN BACTERIOL,GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT MED MICROBIOL & IMMUNOL,GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT GERIATR MED,GOTHENBURG,SWEDEN. NICHHD,NIH,BETHESDA,MD. NR 14 TC 30 Z9 30 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 1997 VL 16 IS 2 BP 180 EP 184 DI 10.1097/00006454-199702000-00003 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA WH263 UT WOS:A1997WH26300002 PM 9041597 ER PT J AU Shetty, D Giri, N Gonzalez, CE Pizzo, PA Walsh, TJ AF Shetty, D Giri, N Gonzalez, CE Pizzo, PA Walsh, TJ TI Invasive aspergillosis in human immunodeficiency virus-infected children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE acquired immunodeficiency syndrome; aspergillosis; amphotericin E ID ACQUIRED IMMUNE-DEFICIENCY; PRIMARY CUTANEOUS ASPERGILLOSIS; PULMONARY ASPERGILLOSIS; ANTIFUNGAL ACTIVITY; LYMPHOCYTE SUBSETS; LEUKEMIC CHILDREN; AIDS; FUMIGATUS; DISEASE AB Background. Aspergillosis is an uncommon yet serious opportunistic infection in patients with AIDS, It has been extensively reported in HIV-infected adult patients. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of aspergillosis in a large HIV-infected pediatric population. Methods. We reviewed the records of all 473 HIV-infected children followed in the Pediatric Branch of the National Cancer Institute for 9 years from 1987 through 1995 for the presence of Aspergillus infection. Results. Seven (1.5%) patients developed invasive aspergillosis during the study period. All patients had low CD4 counts reflecting severe immunosuppression. Sustained neutropenia (>7 days) or corticosteroid therapy asa predisposing factor for invasive aspergillosis was encountered in only two patients (28%). Invasive pulmonary aspergillosis developed in five patients and cutaneous aspergillosis in two, The most common presenting features in patients with pulmonary aspergillosis were fever, cough and dyspnea, Patients with cutaneous aspergillosis were diagnosed during life and successfully treated with amphotericin B and surgery, whereas diagnosis of pulmonary aspergillosis was made clinically in only one patient. Conclusions. Aspergillosis is an uncommon but highly lethal opportunistic infection in HIV-infected children. Invasive pulmonary aspergillosis should be considered in the differential diagnosis in febrile, HIV-infected children with persistent pulmonary infiltrates. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. NR 28 TC 47 Z9 52 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 1997 VL 16 IS 2 BP 216 EP 221 DI 10.1097/00006454-199702000-00010 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA WH263 UT WOS:A1997WH26300009 PM 9041604 ER PT J AU Swayze, VW Johnson, VP Hanson, JW Piven, J Sato, Y Giedd, JN Mosnik, D Andreasen, NC AF Swayze, VW Johnson, VP Hanson, JW Piven, J Sato, Y Giedd, JN Mosnik, D Andreasen, NC TI Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome SO PEDIATRICS LA English DT Article DE agenesis of the corpus callosum; cavum septi pellucidi; cavum vergae; developmental field; embryogenesis; fetal alcohol syndrome; magnetic resonance imaging; teratogenesis ID CAVUM-SEPTUM-PELLUCIDUM; NEURAL-TUBE DEFECTS; CORPUS-CALLOSUM; PRENATAL ALCOHOL; CRANIOFACIAL MORPHOLOGY; INCREASED PREVALENCE; DEVELOPMENTAL FIELD; FOLLOW-UP; EXPOSURE; ETHANOL AB Objective. Postmortem studies of fetuses, infants, and young children with fetal alcohol syndrome (FAS) have demonstrated a variety of severe central nervous system (CNS) anomalies. We undertook this magnetic resonance study (1) to assess the spectrum of CNS anomalies that occur in a clinical sample of typical patients with FAS who are medically stable; and (2) to examine the relationship between CNS and facial anomalies. Methodology. Magnetic resonance imaging was performed on a series of 10 patients (4 children, 3 adolescents, and 3 adults) who met criteria for FAS. We systematically evaluated each scan for brain anomalies and compared total brain tissue volume with that of healthy child, adolescent, and adult control subjects. Results. Six patients had some type of midline anomaly, ranging from partial to complete callosal agenesis (three patients) to hypoplastic corpus callosum (one patient), cavum septi pellucidi (three patients), and cavum vergae (two patients). These midline anomalies were associated with a greater number of facial anomalies. Other brain anomalies identified included micrencephaly, ventriculomegaly, and hypoplasia of the inferior olivary eminences. Conclusion. Patients with classic FAS have a high incidence of midline brain anomalies. This finding is consistent with the concept that the midline CNS is a developmental field that is particularly susceptible to the teratogenic effects of alcohol. Furthermore, patients with more severe facial dysmorphologic characteristics are more likely to have midline brain anomalies. In addition, we observed a high incidence of micrencephaly with a wide range of severity. C1 UNIV IOWA HOSP & CLIN,COLL MED,DEPT PSYCHIAT,IOWA CITY,IA 52242. UNIV IOWA HOSP & CLIN,COLL MED,DEPT PEDIAT,IOWA CITY,IA 52242. UNIV IOWA HOSP & CLIN,COLL MED,DEPT RADIOL,IOWA CITY,IA 52242. UNIV S DAKOTA,SCH MED,DEPT OBSTET & GYNECOL,BIRTH DEFECTS GENET CTR,VERMILLION,SD 57069. UNIV S DAKOTA,SCH MED,DEPT PEDIAT,VERMILLION,SD 57069. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Swayze, VW (reprint author), VET AFFAIRS MED CTR,IOWA CITY,IA 52246, 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 FU NIMH NIH HHS [MH31593, MH40856, MHCRC 43271] NR 94 TC 157 Z9 158 U1 3 U2 15 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1997 VL 99 IS 2 BP 232 EP 240 DI 10.1542/peds.99.2.232 PG 9 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200017 PM 9024452 ER PT J AU Berlin, CM McCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Mulinare, J Hoskins, IA Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Smolinske, SC AF Berlin, CM McCarver, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT Bennett, DR Mulinare, J Hoskins, IA Kaufman, P Rieder, MJ Troendle, G Yaffe, SJ Cote, CJ Szefler, SJ Smolinske, SC TI ''Inactive'' ingredients in pharmaceutical products: Update (subject review) SO PEDIATRICS LA English DT Review ID BIRTH-WEIGHT INFANTS; INDUCED HISTAMINE-RELEASE; BENZYL ALCOHOL TOXICITY; PROPYLENE-GLYCOL; BENZALKONIUM CHLORIDE; DOUBLE-BLIND; ADVERSE REACTIONS; CHILDHOOD ASTHMA; DRUG ADDITIVES; INTRAVENTRICULAR HEMORRHAGE AB Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement(1) recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Berlin, CM (reprint author), AMER MED ASSOC,US PHARMACOPEIA,515 N STATE ST,CHICAGO,IL 60610, USA. NR 187 TC 82 Z9 84 U1 2 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1997 VL 99 IS 2 BP 268 EP 278 PG 11 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200026 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Hall, CB Hadler, S Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Hall, CB Hadler, S Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B TI Acellular pertussis vaccine: Recommendations for use as the initial series in infants and children SO PEDIATRICS LA English DT Article ID EFFICACY; TETANUS; TRIAL AB In 1991 and 1992, the US Food and Drug Administration approved two acellular pertussis vaccines combined with diphtheria and tetanus toxoids for use as the fourth and fifth doses after the initial three-dose primary series with the standard whole-cell pertussis vaccine administered at 2, 4, and 6 months of age. Recently completed trials of acellular pertussis vaccines conducted in Europe have documented the efficacy of these vaccines when administered as a primary series in infancy. Based on these studies, two acellular pertussis vaccines, Tripedia (Connaught Laboratories, Swiftwater, PA) and ACEL-IMUNE (Wyeth-Lederle Laboratories, Pearl River, NY), were licensed by the Food and Drug Administration for the initial three-dose series. Additional acellular pertussis vaccines are likely to be licensed for use in infants in the future. The recommendations in this statement supplement previous American Academy of Pediatrics guidelines for the use of acellular pertussis vaccines.(1-4) C1 US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Halsey, NA (reprint author), CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333, USA. NR 22 TC 20 Z9 21 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1997 VL 99 IS 2 BP 282 EP 288 PG 7 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200028 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Hall, CB Breiman, R Hadler, SC Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B McCracken, GH Kaplan, SL Jorgensen, JH AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Hall, CB Breiman, R Hadler, SC Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B McCracken, GH Kaplan, SL Jorgensen, JH TI Therapy for children with invasive pneumococcal infections SO PEDIATRICS LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; BETA-LACTAM ANTIBIOTICS; EXPERIMENTAL PENICILLIN-RESISTANT; HIGH-LEVEL PENICILLIN; SICKLE-CELL DISEASE; BACTERIAL-MENINGITIS; CEREBROSPINAL-FLUID; UNITED-STATES; ANTIMICROBIAL RESISTANCE; HAEMOPHILUS-INFLUENZAE AB This statement provides guidelines for therapy of children with serious infections possibly caused by Streptococcus pneumoniae. Resistance of invasive pneumococcal strains to penicillin, cefotaxime, and ceftriaxone has increased over the past few years. Reports of failures of cefotaxime or ceftriaxone in the treatment of children with meningitis caused by resistant S pneumoniae necessitates a revision of Academy recommendations. For nonmeningeal infections, modifications of the initial therapy need to be considered only for patients who are critically ill and those who have a severe underlying or potentially immunocompromising condition or patients from whom a highly resistant strain is isolated. Because vancomycin is the only antibiotic to which all S pneumoniae strains are susceptible, its use should be restricted to minimize the emergence of vancomycin-resistant organisms. Patients with probable aseptic (viral) meningitis should not be treated with vancomycin. These recommendations are subject to change as new information becomes available. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. NR 82 TC 115 Z9 121 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1997 VL 99 IS 2 BP 289 EP 299 PG 11 WC Pediatrics SC Pediatrics GA WE302 UT WOS:A1997WE30200029 ER PT J AU Robinson, DL AF Robinson, DL TI A test of the Hendrickson postulate that reduced EEG response variance causes increased AEP contour length: Implications for the 'neural transmission errors' theory of intelligence SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article ID PSYCHOMETRIC INTELLIGENCE; STRING LENGTH; POTENTIALS; IQ AB EEG responses to auditory tones were recorded from 76 human subjects in six different age groups with equal numbers of males and females in each group. Care was taken to reproduce the conditions described by D. E. Hendrickson (1982) who had earlier reported high correlations between intelligence test scores and her new 'string' and 'variance' measures of EEG response differences. The results obtained in the present study show that the Hendrickson string variable derives from EEG activity in the high frequency band whereas the Hendrickson variance variable derives from activity in the low frequency band. In addition, there is a high positive correlation between the string variable and the variance of corresponding high frequency activity in individual sweeps. These results disprove the Hendricksons' 'neural transmission errors' theory of intelligence which requires a negative correlation between the number and amplitude of peaks in the averaged evoked potential (AEP) waveform and the variance of corresponding activity in the individual EEG epochs from which the AEP is derived. It is concluded that the Hendrickson theory fails at the critical point where it seeks to link its hypothetical transmission errors to actual EEG differences that sometimes correlate with intelligence differences. (C) 1997 Elsevier Science Ltd. C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. KUWAIT UNIV,FAC MED,DEPT COMMUN MED & BEHAV SCI,SAFAT 13110,KUWAIT. NR 22 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD FEB PY 1997 VL 22 IS 2 BP 173 EP 182 DI 10.1016/S0191-8869(96)00197-3 PG 10 WC Psychology, Social SC Psychology GA WG707 UT WOS:A1997WG70700005 ER PT J AU Li, CY Peoples, RW Weight, FF AF Li, CY Peoples, RW Weight, FF TI Enhancement of ATP-activated current by protons in dorsal root ganglion neurons SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ATP; pH; ion channel; P-2X purinoceptors; sensory neuron; patch-clamp ID BULLFROG SENSORY NEURONS; RAT SYMPATHETIC NEURONS; MAMMALIAN NEURONS; SYNAPTIC TRANSMISSION; HIPPOCAMPAL-NEURONS; RECEPTOR CHANNELS; ION CHANNELS; RESPONSES; PH; MEMBRANE AB The effect of pH on ATP-activated current in bullfrog dorsal root ganglion neurons was studied using the whole-cell patch-clamp technique. ATP-activated current amplitude was highly dependent upon extracellular pH. An acid pH increased, whereas alkaline pH decreased, ATP-activated current amplitude. The half-maximal pH (EC(50)) for potentiation of 2.5 mu M ATP-activated current was 7.2. Acidification alone did not activate detectable current and, at an acid pH, ATP-activated current was abolished by suramin. Proton-induced enhancement of ATP-activated current was not sensitive to membrane potential between -80 and +40 mV, and did not involve a shift in reversal potential. Lowering pH from 7.2 to 6.5 or elevating pH from 7.2 to 8.0 shifted the ATP concentration/response curve to the left or right, respectively, without changing the maximal response to ATP Protons increased the time constant of deactivation without affecting the time constant of activation or desensitization of ATP-activated current. Alteration of patch-pipette (intracellular) pH did not affect the enhancement of ATP-activated current by extracellular protons. Diethylpyrocarbonate (DEP). dithiothreitol (DTT), 5,5'-dithio-bis-(2-nitro-benzoic acid) (DTNB), or N-ethylmaleimide (NEM) did not affect enhancement of ATP-activated current by protons. The results suggest that extracellular protons, at physiological concentrations, can regulate the function of P-2X purinoceptors by modulating the affinity of the ATP-binding site. RP Li, CY (reprint author), NIAAA,CELLULAR & MOL NEUROBIOL LAB,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 44 TC 36 Z9 37 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD FEB PY 1997 VL 433 IS 4 BP 446 EP 454 DI 10.1007/s004240050299 PG 9 WC Physiology SC Physiology GA WH426 UT WOS:A1997WH42600009 PM 9000423 ER PT J AU Sakai, T Ambudkar, IS AF Sakai, T Ambudkar, IS TI Role for protein kinase in Ca2+-dependent feedback modulation of divalent cation influx in internal-Ca2+-store-depleted rat parotid gland cells SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE Ca2+ entry; Mn2+ entry; protein kinase; staurosporine; K-252a; salivary glands ID CAPACITATIVE CALCIUM-ENTRY; INTRACELLULAR CA2+ STORES; ACINAR-CELLS; PLASMA-MEMBRANE; INOSITOL PHOSPHATE; HUMAN PLATELETS; THAPSIGARGIN; DEPLETION; ACTIVATION; INHIBITION AB Divalent cation (Ca2+ and Mn2+) influx, stimulated by internal Ca2+ store depletion, into rat parotid acinar cells is inhibited by conditions which increase protein phosphorylation [T. Sakai and I.S. Ambudkar (1996) Am J Physiol 271:C284-C294]. The present study examines the involvement of this protein phosphorylation and Ca2+ in the store-dependent inactivation of divalent cation entry. Internal Ca2+ store depletion, achieved by incubation (30 min) of cells in nominally Ca2+-free medium containing either carbachol or thapsigargin, stimulated Ca2+. and Mn2+. influx into cells. In either case, inclusion of 1.5 mM Ca2+ for the last 5 min of incubation resulted in a decrease in Ca2+ (33-41%) and Mn2+ (50%) influx, which could not be accounted for by internal Ca2+ store refill. The inhibition was prevented when internal-store-depleted cells were treated (prior to incubation with Ca2+) with either staurosporine or K-252a, but not with H-7 or KN-93. Refilling of internal Ca2+ store(s) in carbachol-treated cells (incubation with Ca(2+)atropine) induced complete inhibition of divalent cation influx, which was not prevented by treatment with protein kinase inhibitors. These data suggest the staurosporine-sensitive (and K-252a-sensitive) protein phosphorylation is not involved in Ca2+-store-refilling-dependent inactivation of Ca2+ influx but mediates a Ca2+-dependent feedback modulation of divalent cation influx in rat parotid gland acinar cells. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,SECRETORY PHYSIOL SECT,NIH,BETHESDA,MD 20892. NR 32 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD FEB PY 1997 VL 433 IS 4 BP 464 EP 471 DI 10.1007/s004240050301 PG 8 WC Physiology SC Physiology GA WH426 UT WOS:A1997WH42600011 PM 9000425 ER PT J AU Goldstein, JA Ishizaki, T Chiba, K deMorais, SMF Bell, D Krahn, PM Evans, DAP AF Goldstein, JA Ishizaki, T Chiba, K deMorais, SMF Bell, D Krahn, PM Evans, DAP TI Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations SO PHARMACOGENETICS LA English DT Article DE CYP2C19; mephenytoin polymorphism ID S-MEPHENYTOIN; GENETIC-POLYMORPHISM; HYDROXYLATION DEFICIENCY; CHINESE POPULATION; NATIVE CHINESE; DEBRISOQUINE; OXIDATION; JAPANESE; PHARMACOKINETICS; EXPRESSION AB The 4'-hydroxylation of S-mephenytoin is polymorphic in man. The poor metabolizer (PM) phenotype exhibits a lower frequency in Caucasians (2-5%) compared to Oriental populations (13-23%). Previous studies from our laboratory have described two mutations (CYP2C19(m1) and CYP2C19(m2)) which account for similar to 100% of Oriental and similar to 85% of Caucasian PM alleles. The present study examined whether the genotype predicted the phenotype in Japanese, Filipino and Saudi Arabian populations, and compared the frequencies of the defective CYP2C19 alleles in these populations with those found in European-Americans, Chinese-Taiwanese, and African-Americans from North Carolina. Among 53 Japanese, 15% were PMs and among 52 Filipinos 23% were PMs. Among 97 Saudi Arabians, only two were PMs. There was a complete concordance between genotype and phenotype in all three populations. The incidence of CYP2C19(m1) was 0.23 (95% confidence limits 0.15-0.31) in Japanese, 0.39 (95% confidence limits 0.29-0.48) in Filipinos, 0.32 (95% confidence limits 0.26-0.38) in Chinese-Taiwanese, 0.15 (95% confidence limits 0.10-0.20) in Saudi Arabians, 0.13 (95% confidence limits 0.08-0.17) in European-Americans, and 0.25 in African-Americans from North Carolina (95% confidence limits 0.14-0.31). The incidence of CYP2C19(m1) in Saudi Arabians was similar to that found in European-Americans, and significantly lower-than that found in Oriental populations for African-Americans (p < 0.05). CYP2C19(m2) was not found in European-Americans, Saudi Arabians or African-Americans (95%, confidence limits 0-0.014). The incidence of CYP2C19(m2) in the three Oriental populations ranged from 0.10 (95% confidence limits 0.05-0.17) in Japanese and 0.08 (95% confidence limits 0.03-0.13) in Filipinos to 0.06 (95% confidence limits 0.03-0.08) in Chinese-Taiwanese. C1 INT MED CTR JAPAN,RES INST,DEPT CLIN PHARMACOL,SHINJUKU KU,TOYAMA 162,JAPAN. KING FAISAL SPECIALIST HOSP & RES CTR,RIYADH 11211,SAUDI ARABIA. RIYADH ARMED FORCES HOSP,RIYADH 11159,SAUDI ARABIA. RP Goldstein, JA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 33 TC 227 Z9 238 U1 0 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1997 VL 7 IS 1 BP 59 EP 64 DI 10.1097/00008571-199702000-00008 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA WT253 UT WOS:A1997WT25300008 PM 9110363 ER PT J AU Shoaib, M Thorndike, E Schindler, CW Goldberg, SR AF Shoaib, M Thorndike, E Schindler, CW Goldberg, SR TI Discriminative stimulus effects of nicotine and chronic tolerance SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE nicotine; discrimination; tolerance; chronic treatment; acute treatment ID LOCOMOTOR-ACTIVITY; SQUIRREL-MONKEYS; CROSS-TOLERANCE; RATS; BEHAVIOR; SUPPRESSION; INJECTIONS AB Tolerance to discriminative stimulus (DS) effects of drugs, as observed by a shift of the dose-response curve to the right, has been observed with many addictive drugs (e.g. amphetamine, cocaine and morphine). Chronic administration of nicotine has been reported to produce tolerance to the locomotor depressant effects and aversive stimulus properties of nicotine; however, the DS effects of nicotine have not been examined for development of tolerance following chronic treatment. We report on experiments utilising a cumulative-dosing drug discrimination paradigm. Eight, male Sprague-Dawley rats were trained to discriminate nicotine (0.4 mg/kg s.c.) from saline under a fixed ratio (FR 10) schedule for food reinforcement. Multiple training sessions were given daily, and once criteria was met, cumulative doses of nicotine (0.025-1.2 mg/kg s.c.) were evaluated. Rats acquired the nicotine discrimination after 80 sessions. During this period, rats developed tolerance to the rate-depressing effects of nicotine after 20 nicotine-training sessions. Chronic treatments of nicotine in the rat's home cage for 7 days during suspended training failed to shift the dose-response curve for nicotine. Increasing the frequency to three daily injections also had no effect on nicotine discrimination. Furthermore, continuous infusions of nicotine (6.4 mg/kg/day) delivered via osmotic minipumps failed to shift the dose-response curve. No physical signs of withdrawal were apparent, particularly on lever responding, following removal of the minipump. These results suggest that under the conditions described, chronic tolerance to nicotine's DS does not develop readily. Copyright (C) 1997 Elsevier Science Inc. RP Shoaib, M (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 26 TC 16 Z9 16 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1997 VL 56 IS 2 BP 167 EP 173 DI 10.1016/S0091-3057(96)00174-8 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WJ643 UT WOS:A1997WJ64300002 PM 9050071 ER PT J AU Pickworth, WB Fant, RV Butschky, MF Henningfield, JE AF Pickworth, WB Fant, RV Butschky, MF Henningfield, JE TI Effects of mecamylamine on spontaneous EEG and performance in smokers and non-smokers SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE mecamylamine; EEG; performance; cognition; nicotine ID SHORT-TERM-MEMORY; TOBACCO WITHDRAWAL; CIGARETTE-SMOKING; HUMAN VOLUNTEERS; NICOTINE; ALZHEIMERS; ABSTINENCE; ATTENTION; RAT AB In a previous study, mecamylamine, a centrally active nicotine antagonist, exacerbated EEG signs of tobacco abstinence in abstinent smokers. In the present study, the effects of mecamylamine were compared in non-smokers and nondeprived smokers. Mecamylamine (0, 5 and 10 mg, p.o.) was administered to six smokers and six non-smokers; eight of these subjects were also given a 20 mg dose. Before drug administration, resting EEG was similar in both groups. In both groups, mecamylamine caused dose-related decreases in alpha frequency and increases in delta frequency; beta frequency was increased by the 5 and 10 mg doses. The similarity of effects in smokers and non-smokers suggests a direct pharmacological action rather than precipitated nicotine withdrawal. Significant baseline differences existed between smokers and nonsmokers in systolic blood pressure, pulse rate, skin temperature and pupil diameter. Response time slowed in both vigilance and distractibility tasks and delayed recall was impaired. Mecamylamine increased ratings of: ''relaxed,'' ''nodding,'' ''sleepy'' and ''coasting.'' This small-sample study tentatively suggests that nicotinic cholinergic mechanisms modulate brain electrical activity and cognitive function in smokers and non-smokers. Disruption of these neural systems could mediate the symptoms of tobacco withdrawal and be involved in the pathophysiology of Alzheimer's disease. RP Pickworth, WB (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 38 TC 29 Z9 29 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1997 VL 56 IS 2 BP 181 EP 187 DI 10.1016/S0091-3057(96)00183-9 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WJ643 UT WOS:A1997WJ64300004 PM 9050073 ER PT J AU Lapin, IP Yuwiler, A AF Lapin, IP Yuwiler, A TI Modulation of the inhibitory effect of phenylethylamine on spontaneous motor activity in mice by CPP-(+/-)-3-(2-Carboxypiperazin-4-YL)-propyl-1-phosphonic acid SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE phenylethylamine; CPP; antagonists of NMDA receptors; MAO-B; spontaneous motor activity; mice AB beta-phenyl-ethylamine (PEA) at dose of 50 mg/kg inhibits spontaneous motor activity in mice. CPP-(+/-)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid, a selective and competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, in doses of 0.2-10 mg/kg dose-dependently antagonizes this inhibitory effect of PEA. This effect of CPP appeared to be selective because the inhibitory action of PEA was not altered by pretreament with noncompetitive antagonists of NMDA receptors, such as dizocilpine (MK-801), phencyclidine (PCP), 1-phenylcyclohexylamine (PCA) or by antagonists of other behavioral effects of PEA such as haloperidol, baclofen and phenibut (beta-phenyl-GABA). CPP failed to antagonize the inhibitory effect of other tested drugs such as diazepam, haloperidol, baclofen and phenibut. Intracerebroventricularly administered NMDA (0.2 mu M), an agonist of NMDA receptors, suppressed the antagonistic effects of CPP against PEA. This suggests that anti-PEA effect of CPP is related to NMDA receptors. Anti-PEA effect of CPP is not due to accelerated deamination of PEA in CPP-treated mice. When small doses of PEA (5 and 10 mg/kg) and CPP (0.2 and 1 mg/kg) were used, the synergism of two drugs was observed. CPP (1 mg/kg) and deprenyl (0.5 mg/kg), an inhibitor monoamine oxidase of B type (MAO-B), had additive effects on PEA-induced inhibition of locomotion. This effect was not associated with any further inhibition of activity of brain MAO-B (over the inhibition induced by deprenyl alone-by 65%) under high (80 mu M) or low (4.3 mu M) concentration of PEA as a substrate in the medium. Mechanism of the interaction of CPP and PEA, two drugs belonging to different groups of biologically active compounds, deserves further studies. Copyright (C) 1997 Elsevier Science Inc. C1 VET ADM MED CTR BRENTWOOD, NEUROCHEM RES LAB, LOS ANGELES, CA 90073 USA. NINCDS, NEURONAL EXCITABIL SECT, NIH, BETHESDA, MD 20892 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1997 VL 56 IS 2 BP 199 EP 204 DI 10.1016/S0091-3057(97)00181-0 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WJ643 UT WOS:A1997WJ64300006 PM 9050075 ER PT J AU Tachibana, M AF Tachibana, M TI Evidence to suggest that expression of MITF induces melanocyte differentiation and haploinsufficiency of MITF causes Waardenburg syndrome type 2A SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT XVIth International Pigment Cell Conference CY OCT 28-NOV 03, 1996 CL ANAHEIM, CA DE MITF; melanocyte differentiation; Waardenburg syndrome ID LOOP-HELIX PROTEIN; MOUSE FIBROBLASTS; TYROSINASE CDNA; PAIRED DOMAIN; HUMAN HOMOLOG; GENE; MUTATIONS; DISORDER; DISEASE; GROWTH AB MITF (microphthalmia-associated transcription factor) encodes a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif. Ectopic expression of MITF is found to convert NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci, which superficially resembled those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dendritic cells that express melanogenic marker proteins such as tyrosinase and tyrosinase-related protein 1. Such properties were not observed in cells transfected with the closely related gene, TFE3. These findings indicated that MITF is involved in melanocyte differentiation. Two mutations (C760-->T and C895-->T) in MITF are found to be associated with individuals with Waardenburg syndrome type 2 (WS2). These mutations create stop codons in exon 7 and 8, respectively and probably result in truncated proteins lacking HLH-Zip or Zip structure. To understand how these MITF mutations cause WS2 in heterozygotes, mutant MITF proteins were generated and used for DNA-binding and luciferase reporter assays. The mutated MITF proteins lose their DNA-binding activity and fail to transactivate the promoter of the tyrosinase gene. However, these mutated proteins do not appear to interfere with the activity of wild-type MITF protein in these assays, indicating that they do not show a dominant-negative effect. These findings suggest that the phenotypes of the two WS2 families are caused by loss-of-function mutations in one of the two MITF alleles, resulting in haploinsufficiency of the MITF protein, the transcription factor necessary for normal melanocyte differentiation. RP Tachibana, M (reprint author), NIDOCD,MOL GENET LAB,SECT GENE EXPRESS & FUNCT,5 RES COURT,ROCKVILLE,MD 20850, USA. NR 32 TC 48 Z9 49 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD FEB-APR PY 1997 VL 10 IS 1-2 BP 25 EP 33 DI 10.1111/j.1600-0749.1997.tb00462.x PG 9 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA XA554 UT WOS:A1997XA55400006 PM 9170159 ER PT J AU Kim, LT Yamada, KM AF Kim, LT Yamada, KM TI The regulation of expression of integrin receptors SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review ID GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX PROTEINS; ALKALINE-PHOSPHATASE ACTIVITY; CELL-ADHESION RECEPTORS; HUMAN ENDOTHELIAL-CELLS; GLYCOPROTEIN-IIB GENE; OSTEO-SARCOMA CELLS; CYTOPLASMIC DOMAIN; RETINOIC ACID; MESSENGER-RNA AB The integrins are a family of cell surface receptors that mediate cell extracellular matrix and cell-cell interactions. The quantities and activities of these receptors are modulated during a wide variety of biological processes. A variety of agents have been found to affect expression of integrins and their function. These include cytokines, hormones, and pharmacologic agents. Mechanisms regulating integrin expression and function include regulation of protein levels by transcriptional or posttranscriptional mechanisms, alteration of protein structure by alternative splicing of mRNA, mobilization to the cell surface of preexisting intracellular stores of integrins, and modulation of receptor activity (inside-out signaling). We review studies that assess the effects of external agents on integrin levels using the cytokine TGF beta as an example. We also review studies that analyze integrin regulation with an emphasis on the control of integrin gene transcription. This review shows that the strategies for integrin modulation are quite complex. This regulatory sophistication is likely necessary, given the critical role that integrins play in the myriad social interactions of cells. RP Kim, LT (reprint author), NIDR,LDB,DIR,NIH,BLDG 30,ROOM 424,30 CONVENT DR,MSC 4370,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 118 TC 80 Z9 82 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD FEB PY 1997 VL 214 IS 2 BP 123 EP 131 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WJ064 UT WOS:A1997WJ06400004 PM 9034129 ER PT J AU Oriji, GK Keiser, HR AF Oriji, GK Keiser, HR TI Cyclosporine A-induced contractions and prostacyclin release are maintained by extracellular calcium in rat aortic rings: Role of protein kinase C SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID VASCULAR RELAXATION; ANGIOTENSIN-II; PHORBOL; PHOSPHOLIPASE-A2; PHOSPHORYLATION; DIFFERENTIATION; HEPATOCYTES; LIPOMODULIN; RESPONSES; RABBIT AB Chronic treatment with the immunosuppressive drug, Cyclosporine A (CsA), is associated with increased intracellular calcium in vascular smooth muscle cells, which may cause vasoconstriction and/or activate phospholipase A(2). We used rat aortic rings to investigate the role of protein kinase C (PKC) in CsA-induced contractions and secondary prostacyclin (PGI(2)) release. CsA (10(-9) M) produced a sustained contraction in rat aortic rings. Both CsA-induced contractions and PGI(2) release were inhibited 84 to 89% by 10(-9) M, and 99 to 100% by 10(-6) M pretreatment doses of any of three different PKC inhibitors, i.e. 1-(5-isoquinolinesulfonylmethyl) piperazine (H7), staurosporine or 1-(5-isoquinolinesulfonyl) piperazine. Pretreatment with (10(-9) M) of diltiazem (a voltage-sensitive L-type calcium channel blocker) completely inhibited both CsA-induced contractions and PGI(2) release. Conversely, pretreatment with (10(-9) M) of thapsigargin (an intracellular calcium channel blocker) did not alter the action of CsA. These results strongly suggest that PKC, in association with an influx of extracellular calcium mediates CsA-induced contractions and secondary PGI(2) release in rat aortic rings. RP Oriji, GK (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,BETHESDA,MD 20892, USA. NR 39 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD FEB PY 1997 VL 56 IS 2 BP 151 EP 156 DI 10.1016/S0952-3278(97)90512-3 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA WH609 UT WOS:A1997WH60900011 PM 9051725 ER PT J AU Copeland, WC AF Copeland, WC TI Expression, purification, and characterization of the two human primase subunits and truncated complexes from Escherichia coli SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID DNA-POLYMERASE-ALPHA; DROSOPHILA-MELANOGASTER EMBRYOS; CALF THYMUS; MOLECULAR-CLONING; RNA-POLYMERASE; ACTIVE-CENTER; IN-VITRO; REPLICATION; CELLS; INITIATION AB Eukaryotic DNA replication is primed by small RNA primers synthesized by the two-subunit primase complex, p58 and p49, where the p49 subunit contains the catalytic activity. The cDNA's for these two human DNA primase subunits were amplified, sequenced, and overexpressed in Escherichia coli. Specific assays for initiation revealed that although the smaller subunit contains catalytic function, initiation requires the presence of the larger subunit. A two-plasmid system was developed for the coexpression of both subunits in E. coli. This system was exploited to express and study truncations of the larger, human p58 subunit in order to investigate its role in primer formation. Analysis of the complexes formed between the truncated human p58 subunits and the native human p49 subunit revealed that protein-protein contacts between these two subunits occur over several regions of the human p58 subunit. Of four primase complexes containing different truncated p58 subunits only one complex supported initiation as measured by the formation of dinucleotides. All complexes supported the extension of oligoA-primed polydT, suggesting that the intrinsic RNA polymerase activity residing in the smaller subunit was not affected. These results suggest that several regions of the human p58 subunit are in contact with the human p49 subunit during the initiation of primer synthesis. (C) 1997 Academic Press. RP Copeland, WC (reprint author), NIEHS,GENET MOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 29 TC 24 Z9 24 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD FEB PY 1997 VL 9 IS 1 BP 1 EP 9 DI 10.1006/prep.1996.0665 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA WG003 UT WOS:A1997WG00300001 PM 9116489 ER PT J AU Hurley, JH Newton, AC Parker, PJ Blumberg, PM Nishizuka, Y AF Hurley, JH Newton, AC Parker, PJ Blumberg, PM Nishizuka, Y TI Taxonomy and function of C1 protein kinase C homology domains SO PROTEIN SCIENCE LA English DT Article DE diacylglycerol kinase; GTPase activating protein; guanine nucleotide exchange factor; kinase suppressor of Pas; n-chimaerin; phorbol ester; Raf; unc-13; Vav ID PHORBOL ESTER BINDING; CYSTEINE-RICH DOMAIN; DIACYLGLYCEROL KINASE; ACTIVATION; ZINC; PROTOONCOGENE; TARGET; VAV AB C1 domains are compact alpha/beta structural units of about 50 amino acids which tightly bind two zinc ions. These domains were first discovered as the loci of phorbol ester and diacylglycerol binding to conventional protein kinase C isozymes, which contain two C1 domains (C1A and C1B) in their N-terminal regulatory regions. We present a comprehensive list of 54 C1 domains occurring singly or doubly in 34 different proteins. Many C1 domains and C1 domain-containing proteins bind phorbol esters, but many others do not. By combining analysis of 54 C1 domain sequences with information from previously reported solution and crystal structure determinations and site-directed mutagenesis, profiles are derived and used to classify C1 domains. Twenty-six C1 domains fit the profile for phorbol-ester binding and are termed "typical." Twenty-eight other domains fit the profile for the overall C1 domain fold but do not fit the profile for phorbol ester binding, and are termed "atypical." Proteins containing typical C1 domains are predicted to be regulated by diacylglycerol, whereas those containing only atypical domains are not. C1 UNIV CALIF SAN DIEGO, DEPT PHARMACOL, LA JOLLA, CA 92093 USA. IMPERIAL CANC RES FUND, PROT PHOSPHORYLAT LAB, LONDON WC2A 3PX, ENGLAND. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, MOL MECH TUMOR PROMOT SECT, BETHESDA, MD 20892 USA. KOBE UNIV, BIOSIGNAL RES CTR, NADA KU, KOBE 657, JAPAN. RP Hurley, JH (reprint author), NIDDKD, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. RI Parker, Peter/D-5192-2013 NR 28 TC 265 Z9 268 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD FEB PY 1997 VL 6 IS 2 BP 477 EP 480 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH566 UT WOS:A1997WH56600028 PM 9041654 ER PT J AU Mozzarelli, A Rivetti, C Rossi, GL Eaton, WA Henry, ER AF Mozzarelli, A Rivetti, C Rossi, GL Eaton, WA Henry, ER TI Allosteric effectors do not alter the oxygen affinity of hemoglobin crystals SO PROTEIN SCIENCE LA English DT Article DE allosteric models; hemoglobin crystals; microspectrophotometry; oxygen binding ID COOPERATIVE FREE-ENERGIES; T-STATE; LIGATION STATES; LIGAND-BINDING; STEREOCHEMISTRY; RESOLUTION; DEOXYHEMOGLOBIN; MODEL AB In solution, the oxygen affinity of hemoglobin in the T quaternary structure is decreased in the presence of allosteric effecters such as protons and organic phosphates. To explain these effects, as well as the absence of the Bohr effect and the lower oxygen affinity of T-state hemoglobin in the crystal compared to solution, Rivetti C et al. (1993a, Biochemistry 32:2888-2906) suggested that there are high- and low-affinity subunit conformations of T, associated with broken and unbroken intersubunit salt bridges. In this model, the crystal of T-state hemoglobin has the lowest possible oxygen affinity because the salt bridges remain intact upon oxygenation. Binding of allosteric effecters in the crystal should therefore not influence the oxygen affinity. To test this hypothesis, we used polarized absorption spectroscopy to measure oxygen binding curves of single crystals of hemoglobin in the T quaternary structure in the presence of the ''strong'' allosteric effecters, inositol hexaphosphate and bezafibrate. In solution, these effecters reduce the oxygen affinity of the T state by 10-30-fold. We find no change in affinity (< 10%) of the crystal. The crystal binding curve, moreover, is noncooperative, which is consistent with the essential feature of the two-state allosteric model of Monod J, Wyman J, and Changeux JP (1965, J Mol Biol 12:88-118) that cooperative binding requires a change in quaternary structure. Noncooperative binding by the crystal is not caused by cooperative interactions being masked by fortuitous compensation from a difference in the affinity of the alpha and beta subunits. This was shown by calculating the separate alpha and beta subunit binding curves from the two sets of polarized optical spectra using geometric factors from the X-ray structures of deoxygenated and fully oxygenated T-state molecules determined by Paoli M et al. (1996, J Mol Biol 256:775-792). C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Mozzarelli, A (reprint author), UNIV PARMA,INST BIOCHEM SCI,I-43100 PARMA,ITALY. RI Henry, Eric/J-3414-2013; Mozzarelli, Andrea/C-3615-2014; OI Henry, Eric/0000-0002-5648-8696; Mozzarelli, Andrea/0000-0003-3762-0062; Rivetti, Claudio/0000-0003-3775-6779 NR 39 TC 48 Z9 48 U1 0 U2 2 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 FEB PY 1997 VL 6 IS 2 BP 484 EP 489 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH566 UT WOS:A1997WH56600030 PM 9041656 ER PT J AU Hoffman, RC Castner, BJ Gerhart, M Gibson, MG Rasmussen, BD March, CJ Weatherbee, J Tsang, M Gustchina, A SchalkHihi, C Reshetnikova, L Wlodawer, A AF Hoffman, RC Castner, BJ Gerhart, M Gibson, MG Rasmussen, BD March, CJ Weatherbee, J Tsang, M Gustchina, A SchalkHihi, C Reshetnikova, L Wlodawer, A TI Direct evidence of a heterotrimeric complex of human interleukin-4 with its receptors (vol 4, pg 382, 1995) SO PROTEIN SCIENCE LA English DT Correction, Addition C1 R&D SYST,DIV BIOTECHNOL,MINNEAPOLIS,MN 55413. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL STRUCT LAB,FREDERICK,MD 21702. RP Hoffman, RC (reprint author), IMMUNEX RES & DEV CORP,51 UNIV ST,SEATTLE,WA 98101, USA. NR 1 TC 2 Z9 2 U1 1 U2 1 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 FEB PY 1997 VL 6 IS 2 BP 494 EP 494 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH566 UT WOS:A1997WH56600031 ER PT J AU Geller, M Miller, M Swanson, SM Maizel, J AF Geller, M Miller, M Swanson, SM Maizel, J TI Analysis of the structure of HIV-1 protease complexed with a hexapeptide inhibitor .2. Molecular dynamic studies of the active site region SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE aspartic protease; HIV-1; molecular dynamics; molecular modeling ID IMMUNODEFICIENCY VIRUS-1 PROTEASE; ASPARTIC PROTEINASES; BINDING; PERTURBATION; SIMULATION AB Six models of the catalytic site of HIV-1 protease complexed with a reduced peptide inhibitor, MVT-101, were investigated, These studies focused on the details of protonation of the active site, its total net charge and hydrogen bonding pattern, which was consistent with both the observed coplanar configuration of the acidic groups of the catalytic aspartates (Asp-25 and Asp-125) and the observed binding mode of the inhibitor, Molecular dynamic simulations using AMBER 4.0 indicated that the active site should be neutral, The planarity of the aspartate dyad may be due to the formation of two hydrogen bonds: one between the inner O-delta 1 oxygen atoms of the two catalytic aspartates and another between the O-delta 2 atom of Asp-125 and the nitrogen atom of the reduced peptide bond of the bound inhibitor, This would require two additional protonations, either of both aspartates, or of one Asp and the amido nitrogen atom of Nle-204, Our results favor the Asp-inhibitor protonation but the other one is not excluded, Implications of these findings for the mechanism of enzymatic catalysis are discussed, Dynamic properties of the hydrogen bond network in the active site and an analysis of the interaction energy between the inhibitor and the protease are presented. (C) 1997 Wiley-Liss, Inc. C1 NCI, FREDERICK CANC RES FACIL & DEV CTR, MACROMOL STRUCT LAB, FREDERICK, MD 21702 USA. UNIV WARSAW, INST EXPT PHYS, DEPT BIOPHYS, WARSAW, POLAND. TEXAS A&M UNIV, DEPT BIOCHEM & BIOPHYS, COLLEGE STN, TX 77843 USA. RP Geller, M (reprint author), NCI, FREDERICK CANC RES FACIL & DEV CTR, MATH BIOL LAB, POB B, FREDERICK, MD 21702 USA. RI Miller, Maria/I-1636-2013 OI Miller, Maria/0000-0003-0252-5348 FU NCI NIH HHS [N01-CO-46000] NR 26 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-3585 J9 PROTEINS JI Proteins PD FEB PY 1997 VL 27 IS 2 BP 195 EP 203 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WL689 UT WOS:A1997WL68900005 PM 9061783 ER PT J AU Miller, M Geller, M Gribskov, M Kent, SBH AF Miller, M Geller, M Gribskov, M Kent, SBH TI Analysis of the structure of chemically synthesized HIV-1 protease complexed with a hexapeptide inhibitor .1. Crystallographic refinement of 2 angstrom data SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE aspartic protease; HIV-1; complex with inhibitor ID HUMAN IMMUNODEFICIENCY VIRUS-1; CRYSTAL-STRUCTURE; TYPE-1 PROTEASE; ASPARTIC PROTEINASES; MOLECULAR-DYNAMICS; RESOLUTION; BINDING; DESIGN AB The structure of a complex between a hexapeptide-based inhibitor, MVT-101, and the chemically synthesized (Aba 67,95,167,195; Aba: L-alpha-amino-butyric acid) protease from the human immunodeficiency virus (HIV-1), reported previously at 2.3 Angstrom has now been refined to a crystallographic R factor of 15.4% at 2.0 Angstrom resolution, Root mean square deviations from ideality are 0.18 Angstrom for bond lengths and 2.4 degrees for the angles, The inhibitor can be fitted to the difference electron density map in two alternative orientations, Drastic differences are observed for positions and interactions at P3/S3 and P3'/S3' subsites of the two orientations due to different crystallographic environments. (C) 1997 Wiley-Liss, Inc. C1 NCI, FREDERICK CANC RES FACIL & DEV CTR, MATH BIOL LAB, FREDERICK, MD 21701 USA. UNIV WARSAW, INST EXPT PHYS, DEPT BIOPHYS, WARSAW, POLAND. SCRIPPS RES INST, LA JOLLA, CA USA. RP Miller, M (reprint author), NCI, FREDERICK CANC RES FACIL & DEV CTR, MACROMOL STRUCT LAB, POB B, FREDERICK, MD 21702 USA. RI Miller, Maria/I-1636-2013 OI Miller, Maria/0000-0003-0252-5348 FU NCI NIH HHS [N0I-CO-46000] NR 39 TC 16 Z9 16 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 0887-3585 J9 PROTEINS JI Proteins PD FEB PY 1997 VL 27 IS 2 BP 184 EP 194 DI 10.1002/(SICI)1097-0134(199702)27:2<184::AID-PROT4>3.0.CO;2-G PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WL689 UT WOS:A1997WL68900004 PM 9061782 ER PT J AU Torrey, EF AF Torrey, EF TI Psychiatric survivors and nonsurvivors SO PSYCHIATRIC SERVICES LA English DT Editorial Material RP Torrey, EF (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD FEB PY 1997 VL 48 IS 2 BP 143 EP 143 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA WG884 UT WOS:A1997WG88400001 PM 9021843 ER PT J AU Hauser, P Soler, R BruckerDavis, F Weintraub, BD AF Hauser, P Soler, R BruckerDavis, F Weintraub, BD TI Thyroid hormones correlate with symptoms of hyperactivity but not inattention in attention deficit hyperactivity disorder SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE thyroid hormone; resistance to thyroid hormone; hyperactivity; attention deficit hyperactivity disorder ID RESISTANCE; CHILDREN; BRAIN AB The diagnostic validity of dividing attention deficit hyperactivity disorder (ADHD) into two distinct subgroups, one with and one without hyperactivity, is controversial since there have been no physiological differences demonstrated between these two subgroups. In this study, the relationship between thyroid hormones and symptoms of hyperactivity was examined in subjects with resistance to thyroid hormone (RTH) and their unaffected family members. Clinical data were collected on 152 subjects; 75 subjects with RTH and 77 family members without RTH. Each subject was assessed using DSM-III-R criterion based, structured psychiatric interviews, and Total T3 (TT3), Total T4 (TT4) and TSH concentrations were measured. The total number of ADHD symptoms were assigned to either inattention or hyperactivity subgroups using DSM-III-R criteria. The total number of ADHD symptoms were then reassigned to inattention or hyperactivity/impulsivity subgroups using DSM-IV criteria. Pearson R correlation coefficients were calculated separately for the RTH and unaffected family members groups in order to determine the relationships between TSH, TIT and TT4 concentrations, and the DSM-III-R and DSM-IV symptom categories of ADHD in both groups. TSH concentrations were not significantly correlated with any of the symptom categories in either group. However, in the RTH group, both TT3 and TT4 concentrations were significantly and positively correlated with total symptoms of ADHD (DSM-III-R) as well as symptoms of inattention (DSM-III-R) and symptoms of hyperactivity (DSM-III-R). When DSM-IV criteria were used, which reassigns symptoms of impulsivity from the inattention to the hyperactivity category, only the positive correlation between TT3 and TT4 concentrations and symptoms of hyperactivity/impulsivity (DSM-IV) remained significant. In the group of unaffected family members, the relationship between TT3 concentrations and symptoms of hyperactivity/impulsivity (DSM-IV) was the only significant correlation. The data support the hypothesis that thyroid hormones may provide a physiological basis for the dichotomy between symptoms of inattention and symptoms of hyperactivity, particularly when DSM-IV criteria are applied. C1 UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21201. NIDDK,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. INST HUMAN VIROL,LAB GLYCOPROT HORMONES,BALTIMORE,MD 21201. RP Hauser, P (reprint author), VET AFFAIRS MED CTR,PSYCHIAT SERV,10 N GREENE ST,BALTIMORE,MD 21201, USA. NR 25 TC 28 Z9 28 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD FEB PY 1997 VL 22 IS 2 BP 107 EP 114 DI 10.1016/S0306-4530(96)00043-1 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA WW799 UT WOS:A1997WW79900004 PM 9149332 ER PT J AU Strain, EC Walsh, SL Preston, KL Liebson, IA Bigelow, GE AF Strain, EC Walsh, SL Preston, KL Liebson, IA Bigelow, GE TI The effects of buprenorphine in buprenorphine maintained volunteers SO PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual meeting of the College-on-the-Problems-of-Drug-Dependence CY JUN 18-23, 1994 CL PALM BEACH, FL SP Coll Problems Drug Dependence DE abuse liability testing; agonist-antagonist; buprenorphine; hydromorphone; opioid dependence ID DEPENDENT HUMAN VOLUNTEERS; OPIOID DEPENDENCE; CLINICAL-TRIAL; PRECIPITATED WITHDRAWAL; ANTAGONIST PROPERTIES; DRUG DISCRIMINATION; PARTIAL AGONIST; METHADONE; MORPHINE; NALOXONE AB Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained on daily sublingual (SL) buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges two times per week. Medication challenges were 16 h after the daily dose of buprenorphine, and consisted of double-blind IM injections of buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments consisted of physiologic monitoring, subjects' self-reports, and a trained observer's ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM buprenorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral buprenorphine in buprenorphine-maintained patients. There was incomplete cross-tolerance to the effects of hydromorphone, suggesting that higher maintenance doses of buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that buprenorphine's combination of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full agonists. Finally, participants tolerated cumulative doses of maintenance buprenorphine plus challenge buprenorphine without adverse effects, suggesting higher doses of buprenorphine can be safely administered to opioid dependent patients. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP Strain, EC (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BEHAV PHARMACOL RES UNIT,BALTIMORE,MD 21224, USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [K20 DA00166, R01 DA08045, K05 DA00050] NR 61 TC 38 Z9 38 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 1997 VL 129 IS 4 BP 329 EP 338 DI 10.1007/s002130050199 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WM043 UT WOS:A1997WM04300004 PM 9085402 ER PT J AU Lubin, JH Tomasek, L Edling, C Hornung, RW Howe, G Kunz, E Kusiak, RA Morrison, HI Radford, EP Samet, JM Tirmarche, M Woodward, A Yao, SX AF Lubin, JH Tomasek, L Edling, C Hornung, RW Howe, G Kunz, E Kusiak, RA Morrison, HI Radford, EP Samet, JM Tirmarche, M Woodward, A Yao, SX TI Estimating lung cancer mortality from residential radon using data for low exposures of miners SO RADIATION RESEARCH LA English DT Article ID URANIUM MINERS; DOSE-RATE; ONCOGENIC TRANSFORMATION; DAUGHTER EXPOSURES; COHORT; PROGENY; WORKERS; RISK; DEPENDENCE; NEUTRONS AB Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the ''action level'' suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures. (C) 1997 by Radiation Research Society. C1 NATL RADIAT PROTECT INST,PRAGUE 100000,CZECH REPUBLIC. UPPSALA UNIV,DEPT OCCUPAT MED,UPPSALA,SWEDEN. NIOSH,CINCINNATI,OH 45226. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY 10032. MINIST LABOR,HLTH & SAFETY STUDIES UNIT,OCCUPAT HLTH BRANCH,TORONTO,ON M7A 1T7,CANADA. HLTH CANADA,CANC BUR,OTTAWA,ON K1A 0L2,CANADA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. INST PROTECT & NUCL SAFETY,HUMAN HLTH PROTECT & DOSIMETRY DEPT,F-92265 FONTENAY ROSES,FRANCE. WELLINGTON SCH MED,DEPT PUBL HLTH,WELLINGTON,NEW ZEALAND. CHINA NATL NONFERROUS MET IND CORP,YUNNAN TIN CORP,INST LABOR PROTECT,GEJIU,YUNNAN,PEOPLES R CHINA. RP Lubin, JH (reprint author), NCI,BIOSTAT BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,EPN-403,BETHESDA,MD 20892, USA. OI Woodward, Alistair/0000-0001-5425-6018 NR 34 TC 66 Z9 76 U1 1 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1997 VL 147 IS 2 BP 126 EP 134 DI 10.2307/3579412 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA WE917 UT WOS:A1997WE91700002 PM 9008203 ER PT J AU Bigbee, WL Jensen, RH Veidebaum, T Tekkel, M Rahu, M Stengrevics, A Auvinen, A Hakulinen, T Servomaa, K Rytomaa, T Obrams, GI Boice, JD AF Bigbee, WL Jensen, RH Veidebaum, T Tekkel, M Rahu, M Stengrevics, A Auvinen, A Hakulinen, T Servomaa, K Rytomaa, T Obrams, GI Boice, JD TI Biodosimetry of Chernobyl cleanup workers from Estonia and Latvia using the glycophorin a in vivo somatic cell mutation assay SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; A LOCUS; ERYTHROCYTES; FREQUENCY; ACCIDENT; VICTIMS; HUMANS AB The reactor accident at Chernobyl in 1986 necessitated a massive environmental cleanup that involved over 600,000 workers from all 15 Republics of the former Soviet Union. To determine whether the whole-body radiation received by workers in the course of these decontamination activities resulted in a detectable biological response, over 1,500 blood samples were obtained from cleanup workers sent from two Baltic countries, Estonia and Latvia. Here we report the results of studies of biodosimetry using the glycophorin A (GPA) locus in vivo somatic cell mutation assay applied to 734 blood samples from these workers, to 51 control samples from unexposed Baltic populations and to 94 samples from historical U.S. controls. The data reveal inconsistent evidence that the protracted radiation exposures received by these workers resulted in a significant dose-associated increase in GPA locus mutations compared with the controls. Taken together, these data suggest that the average radiation exposure to these workers does not greatly exceed 10 cGy, the minimum levels at which radiation effects might be detectable by the assay. Although the protracted nature of the exposure may have reduced the efficiency of induction of GPA locus mutations, it is likely that the estimated physical doses for these cleanup worker populations (median reported dose 9.5 cGy) were too low to result in radiation damage to erythroid stem cells that can be detected reliably by this method. (C) 1997 by Radiation Research Society. C1 UNIV PITTSBURGH,INST CANC,MOL CARCINOGENESIS PROGRAM,PITTSBURGH,PA 15238. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. INST CLIN & EXPT MED,DEPT BIOSTAT & EPIDEMIOL,EE-0016 TALLINN,ESTONIA. LATVIAN ONCOL CTR,LATVIAN HLTH DEPT,LV-1079 RIGA,LATVIA. FINNISH CANC REGISTRY,FIN-00179 HELSINKI,FINLAND. KAROLINSKA INST,CANC EPIDEMIOL UNIT,S-17176 STOCKHOLM,SWEDEN. FINNISH CTR RADIAT & NUCL SAFETY,FIN-00880 HELSINKI,FINLAND. NATL CANC INST,EXTRAMURAL PROGRAMS BRANCH,ROCKVILLE,MD 20852. NATL CANC INST,RADIAT EPIDEMIOL BRANCH,ROCKVILLE,MD 20852. RP Bigbee, WL (reprint author), UNIV PITTSBURGH,CTR ENVIRONM & OCCUPAT HLTH & TOXICOL,PITTSBURGH,PA 15238, USA. RI Rahu, Mati/A-9981-2008; OI Auvinen, Anssi/0000-0003-1125-4818 FU NCI NIH HHS [N01-CP-50520] NR 25 TC 45 Z9 48 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1997 VL 147 IS 2 BP 215 EP 224 DI 10.2307/3579423 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA WE917 UT WOS:A1997WE91700013 PM 9008214 ER PT J AU Inskip, PD Hartshorne, MF Tekkel, M Rahu, M Veidebaum, T Auvinen, A Crooks, LA Littlefield, LG McFee, AF Salomaa, S Makinen, S Tucker, JD Sorensen, KJ Bigbee, WL Boice, JD AF Inskip, PD Hartshorne, MF Tekkel, M Rahu, M Veidebaum, T Auvinen, A Crooks, LA Littlefield, LG McFee, AF Salomaa, S Makinen, S Tucker, JD Sorensen, KJ Bigbee, WL Boice, JD TI Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; GLYCOPHORIN-A LOCUS; SOMATIC-CELL MUTATIONS; CHROMOSOME-ABERRATIONS; IONIZING-RADIATION; FREQUENCY; CHILDHOOD; ACCIDENT; ERYTHROCYTES; LYMPHOCYTES AB Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. Ultrasound examinations revealed thyroid nodules in 201 individuals (10.2%). The prevalence of nodules increased with age at examination, but no significant associations were observed with recorded dose, date of first duty at Chernobyl, duration of service at Chernobyl, building the sarcophagus or working on the roof of neighboring buildings or close to the damaged reactor. Nodularity showed a nonsignificant (p((1)) = 0.10) positive association with the proportion of lymphocytes with chromosome translocations, but associations with the frequency of variant erythrocytes in the GPA assay were weak and unstable (p((1)) greater than or equal to 0.46). The majority of fine-needle biopsies taken on 77 study participants indicated benign nodular disease. However, two cases of papillary carcinoma and three benign follicular neoplasms were identified and referred for treatment. Both men with thyroid cancer had been sent to Chernobyl in May of 1986, when the potential for exposure to radioactive iodines was greatest. Chernobyl cleanup workers from Estonia did not experience a markedly increased risk of nodular thyroid disease associated with exposure to external radiation. Possible reasons for the apparent absence of effect include low radiation doses, the protracted nature of the exposure, errors in dose measurement, low sensitivity of the adult thyroid gland or the insufficient passage of time for a radiation effect to be expressed. (C) 1997 by Radiation Research Society. C1 NCI, RADIAT EPIDEMIOL BRANCH, EPIDEMIOL & BIOSTAT PROGRAM, DIV CANC EPIDEMIOL & GENET, BETHESDA, MD 20892 USA. UNIV NEW MEXICO, DEPT RADIOL, ALBUQUERQUE, NM 87131 USA. INST CLIN & EXPT MED, TALLINN, ESTONIA. FINNISH CANC REGISTRY, FIN-00170 HELSINKI, FINLAND. VET ADM MED CTR, DEPT PATHOL, ALBUQUERQUE, NM 87131 USA. OAK RIDGE INST SCI & EDUC, DIV MED SCI, OAK RIDGE, TN 37831 USA. FINNISH CTR RADIAT & NUCL SAFETY, HELSINKI, FINLAND. LAWRENCE LIVERMORE NATL LAB, BIOL & BIOTECHNOL RES PROGRAM, LIVERMORE, CA 94551 USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT ENVIRONM & OCCUPAT HLTH, PITTSBURGH, PA 15238 USA. RI Rahu, Mati/A-9981-2008; OI Auvinen, Anssi/0000-0003-1125-4818 FU NCI NIH HHS [N01-CP-50520, N01-CP-85638-03, YO1-CP4-0599-01] NR 47 TC 46 Z9 47 U1 1 U2 8 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1997 VL 147 IS 2 BP 225 EP 235 DI 10.2307/3579424 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA WE917 UT WOS:A1997WE91700014 PM 9008215 ER PT J AU Davidson, AJ Hartman, DS Choyke, PL Wagner, BJ AF Davidson, AJ Hartman, DS Choyke, PL Wagner, BJ TI Radiologic assessment of renal masses: Implications for patient care SO RADIOLOGY LA English DT Article DE kidney; kidney, cysts,; kidney neoplasms, diagnosis; kidney neoplasms, therapy; state-of-art reviews ID CELL CARCINOMA; ARTERIOVENOUS-MALFORMATIONS; COMPUTED-TOMOGRAPHY; PATHOLOGICAL CORRELATION; EXCRETORY UROGRAPHY; IMAGING MODALITIES; NATURAL-HISTORY; CT; DIAGNOSIS; CYSTS AB THE ability to detect and characterize a mass arising in a kidney has been refined to an unprecedented degree over the past 2 decades due to technologic developments in sonography, computed tomography (CT), and magnetic resonance (MR) imaging (1-9). As these technologies have evolved, the varied imaging characteristics of renal masses have become apparent on the basis of both extensive formal investigations as well as a widely shared clinical experience. Criteria for the radiologic diagnosis of simple and complicated nephrogenic cysts (10-12), abscess (13,14), angiomyolipoma (15-17), hemangioma (18-21), benign and malignant neoplasms (22-39), and inflammatory mass (40) have been thoroughly described. The value of these advances can hardly be disputed. However, it is also clear that their prospective application in a given patient is often subject to uncertainty or associated with wastefulness and futility (1,2,4). For example, the radiologic characteristics of different pathologic entities may overlap. Some features are highly diagnostic of a certain pathologic condition, whereas others are equivocal (11,35,36,41-44). The use of multiple imaging modalities frequently produces data that are either redundant or contradictory. Further, radiologic interpretation is sometimes confounded by small size of the lesion (44,45). In any of these circumstances, the diagnostic radiologic effort may fail to provide data that usefully inform subsequent therapeutic choices and/or patient outcome. Contemporary imaging has also opened a Pandora's box, revealing conditions previously undetectable with imaging. These conditions include the discovery of a small solid mass or a hyperattenuating fluid-filled mass in the kidney of an asymptomatic patient (25,46-64). Many of these small solid masses prove to be cancer at an early stage, and their early detection may account for the much heralded improvement in survival rates for renal cancer recently reported (65-67). The true implications of these apparent salutary effects of CT and sonography, however, are yet to be determined, as emphasized by questions regarding lead time bias of early detection and the biologic activity of incidentally discovered small lesions (68). In this review of the role of the radiologic evaluation of a renal mass in clinical decision making, we use pathologic characteristics as our benchmark. Radiologic data are considered as indirect analogues for these pathologic features. Further, a final tissue diagnosis is considered the province of the pathologist, not the radiologist. In this sense, a proper radiologic diagnosis is viewed as a prediction of a final tissue diagnosis, with an implied level of probability that is based on what is known about the inherent pathologic characteristics of the proposed diagnosis, on the sensitivity of the modality or modalities used, and, to a lesser extent, on the prevalence and demographic features of the diagnoses under consideration. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT RADIOL,UNIVERSITY PK,PA. NIH,CTR CLIN,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT RADIOL,BALTIMORE,MD 21201. RP Davidson, AJ (reprint author), ARMED FORCES INST PATHOL,DEPT RADIOL PATHOL,AMER REGIST PATHOL,6825 16TH ST NW,WASHINGTON,DC 20306, USA. NR 97 TC 47 Z9 48 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1997 VL 202 IS 2 BP 297 EP 305 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD822 UT WOS:A1997WD82200002 PM 9015046 ER PT J AU Avila, NA Ling, A Worobec, AS Mican, JAM Metcalfe, DD AF Avila, NA Ling, A Worobec, AS Mican, JAM Metcalfe, DD TI Systemic mastocytosis: CT and US features of abdominal manifestations SO RADIOLOGY LA English DT Article DE abdomen, CT; abdomen, diseases; abdomen, US; mastocytosis ID MAST-CELL DISEASE AB PURPOSE: To study the imaging findings in patients with systemic mastocytosis and to correlate the findings with the severity of disease on the basis of an established classification system. Pathologic findings, when available, were correlated with imaging findings. MATERIALS AND METHODS: Computed tomographic (CT) and ultrasound (US) scans and corresponding pathologic findings, when available, were retrospectively reviewed in 27 patients with systemic mastocytosis. RESULTS: Only five (19%) of the patients in our series had normal abdominal CT and/or US examination results. Common abdominal imaging findings associated with systemic mastocytosis were hepatosplenomegaly, retroperitoneal adenopathy, periportal adenopathy, mesenteric adenopathy, thickening of the omentum and the mesentery, and ascites. Less common findings included hepatofugal portal venous flow, Budd-Chiari syndrome, cavernous transformation of the portal vein, ovarian mass, and complications such as chloroma. The findings were more common in patients with category II and those with category III disease. CONCLUSION: Abdominal findings at CT and US are common in patients with systemic mastocytosis. Although the findings in patients with systemic mastocytosis are not specific to the disease, they are useful in directing further studies for diagnostic confirmation and in estimating the extent of systemic involvement. C1 NIAID,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892. RP Avila, NA (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C-660,10 CTR DR,MSC 1182,BETHESDA,MD 20892, USA. NR 22 TC 19 Z9 19 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 FEB PY 1997 VL 202 IS 2 BP 367 EP 372 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WD822 UT WOS:A1997WD82200015 PM 9015059 ER PT J AU Marini, M Musiani, D Raggi, MA Schiavone, P Levine, RL AF Marini, M Musiani, D Raggi, MA Schiavone, P Levine, RL TI Oxidative stress does not mediate heat shock-induced cell damage and apoptosis SO REDOX REPORT LA English DT Article ID GLUTATHIONE; DEATH; PROTEINS; LYMPHOCYTES; INHIBITION; ACTIVATION; MODULATION; CYSTEINE AB The hypothesis that oxidative damage arising from heat shock might significantly contribute to cell death and in particular to apoptosis has been tested in human peripheral blood lymphocytes. Cellular glutathione content and protein carbonyl groups were measured as indicators of oxidative injury. Cell viability and proliferative capacity were evaluated as measures of irreversible damage. Heat shock caused dose-dependent decreases in cell viability, and apoptotic cell death was found to be a major component of heat-shock-mediated mortality, However, only the more severe heat treatment (1 h, 45 degrees C) caused an immediate decrease in glutathione content. The content in carbonyl groups was not significantly affected by heat shock. N-acetyl-cysteine, when added before the hyperthermic treatment, did increase the glutathione content of the cells, but this did not favourably affect the survival of heat-shocked lymphocytes. It is suggested that oxidative damage is not a significant component of heat shock-mediated cell injury, and that, at least in this experimental model, apoptosis is triggered by stimuli other than an altered redox state of the cell. C1 UNIV BOLOGNA,DIPARTIMENTO SCI FARMACEUT,I-40126 BOLOGNA,ITALY. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP Marini, M (reprint author), UNIV BOLOGNA,FAC MED,IST ISTOL & EMBRIOL GEN,VIA BELMELORO 8,I-40126 BOLOGNA,ITALY. RI Raggi, Maria Augusta/A-4545-2011; Marini, Marina/B-1490-2012; Levine, Rodney/D-9885-2011 OI Marini, Marina/0000-0003-1932-7380; NR 28 TC 3 Z9 3 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1351-0002 J9 REDOX REP JI Redox Rep. PD FEB PY 1997 VL 3 IS 1 BP 57 EP 63 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY897 UT WOS:A1997WY89700008 PM 27414772 ER PT J AU ElenitobaJohnson, KSJ Jaffe, ES AF ElenitobaJohnson, KSJ Jaffe, ES TI Lymphoproliferative disorders associated with congenital immunodeficiencies SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE congenital immunodeficiency; lymphoproliferative disorders ID WISKOTT-ALDRICH SYNDROME; COMMON VARIABLE IMMUNODEFICIENCY; NIJMEGEN BREAKAGE SYNDROME; ATAXIA-TELANGIECTASIA GENE; T-CELL LYMPHOMA; MALIGNANT-LYMPHOMA; CHROMOSOMAL INSTABILITY; B-CELLS; HYPOGAMMAGLOBULINEMIA; IMMUNOGLOBULIN AB This report reviews the clinicopathologic, immunologic, and molecular biological features of the congenital immunodeficiencies and their associated lymphoproliferative disorders (LPD) including cases presented at the Third Slide Workshop of the Society of Hematopathology, held in Duarte California, in October 1995, The congenital immunodeficiencies most commonly associated with LPD include Wiskott-Aldrich syndrome (WAS), common variable immunodeficiency (CVID), ataxia telangiectasia (AT), severe combined immunodeficiency (SCID), X-linked lymphoproliferative disorder (XP), and hyper-IgM syndrome, Each form of immunodeficiency disorder is associated with its own risk factors, which affect the pattern of LPD encountered, AT is characterized by a defect in DNA repair, The lymphomas and leukemias in this syndrome resemble those seen in sporadic LPD, but tend to occur at an earlier age, Epstein-Barr virus (EBV) plays an important role in the LPD associated with many immunodeficiency disorders including WAS, CVID, SCID, and XLP, One should use a combination of clinical, histopathologic and molecular data in the evaluation of lymphoproliferative lesions in this group of patients, Immunophenotypic and molecular evidence of clonality does not necessarily imply an aggressive clinical course, as exemplified by some LPD in WAS, which may show evidence of monoclonality in serum and lymph nodes, and yet still behave in a benign or indolent fashion. Copyright (C) 1997 by W.B. Saunders Company. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 75 TC 61 Z9 64 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD FEB PY 1997 VL 14 IS 1 BP 35 EP 47 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA WK169 UT WOS:A1997WK16900006 PM 9044508 ER PT J AU Sandler, DP Ross, JA AF Sandler, DP Ross, JA TI Epidemiology of acute leukemia in children and adults SO SEMINARS IN ONCOLOGY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; HAIR DYE USE; MORTALITY RATIO ANALYSIS; ATOMIC-BOMB SURVIVORS; DRY CLEANING WORKERS; X-RAY-EXPOSURE; CHILDHOOD LEUKEMIA C1 UNIV MINNESOTA,CTR CANC,DEPT PEDIAT,MINNEAPOLIS,MN 55455. RP Sandler, DP (reprint author), NATL INST ENVIRONM HLTH SCI,POB 12233,MC A3-05,111 TW ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. OI Sandler, Dale/0000-0002-6776-0018 NR 223 TC 89 Z9 96 U1 4 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1997 VL 24 IS 1 BP 3 EP 16 PG 14 WC Oncology SC Oncology GA WH668 UT WOS:A1997WH66800004 PM 9045302 ER PT J AU Karp, JE Smith, MA AF Karp, JE Smith, MA TI The molecular pathogenesis of treatment-induced (secondary) leukemias: Foundations for treatment and prevention SO SEMINARS IN ONCOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ATAXIA-TELANGIECTASIA GENE; NUCLEOTIDE EXCISION-REPAIR; CYCLE CHECKPOINT PATHWAY; THERAPY-RELATED LEUKEMIA; DNA TOPOISOMERASE-II; XERODERMA-PIGMENTOSUM; CHROMOSOME TRANSLOCATIONS; SACCHAROMYCES-CEREVISIAE C1 NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NR 89 TC 58 Z9 59 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1997 VL 24 IS 1 BP 103 EP 113 PG 11 WC Oncology SC Oncology GA WH668 UT WOS:A1997WH66800012 PM 9045296 ER PT J AU Chanock, SJ Pizzo, PA AF Chanock, SJ Pizzo, PA TI Infectious complications of patients undergoing therapy for acute leukemia: Current status and future prospects SO SEMINARS IN ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; SIMPLEX VIRUS-INFECTION; PNEUMOCYSTIS-CARINII PNEUMONITIS; FEBRILE NEUTROPENIC PATIENTS; BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; EVOLVING RISK-FACTORS; CANCER-PATIENTS; FUNGAL-INFECTIONS; DOUBLE-BLIND C1 CHILDRENS HOSP,BOSTON,MA. RP Chanock, SJ (reprint author), NCI,INFECT DIS SECT,PEDIAT BRANCH,10-13N240,BETHESDA,MD 20892, USA. NR 65 TC 37 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1997 VL 24 IS 1 BP 132 EP 140 PG 9 WC Oncology SC Oncology GA WH668 UT WOS:A1997WH66800015 PM 9045299 ER PT J AU Saltz, L Janik, JE AF Saltz, L Janik, JE TI Topotecan and the treatment of recurrent ovarian cancer: Is there a role for granulocyte colony-stimulating factor? SO SEMINARS IN ONCOLOGY LA English DT Article ID TOPOISOMERASE-I INHIBITOR; PHASE-I; DOSE INTENSITY; CHEMOTHERAPY; CARCINOMA C1 NCI,CLIN RES BRANCH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RP Saltz, L (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1997 VL 24 IS 1 SU 5 BP S26 EP S30 PG 5 WC Oncology SC Oncology GA WQ897 UT WOS:A1997WQ89700005 ER PT J AU Schmidt, PJ Roca, CA Bloch, M Rubinow, DR AF Schmidt, PJ Roca, CA Bloch, M Rubinow, DR TI The perimenopause and affective disorders SO SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY LA English DT Article DE depression; midlife; perimenopause ID SURGICALLY MENOPAUSAL WOMEN; NATIONAL-COMORBIDITY-SURVEY; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; SEX-DIFFERENCES; DOUBLE-BLIND; INVOLUTIONAL MELANCHOLIA; ESTROGEN REPLACEMENT; DEPRESSIVE SYMPTOMS; GENDER DIFFERENCES AB A variety of epidemiologic studies have identified that the majority of postmenopausal women do Mot experience a depression during the perimenopause. In contrast, results of several epidemiologic studies and clinic-based surveys suggest that a substantial number of perimenopausal women, in fact, do experience a clinically significant depression. In this article, we review these studies. Case examples are described to introduce a discussion of the characteristics of perimenopause-related depression, and toe identify several factors occurring during midlife in women that may potentially contribute to mood dysregulation at this time. Finally, we provide suggestions for the evaluation and management of women presenting with perimenopause-related depression. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. NR 82 TC 49 Z9 51 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0734-8630 J9 SEMIN REPROD ENDOCR JI Semin. Reprod. Endocrinol. PD FEB PY 1997 VL 15 IS 1 BP 91 EP 100 DI 10.1055/s-2008-1067971 PG 10 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA 176AW UT WOS:000079129200010 PM 9065981 ER PT J AU Soderfeldt, B Soderfeldt, M Jones, K OCampo, P Muntaner, C Ohlson, CG Warg, LE AF Soderfeldt, B Soderfeldt, M Jones, K OCampo, P Muntaner, C Ohlson, CG Warg, LE TI Does organization matter? A multilevel analysis of the demand-control model applied to human services SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE multi-level analysis; demand-control model; human services ID JOB DECISION LATITUDE; WORKERS; STRAIN; BEHAVIOR; BURNOUT; STRESS AB The demand-control model (DC model) in occupational epidemiology suggests that health, an individual attribute, is partly determined by work organization, via the interplay of demand and control, job strain. The objective of this study was empirical assessment of the model's tenet of an organizational determination of individual health. An emerging analytic method, multi-level modelling, permits such an assessment The study encompasses two large Swedish human service organizations. It was based on a nationally representative sample of 291 local organizational units (level 2) with 8296 employees (level 1), a median of 18 employees per unit. 5730 persons (69.1%) completed the questionnaire. Listwise deletion of missing data left a net study base of 4756 individuals in 284 units. Missing data were largely random. Demand and control were measured by standard questions and combined into a job strain index. Two such indices were calculated, one for quantitative demands and one for emotional demands. Individual attributes included age, gender, marital status, having children, social anchorage, and education. There were two dependent variables, self-assessed psychovegetative symptoms (worry, anxiousness, sadness, sleep difficulties, restlessness, and tension) and exhaustion (fatigue, feelings of being used up and overworked), both measured as summative indices. For psychovegetative health, a null model yielded 2.2% level 2 variance, unchanging when individual attributes were included in a random intercepts model. Inclusion of the strain variables rendered level 2 variance non-significant, decreasing level 1 variance by 23% and level 2 variance by 62%. For exhaustion, level 2 variation was 8.3% in the null model and 1.6% in the final model, with strain variables. The strain variables utilized in the DC-model thus draw a substantial part of their variation from the organizational level. It is concluded that the claim of the DC model to rely on organizational factors receives support. Copyright (C) 1997 Elsevier Science Ltd C1 LUND UNIV,CTR ORAL HLTH SCI,MALMO,SWEDEN. LUND UNIV,DEPT SOCIAL WORK,LUND,SWEDEN. OREBRO MED CTR HOSP,DEPT ENVIRONM & OCCUPAT MED,S-70185 OREBRO,SWEDEN. UNIV PORTSMOUTH,DEPT GEOG,PORTSMOUTH PO1 2UP,HANTS,ENGLAND. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MATERNAL & CHILD HLTH,BALTIMORE,MD. NIMH,LAB SOCIOENVIRONM STUDIES,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. RP Soderfeldt, B (reprint author), KAROLINSKA INST,DEPT INT HLTH & SOCIAL MED,STOCKHOLM,SWEDEN. RI Muntaner, C/A-5043-2010; Jones, Kelvyn/A-3939-2011 OI Jones, Kelvyn/0000-0001-8398-2190 NR 39 TC 69 Z9 70 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 1997 VL 44 IS 4 BP 527 EP 534 DI 10.1016/S0277-9536(96)00179-7 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA WC020 UT WOS:A1997WC02000009 PM 9015887 ER PT J AU Tsao, LI Su, TP AF Tsao, LI Su, TP TI Naloxone-sensitive, haloperidol-sensitive [H-3](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: An opioid/sigma receptor? SO SYNAPSE LA English DT Article DE sigma receptor; sigma opioid receptor; naloxone; SKF-10047; N-allylnormetazocine; opioid receptor; haloperidol; affinity chromatography; rat liver; rat brain; protein ID SIGMA-RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; OPIATE RECEPTORS; BINDING-SITES; CLONING; LIGAND; CLASSIFICATION; ANTAGONISM; IMPAIRMENT AB A naloxone-sensitive, haloperidol-sensitive, [H-3](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2-[3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl])ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [H-3](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor [H-3](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:5 17-532.]. A high degree of purification of this protein has been achieved in the present study. (C) 1997 Wiley-Liss, Inc. C1 NIDA,MOL NEUROPSYCHIAT SECT,DIR,NIH,BALTIMORE,MD 21224. NR 33 TC 17 Z9 18 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1997 VL 25 IS 2 BP 117 EP 124 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WF219 UT WOS:A1997WF21900002 PM 9021892 ER PT J AU Cadet, JL Ordonez, SV Ordonez, JV AF Cadet, JL Ordonez, SV Ordonez, JV TI Methamphetamine induces apoptosis in immortalized neural cells: Protection by the proto-oncogene, bcl-2 SO SYNAPSE LA English DT Article DE methamphetamine; neural cells; free radicals; superoxide; flow cytometry; DNA ladders; apoptosis; bcl-2; Parkinson's disease; dopamine; neurodegeneration ID DISMUTASE TRANSGENIC MICE; DNA STRAND-BREAKS; RAT-BRAIN; ENDONUCLEASE ACTIVATION; STRIATAL DOPAMINE; MEMBRANE PROTEIN; DEATH; SUPEROXIDE; NEUROTOXICITY; SURVIVAL AB Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2, could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. AU these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway. (C) 1997 Wiley-Liss, Inc. C1 UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. RP Cadet, JL (reprint author), NIDA,MOL NEUROPSYCHIAT SECT,NIH,DIV INTRAMURAL RES,IRP,BOX 5180,BALTIMORE,MD 21224, USA. NR 62 TC 91 Z9 94 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 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1997 VL 25 IS 2 BP 176 EP 184 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WF219 UT WOS:A1997WF21900008 PM 9021898 ER PT J AU Watanabe, Y Tahara, K Hirai, A Tada, H Kohn, LD Amino, N AF Watanabe, Y Tahara, K Hirai, A Tada, H Kohn, LD Amino, N TI Subtypes of anti-TSH receptor antibodies classified by various assays using CHO cells expressing wild-type or chimeric human TSH receptor SO THYROID LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; EXTRACELLULAR DOMAIN; IDIOPATHIC MYXEDEMA; MOLECULAR-CLONING; BINDING; AUTOANTIBODIES; PEPTIDES; SITES AB To analyze the heterogeneity of anti-TSH receptor antibodies (TSHRAb), we measured serum TSH-binding inhibitory immunoglobulin (TBII), thyroid-stimulating antibody (TSAb), and thyroid stimulation blocking antibody (TSBAb) activities in 31 patients with positive TSHRAb, using CHO cells expressing wild-type TSHR (WT) or TSHR chimera (Mc2) wherein residues 90-165 were substituted by the LH/CG receptor. Using membranes from WT cells, we detected TBII activity in all 31 patients; 10 (32%), all with TSAb activity only, completely lost TBII activity using Mc2 membranes. TSAb activity was found in 26 sera using WT cells; 20 (77%) completely lost TSAb activity in Mc2 cells. Comparisons of TBII and TSAb activity in WT cells did not exhibit a strong positive correlation (r = 0.52). Of the 20 sera that completely lost TSAb activity in Mc2 cells, 10 retained some TBII activity in Mc2 cells. In each of the sera with retained TBII activity, TSAb activity was recovered in Mc2 cells using the conversion assay, which measures the conversion of a nonstimulating TSHRAb to a TSAb by the action of an anti-human IgG. Additionally, the TBII and conversion assay values in Mc2 cells exhibited a strong positive correlation (r = 0.86). Of the 31 sera, TSBAb was found in 7 samples, with no difference in WT and Mc2 cells. TBII activity was detected in all 7 sera with WT cells; TSAb activity in only 2. In the 5 sera with TS-BAb but no TSAb activity, and with only a minimal or no decrease in TBII activity in Mc2 cell membranes, the in vitro conversion assay uncovered TSAb activity. Analyzing these data, we classify the sera into 5 groups containing multiple, different TSHR autoantibodies, including two different TSAbs, three different TBIIs, and one nonfunctional antibody. The heterogeneity of TBIIs as well as TSAbs provides a basis to explain the lack of correlation between TBII and TSAb activities in some past studies of Graves' sera. C1 OSAKA UNIV, SCH MED, DEPT LAB MED, SUITA, OSAKA 565, JAPAN. CHIBA UNIV, SCH MED, DEPT INTERNAL MED 2, CHUO KU, CHIBA 260, JAPAN. NIDDKD, METAB DIS BRANCH, BETHESDA, MD 20892 USA. SRL INC, HACHIOJI, TOKYO 192, JAPAN. NR 30 TC 44 Z9 46 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD FEB PY 1997 VL 7 IS 1 BP 13 EP 19 DI 10.1089/thy.1997.7.13 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WN392 UT WOS:A1997WN39200003 PM 9086564 ER PT J AU Davis, BJ Almekinder, JL Flagler, N Travlos, G Wilson, R Maronpot, RR AF Davis, BJ Almekinder, JL Flagler, N Travlos, G Wilson, R Maronpot, RR TI Ovarian luteal cell toxicity of ethylene glycol monomethyl ether and methoxy acetic acid in vivo and in vitro SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID PHTHALATE SUPPRESSES ESTRADIOL; TESTICULAR TOXICITY; GRANULOSA-CELLS; INHALATION TOXICITY; MONOETHYL ETHERS; CORPORA-LUTEA; F344 RATS; MICE; TERATOGENICITY; PROGESTERONE AB These studies define the site and mechanisms of reproductive toxicity of ethylene glycol monomethyl ether (EGME) in a nongravid female animal model using in vivo and in vitro methods. In vivo studies assessed vaginal cytology and histology, ovarian histology, and serum hormones in 80- to 90-day-old, adult, regularly cycling, female Sprague-Dawley rats treated daily with EGME or vehicle by oral gavage. Dose-response and time-course studies (four to nine rats per group per treatment) determined that 300 mg/kg EGME suppressed cyclicity without systemic toxicity within 3 to 8 days, and doses less than 100 mg/kg had no effect. Pathogenesis studies (six to nine rats per time and treatment) determined that 300 mg/kg EGME elevated serum progesterone within 32 hr after dosing, while serum estradiol, FSH, LH, and prolactin remained at baseline levels. In EGME-treated rats, cyclicity was suppressed, ovulation was inhibited, and corpora lutea were hypertrophied. Thus, EGME appeared to target the ovarian luteal cell. To further examine the toxicity in vitro, luteal cells were recovered from 23-day-old, hCG-primed Sprague-Dawley rats and treated with 0-10 mM methoxy acetic acid (MAA), the proximate toxic metabolite of EGME. MAA (1-10 mM) maintained elevated progesterone levels as production declined in untreated cells at 24 and 48 hr of culture. Progesterone production was maintained independent of LH-stimulated cAMP levels. MAA decreased ATP, but only at 48 hr and at 2.5 mM or greater concentrations. Thus, these studies establish that the ovarian luteal cell is a target of EGME and MAA in vivo and in vitro and that the effect on luteal cell progesterone production is likely independent of LH-stimulated cAMP pathways. (C) 1997 Academic Press. C1 N CAROLINA STATE UNIV, COLL VET MED, DEPT MICROBIOL PATHOL & PARASITOL, RALEIGH, NC 27606 USA. RP Davis, BJ (reprint author), NIEHS, LAB EXPT PATHOL, MD B3-06, POB 12233, RES TRIANGLE PK, NC 27709 USA. FU NIEHS NIH HHS [ES00233] NR 40 TC 26 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1997 VL 142 IS 2 BP 328 EP 337 DI 10.1006/taap.1996.8035 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WK174 UT WOS:A1997WK17400014 PM 9070356 ER PT J AU Fechner, JH Vargo, DJ Geissler, EK Wang, J Neville, DM Knechtle, SJ AF Fechner, JH Vargo, DJ Geissler, EK Wang, J Neville, DM Knechtle, SJ TI Mechanisms of tolerance induced by an immunotoxin against CD3 epsilon in a rhesus kidney allograft model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XVI International Congress of the Transplantation-Society CY AUG 25-30, 1996 CL BARCELONA, SPAIN SP Sandoz, Fujisawa, Congress Org Comm, Transplantat Soc C1 UNIV WISCONSIN,DEPT SURG,MADISON,WI 53792. NIMH,MOL BIOL LAB,BETHESDA,MD 20892. RI Fechner, John/C-5962-2016; Geissler, Edward/R-4131-2016 OI Fechner, John/0000-0002-8220-7237; NR 1 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB-MAR PY 1997 VL 29 IS 1-2 BP 1158 EP 1158 DI 10.1016/S0041-1345(96)00503-9 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WM127 UT WOS:A1997WM12700515 PM 9123249 ER PT J AU Lands, WEM Surolia, A AF Lands, WEM Surolia, A TI Professor Bimal Kumar Bachhawat, 1925-1996 - Obituary SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Item About an Individual C1 INDIAN INST SCI,MOL BIOPHYS UNIT,BANGALORE 560012,KARNATAKA,INDIA. RP Lands, WEM (reprint author), NIAAA,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. RI SUROLIA, AVADESHA/C-5442-2009 NR 0 TC 0 Z9 0 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 FEB PY 1997 VL 22 IS 2 BP 48 EP 48 DI 10.1016/S0968-0004(96)30048-0 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH496 UT WOS:A1997WH49600004 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Emergency sterilization using microwaves SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article 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 discusses the use of a home microwave oven for sterilizing laboratory equipment. 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 1 TC 0 Z9 0 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 FEB PY 1997 VL 22 IS 2 BP 68 EP 69 DI 10.1016/S0968-0004(97)01002-5 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH496 UT WOS:A1997WH49600012 PM 9048486 ER PT J AU ConryCantilena, C AF ConryCantilena, C TI Hepatitis C virus diagnostics: Technology, clinical applications and impacts SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID RECOMBINANT IMMUNOBLOT ASSAY; POLYMERASE CHAIN-REACTION; NON-B-HEPATITIS; BLOOD-DONORS; NON-A; POSTTRANSFUSION HEPATITIS; VIRAL-HEPATITIS; SCREENING-TESTS; ANTI-HCV; INFECTION AB Infection with hepatitis C virus (HCV) can cause several significant health problems. Sensitive and specific assays for antibodies to HCV are available to identify and confirm individuals infected with HCV. Evaluation of the clinical impact of HCV infection in a patient includes measuring liver biochemistries and possibly liver biopsy. Molecular assays such as HCV genotype identification and qualitative/quantitative HCV RNA analyses may be valuable in considerations of prognosis and therapy. Further refinement of antibody screening and confirmatory assays and standardization of molecular testing are necessary to optimize testing and thus fully characterize the diagnosis of HCV infection. RP ConryCantilena, C (reprint author), NIH,DEPT TRANSFUS MED,BLDG 10,ROOM 1C711,BETHESDA,MD 20892, USA. NR 47 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD FEB PY 1997 VL 15 IS 2 BP 71 EP 76 DI 10.1016/S0167-7799(97)84206-0 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WH459 UT WOS:A1997WH45900007 PM 9081301 ER PT J AU Caughey, B Chesebro, B AF Caughey, B Chesebro, B TI Prion protein and the transmissible spongiform encephalopathies SO TRENDS IN CELL BIOLOGY LA English DT Review ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE-ASSOCIATED FORMS; CULTURED-CELLS; NEUROBLASTOMA-CELLS; TRANSGENIC MICE; RESISTANT PRP; PHOSPHOLIPASE; CONVERSION; FIBRILS; BRAIN AB Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that occur in a wine variety of mammals. In humans, TSE diseases include kuru, sporadic and iatrogenic Creutzfeldt-Jakob disease (CJD) Gerstmann-Straussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI). So far, TSE diseases occur only rarely in humans; however, scrapie is a widespread problem in sheep, and the recent epidemic of bovine spongiform encephalopathy (BSE or mad cow disease) has seriously affected the British cattle industry. Of special concern is the recent appearance of a new variant of CJD in humans that is suspected of being caused by infections from BSE-infected cattle products. In all these diseases, an abnormal form of a host protein, prion protein (PrP) is essential for the pathogenic process. The relationship of this protein to the transmissible agent is currently the subject of great interest and controversy and is the subject of this review. RP Caughey, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 65 TC 162 Z9 166 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD FEB PY 1997 VL 7 IS 2 BP 56 EP 62 DI 10.1016/S0962-8924(96)10054-4 PG 7 WC Cell Biology SC Cell Biology GA WG351 UT WOS:A1997WG35100003 PM 17708907 ER PT J AU Bolker, JA Butler, M Kissinger, J Riley, MA AF Bolker, JA Butler, M Kissinger, J Riley, MA TI Addressing the gender gap in evolutionary biology SO TRENDS IN ECOLOGY & EVOLUTION LA English DT Editorial Material C1 WASHINGTON UNIV,DEPT BIOL,ST LOUIS,MO 63130. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. YALE UNIV,DEPT ECOL & EVOLUT,NEW HAVEN,CT 06511. RP Bolker, JA (reprint author), INDIANA UNIV,DEPT BIOL,BLOOMINGTON,IN 47408, USA. RI Kissinger, Jessica/E-9610-2010; Butler, Marguerite/B-6700-2011 OI Kissinger, Jessica/0000-0002-6413-1101; Butler, Marguerite/0000-0002-2039-5965 NR 3 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-5347 J9 TRENDS ECOL EVOL JI Trends Ecol. Evol. PD FEB PY 1997 VL 12 IS 2 BP 46 EP 47 DI 10.1016/S0169-5347(96)30064-5 PG 2 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA WF304 UT WOS:A1997WF30400003 PM 21237968 ER PT J AU Kotb, M Mudd, SH Mato, JM Geller, AM Kredich, NM Chou, JY Cantoni, GL AF Kotb, M Mudd, SH Mato, JM Geller, AM Kredich, NM Chou, JY Cantoni, GL TI Consensus nomenclature for the mammalian methionine adenosyltransferase genes and gene products SO TRENDS IN GENETICS LA English DT Letter ID S-ADENOSYLMETHIONINE SYNTHETASE; RAT-LIVER; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; MESSENGER-RNA; PURIFICATION; EXPRESSION C1 NIMH,BETHESDA,MD 20892. CSIC,INST INVEST BIOMED,E-28029 MADRID,SPAIN. DUKE UNIV,MED CTR,DURHAM,NC 27710. NICHHD,BETHESDA,MD 20892. RP Kotb, M (reprint author), UNIV TENNESSEE,MEMPHIS,TN 38163, USA. RI MATO, JOSE/A-5187-2011 NR 23 TC 137 Z9 137 U1 0 U2 3 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 FEB PY 1997 VL 13 IS 2 BP 51 EP 52 DI 10.1016/S0168-9525(97)01013-5 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA WG903 UT WOS:A1997WG90300005 PM 9055605 ER PT J AU Crammond, DJ AF Crammond, DJ TI Motor imagery: Never in your wildest dream SO TRENDS IN NEUROSCIENCES LA English DT News Item ID MENTAL MOVEMENT SIMULATION; PARIETAL CORTEX; REPRESENTATION; INTENTION; MONKEY; BRAIN; TASK; LIMB RP Crammond, DJ (reprint author), NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837, USA. RI Winstein, Carolee/A-8375-2008 NR 28 TC 155 Z9 159 U1 1 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD FEB PY 1997 VL 20 IS 2 BP 54 EP 57 DI 10.1016/S0166-2236(96)30019-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WF281 UT WOS:A1997WF28100002 PM 9023871 ER PT J AU Brown, M Feuer, E AF Brown, M Feuer, E TI Diagnosis of advanced or noncurable prostate cancer can be practically eliminated by prostate-specific antigen SO UROLOGY LA English DT Letter RP Brown, M (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 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 FEB PY 1997 VL 49 IS 2 BP 306 EP 307 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA WH467 UT WOS:A1997WH46700040 PM 9037307 ER PT J AU Chengalvala, MV Bhat, BM Bhat, RA Dheer, SK Lubeck, MD Purcell, RH Murthy, KK AF Chengalvala, MV Bhat, BM Bhat, RA Dheer, SK Lubeck, MD Purcell, RH Murthy, KK TI Replication and immunogenicity of Ad7-, Ad4-, and Ad5-hepatitis B virus surface antigen recombinants, with or without a portion of E3 region, in chimpanzees SO VACCINE LA English DT Article DE adenovirus; hepatitis B; animal model; E(3) genes ID GROWTH-FACTOR RECEPTOR; MIDDLE-T ANTIGEN; ADENOVIRUS VECTORS; MOLECULAR EPIDEMIOLOGY; GENOME TYPES; EXPRESSION; VACCINES; PROTEIN; GENES; INVITRO AB Human adenovirus vectors containing intact or largely deleted E(3) region were used to construct adenovirus-hepatitis B recombinant viruses (Ad-HepB) and shown to produce substantial amount of recombinant protein, hepatitis B surface antigen (HBsAg), in tissue culture. Previously we showed that these viruses were able to elicit good anti-HBs antibodies in a dog model. In the present study, the Ad-HepB viruses were evaluated for replication and immunogenicity in chimpanzees which sustain permissive infection by human adenoviruses. Recombinants containing entire E(3) region showed better replication pattern than their E(3) deleted counterparts as evidenced by longer duration and high titers of virus shedding. The effect of E(3) region was also seen in the antibody titers against HBsAg in that the E(3) containing viruses showed better response than the E(3) deleted viruses. The importance off, region for the development of adenovirus vectored vaccines is further discussed. (C) 1997 Published by Elsevier Science Ltd. C1 NIAID,NIH,INFECT DIS LAB,BETHESDA,MD. SW FDN BIOMED RES,SAN ANTONIO,TX 78284. RP Chengalvala, MV (reprint author), WYETH AYERST RES,DISCOVERY RES,PHILADELPHIA,PA 19101, USA. NR 24 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD FEB PY 1997 VL 15 IS 3 BP 335 EP 339 DI 10.1016/S0264-410X(96)00174-0 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WM344 UT WOS:A1997WM34400016 PM 9139496 ER PT J AU Bystricky, S Pavliak, V Szu, SC AF Bystricky, S Pavliak, V Szu, SC TI Characterization of colominic acid by circular dichroism and viscosity analysis SO BIOPHYSICAL CHEMISTRY LA English DT Article DE circular dichroism; colominic acid; viscosity analysis ID GROUP-B POLYSACCHARIDE; ESCHERICHIA-COLI K1; NEISSERIA-MENINGITIDIS; CAPSULAR POLYSACCHARIDES; C-POLYSACCHARIDE; POLYSIALIC ACID; EPITOPE; BINDING; CONFORMATION; ANTIBODIES AB Conformations of oligo- and poly-(alpha(2 --> 8)-D-Neu pNAc) (colominic acid) and its derivatives were studied by circular dichroism (CD) spectroscopy and viscometry to understand the molecular basis of their unusual antigenic properties. No temperature-dependent conformational transition between 5 and 70 degrees C or divalent salt effect of Ca2+ or Mg2+ was observed in colominic acid or its N-deacetylated form by CD spectroscopy. However, CD spectroscopy indicated that the distribution of conformers in oligocolominic acid changes continuously from n=2 to octamer, and there was no further change of the conformer distribution for n>9. Colominic acid exhibited a much lower intrinsic viscosity compared with the values for other polyelectrolytes of similar linear charge density, such as polynucleic acids. The apparent absence of induced conformational transition by salt or temperature, and the high flexibility indicated that the binding of colominic acid to its antibodies may not contain a significant amount of specific conformationally controlled determinant. Instead, our data suggest that more than nine saccharide units are needed for a cooperative binding process. C1 NABI,ROCKVILLE,MD 20852. SLOVAK ACAD SCI,INST CHEM,BRATISLAVA,SLOVAKIA. RP Bystricky, S (reprint author), NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD 20892, USA. NR 24 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD JAN 31 PY 1997 VL 63 IS 2-3 BP 147 EP 152 DI 10.1016/S0301-4622(96)02242-9 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA WR477 UT WOS:A1997WR47700007 PM 9108689 ER PT J AU EllingerZiegelbauer, H Brown, K Kelly, K Siebenlist, U AF EllingerZiegelbauer, H Brown, K Kelly, K Siebenlist, U TI Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein kinase/ERK kinase kinase 3 (MEKK) derivative SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B SITE; C-JUN; REQUIRES RAF-1; GENE-PRODUCT; CELLS; RAS; PHOSPHORYLATION; TRANSFORMATION; EXPRESSION; CASCADE AB The extracellular signal-regulated kinase (ERK) pathway, the stress-activated protein kinase (SAPK) pathway, and the p38 pathway are three major mitogen-activated protein kinase (MAPK) cascades known to participate in the regulation of cellular responses to a variety of extracellular signals. Upstream regulatory components of these kinase cascades, the MAPK/ERK kinase kinases (MEKK), have been described in several systems. We have isolated a cDNA encoding human MEKK3. Transfected MEKK3 has the ability to activate both SAPK and ERK pathways, but does not induce p38 activity, in agreement with a previous report on murine MEKK3 (Blank, J. L., Gerwins, P., Elliott, E. M., Sather, S., and Johnson, G. L. (1996) J. Biol. Chem. 271, 5361-5368). We now demonstrate that MEKK3 activates SEK and MEK, the known kinases targeting SAPK and ERK, respectively. Utilizing an estrogen ligand-activated MEKK3 derivative, we furthermore demonstrate that MEKK3 regulates the SAPK and the ERK pathway directly. Consistent with the fact that several SAPK-inducing agents activate the transcription factor NF kappa B, we now show that MEKK3 also enhances transcription from an NF kappa B-dependent reporter gene in cotransfection assays. The ability of MEKK3 to simultaneously activate the SAPK and ERK pathways is remarkable, given that they have divergent roles in cellular homeostasis. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NR 65 TC 77 Z9 79 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 JAN 31 PY 1997 VL 272 IS 5 BP 2668 EP 2674 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE667 UT WOS:A1997WE66700015 PM 9006902 ER PT J AU Utani, A Nomizu, M Yamada, Y AF Utani, A Nomizu, M Yamada, Y TI Fibulin-2 binds to the short arms of laminin-5 and laminin-1 via conserved amino acid sequences SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; DERMAL-EPIDERMAL JUNCTION; BASEMENT-MEMBRANE PROTEIN; EGF-LIKE MOTIF; VII COLLAGEN; BETA-3 CHAIN; INTEGRIN BETA-4; NIDOGEN BINDING; KALININ; MOUSE AB Epithelial cell-specific laminin-5, consisting of three chains, alpha 3, beta 3, and gamma 2, is a component of the anchoring filament that traverses the lamina lucida beneath the hemidesmosomes of epidermal cells and functions to link these cells to the basement membrane. We have studied the molecular interaction between laminin-5 and extracellular matrix proteins using recombinant proteins and synthetic peptides. Affinity chromatography assays with recombinant fragments of the laminin gamma 2 short arm identified a 195-kDa binding protein in the conditioned media from the mouse epidermal cell line Pam 212 and from primary dermal fibroblasts. This molecule was identified by Western blotting as fibulin-2, a recently identified extracellular matrix protein. Using deletion mutants and various synthetic peptides in competition assays, the g-amino acid sequence SADFSVHKI (residues 199-207) in domain IV of the gamma 2 chain was defined as a critical site for fibulin-2 binding. An anti-gamma 2 antibody co-immunoprecipitated fibulin-2 from the conditioned media, further confirming the interaction of fibulin-2 with laminin-5. Fibulin-2 was also found to interact with laminin-1 (alpha 1 beta 1 gamma 1) through a region (residues 654-665) of the alpha 1 chain short arm whose sequence is similar to that of the fibulin-2 binding site of the gamma 2 chain. Together these results suggest that fibulin-2 functions to bridge laminin-1 and laminin-5 with other extracellular matrix proteins, providing a linkage between the cell surface and the basement membrane. C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 46 TC 56 Z9 56 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 JAN 31 PY 1997 VL 272 IS 5 BP 2814 EP 2820 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE667 UT WOS:A1997WE66700035 PM 9006922 ER PT J AU Chang, MCJ Grange, E Rabin, O Bell, JM Allen, DD Rapoport, SI AF Chang, MCJ Grange, E Rabin, O Bell, JM Allen, DD Rapoport, SI TI Lithium decreases turnover of arachidonate in several brain phospholipids (vol 220, pg 171, 1996) SO NEUROSCIENCE LETTERS LA English DT Correction, Addition RP Chang, MCJ (reprint author), NIA,NEUROSCI LAB,NIH,10 CTR DR MSC 1582,BETHESDA,MD 20892, USA. NR 1 TC 2 Z9 2 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 JAN 31 PY 1997 VL 222 IS 2 BP 141 EP 141 PG 1 WC Neurosciences SC Neurosciences & Neurology GA WH247 UT WOS:A1997WH24700019 ER PT J AU Franke, TF Kaplan, DR Cantley, LC Toker, A AF Franke, TF Kaplan, DR Cantley, LC Toker, A TI Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate SO SCIENCE LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; TARGET; KINASE AB The regulation of the serine-threonine kinase Akt by lipid products of phosphoinositide 3-kinase (PI 3-kinase) was investigated. Akt activity was found to correlate with the amount of phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P-2) in vivo, and synthetic PtdIns-3,4-P-2 activated Akt both in vitro and in vivo. Binding of PtdIns-3,4-P-2 occurred within the Akt pleckstrin homology (PH) domain and facilitated dimerization of Akt. Akt mutated in the PH domain was not activated by PI 3-kinase in vivo or by PtdIns-3,4-P-2 in vitro, and it was impaired in binding to PtdIns-3,4-P-2. Examination of the binding to other phosphoinositides revealed that they bound to the Akt PH domain with much lower affinity than did PtdIns-3,4-P-2 and failed to increase Akt activity. Thus, Akt is apparently regulated by the direct interaction of PtdIns-3,4-P-2 with the Akt PH domain. C1 MCGILL UNIV,MONTREAL NEUROL INST,MONTREAL,PQ H3A 2B4,CANADA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT CELL BIOL,DIV SIGNAL TRANSDUCTION,BOSTON,MA 02115. RP Franke, TF (reprint author), NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES FACIL & DEV CTR,FREDERICK,MD 21702, USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 18 TC 1126 Z9 1141 U1 3 U2 20 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 31 PY 1997 VL 275 IS 5300 BP 665 EP 668 DI 10.1126/science.275.5300.665 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WF077 UT WOS:A1997WF07700039 PM 9005852 ER PT J AU Hoofnagle, JH DiBisceglie, AM AF Hoofnagle, JH DiBisceglie, AM TI The treatment of chronic viral hepatitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; NON-B-HEPATITIS; PLACEBO-CONTROLLED TRIAL; HUMAN ALPHA-INTERFERON; C VIRUS-INFECTION; CHRONIC NON-A; LONG-TERM; POSTTRANSFUSION HEPATITIS; LIVER-DISEASE; RECOMBINANT INTERFERON-ALPHA-2B C1 ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,ST LOUIS,MO. RP Hoofnagle, JH (reprint author), NIDDKD,LIVER DIS SECT,DIGEST DIS BRANCH,NIH,BLDG 31,RM 9A23,BETHESDA,MD 20892, USA. NR 107 TC 795 Z9 820 U1 2 U2 13 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 JAN 30 PY 1997 VL 336 IS 5 BP 347 EP 356 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA WG233 UT WOS:A1997WG23300007 PM 9011789 ER PT J AU Ladenheim, EE Moore, KA Salorio, CF Mantey, SA Taylor, JE Coy, DH Jensen, RT Moran, TH AF Ladenheim, EE Moore, KA Salorio, CF Mantey, SA Taylor, JE Coy, DH Jensen, RT Moran, TH TI Characterization of bombesin binding sites in the rat stomach SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE gastrin-releasing peptide; neuromedin B; smooth muscle contraction ID GASTRIN-RELEASING PEPTIDE; PORCINE SPINAL-CORD; RECEPTOR SUBTYPES; NEUROMEDIN-B; SMOOTH-MUSCLE; GUINEA-PIG; ANTAGONISTS; IMMUNOREACTIVITY; BRAIN AB We characterized the bombesin receptor population in the rat stomach and determined the receptor subtype mediating the contractile effect of bombesin in the gastric fundus. Using in vitro receptor autoradiography, we evaluated the ability of the specific gastrin-releasing peptide-preferring receptor antagonist [D-F-5,Phe(6),D-Ala(11)]bombesin-(6-13) methyl ester to inhibit binding of I-125-[Tyr(4)]bombesin to the gastric fundus, corpus and antrum. Binding to these regions was completely inhibited by [D-F-5,Phe(6),D-Ala(11)]bombesin-(6-13) methyl ester suggesting that these receptors are the gastrin-releasing peptide-preferring subtype. We found that the rank order of potency for the contractile effect of bombesin, and the related mammalian peptides neuromedin C and neuromedin B, was bombesin > neuromedin C > neuromedin B. [D-F-5,Phe(6),D-Ala(11)]bombesin-(6-13) methyl ester was equipotent in antagonizing contractions produced by all three peptides. Furthermore, receptor tachyphylaxis to either neuromedin C or neuromedin B abolished the subsequent contractile response elicited by neuromedin C and neuromedin B, suggesting that one bombesin receptor subtype mediates rat gastric fundal contractions. Together, these results demonstrate that the bombesin receptor subtype in the rat stomach is gastrin-releasing peptide-preferring subtype and that this subtype is responsible for the effects of bombesin-like peptides on fundal smooth muscle contraction. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NIDDK,NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. BIOMEASURE INC,MILFORD,MA 01757. TULANE UNIV,MED CTR,DEPT MED,PEPTIDE RES LABS,NEW ORLEANS,LA 70112. FU NIDDK NIH HHS [DK46448] NR 21 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 29 PY 1997 VL 319 IS 2-3 BP 245 EP 251 DI 10.1016/S0014-2999(96)00854-0 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WF589 UT WOS:A1997WF58900014 PM 9042597 ER PT J AU Lasic, DD Strey, H Stuart, MCA Podgornik, R Frederik, PM AF Lasic, DD Strey, H Stuart, MCA Podgornik, R Frederik, PM TI The structure of DNA-liposome complexes SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TRANSFECTION; EFFICIENT C1 NIH,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,BETHESDA,MD. MEGABIOS CORP,BURLINGAME,CA. UNIV LIMBURG,DEPT PATHOL,ELECTRON MICROSCOPY UNIT,MAASTRICHT,NETHERLANDS. RI Stuart, Marc/B-6274-2008; Strey, Helmut/B-5456-2009; Podgornik, Rudolf/C-6209-2008 OI Stuart, Marc/0000-0003-0667-6338; Podgornik, Rudolf/0000-0002-3855-4637 NR 20 TC 319 Z9 323 U1 0 U2 16 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 JAN 29 PY 1997 VL 119 IS 4 BP 832 EP 833 DI 10.1021/ja962713g PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WE826 UT WOS:A1997WE82600026 ER PT J AU Ji, BT Chow, WH Hsing, AW McLaughlin, JK Dai, Q Gao, YT Blot, WJ Fraumeni, JF AF Ji, BT Chow, WH Hsing, AW McLaughlin, JK Dai, Q Gao, YT Blot, WJ Fraumeni, JF TI Green tea consumption and the risk of pancreatic and colorectal cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LARGE INTESTINAL CANCERS; BEVERAGE CONSUMPTION; CIGARETTE-SMOKING; DIETARY HABITS; BLACK TEA; COFFEE; ALCOHOL; CARCINOGENESIS; POLYPHENOLS; CHINA AB The effect of green tea drinking in reducing human cancer risk is unclear, though a protective effect has been reported in numerous animal studies and several epidemiologic investigations. Herein the hypothesis that green tea consumption may reduce the risk of cancers of the colon, rectum and pancreas is examined in a large population-based case-control study conducted in Shanghai, China. Newly diagnosed cancer cases (931 colon, 884 rectum and 451 pancreas) during 1990-1993 among residents 30-74 years of age were included. Controls (n = 1,552) were selected among Shanghai residents and frequency-matched to cases by gender and age. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of each cancer associated with green tea consumption were derived after adjustment for age, income, education and cigarette smoking. Additional adjustment for dietary items and body size was found to have minimal impact. An inverse association with each cancer was observed with increasing amount of green tea consumption, with the strongest trends for rectal and pancreatic cancers. For men, compared with non-regular tea drinkers, ORs among those in the highest tea consumption category (greater than or equal to 300 g/month) were 0.82 for colon cancer, 0.72 for rectal cancer and 0.63 for pancreatic cancer, with p values for trend being 0.38, 0.04 and 0.04, respectively. For women, the respective ORs for the highest consumption category (greater than or equal to 200 g/month) were 0.67, 0.57 and 0.53, with the respective p values for trend being 0.07, 0.001 and 0.008. Our findings provide further evidence that green tea drinking may lower the risk of colorectal and pancreatic cancers. (C) 1997 Wiley-Liss, Inc.* C1 COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. INT EPIDEMIOL INST,ROCKVILLE,MD. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. NR 43 TC 158 Z9 168 U1 2 U2 11 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 JAN 27 PY 1997 VL 70 IS 3 BP 255 EP 258 DI 10.1002/(SICI)1097-0215(19970127)70:3<255::AID-IJC1>3.0.CO;2-W PG 4 WC Oncology SC Oncology GA WF989 UT WOS:A1997WF98900001 PM 9033623 ER PT J AU Liaw, KL Linet, MS McLaughlin, JK Yu, MC Schoenberg, JB Lynch, ME Niwa, S Fraumeni, JF AF Liaw, KL Linet, MS McLaughlin, JK Yu, MC Schoenberg, JB Lynch, ME Niwa, S Fraumeni, JF TI Possible relation between hypertension and cancers of the renal pelvis and ureter SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NEW-SOUTH-WALES; RISK-FACTORS; CIGARETTE-SMOKING; CELL CARCINOMA; KIDNEY CANCER; ANALGESICS; DIURETICS AB To evaluate the relationship of selected medical conditions and medications with cancers of the renal pelvis and ureter, we interviewed 308 subjects with renal pelvis cancer, 194 subjects with ureter cancer and 496 control subjects in 3 areas of the United States. After controlling for the effects of smoking, age, gender and geographic residence, a history of hypertension (reported to have been diagnosed more than 5 years before interview) was associated with a small but significantly increased risk (odds ratio [OR] 1.3; 95% confidence interval [CI], 1.0-1.8), whereas no relationship was observed with a variety of other medical conditions or medications. Stratified analysis showed that the risk associated with hypertension was twice as high among users of diuretics or other antihypertensive drugs (OR = 2.4; 95% CI, 1.1-4.9) as it was among those who never used these medications (OR = 1.2; 95% CI, 0.8-1.7). Our findings suggest that the association previously reported between hypertension and renal cell cancer may extend to cancers of the renal pelvis and ureter. (C) 1997 Wiley-Liss, Inc.* C1 INT EPIDEMIOL INST,ROCKVILLE,MD. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. NEW JERSEY STATE DEPT HLTH,TRENTON,NJ 08625. UNIV IOWA,COLL MED,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA. WESTAT CORP,ROCKVILLE,MD. RP Liaw, KL (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,6130 EXECUT BLVD,EPN 443,ROCKVILLE,MD 20852, USA. NR 25 TC 20 Z9 20 U1 0 U2 1 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 JAN 27 PY 1997 VL 70 IS 3 BP 265 EP 268 DI 10.1002/(SICI)1097-0215(19970127)70:3<265::AID-IJC3>3.0.CO;2-V PG 4 WC Oncology SC Oncology GA WF989 UT WOS:A1997WF98900003 PM 9033625 ER PT J AU Trach, DD Clemens, JD Ke, NT Thuy, HT Son, ND Canh, DG Hang, PVD Rao, MR AF Trach, DD Clemens, JD Ke, NT Thuy, HT Son, ND Canh, DG Hang, PVD Rao, MR TI Field trial of a locally produced, killed, oral cholera vaccine in Vietnam SO LANCET LA English DT Article ID VIBRIO-CHOLERAE; WHOLE-CELL; FOLLOW-UP; B-SUBUNIT; BANGLADESH; MODEL AB Background Several studies have shown that orally administered killed cholera vaccines are safe and protective in populations at risk of cholera in developing countries. However, these vaccines have not been adopted for use in developing countries because of their expense and limited efficacy in young children. We have tested an inexpensive, killed whole-cell cholera vaccine developed and produced in Vietnam. Methods The efficacy of the vaccine was assessed in a large-scale, open field trial in people at least 1 year old residing in 22 653 households in the central coastal city of Hue. Alternate households were assigned vaccine (67 395 people; two doses per person) or no vaccine (67 058 people). Surveillance for cholera was conducted in all Ministry of Health facilities serving this population. Analysis was by intention to treat. Findings During an outbreak of El Tor cholera 8-10 months after vaccination, 37 cases of cholera requiring inpatient care occurred among age-eligible people allocated to the vaccine group, and 92 cases among age-eligible people allocated to the no-vaccine group (protective impact 60% [95% CI 40-73]). Among the 51 975 people who received the complete two-dose vaccine regimen, the protective efficacy was 66% (46-79); in this subset, the protective efficacy was similar for children aged 1-5 years (68%) and for older people (66%). Interpretation These findings suggest that oral killed whole-cell vaccines can confer substantial protection against El Tor cholera in young children, who are at highest risk of cholera in endemic settings. An inexpensive, locally produced, and effective oral cholera vaccine may be within reach of the limited healthcare budgets of poor countries with endemic cholera, if our findings can be replicated in a randomised double-blind trial. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. NATL INST HYG & EPIDEMIOL,HANOI,VIETNAM. CTR PREVENT MED,HUE,VIETNAM. INST VACCINES,NHA TRANG,VIETNAM. NR 17 TC 121 Z9 123 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JAN 25 PY 1997 VL 349 IS 9047 BP 231 EP 235 DI 10.1016/S0140-6736(96)06107-7 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WD906 UT WOS:A1997WD90600009 PM 9014909 ER PT J AU Kunkel, TA Resnick, MA Gordenin, DA AF Kunkel, TA Resnick, MA Gordenin, DA TI Mutator specificity and disease: Looking over the FENce SO CELL LA English DT Review ID DNA-SYNTHESIS; REPEATS; REPLICATION RP Kunkel, TA (reprint author), NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709, USA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 20 TC 40 Z9 40 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 24 PY 1997 VL 88 IS 2 BP 155 EP 158 DI 10.1016/S0092-8674(00)81832-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE970 UT WOS:A1997WE97000001 PM 9008154 ER PT J AU Freed, EO Englund, G Maldarelli, F Martin, MA AF Freed, EO Englund, G Maldarelli, F Martin, MA TI Phosphorylation of residue 131 of HIV-1 matrix is not required for macrophage infection SO CELL LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEAR-LOCALIZATION SIGNAL; NONDIVIDING CELLS; PRODUCTIVE INFECTION; PROTEIN; INVITRO; DOMAIN RP Freed, EO (reprint author), NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 16 TC 53 Z9 53 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 24 PY 1997 VL 88 IS 2 BP 171 EP 173 DI 10.1016/S0092-8674(00)81836-X PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE970 UT WOS:A1997WE97000004 PM 9008157 ER PT J AU Ulbrandt, ND Newitt, JA Bernstein, HD AF Ulbrandt, ND Newitt, JA Bernstein, HD TI The E-coli signal recognition particle is required for the insertion of a subset of inner membrane proteins SO CELL LA English DT Article ID ESCHERICHIA-COLI; 4.5S RNA; SEQUENCE RECOGNITION; ALKALINE-PHOSPHATASE; ALPHA-SUBUNIT; GENE; TOPOLOGY; EXPORT; RIBONUCLEOPROTEIN; RECEPTOR AB E. coli homologs of the signal recognition particle (SRP) and its receptor are essential for viability, but their role in protein export is unclear. To elucidate their function, we devised a genome-wide screen to identify genes that encode SRP substrates. Inhibition of the SRP pathway sharply blocked the membrane insertion of several polytopic inner membrane proteins (IMPs) that were predicted to be SRP substrates, but had a smaller effect on the insertion of other IMPs and no significant effect on preprotein translocation. Our results suggest that whereas most E. coli preproteins and some IMPs can utilize SRP-independent targeting pathways effectively, the structural features of a subset of IMPs have required the conservation of an SRP-based targeting machinery. RP NIDDKD, GENET & BIOCHEM BRANCH, NIH, BETHESDA, MD 20892 USA. NR 47 TC 260 Z9 262 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 24 PY 1997 VL 88 IS 2 BP 187 EP 196 DI 10.1016/S0092-8674(00)81839-5 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE970 UT WOS:A1997WE97000007 PM 9008159 ER PT J AU Velculescu, VE Zhang, L Zhou, W Vogelstein, J Basrai, MA Bassett, DE Hieter, P Vogelstein, B Kinzler, KW AF Velculescu, VE Zhang, L Zhou, W Vogelstein, J Basrai, MA Bassett, DE Hieter, P Vogelstein, B Kinzler, KW TI Characterization of the yeast transcriptome SO CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; GENE-EXPRESSION; ALPHA-FACTOR; FACTOR PHEROMONE; DNA; SEQUENCE; IDENTIFICATION; HYBRIDIZATION; TERMINATION AB We have analyzed the set of genes expressed from the yeast genome, herein called the transcriptome, using serial analysis of gene expression. Analysis of 60,633 transcripts revealed 4,665 genes, with expression levels ranging from 0.3 to over 200 transcripts per cell. Of these genes, 1981 had known functions, while 2684 were previously uncharacterized. The integration of positional information with gene expression data allowed for the generation of chromosomal expression maps identifying physical regions of transcriptional activity and identified genes that had not been predicted by sequence information alone. These studies provide insight into global patterns of gene expression in yeast and demonstrate the feasibility of genome-wide expression studies in eukaryotes. C1 JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21231. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21231. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21231. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Velculescu, VE (reprint author), JOHNS HOPKINS UNIV,SCH MED,PROGRAM HUMAN & GENET & MOL BIOL,BALTIMORE,MD 21231, USA. FU NCI NIH HHS [CA35494, CA57345]; NIGMS NIH HHS [GM07309] NR 34 TC 759 Z9 819 U1 5 U2 50 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 24 PY 1997 VL 88 IS 2 BP 243 EP 251 DI 10.1016/S0092-8674(00)81845-0 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE970 UT WOS:A1997WE97000013 PM 9008165 ER PT J AU McConkey, GA Rogers, MJ McCutchan, TF AF McConkey, GA Rogers, MJ McCutchan, TF TI Inhibition of Plasmodium falciparum protein synthesis - Targeting the plastid-like organelle with thiostrepton SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBUNIT RIBOSOMAL-RNA; TOXOPLASMA-GONDII; PHYLOGENETIC ANALYSIS; MALARIA PARASITES; MOLECULAR-BASIS; GTPASE CENTER; CIRCULAR DNA; RESISTANCE; INVITRO; ANTIBIOTICS AB The human malaria parasite Plasmodium falciparum has two extrachromosomal DNAs associated with organelles whose function is unclear. Both genomes encode ribosomal RNAs (rRNAs) that are distinct from the nuclear-encoded rRNAs. Secondary structure analysis of all the P. falciparum rRNAs indicates that only the large subunit (LSU) rRNA encoded by the plastid-like genome is the target for thiostrepton. Indeed we find that thiostrepton inhibits growth of the parasite in the micromolar range which is 10-fold below concentrations with observable effects on total protein synthesis. me have further examined selective effects of thiostrepton on the plastid function by comparing differential effects of the drug on cytoplasmic and organellar encoded transcripts. Treatment with either thiostrepton or rifampin, an inhibitor of organellar and eubacterial RNA polymerase, both showed disappearance of organellar-encoded RNA transcripts within 6 h of treatment while transcripts of a nuclear-encoded mRNA remained constant for at least 8 h of treatment. Hence, we show a selective effect on organelle function that is suggestive of interference in the protein synthesis apparatus of the plastid. Sensitivity of P. falciparum to thiostrepton confirms that the plastid-like genome is essential for the erythrocytic cycle and presents a novel therapeutic site for this class of antibiotics. C1 NIAID,GROWTH & DEV SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NR 45 TC 131 Z9 135 U1 0 U2 4 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 JAN 24 PY 1997 VL 272 IS 4 BP 2046 EP 2049 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900005 PM 8999899 ER PT J AU Ferrier, AF Lee, M Anderson, WB Benvenuto, G Morrison, DK Lowy, DR DeClue, JE AF Ferrier, AF Lee, M Anderson, WB Benvenuto, G Morrison, DK Lowy, DR DeClue, JE TI Sequential modification of serines 621 and 624 in the Raf-1 carboxyl terminus produces alterations in its electrophoretic mobility SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; SIGNAL-TRANSDUCTION PATHWAYS; POLYMERASE CHAIN-REACTION; NIH 3T3 CELLS; TYROSINE PHOSPHORYLATION; PLASMA-MEMBRANES; MAMMALIAN-CELLS; ACTIVATION; RAS; REQUIREMENT AB The Raf-1 serine/threonine protein kinase plays a central role in many of the mitogenic signaling pathways regulating cell growth and differentiation. The regulation of Raf-1 is complex, and involves protein-protein interactions as well as changes in the phosphorylation state of Raf-1 that are accompanied by alterations in its electrophoretic mobility. We have previously shown that a 33-kDa COOH-terminal, kinase-inactive fragment of Raf-1 underwent a mobility shift in response to the stimulation of cells with serum or phorbol esters. Here we demonstrate that treatment of NIH 3T3 cells or Sf9 cells with hydrogen peroxide (H2O2) also induces the mobility shift of the kinase-inactive Raf-1 fragment. A series of deletion mutants of the Raf-1 COOH terminus were analyzed, and the region required for the mobility shift was localized to a 78-amino acid fragment (residues 566-643). Metabolic labeling revealed that the slower migrating forms of the 33-kDa and of the smaller fragment contained phosphorus. Mutation of a previously characterized phosphorylation site, serine 621, to alanine prevented the mobility shift as well as phosphate incorporation or Src and Ras-dependent kinase activation in Sf9 cells when this mutation was engineered into the full-length Raf-1. Mutation of 621 to aspartate yielded a protein that existed in both the shifted and unshifted forms, demonstrating that a negative charge at 621 was necessary, but not sufficient, for the mobility shift to occur; however, its full-length form was still resistant to activation in the Sf9 system. Additional mutation of nearby serine 624 to alanine blocked the shift, implicating this residue as the site of the second of a two-step modification process leading to the slower migrating form. Co-expression of the 33-kDa fragment with an activated form of mitogen-activated protein kinase kinase in NIH 3T3 led to the appearance of the shifted form in a serum-independent manner. These results demonstrate that a mitogen-activated protein kinase kinase-induced event involving modification of serines 621 and 624 leads to the mobility shift of Raf-1. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NCI,MOL MECHANISMS CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 61 TC 22 Z9 23 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 JAN 24 PY 1997 VL 272 IS 4 BP 2136 EP 2142 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900020 PM 8999914 ER PT J AU Tan, Z Bruzik, KS Shears, SB AF Tan, Z Bruzik, KS Shears, SB TI Properties of the inositol 3,4,5,6-tetrakisphosphate 1-kinase purified from rat liver - Regulation of enzyme activity by inositol 1,3,4-trisphosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACINAR-CELLS; MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; CHLORIDE SECRETION; T84 CELLS; CALCIUM; 1,4,5,6-TETRAKISPHOSPHATE; 1,3,4,6-TETRAKISPHOSPHATE; POLYPHOSPHATES; PHOSPHATES; SIGNALS AB Inositol 3,4,5,6-tetrakisphosphate is a novel intracellular signal that regulates calcium-dependent chloride conductance (Xie, W., Kaetzel, M. A., Bruzik, H. S., Dedman, J. R., Shears, S. B., and Nelson, D. J. (1996) J. Biol. Chem. 271, 14092-14097). The molecular mechanisms that regulate the cellular levels of this signal are not characterized. To pursue this problem we have now studied the 1-kinase that deactivates inositol 3,4,5,6-tetrakisphosphate. The enzyme was purified from rat liver 1600-fold with a 1% yield. The native molecular mass was determined to be 46 kDa by gel filtration. The K-m values for inositol 3,4,5,6-tetrakisphosphate and ATP were 0.3 and 10.6 mu M, respectively. The kinase was unaffected by either protein kinase A or protein kinase C. Increases in Ca2+ concentration from 0.1 to 1-2 mu M inhibited activity by 10-20%. Most importantly, inositol 1,3,4-trisphosphate was shown to be a potent (K-i = 0.2 mu M), specific, and competitive inhibitor of the 1-kinase. Our new kinetic data show that typical receptor-dependent adjustments in cellular levels of inositol 1,3,4-trisphosphate provide a mechanism by which the concentration of inositol 3,4,5,6-tetrakisphosphate is dependent on changes in phospholipase C activity. These conclusions also provide a new perspective to our understanding of the physiological importance of the pathway of inositol phosphate turnover initiated by the inositol 1,4,5-trisphosphate 3-kinase. C1 NIEHS,LAB SIGNAL TRANSDUCT,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY MC781,CHICAGO,IL 60612. NR 26 TC 24 Z9 25 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 JAN 24 PY 1997 VL 272 IS 4 BP 2285 EP 2290 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900041 PM 8999935 ER PT J AU Kundu, GC Mukherjee, AB AF Kundu, GC Mukherjee, AB TI Evidence that porcine pancreatic phospholipase A(2) via its high affinity receptor stimulates extracellular matrix invasion by normal and cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-SITES; PLASMINOGEN-ACTIVATOR; MOLECULAR-CLONING; EXPRESSION; LOCALIZATION; INFLAMMATION; RAT AB Cellular migration and extracellular matrix (ECM) invasion are some of the critical steps in embryonic implantation, inflammation, mound healing, and cancer metastasis. Extracellular phospholipases A(2) (PLA(2)s), belonging to either group I (PLA(2)-I) or group II (PLA(2)-II), play an essential role in the generation of proinflammatory lipid mediators (e.g. prostaglandins, leukotrienes, etc.). Recent reports indicate that PLA(2)-I, in addition to its digestive function, has receptor-mediated effects. For instance, PLA(2)-I, via its receptor, can induce cell proliferation and airway as well as vascular smooth muscle contraction. Here, we report that both porcine pancreatic and Naja naja PLA(2)s, in a dose-dependent manner, stimulate dramatic invasion of an artificial ECM (Matrigel(TM)) by MH 3T3, mouse fibrosarcoma, and sarcoma cells in vitro, but it has no such effect on lymphoma and mastocytoma cells. That this is a receptor-mediated process is strongly suggested by the following findings. (a) While NIH 3T3, mouse fibrosarcoma, and sarcoma cells, which respond to PLA(2)-I stimulation, express high affinity PLA(2)-I receptor mRNA and protein, this receptor expression is not detectable in nonresponder lymphoma and mastocytoma cells. (b) There is a close correlation between the K-d values for I-I25-PLA(2)-I binding to its receptor and the ED(50) values for PLA(2)-I-induced ECM-invasion. (c) Catalytically inactivated PLA(2)-I is as effective as the active enzyme in stimulating invasion. (d) Suppression of PLA(2)-I receptor expression in responder cells causes inhibition of ECM invasion. (e) Treatment of the same cells with PLA(2)-I receptor-antibody also produces virtually identical effects. Taken together, our results identify a novel receptor-mediated function of PLA(2)-I and raises the possibility that extracellular PLA(2)s play important physiological as well as pathological roles via this receptor. To our knowledge, this is the first report of this novel receptor-mediated effect (i.e. ECM invasion) of PLA(2)-I on normal as well as malignant cancer cells. C1 NICHHD, SECT DEV GENET, HERITABLE DISORDERS BRANCH, NIH, BETHESDA, MD 20892 USA. NR 37 TC 64 Z9 64 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 24 PY 1997 VL 272 IS 4 BP 2346 EP 2353 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900050 PM 8999944 ER PT J AU DeGray, JA Gunther, MR TschirretGuth, R deMontellano, PRO Mason, RP AF DeGray, JA Gunther, MR TschirretGuth, R deMontellano, PRO Mason, RP TI Peroxidation of a specific tryptophan of metmyoglobin by hydrogen peroxide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPERM WHALE MYOGLOBIN; ELECTRON-TRANSFER REACTIONS; OXIDATION; ORIENTATION; TYR-151; OXYMYOGLOBIN; PROTEINS; ENZYMES; MODEL AB Globin-centered radicals at tyrosine and tryptophan residues and a peroxyl radical at an unknown location have been reported previously as products of the reaction of metmyoglobin with hydrogen peroxide. The peroxyl radical is shown here to be localized on tryptophan through the use of recombinant sperm whale myoglobin labeled with C-13 at the indole ring C-3. Peroxyl radical formation was not prevented by site-directed mutations that replaced all three tyrosines, the distal histidine, or tryptophan 7 with non-oxidizable residues. In contrast, mutation of tryptophan 14 prevents peroxyl radical formation, implicating tryptophan 14 as the specific site of the peroxidation. C1 NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709. UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHARMACOL,SAN FRANCISCO,CA 94143. NR 30 TC 96 Z9 96 U1 0 U2 4 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 JAN 24 PY 1997 VL 272 IS 4 BP 2359 EP 2362 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900052 PM 8999946 ER PT J AU Ono, S Yamakita, Y Yamashiro, S Matsudaira, PT Gnarra, JR Obinata, T Matsumura, F AF Ono, S Yamakita, Y Yamashiro, S Matsudaira, PT Gnarra, JR Obinata, T Matsumura, F TI Identification of an actin binding region and a protein kinase C phospkorylation site on human fascin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEA-URCHIN EGGS; CROSS-LINKING PROTEIN; BUNDLING PROTEIN; CULTURED-CELLS; HOMOLOG; MARCKS; EXPRESSION; FAMILY; PHOSPHOPROTEINS; LOCALIZATION AB Fascin is a 5538-kDa actin-bundling protein, the actin binding of which is regulated by phosphorylation (Yamakita, Y., One, S., Matsumura, F., add Yamashiro, S, (1996) J. Biol. Chem. 271, 12632-12638). To understand the mechanism of fascin-actin interactions, we dissected the actin binding region and its regulatory site by phosphorylation of human fascin. First, we found that the C-terminal half constitutes an actin binding domain, Partial digestion of human recombinant fascin with trypsin yielded the C-terminal fragment with molecular masses of 32, 30, and 27 kDa. The 32- and 27-kDa fragments purified as a mixture formed a dimer and bound to F-actin at a saturation ratio of 1 dimer:11 actin molecules with an affinity of 1.4 x 10(6) M(-1). Second, we identified the phosphorylation site of fascin as Ser-39 by sequencing a tryptic phosphopeptide purified by chelating column chromatography followed by C-18 reverse phase high performance liquid chromatography. Pep tide map analyses revealed that the purified peptide represented the major phosphorylation site of in vivo as well as in vitro phosphorylated fascin. The mutation replacing Ser-39 with Ala eliminated the phosphorylation-dependent regulation of actin binding of fascin, indicating that phosphorylation at this site regulates the actin binding ability of fascin. C1 RUTGERS STATE UNIV,DEPT MOL BIOL & BIOCHEM,NELSON LABS,PISCATAWAY,NJ 08855. CHIBA UNIV,DEPT BIOL,INAGE KU,CHIBA 263,JAPAN. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. NCI,UROL ONCOL SECT,SURG BRANCH,NATL INST HLTH,BETHESDA,MD 20892. RI Matsudaira, Paul/H-1475-2012; Yamakita, Yoshihiko/A-3003-2016; Ono, Shoichiro/A-6475-2015 OI Matsudaira, Paul/0000-0002-8399-3276; Ono, Shoichiro/0000-0002-4763-0398 FU NCI NIH HHS [R37 CA42742] NR 40 TC 117 Z9 123 U1 0 U2 6 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 JAN 24 PY 1997 VL 272 IS 4 BP 2527 EP 2533 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900075 PM 8999969 ER PT J AU Kowalski, RJ Giannakakou, P Hamel, E AF Kowalski, RJ Giannakakou, P Hamel, E TI Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYNAMIC INSTABILITY; GUANINE-NUCLEOTIDES; BINDING-SITE; BETA-TUBULIN; AMINO-ACIDS; PROTEINS; ANALOGS; POLYMERIZATION; MECHANISM; 5'-TRIPHOSPHATE AB Epothilones A and B, natural products with minimal structural analogy to taxoids, have effects similar to those of paclitaxel (Taxol(R)) in cultured cells and on microtubule protein, but differ from paclitaxel in retaining activity in multidrug-resistant cells. We examined interactions of the epothilones with purified tubulin and additional cell Lines, including a paclitaxel-resistant ovarian carcinoma Line with an altered beta-tubulin. The epothilones, like paclitaxel, induced tubulin to form microtubules at low temperatures and without GTP and/or microtubule-associated proteins. The epothilones are competitive inhibitors of the binding of [H-3]paclitaxel to tubulin polymers. The apparent K-i values for epothilones A and B were 1.4 and 0.7 mu M by Hanes analysis and 0.6 and 0.4 mu M by Dixon analysis. In the paclitaxel-sensitive human cell lines we examined, epothilone B had greater antiproliferative activity than epothilone A or paclitaxel, while epothilone A was usually less active than paclitaxel. A multidrug-resistant colon carcinoma line and the paclitaxel-resistant ovarian line retained sensitivity to the epothilones. With Potorous tridactylis kidney epithelial (PtK2) cells examined by indirect immunofluorescence, microtubule bundles appeared more rapidly following epothilone B treatment, and there were different proportions of various mitotic aberrations following treatment with different drugs. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 36 TC 432 Z9 449 U1 1 U2 19 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 JAN 24 PY 1997 VL 272 IS 4 BP 2534 EP 2541 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD679 UT WOS:A1997WD67900076 PM 8999970 ER PT J AU Shibusawa, Y Hagiwara, Y Chao, ZM Ma, Y Ito, Y AF Shibusawa, Y Hagiwara, Y Chao, ZM Ma, Y Ito, Y TI Application of high-speed counter-current chromatography to the separation of coumarin and related compounds SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; coumarin; hydroxycinnamic acids; esculin; organic acids ID COIL PLANET CENTRIFUGE; STATIONARY PHASE; RETENTION; APPARATUS; SYSTEMS; XLL AB Coumarin and related compounds were successfully separated by high-speed counter-current chromatography (CCC). Using the conventional technique with the cross-axis coil planet centrifuge, coumarin, esculin, 2- and 3- or 4-hydroxycinnamic acids were well resolved with a solvent system composed of ethyl acetate-10 mM potassium phosphate (1:1, v/v) at pH 6.5, while the separation between 3- and 4-hydroxycinnamic acids was difficult. The separation of 2-, 3- and 4-hydroxycinnamic acids, was achieved by pH-zone-refining CCC using a type-J multilayer coil planet centrifuge with a methyl-tert.-butyl ether-acetonitrile-water (1:0:1, or 4:1:5, v/v) system where trifluoroacetic acid was added to the organic mobile phase as an eluter and while ammonia was added to the aqueous stationary phase as a retainer. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Shibusawa, Y (reprint author), TOKYO UNIV PHARM & LIFE SCI,DEPT ANALYT CHEM,1432-1 HACHIOJI,HORINOUCHI,TOKYO 19203,JAPAN. NR 11 TC 9 Z9 11 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 24 PY 1997 VL 759 IS 1-2 BP 47 EP 53 DI 10.1016/S0021-9673(96)00762-5 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WH312 UT WOS:A1997WH31200005 ER PT J AU Ezennia, EI Phillips, LR Wolfe, TL Tabibi, SE AF Ezennia, EI Phillips, LR Wolfe, TL Tabibi, SE TI Analysis of perillic acid in plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE perillic acid ID METABOLITES; LIMONENE; ALCOHOL; AGENT AB A simple and sensitive isocratic high-performance liquid chromatographic (HPLC) method with UV detection for the quantitation of perillic acid, a major circulating metabolite of perillyl alcohol and d-limonene, in plasma is described. Sample preparation involved protein precipitation and subsequent transfer and dilution with 10 mM NaHCO3. The mobile phase consisted of acetonitrile (36%) and 0.05 M ammonium acetate buffer pH 5.0 (64%). Separations were achieved on a C-18. column and the effluent monitored for UV absorption at the analytes' respective UVmax. Separation was excellent with no interference from endogenous plasma constituents. This method was found suitable for quantifying drug concentrations in the range of 0.25 to 200.0 mu g/ml using a 0.05-ml plasma sample, and was used to study the plasma pharmacokinetics of perillic acid in mice. C1 NCI,LAB PHARMACEUT CHEM,DIV CANC BIOL DIAG & CTR,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NIH,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. RP Ezennia, EI (reprint author), NCI,DRUG FORMULAT LAB,SCI APPLICAT INT CO,FREDERICK CANC RES & DEV CTR,BLDG 562,ROOM 101,FREDERICK,MD 21702, USA. NR 7 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 24 PY 1997 VL 688 IS 2 BP 354 EP 358 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WV312 UT WOS:A1997WV31200024 ER PT J AU Murphy, PM AF Murphy, PM TI AIDS - Pirated genes in Kaposi's sarcoma SO NATURE LA English DT Editorial Material ID HERPESVIRUS SAIMIRI RP Murphy, PM (reprint author), NIAID,HOST DEF LAB,NIH,BLDG 10,ROOM 11N113,BETHESDA,MD 20892, USA. NR 15 TC 32 Z9 32 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 23 PY 1997 VL 385 IS 6614 BP 296 EP & DI 10.1038/385296a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD914 UT WOS:A1997WD91400023 PM 9002510 ER PT J AU Bezrukov, SM Vodyanoy, I AF Bezrukov, SM Vodyanoy, I TI Stochastic resonance in non-dynamical systems without response thresholds SO NATURE LA English DT Article ID NOISE AB The addition of noise to a system can sometimes improve its ability to transfer information reliably. This phenomenon-known as stochastic resonance-was originally proposed to account for periodicity in the Earth's ice ages', but has now been shown to occur in many systems in physics and biology(2-4). Recent experimental and theoretical work has shown that the simplest system exhibiting 'stochastic resonance' consists of nothing more than signal and noise with a threshold-triggered device (when the signal plus noise exceeds the threshold, the system responds momentarily, then relaxes to equilibrium to await the next triggering event)(4-6). Here we introduce a class of non-dynamical and threshold-free systems that also exhibit stochastic resonance. We present and analyse a general mathematical model for such systems, in which a sequence of pulses is generated randomly with a probability (per unit time) that depends exponentially on an input. When this input is a sine-wave masked by additive noise, we observe an increase in the output signal-to-noise ratio as the level of noise increases. This result shows that stochastic resonance can occur in a broad class of thermally driven physico-chemical systems, such as semiconductor p-n junctions, mesoscopic electronic devices and voltage-dependent ion channels(7), in which reaction rates are controlled by activation barriers. C1 ST PETERSBURG NUCL PHYS INST, GATCHINA 188530, RUSSIA. OFF NAVAL RES EUROPE, LONDON NW1 5TH, ENGLAND. UCL, LONDON, ENGLAND. RP Bezrukov, SM (reprint author), NIH, DIV COMP RES & TECHNOL, BETHESDA, MD USA. NR 17 TC 194 Z9 197 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 23 PY 1997 VL 385 IS 6614 BP 319 EP 321 DI 10.1038/385319a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD914 UT WOS:A1997WD91400043 PM 9002515 ER PT J AU Stanley, EF Mirotznik, RR AF Stanley, EF Mirotznik, RR TI Cleavage of syntaxin prevents G-protein regulation of presynaptic calcium channels SO NATURE LA English DT Article ID CHICK CILIARY GANGLION; ACETYLCHOLINE-RELEASE; SENSORY NEURONS; GIANT SYNAPSE; N-TYPE; CURRENTS; SYNAPTOTAGMIN; MODULATION; INHIBITION AB Neurotransmitter release into the synapse is stimulated by calcium influx through ion channels that are closely associated with the transmitter release sites(1,2). This link may involve the membrane protein syntaxin, which is known to be associated with the release sites and to bind to the calcium channels(3,4). There is evidence that presynaptic calcium channels are downregulated by second messenger pathways involving G proteins(5,6). Here we use the patch-clamp technique to test whether calcium current is regulated by G proteins in a vertebrate presynaptic nerve terminal(7), and whether this regulation is affected by the Linkage to syntaxin. The calcium current in the nerve terminal showed typical G-protein-mediated changes in amplitude and activation kinetics which were reversed by a preceding depolarization. These effects of the G protein were virtually eliminated if syntaxin was I first cleaved with botulinum toxin CI. Our findings indicate that this sensitivity of the current to modulation by G proteins requires the association of the presynaptic calcium channel with elements of the transmitter release site, which may ensure that channels tethered at release sites(2,8) are preferentially regulated by the G-protein second messenger pathway. RP Stanley, EF (reprint author), NINCDS,SYNAPT MECH SECT,NIH,BLD 36,RM 5A25,BETHESDA,MD 20892, USA. NR 29 TC 148 Z9 151 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 23 PY 1997 VL 385 IS 6614 BP 340 EP 343 DI 10.1038/385340a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD914 UT WOS:A1997WD91400050 PM 9002518 ER PT J AU deMedina, SGD Chopin, D ElMarjou, A Delouvee, A LaRochelle, WJ Hoznek, A Abbou, C Aaronson, SA Thiery, JP Radvanyi, F AF deMedina, SGD Chopin, D ElMarjou, A Delouvee, A LaRochelle, WJ Hoznek, A Abbou, C Aaronson, SA Thiery, JP Radvanyi, F TI Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas SO ONCOGENE LA English DT Article DE bladder; fibroblast growth factor receptor; human; transitional cell carcinoma; tumor progression ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE GENE; LIGAND-BINDING SPECIFICITY; FGF RECEPTOR; K-SAM; TARGETED EXPRESSION; HUMAN KERATIN-18; CANCER; MOUSE; CLONING; FAMILY AB Growth factors and growth factor receptors are involved in tumor progression, The fibroblast growth factor receptor 2 gene encodes distinct isoforms, The isoforms which bind KGF (keratinocyte growth factor or FGF-7) are called KGF-R or FGFR2b. KGF-R is expressed in different epithelia and is involved in the control of epithelial-mesenchymal interactions. Expression of KGF-R mRNA was examined in normal human bladder and transitional cell carcinoma of the bladder (TCC) by semi-quantitative RT-PCR using TFIID and GAPDH as internal standards, In normal bladder, the KGF-R mRNA was detected in the urothelium but not in the underlying stroma, In TCCs, the level of KGF-R mRNA was generally either normal or low, Eighteen out of 54 TCCs had a KGF-R mRNA level below 30% of that found in normal urothelium, This decrease in KGF-R mRNA was not accompanied by an increase in BEK (FGFR2c) mRNA, the other major splice variant of the fibroblast growth factor receptor 2 gene, Expression of the KGF-R was also monitored by immunohistochemistry using a functional KGF-immunoglobulin chimera, The receptor was uniformly expressed throughout the normal urothelium except for the umbrella cells, Immunoreactivity for KGF-R was found to be negative in tumors with low levels of KGF-R mRNA, while the peritumoral normal urothelium was positive, Among patients with muscle invasive tumors, those exhibiting a low level of HGF-R mRNA had a significantly higher proportion of cancer deaths, Our results suggest that decreased expression of KGF-R can be considered as a marker of tumor progression in muscle invasive TCCs. C1 INST CURIE, CNRS, UMR 144, F-75248 PARIS 05, FRANCE. CHU HENRI MONDOR, GRP ETUD TUMEURS UROL, CRCHM, F-94010 CRETEIL, FRANCE. CHU HENRI MONDOR, UROL SERV, F-94010 CRETEIL, FRANCE. NCI, NIH, BETHESDA, MD 20892 USA. MT SINAI SCH MED, RUTTENBERG CANC CTR, NEW YORK, NY USA. NR 55 TC 65 Z9 65 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JAN 23 PY 1997 VL 14 IS 3 BP 323 EP 330 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WD516 UT WOS:A1997WD51600008 ER PT J AU Kashanchi, F Araujo, J Doniger, J Muralidhar, S Hoch, R Khleif, S Mendelson, E Thompson, J Azumi, N Brady, JN Luppi, M Torelli, G Rosenthal, LJ AF Kashanchi, F Araujo, J Doniger, J Muralidhar, S Hoch, R Khleif, S Mendelson, E Thompson, J Azumi, N Brady, JN Luppi, M Torelli, G Rosenthal, LJ TI Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant transforming activity and its protein binds to p53 SO ONCOGENE LA English DT Article DE p53 binding; p53-activated transcription; HHV-6 transformation gene ID POLYMERASE CHAIN-REACTION; VIRUS HUMAN HERPESVIRUS-6; EXANTHEM-SUBITUM; TRANSCRIPTIONAL ACTIVATION; NEOPLASTIC TRANSFORMATION; HUMAN CYTOMEGALOVIRUS; TRANSGENIC MICE; HUMAN LYMPHOMAS; LYMPHOCYTES-T; CELL-LINES AB The 357 amino acid open reading frame 1 (OFF-1), also designated DR7, within the SalI-L fragment of human herpesvirus 6 (HHV-6) exhibited transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter and increased HIV-1 replication (Kashanchi et al., Virology, 201, 95-106, 1994). Tn the current study, the SalI-L transforming region was localized to the SalI-L-SH subfragment, Several ORFs identified in SalI-L-SH by sequence analysis were cloned into a selectable mammalian expression vector, pBK-CMV, Only pBK/ORF1 transformed NIH3T3 cells. Furthermore, cells expressing ORF-1 protein produced fibrosarcomas when injected into nude mice, whereas control cells, expressing either no ORF-1 protein or C-terminal truncated (after residue 172) ORF-1 protein, were not tumorigenic, Western blot analysis of proteins extracted from the tumors revealed ORF-1 protein. Additional studies indicated that ORF-1 was expressed in HHV-6-infected human T-cells by 18 h. Co-immunoprecipitation experiments showed that ORF-1 protein bound to tumor suppressor protein p53, and the OFF-1 binding domain on p53 was located between residues 28 and 187 of p53, overlapping with the specific DNA binding domain. Functional studies showed that p53-activated transcription was inhibited in ORF-1, but not in truncated OFF-1, expressing cells. Importantly, the truncated ORF-1 mutant also failed to cause transformation. Analysis of several human tumors by PCR revealed OFF-1 DNA sequences in some angioimmunoblastic lymphadenopathies, Hodgkin's and non-Hodgkin's lymphomas and glioblastomas. The detection of OFF-1 sequences in human tumors, while not proof per se, is a prerequisite for establishing its role in tumor development. Taken together, the results demonstrate that OFF-1 is an HHV-6 oncogene that binds to and affects p53. The identification of both transforming and transactivating activities within ORF-1 is a characteristic of other viral oncogenes and is the first reported for HHV-6. C1 GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. UNIV MODENA,CTR EXPT HEMATOL,I-41100 MODENA,ITALY. RI Luppi, Mario/J-3668-2016 OI Luppi, Mario/0000-0002-0373-1154 FU NCI NIH HHS [CA 60577] NR 68 TC 55 Z9 62 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 23 PY 1997 VL 14 IS 3 BP 359 EP 367 DI 10.1038/sj.onc.1200840 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WD516 UT WOS:A1997WD51600012 PM 9018122 ER PT J AU Mulcahy, D Husain, S Zalos, G Rehman, A Andrews, NP Schenke, WH Geller, NL Quyyumi, AA AF Mulcahy, D Husain, S Zalos, G Rehman, A Andrews, NP Schenke, WH Geller, NL Quyyumi, AA TI Ischemia during ambulatory monitoring as a prognostic indicator in patients with stable coronary artery disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SILENT-MYOCARDIAL-ISCHEMIA; LEFT-VENTRICULAR FUNCTION; LONG-TERM PROGNOSIS; ST SEGMENT CHANGES; FOLLOW-UP; ANGINA-PECTORIS; MEDICAL THERAPY; BYPASS-SURGERY; HEART-DISEASE; DAILY LIFE AB Objective.-To assess long-term prognostic significance of transient ischemia in patients with documented coronary artery disease and stable symptoms and to examine the relation between transient ischemia and the site of angiographic disease progression following acute cardiac events. Design.-Cohort study with a mean+/-SD follow-up of 51.5+/-23.8 months. Setting.--Ambulatory patients with stable coronary artery disease, assigned to medical therapy. Patients.-A total 221 patients (173 men; mean age, 60.8 years) were recruited, Of the 221 patients, 101 (45.7%) had single-vessel, 86 (38.9%) had 2-vessel, and 34 (15.4%) had 3-vessel disease. A total of 135 had a positive exercise test for ischemia, and mean+/-SD resting left ventricular ejection fraction (LVEF) was 49.8%+/-11.4%. Using conventional criteria, patients were prospectively stratified as low risk for continued medical therapy (single-vessel disease, 2-vessel disease with negative exercise test, or LVEF greater than or equal to 40%; n=189 [85.5%]) or high risk for continued medical therapy (multivessel disease with ischemia and/or left ventricular dysfunction; n=32 [14.5%]). Interventions.-Ambulalory ST-segment monitoring, treadmill exercise testing, radionuclide ventriculography, and coronary angiography. Main Outcome Measures.-Demographic, clinical, ambulatory monitoring, treadmill exercise, and left ventricular function variables as independent predictors of acute (cardiac death, myocardial infarction, or unstable angina) or all (including revascularization) cardiac events in the overall and the low-risk population. Results.-None of the clinical or noninvasive measures of ischemia were of prognostic significance in the overall or the low-risk group. The only significant independent predictor of outcome in all patients for all events, including revascularization, was the number of diseased vessels (chi(2)=13.5 [df=1]; P<.001). Exclusion of vessel disease resulted in conventional risk stratification as the most significant predictor of outcome from all events in all patients (chi(2)=10.3 [df=1]; P=.001). In the low-risk group, the number of diseased vessels was the only predictor for all events (chi(2)=4.6; P=.03). For acute cardiac events, none of the variables tested were of prognostic significance. Based on the frequency of events in the low-risk patients, a 2-fold increase in the rate of cardiac events in patients with transient ischemia compared with those without transient ischemia during ambulatory monitoring could be excluded with greater than 85% power and alpha of .05. Of 30 patients suffering acute nonfatal cardiac events during follow-up, angiography was performed in 27, revealing significant progression of coronary disease in 24 (88.8%) and the development of new significant lesions al sites remote from previously significant lesions in 20 (74%) cases. These new lesions were equally likely to occur in those with or without transient ischemia at initial assessment. Conclusions.-Acute cardiac events in predominantly low-risk stable angina patients with confirmed coronary disease are unpredictable, and those more likely to suffer such an event cannot be identified by the detection of ambulatory ischemia. Acute nonfatal cardiac events result predominantly from the development of significant new coronary lesions, not initially severe enough to cause ischemia. Patients categorized as high risk for long-term medical therapy have an increased rate of cardiac events (mainly revascularization) when compared with low-risk patients. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,OFF BIOSTAT RES,NIH,BETHESDA,MD 20892. NR 45 TC 30 Z9 30 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 JAN 22 PY 1997 VL 277 IS 4 BP 318 EP 324 DI 10.1001/jama.277.4.318 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WC458 UT WOS:A1997WC45800032 PM 9002495 ER PT J AU Hirschfield, RMA Keller, MB Panico, S Arons, BS Barlow, D Davidoff, F Endicott, J Froom, J Goldstein, M Horman, JM Guthrie, D Marek, RG Maurer, TA Meyer, R Phillips, K Ross, J Schwenk, TL Sharfstein, SS Thase, ME Wyatt, RJ AF Hirschfield, RMA Keller, MB Panico, S Arons, BS Barlow, D Davidoff, F Endicott, J Froom, J Goldstein, M Horman, JM Guthrie, D Marek, RG Maurer, TA Meyer, R Phillips, K Ross, J Schwenk, TL Sharfstein, SS Thase, ME Wyatt, RJ TI The national depressive and manic-depressive association consensus statement on the undertreatment of depression SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PRIMARY-CARE; TREATING DEPRESSION; ECONOMIC BURDEN; DISORDERS; COST; PSYCHOTHERAPY; COMORBIDITY; IMIPRAMINE; PREVALENCE; PREDICTORS AB Objective.-A consensus conference on the reasons for the undertreatment of depression was organized by the National Depressive and Manic Depressive Association (NDMDA) on January 17-18, 1996, The target audience included health policymakers, clinicians, patients and their families, and the public at large, Six key questions were addressed: (1) Is depression undertreated in the community and in the clinic? (2) What is the economic cost to society of depression? (3) What have been the efforts in the past to redress undertreatment and how successful have they been? (4) What are the reasons for the gap between our knowledge of the diagnosis and treatment of depression and actual treatment received in this country? (5) What can we do to narrow this gap? (6) What can we do immediately to narrow this gap? Participants.-Consensus panel members were drawn from psychiatry, psychology, family practice, internal medicine, managed care and public health, consumers, and the general public. The panelists listened to a set of presentations with background papers from experts on diagnosis, epidemiology, treatment, and cost of treatment. Evidence.-Experts summarized relevant data from the world scientific literature on the 6 questions posed for the conference. Consensus Process.-Panel members discussed openly all material presented to them in executive session. Selected panelists prepared first drafts of the consensus statements for each question. All of these drafts were read by all panelists and were edited and reedited until consensus was achieved. Conclusions.-There is overwhelming evidence that individuals with depression are being seriously undertreated. Safe, effective, and economical treatments are available. The cost to individuals and society of this undertreatment is substantial. Long suffering, suicide, occupational impairment, and impairment in interpersonal and family relationships exist. Efforts to redress this gap have included provider educational programs and public educational programs. Reasons for the continuing gap include patient, provider, and health care system factors. Patient-based reasons include failure to recognize the symptoms, underestimating the severity, limited access, reluctance to see a mental health care specialist due to stigma, noncompliance with treatment, and lack of health insurance. Provider factors include poor professional school education about depression, limited training in interpersonal skills, stigma, inadequate time to evaluate and treat depression, failure to consider psychotherapeutic approaches, and prescription of inadequate doses of antidepressant medication for inadequate durations. Mental health care systems create barriers to receiving optimal treatment. Strategies to narrow the gap include enhancing the role of patients and families as participants in care and advocates; developing performance standards for behavioral health care systems, including incentives for positive identification, assessment, and treatment of depression; enhancing educational programs for providers and the public; enhancing collaboration among provider subtypes (eg, primary care providers and mental health professionals); and conducting research on development and testing of new treatments for depression. C1 NATL DEPRESS & MANIC DEPRESS ASSOC,CHICAGO,IL. SUBST ABUSE & MENTAL HLTH SERV ADM,ROCKVILLE,MD. BOSTON UNIV,BOSTON,MA 02215. AMER COLL PHYSICIANS,PHILADELPHIA,PA. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY. SUNY STONY BROOK,STONY BROOK,NY 11794. BROWN UNIV,PROVIDENCE,RI 02912. COLUMBIA UNIV,NEW YORK,NY. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. LOVELACE HLTH SYST INC,ALBUQUERQUE,NM. COMMON HLTH USA,LITTLE FALLS,NY. ASSOC ACAD HLTH CTR,WASHINGTON,DC. ANXIETY DISORDERS ASSOC AMER,ROCKVILLE,MD. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI. SHEPPARD PRATT HLTH SYST,BALTIMORE,MD. WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA. NIMH,BETHESDA,MD 20892. FU NIMH NIH HHS [R01 MH025478] NR 38 TC 628 Z9 635 U1 3 U2 61 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 JAN 22 PY 1997 VL 277 IS 4 BP 333 EP 340 DI 10.1001/jama.277.4.333 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WC458 UT WOS:A1997WC45800034 PM 9002497 ER PT J AU Kasas, S Thomson, NH Smith, BL Hansma, HG Zhu, XS Guthold, M Bustamante, C Kool, ET Kashlev, M Hansma, PK AF Kasas, S Thomson, NH Smith, BL Hansma, HG Zhu, XS Guthold, M Bustamante, C Kool, ET Kashlev, M Hansma, PK TI Escherichia coli RNA polymerase activity observed using atomic force microscopy SO BIOCHEMISTRY LA English DT Article ID AQUEOUS-SOLUTIONS; TRANSCRIPTION; DNA; COMPLEXES; PROTEINS; MOTION AB Fluid tapping-mode atomic force microscopy (AFM) was used to observe Escherichia coli RNA polymerase (RNAP) transcribing two different linear double-stranded (ds) DNA templates. The transcription process was detected by observing the translocation of the DNA template by RNAP on addition of ribonucleoside 5'-triphosphates (NTPs) in sequential AFM images, Stalled ternary complexes of RNAP, dsDNA and nascent RNA were adsorbed onto a mica surface and imaged under continuously flowing buffer. On introduction of all four NTPs, we observed some DNA molecules being pulled through the RNAP, some dissociating from the RNAP and others which did not move relative to the RNAP. The transcription rates were observed to be approximately 0.5-2 bases/s at our NTP concentrations, approximately 5 mu M. The RNA transcripts were not unambiguously imaged in fluid. However, in experiments using a small single-stranded (ss) circular DNA template, known as a rolling circle, transcripts up to 1 or 2 microns long could be observed with tapping mode AFM once the samples were dried and imaged in air, This confirmed our observations of the transcriptional activity of RNAP adsorbed onto mica, This work illustrates that the development of tapping-mode in fluid has made it possible to use AFM to follow biological processes at the molecular level and get new insights about the variability of activity of individual molecules bound to a surface. C1 UNIV CALIF SANTA BARBARA,DEPT PHYS,SANTA BARBARA,CA 93106. UNIV OREGON,INST MOL BIOL,EUGENE,OR 97403. UNIV OREGON,DEPT CHEM,EUGENE,OR 97403. UNIV ROCHESTER,DEPT CHEM,ROCHESTER,NY 14627. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Thomson, Neil./O-4198-2016; Maddux, Bettye/D-1269-2009 OI Thomson, Neil./0000-0001-7332-790X; Maddux, Bettye/0000-0001-5890-5249 FU NIGMS NIH HHS [GM-32543] NR 27 TC 250 Z9 252 U1 2 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 21 PY 1997 VL 36 IS 3 BP 461 EP 468 DI 10.1021/bi9624402 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD698 UT WOS:A1997WD69800001 PM 9012661 ER PT J AU Xu, XM Wang, Y Barry, DC Chanock, SJ Bokoch, GM AF Xu, XM Wang, Y Barry, DC Chanock, SJ Bokoch, GM TI Guanine nucleotide binding properties of Rac2 mutant proteins and analysis of the responsiveness to guanine nucleotide dissociation stimulator SO BIOCHEMISTRY LA English DT Article ID NEUTROPHIL NADPH OXIDASE; GDP-GTP EXCHANGERS; H-RAS P21; RESPIRATORY BURST; SMG P21S; RESIDUES; IDENTIFICATION; ACTIVATION; KINASE; PURIFICATION AB The Pac GTPases are currently being subjected to intensive study due to their involvement in a wide array of cellular phenomena. Many studies of Pac function have relied upon the use of relatively uncharacterized Rac dominant active, dominant negative, and effector domain mutants on the basis of the analogy to Pas structure. We have generated and purified such Rac2 mutants and characterized their guanine nucleotide binding properties in vitro. The Rac2 G12V and Q61L activating mutations were shown to hydrolyze bound GTP very slowly and were unresponsive to p190 Rac GTPase-activating protein. Distinct differences in the kinetics of nucleotide binding to individual mutant proteins were observed, accounting for the behavior of these proteins in biological assays. The structural features required for the responsiveness of Rac2 to the guanine nucleotide exchange protein smgGDS were examined. We show that guanine nucleotide exchange by smgGDS is dependent upon intact switch 1 and switch 2 regions in Rac2. Functional interactions between the switch 1 and switch 2 regions and the G12V mutation of Rac2 are described. These data form the basis for rational use of Pac mutants in biological studies. C1 Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA 92037 USA. NCI, NIH, PEDIAT BRANCH, IMMUNOCOMPROMISED HOST SECT, BETHESDA, MD 20892 USA. OI xu, xuemin/0000-0002-7426-272X FU NHLBI NIH HHS [HL48008]; NIGMS NIH HHS [GM39434] NR 46 TC 20 Z9 20 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 JAN 21 PY 1997 VL 36 IS 3 BP 626 EP 632 DI 10.1021/bi962059h PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD698 UT WOS:A1997WD69800017 PM 9012677 ER PT J AU Banwell, MG Flynn, BL Hamel, E Hockless, DCR AF Banwell, MG Flynn, BL Hamel, E Hockless, DCR TI Convergent syntheses of the pyrrolic marine natural products lamellarin-O, lamellarin-Q, lukianol-A and some more highly oxygenated congeners SO CHEMICAL COMMUNICATIONS LA English DT Article ID CROSS-COUPLING REACTIONS; AROMATIC METABOLITES; DENDRILLA-CACTOS; ALKALOIDS; COMBRETASTATIN; POLYCITRIN; REAGENTS; SPONGE AB The marine alkaloids lamellarin-Q 1, lamellarin-O 2 and lukianol-A 3 as well as their more highly oxygenated congeners 22 and 23 are synthesised using Stille, Suzuki and Negishi cross-coupling reactions as the key step. C1 NCI,DBS,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. RP Banwell, MG (reprint author), AUSTRALIAN NATL UNIV,INST ADV STUDIES,RES SCH CHEM,CANBERRA,ACT 0200,AUSTRALIA. RI Banwell, Martin/H-8354-2014 NR 25 TC 74 Z9 75 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PD JAN 21 PY 1997 IS 2 BP 207 EP 208 DI 10.1039/a606793j PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WG497 UT WOS:A1997WG49700032 ER PT J AU Chilian, WM Bassingthwaighte, JB Cannon, RO Curry, FRE Davis, MJ Dellsperger, KC Duling, BR Fuster, V Gerritsen, ME Hoffman, JIE Kajiya, F Ku, DD Lamping, KG Laughlin, MH Ritman, EL Taylor, AE Small, A AF Chilian, WM Bassingthwaighte, JB Cannon, RO Curry, FRE Davis, MJ Dellsperger, KC Duling, BR Fuster, V Gerritsen, ME Hoffman, JIE Kajiya, F Ku, DD Lamping, KG Laughlin, MH Ritman, EL Taylor, AE Small, A TI Coronary microcirculation in health and disease - Summary of an NHLBI Workshop SO CIRCULATION LA English DT Article DE microcirculation; endothelium-derived factors; syndrome X; ischemia; myocardium ID MYOCARDIAL BLOOD-FLOW; VENULAR MICROVESSEL PERMEABILITY; SPONTANEOUSLY HYPERTENSIVE RATS; HYPERTROPHIC CARDIOMYOPATHY; SUBENDOCARDIAL ARTERIOLES; MICROVASCULAR RESISTANCE; MONOCLONAL-ANTIBODY; VASCULAR-RESPONSES; CALCIUM INFLUX; ARTERY DISEASE AB This article summarizes a 2-day workshop on the coronary microcirculation held in Bethesda, Md, in September 1994 and sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health. The workshop explored a variety of topics pertaining to coronary microvascular physiology and pathophysiology. The latest methodologies that are brine used to investigate the coronary microvasculature, including endoscopic microscopy of the intramural coronary microvasculature and micro-x-ray computerized tomography, were discussed. The most recent advances in the regulation of the coronary microcirculation-for example, myogenic and flow-dependent responses. K-ATP channels. and regional heterogeneity-were reported. The workshop touched on the relation of the microcirculation to clinically important conditions and offered recommendations for future research in this important area. Comparisons are made to recent advances in the peripheral circulation and current. gaps in our knowledge concerning the coronary microcirculation. In recent years, research on the coronary microcirculation has made substantial advances, in part as a result of investigations in the peripheral microcirculation but also because of the application of unique methodologies. This research is providing new ways to investigate abnormalities of myocardial perfusion, an area of inquiry that until recently has been limited to examination of coronary pressure-flow relationships. C1 NHLBI,DIV HEART & VASC DIS,VASC RES PROGRAM,BETHESDA,MD 20892. UNIV WASHINGTON,CTR BIOENGN,SEATTLE,WA 98195. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. UNIV CALIF DAVIS,SCH MED,DAVIS,CA 95616. TEXAS A&M UNIV,DEPT MED PHYSIOL,COLLEGE STN,TX. UNIV IOWA,DEPT INTERNAL MED,IOWA CITY,IA 52242. UNIV VIRGINIA,SCH MED,DEPT PHYSIOL,CHARLOTTESVILLE,VA 22908. MT SINAI MED CTR,INST CARDIOVASC,NEW YORK,NY 10029. MILES INST,W HAVEN,CT. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. KAWASAKI MED UNIV,DEPT MED ENGN & SYST CARDIOL,OKAYAMA,JAPAN. UNIV ALABAMA,DEPT PHARMACOL,BIRMINGHAM,AL 35294. UNIV MISSOURI,COLUMBIA,MO. MAYO CLIN & MAYO GRAD SCH MED,BIODYNAM RES UNIT,ROCHESTER,MN. UNIV S ALABAMA,SCH MED,DEPT PHYSIOL,MOBILE,AL 36688. NHLBI,VASC RES PROGRAM,NIH,BETHESDA,MD 20892. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 FU NHLBI NIH HHS [T32 HL007403, T32 HL007403-21] NR 80 TC 111 Z9 112 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 21 PY 1997 VL 95 IS 2 BP 522 EP 528 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WC725 UT WOS:A1997WC72500039 PM 9008472 ER PT J AU Kim, IY Guimaraes, MJ Zlotnik, A Bazan, JF Stadtman, TC AF Kim, IY Guimaraes, MJ Zlotnik, A Bazan, JF Stadtman, TC TI Fetal mouse selenophosphate synthetase 2 (SPS2): Characterization of the cysteine mutant form overproduced in a baculovirus-insect cell system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE eukaryotic selenophosphate synthetase ID SELD GENE-PRODUCT; FUNCTIONAL-CHARACTERIZATION; SELENIUM DONOR; ENZYME; UGA AB A novel gene detected in mouse embryonic sites of hematopoiesis was cloned and shown to be a eukaryotic analog of the Escherichia coli selenophosphate synthetase gene, Unlike the E. coli enzyme, which is not a selenoprotein, the presence of selenocysteine in the mouse enzyme is indicated by a TGA codon in the open reading frame of the gene in a position corresponding to the essential cysteine of the E. coli enzyme, An ionized selenol group in place of a cysteine sulfhydryl group could render this mammalian selenocysteine containing enzyme a more active catalyst, The native cDNA clone and also a mutant form containing a TGC (cysteine) codon in place of TGA were expressed in a baculovirus-insect cell system, Based on recovery of purified proteins, expression of the mutant enzyme was about 40 times higher than wild-type enzyme, The cysteine mutant enzyme exhibited selenophosphate synthetase activity in the assay that measures selenide-dependent AMP formation from ATP, Although expression of wild-type enzyme has not been optimized, the mutant form of the fetal mouse enzyme can be produced in amounts sufficient for isolation in homogeneous form and precise physicochemical and mechanistic studies allowing direct comparison with the analogous cysteine-containing prokaryotic enzyme. C1 NHLBI,BIOCHEM LAB,NATL INST HLTH,BETHESDA,MD 20892. DNAX RES INST MOL & CELLULAR BIOL INC,PALO ALTO,CA 94304. RI Bazan, J. Fernando/B-4562-2010; Zlotnik, Albert/C-3791-2011 NR 18 TC 50 Z9 52 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 JAN 21 PY 1997 VL 94 IS 2 BP 418 EP 421 DI 10.1073/pnas.94.2.418 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD885 UT WOS:A1997WD88500009 PM 9012797 ER PT J AU Davis, MD Parniak, MA Kaufman, S Kempner, E AF Davis, MD Parniak, MA Kaufman, S Kempner, E TI The role of phenylalanine in structure-function relationships of phenylalanine hydroxylase revealed by radiation target analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE regulation; subunit interaction; tetramer; dimer ID RAT-LIVER; ACTIVATION; INACTIVATION; LYSOLECITHIN; STIMULATION; MECHANISM; ENZYMES; INVIVO AB The activity of rat liver phenylalanine hydroxylase (PAH; phenylalanine 4-monooxygenase, EC 1.14.16.1) is regulated by interaction with its substrate, phenylalanine, and its coenzyme, BH4 [tetrahydrobiopterin (6R-dihydroxypropyl-L-erythro-5,6,7,8-tetrahydropterin)]. The structural changes accompanying these interactions have been studied by radiation target analysis, PAH purified from rat liver was incubated with 2 mM phenylalanine to achieve complete activation of the enzyme, Frozen samples were irradiated with various doses of high energy electrons; samples were subsequently thawed, and several surviving properties of the enzyme were determined. Each parameter decreased as a single exponential function of radiation dose, Radiation target analysis of enzymatic activity yielded a dimeric target size, Similar radiation effects on subunit monomers and on tetrameric structure were observed. Together with results from unactivated enzyme, these data show that phenylalanine increases the interactions between the subunits in a dimer and weakens the interactions between dimers in a tetramer. These alterations prevent the natural cofactor, a tetrahydrobiopterin, from exerting a negative effect on activity. C1 NIAMSD,PHYS BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST MED RES,MONTREAL,PQ H3T 1E2,CANADA. MCGILL UNIV,DEPT MED,MONTREAL,PQ H3T 1E2,CANADA. NR 33 TC 15 Z9 15 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 JAN 21 PY 1997 VL 94 IS 2 BP 491 EP 495 DI 10.1073/pnas.94.2.491 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD885 UT WOS:A1997WD88500023 PM 9012811 ER PT J AU Chung, JH Bell, AC Felsenfeld, G AF Chung, JH Bell, AC Felsenfeld, G TI Characterization of the chicken beta-globin insulator SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin; domain; locus control region ID GENE-EXPRESSION; DEVELOPMENTAL REGULATION; TRANSCRIPTION FACTOR; ERYTHROID-CELLS; CPG ISLANDS; ENHANCER; LOCUS; DROSOPHILA; SEQUENCES; PROMOTER AB Insulators, first identified in Drosophila, are DNA sequence elements that shield a promoter from nearby regulatory elements. We have previously reported that a DNA sequence at the 5' end of the chicken beta-globin locus can function as an insulator. It is capable of shielding a reporter gene from the activating effects of a nearby mouse beta-globin locus control region element in the human erythroleukemic cell line K562. In this report, we show that most of the insulating activity lies in a 250-bp CpG island (core element), which contains the constitutive DNase I-hypersensitive site (5'HS4), DNA binding assays with the core sequence reveal a complex protein binding pattern, The insulating activity of the core element is multiplied when tandem copies are used. Although CpG islands are often associated with promoters of housekeeping genes, we find little evidence that the core element is a promoter, Furthermore, the insulator differs from a promoter in its ability to block the locus control region effect directionally. C1 NHLBI,MOL HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 21 TC 278 Z9 292 U1 1 U2 12 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 JAN 21 PY 1997 VL 94 IS 2 BP 575 EP 580 DI 10.1073/pnas.94.2.575 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD885 UT WOS:A1997WD88500038 PM 9012826 ER PT J AU Freedman, R Coon, H MylesWorsley, M OrrUrtreger, A Olincy, A Davis, A Polymeropoulos, M Holik, J Hopkins, J Hoff, M Rosenthal, J Waldo, MC Reimherr, F Wender, P Yaw, J Young, DA Breese, CR Adams, C Patterson, D Adler, LE Kruglyak, L Leonard, S Byerley, W AF Freedman, R Coon, H MylesWorsley, M OrrUrtreger, A Olincy, A Davis, A Polymeropoulos, M Holik, J Hopkins, J Hoff, M Rosenthal, J Waldo, MC Reimherr, F Wender, P Yaw, J Young, DA Breese, CR Adams, C Patterson, D Adler, LE Kruglyak, L Leonard, S Byerley, W TI Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE human chromosome 15; nicotinic receptors; genetic linkage ID NICOTINIC ACETYLCHOLINE-RECEPTOR; ALPHA-BUNGAROTOXIN BINDING; AUDITORY EVOKED-RESPONSES; HIPPOCAMPAL INTERNEURONS; CIGARETTE-SMOKING; RAT HIPPOCAMPUS; SUBUNIT GENE; STIMULI; BRAIN; NORMALIZATION AB Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal inhibition of the P50 auditory evoked response to the second of paired stimuli, is associated with attentional disturbances in schizophrenia, Decreased P50 inhibition occurs not only in most schizophrenics, but also in many of their nonschizophrenic relatives, in a distribution consistent with inherited vulnerability for the illness, Neurobiological investigations in both humans and animal models indicated that decreased function of the alpha 7-nicotinic cholinergic receptor could underlie the physiological defect. In the present study, a genome-wide linkage analysis, assuming autosomal dominant transmission, showed that the defect is linked [maximum logarithm of the odds (lod) score = 5.3 with zero recombination] to a dinucleotide polymorphism at chromosome 15q13-14, the site of the alpha 7-nicotinic receptor. Despite many schizophrenics' extremely heavy nicotine use, nicotinic receptors were not previously thought to be involved in schizophrenia. The linkage data thus provide unique new evidence that the alpha 7-nicotinic receptor gene may be responsible for the inheritance of a pathophysiological aspect of the illness. C1 UNIV COLORADO,SCH MED,DEPT PHARMACOL,DENVER,CO 80262. UNIV COLORADO,SCH MED,DEPT BIOCHEM,DENVER,CO 80262. UNIV COLORADO,SCH MED,DEPT PREVENT MED & BIOPHYS,DENVER,CO 80262. VET AFFAIRS MED CTR,DENVER,CO 80262. ELEANOR ROOSEVELT INST CANC RES,DENVER,CO 80262. UNIV UTAH,SCH MED,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20982. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. RP Freedman, R (reprint author), UNIV COLORADO,SCH MED,DEPT PSYCHIAT,DENVER,CO 80262, USA. FU NCRR NIH HHS [M01 RR000064, P41 RR003655]; NIA NIH HHS [T32 AG000029]; NIDA NIH HHS [R01 DA009457]; NIMH NIH HHS [MH10168-F32, MH01089, MH44212] NR 63 TC 855 Z9 872 U1 2 U2 16 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 JAN 21 PY 1997 VL 94 IS 2 BP 587 EP 592 DI 10.1073/pnas.94.2.587 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD885 UT WOS:A1997WD88500040 PM 9012828 ER PT J AU Takayama, H LaRochelle, WJ Sharp, R Otsuka, T Kriebel, P Anver, M Aaronson, SA Merlino, G AF Takayama, H LaRochelle, WJ Sharp, R Otsuka, T Kriebel, P Anver, M Aaronson, SA Merlino, G TI Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor scatter factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autocrine loop; breast cancer; malignant melanoma; Met; transgenic mice ID MET PROTOONCOGENE PRODUCT; EPITHELIAL-CELLS; HGF RECEPTOR; TRANSGENIC MICE; MAMMARY-GLAND; FACTOR-ALPHA; FACTOR/SCATTER FACTOR; MET/HGF RECEPTOR; TYROSINE KINASE; CARCINOMA-CELLS AB Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived, multifunctional paracrine regulator possessing mitogenic, mitogenic, and morphogenetic activities in cultured epithelial cells containing its tyrosine kinase receptor, Met, c-met has been implicated in oncogenesis through correlation of expression with malignant phenotype in specific cell lines and tumors, Paradoxically, however, HGF/SF can also inhibit the growth of some tumor cells. To elucidate the oncogenic role of HGF/SF in vivo, transgenic mice were created such that HGF/SF was inappropriately targeted to a variety of tissues, HGF/SF transb genic mice developed a remarkably broad array of histologically distinct tumors of both mesenchymal and epithelial origin, Many neoplasms arose from tissues exhibiting abnormal development, including the mammary gland, skeletal muscle, and melanocytes, suggesting a functional link between mechanisms regulating morphogenesis and those promoting tumorigenesis, Most neoplasms, especially melanomas, demonstrated overexpression of both the HGF/SF transgene and endogenous c-met, and had enhanced Met kinase activity, strongly suggesting that autocrine signaling broadly promotes tumorigenesis. Thus, subversion of normal mesenchymal-epithelial paracrine regulation through the forced misdirection of HGF/SF expression induces aberrant morphogenesis and subsequent malignant transformation of cells of diverse origin. C1 NCI,MOL GENET SECT,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PATHOL HISTOTECHNOL LAB,SCI APPLICAT INT CORP,FREDERICK,MD 21702. MT SINAI MED CTR,RUTTENBERG CANC CTR,NEW YORK,NY 10029. FU NEI NIH HHS [1-T32-EY07131-03] NR 52 TC 342 Z9 344 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 JAN 21 PY 1997 VL 94 IS 2 BP 701 EP 706 DI 10.1073/pnas.94.2.701 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD885 UT WOS:A1997WD88500060 PM 9012848 ER PT J AU Hellmich, MR Battey, JF Northup, JK AF Hellmich, MR Battey, JF Northup, JK TI Selective reconstitution of gastrin-releasing peptide receptor with G alpha(q) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SWISS 3T3 CELLS; BOMBESIN STIMULATES GROWTH; PHOSPHOLIPASE-C ISOZYMES; PROTEIN-ALPHA-SUBUNITS; LUNG-CARCINOMA CELLS; BETA-GAMMA-SUBUNITS; PERTUSSIS-TOXIN; DNA-SYNTHESIS; GUANINE-NUCLEOTIDES; MOLECULAR-CLONING AB Identification of the molecular mechanisms that determine specificity of coupling interactions between gastrin releasing peptide receptors (GRPrs) and their cognate heterotrimeric GTP-binding proteins is a fundamental step in understanding the signal transduction cascade initiated by receptor-ligand interaction, To explore these mechanisms in greater detail, we have developed an in situ reconstitution assay in chaotrope-extracted membranes from mouse fibroblasts expressing the GRPr, and we have used it to measure GRPr catalyzed binding of GTP gamma S to purified G protein cu subunits. finding studies with I-125-labeled [D.Tyr(6)] bombesin(6-13) methyl ester (I-125-Tyr-ME), a GRPr specific antagonist, show a single binding site with a K-d = 1.4 nM +/- 0.4 (mean +/- SD, n = 3) and capacity of 15-22 pmol of receptor per mg of protein in the extracted membrane preparations, representing a 2- to 3-fold enrichment of binding sites compared with the membranes before extraction, Quantitative ligand displacement analysis using various unlabeled GRPr agonists shows a rank order of potency characteristic of the GRPr: bombesin greater than or equal to GRP >> neuromedin B, Reconstitution of urea extracted membranes with a purified G alpha(q) showed that receptor-catalyzed binding of GTP gamma S was dependent on agonist (GRP) and G beta gamma subunits. The EC(50) for GRP was 3.5 nM, which correlates well with the reported K-d of 3.1 nM for GRP binding to GRPr expressed in mouse fibroblasts [Benya, R. V., et nl. (1994) Mol. Pharmacol. 46, 235-245], The apparent Kd for bovine brain G beta gamma in this assay was 60 nM, and the K, for squid retinal G alpha(q) was 90 nM. The GRPr-catalyzed binding of GTP gamma S is selective for G(Yq, since we did not detect receptor-catalyzed exchange using either G alpha(i/o), or G alpha(t), These data demonstrate that GRPr can functionally couple to G alpha(q) but not to the pertussis toxin-sensitive G alpha(i/o), or retinal specific G alpha(t)-, This in situ receptor reconstitution method will allow molecular characterization of G protein coupling to other hepta-helical receptors. C1 NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NIDOCD,MOL BIOL LAB,ROCKVILLE,MD 20850. NR 44 TC 56 Z9 56 U1 0 U2 2 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 JAN 21 PY 1997 VL 94 IS 2 BP 751 EP 756 DI 10.1073/pnas.94.2.751 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WD885 UT WOS:A1997WD88500069 PM 9012857 ER PT J AU Ciotti, M Obaray, R Martin, MG Owens, IS AF Ciotti, M Obaray, R Martin, MG Owens, IS TI Genetic defects at the UGT1 locus associated with Crigler-Najjar type I disease, including a prenatal diagnosis SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Crigler-Najjar disease types I and II; Gilbert syndrome; bilirubin UDP-glucuronosyltransferase; prenatal diagnosis; hyperbilirubinemia; pH-sensitive activity; jaundice ID BILIRUBIN-UDP-GLUCURONOSYLTRANSFERASE; URIDINE-DIPHOSPHATE GLUCURONOSYLTRANSFERASE; COMPLEX LOCUS; COS-1 CELLS; IDENTIFICATION; PATIENT; MUTATION; EXPRESSION; HYPERBILIRUBINEMIA; TRANSFERASE AB Characterization of the UGT1 gene complex locus encoding both multiple bilirubin and phenol UDP-glucuronosyltransferases (transferases) has been critical in identifying mutations in the bilirubin isoforms, This study utilizes this information to identify the bases of deficient bilirubin UDP-glucuronosyltransferase activity encoded by the UGT1A gene for the major bilirubin isozyme, HUG-Brl, in 3 Crigler-Najjar type I individuals and the genotype of an at-risk unborn sibling of one patient, A homozygous and heterozygous two-base mutation (CCC to CGT) created the HUG-BrlP387R mutant of the major bilirubin transferase in 2 different Crigler-Najjar type I patients, B.G. and G.D., respectively, Both parents of B.G. and his unborn sibling, J.G., were determined to be carriers of the P387R mutation. G.D. also contains the CAA to TAA nonsense mutation (Gln357st), Y,A, has a homozygous CT deletion in codons 40/41, The HUG-BrlP387R mutant protein was totally inactive at the major pH optimum (6.4), but retained 26% normal activity at the minor pH optimum (7.6), which was 5.4% of the combined activities measured at the two pH values. (C) 1997 Wiley-Liss, Inc. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. NR 27 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 20 PY 1997 VL 68 IS 2 BP 173 EP 178 DI 10.1002/(SICI)1096-8628(19970120)68:2<173::AID-AJMG10>3.0.CO;2-R PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WF474 UT WOS:A1997WF47400010 PM 9028453 ER PT J AU Chen, L Perlick, H Morgan, RA AF Chen, L Perlick, H Morgan, RA TI Comparison of retroviral and adeno-associated viral vectors designed to express human clotting factor IX SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MEDIATED GENE-TRANSFER; HEMOPHILIA-B; ADENOASSOCIATED VIRUS; INVIVO EXPRESSION; SKIN FIBROBLASTS; IN-VIVO; THERAPY; LONG; MICE AB Several different designs for retroviral and adeno-associated virus (AAV) vectors were developed to express human clotting factor IX. Seven separate retroviral vectors were constructed, including chimeric long terminal repeat (LTR)-based designs, vectors containing splice donor/acceptor sites with internal ribosome entry sites (IRES), and vectors with an internal cytomegalovirus (CMV)- or hepatitis B virus (HBV)-derived promoter. Five AAV vectors were produced using the same cassette design where a viral promoter was used to transcribe a bicistronic mRNA containing factor IX and an IRES/neo gene. In the human hepatocyte cell line HepG2, the constructs were tested for factor IX production by ELISA, Northern blot, and Western blot, and for biological activity by normalization of the prolonged activated partial thromboplastin time (APTT) of factor IX-deficient plasma. All of the constructs produced biologically active factor IX in the range of 0.23-152 ng/24 hr per 10(6) cells (the HBV-promoted factor IX AAV vector was the least effective, and the CMV-promoted retroviral vector was the most active). Primary fibroblasts of both human and rabbit origin were also evaluated for factor IX production following transduction with viral vectors. Fibroblasts produced substantially more factor IX than the HepG2 cell line, with the best AAV vector synthesizing >250 ng/24 hr per 10(6) cells and the best retroviral vector making >900 ng/24 hr per 10(6) cells. Generally, we observed lower transduction efficiency and poorer expression with the AAV vectors versus retroviral vectors in these cell types. C1 NIH,CLIN GENE THERAPY BRANCH,NATL CTR HUMAN GENOME RES,GENE TRANSFER TECHNOL SECT,BETHESDA,MD 20892. NR 35 TC 15 Z9 15 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN 20 PY 1997 VL 8 IS 2 BP 125 EP 135 DI 10.1089/hum.1997.8.2-125 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD331 UT WOS:A1997WD33100001 PM 9017417 ER PT J AU Nakajima, H Shores, EW Noguchi, M Leonard, WJ AF Nakajima, H Shores, EW Noguchi, M Leonard, WJ TI The common cytokine receptor gamma chain plays an essential role in regulating lymphoid homeostasis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; RESTRICTED ANTIGEN RECEPTOR; T-CELLS; APOPTOSIS; MICE; THYMOCYTES; EXPRESSION; LYMPHOCYTES; ACTIVATION; BCL-2 AB In the immune system, there is a careful regulation not only of lymphoid development and proliferation, but also of the fate of activated and proliferating cells. Although the manner in which these diverse events are coordinated is incompletely understood, cytokines are known to play major roles. Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for lymphocyte proliferation. The receptors for each of these cytokines contain the common cytokine receptor gamma chain (gamma(c)), and it was previously shown that gamma(c)-deficient mice exhibit severely compromised development and responsiveness to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent accumulation of splenic CD4(+) T cells, the majority of which have a phenotype typical of memory/activated cells. When gamma(c)-deficient mice were mated to DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing endogenous TCRs had this phenotype, suggesting that its acquisition was TCR dependent. Not only do the CD4(+) T cells from gamma(c)-deficient mice exhibit an activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but, consistent with the lack of gamma(c)-dependent survival signals, they also exhibit an augmented rate of apoptosis. However, because the CD4(+) T cells accumulate, it is clear that the rate of proliferation exceeds the rate of cell death. Thus, surprisingly, although gamma(c)-independent signals are sufficient to mediate expansion of CD4(+) T cells in these mice, gamma(c)-dependent signals are required to regulate the fate of activated CD4(+) T cells, underscoring the importance of gamma(c)-dependent signals in controlling lymphoid homeostasis. C1 NHLBI,LAB MOL IMMUNOL,BETHESDA,MD 20892. US FDA,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 33 TC 134 Z9 136 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 20 PY 1997 VL 185 IS 2 BP 189 EP 195 DI 10.1084/jem.185.2.189 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WE644 UT WOS:A1997WE64400002 PM 9016868 ER PT J AU Madrenas, J Chau, LA Smith, J Bluestone, JA Germain, RN AF Madrenas, J Chau, LA Smith, J Bluestone, JA Germain, RN TI The efficiency of CD4 recruitment to ligand-engaged TCR controls the agonist/partial agonist properties of peptide-MHC molecule ligands SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL-RECEPTOR; PROTEIN-KINASE P56LCK; ANTIGEN-PRESENTING CELLS; CLASS-II; TRANSPLANTATION TOLERANCE; MONOCLONAL-ANTIBODIES; SIGNAL-TRANSDUCTION; PHYSICAL ASSOCIATION; POSITIVE SELECTION; THYMIC SELECTION AB One hypothesis seeking to explain the signaling and biological properties of T cell receptor for antigen (TCR) partial agonists and antagonists is the coreceptor density/kinetic model, which proposes that the pharmacologic behavior of a TCR ligand is largely determined by the relative rates of (a) dissociation of ligand from an engaged TCR and (b) recruitment of lck-linked coreceptors to this ligand-engaged receptor. Using several approaches to prevent or reduce the association of CD4 with occupied TCR, we demonstrate that consistent with this hypothesis, the biological and biochemical consequence of limiting this interaction is to convert typical agonists into partial agonist stimuli. Thus, adding anti-CD4 antibody to T cells recognizing a wild-type peptide-MHC class II ligand leads to disproportionate inhibition of interleukin-2 (IL-2) relative to IL-3 production, the same pattern seen using a TCR partial agonist/antagonist. In addition, T cells exposed to wild-type ligand in the presence of anti-CD4 antibodies show a pattern of TCR signaling resembling that seen using partial agonists, with predominant accumulation of the p 21 tyrosine-phosphorylated form of TCR-zeta, reduced tyrosine phosphorylation of CD3 epsilon, and no detectable phosphorylation of ZAP-70. Similar results are obtained when the wild-type Ligand is presented by mutant class II MHC molecules unable to bind CD4. Likewise, antibody coligation of CD3 and CD4 results in an agonist-like phosphorylation pattern, whereas bivalent engagement of CD3 alone gives a partial agonist-like pattern. Finally, in accord with data showing that partial agonists often induce T cell anergy, CD4 blockade during antigen exposure renders cloned T cells unable to produce IL-2 upon restimulation. These results demonstrate that the biochemical and functional responses to variant TCR ligands with partial agonist properties can be largely reproduced by inhibiting recruitment of CD4 to a TCR binding a wild-type ligand, consistent with the idea that the relative rates of TCR-ligand disengagement and of association of engaged TCR with CD4 may play a key role in determining the pharmacologic properties of peptide-MHC molecule ligands. Beyond this insight into signaling through the TCR, these results have implications for models of thymocyte selection and the use of anti-coreceptor antibodies in vivo for the establishment of immunological tolerance. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,NIH,BETHESDA,MD 20892. UNIV WESTERN ONTARIO,JOHN P ROBARTS RES INST,TRANSPLANTAT & IMMUNOBIOL GRP,LONDON,ON,CANADA. UNIV WESTERN ONTARIO,DEPT MICROBIOL & IMMUNOL,LONDON,ENGLAND. UNIV CHICAGO,BEN MAY INST CANC RES,COMM IMMUNOL,CHICAGO,IL 60637. FU NHLBI NIH HHS [HL 07605, T32 HL007605]; NIAID NIH HHS [P01 AI29531] NR 76 TC 157 Z9 157 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 20 PY 1997 VL 185 IS 2 BP 219 EP 229 DI 10.1084/jem.185.2.219 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WE644 UT WOS:A1997WE64400005 PM 9016871 ER PT J AU Espey, MG Chernyshev, ON Reinhard, JF Namboodiri, MAA Colton, CA AF Espey, MG Chernyshev, ON Reinhard, JF Namboodiri, MAA Colton, CA TI Activated human microglia produce the excitotoxin quinolinic acid SO NEUROREPORT LA English DT Article DE brain; excitotoxicity; kynurenines; neuropathology ID RAT-BRAIN; NEUROLOGICAL DISEASE; IMMUNE-SYSTEM; METABOLISM; LESIONS; LIPOPOLYSACCHARIDE; KYNURENINES; TRYPTOPHAN; OXYGENASE; INVITRO AB WE aimed to determine the relative role of quinolinic acid synthesis in purified human microglia, monocyte-derived macrophages and astrocytes in the human brain following immune stimulation. Microglia and macrophages significantly increased quinolinic acid synthesis from tryptophan following activation by either lipopolysaccharide or interferon-gamma. Quinolinic acid synthesis by individual microglia was heterogeneous, and its production by activated macrophages was approximately 32-fold greater than its microglial synthesis. Quinolinic acid synthesis by astrocytes was undetectable. Microglia may, therefore, be the primary endogenous cell type responsible for quinolinic acid synthesis in the brain parenchyma. However, under pathological conditions which precipitate blood-brain barrier compromise and/or leukocytic infiltration, intracerebral quinolinic acid may be derived chiefly from cells of the peripheral immune system such as activated macrophages. C1 GEORGETOWN UNIV,DEPT BIOL,WASHINGTON,DC 20057. GEORGETOWN UNIV,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20057. GLAXO WELLCOME INC,DEPT MOL PHARMACOL,RES TRIANGLE PK,NC 27709. RP Espey, MG (reprint author), NIDDK,NEUROSCI LAB,NIH,BLDG 8,BETHESDA,MD 20892, USA. NR 25 TC 127 Z9 129 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 JAN 20 PY 1997 VL 8 IS 2 BP 431 EP 434 DI 10.1097/00001756-199701200-00011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WX340 UT WOS:A1997WX34000012 PM 9080423 ER PT J AU Kashanchi, F Sadaie, MR Brady, JN AF Kashanchi, F Sadaie, MR Brady, JN TI Inhibition of HIV-1 transcription and virus replication using soluble Tat peptide analogs SO VIROLOGY LA English DT Article ID GENE-EXPRESSION; BINDING PROTEIN; RNA-POLYMERASE; IN-VITRO; TRANSACTIVATOR; TYPE-1; ACTIVATORS; SUBUNIT; MUTANT; DOMAIN AB The human immunodeficiency virus type 1 (HIV-1) transactivator Tat protein is essential for efficient viral gene expression and virus replication. The Tat core domain, a stretch of 12 amino acids between the cysteine-rich and the basic domain, is conserved in all HIV isolates and required for interaction with a number of cellular transcriptional regulatory proteins. Here we demonstrate that soluble peptide analogs of the Tat core domain (amino acid 36-50) are able to effectively block LTR transactivation. In transfection experiments, Tat core peptide analogs containing amino acid substitutions at position 41 and 44 inhibited Tat transactivation of an HIV-I LTR-CAT reporter construct up to 80-fold. In contrast, inhibition of other promoters such as HTLV-I and CMV was approximately 2-fold. Tat peptide analog 36-50 (41/44) inhibited HIV virus replication by 85% in latently infected U1 cells induced with Tat. Furthermore, U1 cells treated with the Tat peptide 36-50 (41/44) analog showed markedly delayed virus transmission when cocultivated with parental U937 cells. Interestingly, while both short and long peptide analogs (amino acids 36-50 vs 36-72) inhibited Tat transactivation in transient assays, the short peptides were more effective inhibitors of virus replication in U1 cells. The Tat peptide analog did not decrease expression of cellular genes including beta-actin, GAPDH, and histone H2B. (C) 1997 Academic Press C1 NCI,VIRUS TUMOR BIOL SECT,MOL VIROL LAB,NIH,BETHESDA,MD 20892. US FDA,MOL IMMUNOL SECT,LAB IMMUNOCHEM,DIV TRANSFUS TRANSMITTED DIS,CBER,ROCKVILLE,MD 20852. NR 26 TC 25 Z9 27 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 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 1997 VL 227 IS 2 BP 431 EP 438 DI 10.1006/viro.1996.8346 PG 8 WC Virology SC Virology GA WD572 UT WOS:A1997WD57200017 PM 9018142 ER PT J AU LaMontagne, JR AF LaMontagne, JR TI RSV pneumonia, a community-acquired infection in adults SO LANCET LA English DT Editorial Material ID RESPIRATORY SYNCYTIAL VIRUS; YOUNG-CHILDREN; INFANTS; RISK RP LaMontagne, JR (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,ROCKVILLE,MD 20892, USA. NR 7 TC 11 Z9 11 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 JAN 18 PY 1997 VL 349 IS 9046 BP 149 EP 150 DI 10.1016/S0140-6736(05)60974-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WC861 UT WOS:A1997WC86100005 PM 9111535 ER PT J AU Cohen, D Ashkenazi, S Green, MS Gdalevich, M Robin, G Slepon, R Yavzori, M Orr, N Block, C Ashkenazi, I Shemer, J Taylor, DN Hale, TL Sadoff, JC Pavliakova, D Schneerson, R Robbins, JB AF Cohen, D Ashkenazi, S Green, MS Gdalevich, M Robin, G Slepon, R Yavzori, M Orr, N Block, C Ashkenazi, I Shemer, J Taylor, DN Hale, TL Sadoff, JC Pavliakova, D Schneerson, R Robbins, JB TI Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults SO LANCET LA English DT Article ID LIPOPOLYSACCHARIDE O-ANTIGEN; SERUM ANTIBODIES; ORAL VACCINATION; FLEXNERI; POLYSACCHARIDE; TRANSMISSION; IMMUNIZATION; CANDIDATE; IMMUNITY; ISRAEL AB Background The aim of this double-blind randomised vaccine-controlled trial was to assess the efficacy of a conjugate vaccine composed of Shigella sonnei O-specific polysaccharide bound to Pseudomonas aeruginosa recombinant exoprotein A (S sonnei-rEPA) and of an oral, live-attenuated Escherichia coli/S flexneri 2a (EcSf2a-2) hybrid vaccine among military recruits in Israel at high risk of exposure to Shigella spp. We report here our preliminary findings on the efficacy of S sonnei-rEPA; we have not documented sufficient cases to assess the efficacy of EcSf2a-2. Methods Between April, 1993, and August, 1994, male Israeli military recruits aged 18-22 years were asked to take part in our study. We enrolled 1446 soldiers from seven separate field sites (groups A-G). Soldiers were randomly allocated one injection of S sonnei-rEPA and four doses of oral placebo (n=576), four oral doses of EcSf2a-2 and one injection of saline placebo (n=580), or one injection of meningococcal tetravalent control vaccine and four doses of oral placebo (n=290). Because there were no cases of S flexneri 2a, the EcSf2a-2 and meningococcal vaccines were the control group. We defined S sonnei shigellosis as diarrhoea with a positive faecal culture for S sonnei. Each group of soldiers was followed up for 2.5-7.0 months. The primary endpoint was protective efficacy of S sonnei-rEPA against S sonnei shigellosis. Findings Cases of culture-proven S sonnei shigellosis occurred in four groups of soldiers (groups A-D), which comprised 787 volunteers (312 received S sonnei-rEPA, 316 received EcSf2a-2, and 159 received meningococcal control vaccine). In groups A-C, cases of shigellosis occurred 70-155 days after vaccination, whereas in group D cases occurred after 1-17 days. In groups A-C, the attack rate of shigellosis was 2.2% in recipients of S sonnei-rEPA compared with 8.6% in controls (protective efficacy 74% [95% CI 28-100], p=0.006). S sonnei-rEPA also showed significant protection against shigellosis in group D (43% [4-82], p=0.039). Prevaccination and postvaccination ELISA measurements of antibody to S sonnei lipopolysaccharide among recipients of S sonnei-rEPA showed that the vaccinees who developed S sonnei shigellosis had significantly lower serum IgG and IgA responses to the homologous lipopolysaccharide than those who did not (p=<0.05). Interpretation One injection of S sonnei-rEPA confers type specific protection against S sonnei shigellosis. The high antibody concentration induced by the conjugate vaccine in volunteers who did not develop shigellosis suggests that there is an association between serum antibody titre and protection. C1 TEL AVIV UNIV,SACKLER SCH MED,IL-69978 TEL AVIV,ISRAEL. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,IL-91010 JERUSALEM,ISRAEL. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD. RP Cohen, D (reprint author), CHAIM SHEBA MED CTR,ISRAEL DEF FORCES MED CORPS,MIL POST 02149,IL-52621 TEL HASHOMER,ISRAEL. NR 28 TC 137 Z9 143 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 JAN 18 PY 1997 VL 349 IS 9046 BP 155 EP 159 DI 10.1016/S0140-6736(96)06255-1 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WC861 UT WOS:A1997WC86100008 PM 9111538 ER PT J AU Schairer, C Persson, I Falkeborn, M Naessen, T Troisi, R Brinton, LA AF Schairer, C Persson, I Falkeborn, M Naessen, T Troisi, R Brinton, LA TI Breast cancer risk associated with gynecologic surgery and indications for such surgery SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID WOMEN; ESTROGEN; HORMONES; HYSTERECTOMY AB Risk of breast cancer was assessed in relationship to gynecologic operations using data from a record-linkage study involving 15,844 women in the Uppsala Health Care Region of Sweden, who underwent surgery between 1965 and 1983, Data abstracted from medical records for the breast cancer cases and a random sample of the cohort allowed examination of risk associated with these operations in regard to menopausal status and indications for the operations. Among women who were pre-menopausal at the time of operation, a bilateral oophorectomy before the age of 50 years was associated with a 50% reduction in the risk of breast cancer compared with the background population, a reduction in risk evident within 10 years of the operation. A bilateral oophorectomy after the age of 50 years in premenopausal women or after a natural menopause was not associated with any reduction in risk. There were no reductions in risk associated with a unilateral oophorectomy or hysterectomy among women who were pre-menopausal at the time of operation. In fact, hysterectomy alone was associated with a slight increase in breast cancer risk when the operation was due to myomas, abnormal bleeding, and, possibly, severe forms of endometriosis but not to other reasons, Risk did not vary substantially by indications for oophorectomy, including benign ovarian neoplasms and functional ovarian cysts, though endometriosis was associated with a non-significant increase in breast cancer risk. (C) 1997 Wiley-Liss, Inc. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD. UNIV UPPSALA HOSP,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. UNIV UPPSALA HOSP,DEPT OBSTET & GYNECOL,UPPSALA,SWEDEN. UNIV UPPSALA,DEPT GERIATR,UPPSALA,SWEDEN. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 19 TC 81 Z9 82 U1 0 U2 9 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 JAN 17 PY 1997 VL 70 IS 2 BP 150 EP 154 DI 10.1002/(SICI)1097-0215(19970117)70:2<150::AID-IJC2>3.0.CO;2-W PG 5 WC Oncology SC Oncology GA WF370 UT WOS:A1997WF37000002 PM 9009152 ER PT J AU Tsutsui, T Taguchi, S Tanaka, Y Barrett, JC AF Tsutsui, T Taguchi, S Tanaka, Y Barrett, JC TI 17 beta-estradiol, diethylstilbestrol, tamoxifen, toremifene and ICI 164,384 induce morphological transformation and aneuploidy in cultured Syrian hamster embryo cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER; FEMALE RATS; DNA-ADDUCTS; ACTIVATION; ANTIESTROGENS; PROMOTION; ESTROGENS; MECHANISM; BINDING; SPINDLE AB To examine the ability of estrogens and anti-estrogens to induce cellular transformation and genetic effects, Syrian hamster embryo (SHE) cells were treated with estrogens, 17 beta-estradiol (E(2)) or diethylstilbestrol (DES), or with antiestrogens, tamoxifen (TAM), toremifene (TOR) or ICI 164,384. Treatment with each substance for 1-3 days suppressed cellular growth in a dose dependent manner. Colony-forming efficiency (CFE) increased following treatment of cells with E(2) or DES for 48 hr at 3 or 10 mu M but decreased at 20 or 30 mu M. In contrast, CFE was increased by treatment with TAM, TOR or ICI 164,348 over the concentration range examined (1-30 mu M). Treatment with each chemical at 1-30 mu M for 48 hr caused morphological transformation of SHE cells in a dose-related fashion. The highest frequency was exhibited in SHE cells treated with DES at 20 mu M and was 2 times higher than that induced by treatment with benzo[alpha]pyrene (B[alpha]P) at 4 mu M Transformation frequencies induced by other substances (E(2), TAM, TOR and ICI 164,348) did not exceed that induced by the B[alpha]P treatment. TOR showed a higher transforming ability over all concentrations examined when compared to the other antiestrogens (TAM and ICI 164,348). No significant increases in the frequencies of chromosomal aberrations were observed in SHE cells that were treated with any of the chemicals. However, treatment of SHE cells with each chemical induced a dose-dependent increase of aneuploid cells in the near diploid range. Our results indicate that the ability of the estrogens and anti-estrogens to induce numerical chromosomal abnormality may be involved in their cell transformation activity and potential carcinogenicity. (C) 1997 Wiley-Liss, Inc. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIPPON DENT UNIV TOKYO,DEPT PHARMACOL,TOKYO,JAPAN. NR 30 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1997 VL 70 IS 2 BP 188 EP 193 DI 10.1002/(SICI)1097-0215(19970117)70:2<188::AID-IJC9>3.0.CO;2-T PG 6 WC Oncology SC Oncology GA WF370 UT WOS:A1997WF37000009 PM 9009159 ER PT J AU Hartmann, F Horak, EM Cho, C Lupu, R Bolen, JB StetlerStevenson, MA Pfreundschuh, M Waldmann, TA Horak, ID AF Hartmann, F Horak, EM Cho, C Lupu, R Bolen, JB StetlerStevenson, MA Pfreundschuh, M Waldmann, TA Horak, ID TI Effects of the tyrosine-kinase inhibitor geldanamycin on ligand-induced Her-2/neu activation, receptor expression and proliferation of Her-2-positive malignant cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BENZOQUINOID ANSAMYCIN GROUP; ROUS-SARCOMA VIRUS; HERBIMYCIN-A; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; EGF RECEPTOR; TUMOR-CELLS; SRC; TRANSFORMATION; GROWTH AB Geldanamycin belongs to the family of benzoquinoid ansamycin tyrosine kinase inhibitors. We have examined its effects on Her-2/neu kinase activity, protein expression level, and proliferation of Her-2(+) malignant cells. In SK-BR-3 breast-cancer cells, short-time treatment with geldanamycin completely abrogated gp30-ligand-induced activation of Her-2 without a change of receptor-expression level. Longer treatment of intact cells with geldanamycin induced decreased steady-state Her-2 autophosphorylation activity, which correlated with reduction of Her-2 protein expression and phosphotyrosine content of several proteins. The decrease was time- and dose dependent, starting after 1 hr at 100 nM concentration and reaching completion by 24 hr. The reduction of the Her-2 protein level probably resulted from in creased degradation, since the Her-2 mRNA level remained constant. Geldanamycin effects were not specific for Her-2, since the non-receptor tyrosine-kinase fyn was inhibited equally. In contrast to these results, protein-kinase-C activity was not affected. In 3 other malignant cell lines expressing different amounts of Her-2 (SK-BR-3 > SK-OV-3 > OVCAR3 > MCF7), geldanamycin also effectively reduced Her-2-kinase activity proportionally to the decrease of protein expression. In contrast, in a [H-3]-thymidine-uptake assay, cell growth was meaningfully inhibited by geldanamycin at nanomolar concentrations only in SK-BR-3 (IC50 2nM) and MCF7 (IC50 20nM), while OVCAR3 was only moderately sensitive (IC50 2 mu M) and SK-OV-3 was clearly resistant to geldanamycin. In direct comparison with herbimycin A, another benzoquinoid ansamycin that has been more thoroughly characterized, the biologic effects of geldanamycin were more pronounced. (C) 1997 Wiley-Liss, Inc. C1 NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. DNAX RES INST MOL & CELLULAR BIOL INC,DEPT CELLULAR SIGNALING,PALO ALTO,CA 94304. NCI,DEPT PATHOL,NIH,BETHESDA,MD 20892. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,BERKELEY,CA 94720. RP Hartmann, F (reprint author), UNIV SAARLANDES KLINIKEN,D-66421 HOMBURG,GERMANY. NR 32 TC 47 Z9 47 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1997 VL 70 IS 2 BP 221 EP 229 DI 10.1002/(SICI)1097-0215(19970117)70:2<221::AID-IJC14>3.0.CO;2-L PG 9 WC Oncology SC Oncology GA WF370 UT WOS:A1997WF37000014 PM 9009164 ER PT J AU Handen, JS Rosenberg, HF AF Handen, JS Rosenberg, HF TI Intronic enhancer activity of the eosinophil-derived neurotoxin (RNS2) and eosinophil cationic protein (RNS3) genes is mediated by an NFAT-1 consensus binding sequence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR NFATP; T-CELLS; NF-AT; REGULATORY ELEMENTS; GRANULE DEFICIENCY; MOLECULAR-CLONING; NUCLEAR FACTOR; EXPRESSION; PROMOTER; FAMILY AB The eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are both small, cationic ribonuclease toxins that are stored in and secreted by activated human eosinophilic leukocytes. We have previously shown that optimal expression of the EDN gene is dependent on an interaction between an intronic enhancer element or elements and the 5' promoter region. Here we present evidence demonstrating that the gene encoding ECP is regulated in an analogous fashion and that an intronic enhancer element functioning in both genes is a consensus binding sequence for the transcription factor NFAT-1. Our initial results demonstrate that one or more nuclear proteins isolated from human promyelocytic leukemia (HL-60) cells bind specifically at this consensus site (5'-GGAGAA-3') within the intron of the EDN gene and that disruption of this sequence reduced the characteristic 20-30-fold increase in reporter gene activity observed with the tandem EDN promoter/exon 1/intron construct to background levels. The NFAT-1 consensus site in the ECP gene differs from that found in the EDN gene by a single nucleotide (5'-GGAGAG-3'); the conversion of the 3' G to an A resulted in a further enhancement of the reporter gene activity supported by the ECP promoter/exon 1/intron construct. Interestingly, no ''supershift'' was observed in gel shift assays performed in the presence of anti NFAT-1 antiserum, suggesting that a nuclear protein other than NFAT-1 may be acting at this consensus site. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 37 TC 41 Z9 41 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 JAN 17 PY 1997 VL 272 IS 3 BP 1665 EP 1669 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD058 UT WOS:A1997WD05800041 PM 8999843 ER PT J AU Yang, M Ellenberg, J Bonifacino, JS Weissman, AM AF Yang, M Ellenberg, J Bonifacino, JS Weissman, AM TI The transmembrane domain of a carboxyl-terminal anchored protein determines localization to the endoplasmic reticulum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREFELDIN-A; MEMBRANE-PROTEINS; GOLGI-APPARATUS; INTERLEUKIN-2 RECEPTOR; SECRETORY PATHWAY; PLASMA-MEMBRANE; KIN RECOGNITION; MANNOSIDASE-II; ER RETENTION; ZETA-CHAIN AB UBC6 is a C-terminal membrane-anchored (type IV) protein, native to Saccharomyces cerevisiae, where it is found in the endoplasmic reticulum. When expressed in mammalian cells, this novel ubiquitin-conjugating enzyme also localizes to the endoplasmic reticulum. UBC6 lacks a lumenal domain and contains no known endoplasmic reticulum retention signals. Analysis of chimeric proteins in which the cytosolic domain of UBC is linked to a heterologous transmembrane domain, or in which the UBC6 transmembrane domain is appended to an unrelated soluble protein, led to the determination that the transmembrane domain of UBC6 plays a dominant role in its compartmental localization. The basis for the transmembrane domain-mediated subcellular targeting of UBC6 was evaluated by lengthening the wild type UBC6 hydrophobic segment from 17 to 21 amino acids, which resulted in re-targeting to the Golgi complex. A further increase in length to 26 amino acids allowed this modified protein to traverse the secretory pathway and gain expression at the plasma membrane. These findings are consistent with models in which, in the absence of dominant cytosolic or lumenal targeting determinants, proteins may be sorted within the secretory pathway based on interactions between their trans membrane domains and the surrounding lipid bilayer. C1 NCI,LAB IMMUNE CELL BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 61 TC 103 Z9 103 U1 2 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 JAN 17 PY 1997 VL 272 IS 3 BP 1970 EP 1975 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD058 UT WOS:A1997WD05800086 PM 8999888 ER PT J AU Steinert, PM Marekov, LN AF Steinert, PM Marekov, LN TI Direct evidence that involucrin is a major early isopeptide crosslinked component of the keratinocyte cornified cell envelope SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CROSS-LINKED ENVELOPE; BULLOUS PEMPHIGOID ANTIGEN; PROLINE-RICH PROTEINS; HUMAN LORICRIN; INTERMEDIATE FILAMENTS; TRANSGLUTAMINASE SUBSTRATE; ELASTASE INHIBITOR; GENE-EXPRESSION; TRANSGENIC MICE AB Involucrin was the first protein to be identified as a likely constituent of the insoluble cornified cell envelope lope (CE) of stratified squamous epithelia. However, to date, direct isolation from CEs of involucrin crosslinked by way of the transglutaminase-induced isopeptide bond has not been reported. We have treated human foreskin CEs with methanol/KOH (saponification) to hydrolyze off much of the lipids. By immunogold electron microscopy, this exposed large amounts of involucrin epitopes as well as of desmoplakin, a desmosomal structural protein. About 20% of the total CE protein could be solubilized by proteolytic digestion after saponification, of which involucrin was the most abundant. Subsequent amino acid sequencing revealed many peptides involving involucrin cross-linked either to itself or to a variety of other known CE protein components, including cystatin or, desmoplakin, elafin, keratins, members of the small proline-rich superfamily, loricrin, and unknown proteins related to the desmoplakin family. Specific glutamines or lysines of involucrin were used to cross-link the different proteins, such as glutamines 495 and 496 to desmoplakin, glutamine 288 to keratins, and lysines 468, 485, and 508 and glutamines 465 and 489 for interchain involucrin cross-links. Many identical peptides were obtained from immature CEs isolated from the inner living cell layers of foreskin epidermis. The multiple crosslinked partners of involucrin provide experimental confirmation that involucrin is an important early scaffold protein in the CE. Further, these data suggest that there is significant redundancy in the structural organization of the CE. RP Steinert, PM (reprint author), NIAMSD,SKIN BIOL LAB,NIH,BLDG 6 ROOM 425,BETHESDA,MD 20892, USA. NR 76 TC 167 Z9 169 U1 0 U2 7 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 JAN 17 PY 1997 VL 272 IS 3 BP 2021 EP 2030 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD058 UT WOS:A1997WD05800093 PM 8999895 ER PT J AU Zhao, H Neamati, N Hong, HX Mazumder, A Wang, SM Sunder, S Milne, GWA Pommier, Y Burke, TR AF Zhao, H Neamati, N Hong, HX Mazumder, A Wang, SM Sunder, S Milne, GWA Pommier, Y Burke, TR TI Coumarin-based inhibitors of HIV integrase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article; Proceedings Paper CT 212th National ACS Meeting CY AUG 25-29, 1996 CL ORLANDO, FL SP ACS AB The structures of a large number of HIV-1 integrase inhibitors have in common two aryl units separated by a central linker. Frequently at least one of these aryl moieties must contain 1,2-dihydroxy substituents in order to exhibit high inhibitory potency. The ability of o-dihydroxy-containing species to undergo in situ oxidation to reactive quinones presents a potential limitation to the utility of such compounds. The recent report of tetrameric 4-hydroxycoumarin-derived inhibitor 5 provided a lead example of an inhibitor which does not contain the catechol moiety. Compound 5 represents a large, highly complex yet symmetrical molecule. It was the purpose of the present study to determine the critical components of 5 and if possible to simplify its structure while maintaining potency. In the present study, dissection of tetrameric 5 (IC50 = 1.5 mu M) into its constituent parts showed that the minimum active pharmacophore consisted of a coumarin dimer containing an aryl substituent on the central linker methylene. However, in the simplest case in which the central linker aryl unit consisted of a,phenyl ring (compound 8, IC50 = 43 mu M), a significant reduction in potency resulted by removing two of the original four coumarin units. Replacement of this central phenyl ring by more extended aromatic systems having higher lipophilicity improved potency, as did the addition of 7-hydroxy substituents to the coumarin rings. Combining these latter two modifications resulted in compounds such as 3,3'-(2-naphthalenomethylene)bis[4,7-dihydroxycoumarin] (34, IC50 = 4.2 mu M) which exhibited nearly the full potency of the parent tetramer 5 yet were structurally much simpler. C1 NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Wang, Shaomeng/E-9686-2010; Burke, Terrence/N-2601-2014 NR 16 TC 227 Z9 232 U1 1 U2 10 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 JAN 17 PY 1997 VL 40 IS 2 BP 242 EP 249 DI 10.1021/jm960450v PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WC980 UT WOS:A1997WC98000011 PM 9003523 ER PT J AU Herzberg, U Eliav, E Bennett, GJ Kopin, IJ AF Herzberg, U Eliav, E Bennett, GJ Kopin, IJ TI The analgesic effects of R(+)-WIN 55,212-2 mesylate, a high affinity cannabinoid agonist, in a rat model of neuropathic pain SO NEUROSCIENCE LETTERS LA English DT Article DE R(+)-WIN 55,212-2; cannabinoid agonist; neuropathic pain ID PERIPHERAL MONONEUROPATHY; HYPERALGESIA; RECEPTOR; DEXTRORPHAN; POTENT; NERVE AB The effects of a high affinity cannabinoid receptor agonist were evaluated in rats subjected to chronic constriction injury of the sciatic nerve (CCI) or a sham operation. Intraperitoneal (i.p.) injections of the active, but not the inactive enantiomer, alleviated the pain behavior exhibited by CCI animals in a dose dependent manner. Moreover, at doses ranging from 0.43 to 4.3 mg/kg effects on sensitivity to a heat stimulus were observed neither in the paw contralateral to the sciatic ligation, nor in animals subjected to sham surgery. Animals subjected to CCI and treated with 4.3 mg/kg exhibited hypoalgesia in the paw ipsilateral to the ligated sciatic, i.e. heat hypoalgesia was completely reversed. The hypoalgesia is presumed to be the results of unmasking of a sensory deficit reflecting the known loss of C and A delta with CCI. Although side effects were present in some CCI animals subjected to the high dose (4.3 mg/kg), a moderate dose (2.14 mg/kg) completely alleviated the thermal and mechanical hyperalgesia, and mechanical allodynia without side effects, In addition to identifying a potential drug treatment for painful neuropathy, this study suggests that changes in cannabinoid receptors occurs in nerve injured animals. (C) 1997 Elsevier Science Ireland Ltd. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. RP Herzberg, U (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 205 Z9 208 U1 1 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 17 PY 1997 VL 221 IS 2-3 BP 157 EP 160 DI 10.1016/S0304-3940(96)13308-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WF006 UT WOS:A1997WF00600022 PM 9121688 ER PT J AU Weinstein, JN Myers, TG OConnor, PM Friend, SH Fornace, AJ Kohn, KW Fojo, T Bates, SE Rubinstein, LV Anderson, NL Buolamwini, JK vanOsdol, WW Monks, AP Scudiero, DA Sausville, EA Zaharevitz, DW Bunow, B Viswanadhan, VN Johnson, GS Wittes, RE Paull, KD AF Weinstein, JN Myers, TG OConnor, PM Friend, SH Fornace, AJ Kohn, KW Fojo, T Bates, SE Rubinstein, LV Anderson, NL Buolamwini, JK vanOsdol, WW Monks, AP Scudiero, DA Sausville, EA Zaharevitz, DW Bunow, B Viswanadhan, VN Johnson, GS Wittes, RE Paull, KD TI An information-intensive approach to the molecular pharmacology of cancer SO SCIENCE LA English DT Article ID TUMOR-CELL-LINES; ANTICANCER DRUG SCREEN; DIFFERENTIAL CYTOTOXICITY DATA; TOPOISOMERASE-II; DISCOVERY SCREEN; SUPPRESSOR GENE; INSTITUTE; P53; TUBULIN; AGENTS AB Since 1990, the National Cancer institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines, The 50-percent growth-inhibitory concentration (GI(50)) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI(50) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines, For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents. C1 FRED HUTCHINSON CANC RES CTR, NCI, SEATTLE, WA 98105 USA. NCI, DIV CLIN SCI, MED BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT DIAGNOSIS & CTR, CANC THERAPY EVALUAT PROGRAM,BIOMETR RES BRANCH, NIH, BETHESDA, MD 20892 USA. LARGE SCALE BIOL, ROCKVILLE, MD 20850 USA. NCI, FREDERICK CANC RES & DEV CTR, SAIC, FREDERICK, MD 21701 USA. NCI, DEV THERAPEUT PROGRAM, DCTDC, NIH, BETHESDA, MD 20892 USA. NCI, INFORMAT TECHNOL BRANCH,DEV THERAPEUT PROGRAM, DCTDC,NIH, BETHESDA, MD 20892 USA. NCI, GRANTS & CONTRACTS OPERAT BRANCH, DEV THERAPEUT PROGRAM,DCTDC,NIH, BETHESDA, MD 20892 USA. NCI, OFF DIRECTOR, DCTDC, NIH, BETHESDA, MD 20892 USA. RP NCI, DIV BASIC SCI,MOL PHARMACOL LAB,NIH,BLDG 37, ROOM 5C-25, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 53 TC 847 Z9 861 U1 3 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JAN 17 PY 1997 VL 275 IS 5298 BP 343 EP 349 DI 10.1126/science.275.5298.343 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC873 UT WOS:A1997WC87300035 PM 8994024 ER PT J AU LopezIlasaca, M Crespo, P Pellici, PG Gutkind, JS Wetzker, R AF LopezIlasaca, M Crespo, P Pellici, PG Gutkind, JS Wetzker, R TI Linkage of G protein-coupled receptors to the MAPK signaling pathway through PI 3-kinase gamma SO SCIENCE LA English DT Article ID DEPENDENT ACTIVATION; KINASE; COMPLEXES AB The tyrosine kinase class of receptors induces mitogen-activated protein kinase (MAPK) activation through the sequential interaction of the signaling proteins Grb2, Sos, Ras, Raf, and MEK. Receptors coupled to heterotrimeric guanine triphosphate-binding protein (G protein) stimulate MAPK through G(beta gamma) subunits, but the subsequent intervening molecules are still poorly defined. Overexpression of phosphoinositide 3-kinase gamma (PI3K gamma) in COS-7 cells activated MAPK in a G(beta gamma)-dependent fashion, and expression of a catalytically inactive mutant of PI3K gamma abolished the stimulation of MAPK by G(beta gamma) or in response to stimulation of muscarinic (m2) G protein-coupled receptors. Signaling from PI3K gamma to MAPK appears to require a tyrosine kinase, Shc, Grb2, Sos, Ras, and Raf. These findings indicate that PI3K gamma mediates G(beta gamma)-dependent regulation of the MAPK signaling pathway. C1 NIDR,MOL SIGNALING UNIT,ORAL & PHARYNGEAL CANC BRANCH,NATL INST HLTH,BETHESDA,MD 20892. UNIV JENA,FAC MED,MAX PLANCK UNIT MOL CELL BIOL,D-07747 JENA,GERMANY. UNIV PERUGIA,MONTELUCE POLICLIN,MOL BIOL LAB,IST MED INTERNA & SCI ONCOL,I-20141 MILAN,ITALY. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 22 TC 589 Z9 596 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 17 PY 1997 VL 275 IS 5298 BP 394 EP 397 DI 10.1126/science.275.5298.394 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC873 UT WOS:A1997WC87300049 PM 8994038 ER PT J AU Ramamoorthy, K Wang, F Chen, IC Safe, S Norris, JD McDonnell, DP Gaido, KW Bocchinfuso, WP Korach, KS AF Ramamoorthy, K Wang, F Chen, IC Safe, S Norris, JD McDonnell, DP Gaido, KW Bocchinfuso, WP Korach, KS TI Potency of combined estrogenic pesticides SO SCIENCE LA English DT Article ID RECEPTOR; YEAST C1 DUKE UNIV,SCH MED,DEPT PHARMACOL,DURHAM,NC 27709. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP Ramamoorthy, K (reprint author), TEXAS A&M UNIV,DEPT VET PHYSIOL & PHARMACOL,COLLEGE STN,TX 77843, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 4 TC 71 Z9 73 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 JAN 17 PY 1997 VL 275 IS 5298 BP 405 EP 405 DI 10.1126/science.275.5298.405 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC873 UT WOS:A1997WC87300053 PM 9005556 ER PT J AU Smith, MA Weiss, SRB Berry, RL Zhang, LX Clark, M Massenburg, G Post, RM AF Smith, MA Weiss, SRB Berry, RL Zhang, LX Clark, M Massenburg, G Post, RM TI Amygdala-kindled seizures increase the expression of corticotropin-releasing factor (CRF) and CRF-binding protein in GABAergic interneurons of the dentate hilus SO BRAIN RESEARCH LA English DT Article DE corticotropin-releasing factor; CRF-binding protein; hippocampus; kindling; co-expression; neuropeptide Y; cholecystokinin ID SOMATOSTATIN-LIKE IMMUNOREACTIVITY; GLUTAMIC-ACID DECARBOXYLASE; RAT-BRAIN; MESSENGER-RNA; PARAVENTRICULAR NUCLEUS; SYNAPTIC CONNECTIONS; FACTOR-RECEPTOR; NEURONS; HIPPOCAMPUS; GYRUS AB Kindling, a model of temporal lobe epilepsy, induces a number of neuropeptides including corticotropin-releasing factor (CRF CRF itself can produce limbic seizures which resemble kindling in some aspects. However, tolerance to the convulsant effects of CRF develops rapidly. Hypothetically, this could be explained should seizures also induce the CRF-binding protein (CRF-BP), which has been postulated to restrict the actions of CRF. Therefore, in the present study, we used in situ hybridization to examine the effects of amygdala-kindled seizures on the mRNA levels of CRF and CRF-BP. Kindled seizures markedly elevated CRF and CRF-BP in the dentate gyrus of rats. CRF and CRF-BP were induced almost exclusively in GABAergic interneurons of the dentate hilus. The CRF and CRF-BP interneurons also expressed neuropeptide Y but not cholecystokinin. CRF appeared to have an excitatory role in the dentate gyrus as it decreased the afterhyperpolarization of dentate granule neurons. These results suggest that CRF may contribute to the development of amygdala kindling. However, the compensatory induction of CRF-BP may serve to limit the excitatory effects of CRF in the dentate gyrus. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. NR 41 TC 57 Z9 58 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 16 PY 1997 VL 745 IS 1-2 BP 248 EP 256 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WX974 UT WOS:A1997WX97400029 PM 9037416 ER PT J AU BenTal, N Sitkoff, D Topol, IA Yang, AS Burt, SK Honig, B AF BenTal, N Sitkoff, D Topol, IA Yang, AS Burt, SK Honig, B TI Free energy of amide hydrogen bond formation in vacuum, in water, and in liquid alkane solution SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SOLVATION FREE-ENERGIES; DENSITY FUNCTIONAL CALCULATIONS; BASIS-SETS; GLOBULAR-PROTEINS; THERMODYNAMICS; STABILITY; SOLVENT; MODEL; HYDROPHOBICITY; ASSOCIATION AB The energy of dimerization of two N-methylacetamide (NMA) molecules in vacuum is calculated using density functional theory. Natural orbital analysis suggests that the dimerization energy of -6.6 kcal/mol is predominantly due to the (N-H ... O=C) donor-acceptor interaction. The gas phase to water hydration free energies and the free energies of transfer from the aqueous phase to liquid alkane of hydrogen bonded, (N-H ... O=C), and nonbonded, (N-H,O=C), groups are calculated using a continuum solvent model. On the basis of these calculations, we estimate the free energy of forming an amide hydrogen bond in the context of the NMA dimer in water and in liquid alkane as similar to-1 and similar to-5 kcal/mol, respectively. The relevance of these calculations to processes such as protein folding and membrane insertion of proteins is discussed. C1 COLUMBIA UNIV,DEPT BIOCHEM & MOL BIOPHYS,NEW YORK,NY 10032. COLUMBIA UNIV,CTR BIOMOL SIMULAT,NEW YORK,NY 10032. NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NR 73 TC 108 Z9 110 U1 1 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 16 PY 1997 VL 101 IS 3 BP 450 EP 457 DI 10.1021/jp961825r PG 8 WC Chemistry, Physical SC Chemistry GA WL105 UT WOS:A1997WL10500020 ER PT J AU Antz, C Geyer, M Fakler, B Schott, MK Guy, HR Frank, R Ruppersberg, JP Kalbitzer, HR AF Antz, C Geyer, M Fakler, B Schott, MK Guy, HR Frank, R Ruppersberg, JP Kalbitzer, HR TI NMR structure of inactivation gates from mammalian voltage-dependent potassium channels SO NATURE LA English DT Article ID SHAKER K-CHANNELS; IK(A) CHANNELS; BALL PEPTIDE; SPECTROSCOPY; PROTEINS; SPECTRA; BRAIN AB The electrical signalling properties of neurons originate largely from the gating properties of their ion channels, N-type inactivation of voltage-gated potassium (K-v) channels is the best-understood gating transition in ion channels, and occurs by a 'ball-and-chain' type mechanism. In this mechanism an N-terminal domain (inactivation gate), which is tethered to the cytoplasmic side of the channel protein by a protease-cleavable chain, binds to its receptor at the inner vestibule of the channel, thereby physically blocking the pore(1,2). Even when synthesized as a peptide, ball domains restore inactivation in K-v channels whose inactivation domains have been deleted(2,3), Using high-resolution nuclear magnetic resonance (NMR) spectroscopy, we analysed the three-dimensional structure of the ball peptides from two rapidly inactivating mammalian K-v channels (Raw3 (K(v)3.4) and RCK4 (K(v)1.4)). The inactivation peptide of Raw3 (Raw3-IP) has a compact structure that exposes two phosphorylation sites and allows the formation of an intramolecular disulphide bridge between two spatially close cysteine residues. Raw3-IP exhibits a characteristic surface charge pattern with a positively charged, a hydrophobic, and a negatively charged region, The RCK4 inactivation peptide (RCK4-IP) shows a similar spatial distribution of charged and uncharged regions, but is more flexible and less ordered in its amino-terminal part. C1 MAX PLANCK INST MED RES,DEPT BIOPHYS,D-69120 HEIDELBERG,GERMANY. NIH,MATH BIOL LAB,BETHESDA,MD 20892. ZENTRUM MOL BIOL,D-69120 HEIDELBERG,GERMANY. UNIV TUBINGEN,INST PHYSIOL,D-72076 TUBINGEN,GERMANY. NR 24 TC 91 Z9 95 U1 4 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 16 PY 1997 VL 385 IS 6613 BP 272 EP 275 DI 10.1038/385272a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC711 UT WOS:A1997WC71100053 PM 9000078 ER PT J AU Campeau, L Knatterud, GLMK Domanski, M Hunninghake, DB White, CW Geller, NL Rosenberg, Y Herd, A Cocanougher, MK Dunn, K Farmer, J Foreyt, J Gregory, K Insull, W Jackson, M Kleiman, N Lewis, R Lloyd, C Maresh, K Matthew, C Minor, S Roberts, R Salmon, A Shackelford, P Stewart, R Thompson, M Young, J Guinn, A Harris, G Heibig, J Levy, VV Forrester, J Hickey, A Buchbinder, N Davidson, R Drury, K Eber, L Eigler, N Geft, I Goldberg, S Grodan, P Hendel, J Higgins, S Hodgson, T Hughes, L Karlsberg, R Katz, J Lepor, N Litvak, F Luptak, Y Madera, G Marcus, H Mondkar, A Neidorf, B Neumann, M Nivatpumin, T Rabinowitz, Y Raymond, M Reader, A Rurycz, V Schapira, J Schlanger, J Silverberg, R Smith, A Tabak, S Valovis, R Gray, R Hoogwerf, B Stewart, W Baervedt, G BottSilverman, C Breen, C Buckner, P Cabral, J Cressman, M Fonseca, C Foster, J Foster, R Gutman, F Harris, L Heupler, F Hobbs, R Huang, S Kalenak, J Kassem, M Kosmorsky, G Kramer, J Kurzawa, C Langston, R Lincoff, M Lindberg, J Lowder, C McCafferty, F McKeown, D Meisler, D Mendlovic, D Meyers, S Moore, J Nousek, J Raymond, R Rincon, G Robin, J Rockwood, E Sheldon, W Simpfendorfer, C Walsh, H Waness, A Wright, K Yanak, F Goulet, C Bedard, H Bois, M Bujold, S Cote, G Davignon, J deBelder, M Ducharme, AM Doucet, S Dumas, J Dydra, I Foucher, S Crepeau, J Gosselin, G Groulx, D Joyal, M Juneau, M Lesperance, J Levesque, C Levesque, J Marcil, M Olivier, M Pasternac, A Poitras, AM Poitras, D Quevillon, A Rioux, C Robitaille, D Sisouphone, K Solymoss, C Hunninghake, D Christianson, B DiAngelis, N Gardner, K Helgren, R Iacarella, C Knobloch, W Lau, L Laxson, D Leon, A London, E Manion, R McDonald, K McGinn, A Mianulli, M Robinson, J Turner, G Wang, Y White, C Wilson, R Zimmer, S Gobel, F Anderson, P Baumgard, C Christensen, J Fulco, A Hanson, K Johnson, C Larson, B Madison, J McCormack, P Ostrov, C Pecha, R Pederson, W Pier, T Randall, M Rodman, W Roeller, S Scott, K Sher, N Speilman, J Thompson, R Zupfer, S Goldenberg, I Healy, B Knatterud, G Terrin, M Canner, M Fick, S Forman, S Hanson, D Howard, J Huang, AL Karabelas, S LoPresti, F Mercer, W Ra, K Randall, A Schactman, M Schleigh, B Snider, R Mirenzi, E Fisher, M Fox, NL Czajkowski, S Geller, N Probstfield, J Shumaker, S Wittes, J Yusuf, S Zucker, D Cartland, J Das, G Meyer, S Powers, T Ringdal, D Rosza, Z Shaheen, B Sirek, M Stone, C Snider, J Vanyi, J Alaupovic, P Fesmire, J Walenga, J Bermes, E Hoppensteadt, D Pifarre, R Carleton, R Bailey, K Brody, B Cairns, J Furberg, C Fuster, V Grondin, C Jenkins, D LaRosa, J Meier, P AF Campeau, L Knatterud, GLMK Domanski, M Hunninghake, DB White, CW Geller, NL Rosenberg, Y Herd, A Cocanougher, MK Dunn, K Farmer, J Foreyt, J Gregory, K Insull, W Jackson, M Kleiman, N Lewis, R Lloyd, C Maresh, K Matthew, C Minor, S Roberts, R Salmon, A Shackelford, P Stewart, R Thompson, M Young, J Guinn, A Harris, G Heibig, J Levy, VV Forrester, J Hickey, A Buchbinder, N Davidson, R Drury, K Eber, L Eigler, N Geft, I Goldberg, S Grodan, P Hendel, J Higgins, S Hodgson, T Hughes, L Karlsberg, R Katz, J Lepor, N Litvak, F Luptak, Y Madera, G Marcus, H Mondkar, A Neidorf, B Neumann, M Nivatpumin, T Rabinowitz, Y Raymond, M Reader, A Rurycz, V Schapira, J Schlanger, J Silverberg, R Smith, A Tabak, S Valovis, R Gray, R Hoogwerf, B Stewart, W Baervedt, G BottSilverman, C Breen, C Buckner, P Cabral, J Cressman, M Fonseca, C Foster, J Foster, R Gutman, F Harris, L Heupler, F Hobbs, R Huang, S Kalenak, J Kassem, M Kosmorsky, G Kramer, J Kurzawa, C Langston, R Lincoff, M Lindberg, J Lowder, C McCafferty, F McKeown, D Meisler, D Mendlovic, D Meyers, S Moore, J Nousek, J Raymond, R Rincon, G Robin, J Rockwood, E Sheldon, W Simpfendorfer, C Walsh, H Waness, A Wright, K Yanak, F Goulet, C Bedard, H Bois, M Bujold, S Cote, G Davignon, J deBelder, M Ducharme, AM Doucet, S Dumas, J Dydra, I Foucher, S Crepeau, J Gosselin, G Groulx, D Joyal, M Juneau, M Lesperance, J Levesque, C Levesque, J Marcil, M Olivier, M Pasternac, A Poitras, AM Poitras, D Quevillon, A Rioux, C Robitaille, D Sisouphone, K Solymoss, C Hunninghake, D Christianson, B DiAngelis, N Gardner, K Helgren, R Iacarella, C Knobloch, W Lau, L Laxson, D Leon, A London, E Manion, R McDonald, K McGinn, A Mianulli, M Robinson, J Turner, G Wang, Y White, C Wilson, R Zimmer, S Gobel, F Anderson, P Baumgard, C Christensen, J Fulco, A Hanson, K Johnson, C Larson, B Madison, J McCormack, P Ostrov, C Pecha, R Pederson, W Pier, T Randall, M Rodman, W Roeller, S Scott, K Sher, N Speilman, J Thompson, R Zupfer, S Goldenberg, I Healy, B Knatterud, G Terrin, M Canner, M Fick, S Forman, S Hanson, D Howard, J Huang, AL Karabelas, S LoPresti, F Mercer, W Ra, K Randall, A Schactman, M Schleigh, B Snider, R Mirenzi, E Fisher, M Fox, NL Czajkowski, S Geller, N Probstfield, J Shumaker, S Wittes, J Yusuf, S Zucker, D Cartland, J Das, G Meyer, S Powers, T Ringdal, D Rosza, Z Shaheen, B Sirek, M Stone, C Snider, J Vanyi, J Alaupovic, P Fesmire, J Walenga, J Bermes, E Hoppensteadt, D Pifarre, R Carleton, R Bailey, K Brody, B Cairns, J Furberg, C Fuster, V Grondin, C Jenkins, D LaRosa, J Meier, P TI The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ATHEROSCLEROSIS-REGRESSION; QUANTITATIVE ARTERIOGRAPHY; SERUM-CHOLESTEROL; HEART-DISEASE; RISK-FACTORS; SURGERY; THERAPY; MEN; PROGRESSION; HYPERCHOLESTEROLEMIA AB Background Obstructive changes often occur in aortocoronary saphenous-vein bypass grafts because of atherosclerosis and thrombosis. We studied whether aggressive lowering of low-density lipoprotein (LDL) cholesterol levels or low-dose anticoagulation would delay the progression of atherosclerosis in grafts. Methods We studied 1351 patients who had undergone bypass surgery 1 to 11 years before base line and who had an LDL cholesterol level between 130 and 175 mg per deciliter and at least one patent vein graft as seen on angiography. We used a two-by-two factorial design to assign patients to aggressive or moderate treatment to lower LDL cholesterol levels (with lovastatin and, if needed, cholestyramine) and to treatment with warfarin or placebo. Angiography was repeated an average of 4.3 years after base line. The primary angiographic outcome was the mean percentage per patient of grafts with a decrease of 0.6 mm or more in lumen diameter. Results As measured annually during the study period, the mean LDL cholesterol level of patients who received aggressive treatment ranged from 93 to 97 mg per deciliter; with moderate treatment, the range was from 132 to 136 mg per deciliter (P<0.001). The mean international normalized ratio was 1.4 in the warfarin group and 1.1 in the placebo group (P<0.001). The mean percentage of grafts with progression of atherosclerosis was 27 percent for patients whose LDL cholesterol level was lowered with aggressive treatment and 39 percent for those who received moderate treatment (P<0.001). There was no significant difference in angiographic outcome between the warfarin and placebo groups. The rate of revascularization over four years was 29 percent lower in the group whose LDL cholesterol level was lowered aggressively than in the group receiving moderate treatment (6.5 percent vs. 9.2 percent, P=0.03). Conclusions Aggressive lowering of LDL cholesterol levels to below 100 mg per deciliter reduced the progression of atherosclerosis in grafts. Low-dose warfarin did not reduce the progression of atherosclerosis. (C) 1997, Massachusetts Medical Society. C1 BAYLOR COLL MED,METHODIST HOSP,HOUSTON,TX 77030. BAYLOR COLL MED,VET AFFAIRS MED CTR,HOUSTON,TX 77030. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. MONTREAL HEART INST,MONTREAL,PQ,CANADA. UNIV MINNESOTA,MINNEAPOLIS HEART INST,MINNEAPOLIS,MN 55455. NHLBI,BETHESDA,MD 20892. UNIV MINNESOTA,ANGIOGRAM READING CTR,MINNEAPOLIS,MN 55455. OKLAHOMA MED RES FDN,APOLIPOPROT CORE LAB,OKLAHOMA CITY,OK 73104. LOYOLA UNIV,HEMATOL CORE LAB,NEW ORLEANS,LA 70118. RP Campeau, L (reprint author), MARYLAND MED RES INST,POST CABG COORDINATING CTR,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 35 TC 657 Z9 664 U1 1 U2 12 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 JAN 16 PY 1997 VL 336 IS 3 BP 153 EP 162 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA WC266 UT WOS:A1997WC26600001 ER PT J AU Uren, A Yu, JC Karcaaltincaba, M Pierce, JH Heidaran, MA AF Uren, A Yu, JC Karcaaltincaba, M Pierce, JH Heidaran, MA TI Oncogenic activation of the alpha PDGFR defines a domain that negatively regulates receptor dimerization SO ONCOGENE LA English DT Article DE PDGFR; dimerization; tyrosine kinase; transformation ID GROWTH-FACTOR RECEPTORS; FMS PROTO-ONCOGENE; EXTRACELLULAR DOMAIN; SIGNAL-TRANSDUCTION; LIGAND-BINDING; MONOCLONAL-ANTIBODY; POINT MUTATION; BB BINDING; AA; EXPRESSION AB The alpha platelet derived growth factor receptor (alpha PDGFR) extracellular Immunoglobulin (Ig) like domains 1-3 contain major determinants for ligand interaction. We now report that a deletion of Ig-like loop 3, but not Ig-like loop 1 or 2, of the alpha PDGFR causes ligandindependent transformation in NIH3T3 cells. Biochemical analyses of alpha PDGFR mutants lacking Ig-like loop 3 indicate that cellular transformation is mediated by ligand-independent activation of the alpha PDGFR tyrosine kinase activity as determined by receptor autophosphorylation both in vivo and in vitro. Moreover, crosslinking analysis of alpha PDGFR mutants expressed ectopically in NIH3T3 cells indicate that deletion within extracellular domain 3 leads to ligand-independent receptor dimerization. All of these findings suggest that the Ig-like loop 3 of the alpha PDGFR contains the major determinants which inhibit receptor dimerization in the quiescent cells and that the ligand binding induces receptor activation by neutralizing the inhibitory effect of this domain. C1 NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Karcaaltincaba, Musturay/A-3866-2016 OI Karcaaltincaba, Musturay/0000-0002-3384-0909 NR 25 TC 10 Z9 10 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 16 PY 1997 VL 14 IS 2 BP 157 EP 162 DI 10.1038/sj.onc.1200810 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WC818 UT WOS:A1997WC81800003 PM 9010217 ER PT J AU Bies, J Wolff, L AF Bies, J Wolff, L TI Oncogenic activation of c-Myb by carboxyl-terminal truncation leads to decreased proteolysis by the ubiquitin-26S proteasome pathway SO ONCOGENE LA English DT Article DE c-Myb; proteolytic stability; 26S proteasome; ubiquitin; PEST sequence ID NEGATIVE REGULATORY DOMAIN; LEUKEMIA-CELL-LINE; V-MYB; TRANSCRIPTIONAL ACTIVATION; IN-VIVO; PROTEIN-DEGRADATION; TRANS-ACTIVATION; MESSENGER-RNA; GENE; EXPRESSION AB c-myb activation by insertional mutagenesis in murine myeloid leukemias can lead to amino (NH2)-terminal or carboxyl (COOH)-terminal truncation of its protein product, We observed that in these leukemias, the steady state level of the protein truncated at the COOH terminus was remarkably higher than that of the protein truncated at the NH2-terminus or full length wild-type protein, To examine the rate of proteolysis of different forms of Myb in a uniform cellular background, the proteins were constitutively expressed in the myeloblast cell line M1, using the retrovirus vector LXSN. In pulse chase experiments, using metabolically S-35-labeled proteins, it was determined that COOH-terminal truncation of c-Myb by 248 aa (CT-c-Myb) substantially increases protein stability, resulting in a t(1/2) of about 140 min, as compared to 50 min for full length c-Myb (FL-c-Myb). In an investigation of the mechanism involved in the in vivo degradation of this short lived transcription factor, inhibitors of the lysosomal (chloroquine), proteasomal (ALLM, ALLN, iactacystin) and calpains (EGTA, E-64d, BAPTA/AM) pathways were utilized, Results of this experiment identified the 26S proteasome as a major pathway responsible for rapid breakdown of the protein in hematopoietic cells, Further experiments carried out in vitro demonstrated that c-Myb cap be ubiquitinated, suggesting that this process may be involved in the targeting of wild-type c-Myb to degradation by the 26S proteasome. In addition, it was demonstrated that CT-c-Myb was less efficiently ubiquitinated than wild-type protein indicating that defects in modification account for its escape from rapid turnover, We speculate that the increased half-life of c-Myb resulting from truncation could contribute to its transforming potential. C1 NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. NR 48 TC 51 Z9 51 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 16 PY 1997 VL 14 IS 2 BP 203 EP 212 DI 10.1038/sj.onc.1200828 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WC818 UT WOS:A1997WC81800008 PM 9010222 ER PT J AU Watson, DK Robinson, L Hodge, DR Kola, I Papas, TS Seth, A AF Watson, DK Robinson, L Hodge, DR Kola, I Papas, TS Seth, A TI FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements SO ONCOGENE LA English DT Article DE ETS; FLI1; EWS-FLI1; Egr1; ternary complex factor (TCF); quaternary complex factor (QCF); CArG box; SRE ID EWS/FLI-1 FUSION GENE; DNA-BINDING MOTIF; ETS DOMAIN; C-FOS; TRANSCRIPTIONAL ACTIVATION; C-ETS-1 PROTOONCOGENE; SECONDARY STRUCTURE; ONCOGENIC ACTIVITY; REGULATORY FACTOR; MURINE ETS-1 AB The ETS gene products are a family of transcriptional regulatory proteins that contain a highly conserved and structurally unique DNA binding domain, termed the ETS domain. Several ETS proteins bind to DNA as monomers, however it has been shown that the DNA binding activity is enhanced or modulated in the presence of other factors. By differential display and whole genome PCR techniques, we have recently shown that the Erg1 gene is a target for ETS proteins. The Egr1 promoter contains multiple ETS binding sites, three of which exist as parts of two serum response elements (SREI and SREII). The SRE is a cis-element that regulates the expression of many growth factor responsive genes. ELK1 and SAP1a have been shown to form ternary complexes with SRF on the SRE located in the c-fos promoter. Similarly, we examined whether the ELK1, SAP1a, FLI1, EWS-FLI1, ETS1, ETS2, PEA3 and PU.1 proteins can form ternary complexes with SRF on the Egr1 SREI and II. Our results demonstrate that indeed ELK1, SAP1a, FLI1 and EWS-FLI1 are able to form ternary complexes with SRF on Egr1 SREs. In addition, ELK1 and SAP1a can also form quarternary complexes on the Egr1 SRE1. However, the proteins ETS1, ETS2, PEA3 and PU.1 were unable to form ternary complexes with SRF on either the Egr1 or c-fos SREs. Our data demonstrate that FLI1 and EWS-FLI1 constitute new members of a subgroup of ETS proteins that can function as ternary complex factors and further implicate a novel function for these ETS transcription factors in the regulation of the Egr1 gene. By amino acid sequence comparison we found that, in fact, 50% of the amino acids present in the B-box of SAP1a and ELK1, which are required for interaction with SRF, are identical to those present in both FLI1 (amino acids 231-248) and EWS-FLI1 proteins. This B-box is not present in ETS1, ETS2, PEA3 or PU.1 and these proteins were unable to form ternary complexes with SRF and Egr1-SREs or c-fos SRE. Furthermore, deletion of 194 amino terminal amino acids of FLI1 did not interfere with its ability to interact with SRF, in fact, this truncation increased the stability of the ternary complex. The FLI1 protein has a unique R-domain located next to the DNA binding region. This R-domain may modulate the interaction with SRF, providing a mechanism that would be unique to FLI1 and EWS-FLI1, thus implicating a novel function for these ETS transcription factors in the regulation of the Egr1 gene. C1 UNIV TORONTO,MRC,GRP PERIODONTAL PHYSIOL,TORONTO,ON M5S 1B2,CANADA. WOMENS COLL HOSP,LAB MOL PATHOL,TORONTO,ON M5S 1B2,CANADA. MED UNIV S CAROLINA,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425. NCI,FREDERICK CANC RES & DEV CTR,ABL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ONCOL MOL LAB,FREDERICK,MD 21702. MONASH UNIV,MOL GENET & DEV GRP,MELBOURNE,VIC 3168,AUSTRALIA. RI Kola, Ismail/C-5254-2013 NR 49 TC 89 Z9 90 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 16 PY 1997 VL 14 IS 2 BP 213 EP 221 DI 10.1038/sj.onc.1200839 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WC818 UT WOS:A1997WC81800009 PM 9010223 ER PT J AU Biesova, Z Piccoli, C Wong, WT AF Biesova, Z Piccoli, C Wong, WT TI Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth SO ONCOGENE LA English DT Article DE epidermal growth factor receptor; eps8; SH3 domain; e3B1; signal transduction ID TRANSFORMING ACTIVITY; FACTOR RECEPTOR; SUBSTRATE; KINASE; IDENTIFICATION; PROTOONCOGENE; PRODUCT; CLONING; DOMAIN AB Eps8, a substrate of receptor tyrosine kinases, is an SH3 domain containing protein that plays an important role in mitogenic signaling. To determine the cellular function of eps8, we used the SH3 domain of eps8 to screen a human fibroblast M426 expression library and identified, a full-length cDNA clone of 3.2 kb. We designated this clone e3B1 for eps8 SH3 domain binding protein 1. Northern analysis revealed that expression of e3B1 mRNA was ubiquitious in human tissues. The e3B1 gene encodes a SH3 domain containing protein. We show that anti-e3B1 antibodies detect three cytosolic protein species of 65, 68 and 72 kDa in cell lysate isolated from asynchronously growing NIH3T3 cells. E3B1 binds to the SH3 domain of eps8 and Abi in vitro. We also demonstrated that e3B1 associates with eps8 in vivo. Phosphatase digestion and phosphoamino acid analysis revealed that p65(e3B1) is a phosphoserine containing protein and p72(e3B1) and p68(e3B1) are hyperserine-phosphorylated form of p65(e3B1). We further determined that the p65(e3B1) was the most abundant in serum-starved NIH/EGFR cells. Time course studies initiated by the addition of epidermal growth factor (EGF) revealed that the p72(e3B1) started to accumulate at 4 h, peaked at 8 h and remained high until 24 h. Finally, we demonstrate that NIH/EGFR fibroblasts overexpressing e3B1 grow more slowly relative to matched controls. C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NR 23 TC 80 Z9 87 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 16 PY 1997 VL 14 IS 2 BP 233 EP 241 DI 10.1038/sj.onc.1200822 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WC818 UT WOS:A1997WC81800011 PM 9010225 ER PT J AU Horton, D Levine, BR Norris, P Luck, RL Silverton, JV AF Horton, D Levine, BR Norris, P Luck, RL Silverton, JV TI 5-deoxy-5-C-(5-ethoxycarbonyl-1,2,3-triazol-1-yl)-1,2-O-isopropylidene-a lpha-D-xylofuranose SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS LA English DT Article AB Two unrelated molecules of the title compound, ethyl 1-(5-deoxy-1,2-O-isopropylidene-alpha-D-xylofuranos-5-C-yl) -1,2,3-triazole-5-carboxylate, C13H19N3O6, that are not linked by hydrogen bonding, comprise the asymmetric unit, There are no unusual bond lengths or angles, The two molecules differ in the degree of rotation around the methylene C atom that joins the triazole ring to the sugar part of the molecule, Molecules of the same conformation form infinite chains joined by hydrogen bonding between a HI atom on the hydroxyl group of one molecule and an N atom in the triazole ring of another molecule generated by the 2(I) screw axis, Relevant intermolecular N ... O distances are 3.013(3) and 2,806(3) Angstrom. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Horton, D (reprint author), AMERICAN UNIV,DEPT CHEM,4400 MASSACHUSETTS AVE NW,WASHINGTON,DC 20016, USA. NR 5 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 0108-2701 J9 ACTA CRYSTALLOGR C JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun. PD JAN 15 PY 1997 VL 53 BP 120 EP 122 DI 10.1107/S0108270196012097 PN 1 PG 3 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA WJ220 UT WOS:A1997WJ22000044 PM 9037751 ER PT J AU Corti, MC Guralnik, JM Salive, ME Ferrucci, L Pahor, M Wallace, RB Hennekens, CH AF Corti, MC Guralnik, JM Salive, ME Ferrucci, L Pahor, M Wallace, RB Hennekens, CH TI Serum iron level, coronary artery disease, and all-cause mortality in older men and women SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ISCHEMIC-HEART-DISEASE; MYOCARDIAL-INFARCTION; RISK FACTOR; HEALTH-STATUS; STORED IRON; FERRITIN; PARADIGM AB The association between iron levels and coronary artery disease (CAD) morality is controversial. Whereas most data show no association, some have raised the possibility of a causal role, white others have suggested (I protective effect of iron on CAD. To address these possibilities, we examined the association between serum iron and CAD, cardiovascular disease, and all-cause mortality in a large cohort of 3,936 persons aged greater than or equal to 71 years who completed an interview, had a serum iron determination, and survived at least 1 year after baseline. The median follow-up time was 4.4 years. Serum iron levels were categorized according to sex-specific quartiles. Relative risks (RR) and 95% confidence intervals (CI) were calculated from proportional-hazards regression models adjusted for age, race, education, creatinine, serum albumin, serum lipids, use of iron supplementation, smoking, use of alcohol, blood pressure, body mass index, and presence of chronic conditions. There was a gradual decrease in the RRs of CAD, cardiovascular disease, and all-cause mortality with increasing serum iron levels tall tests for trend, p<0.05). Men in the highest iron quartile were one fifth as likely to die of CAD as men in the lowest iron quartile (RR 0.22; 95% CI 0.11 to 0.48), and women in the highest quartile had half the risk of women in the lowest quartile (RR 0.48; 95% CI 0.27 to 0.87). When compared with the lowest quartile, risk of all-cause mortality wets 38% lower in men in the highest iron quartile (RR 0.62; 95% CI 0.46 to 0.85) and 28% tower in women in the highest quartile (RR 0.72; 95% CI 0.53 to 0.96). Results of similar strength and magnitude were observed for cardiovascular disease mortality and in analyses that excluded the first 3 years of follow-up. In this large cohort of persons aged greater than or equal to 71 years, there was consistent evidence of increasing risk of mortality at lower serum iron levels. In fact, lower serum iron levels were associated with an increased risk of CAD, cardiovascular disease, and all-cause mortality. The results ore compatible with the possibility that in on older population, there is an inverse association between serum iron levels and risk of mortality. (C) 1997 by Excerpta Medica, Inc. C1 OSPED I FRATICINI, DEPT GERIATR, INRCA, FLORENCE, ITALY. CATHOLIC UNIV ROME, DEPT INTERNAL MED & GERIATR, ROME, ITALY. UNIV IOWA, DEPT PREVENT MED & ENVIRONM HLTH, IOWA CITY, IA 52242 USA. BRIGHAM & WOMENS HOSP, DEPT MED, DIV PREVENT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. RP Corti, MC (reprint author), NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, NIH, 7201 WISCONSIN AVE, ROOM 3C-309, BETHESDA, MD 20892 USA. FU NIA NIH HHS [N01-AG-02105, N01-AG-02106, N01-AG-02107] NR 30 TC 47 Z9 48 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 1997 VL 79 IS 2 BP 120 EP 127 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WC651 UT WOS:A1997WC65100002 PM 9193009 ER PT J AU Huang, ZH Wu, J Roth, KDW Yang, Y Gage, DA Watson, JT AF Huang, ZH Wu, J Roth, KDW Yang, Y Gage, DA Watson, JT TI A picomole-scale method for charge derivatization of peptides for sequence analysis by mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID COLLISION-INDUCED DISSOCIATION; FRAGMENTATION; IONS; DECOMPOSITION; SPECTRA; ESTERS AB A highly activated ester containing a fixed positive charge, S-pentafluorophenyl [tris(2,4,6-trimethoxyphenyl)phosphonium]acetate bromide (TMPP-AcSC6F5 bromide), has been synthesized as a reagent for N-terminal modification of peptides. Stable in aqueous acetonitrile solution during extended storage, TMPP-AcSC6F5 bromide reacts with unprotected peptides through p-(dimethylamino)pyridine (DMAP)-promoted amidation in aqueous acetonitrile (15 min, ambient temperature) to form N-TMPP-Ac derivatives of peptides, These peptide derivatives are readily amenable to analysis by fast atom bombardment (FAB) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Greater than 90% conversion has been observed in transforming low-nanomole quantities of analyte using molar ratios of 1:5:10 (peptide/reagent/DMAP). For reactions at the picomole level a slightly modified stoichiometry, with molar ratios of 1:10:500, is employed, Owing to the high reaction efficiency and the tolerance to moderate excess reagent and base during analysis by FAB- and MALDI-MS, the reaction mixture containing the modified peptides can be analyzed directly in most cases, without sample cleanup, Examples of the preparation and analysis of a variety of N-TMPP-acetyl-peptides (TMPP-Ac-peptides) ranging from hexamers to 15-mers are given. Collisionally activated dissociation tandem mass spectrometry of TMPP-Ac-derivatives showed dominant a-type ions, accompanied by d- and c-type ions in some cases, allowing sequence determination to be made in a straightforward manner. C1 MICHIGAN STATE UNIV,DEPT BIOCHEM,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT CHEM,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. FU NCRR NIH HHS [RR00480] NR 39 TC 105 Z9 106 U1 3 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 15 PY 1997 VL 69 IS 2 BP 137 EP 144 DI 10.1021/ac9608578 PG 8 WC Chemistry, Analytical SC Chemistry GA WC045 UT WOS:A1997WC04500004 PM 8997893 ER PT J AU Young, NS AF Young, NS TI Autoimmunity and its treatment in aplastic anemia SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; SAA WORKING PARTY; ANTITHYMOCYTE GLOBULIN; ANTILYMPHOCYTE GLOBULIN; CYCLOSPORINE; IMMUNOSUPPRESSION; THERAPY; ADULTS; GRAFT RP Young, NS (reprint author), NHLBI,BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 26 Z9 33 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 JAN 15 PY 1997 VL 126 IS 2 BP 166 EP 168 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA WD298 UT WOS:A1997WD29800014 PM 9005753 ER PT J AU Gergel, D Misik, V Riesz, P Cederbaum, AI AF Gergel, D Misik, V Riesz, P Cederbaum, AI TI Inhibition of rat and human cytochrome P4502E1 catalytic activity and reactive oxygen radical formation by nitric oxide SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID DEPENDENT LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; STABLE EXPRESSION; NITROSYL COMPLEX; LIVER-MICROSOMES; PARA-NITROPHENOL; MAMMALIAN-CELLS; HEPG2 CELLS; ETHANOL; METABOLISM AB Nitric oxide (NO) reacts with heme-containing enzymes, including certain isoforms of cytochrome P450. Cytochrome P4502E1 (CYP2E1) is induced by ethanol and plays an important role in the toxicity of ethanol and other hepatotoxins. CYP2E1 is also very effective in generating reactive oxygen intermediates such as superoxide radical and H2O2, oxidizing ethanol to the 1-hydroxyethyl radical, and has a high NADPH oxidase activity. The effect of NO on CYP2E1 catalytic activity and generation of reactive oxygen intermediates was evaluated. Incubating liver microsomes isolated from rats treated with pyrazole to induce high levels of CYP2E1, with gaseous NO or NO released from a variety of NO donors such as SNAP, DEA/NO, spermine/NO, and GSNO, resulted in a loss of CYP2E1 catalytic activity with specific substrates such as p-nitrophenol or dimethylnitrosamine. Trapping of NO with hemoglobin resulted in protection of CYP2E1 activity against the inactivation by NO. There was no effect by analogues of the donors which do not release NO nor was there any effect by NO on NADPH-cytochrome P450 reductase activity, Inactivation of CYP2E1 by NO was not prevented by superoxide dismutase or catalase, suggesting that superoxide, H2O2, or peroxynitrite were not responsible for the actions of NO. The inactivated CYP2E1 was not degraded nor did it lose its epitope sites as shown by Western blot analysis. Associated with loss of CYP2E1 catalytic activity was a decrease in the formation of superoxide radical and H2O2, in microsomal lipid peroxidation catalyzed by low, but not high concentration of iron, and in consumption of NADPH. Oxidation of ethanol to the 1-hydroxyethyl radical was also inhibited by NO. ESR experiments indicated the formation of stable heme-NO complexes with CYP2E1. NO appears to compete with O-2 and CO for binding to CYP2E1 as incubation with gaseous NO, or NO donors inhibited formation of the characteristic CO binding spectrum of P450, Microsomes isolated from a stably transfected HepG2 cell line expressing only CYP2E1 were also inactivated by NO, validating interaction of NO with this isoform of P450. These results indicate that NO inhibits CYP2E1 catalytic activity and generation of reactive radical intermediates. NO may prevent toxicity of agents which require bioactivation by P450 isoforms such as CYP2E1 and in generation of reactive intermediates by CYP2E1. (C) 1997 Academic Press. C1 MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. NCI,NIH,BETHESDA,MD 20892. FU NIAAA NIH HHS [AA-06610, AA-09460] NR 60 TC 55 Z9 57 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 1997 VL 337 IS 2 BP 239 EP 250 DI 10.1006/abbi.1996.9765 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WD535 UT WOS:A1997WD53500013 PM 9016819 ER PT J AU Manji, HK Chen, G Potter, W Kosten, TR AF Manji, HK Chen, G Potter, W Kosten, TR TI Guanine nucleotide binding proteins in opioid-dependent patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE guanine nucleotide binding protein; methadone; pertussis toxin; platelets ID SIGNAL-TRANSDUCTION; MORPHINE; PATHWAYS; SUBUNITS AB Guanine nucleotide binding (G) protein levels and functioning in the platelets of 19 methadone-maintained patients were compared to age and sex matched, normal controls, We found that in the methadone patients, Gels-levels were significantly higher, while the levels of G alpha i 1/2 and pertussis toxin catalyzed [P-32]ADP ribosylation were significantly lower compared to control subjects in platelet membranes. We have further found that when all three of these biochemical indicators were combined in a discriminant function analysis, 79% of the methadone patients were correctly classified and 83% of the controls were correctly classified. (C) 1997 Society of Biological Psychiatry C1 YALE UNIV,SCH MED,DIV SUBST ABUSE,SUBST ABUSE CTR,DEPT PSYCHIAT,NEW HAVEN,CT 06519. WAYNE STATE UNIV,DEPT PSYCHIAT & BEHAV NEUROSCI,SCHIZOPHRENIA & MOOD DISORDERS CLIN RES DIV,DETROIT,MI. NIMH,BETHESDA,MD 20892. RI Chen, Guang/A-2570-2017 FU NIDA NIH HHS [P50-DA04060, K02-DA0112] NR 21 TC 9 Z9 10 U1 0 U2 0 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 JAN 15 PY 1997 VL 41 IS 2 BP 130 EP 134 DI 10.1016/S0006-3223(96)00216-8 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WB846 UT WOS:A1997WB84600002 PM 9018382 ER PT J AU Yang, YL Liu, ZH Ware, CF Ashwell, JD AF Yang, YL Liu, ZH Ware, CF Ashwell, JD TI A cysteine protease inhibitor prevents activation-induced T-cell apoptosis and death of peripheral blood cells from human immunodeficiency virus-infected individuals by inhibiting upregulation of Fas ligand SO BLOOD LA English DT Article ID LYMPHOPROLIFERATIVE SYNDROME; MEDIATED CYTOTOXICITY; DNA FRAGMENTATION; HIV-1 INFECTION; LYMPH-NODES; TAT PROTEIN; C-ELEGANS; LYMPHOCYTES; INVOLVEMENT; EXPRESSION AB Activation of T-cell hybridomas, preactivated normal T cells, and peripheral blood lymphocytes (PBL) from human immunodeficiency virus (HIV)-infected individuals results in apoptosis. In the first two cases, apoptosis is caused by the upregulation of Fas ligand (FasL) and its subsequent interaction with Fas; the mechanism for the spontaneous and activation-induced death of lymph node cells and PBL from HIV+ blood is not known. A number of protease inhibitors have been shown to prevent T-cell apoptosis under all of these circumstances, but the mechanism of action has not been determined. Here we show that the cysteine protease inhibitor E64d prevents activation-induced T hybridoma cell death by inhibiting the upregulation of FasL. Quantitative polymerase chain reaction (PCR) demonstrated that mRNA for FasL is expressed at low levels in fresh PBL from HIV-infected blood, but increases in cultured PBL from both uninfected and HIV-infected donors. The ex vivo apoptosis of PBL from HIV+ donors was prevented by adding the soluble extracellular domain of Fas, demonstrating a requisite role for Fas/FasL interactions in this form of cell death. Furthermore, while having no effect on the death of PBL from HIV-infected blood stimulated directly via Fas, E64d inhibited FasL upregulation. Thus, aberrant apoptosis of cultured PBL from HIV-infected individuals is mediated by FasL and Fas, and E64d blocks this apoptosis by inhibiting the upregulation of FasL. These results are consistent with the hypothesis that the abnormal expression of Fas and the inducible expression of FasL contributes to the immunodeficiency of patients with acquired immune deficiency syndrome and suggest that modulation of FasL expression could be an effective target for therapeutic intervention. This is a US government work. There are no restrictions on its use. C1 NCI,IMMUNE CELL BIOL LAB,BETHESDA,MD. NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,NIH,BETHESDA,MD 20892. UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521. FU NIAID NIH HHS [AI33068] NR 59 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 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1997 VL 89 IS 2 BP 550 EP 557 PG 8 WC Hematology SC Hematology GA WD034 UT WOS:A1997WD03400023 PM 9002958 ER PT J AU Young, HA Klinman, DM Reynolds, DA Grzegorzewski, KJ Nii, A Ward, JM WinklerPickett, RT Ortaldo, JR Kenny, JJ Komschlies, KL AF Young, HA Klinman, DM Reynolds, DA Grzegorzewski, KJ Nii, A Ward, JM WinklerPickett, RT Ortaldo, JR Kenny, JJ Komschlies, KL TI Bone marrow and thymus expression of interferon-gamma results in severe B-cell lineage reduction, T-cell lineage alterations, and hematopoietic progenitor deficiencies SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; IFN-GAMMA; TRANSGENIC MICE; STEM-CELLS; SYNDROME TRISOMY-21; GENE-EXPRESSION; IMMUNE-RESPONSE; MOUSE; PROLIFERATION; LIPOPOLYSACCHARIDE AB Interferon-gamma (IFN-gamma) is an immunoregulatory lymphokine that is primarily produced by T cells and natural killer cells. It has effects on T-cell, B-cell, and macrophage differentiation and maturation. We have developed transgenic mice that express elevated levels of IFN-gamma mRNA and protein by inserting multiple copies of murine IFN-gamma genomic DNA containing an Ig lambda-chain enhancer in the first intron. The founder line carrying eight copies of this transgene has eightfold to 15-fold more IFN-gamma-producing cells in the bone marrow and spleen than do nontransgenic littermates. Transgenic mice show a pronounced reduction in B-lineage cells in the bone marrow, spleen, and lymph nodes. In addition, single positive (CD4(+),CD8(-) and CD4(-),CD8(+)) thymocyte numbers are increased twofold, yet the number of splenic T cells is reduced by 50%. There is also a twofold to threefold decrease in the frequency and total number of myeloid progenitors in the bone marrow. Granulomatous lesions and residual degenerating cartilaginous masses are also present in the bones of these mice. Overall, our data show that the abnormal expression of IFN-gamma in these transgenic mice results in multiple alterations in the immune system. These animals provide an important model to examine the role of IFN-gamma expression on lymphoid and myeloid differentiation and function. This is a US government work. There are no restrictions on its use. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. US FDA,SECT RETROVIRAL RES,DIV VIRAL PROD,BETHESDA,MD 20014. RP Young, HA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,DIV BASIC SCI,BLDG 560,ROOM 31-93,FREDERICK,MD 21702, USA. NR 67 TC 53 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 JAN 15 PY 1997 VL 89 IS 2 BP 583 EP 595 PG 13 WC Hematology SC Hematology GA WD034 UT WOS:A1997WD03400027 PM 9002962 ER PT J AU Wilson, WH TeruyaFeldstein, J Fest, T Harris, C Steinberg, SM Jaffe, ES Raffeld, M AF Wilson, WH TeruyaFeldstein, J Fest, T Harris, C Steinberg, SM Jaffe, ES Raffeld, M TI Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas SO BLOOD LA English DT Article ID EPOCH CHEMOTHERAPY; CELL LYMPHOMAS; IN-VIVO; EXPRESSION; GENE; MUTATIONS; SURVIVAL; PROGRESSION; REGRESSION; EFFICACY AB Although the cause(s) of clinical drug resistance in non-Hodgkin's lymphomas (NHL) is unknown, in vitro studies suggest that abnormalities of the p53 gene, bcl-2 overexpression, and low tumor proliferation rates may increase chemotherapy resistance. We analyzed tumor tissue from 75 patients with relapsed/refractory NHL (Working Formulatio n A through H) for p53 mutation/overexpression (abnormality), bcl-2 expression, and tumor proliferation and correlated them with multiple clinical characteristics, response to therapy, disease-free survival, and overall survival (OS). All tumor biopsy specimens were obtained within 6 weeks of treatment with EPOCH (infusional etoposide, vincristine, and doxorubicin and bolus prednisone and cyclophosphamide) chemotherapy. Overall, 16 (21%) tumors had a p53 abnormality. Of 13 tumors with overexpression, mutations were confirmed by sequence analysis in 11, and, in 44 tumors without overexpression, 3 showed mutations. A multivariate analysis showed that tumors with a p53 abnormality were more likely to be drug resistant than tumors with normal p53 (56% v 17%; P-2 = .008) and to have a shorter median progression-free survival (PFS; 2.1 v 8.2 months; P-2 = .008) and OS (11.7 v 21.5 months; P-2 = .038), respectively. The presence of a p53 abnormality did not correlate with any clinical characteristic, bcl-2 expression, or tumor proliferation. A significant correlation was found between low tumor proliferation and drug resistance in a univariate (P-2 < .006) but not multivariate analysis. Patients with tumor proliferation of less than 80% were significantly more likely to have no response to therapy (31% v 6%) or to fail to achieve a complete response (16% v 44%) and tended to have shorter PFS and OS than did patients with higher proliferation. No significant association was found between bcl-2 expression and drug resistance, PFS or OS, although patients with intermediate-grade histologies and high bcl-2 expression tended to be drug resistant as compared with low level expressors (P-2 < .065). Of interest was the finding of a significant association between high bcl-2 and low tumor proliferation (P-2 = .0045). In studies that have found an association between high bcl-2 expression and short PFS, bcl-2 may have been a surrogate for low tumor proliferation. Further studies are warranted to examine this question. These results suggest that p53 mutation and low tumor proliferation, but not bc12, may be important causes of clinical drug resistance in NHL. (C) 1997 by The American Society of Hematology. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP Wilson, WH (reprint author), NCI,MED BRANCH,BLDG 10,ROOM 12N-226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 177 Z9 183 U1 0 U2 2 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 JAN 15 PY 1997 VL 89 IS 2 BP 601 EP 609 PG 9 WC Hematology SC Hematology GA WD034 UT WOS:A1997WD03400029 PM 9002964 ER PT J AU Kang, XQ Robbins, PF Fitzgerald, EB Wang, RF Rosenberg, SA Kawakami, Y AF Kang, XQ Robbins, PF Fitzgerald, EB Wang, RF Rosenberg, SA Kawakami, Y TI Induction of melanoma reactive T cells by stimulator cells expressing melanoma epitope-major histocompatibility complex class I fusion proteins SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MULTIPLE EPITOPES; PERIPHERAL-BLOOD; ANTIGEN GP100; PEPTIDE; IDENTIFICATION; RECOGNITION; VITRO; MOLECULE; MART-1 AB Several epitopes in the human melanoma antigens recognized by HLA-A2-restricted CTLs have a relatively low MHC-binding affinity and as a result may be expressed at very low densities on the cell surface, indicating that these epitopes may not be efficient immunogens. To express these epitopes at higher densities on the surface of antigen-presenting cells and therefore improve their immunogenicity, a DNA construct in which a cDNA fragment encoding the melanoma epitope MART-1(27-35) or gp100(280-288) was inserted between sequences encoding the leader and the HLA-A*0201 protein, Cells transfected with these epitope-HLA fusion constructs were recognized by HLA-A2-restricted melanoma-reactive CTLs specific for the MART-1 or gp100 epitope, In addition, tumor-reactive CTLs could be induced from PBMCs of patients with metastatic melanoma by in vitro stimulation with HMY-C1R B-cell lines expressing the MART-1 or gp100 epitope-HLA-A*0201 fusion protein, These epitope-HLA fusion constructs may be useful for the development of immunotherapies for patients with melanoma. RP Kang, XQ (reprint author), NCI,NIH,DIV CLIN SCI,SURG BRANCH,BLDG 10,ROOM 2B42,10 CTR DR,MSC 1502,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 18 TC 16 Z9 16 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 JAN 15 PY 1997 VL 57 IS 2 BP 202 EP 205 PG 4 WC Oncology SC Oncology GA WC721 UT WOS:A1997WC72100004 PM 9000554 ER PT J AU AndresBarquin, PJ Hernandez, MC Hayes, TE McKay, RDG Israel, MA AF AndresBarquin, PJ Hernandez, MC Hayes, TE McKay, RDG Israel, MA TI Id genes encoding inhibitors of transcription are expressed during in vitro astrocyte differentiation and in cell lines derived from astrocytic tumors SO CANCER RESEARCH LA English DT Article ID LOOP-HELIX PROTEIN; FIBRILLARY ACIDIC PROTEIN; MOLECULAR-CLONING; PRECURSOR CELLS; DNA-BINDING; PROLIFERATION; ACTIVATION; MYOGENESIS; CNS AB Id proteins belong to a class of nuclear transcription factors known as helix-loop-helix proteins, It has been reported that Id genes function as negative regulators of differentiation, and Id gene expression is downregulated during cell differentiation. We examined the regulation of Id genes during astrocyte differentiation in a murine nervous system precursor cell line, NSEHip2-28, which is able to differentiate along the astroglial lineage, as well as in human astroglial tumor cell lines. Upon induction of NSEHip2-28 differentiation, at a time when glial fibrillary acidic protein expression became detectable, the expression of all four Id family members initially increased dramatically, and subsequently decreased. Furthermore, varying levels of Id gene expression were found in astroglial tumor cell lines displaying variable degrees of lineage-specific differentiation. These results suggest that the expression of Id family members may play an important role in the control of astrocyte differentiation. C1 UNIV CALIF SAN FRANCISCO,DEPT NEUROL SURG,BRAIN TUMOR RES CTR,PREUSS LAB MOL NEUROONCOL,SCH MED,SAN FRANCISCO,CA 94143. NINCDS,NIH,MOL BIOL LAB,BETHESDA,MD 20892. NR 35 TC 37 Z9 37 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 JAN 15 PY 1997 VL 57 IS 2 BP 215 EP 220 PG 6 WC Oncology SC Oncology GA WC721 UT WOS:A1997WC72100007 PM 9000557 ER PT J AU vanderSpek, JC Sutherland, JA Zeng, HY Battey, JF Jensen, RT Murphy, JR AF vanderSpek, JC Sutherland, JA Zeng, HY Battey, JF Jensen, RT Murphy, JR TI Inhibition of protein synthesis in small cell lung cancer cells induced by the diphtheria toxin-related fusion protein DAB(389) GRP SO CANCER RESEARCH LA English DT Article ID GASTRIN-RELEASING PEPTIDE; SOMATOSTATIN ANALOG RC-160; BOMBESIN-LIKE PEPTIDES; ANTAGONIST RC-3095; NUDE-MICE; GROWTH; LINES; RECEPTOR; STIMULATION; XENOGRAFTS AB DAB(389) GRP is composed of the catalytic and transmembrane domains of diphtheria toxin fused to gastrin-releasing peptide (GRP). DAB(389) GRP is selectively targeted to, and inhibits protein synthesis in, cell lines expressing GRP receptors. Protein synthesis in 5'ET4 cells (BALB/3T3 fibroblasts transfected with the gene encoding the GRP receptor) was inhibited by 50% in the presence of 20 phl DAB(389) GRP (IC50, 20 pM). DAB(389) GRP did not inhibit protein synthesis in untransfected BALB/3T3 cells. A second neuropeptide-conjugated toxin, DAB(389) SP, directed to cells expressing substance P receptors, was not cytotoxic to 5'ET4 cells, nor was DAB(389) GRP cytotoxic to substance P receptor-bearing cells. DAB(389) GRP cytotoxic effects were receptor specific and sere inhibited either by excess GRP or anti-GRP antibody. Cytotoxicity was mediated by passage through an acidic vesicle, because addition of 10 mu M chloroquine to the reaction inhibited cytotoxicity. DAB(389) GRP and DAB(389) SP were tested on a number of tumor cell lines. DAB(389) GRP inhibited protein synthesis in AR42J rat pancreatic acinar cells and HuTu 80 human duodenal adenocarcinoma cells with IC(50)s of 65 and 200 pM, respectively. DAB(389) SP had an IC50 of 9.5 pM for the AR42J cells and 12 nM for the HuTu 80 cell line. A number of small cell lung cancer cell (SCLC) lines were tested, and the IC50 for DAB(389) GRP ranged from 1.1 to 85 nM. Sensitivity to DAB(389) GRP appeared to be based on receptor number and receptor type (i.e., GRP or neuromedin B preferring). SCLC cells were also sensitive to DAB(389) SP, with IC(50)s ranging from 2.4 to 11.5 nM. These results suggest that a potential use exists for diphtheria-based fusion toxins as therapeutic agents for treatment of SCLC and other neuropeptide receptor-bearing cancers. C1 EVANS MEM DEPT CLIN RES,BOSTON,MA. DEPT MED,BOSTON,MA. NIDOCD,BETHESDA,MD 20892. NIDDKD,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-60934] NR 24 TC 13 Z9 13 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1997 VL 57 IS 2 BP 290 EP 294 PG 5 WC Oncology SC Oncology GA WC721 UT WOS:A1997WC72100020 PM 9000570 ER PT J AU Koivisto, P Kononen, J Palmberg, C Tammela, T Hyytinen, E Isola, J Trapman, J Cleutjens, K Noordzij, A Visakorpi, T Kallioniemi, OP AF Koivisto, P Kononen, J Palmberg, C Tammela, T Hyytinen, E Isola, J Trapman, J Cleutjens, K Noordzij, A Visakorpi, T Kallioniemi, OP TI Androgen receptor gene amplification: A possible molecular mechanism for androgen deprivation therapy failure in prostate cancer SO CANCER RESEARCH LA English DT Article ID HORMONE-BINDING; CARCINOMA; MUTATION; CELLS; DNA; METHOTREXATE; PROGRESSION; EXPRESSION; DOMAIN AB Progression of prostate cancer during endocrine therapy is a major clinical problem, the molecular mechanisms of which remain poorly understood, Amplification of the androgen receptor (AR) gene was recently described in recurrent prostate carcinomas from patients who had failed androgen deprivation therapy, To evaluate the hypothesis that amplification of the AR gene is a cause for the failure of androgen deprivation therapy in prostate cancer, we studied whether AR amplification leads to gene overexpression, whether the amplified AR gene is structurally intact, and whether tumors with AR amplification have distinct biological and clinical characteristics. Tumor specimens were collected from 54 prostate cancer patients at the time of a local recurrence following therapy failure, In 26 cases, paired primary tumor specimens from the same patients prior to therapy were also available, Fifteen (28%) of the recurrent therapy-resistant tumors, but none of the untreated primary tumors, contained AR gene amplification as determined by fluorescence in situ hybridization. According to single-stranded conformation polymorphism analysis, the AR gene was wild type in all but one of the 13 AR amplified cases studied, In one tumor, a presumed mutation in the hormone-binding domain at codon 674 leading to a Gly --> Ala substitution was found, but functional studies indicated that this mutation did not change the transactivational properties of the receptor, AR amplification was associated with a substantially increased level of mRNA expression of the gene by in situ hybridization. Clinicopathological correlations indicated that AR amplification was most likely to occur in tumors that had initially responded well to endocrine therapy and whose response duration was more than 12 months, Tumors that recurred earlier or those that shelved no initial therapy response did not contain AR amplification, The median survival time after recurrence was two times longer for patients with AR amplification in comparison to those with no amplification (P = 0.03, Willcoxon-Breslow test), In conclusion, failure of conventional androgen deprivation therapy in prostate cancer may be caused by a clonal expansion of tumor cells that are able to continue androgen-dependent growth despite of the low concentrations of serum androgens, Amplification and the increased expression of a wild-type AR gene may play a key role in this process. C1 NIH, NATL CTR HUMAN GENOME RES, CANC GENET LAB, BETHESDA, MD 20892 USA. TAMPERE UNIV, INST MED TECHNOL, CANC GENET LAB, TAMPERE 33521, FINLAND. TAMPERE UNIV HOSP, DIV UROL, TAMPERE 33521, FINLAND. ERASMUS UNIV ROTTERDAM, DEPT PATHOL, NL-3000 DR ROTTERDAM, NETHERLANDS. ERASMUS UNIV ROTTERDAM, DEPT UROL, NL-3000 DR ROTTERDAM, NETHERLANDS. 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 35 TC 474 Z9 494 U1 2 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1997 VL 57 IS 2 BP 314 EP 319 PG 6 WC Oncology SC Oncology GA WC721 UT WOS:A1997WC72100025 PM 9000575 ER PT J AU Puri, PL Avantaggiati, ML Balsano, C Sang, NL Graessmann, A Giordano, A Levrero, M AF Puri, PL Avantaggiati, ML Balsano, C Sang, NL Graessmann, A Giordano, A Levrero, M TI P300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene transcription SO EMBO JOURNAL LA English DT Article DE cell cycle arrest; MyoD; p300; skeletal muscle; E1A ID E1A-ASSOCIATED PROTEIN P300; ADENOVIRUS E1A; MYOGENIC DIFFERENTIATION; DNA-BINDING; TERMINAL DIFFERENTIATION; MYOBLAST DIFFERENTIATION; FUNCTIONAL HOMOLOG; C-JUN; EXPRESSION; FAMILY AB The nuclear phosphoprotein p300 is a new member of a family of 'co-activators' (which also includes the CREB binding protein CBP), that directly modulate transcription by interacting with components of the basal transcriptional machinery, Both p300 and CBP are targeted by the adenovirus E1A protein, and binding to p300 is required for E1A to inhibit terminal differentiation in both keratinocytes and myoblasts, Here we demonstrate that, in differentiating skeletal muscle cells, p300 physically interacts with the myogenic basic helix-loop-helix (bHLH) regulatory protein MyoD at its DNA binding sites, During muscle differentiation, MyoD plays a dual role: besides activating muscle-specific transcription, it induces permanent cell cycle arrest by up-regulating the cyclin-dependent kinase inhibitor p21, We show that p300 is involved in both these activities, Indeed, E1A mutants lacking the ability to bind p300 are greatly impaired in the repression of E-box-driven transcription, and p300 overexpression rescues the wild-type E1A-mediated repression. Moreover, p300 potentiates MyoD- and myogenin-dependent activation of transcription from E-box-containing reporter genes, We also provide evidence, obtained by microinjection of anti-p300 antibodies, that p300 is required for MyoD-dependent cell cycle arrest in either myogenic cells induced to differentiate or in MyoD-converted C3H10T1/2 fibroblasts, but is dispensable for maintenance of the postmitotic state of myotubes. C1 UNIV ROMA LA SAPIENZA,POLICLIN UMBERTO I,IST CLIN MED 1,I-00161 ROME,ITALY. NCI,DCBOC PATH,NIH,BETHESDA,MD 20892. UNIV AQUILA,DIPARTIMENTO MED INTERNA,I-67100 LAQUILA,ITALY. THOMAS JEFFERSON UNIV,SBARRO INST CANC RES & MOL MED,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT MICROBIOL IMMUNOL,PHILADELPHIA,PA 19107. FREE UNIV BERLIN,INST BIOCHEM & MOL BIOL,D-33 BERLIN,GERMANY. UNIV CAGLIARI,IST MED INTERNA,I-09124 CAGLIARI,ITALY. RP Puri, PL (reprint author), UNIV ROMA LA SAPIENZA,FDN ANDREA CESALPINO,GENET EXPRESS LAB,PIAZZALE ALDO MORO 5,I-00161 ROME,ITALY. RI Giordano, Antonio/F-1927-2010 OI Giordano, Antonio/0000-0002-5959-016X FU NCI NIH HHS [R01 CA60999-01A1]; Telethon [A.064] NR 70 TC 210 Z9 212 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 15 PY 1997 VL 16 IS 2 BP 369 EP 383 DI 10.1093/emboj/16.2.369 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WF380 UT WOS:A1997WF38000015 PM 9029156 ER PT J AU Sharma, Y Chandani, S Sukhaswami, MB Uma, L Balasubramanian, D Fairwell, T AF Sharma, Y Chandani, S Sukhaswami, MB Uma, L Balasubramanian, D Fairwell, T TI Modified helix-loop-helix motifs of calmodulin - The influence of the exchange of helical regions on calcium-binding affinity SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE calmodulin; helix-loop-helix motif; 4,4,4',5'-dibenzo-3,3'-diethyl-9-methyl-thiacarbocyanine bromide; synthetic peptide; molecular modeling ID DYE STAINS-ALL; SKELETAL TROPONIN-C; SITE-III; PROTEINS; H-1-NMR; CONFORMATION; FRAGMENTS; VARIANTS; DOMAINS; ANALOGS AB The four calcium-binding sites, called the helix-loop-helix, or the EF-hand motifs, of calmodulin differ in their ion-binding affinities; this has been thought to arise due to the variations in the sequences of the loop regions where the ion binds. We focus attention here on the role of the flanking helical regions on the calcium-binding affinities. Peptides were synthesized in a manner that simulates the E and F helical flanks of site 4 (the strongest calcium-binding site of the calmodulin) to sandwich the loop sequences of sites 1, 2, 3 and 4 so as to produce peptides named 414, 424, 434 and 444, as well as using the helical flanks of site 1 (the weakest site) to produce peptides 111, 121, 131 and 141. Calcium binding was monitored using the calcium-mimic dye Stains-all (4,4,4',5'-dibenzo-3,3'-diethyl-9-methyl-thiacarbocyanine bromide). Binding abilities were seen to increase several-fold when the E and F helices of site 1 were replaced by those of site 4 (i.e., 111-414). in contrast, the intensity of circular dichroism induced in the absorption bands of the bound achiral dye decreased significantly when the helical flanks of site 4 were replaced with those of site 1 (i.e., 444-141). The helical flanks of site 4 impart greater binding ability to a given loop region, while the helical flanks of site 1 tend to weaken it. C1 NHLBI,NATL INST HLTH,BETHESDA,MD 20892. CTR CELLULAR & MOL BIOL,HYDERABAD 500007,ANDHRA PRADESH,INDIA. RSCHS,SIKH VILLAGE EXTN,SECUNDERABAD,INDIA. NR 35 TC 12 Z9 12 U1 0 U2 1 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 JAN 15 PY 1997 VL 243 IS 1-2 BP 42 EP 48 DI 10.1111/j.1432-1033.1997.0042a.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE132 UT WOS:A1997WE13200006 PM 9030720 ER PT J AU Costell, M Mann, K Yamada, Y Timpl, R AF Costell, M Mann, K Yamada, Y Timpl, R TI Characterization of recombinant perlecan domain I and its substitution by glycosaminoglycans and oligosaccharides SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE basement membrane; protein module; proteoglycan; recombinant production ID HEPARAN-SULFATE PROTEOGLYCAN; DENSITY-LIPOPROTEIN-RECEPTOR; EPIDERMAL-GROWTH-FACTOR; CELL-ADHESION MOLECULES; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; CORE PROTEIN; GLYCOSYLATION SITES; O-GLYCOSYLATION; BINDING AB Recombinant mouse perlecan domain I (173 residues) was produced in transfected embryonic kidney cells and purified from the culture medium on DEAE-cellulose. It was shown to be modified by glycosaminoglycans and could be partially separated into two protein pools which were either substituted with heparan sulfate (fragment IA) or, to a smaller extent (20%), with chondroitin/dermatan sulfate or a mixture of both glycosaminoglycans (fragment IB). The average molecular mass of the glycosaminoglycans was about 8-10 kDa and, thus, smaller than in tissue-derived perlecans. Sequence and carbohydrate analyses localized the heparan sulfate attachment site to three Ser residues within SGD consensus sequences. Furthermore, the N-terminal part of fragment IA contained six Thr/Ser residues substituted by branched galactosamine-containing oligosaccharides and an N-substituted Asn residue. Fragment I was also shown to contain unique immunological epitopes which are not dependent on glycosaminoglycans and are shared by tissue-derived perlecan. Circular dichroism demonstrated a distinct alpha helix (20%) and beta structure (60%) in fragment IA, consistent with predictions of a novel SEA protein module located in the C-terminal part of domain I. C1 MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. NIDR,NATL INST HLTH,BETHESDA,MD 20892. RI Mann, Karlheinz/C-4254-2008 NR 35 TC 61 Z9 61 U1 0 U2 1 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 JAN 15 PY 1997 VL 243 IS 1-2 BP 115 EP 121 DI 10.1111/j.1432-1033.1997.t01-1-00115.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WE132 UT WOS:A1997WE13200015 PM 9030729 ER PT J AU Liu, XW Robinson, GW Wagner, KU Garrett, L WynshawBoris, A Hennighausen, L AF Liu, XW Robinson, GW Wagner, KU Garrett, L WynshawBoris, A Hennighausen, L TI Stat5a is mandatory for adult mammary gland development and lactogenesis SO GENES & DEVELOPMENT LA English DT Article DE Stat5 proteins; epithelial cell differentiation; lactogenesis; mammopoiesis ID WHEY ACIDIC PROTEIN; TRANSGENIC MICE; GENE PROMOTER; TRANSCRIPTIONAL ACTIVATION; EPITHELIAL-CELLS; NUCLEAR FACTOR; DNA-BINDING; EXPRESSION; PROLACTIN; HORMONE AB Prolactin (PRL) induces mammary gland development (defined as mammopoiesis) and lactogenesis. Binding of PRL to its receptor leads to the phosphorylation and activation of STAT (signal transducers and activators of transcription) proteins, which in turn promote the expression of specific genes. The activity pattern of two STAT proteins, Stat5a and Stat5b, in mammary tissue during pregnancy suggests an active role for these transcription factors in epithelial cell differentiation and milk protein gene expression. To investigate the function of Stat5a in mammopoiesis and lactogenesis we disrupted this gene in mice by gene targeting. Stat5a-deficient mice developed normally and were indistinguishable from hemizygous and wild-type littermates in size, weight, and fertility. However, mammary lobuloalveolar outgrowth during pregnancy was curtailed, and females failed to lactate after parturition because of a failure of terminal differentiation. Although Stat5b has a 96% similarity with Stat5a and a superimposable expression pattern during mammary gland development it failed to counterbalance for the absence of Stat5a. These results document that Stat5a is the principal and an obligate mediator of mammopoietic and lactogenic signaling. C1 NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. RI Wagner, Kay-Uwe/B-6044-2009; Robinson, Gertraud/I-2136-2012 NR 36 TC 778 Z9 793 U1 4 U2 18 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 JAN 15 PY 1997 VL 11 IS 2 BP 179 EP 186 DI 10.1101/gad.11.2.179 PG 8 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WG668 UT WOS:A1997WG66800004 PM 9009201 ER PT J AU Bryk, M Banerjee, M Murphy, M Knudsen, KE Garfinkel, DJ Curcio, MJ AF Bryk, M Banerjee, M Murphy, M Knudsen, KE Garfinkel, DJ Curcio, MJ TI Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast SO GENES & DEVELOPMENT LA English DT Article DE Tyl; rDNA; chromatin; transcriptional silencing; UBC2; histones H2A-H2B ID UBIQUITIN-CONJUGATING ENZYME; N-END RULE; SACCHAROMYCES-CEREVISIAE; CHROMATIN STRUCTURE; RIBOSOMAL DNA; DROSOPHILA-MELANOGASTER; MEIOTIC RECOMBINATION; AMINO-TERMINUS; RAD6 PROTEIN; RNA GENES AB We demonstrate that in Saccharomyces cerevisiae, the tandem array of ribosomal RNA genes (RDN1) is a target for integration of the Ty1 retrotransposon that results in silencing of Ty1 transcription and transposition. Ty1 elements transpose into random rDNA repeat units and are mitotically stable. In addition, we have found that mutation of several putative modifiers of RDN1 chromatin structure abolishes silencing of Ty1 elements in the rDNA array. Disruption of SIR2, which elevates recombination in RDN1, or TOP1, which increases psoralen accessibility in rDNA, or HTA1-HTB1, which reduces histone H2A-H2B levels and causes localized chromatin perturbations, abolishes transcriptional silencing of Ty1 elements in RDN1. Furthermore, deletion of the gene for the ubiquitin conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not only Ty1 transcription but also mitotic recombination in RDN1. On the basis of these results, we propose that a specialized chromatin structure exists in RDN1 that silences transcription of the Ty1 retrotransposon. C1 SUNY ALBANY,MOL GENET PROGRAM,WADSWORTH CTR,ALBANY,NY 12201. SUNY ALBANY,SCH PUBL HLTH,ALBANY,NY 12201. NCI,GENE REGULAT & CHROMOSOME BIOL LAB,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. OI Curcio, M. Joan/0000-0001-5361-3909 FU NIGMS NIH HHS [GM52072] NR 79 TC 300 Z9 301 U1 0 U2 3 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 JAN 15 PY 1997 VL 11 IS 2 BP 255 EP 269 DI 10.1101/gad.11.2.255 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WG668 UT WOS:A1997WG66800010 PM 9009207 ER PT J AU Lin, JH Levin, HL AF Lin, JH Levin, HL TI A complex structure in the mRNA of Tf1 is recognized and cleaved to generate the primer of reverse transcription SO GENES & DEVELOPMENT LA English DT Article DE priming; retrotransposon; RNA; RT; S-pombe; Tf1 ID OPEN READING FRAMES; VIRUS LEADER RNA; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; TY1 TRANSPOSITION; TRANSLATION; PARTICLES; MECHANISM; RETROTRANSPOSITION; INITIATION AB All retroviruses and LTR-containing retrotransposons are thought to require specific tRNA molecules to serve as primers of reverse transcription. An exception is the LTR-containing retrotransposon Tf1, isolated from Schizosaccharomyces pombe. Instead of requiring a tRNA, the reverse transcriptase of Tf1 uses the first 11 bases of the Tf1 transcript as the primer for reverse transcription. The primer is generated by a cleavage that occurs between bases 11 and 12 of the Tf1 mRNA. Sequence analysis of the 5' untranslated region of the Tf1 mRNA resulted in the identification of a region with the potential to form an RNA structure of 89 bases that included the primer binding site and the first 11 bases of the Tf1 mRNA. Systematic mutagenesis of this region revealed 34 single-point mutants in the structure that resulted in reduced transposition activity. The defects in transposition correlated with reduced level of Tf1 reverse transcripts as determined by DNA blot analysis. Evidence that the RNA structure did form in vivo included the result that strains with second site mutations that restored complementarity resulted in increased levels of reverse transcripts and Tf1 transposition. The majority of the mutants defective for reverse transcription were unable to cleave the Tf1 mRNA between bases 11 and 12. These data indicate that formation of an extensive RNA structure was required for the cleavage reaction that generated the primer for Tf1 reverse transcription. C1 NICHHD, LAB EUKARYOT GENET REGULAT, BETHESDA, MD 20892 USA. NR 25 TC 37 Z9 37 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 1997 VL 11 IS 2 BP 270 EP 285 DI 10.1101/gad.11.2.270 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WG668 UT WOS:A1997WG66800011 PM 9009208 ER PT J AU Rogers, GR Markova, NG DeLaurenzi, V Rizzo, WB Compton, JG AF Rogers, GR Markova, NG DeLaurenzi, V Rizzo, WB Compton, JG TI Genomic organization and expression of the human fatty aldehyde dehydrogenase gene (FALDH) SO GENOMICS LA English DT Article ID SJOGREN-LARSSON SYNDROME; TRANSCRIPTION; CLONING; LINKAGE; CDNA AB Mutations in the fatty aldehyde dehydrogenase (FALDH) gene cause Sjogren-Larsson syndrome (SLS)-a disease characterized by mental retardation, spasticity, and congenital ichthyosis. To facilitate mutation analysis in SLS and to study the pathogenesis of FALDH deficiency, we have determined the structural organization and characterized expression of the FALDH (proposed designation ALDH10) gene. The gene consists of 10 exons spanning about 30.5 kb. A TATA-less promoter is associated with the major transcription initiation site found to be 258 bp upstream of the ATG codon The GC-rich sequences surrounding the transcription initiation site encompassed regulatory elements that interacted with proteins in HeLa nuclear extracts and were able to promote transcription in vitro. FALDH is widely expressed as three transcripts of 2, 3.8, and 4.0 kb, which originate from multiple polyadenylation signals in the 3' UTR. An alternatively spliced mRNA was detected that contains an extra exon and encodes an enzyme that is likely to have altered membrane-binding properties. The FALDH gene lies only 50-85 kb hom ALDH3, an aldehyde dehydrogenase gene that has homologous sequence and intron/exon structure. (C) 1997 Academic Press C1 NIAMSD,NIH,GENET STUDIES SECT,SKIN BIOL LAB,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,DEPT EXPT MED,BIOCHEM LAB,IST DERMOPAT IMMACOLATA,IRCCS,I-00167 ROME,ITALY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. FU Telethon [E.0413] NR 25 TC 43 Z9 44 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 JAN 15 PY 1997 VL 39 IS 2 BP 127 EP 135 DI 10.1006/geno.1996.4501 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WE849 UT WOS:A1997WE84900001 PM 9027499 ER PT J AU Shaughnessy, JD Jenkins, NA Copeland, NG AF Shaughnessy, JD Jenkins, NA Copeland, NG TI cDNA cloning, expression analysis, and chromosomal localization of a gene with high homology to wheat eIF-(iso)4F and mammalian eIF-4G SO GENOMICS LA English DT Article ID PROTEIN-SYNTHESIS INITIATION; MESSENGER-RNA; ISOZYME FORM; SEQUENCE; GERM; CAP; BINDING; IDENTIFICATION; TRANSLATION; INVOLVEMENT AB A novel mammalian gene, Eif4g2, with a high degree of homology to the p82 subunit of the wheat germ eukaryotic translation initiation factor eIF-(iso)4F and mammalian eIF-4G has been isolated. Zoo blot analysis indicates that Eif4g2 is a single-copy gene that is highly conserved among vertebrates. Northern blot analysis shows that Eif4g2 is ubiquitously expressed at high levels in all human and mouse tissues examined. The 3810-nucleotide Eif4g2 cDNA contains a 907-amino-acid open reading frame that codes for a polypeptide with a predicted molecular mass of 102 kDa. The Eif4g2 polypeptide exhibits an overall similarity to wheat p82 of 52%. A 248-amino-acid segment at the amino-terminal end of both peptides exhibits 63% similarity and contains conserved potential RNA binding domains and a phosphorylation site. The Eif4g2 polypeptide contains multiple potential N-linked glycosylation sites as well as protein kinase C and casein kinase II phosphorylation sites. Southern blot analysis of DNA from interspecific backcross mice shows that Eif4g2 is localized to distal mouse chromosome 7 in a region syntenic with human chromosome 11p15. (C) 1997 Academic Press C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 25 TC 29 Z9 30 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 JAN 15 PY 1997 VL 39 IS 2 BP 192 EP 197 DI 10.1006/geno.1996.4502 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WE849 UT WOS:A1997WE84900008 PM 9027506 ER PT J AU Thompson, DB Sutherland, J Apel, W Ossowski, V AF Thompson, DB Sutherland, J Apel, W Ossowski, V TI A physical map at 1p31 encompassing the acute insulin response locus and the leptin receptor SO GENOMICS LA English DT Article ID PIMA-INDIANS; HUMAN GENOME; GENE; SECRETION; LINKAGE; REGION; FAMILY AB Recently, we reported genetic linkage in Pima Indians between the acute insulin response to an intravenous glucose challenge and the short tandem repeat marker D1S198, indicative of a genetic element in this region that controls the phenotypic variation in the first phase of insulin secretion, As a first step to isolating the gene responsible for the acute insulin response, we have constructed a yeast artificial chromosome (YAC) contig map that spans the DNA microsatellites D1S438 through D1S464. The contig comprises 34 YACs on which we have mapped 44 ends of the genomic DNA inserts from the 34 YACs, 13 short tandem repeats, eight expressed sequence tags, and six genes, In addition, we have used this contig to construct a physical map encompassing approximately 9 Mb of DNA in this region. (C) 1997 Academic Press RP Thompson, DB (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 21 TC 10 Z9 10 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 JAN 15 PY 1997 VL 39 IS 2 BP 227 EP 230 DI 10.1006/geno.1996.4504 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WE849 UT WOS:A1997WE84900012 PM 9027510 ER PT J AU Budarf, M McDonald, T Sellinger, B Kozak, C Graham, C Wistow, G AF Budarf, M McDonald, T Sellinger, B Kozak, C Graham, C Wistow, G TI Localization of the human gene for macrophage migration inhibitory factor (MIF) to chromosome 22q11.2 SO GENOMICS LA English DT Article ID MOLECULAR-CLONING; PSEUDOGENES C1 NEI,LMDB,NIH,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. CHILDRENS HOSP,PHILADELPHIA,PA 19104. NIAID,NIH,BETHESDA,MD 20892. FU NHGRI NIH HHS [HG00425] NR 16 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 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1997 VL 39 IS 2 BP 235 EP 236 DI 10.1006/geno.1996.4505 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WE849 UT WOS:A1997WE84900014 PM 9027512 ER PT J AU Collins, FS AF Collins, FS TI Sequencing the human genome SO HOSPITAL PRACTICE LA English DT Article AB By 2005, or sooner, the three billion code letters of a representative human genome will be known, along with the locations of all of its genes. Even today, however, the work is greatly accelerating identification of disease-related genes. One outcome will be tests for genetic components of risk in the majority of common illnesses. In the longer run, genetic discoveries will surely lead to new treatments. RP Collins, FS (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 10 TC 19 Z9 19 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD JAN 15 PY 1997 VL 32 IS 1 BP 35 EP & PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA WN985 UT WOS:A1997WN98500005 PM 9006582 ER PT J AU Wright, JJ Hoffmeister, KJ Cotelingam, JD Allegra, CJ AF Wright, JJ Hoffmeister, KJ Cotelingam, JD Allegra, CJ TI Neutrophilia and organomegaly in two patients with cancer SO HOSPITAL PRACTICE LA English DT Article ID BLADDER-CARCINOMA; LEUKOCYTOSIS; LEUKEMIA; TUMOR RP Wright, JJ (reprint author), NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD JAN 15 PY 1997 VL 32 IS 1 BP 135 EP & PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WN985 UT WOS:A1997WN98500013 PM 9064302 ER PT J AU Petty, TL Weinmann, GG AF Petty, TL Weinmann, GG TI Building a national strategy for the prevention and management of and research in chronic obstructive pulmonary disease - National Heart, Lung, and Blood Institute Workshop summary SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SMOKING-CESSATION; CIGARETTE-SMOKING; PASSIVE SMOKING; RISK FACTOR; NEW-MEXICO; CANCER; CARE; HEALTH; INTERVENTION; POPULATION C1 NHLBI,DIV LUNG DIS,NIH,BETHESDA,MD 20892. NR 60 TC 84 Z9 84 U1 0 U2 1 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 JAN 15 PY 1997 VL 277 IS 3 BP 246 EP 253 DI 10.1001/jama.277.3.246 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WB446 UT WOS:A1997WB44600027 PM 9005275 ER PT J AU Schulick, AH Vassalli, G Dunn, PF Dong, G Rade, JJ Zamarron, C Dichek, DA AF Schulick, AH Vassalli, G Dunn, PF Dong, G Rade, JJ Zamarron, C Dichek, DA TI Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries - Potential for immunosuppression and vector engineering to overcome barriers of immunity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE adenovirus; arteries; gene transfer; immunity; rats ID SMOOTH-MUSCLE CELLS; IN-VIVO; RECOMBINANT ADENOVIRUSES; CYSTIC-FIBROSIS; EXPRESSION; THERAPY; REPLICATION; MODEL; MICE; E2A AB Preclinical arterial gene transfer studies with adenoviral vectors are typically performed in laboratory animals that lack immunity to adenovirus. However, human patients are likely to have prior exposures to adenovirus that might affect: (a) the success of arterial gene transfer; (b) the duration of recombinant gene expression; and (c) the likelihood of a destructive immune response to transduced cells. We confirmed a high prevalence (57%) in adult humans of neutralizing antibodies to adenovirus type 5. We then used a rat model to establish a central role for the immune system in determining the success as well as the duration of recombinant gene expression after adenovirus-mediated gene transfer into isolated arterial segments. Vector-mediated recombinant gene expression, which was successful in naive rats and prolonged by immunosuppression, was unsuccessful in the presence of established immunity to adenovirus. 4 d of immunosuppressive therapy permitted arterial gene transfer and expression in immune rats, but at decreased levels. Ultraviolet-irradiated adenoviral vectors, which mimic advanced-generation vectors (seduced viral gene expression and relatively preserved capsid function), were less immunogenic than were nonirradiated vectors. A primary exposure to ultraviolet-irradiated (but not nonirradiated) vectors permitted expression of a recombinant gene after redelivery of the same vector. in conclusion, arterial gene transfer with current type 5 adenoviral vectors is unlikely to result in significant levels of gene expression in the majority of humans. Both immunosuppression and further engineering of the vector genome to decrease expression of viral genes show promise in circumventing barriers to adenovirus-mediated arterial gene transfer. C1 GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA 94141. NHLBI,MOL HEMATOL BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DAIICHI RES CTR,SAN FRANCISCO,CA 94141. NR 48 TC 120 Z9 124 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 15 PY 1997 VL 99 IS 2 BP 209 EP 219 DI 10.1172/JCI119149 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WE311 UT WOS:A1997WE31100010 PM 9005989 ER PT J AU Pagtalunan, ME Miller, PL JumpingEagle, S Nelson, RG Myers, BD Rennke, HG Coplon, NS Sun, LM Meyer, TW AF Pagtalunan, ME Miller, PL JumpingEagle, S Nelson, RG Myers, BD Rennke, HG Coplon, NS Sun, LM Meyer, TW TI Podocyte loss and progressive glomerular injury in type II diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE glomerulus; proteinuria; mesangium; sclerosis; epithelial cell ID PIMA-INDIANS; OVERT NEPHROPATHY; ALBUMIN EXCRETION; STRUCTURAL BASIS; FILTRATION RATE; MELLITUS; MICROALBUMINURIA; PROTEINURIA; SURFACE; DAMAGE AB Kidney biopsies from Pima Indians with type II diabetes were analyzed. Subjects were classified clinically as having early diabetes (n = 10), microalbuminuria (n = 17), normoalbuminuria, despite a duration of diabetes equal to that of the subjects with microalbuminuria (n = 12), or clinical nephropathy (n = 12). Subjects with microalbuminuria exhibited moderate increases in glomerular and mesangial volume when compared with those with early diabetes, but could not be distinguished from subjects who remained normoalbuminuric after an equal duration of diabetes. Subjects with clinical nephropathy exhibited global glomerular sclerosis and more prominent structural abnormalities in non-sclerosed glomeruli. Marked mesangial expansion was accompanied by a further increase in total glomerular volume. Glomerular capillary surface area remained stable, but the glomerular basement membrane thickness was increased and podocyte foot processes were broadened. Broadening of podocyte foot processes was associated with a reduction in the number of podocytes per glomerulus and an increase in the surface area covered by remaining podocytes. These findings suggest that podocyte loss contributes to the progression of diabetic nephropathy. C1 VA PALO ALTO HEALTHCARE SYST,DEPT MED,PALO ALTO,CA 94304. STANFORD UNIV,STANFORD,CA 94305. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85014. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [DK-72291, DK-07357, DK-43597] NR 39 TC 589 Z9 620 U1 4 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 15 PY 1997 VL 99 IS 2 BP 342 EP 348 DI 10.1172/JCI119163 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WE311 UT WOS:A1997WE31100024 PM 9006003 ER PT J AU Ehrhardt, RO Ludviksson, BR Gray, B Neurath, M Strober, W AF Ehrhardt, RO Ludviksson, BR Gray, B Neurath, M Strober, W TI Induction and prevention of colonic inflammation in IL-2-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; CELL STIMULATORY FACTOR; CD4(+) T-CELLS; BOWEL-DISEASE; AUTOIMMUNE ENCEPHALOMYELITIS; INTERLEUKIN-2 DEFICIENT; CYTOKINE PRODUCTION; ULCERATIVE-COLITIS; IMMUNE-RESPONSES; IL-4 PRODUCTION AB Gene-targeted mice deficient for IL-2 (IL-2 -/- mice) are free of apparent disease when maintained under germfree conditions but develop colitis and autoimmunity in a conventional environment. Here we show that colitis can be reproducibly induced in IL-2 -/- mice, but not in IL-2 +/+ mice, by i.p. immunization with Ag in CFA; thus enabling the systematic study of the immunopathogenesis of the colitis. We found that TNP-KLH or TNP-OVA had the most significant effect in inducing colitis, and while TNP-KLH immunization leads to the early appearance of activated T cells in the colons of both IL-2 -/- and IL-2 +/+ mice, only lamina propria cells of IL-2 -/- mice produced high amounts of INF-gamma. Moreover, both infiltrating colon CD4(+) (69%) and CD8(+) (6%) T cells secrete targe amounts of IFN-gamma; however, only the depletion of CD4(+) T cells leads to abrogation of the inflammation. In further analysis, we showed that the high IFN-gamma production is IL-12 driven, since colonic tissues of IL-2 -/- mice but not IL-2 +/+ mice show the presence of heterodimeric IL-12 and co-administration of anti-IL-12 with TNP-KLH completely prevented colitis and significantly reduced IFN-gamma production. Finally, we demonstrate that IL-2 -/- mice are deficient in their ability to induce Th2 responses after TNP-KLH challenge and that such immunization also leads to autoimmune-like phenomena in other organs of IL-2 -/- mice. These findings suggest that in the absence of IL-2 systemic administration of Ag induces primarily Th1 cells driven by overexpression of heterodimeric IL-12. C1 UNIV MAINZ,MED CLIN 1,IMMUNOL LAB,D-6500 MAINZ,GERMANY. RP Ehrhardt, RO (reprint author), NIH,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BLDG 10,ROOM 11N238,BETHESDA,MD 20892, USA. NR 44 TC 155 Z9 161 U1 1 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 JAN 15 PY 1997 VL 158 IS 2 BP 566 EP 573 PG 8 WC Immunology SC Immunology GA WC638 UT WOS:A1997WC63800005 PM 8992969 ER PT J AU Muragaki, Y Chou, TT Kaplan, DR Trojanowski, JQ Lee, VMY AF Muragaki, Y Chou, TT Kaplan, DR Trojanowski, JQ Lee, VMY TI Nerve growth factor induces apoptosis in human medulloblastoma cell lines that express TrkA receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE nerve growth factor; neurotrophins; medulloblastoma; TrkA; apoptosis; S phase ID PRIMITIVE NEUROECTODERMAL TUMORS; TYROSINE PROTEIN-KINASE; CHILDHOOD BRAIN-TUMORS; HUMAN NGF RECEPTOR; S-PHASE ENTRY; SIGNAL-TRANSDUCTION; CHROMAFFIN CELLS; GENE-TRANSFER; NEURONAL DIFFERENTIATION; PROTOONCOGENE PRODUCT AB Neurotrophins act through their cognate receptors to promote the differentiation and/or survival of neuronal progenitor cells, immature neurons, and other cells. Here, we examined the effects of nerve growth factor (NGF) and its cognate receptor (Trk or TrkA) on the survival of a common childhood brain tumor, i.e., medulloblastoma, a tumor that resembles CNS neuroepithelial progenitor cells. To do this, we engineered two human medulloblastoma cell lines (i.e., D283MED and DAOY cells) to express human TrkA using a retroviral expression vector. Surprisingly, NGF-treated medulloblastoma cells expressing the TrkA receptor (D283trk and DAOYtrk cells) grown in the presence or absence of serum underwent massive apoptosis, but similar treatment did not induce apoptosis in wildtype uninfected cells, cells expressing an empty vector, or cells expressing the TrkC receptor. Furthermore, D283MED cells engineered to express the human p75 NGF receptor (D283p75) also did not undergo apoptosis. Significantly, NGF-induced apoptosis in D283trk and DAOYtrk cells can be inhibited by anti-NGF antibodies and by K-252a, an inhibitor of TrkA tyrosine phosphorylation and mimicked by high concentrations of NT3. Because NGF treatment primarily eliminated D283trk cells from the S phase of the cell cycle, this form of NGF-mediated apoptosis is cell cycle-dependent, These findings suggest that a NGF/TrkA signal transduction pathway could activate apoptotic cell death programs in CNS neuroepithelial progenitor cells and in childhood brain tumors. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. TOKYO WOMENS MED COLL,DEPT NEUROSURG,TOKYO 162,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 68 TC 102 Z9 103 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 1997 VL 17 IS 2 BP 530 EP 542 PG 13 WC Neurosciences SC Neurosciences & Neurology GA WC272 UT WOS:A1997WC27200003 PM 8987776 ER PT J AU Dunwiddie, TV Diao, LH Kim, HO Jiang, JL Jacobson, KA AF Dunwiddie, TV Diao, LH Kim, HO Jiang, JL Jacobson, KA TI Activation of hippocampal adenosine A(3) receptors produces a desensitization of A(1) receptor-mediated responses in rat hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adenosine; A(3) receptor; A(1) receptor; protein kinase C; hippocampus; electrophysiology; receptor desensitization ID CENTRAL-NERVOUS-SYSTEM; MOLECULAR-CLONING; PRESYNAPTIC INHIBITION; POSTSYNAPTIC RECEPTORS; A1 RECEPTORS; INVITRO; BINDING; MODULATION; METHYLXANTHINES; DEPRESSION AB The adenosine A(3) receptor is expressed in brain, but the consequences of activation of this receptor on electrophysiological activity are unknown. We have characterized the actions of a selective adenosine A(3) receptor agonist, 2-chloro-N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), and a selective A(3) receptor antagonist, 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS 1191), in brain slices from rat hippocampus. In the CA1 region, activation of A(3) receptors had no direct effects on synaptically evoked excitatory responses, long-term potentiation, or synaptic facilitation. However, activation of A(3) receptors with Cl-IB-MECA antagonized the adenosine A(1) receptor-mediated inhibition of excitatory neurotransmission. The effects of Cl-IB-MECA were blocked by pretreatment with MRS 1191, which by itself had no effect on A(1) receptor-mediated responses. The presynaptic inhibitory effects of baclofen and carbachol, mediated via GABA(B) and muscarinic receptors, respectively, were unaffected by Cl-IB-MECA. The maximal response to adenosine was unchanged, suggesting that the primary effect of Cl-IB-MECA was to reduce the affinity of adenosine for the receptor rather than to uncouple it. Similar effects could be demonstrated after brief superfusion with high concentrations of adenosine itself. Under normal conditions, endogenous adenosine in brain is unlikely to affect the sensitivity of A(1) receptors via this mechanism. However, when brain concentrations of adenosine are elevated (e.g., during hypoxia, ischemia, or seizures), activation of A(3) receptors and subsequent heterologous desensitization of A(1) receptors could occur, which might limit the cerebroprotective effects of adenosine under these conditions. C1 UNIV COLORADO,HLTH SCI CTR,PROGRAM NEUROSCI,DENVER,CO 80262. VET ADM MED RES SERV,DENVER,CO 80220. NIDDKD,MOL RECOGNIT SECT,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RP Dunwiddie, TV (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,BOX C-236,DENVER,CO 80262, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NINDS NIH HHS [R01 NS 29173] NR 36 TC 126 Z9 127 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 1997 VL 17 IS 2 BP 607 EP 614 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WC272 UT WOS:A1997WC27200010 PM 8987783 ER PT J AU Landsend, AS AmiryMoghaddam, M Matsubara, A Bergersen, L Usami, S Wenthold, RJ Ottersen, OP AF Landsend, AS AmiryMoghaddam, M Matsubara, A Bergersen, L Usami, S Wenthold, RJ Ottersen, OP TI Differential localization of delta glutamate receptors in the rat cerebellum: Coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article DE immunogold; glutamate receptor; freeze substitution; colocalization; synapse; cerebellum ID LONG-TERM DEPRESSION; PURKINJE-CELLS; IMMUNOGOLD LOCALIZATION; SUBUNIT; IMMUNOCYTOCHEMISTRY; ANTIBODIES; MEMBRANE; TOPOLOGY; BRAIN; ANTIGENS AB The delta 2 glutamate receptors are prominently expressed in Purkinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of delta receptors in rat cerebellar cortex was investigated with sensitive and high-resolution immunogold procedures. After postembedding incubation with an antibody raised to a C-terminal peptide of delta 2, high gold particle densities occurred in all parallel fiber synapses with Purkinje cell dendritic spines, whereas other synapses were consistently devoid of labeling. Among the types of immunonegative synapse were climbing fiber synapses with spines and parallel fiber synapses with dendritic stems of interneurons. At the parallel fiber-spine synapse, gold particles signaling delta receptors were restricted to the postsynaptic specialization. By the use of double labeling with two different gold particle sizes, it was shown that delta and AMPA GluR2/3 receptors were colocalized along the entire extent of the postsynaptic specialization without forming separate domains. The distribution of gold particles representing delta receptors was consistent with a cytoplasmic localization of the C terminus and an absence of a significant presynaptic pool of receptor molecules. The present data suggest that the delta 2 receptors are targeted selectively to a subset of Purkinje cell spines and that they are coexpressed with ionotropic receptors in the postsynaptic specialization. This arrangement could allow for a direct interaction between the two classes of receptor. C1 UNIV OSLO,INST BASIC MED SCI,DEPT ANAT,N-0317 OSLO,NORWAY. HIROSAKI UNIV,SCH MED,DEPT OTORHINOLARYNGOL,HIROSAKI,AOMORI 036,JAPAN. NIDOCD,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NR 34 TC 210 Z9 211 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 1997 VL 17 IS 2 BP 834 EP 842 PG 9 WC Neurosciences SC Neurosciences & Neurology GA WC272 UT WOS:A1997WC27200031 PM 8987804 ER PT J AU Lerman, C Biesecker, B Benkendorf, JL Kerner, J GomezCaminero, A Hughes, C Reed, MM AF Lerman, C Biesecker, B Benkendorf, JL Kerner, J GomezCaminero, A Hughes, C Reed, MM TI Controlled trial of pretest education approaches to enhance informed decision-making for BRCA1 gene testing SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OVARIAN-CANCER SUSCEPTIBILITY; BREAST-CANCER AB Background: In response to the isolation of the BRCA1 gene, a breast-ovarian cancer-susceptibility gene, biotechnology companies are already marketing genetic tests to health care providers and to the public. Initial studies indicate interest in BRCA1 testing in the general public and in populations at high risk. However, the optimal strategies for educating and counseling individuals have Set to be determined. Purpose: Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and/or ovarian cancer. Methods: A randomized trial design was used to evaluate the effects of education only (educational approach) and education plus counseling (counseling approach), as compared with a waiting-list (control) condition in = 400 for all groups combined). The educational approach reviewed information about personal risk factors, inheritance of cancer susceptibility, the benefits, limitations, and risks of BRCA1 testing, and cancer screening and prevention options. The counseling approach included this information, as well as a personalized discussion of experiences with canter in the family and the potential psychological and social impact of testing. Data on knowledge of inherited cancer and BRCA1 test characteristics, perceived risk, perceived benefits, limitations and risks of BRCA1 testing, and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up. Provision of a blood sample for future testing served Its a proxy measure of intention to be tested (in the education and counseling arms of the study). The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling (for the blood sample outcome). All P values are for two-sided tests. Results: The educational and counseling approaches both led to significant increases in knowledge, relative to the control condition (P<.001 for both). The counseling approach, but not the educational approach, was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing (P<.01) and decreases in perceived benefits (P<.05). However, neither approach produced changes in intentions to have BRCA1 testing. Prior to and following both education only and education plus counseling, approximately one half of the participants stated that they intended to be tested; after the session, 52% provided a blood sample. Conclusions: Standard educational approaches may be equally effective as expanded counseling approaches in enhancing knowledge. Since knowledge is a key aspect of medical decision-making, standard education mag be adequate in situations where genetic testing must be streamlined. On the other hand, it has been argued that optimal decision-making requires not only knowledge, but also a reasoned evaluation of the positive and negative consequences of alternate decisions. Although the counseling approach is more likely to achieve this goal, it may not diminish interest in testing, even among women at low to moderate risk. Future research should focus on the merits of these alternate approaches for subgroups of individuals with different backgrounds who are being counseled in the variety of settings where BRCA1 testing is likely to be offered. C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Lerman, C (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,2233 WISCONSIN AVE,NW,SUITE 535,WASHINGTON,DC 20007, USA. FU NIMH NIH HHS [R01MH HG54435] NR 27 TC 212 Z9 212 U1 2 U2 13 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 JAN 15 PY 1997 VL 89 IS 2 BP 148 EP 157 DI 10.1093/jnci/89.2.148 PG 10 WC Oncology SC Oncology GA WB925 UT WOS:A1997WB92500016 PM 8998184 ER PT J AU VanNevel, JP AF VanNevel, JP TI Healthy people 2000 - Women's cancers - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP VanNevel, JP (reprint author), NIH,BLDG 31,RM 10A29,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 JAN 15 PY 1997 VL 89 IS 2 BP 172 EP 172 PG 1 WC Oncology SC Oncology GA WB925 UT WOS:A1997WB92500021 ER PT J AU Le, SY Maizel, JV AF Le, SY Maizel, JV TI A common RNA structural motif involved in the internal initiation of translation of cellular mRNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FIBROBLAST GROWTH-FACTOR; GLUCOSE-REGULATED PROTEIN; RIBOSOME ENTRY SITE; 5' NONTRANSLATED REGION; HUMAN RHINOVIRUS RNA; C VIRUS-RNA; MESSENGER-RNA; SECONDARY STRUCTURE; ALTERNATIVE TRANSLATION; NUCLEOTIDE-SEQUENCE AB The 5'-non-translated regions (5'NTR) of human immunoglobulin heavy chain binding protein (BiP), Antennapedia (Antp) of Drosophila and human fibroblast growth factor 2 (FGF-2) mRNAs are reported to mediate translation initiation by an internal ribosome binding mechanism, In this study, we investigate predicted features of the higher order structures folded in these 5'NTR sequences. Statistical analyses of RNA folding detected a 92 nt unusual folding region (UFR) from 129 to 220, close to the initiator AUG in the BiP mRNA. Details of the structural analyses show that the UFR forms a Y-type stem-loop structure with an additional stem-loop in the 3'-end resembling the common structure core found in the internal ribosome entry site (IRES) elements of picornavirus. The Y-type structural motif is also conserved among a number of divergent BiP mRNAs, We also find two RNA elements in the 5'-leader sequence of human FGF-2. The first RNA element (96 nt) is 2 nt upstream of the first CUG start codon located in the reported IRES element of human FGF-2. The second (107 nt) is immediately upstream of the authentic initiator AUG of the main open reading frame, Intriguingly, the folded RNA structural motif in the two RNA elements is conserved in other members of FGF family and shares the same structural features as that found in the 5'NTR of divergent BiP mRNAs, We suggest that the common RNA structural motif conserved in the diverse BiP and FGF-2 mRNAs has a general function in the internal ribosome binding mechanism of cellular mRNAs. RP Le, SY (reprint author), NCI,MATH BIOL LAB,DIV BASIC SCI,NIH,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. NR 60 TC 114 Z9 117 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 15 PY 1997 VL 25 IS 2 BP 362 EP 369 DI 10.1093/nar/25.2.362 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD444 UT WOS:A1997WD44400012 PM 9016566 ER PT J AU Jin, DY Jeang, KT AF Jin, DY Jeang, KT TI HTLV-I tax self-association in optimal trans-activation function SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CELL LEUKEMIA-VIRUS; LONG TERMINAL REPEATS; NF-KAPPA-B; BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATION; TRANSACTIVATOR TAX; GENE-EXPRESSION; 2-HYBRID SYSTEM; BZIP PROTEINS; DNA-BINDING AB HTLV-I Tax protein is a potent transcriptional activator of viral and cellular genes. Tax does not bind DNA directly but interacts through protein-protein contact with host cell factors that recognize the viral long terminal repeat (LTR), Domains within Tax needed for protein-protein interaction have not been fully characterized, In studying transcriptional function in yeast cells, we unexpectedly found that Tax functions optimally not as a monomer, but as a homodimer. Here we have used the one hybrid and two hybrid genetic approaches in yeast to investigate the region(s) within Tax necessary for self-association. Dimer formation was also confirmed biochemically by using electrophoretic mobility shift (EMSA) and supershift assays, Twenty two Tax point mutants were utilized to map relevant residues, Genetic results from this series of mutants revealed that a necessary region for dimerization is contained within a previously characterized zinc finger domain, Two loss-of-function Tax mutants, each poorly active when assayed individually, were found to have complementing activity when co-expressed together, This genetic complementation suggests a mechanism for trans-activation resulting from simultaneous but non-identical contact with a responsive target by each of two Tax monomers in a dimer. C1 NIAID,MOL MICROBIOL LAB,MOL VIROL SECT,NIH,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 64 TC 59 Z9 61 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 15 PY 1997 VL 25 IS 2 BP 379 EP 387 DI 10.1093/nar/25.2.379 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WD444 UT WOS:A1997WD44400014 PM 9016568 ER PT J AU Benichou, J Byrne, C Gail, M AF Benichou, J Byrne, C Gail, M TI An approach to estimating exposure-specific rates of breast cancer from a two-stage case-control study within a cohort SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Statistical Methods for Incomplete Covariate Data in Clinical and Epidemiological Studies CY FEB 16-18, 1995 CL UNIV FREIBURG, INST MED BIOMETRY & MED INFORMAT, FREIBURG, GERMANY HO UNIV FREIBURG, INST MED BIOMETRY & MED INFORMAT ID MAMMOGRAPHIC PARENCHYMAL PATTERN; 2-STAGE CASE-CONTROL; REGRESSION-MODELS; LOGISTIC-REGRESSION; ABSOLUTE RISK; LINEAR-MODELS; VALIDATION; EPIDEMIOLOGY; SELECTION; PROGRAM AB The Breast Cancer Detection and Demonstration Project (BCDDP) included a large cohort of women followed for incidence of breast cancer and from whom an initial case-control sample was drawn and standard risk factors obtained. In order to study the effect of mammographic features on breast cancer risk, a nested subsample of cases and controls was drawn. Therefore, these data can be viewed as two-stage case-control data within a cohort, or as cohort data with two nested levels of missingness, since basic characteristics like age were measured on all members of the cohort, standard risk factors were elicited only in the initial case-control sample, and mammographic features were assessed only in the nested subsample of cases and controls. We present a Poisson pseudo-likelihood approach to estimating age- and exposure-specific breast cancer incidence rates based on the three types of variables, This approach takes into account the nested missingness as well as two other type of missingness, namely, that for basic variables and standard risk factors, some levels (i) were omitted by design in the nested subsample of case and controls or (ii) were empty because of the sparsity of the data in that subsample. Estimates of standard errors are obtained from a parametric bootstrap. The approach seems to be efficient when applied to the BCDDP data and is flexible for modelling breast cancer rates and taking the special missingness features of these data into account. C1 HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. RP Benichou, J (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN-403,MSC 7368,BETHESDA,MD 20892, USA. RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 44 TC 10 Z9 10 U1 1 U2 2 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 JAN 15 PY 1997 VL 16 IS 1-3 BP 133 EP 151 DI 10.1002/(SICI)1097-0258(19970130)16:2<133::AID-SIM476>3.0.CO;2-C PG 19 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 WA625 UT WOS:A1997WA62500010 PM 9004388 ER PT J AU Hochadel, JF Waalkes, MP AF Hochadel, JF Waalkes, MP TI Sequence of exposure to cadmium and arsenic determines the extent of toxic effects in male Fischer rats SO TOXICOLOGY LA English DT Article DE cadmium; arsenic; toxicity; sequence of exposure; rat ID HEPATIC METALLOTHIONEIN; GLUTATHIONE; LIVER; MICE; TOLERANCE; AFFINITY; TISSUES; DEFENSE; INVITRO; METALS AB Arsenic and cadmium are both priority hazardous substances and human carcinogens. Although there is the potential for simultaneous exposure to both metals, the interactions of cadmium and arsenic are not well defined. We examined the toxicity of these metals when given alone or in alternating sequence to adult male Fischer rats. In the first study, a non-toxic dose of arsenic (22.5 mu mol NaAsO2/kg, s.c.) was given 24 h before cadmium (10, 20, or 30 mu mol CdCl2/kg, s.c.) and toxicity was assessed 24 h later. Arsenic pretreatment markedly reduced mortality in rats given the high dose of cadmium (9 survivors/10 treated) compared to rats given cadmium alone (2/10). Arsenic pretreatment also reduced cadmium-induced hepatotoxicity: as indicated by serum glutamic oxalacetic transaminase (SGOT) activity, and markedly reduced cadmium-induced testicular hemorrhagic necrosis. Arsenic pretreatment produced an 8-fold increase in hepatic levels of metallothionein (MT), a metal-binding protein often associated with cadmium tolerance. In the second study, a non-toxic dose of cadmium (3 mu mol CdCl2/kg, s.c.) was given 24 h before alter the lethality of the high dose of arsenic and had no effect on arsenic-induced hepatotoxicity. Although cadmium pretreatment had no effect on arsenic toxicity, it produced large increases in hepatic MT (26-fold) before the arsenic challenge and greatly enhanced MT induction after the challenge. Thus, even though both arsenic and cadmium induce MT synthesis, only arsenic pretreatment protects against cadmium intoxication, and cadmium pretreatment does not effect arsenic toxicity. Thus, toxic interactions of arsenic and cadmium appear to depend on the sequence of exposure. Copyright (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NR 36 TC 30 Z9 31 U1 0 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 15 PY 1997 VL 116 IS 1-3 BP 89 EP 98 DI 10.1016/S0300-483X(96)03536-6 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WD999 UT WOS:A1997WD99900010 PM 9020510 ER PT J AU Shimada, H Bare, RM Hochadel, JF Waalkes, MP AF Shimada, H Bare, RM Hochadel, JF Waalkes, MP TI Testosterone pretreatment mitigates cadmium toxicity in male C57 mice but not in C3H mice SO TOXICOLOGY LA English DT Article ID INDUCED HEPATOTOXICITY; METALLOTHIONEIN INDUCTION; HEPATIC METALLOTHIONEIN; BINDING PROTEINS; SEX-DIFFERENCES; RAT; RESISTANCE; TOLERANCE; LIVER; STEROIDS AB Previous work has indicated that testosterone pretreatment protects against cadmium-induced toxicity in male rats while other data indicate that pretreatment of mice with testosterone offers no such protection against cadmium. Since cadmium toxicity may vary widely with species and strain, we examined the effect of testosterone pretreatment on cadmium toxicity in two strains of mice, one that is sensitive (C3H) and one that is resistant (C57) to cadmium toxicity. A single sc injection of 20 mu mol CdCl2/kg to C3H mice or 45 mu mol CdCl2/kg to C57 mice proved very toxic, causing 50% and 44% mortalities, respectively. However, when C57 mice were pretreated with testosterone (5 mg/kg, s.c., at -48, -24, and 0 h) prior to cadmium (45 mu mol/kg), complete resistance to cadmium-induced lethality developed. Testosterone had no effect on cadmium-induced lethality in C3H mice. Testosterone prevented extensive hepatocellular damage caused by cadmium in C57 mice and also significantly reduced cadmium-induced elevations in serum lactate dehydrogenase (LDH) activity and blood urea nitrogen (BUN), which are indicators of hepatic and renal function, respectively. The toxicokinetics of cadmium were apparently not affected by testosterone pretreatment, as the distribution of cadmium to liver in either strain was unchanged by the steroid. Cadmium-induced melalloth-ionein (MT) levels in liver and kidney of C57 mice were increased in testosterone-pretreated mice given the higher doses of metal but no such enhancement of MT synthesis occurred in C3H mice. This increase in MT may provide some level of protection against cadmium toxicity in the C57 mice. These results indicate that testosterone pretreatment prevents toxicity of cadmium in male C57 mice, possibly through enhancement of MT synthesis, but has no effect in male C3H mice. Copyright (C) 1997 Elsevier Science Ireland Ltd. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NR 49 TC 14 Z9 16 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 15 PY 1997 VL 116 IS 1-3 BP 183 EP 191 DI 10.1016/S0300-483X(96)03544-5 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WD999 UT WOS:A1997WD99900020 PM 9020520 ER PT J AU Knechtle, SJ Vargo, D Fechner, J Zhai, Y Wang, J Hanaway, MJ Scharff, J Hu, HZ Knapp, L Watkins, D Neville, DM AF Knechtle, SJ Vargo, D Fechner, J Zhai, Y Wang, J Hanaway, MJ Scharff, J Hu, HZ Knapp, L Watkins, D Neville, DM TI FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; OKT4A MONOCLONAL-ANTIBODY; RANDOMIZED CLINICAL-TRIAL; ANTITHYMOCYTE GLOBULIN; RHESUS-MONKEYS; BONE-MARROW; INDUCTION; TRANSPLANTATION; RECIPIENTS; DIVERSITY AB Background. Transplant tolerance, rather than immunity, may be favored in the setting of a lower mature lymphoid mass in the recipient induced by anti-T cell agents, A novel immunosuppressive agent, FN18-CRM9, known to specifically kill T cells with great potency, was evaluated in a transplant model. Methods. In order to ablate recipient T cells, the immunotoxin FN18-CRM9 was administered to rhesus monkey recipients of MHC-mismatched renal allografts, Donor lymphocytes were injected intrathymically into some animals. Results. All monkeys with T-cell depletion by immunotoxin had prolonged allograft survival, and tolerance confirmed by skin grafting has been confirmed in five of six long-surviving recipients. Conclusions. In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance. C1 UNIV WISCONSIN,DEPT SURG,MADISON,WI 53792. UNIV WISCONSIN,DEPT PATHOL,MADISON,WI 53792. NIMH,MOL BIOL LAB,BETHESDA,MD 20892. RI Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 NR 25 TC 157 Z9 157 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1997 VL 63 IS 1 BP 1 EP 6 DI 10.1097/00007890-199701150-00002 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WD066 UT WOS:A1997WD06600001 PM 9000652 ER PT J AU Chernomordik, LV Leikina, E Frolov, V Bronk, P Zimmerberg, J AF Chernomordik, LV Leikina, E Frolov, V Bronk, P Zimmerberg, J TI An early stage of membrane fusion mediated by the low pH conformation of influenza hemagglutinin depends upon membrane lipids SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HEXAGONAL PHASE-TRANSITION; PLANAR BILAYER-MEMBRANES; CELL-FUSION; PHOSPHOLIPID-BILAYERS; ERYTHROCYTE-MEMBRANE; BIOLOGICAL-MEMBRANES; CONJUGATED RHODAMINE; VIRUS HEMAGGLUTININ; EXPRESSING CELLS; VIRAL MEMBRANE AB While the specificity and timing of membrane fusion in diverse physiological reactions, including virus-cell fusion, is determined by proteins, fusion always involves the merger of membrane lipid bilayers. We have isolated a lipid-dependent stage of cell-cell fusion mediated by influenza hemagglutinin and triggered by cell exposure to mildly acidic pH. This stage preceded actual membrane merger and fusion pore formation but was subsequent to a low pH-induced change in hemagglutinin conformation that is required for fusion. A low pH conformation of hemagglutinin was required to achieve this lipid-dependent stage and also, downstream of it, to drive fusion to completion. The lower the pH of the medium applied to trigger fusion and, thus, the more hemagglutinin molecules activated, the less profound was the dependence of fusion on lipids. Membrane-incorporated lipids affected fusion in a manner that correlated with their dynamic molecular shape, a characteristic that determines a lipid monolayer's propensity to bend in different directions. The lipid sensitivity of this stage, i.e., inhibition of fusion by inverted cone-shaped lysophosphatidylcholine and promotion by cone-shaped oleic acid, was consistent with the stalk hypothesis of fusion, suggesting that fusion proteins begin membrane merger by promoting the formation of a bent, lipid-involving, stalk intermediate. C1 RUSSIAN ACAD SCI,FRUMKIN INST ELECTROCHEM,LAB BIOELECTROCHEM,MOSCOW 117071,RUSSIA. RP Chernomordik, LV (reprint author), NICHHD,LAB CELLULAR & MOL BIOPHYS,NIH,BLDG 10,ROOM 10D04,10 CTR DR,BETHESDA,MD 20892, USA. OI Frolov, Vadim/0000-0002-0653-5669 NR 77 TC 166 Z9 168 U1 3 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 13 PY 1997 VL 136 IS 1 BP 81 EP 93 DI 10.1083/jcb.136.1.81 PG 13 WC Cell Biology SC Cell Biology GA WC961 UT WOS:A1997WC96100008 PM 9008705 ER PT J AU Schneerson, R Robbins, JB Taranger, J Trollfors, B Lagergard, T AF Schneerson, R Robbins, JB Taranger, J Trollfors, B Lagergard, T TI Toxoid vaccine for pertussis - Reply SO LANCET LA English DT Letter RP Schneerson, R (reprint author), NICHHD,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 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 JAN 11 PY 1997 VL 349 IS 9045 BP 137 EP 138 DI 10.1016/S0140-6736(05)60928-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WB800 UT WOS:A1997WB80000067 ER PT J AU Chen, D Guo, JR Gahl, WA AF Chen, D Guo, JR Gahl, WA TI rab GTPases expressed in human melanoma cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE rab; ras superfamily; melanocyte; platelet ID GTP-BINDING PROTEIN; HUMAN PLATELETS; CLONING; IDENTIFICATION; ORGANELLES; FAMILY; CDNA AB The expression of small GTP-binding protein genes of the ras superfamily was examined in pigmented human melanoma cells by a PCR-based strategy. Twenty six different partial cDNA sequences were isolated, including 17 members of the rab subfamily, of which 9 represented novel genes. Some rabs expressed in melanoma cells overlapped with those of platelets; this should prove relevant to the investigation of murine and human disorders characterized by the combination of pigment dilution and a platelet storage pool defect. C1 NICHHD,SECT HUMAN BIOCHEM GENET,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NR 22 TC 8 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN 10 PY 1997 VL 1355 IS 1 BP 1 EP 6 DI 10.1016/S0167-4889(96)00169-3 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WD858 UT WOS:A1997WD85800001 PM 9030196 ER PT J AU Levin, HL AF Levin, HL TI It's prime time for reverse transcriptase SO CELL LA English DT Review ID INTRON MOBILITY; MECHANISM; RNA RP Levin, HL (reprint author), NICHHD,LAB EUKARYOT GENE REGULAT,BETHESDA,MD 20892, USA. NR 20 TC 28 Z9 30 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 1997 VL 88 IS 1 BP 5 EP 8 DI 10.1016/S0092-8674(00)81851-6 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC569 UT WOS:A1997WC56900002 PM 9019405 ER PT J AU Hiom, K Gellert, M AF Hiom, K Gellert, M TI A stable RAG1-RAG2-DNA complex that is active in V(D)J Cleavage SO CELL LA English DT Article ID BROKEN DNA-MOLECULES; MOUSE THYMOCYTES; STRAND TRANSFER; CODING ENDS; RECOMBINATION; MECHANISM; SEQUENCE; REARRANGEMENT; INTEGRATION; INITIATION AB The RAG1 and RAG2 proteins initiate V(D)J recombination by making specific double-strand DNA breaks at recombination signal sequences. We show here that RAG1 and RAG2 bind specifically to this sequence, forming a stable protein-DNA complex. The complex requires the conserved heptamer and nonamer motifs of the recombination signal as well as both the RAG1 and RAG2 proteins. This complex is able to either nick or form hairpins at the V(D)J signal sequence, depending on the divalent cation present. A complex trapped using Ca2+ is subsequently active when transferred to Mg2+ or Mn2+. After cleavage, the complex is destabilized and the RAG proteins dissociate. We term this early precursor in the V(D)J recombination reaction a ''stable cleavage complex.'' RP Hiom, K (reprint author), NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. RI Hiom, Kevin/B-4374-2009 NR 30 TC 158 Z9 159 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 1997 VL 88 IS 1 BP 65 EP 72 DI 10.1016/S0092-8674(00)81859-0 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC569 UT WOS:A1997WC56900010 PM 9019407 ER PT J AU Cool, DR Normant, E Shen, FS Chen, HC Pannell, L Zhang, Y Loh, YP AF Cool, DR Normant, E Shen, FS Chen, HC Pannell, L Zhang, Y Loh, YP TI Carboxypeptidase E is a regulated secretory pathway sorting receptor: Genetic obliteration leads to endocrine disorders in Cpe(fat) mice SO CELL LA English DT Article ID TRANS-GOLGI NETWORK; PITUITARY INTERMEDIATE LOBE; OPIOMELANOCORTIN CONVERTING ENZYME; PRO-OPIOMELANOCORTIN; SECRETOGRANIN-II; DISULFIDE BOND; CHROMOGRANIN-B; PH; PROOPIOMELANOCORTIN; CELLS AB A proposed mechanism for sorting secretory proteins into granules for release via the regulated secretory pathway in endocrine-neuroendocrine cells involves binding the proteins to a sorting receptor at the transGolgi network, followed by budding and granule formation. We have identified such a sorting receptor as membrane-associated carboxypeptidase E (CPE) in pituitary Golgi-enriched and secretory granule membranes. CPE specifically bound regulated secretory pathway proteins, including prohormones, but not constitutively secreted proteins. We show that in the Cpe(fat) mutant mouse lacking CPE, the pituitary prohormone, pro-opiomelanocortin, was missorted to the constitutive pathway and secreted in an unregulated manner. Thus, obliteration of CPE, the sorting receptor, leads to multiple endocrine disorders in these genetically defective mice, including hyperproinsulinemia and infertility. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,ANALYT CHEM LAB,NIH,BETHESDA,MD 20892. RP Cool, DR (reprint author), NICHHD,CELLULAR NEUROBIOL SECT,NIH,BETHESDA,MD 20892, USA. NR 45 TC 342 Z9 346 U1 4 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 1997 VL 88 IS 1 BP 73 EP 83 DI 10.1016/S0092-8674(00)81860-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC569 UT WOS:A1997WC56900011 PM 9019408 ER PT J AU Kandel, D Chen, K Warner, LA Kessler, RC Grant, B AF Kandel, D Chen, K Warner, LA Kessler, RC Grant, B TI Prevalence and demographic correlates of symptoms of last year dependence on alcohol, nicotine, marijuana and cocaine in the US population SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE alcohol; cigarettes; cocaine; dependence; marijuana; population ID DSM-III-R; NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; PSYCHIATRIC-DISORDERS; YOUNG-ADULTS; DRUG-USE; SMOKING; ABUSE AB The prevalence of last year use of alcohol, cigarettes, marijuana and cocaine in the U.S. population and conditional prevalence of a proxy measure of last year dependence among last year users of each drug class were assessed as a function of age, gender and ethnicity. Analyses were based on three aggregated waves (1991, 1992 and 1993) of the nationally representative samples of the general population aged greater than or equal to 12 interviewed in the National Household Surveys on Drug Abuse (n = 87 915). An approximation of DSM-IV drug-specific last year dependence for each drug class was derived from self-reported symptoms of dependence, data on frequency and quantity of use and drug-related problems reported for the last year. Descriptive and multivariate analyses were conducted. The inclusion of cigarettes among the drugs, the large number of cases and the wide age range of respondents (greater than or equal to 12) enable us to make drug, age, gender and ethnic comparisons not otherwise possible in any other data set. The proxy measure of dependence, however, has limitations. The five major findings are that: (1) nicotine is the most addictive of the four drugs we examined; (2) among female last year users of alcohol and marijuana, adolescents are significantly more at risk for dependence than any other age group of women; (3) conditional prevalences of last year dependence on alcohol, marijuana and cocaine are higher among adolescent females than adolescent males but significantly different only for cocaine; (4) among adults, the rates of dependence are higher among males than among females for alcohol and marijuana, but lower for nicotine; and (5) among last year users, whites are more likely than any other ethnic group to be dependent on nicotine and blacks to be dependent on cocaine. Copyright (C) 1997 Elsevier Science Ireland Ltd. C1 NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. UNIV MICHIGAN,SCH SOCIAL WORK,DEPT SOCIOL,INST SOCIAL RES,ANN ARBOR,MI 48109. HARVARD UNIV,DEPT HLTH CARE POLICY,CAMBRIDGE,MA 02138. NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20852. RP Kandel, D (reprint author), COLUMBIA UNIV,SCH PUBL HLTH,DEPT PSYCHIAT,NEW YORK,NY 10027, USA. FU NIDA NIH HHS [DA 09110, KO5 DA00081]; NIMH NIH HHS [KO5 MH00507] NR 36 TC 261 Z9 264 U1 1 U2 18 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 JAN 10 PY 1997 VL 44 IS 1 BP 11 EP 29 DI 10.1016/S0376-8716(96)01315-4 PG 19 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA WF034 UT WOS:A1997WF03400002 PM 9031816 ER PT J AU Smith, ML Kontny, HU Bortnick, R Fornace, AJ AF Smith, ML Kontny, HU Bortnick, R Fornace, AJ TI The p53-regulated cyclin G gene promotes cell growth: p53 downstream effectors cyclin G and GADD45 exert different effects on cisplatin chemosensitivity SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR; RETINOBLASTOMA PROTEIN; MDM2 GENE; BREAST-CANCER; G(1) ARREST; DNA-DAMAGE; AMPLIFICATION; ASSOCIATION; OVEREXPRESSION; ONCOPROTEIN AB Among the p53-regulated genes that have been identified thus far, cyclin G is a relatively recent one. We conducted a series of experiments aimed at elucidating cyclin G; function. Ectopic overexpression of cyclin G; in human RKO colon carcinoma cells accelerated cell growth. Transfection of normal human fibroblasts with the cyclin G expression vector promoted clonal expansion. Cyclin G immune complexes isolated from the transfected cells exhibited appreciable levels of cyclin-dependent kinase activity, as evidenced using histone H1 as a substrate. The retinoblastoma protein, pRb, was detectable in cyclin G immune complexes, raising the possibility that Rb may be one mediator of cyclin G action. Cyclin G-overexpressing cells were more sensitive to cisplatin cytotoxicity than the parent cells, probably because cyclin G overexpression overrides cell cycle checkpoint(s). Overexpression of another p53-regulated gene, GADD45, by contrast, protected cells from cisplatin killing. These findings suggest that different downstream effecters of the p53 pathway may exert different effects on cellular survival after treatment with cancer chemotherapy drugs such as cisplatin. (C) 1997 Academic Press RP Smith, ML (reprint author), NCI,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,MOL PHARMACOL LAB,BLDG 37,ROOM 5D02,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 45 TC 70 Z9 81 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 10 PY 1997 VL 230 IS 1 BP 61 EP 68 DI 10.1006/excr.1996.3402 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA WD141 UT WOS:A1997WD14100008 PM 9013707 ER PT J AU Taimi, M Breitman, TR AF Taimi, M Breitman, TR TI Growth, differentiation, and death of retinoic acid-treated human acute promyelocytic leukemia NB4 cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID LEUKOCYTE ALKALINE-PHOSPHATASE; ALL-TRANS; LINE NB4; GENE-EXPRESSION; PROTEIN; MATURATION; RESISTANCE; MODULATION; INDUCTION; APOPTOSIS AB Published reports vary markedly on some characteristics of retinoic acid (RA) effects on cell growth and differentiation of the human acute promyelocytic leukemia cell line NB4, We explored possible reasons for this variability and found that the initial cell density of the experimental culture and the stage of growth of the cells used to inoculate experimental cultures were critical parameters for obtaining reproducible growth and differentiation responses of NB4 cells, Thus, the time to reach 50% differentiation in the presence of 1 mu M RA and various initial concentrations of cells was 1.9 days with 2 x 10(6) cells/ml, 3.5 days with 2 x 10(5) cells/ml, and 4.7 days with 2 x 10(4) cells/ml. With an initial concentration of 2 x 10(5) cells/ml we saw time- and dose-dependent differentiation with RA concentrations >250 nM. However, in the presence of 25-250 nM RA, differentiation reached a maximum of about 20% on either Day 1 or Day 2 and then declined with time, The catabolism of RA appeared to be responsible for the decline in differentiation. In addition, large decreases in viability occurred after NB4 cultures, growing without or with RA, reached a density of only 1 x 10(6) cells/ml. The decreases in viability were greater at intermediate concentrations of RA with a nadir at about 100 nM. Loss of viability was associated with DNA fragmentation and changes in morphology typical of apoptosis and necrosis, The loss of viability occurring in control cultures necessitates caution when these cultures are used to seed experimental cultures. (C) 1997 Academic Press C1 NIH,NCI,DIV BASIC SCI,BIOL CHEM LAB,BETHESDA,MD 20892. NR 22 TC 17 Z9 17 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 10 PY 1997 VL 230 IS 1 BP 69 EP 75 DI 10.1006/excr.1996.3413 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA WD141 UT WOS:A1997WD14100009 PM 9013708 ER PT J AU EvansStorms, RB Cidlowski, JA AF EvansStorms, RB Cidlowski, JA TI Dominant suppression of lymphocyte apoptosis by hepatoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID GLUCOCORTICOID RECEPTOR; DEATH; BCL-2; CLONING; PROTEIN; GENE; HETEROKARYONS; ENDONUCLEASE; ACTIVATION; EXPRESSION AB Suppression of apoptosis appears to contribute to the development of various diseases, including autoimmune disorders and cancer. Numerous genes that encode activators and suppressors of apoptosis have been identified; however, such genes have not been shown to be expressed in all cell types. Furthermore, the sensitivity of different cell types to induction of apoptosis varies widely. We have employed a genetic approach using somatic cell hybridization to determine if apoptosis is a dominant or a recessive process in cells. These studies have utilized cell fusion partners with differing sensitivity to induction of apoptosis. The apoptosis-sensitive cells chosen were BW5147 murine thymoma cells. These cells readily undergo apoptosis in response to glucocorticoids and calcium ionophore. The resistant fusion partners were HTC rat hepatoma cells, which possess an intact glucocorticoid signal transduction pathway but are resistant to induction of apoptosis by either agent. Neither cell type expresses detectable Bcl-2 protein. Heterokaryons were identified by their retention of fluorescent cytosolic dyes and by nuclear morphology and cell size. The three types of heterokaryons observed were intratypic HTC/HTC and BW5147/BW5147 heterokaryons and intertypic BW5147/HTC heterokaryons. Glucocorticoid receptor was shown by immunohistochemistry to undergo hormone-dependent translocation to all nuclei in intertypic heterokaryons. BW5147/BW5147 heterokaryons die after treatment with glucocorticoid and calcium ionophore, whereas both HTC/HTC and BW5147/HTC hybrids survive. The presence of multiple BW5147 cells fused to a single HTC cell did not affect this outcome. This demonstrates that HTC cells are able to dominantly suppress apoptosis in all BW5147/HTC heterokaryons. Thus, HTC cells contain activities that can suppress apoptosis in lymphocytes. (C) 1997 Academic Press RP EvansStorms, RB (reprint author), NIEHS,CELLULAR & MOL PHARMACOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA09156-18-NCI, NCI 1 F32 CA65049] NR 36 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 10 PY 1997 VL 230 IS 1 BP 121 EP 132 DI 10.1006/excr.1996.3406 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA WD141 UT WOS:A1997WD14100015 PM 9013714 ER PT J AU Clair, T Lee, HY Liotta, LA Stracke, ML AF Clair, T Lee, HY Liotta, LA Stracke, ML TI Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I NUCLEOTIDE PYROPHOSPHATASE; MOTILITY-STIMULATING PROTEIN; MEMBRANE GLYCOPROTEIN PC-1; FIBROBLAST GROWTH-FACTOR; AMINO-ACID-SEQUENCE; ECTO-ATPASE; CDNA CLONING; NEUTROPHIL CHEMOTAXIS; MOLECULAR-CLONING; PLASMA-MEMBRANE AB Autotaxin (ATX) is an extracellular enzyme and an autocrine motility factor that stimulates pertussis toxin-sensitive chemotaxis in human melanoma cells at picomolar to nanomolar concentrations. This 125-kDa glycoprotein contains a peptide sequence identified as the catalytic site in type I alkaline phosphodiesterases (PDEs), and it possesses 5'-nucleotide PDE (EC 3.1.4.1) activity (Stracke, M. L., Krutzsch, H. C., Unsworth, E. J., Arestad, A., Cioce, V., Schiffmann, E., and Liotta, L. (1992) J. Biol. Chem. 267, 2524-2529 Murata, J., Lee, H. Y., Clair, T., Krutsch, H. C., Arestad, A. A., Sobel, M. E., Liotta, L. A., and Stracke, M. L. (1994) J. Biol. Chem. 269, 30479-30484). ATX binds ATP and is phosphorylated only on threonine. Thr(210) at the PDE active site of ATX is required for phosphorylation, 5'-nucleotide PDE, and motility-stimulating activities (Lee, H. Y., Clair, T., Mulvaney, P. T., Woodhouse, E. C., Aznavoorian, S., Liotta, L. A., and Stracke, M. L. (1996) J. Biol. Chem. 271, 24408-24412). In this article we report that the phosphorylation of ATX is a transient event, being stable at 0 degrees C but unstable at 37 degrees C, and that ATX has adenosine-5'-triphosphatase (ATPase; EC 3.6.1.3) and ATP pyrophosphatase (EC 3.6.1.8) activities. Thus ATX catalyzes the hydrolysis of the phosphodiester bond on either side of the beta-phosphate of ATP. ATX also catalyzes the hydrolysis of GTP to GDP and GMP, of either AMP or PPi to P-i, and the hydrolysis of NAD to AMP, and each of these substrates can serve as a phosphate donor in the phosphorylation of ATX. ATX possesses no detectable protein kinase activity toward histone, myelin basic protein, or casein. These results lead to the proposal that ATX is capable of at least two alternative reaction mechanisms, threonine (T-type) ATPase and 5'-nucleotide PDE/ATP pyrophosphatase, with a common site (Thr(210)) for the formation of covalently bound reaction intermediates threonine phosphate and threonine adenylate, respectively. RP Clair, T (reprint author), NCI, PATHOL LAB,DIV CLIN SCI,NIH,BLDG 10, RM 2A33, BETHESDA, MD 20892 USA. NR 48 TC 125 Z9 128 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 10 PY 1997 VL 272 IS 2 BP 996 EP 1001 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800045 PM 8995394 ER PT J AU HendricksTaylor, LR Motto, DG Zhang, J Siraganian, RP Koretzky, GA AF HendricksTaylor, LR Motto, DG Zhang, J Siraganian, RP Koretzky, GA TI SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION PROTEIN; RI CROSS-LINKING; T-CELL; ANTIGEN RECEPTOR; IMMUNOGLOBULIN-E; SIGNAL-TRANSDUCTION; 2H3 CELLS; PHOSPHOLIPASE C-GAMMA-1; MOLECULAR-CLONING; HISTAMINE-RELEASE AB Stimulation of the IgE high affinity receptor on rat basophilic leukemia RBL-2H3 cells results in activation of protein tyrosine kinases and rapid tyrosine phosphorylation of several substrates, many of which remain unidentified. In this report, we demonstrate that the Grb2 adapter protein, when expressed as a glutathione S-transferase fusion protein, associates with four tyrosine-phosphorylated molecules (116, 76, 36, and 31 kDa) from lysates of stimulated RBL-2H3 cells, We show further that the 76-kDa protein is SLP-76, a hematopoietic cell-specific protein first identified as a Grb2-binding protein in T cells, Upon stimulation of the high affinity receptor for IgE, SLP 76 undergoes rapid tyrosine phosphorylation and associates with two additional tyrosine phosphoproteins of 62 and 130 kDa via the SH2 domain of SLP-76. Additional studies demonstrate that the SLP-76 SH2 domain also binds a protein kinase from stimulated RBL-2H3 cell lysates. Furthermore, the phosphorylation of SLP-76 requires Syk activity but is not dependent on Ca+2 mobilization, These data, together with our previous work documenting its role in T cell activation, suggest that SLP-76 and the proteins with which it associates may play a fundamental role in coupling signaling events in multiple cell types in the immune system. C1 UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA 52246. UNIV IOWA,COLL MED,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52246. UNIV IOWA,COLL MED,GRAD PROGRAM IMMUNOL,IOWA CITY,IA 52246. NIDR,NIH,IMMUNOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [R01GM 53256] NR 49 TC 62 Z9 62 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 JAN 10 PY 1997 VL 272 IS 2 BP 1363 EP 1367 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800096 PM 8995445 ER PT J AU Welham, MJ Bone, H Levings, M Learmonth, L Wang, LM Leslie, KB Pierce, JH Schrader, JW AF Welham, MJ Bone, H Levings, M Learmonth, L Wang, LM Leslie, KB Pierce, JH Schrader, JW TI Insulin receptor substrate-2 is the major 170-kDa protein phosphorylated on tyrosine in response to cytokines in murine lymphohemopoietic cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; COLONY-STIMULATING FACTOR; HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; INTERLEUKIN-4 RECEPTOR; COMMON ELEMENTS; GROWTH-HORMONE; IL-4 RECEPTOR; T-LYMPHOCYTES; ACTIVATION AB Insulin receptor substrate 1 (IRS-1), and its structural relative IRS-2, are both phosphorylated on tyrosine following treatment of cells with interleukin-4 (IL-4) and insulin. We have investigated whether both IRS-I and IRS-P are expressed in murine lymphohemopoietic cells. T and B lymphocytes and macrophages from primary cultures expressed only IRS-2, which became phosphorylated on tyrosine following stimulation with both IL-4 and insulin. Likewise, the murine myeloid cell line FD-5 expressed only IRS-2, which was tyrosine phosphorylated in response to IL-4 and insulin, as well as interleukin-3 and granulocyte-macrophage colony stimulating factor. Neither IRS-1 nor IRS-S were expressed at detectable levels in primary bone marrow mast cells although these cells do respond to IL-4. Moreover, a factor-dependent lymphocyte cell line, CT.4S, which grows continuously in IL-4, did not express detectable levels of IRS-1 or IRS-2. IRS-2 from FD-5 cells stimulated with either IL-4 or insulin bound to glutathione S-transferase fusion proteins of the p85 subunit of phosphoinositol 3'-kinase, Grb2, and Syp, paralleling reported associations of IRS-1 with these molecules and indicating phosphorylation of the corresponding residues on IRS-2. C1 UNIV BRITISH COLUMBIA,BIOMED RES CTR,VANCOUVER,BC V6T 1Z3,CANADA. NIH,CELL & MOL BIOL LAB,BETHESDA,MD 20892. RP Welham, MJ (reprint author), UNIV BATH,SCH PHARM & PHARMACOL,PHARMACOL GRP,CALVERTON DOWN,BATH BA2 7AY,AVON,ENGLAND. NR 36 TC 48 Z9 48 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 JAN 10 PY 1997 VL 272 IS 2 BP 1377 EP 1381 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WC048 UT WOS:A1997WC04800098 PM 8995447 ER PT J AU Xu, D Lin, SL Nussinov, R AF Xu, D Lin, SL Nussinov, R TI Protein binding versus protein folding: The role of hydrophilic bridges in protein associations SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein association; free energy; hydrophobicity; solvation effect; salt bridge ID FREE-ENERGY; ELECTROSTATIC ENERGY; SALT BRIDGES; DIELECTRIC-CONSTANT; DESIGNED PROTEIN; ACTIVE-SITE; RECOGNITION; INHIBITOR; DOCKING; LYSOZYME AB The role of hydrophilic bridges between charged, or polar, atoms in protein associations has been examined from two perspectives. First, statistical analysis has been carried out on 21 data sets to determine the relationship between the binding free energy and the structure of the protein complexes. We find that the number of hydrophilic bridges across the binding interface shows a strong positive correlation with the free energy; second, the electrostatic contribution of salt bridges to binding has been assessed by a continuum electrostatics calculation. In contrast to protein folding, we find that salt bridges across the binding interface can significantly stabilize complexes in some cases. The different contributions of hydrophilic bridges to folding and to binding arise from the different environments to which the involved hydrophilic groups are exposed before and after the bridges are formed. These groups are more solvated in a denatured protein before folding than on the surface of the combining proteins before binding. After binding, they are buried in an environment whose residual composition can be much more hydrophilic than the one after folding. As a result, the desolvation cost of a hydrophilic pair is lower, and the favorable interactions between the hydrophilic pair and its surrounding residues are generally stronger in binding than in folding. These results complement our recent finding that while hydrophobic effect in protein-protein interfaces is significant, it is not as strong as that observed in the interior of monomers. Taken together, these studies suggest that while the types of forces in protein-protein interaction and in protein folding are similar, their relative contributions differ. Hence, association of protein monomers which do not undergo significant conformational change upon binding differs from protein folding, implying that conclusions (e.g. statistics, energetics) drawn from investigating folding may not apply directly to binding, and vice versa. (C) 1997 Academic Press Limited C1 NCI,MATH BIOL LAB,SAIC FREDERICK,FCRDC,FREDERICK,MD 21702. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. FU NCI NIH HHS [1-CO-74102] NR 92 TC 210 Z9 213 U1 1 U2 18 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 10 PY 1997 VL 265 IS 1 BP 68 EP 84 DI 10.1006/jmbi.1996.0712 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WB697 UT WOS:A1997WB69700007 PM 8995525 ER PT J AU Paul, W AF Paul, W TI AIDS: The process of discovery SO SCIENCE LA English DT Letter RP Paul, W (reprint author), NIH,OFF AIDS RES,BETHESDA,MD 20892, 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 JAN 10 PY 1997 VL 275 IS 5297 BP 141 EP 141 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC022 UT WOS:A1997WC02200002 ER PT J AU Crespo, P Schuebel, KE Ostrom, AA Gutkind, JS Bustelo, XR AF Crespo, P Schuebel, KE Ostrom, AA Gutkind, JS Bustelo, XR TI Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product SO NATURE LA English DT Article ID TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; HEMATOPOIETIC-CELLS; RAS TRANSFORMATION; SIGNALING PATHWAY; SH2 DOMAIN; B-CELLS; T-CELL; RHO AB THE oncogenic protein Vav(1,2) harbours a complex array of structural motifs, including leucine-rich, Dbl-homology, pleckstrin-homology, zinc-finger, SH2 and SH3 domains, Upon stimulation by antigens or mitogens, Vav becomes phosphorylated on key tyrosine residues(3-5) and associates with other signalling proteins, including the mitogen receptors(3,4) Zap-70 (ref. 6). Vap-1 (ref. 5) and Slp-76 (ref. 7). Disruption of the vav locus by homologous recombination causes severe defects in signalling by primary antigen receptors, leading to abnormal lymphocyte proliferation and lymphopenia(8,9). Despite the importance of Vav cell signalling, the function of this protein remains unknown, Here we show that tyrosine-phosphorylated Vav, but not the non-phosphorylated protein, catalyses GDP/GTP exchange on Rac-1, a protein implicated in cell proliferation and cytoskeletal organization(10,11), causing this GTPase to switch from its inactive to its active state, Transfection experiments also show that phosphorylation of Vav on tyrosine residues leads to nucleotide exchange on Rac-1 in vivo and stimulates c-Jun kinase, a downstream element in the signalling pathway involving this GTPase, Our results have identified a function for Vav and define a mechanism in which engaged membrane receptors activate its signalling pathway. C1 SUNY STONY BROOK,SCH MED,DEPT PATHOL,STONY BROOK,NY 11794. SUNY STONY BROOK,UNIV HOSP,STONY BROOK,NY 11794. NIDR,MOL SIGNALLING UNIT,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. UNIV CANTABRIA,FAC MED,DEPT MOL BIOL,SANTANDER 39011,CANTABRIA,SPAIN. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 24 TC 623 Z9 627 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 9 PY 1997 VL 385 IS 6612 BP 169 EP 172 DI 10.1038/385169a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WB728 UT WOS:A1997WB72800057 PM 8990121 ER PT J AU Hartge, P AF Hartge, P TI Abortion, breast cancer, and epidemiology SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID WOMEN RP Hartge, P (reprint author), NCI,BETHESDA,MD 20892, USA. NR 7 TC 14 Z9 15 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 JAN 9 PY 1997 VL 336 IS 2 BP 127 EP 128 DI 10.1056/NEJM199701093360209 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WC481 UT WOS:A1997WC48100009 PM 8988892 ER PT J AU Chaitman, B Rosen, AD Sopko, G Detre, KM Frye, RL AF Chaitman, B Rosen, AD Sopko, G Detre, KM Frye, RL TI Bypass angioplasty revascularization investigation - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 UNIV PITTSBURGH,PITTSBURGH,PA 15261. NHLBI,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP Chaitman, B (reprint author), ST LOUIS UNIV,ST LOUIS,MO 63110, USA. NR 4 TC 0 Z9 0 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 JAN 9 PY 1997 VL 336 IS 2 BP 137 EP 138 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WC481 UT WOS:A1997WC48100021 ER PT J AU Marks, JR Huper, G Vaughn, JP Davis, PL Norris, J McDonnell, DP Wiseman, RW Futreal, PA Iglehart, JD AF Marks, JR Huper, G Vaughn, JP Davis, PL Norris, J McDonnell, DP Wiseman, RW Futreal, PA Iglehart, JD TI BRCA1 expression is not directly responsive to estrogen SO ONCOGENE LA English DT Article DE BRCA1; estrogen response; cell cycle; antiestrogen; proliferation ID BREAST-CANCER-CELLS; GROWTH-FACTOR; GENE; RECEPTOR; MUTATIONS; TISSUES; DIFFERENTIATION; TRANSCRIPTION; ANTIESTROGENS; CULTURE AB Expression of the breast cancer susceptibility gene, BRCA1, is induced by 17-beta estradiol (E(2)) in estrogen receptor containing breast cancer cell lines, Our previous studies have shown that BRCA1 transcription is also regulated with the cell cycle, reaching maximal levels just before the onset of DNA synthesis, In this study, we have examined whether the estrogen induction of BRCA1 is direct or is a result of the mitogenic activity of the hormone, Four lines of evidence lead us to conclude that E(2) induces BRCA1 primarily through an increase in DNA synthesis: (1) The kinetics and magnitude of induction are different from the directly E(2) inducible gene, pS2; (2) Induction of BRCA1, but not pS2, is blocked by cycloheximide indicating that de novo protein synthesis is required; (3) Other hormonal and growth factor treatments that induce DNA synthesis have a similar effect, including IGF-1, EGF and DNA synthetic flares induced by tamoxifen and retinoic acid; (4) BRCA1 genomic fragments near the 5' end of the gene containing putative estrogen response elements fail to respond to E(2) when transfected into breast cancer cell lines, The most consistent explanation for these findings and other published studies is that BRCA1 transcription is induced as a result of the mitogenic activity of E(2) in estrogen receptor positive cells. C1 DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. RP Marks, JR (reprint author), DUKE UNIV,MED CTR,DEPT SURG,BOX 3873,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA68438, CA61218, CA63786] NR 37 TC 90 Z9 92 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 9 PY 1997 VL 14 IS 1 BP 115 EP 121 DI 10.1038/sj.onc.1200808 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WB760 UT WOS:A1997WB76000011 PM 9010238 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Internet anatomy 101 - Accessing information on the World Wide Web SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NCI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NR 3 TC 11 Z9 11 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 JAN 8 PY 1997 VL 277 IS 2 BP 171 EP 172 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WA650 UT WOS:A1997WA65000041 PM 8990346 ER PT J AU Lee, SP Xiao, JM Knutson, JR Lewis, MS Han, MK AF Lee, SP Xiao, JM Knutson, JR Lewis, MS Han, MK TI Zn2+ promotes the self-association of human immunodeficiency virus type-1 integrase in vitro SO BIOCHEMISTRY LA English DT Article ID COLI ASPARTATE TRANSCARBAMOYLASE; RETROVIRUS-LIKE DNA; HIV-1 INTEGRASE; ESCHERICHIA-COLI; CONCERTED INTEGRATION; IN-VITRO; BINDING AFFINITIES; CATALYTIC DOMAIN; PROTEIN; MUTATIONS AB It has been recently demonstrated that the Mg2+-dependent 3'-processing activity of purified human immunodeficiency virus type-1 (HIV-I) integrase is stimulated by thr addition oi exogenous Zn2+ [Lee, S. P., & Han, M. K. (1996) Biochemistry 35, 3837-3844]. This activation was hypothesized to result from integrase self-association. In this report, we examine the Zn2+ content of purified HIV-1 integrase by atomic absorption spectroscopy and by application of a thiol modification reagent, p-(hydroxymercuri)benzenesulfonate, with a metallochromic indicator, 4-(2-pyridylazo)resorcinol. We find that the Zn2+ content of HIV-1 integrase varies from 0.1 to 0.92 equiv of Zn2+ per monomer depending on the conditions of protein purification. In vitro activity assays, time-resolved fluorescence emission anisotropy, and gel filtration chromatographic analyses all indicate that EDTA yields an apoprotein which is predominantly monomeric and less active with Mg2+. Further, sedimentation equilibrium studies reveal that reconstitution of the apoprotein with Zn2+ results in a monomer-tetramer-octamer transition. These results suggest that Zn2+ promotes a conformation with enhanced oligomerization and thereby stimulates This may also imply that multimers larger than dimers (tetramers and possibly octamers) are required for in vitro activity of integrase in the presence of Zn2+ and Mg2+. It should be noted, however, that the content of Zn2+ did not significantly affect the 3'-processing and strand transfer reactions with Mn2+ in vitro. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 42 TC 120 Z9 126 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 7 PY 1997 VL 36 IS 1 BP 173 EP 180 DI 10.1021/bi961849o PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WB623 UT WOS:A1997WB62300023 PM 8993331 ER PT J AU Quyyumi, AA Mulcahy, D Andrews, NP Husain, S Panza, JA Cannon, RO AF Quyyumi, AA Mulcahy, D Andrews, NP Husain, S Panza, JA Cannon, RO TI Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia - Comparison of acetylcholine and substance P SO CIRCULATION LA English DT Article DE endothelium; hypercholesterolemia; acetylcholine; endothelium-derived factors; hypertension ID ENDOTHELIUM-DEPENDENT VASODILATION; SMOOTH-MUSCLE; RISK-FACTORS; CARDIAC TRANSPLANTATION; MEDIATED VASODILATION; MUSCARINIC RECEPTOR; STIMULATED RELEASE; VARIANT ANGINA; BLOOD-FLOW; L-ARGININE AB Background Whether the abnormal responses of the human coronary circulation to acetylcholine in patients with hypertension and hypercholesterolemia extend to other, nonmuscarinic stimulators of the endothelium and whether this signifies a specific abnormality of NO is not known. Methods and Results We studied 26 patients with angiographically normal coronary arteries, 10 without risk factors, and 16 with either hypertension (n=9) and/or hypercholesterolemia (n=10). Dose-response curves were performed with acetylcholine, substance P, and sodium nitroprusside before and after N-G-monomethyl-L-arginine (L-NMMA). Substance P produced predominantly epicardial coronary dilation, whereas the dilating effect of acetylcholine was mainly microvascular. There was no correlation between the responses to the two drugs. L-NMMA did not affect the response to sodium nitroprusside, but it suppressed dilation in response to both substance P and acetylcholine, suggesting that the latter promote bioavailability of NO from the coronary vascular endothelium. Compared with patients without risks, those with hypercholesterolemia and hypertension had significantly reduced vasodilation with substance P:21% versus 12.6% (P=.004) increase in epicardial coronary diameter and 35% versus 19% (P<.05) decrease in vascular resistance. Similar differences were noted with acetylcholine but not with sodium nitroprusside or adenosine. Epicardial and microvascular dilations with substance P or acetylcholine after L-NMMA were similar in patients with and without risk factors, indicating that the reduced effect of endothelium-dependent vasodilators in those with hypertension and hypercholesterolemia is due to diminished NO activity. Conclusions (1) Substance P- and acetylcholine-induced coronary vasodilation, like that to acetylcholine, is at least partly due to stimulation of NO activity, indicating that the dysfunction of the coronary vascular endothelial cell layer is not restricted to muscarinic receptors. (2) Hypertension and hypercholesterolemia are associated with depression of both basal and pharmacologically stimulated bioavailability of NO. RP Quyyumi, AA (reprint author), NHLBI,CARDIOL BRANCH,NIH,BLDG 10,ROOM 7B15,10 CENTER DR,MSC 1650,BETHESDA,MD 20892, USA. NR 52 TC 111 Z9 118 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 7 PY 1997 VL 95 IS 1 BP 104 EP 110 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WB307 UT WOS:A1997WB30700031 PM 8994424 ER PT J AU Rundqvist, B Elam, M BergmannSverrisdottir, YB Eisenhofer, G Friberg, P AF Rundqvist, B Elam, M BergmannSverrisdottir, YB Eisenhofer, G Friberg, P TI Increased cardiac adrenergic drive precedes generalized sympathetic activation in human heart failure SO CIRCULATION LA English DT Article DE norepinephrine; heart failure; nervous system, autonomic ID FAILING HUMAN HEARTS; NERVOUS ACTIVITY; NOREPINEPHRINE KINETICS; PLASMA NOREPINEPHRINE; BLOOD-FLOW; ISCHEMIA; RELEASE AB Background Previous studies with radiotracer methods have indicated increases in cardiac norepinephrine (NE) and renal NE spillover in patients with severe congestive heart failure (CHF). However, data on the regional sympathetic profile in early stages of CHF are limited. In this study, sympathetic function in the heart, kidneys, and skeletal muscle was evaluated in patients with mild-to-moderate CHF and compared with that in patients with severe CHF and healthy subjects. Methods and Results Total body and regional NE spillover from the heart and kidney was assessed with isotope dilution with steady state infusions of [H-3]NE. Sympathetic nerve traffic to the skeletal muscle vascular bed (MSA) was recorded intraneurally. Cardiac NE spillover in patients with mild-to-moderate CHF (n=21) was increased threefold versus that in healthy subjects (n=12, P<.05), whereas total body and renal NE spillover and MSA did not differ from those in healthy subjects. In the severe CHF group (n=12), cardiac NE spillover was increased fourfold (P<.05), and total body and renal ME spillover and MSA were high compared with both mild-to-moderate CHF subjects and healthy subjects (P<.05 for both). Fractional extraction of [3H]NE across the heart was reduced by approximate to 40% in both CHF groups versus control subjects (P<.05). Conclusions These results indicate a selective increase in cardiac adrenergic drive (increased amounts of transmitter available at neuroeffector junctions) in patients with mild-to-moderate CHF. This increase appears to precede the augmented sympathetic outflow to the kidneys and skeletal muscle found in advanced CHF. C1 SAHLGRENS UNIV HOSP,HEART & LUNG INST,DEPT CLIN PHYSIOL,S-41345 GOTHENBURG,SWEDEN. SAHLGRENS UNIV HOSP,DEPT CLIN NEUROPHYSIOL,INST CLIN NEUROSCI,S-41345 GOTHENBURG,SWEDEN. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Rundqvist, B (reprint author), SAHLGRENS UNIV HOSP,HEART & LUNG INST,DEPT CARDIOL,S-41345 GOTHENBURG,SWEDEN. NR 36 TC 195 Z9 197 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 7 PY 1997 VL 95 IS 1 BP 169 EP 175 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WB307 UT WOS:A1997WB30700040 PM 8994433 ER PT J AU Laks, MM Arzbaecher, R Bailey, JJ Geselowitz, DB Berson, AS AF Laks, MM Arzbaecher, R Bailey, JJ Geselowitz, DB Berson, AS TI Special report: Recommendations for safe current limits for electrocardiographs - Response SO CIRCULATION LA English DT Letter C1 UNIV ILLINOIS,PRITZKER INST TECHNOL,CHICAGO,IL. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. PENN STATE UNIV,STATE COLL,PA 16804. NHLBI,NIH,BETHESDA,MD 20892. RP Laks, MM (reprint author), UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024, USA. NR 0 TC 1 Z9 1 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 JAN 7 PY 1997 VL 95 IS 1 BP 277 EP 278 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WB307 UT WOS:A1997WB30700059 ER PT J AU Clore, GM Gronenborn, AM AF Clore, GM Gronenborn, AM TI Dissecting intrinsic chaperonin activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID MOLECULAR CHAPERONES; POLYPEPTIDE-BINDING; PROTEIN; GROEL; CYCLE RP Clore, GM (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 2,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 38 TC 1 Z9 1 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 JAN 7 PY 1997 VL 94 IS 1 BP 7 EP 8 DI 10.1073/pnas.94.1.7 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700002 PM 8990150 ER PT J AU Kraemer, KH AF Kraemer, KH TI Sunlight and skin cancer: Another link revealed SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID BASAL-CELL CARCINOMA; XERODERMA-PIGMENTOSUM PATIENTS; REPAIR GENE XPA; DNA-REPAIR; P53 GENE; MICE LACKING; ULTRAVIOLET-B; MUTATIONS; UV; TUMORS RP Kraemer, KH (reprint author), NCI,MOL CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 56 TC 265 Z9 268 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 JAN 7 PY 1997 VL 94 IS 1 BP 11 EP 14 DI 10.1073/pnas.94.1.11 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700004 PM 8990152 ER PT J AU Nishikawa, J Kokubo, T Horikoshi, M Roeder, RG Nakatani, Y AF Nishikawa, J Kokubo, T Horikoshi, M Roeder, RG Nakatani, Y TI Drosophila TAF(II)230 and the transcriptional activator VP16 bind competitively to the TATA box-binding domain of the TATA box-binding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA-POLYMERASE-II; IMMEDIATE EARLY PROTEIN; CRYSTAL-STRUCTURE; DNA-BINDING; IN-VIVO; PREINITIATION COMPLEX; PROMOTER INTERACTIONS; TBP; INVITRO; ELEMENT AB The transcription initiation factor TFIID, consisting of the TATA box-binding protein (TBP) and many TBP-associated factors (TAFs), plays a central role in both basal and activated transcription. An intriguing finding is that the 80-residue N-terminal region of Drosophila TAF(II)230 [dTAF(II)230-(2-81)] can bind directly to TBP and inhibit its function, Here, studies with mutated forms of TBP demonstrate that dTAF(II)230-(2-81) binds to the concave surface of TBP, which is important for TATA box binding, Previously, it was reported that a point mutation (L114K) on this concave surface destroys the ability of TBP to bind VP16 and to mediate VP16-dependent activation in vitro, but has no effect on basal transcription. Importantly the same TBP mutation eliminates TBP binding to dTAF(II)230-(2-81). Consistent with these effects of the L114K mutation, dTAF(II)230-(2-81) and the VP16 activation domain compete for binding to wild-type TBP. These results indicate that transcriptional regulation may involve, in part, competitive interactions between transcriptional activators and TAFs on the TBP surface. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. ROCKEFELLER UNIV,BIOCHEM & MOL BIOL LAB,NEW YORK,NY 10021. UNIV TOKYO,INST MOL & CELLULAR BIOSCI,BUNKYO KU,TOKYO 113,JAPAN. NR 38 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 JAN 7 PY 1997 VL 94 IS 1 BP 85 EP 90 DI 10.1073/pnas.94.1.85 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700017 PM 8990165 ER PT J AU Zwanzig, R AF Zwanzig, R TI Two-state models of protein folding kinetics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KRAMERS AB The folding of some proteins appears to be a two-state kinetic process, A two-state kinetic model is justified if protein molecules rapidly equilibrate between different unfolded conformations prior to complete folding, Here I show that this rapid equilibration is a natural consequence of reasonable assumptions about reaction rate constants and folding thermodynamics. RP Zwanzig, R (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 5,ROOM 116,BETHESDA,MD 20892, USA. NR 7 TC 110 Z9 111 U1 0 U2 15 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 JAN 7 PY 1997 VL 94 IS 1 BP 148 EP 150 DI 10.1073/pnas.94.1.148 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700028 PM 8990176 ER PT J AU Wong, ML Bongiorno, PB Rettori, V McCann, SM Licinio, J AF Wong, ML Bongiorno, PB Rettori, V McCann, SM Licinio, J TI Interleukin (IL) 1 beta, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: Pathophysiological implications SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lipopolysaccharide; hormone; behavior; NO; HIV-1 ID HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGES IN-VITRO; MESSENGER-RNA; NEURONAL DAMAGE; CDNA CLONES; RAT-BRAIN; CELLS; RELEASE; LOCALIZATION; CLONING AB The pathophysiology of systemic inflammation and sepsis involves peripheral organs, causing gastrointestinal, renal, and cardiovascular alterations, as well as the central nervous system (CNS), affecting sleep, temperature regulation, behavior, and neuroendocrine function, The molecular basis of the CNS effects of systemic inflammation are not fully elucidated, Here we show that the CNS responds to systemic inflammation with pronounced IL-1 beta gene expression and limited IL-1 receptor antagonist (IL-1ra), IL-10, and IL-13 gene expression, This pattern occurs throughout the CNS, including areas such as the subfornical organ, pineal gland, neurohypophysis, and hypothalamus. In contrast, in the anterior pituitary, we found limited IL-1 beta gene expression but marked induction of the mRNA encoding for the secreted isoform of IL-1ra, secreted IL-1ra. We conclude that the central manifestations of peripheral inflammation are mediated by endogenous brain IL-1 beta synthesized during systemic inflammation in the context of limited central cytokine counter regulation of IL-1. As IL-1 beta is a potent stimulus for inducible nitric oxide synthase expression and activity, these findings explain our previous observation that systemic inflammation promotes inducible nitric oxide synthase gene expression in the brain and the spillover of NO metabolites into cerebrospinal fluid, The CNS transcription of the HIV-1 replication factor IL-1 beta in the context of limited transcription of the IL-1 replication inhibitors IL-1ra, IL-10, and IL-13 might help explain the negative impact of systemic inflammation on the clinical course of AIDS. In addition, we propose that IL-1ra may be secreted by the anterior pituitary as a systemic anti-inflammatory hormone that is released in response to IL-1 beta originated from multiple sources. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. CTR ESTUDIOS FARMACOL & BOT,RA-1414 BUENOS AIRES,DF,ARGENTINA. LOUISIANA STATE UNIV,PENNINGTON BIOMED RES CTR,BATON ROUGE,LA 70808. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 FU NIMH NIH HHS [MH 51853] NR 51 TC 184 Z9 191 U1 0 U2 2 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 JAN 7 PY 1997 VL 94 IS 1 BP 227 EP 232 DI 10.1073/pnas.94.1.227 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700042 PM 8990190 ER PT J AU Pantaleo, G Demarest, JF Schacker, T Vaccarezza, M Cohen, OJ Daucher, M Graziosi, C Schnittman, SS Quinn, TC Shaw, GM Perrin, L Tambussi, G Lazzarin, A Sekaly, RP Soudeyns, H Corey, L Fauci, AS AF Pantaleo, G Demarest, JF Schacker, T Vaccarezza, M Cohen, OJ Daucher, M Graziosi, C Schnittman, SS Quinn, TC Shaw, GM Perrin, L Tambussi, G Lazzarin, A Sekaly, RP Soudeyns, H Corey, L Fauci, AS TI The qualitative nature of the primary immune response to HIV infection is a prognosticator of disease progression independent of the initial level of plasma viremia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE primary infection; prognosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RECOGNITION; V-BETA REPERTOIRE; TYPE-1 INFECTION; MONOZYGOTIC TWINS; RHESUS-MONKEYS; LYMPHOCYTES-T; CD4+; SEROCONVERSION; SEGMENTS AB Following infection of the host with a virus, the delicate balance between virus replication/spread and the immune response to the virus determines the outcome of infection, i.e., persistence versus elimination of the virus, It is unclear, however, what relative roles immunologic and virologic factors play during primary viral infection in determining the subsequent clinical outcome. By studying a cohort of subjects with primary HIV infection, it has been demonstrated that qualitative differences in the primary immune response to HIV, but not quantitative differences in the initial levels of viremia are associated with different clinical outcomes. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,VIROL RES CLIN,SEATTLE,WA 98122. UNIV GENEVA,VIROL LAB,CH-1211 GENEVA,SWITZERLAND. INST RECH CLIN MONTREAL,MONTREAL,PQ H2W 1R7,CANADA. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. RI Quinn, Thomas/A-2494-2010; Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 40 TC 217 Z9 219 U1 0 U2 5 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 JAN 7 PY 1997 VL 94 IS 1 BP 254 EP 258 DI 10.1073/pnas.94.1.254 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700047 PM 8990195 ER PT J AU Bernard, M Klein, DC Zatz, M AF Bernard, M Klein, DC Zatz, M TI Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in culture SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MELATONIN RHYTHM; PHOTOENDOCRINE TRANSDUCTION; CIRCADIAN OSCILLATOR; CYCLIC-AMP; GLAND; CELLS; PACEMAKER; INVITRO; LIGHT AB Melatonin production in the chick pineal gland is high at night and low during the day. This rhythm reflects circadian changes in the activity of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT; EC 2.3.1.87), the penultimate enzyme in melatonin synthesis. In contrast to the external regulation of pineal rhythms in mammals by the suprachiasmatic nucleus, rhythmic changes in AA-NAT activity in cultured chick pineal cells are controlled by an oscillator located in the pineal cells themselves. Here we present evidence that the chick pineal clock generates a rhythm in the abundance of AA-NAT mRNA in cultured cells that parallels the rhythm in AA-NAT activity. In contrast, elevating cAMP hy forskolin treatment markedly increases AA-NAT activity without producing strong changes in AA-NAT mRNA levels, and lowering cAMP by norepinephrine treatment decreases enzyme activity without markedly decreasing mRNA. These results suggest that clock-controlled changes in AA-NAT activity occur primarily through changes at the mRNA level, whereas cAMP-controlled changes occur primarily through changes at the protein level. Related studies indicate that the clock-dependent nocturnal increase in AA-NAT mRNA requires gene expression but not de novo protein synthesis, and that AA-NAT mRNA levels are suppressed at all times of the day by a rapidly turning over protein. Further analysis of the regulation of chick pineal AA-NAT mRNA is likely to enhance our understanding of the molecular basis of vertebrate circadian rhythms. C1 NIMH,SECT BIOCHEM PHARMACOL,LAB CELLULAR & MOL REGULAT,NATL INST HLTH,BETHESDA,MD 20892. NICHHD,SECT NEUROENDOCRINOL,DEV NEUROBIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 25 TC 80 Z9 80 U1 0 U2 2 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 JAN 7 PY 1997 VL 94 IS 1 BP 304 EP 309 DI 10.1073/pnas.94.1.304 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WC347 UT WOS:A1997WC34700056 PM 8990204 ER PT J AU Sarraf, P Frederich, RC Turner, EM Ma, G Jaskowiak, NT Rivet, DJ Flier, JS Lowell, BB Fraker, DL Alexander, HR AF Sarraf, P Frederich, RC Turner, EM Ma, G Jaskowiak, NT Rivet, DJ Flier, JS Lowell, BB Fraker, DL Alexander, HR TI Multiple cytokines and acute inflammation raise mouse leptin levels: Potential role in inflammatory anorexia SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; LEUKEMIA-INHIBITORY FACTOR; CANCER CACHEXIA; OBESE GENE; FACTOR-ALPHA; BODY-WEIGHT; FOOD-INTAKE; NUDE-MICE; INTERLEUKIN-6; CACHECTIN AB Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase ill serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions. C1 NCI,SURG BRANCH,SURG METAB SECT,NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,DIV ENDOCRINOL,BOSTON,MA 02215. FU NHLBI NIH HHS [K08 HL02564]; NIDDK NIH HHS [P30 DK046200, P30 DK46200] NR 38 TC 584 Z9 611 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 6 PY 1997 VL 185 IS 1 BP 171 EP 175 DI 10.1084/jem.185.1.171 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WC028 UT WOS:A1997WC02800017 PM 8996253 ER PT J AU FagotCampagna, A Narayan, KMV Hanson, RL Imperatore, G Howard, BV Nelson, RG Pettitt, DJ Knowler, WC AF FagotCampagna, A Narayan, KMV Hanson, RL Imperatore, G Howard, BV Nelson, RG Pettitt, DJ Knowler, WC TI Plasma lipoproteins and incidence of non-insulin-dependent diabetes mellitus in Pima Indians: Protective effect of HDL cholesterol in women SO ATHEROSCLEROSIS LA English DT Article DE lipoproteins; insulin resistance; glucose; sex; incidence ID IMPAIRED GLUCOSE-TOLERANCE; DISEASE RISK-FACTORS; CARDIOVASCULAR RISK; FOLLOW-UP; RESISTANCE; MEN; POPULATION; PREVALENCE; PREDICTORS; NIDDM AB The role of plasma lipoproteins in the development of non-insulin-dependent diabetes mellitus (NIDDM) was studied in 787 non-diabetic (2-h glucose < 11.1 mmol/l) Pima Indians (265 men and 522 women). Subjects were followed for a mean of 9.8 (range: 1.8-16.4) years, during which 261 (76 men and 185 women) developed NIDDM. In men and women, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, low-density lipoprotein triglyceride and total triglyceride, controlled for age, predicted NIDDM (P < 0.01 for each). These effects diminished when controlled for age, sex, body mass index, systolic blood pressure and 2-h glucose. However, high-density lipoprotein (HDL) cholesterol, controlled for age, body mass index, systolic blood pressure and 2-h glucose, was a significant protective factor for NIDDM in women (hazard rate ratio (HRR) = 0.35, 95% CI (0.23-0.54), P < 0.001, 90th compared with 10th percentile) but not in men (HRR = 1.04, 95% CI (0.53-2.05), P = 0.915). This association remained significant in women when controlled for fasting or 2-h plasma insulin concentrations, other estimates of insulin resistance or alcohol consumption. The protective effect of HDL cholesterol was similar among women with normal (2-h glucose < 7.8 mmol/l) or impaired (7.8 mmol/l less than or equal to 2-h glucose < 11.1 mmol/l) glucose tolerance at baseline. These results indicate that lipoprotein disorders are an early accompaniment of the abnormalities that lead to NIDDM. C1 MEDLANTIC RES INST,WASHINGTON,DC. RP FagotCampagna, A (reprint author), NIDDKD,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 NR 47 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN 3 PY 1997 VL 128 IS 1 BP 113 EP 119 DI 10.1016/S0021-9150(96)05978-3 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WG248 UT WOS:A1997WG24800013 PM 9051204 ER PT J AU Motojima, K Peters, JM Gonzalez, FJ AF Motojima, K Peters, JM Gonzalez, FJ TI PPAR alpha mediates peroxisome proliferator-induced transcriptional repression of nonperoxisomal gene expression in mouse SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RAT-LIVER; ACTIVATED RECEPTORS; ACID; CLOFIBRATE; SEQUENCE; FAMILY; COA AB The strain difference, peroxisome proliferator specificity and role of PPAR alpha in peroxisome proliferator-induced transcriptional repression of nonperoxisomal transthyretin and alpha(2u)-globulin genes were examined. The genes were repressed by four peroxisome proliferators in all seven mouse strains tested. The extent of repression was strongly dependent on both the mouse strains and type of proliferator, although the mRNA levels of PPAR alpha and its partner in heterodimerization, RXR alpha were not different, The role of PPAR alpha in repression was confirmed by the finding that PPAR alpha-null mice were not responsive to transcriptional repression, These results indicate that PPAR alpha plays an obligatory role in transcription of various genes, some of which are not related to lipid metabolism. (C) 1997 Academic Press C1 NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Motojima, K (reprint author), TOHO UNIV,SCH PHARMACEUT SCI,DEPT BIOCHEM,FUNABASHI,CHIBA 274,JAPAN. RI Peters, Jeffrey/D-8847-2011 NR 21 TC 33 Z9 33 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 JAN 3 PY 1997 VL 230 IS 1 BP 155 EP 158 DI 10.1006/bbrc.1996.5906 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WC043 UT WOS:A1997WC04300035 PM 9020034 ER PT J AU Hirai, A Nakamura, S Noguchi, Y Yasuda, T Kitagawa, M Tatsuno, I Oeda, T Tahara, K Terano, T Narumiya, S Kohn, LD Saito, Y AF Hirai, A Nakamura, S Noguchi, Y Yasuda, T Kitagawa, M Tatsuno, I Oeda, T Tahara, K Terano, T Narumiya, S Kohn, LD Saito, Y TI Geranylgeranylated rho small GTPase(s) are essential for the degradation of p27(Kip1) and facilitate the progression from G(1) to S phase in growth-stimulated rat FRTL-5 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COENZYME-A REDUCTASE; ADP-RIBOSYLTRANSFERASE; CYCLE PROGRESSION; GENE-PRODUCT; 3T3 CELLS; INHIBITOR; ACTIVATION; PROTEIN; KINASE; PROLIFERATION AB Cyclin-dependent kinase (Cdk) enzymes are activated for entry into the S phase of the cell cycle. Elimination of Cdk inhibitor protein p27(Kip1) during the G(1) to S phase is required for the activation process. An inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase prevents its elimination and leads to G(1) arrest. Mevalonate and its metabolite, geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, restore the inhibitory effect of pravastatin on the degradation of p27 and allow Cdk2 activation. By the addition of geranylgeranyl pyrophosphate, Rho small GTPase(s) are geranylgeranylated and translocated to membranes during G(1)/S progression. The restoring effect of geranylgeranyl pyrophosphate is abolished with botulinum C3 exoenzyme, which specifically inactivates Rho. These results indicate (i) among mevalonate metabolites, geranylgeranyl pyrophosphate is absolutely required for the elimination of p27 followed by Cdk2 activation; (ii) geranylgeranylated Rho small GTPase(s) promote the degradation of p27 during G(1)/S transition in FRTL-5 cells. C1 OKAYAMA UNIV,SCH MED,INST CELLULAR & MOL BIOL,DEPT CELL CHEM,OKAYAMA 700,JAPAN. MERCK RES LABS,BANYU TSUKUBA RES INST,TSUKUBA,IBARAKI 30026,JAPAN. CHIBA MUNICIPAL HOSP,DEPT INTERNAL MED,CHUO KU,CHIBA 260,JAPAN. KYOTO UNIV,FAC MED,DEPT PHARMACOL,SAKYO KU,KYOTO 606,JAPAN. NIDDK,METAB RES BRANCH,CELL REGULAT SECT,NIH,BETHESDA,MD 20892. RP Hirai, A (reprint author), CHIBA UNIV,SCH MED,DEPT INTERNAL MED 2,CHUO KU,1-8-1 INOHANA CHO,CHIBA 260,JAPAN. NR 32 TC 188 Z9 189 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 JAN 3 PY 1997 VL 272 IS 1 BP 13 EP 16 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400003 PM 8995216 ER PT J AU Zhu, YA Lambert, K Corless, C Copeland, NG Gilbert, DJ Jenkins, NA DAndrea, AD AF Zhu, YA Lambert, K Corless, C Copeland, NG Gilbert, DJ Jenkins, NA DAndrea, AD TI DUB-2 is a member of a novel family of cytokine-inducible deubiquitinating enzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-CELL-LINE; FAT-FACETS GENE; PROTEIN-DEGRADATION; ANTIGEN RECEPTOR; ISOPEPTIDASE-T; TRE ONCOGENE; UBIQUITIN; MECHANISM; PROTEASOMES; ERYTHROPOIETIN AB Cytokines regulate cell growth by inducing the expression of specific target genes. We have recently identified a cytokine-inducible, immediate-early gene, DUB-1, that encodes a deubiquitinating enzyme with growth regulatory activity. In the current study, we have isolated a highly related gene, DUB-2, that is induced by interleukin-2. The DUB-2 mRNA was induced in T cells as an immediate-early gene and was rapidly down-regulated. Like DUB-1, the DUB-2 protein had deubiquitinating activity in vitro. When a conserved cysteine residue of DUB-2, required for ubiquitin-specific thiol protease activity, was mutated to serine (C60S), deubiquitinating activity was abolished. DUB-1 and DUB-2 proteins are highly related throughout their primary amino acid sequence except for a hypervariable region at their COOH terminus. Moreover, the DUB genes co-localize to a region of mouse chromosome 7, suggesting that they arose by a tandem duplication of an ancestral DUB gene. Additional DUB genes co-localize to this region, suggesting a larger family of cytokine-inducible DUB enzymes. We propose that different cytokines induce specific DUB genes. Each induced DUB enzyme thereby regulates the degradation or the ubiquitination state of an unknown growth regulatory factor, resulting in a cytokine-specific growth response. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [T32CA09361-16]; NIDDK NIH HHS [R01 DK 43889-01] NR 53 TC 95 Z9 96 U1 0 U2 3 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 JAN 3 PY 1997 VL 272 IS 1 BP 51 EP 57 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400013 PM 8995226 ER PT J AU Wang, WJ Acs, P Goodnight, JA Giese, T Blumberg, PM Mischak, H Mushinski, JF AF Wang, WJ Acs, P Goodnight, JA Giese, T Blumberg, PM Mischak, H Mushinski, JF TI The catalytic domain of protein kinase C-delta in reciprocal delta and epsilon chimeras mediates phorbol ester-induced macrophage differentiation of mouse promyelocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NIH 3T3 FIBROBLASTS; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; REGULATORY DOMAIN; PKC-DELTA; ISOZYMES; LOCALIZATION; ACTIVATION; ISOFORM; ALPHA AB The overexpression of protein kinase C-delta (PKC-delta), but not PKC-epsilon, enables the mouse myeloid cell line 32D to differentiate into macrophages when treated with phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). To determine the domain of PKC-delta that is responsible for this isotype-specific function, cDNAs that encode reciprocal chimeras of PKC-delta and -epsilon (PKC-delta epsilon and PKC-epsilon delta) were constructed by exchanging regulatory and kinase domains using polymerase chain reaction technology. Both chimeras were stably expressed in 32D cells using the pLTR expression vector and displayed protein kinase activity upon TPA treatment. TPA treatment of L epsilon delta, cells that overexpressed the PKC-epsilon delta chimera, induced a dramatically increased cell volume, surface adherence, surface expression of Mac-1 and Mac-3, lysozyme production, and phagocytosis. These are the characteristics of the macrophage phenotype found in TPA-treated 32D cells that overexpressed PKC-delta. In contrast, little effect was seen in L delta epsilon, 32D cells that overexpressed PKC-delta epsilon, with or without TPA treatment. A PKC inhibitor directed toward the catalytic domain of PKC, GF109203X, and a selective inhibitor of PKC-delta, Rottlerin, blocked the TPA-induced differentiation of PKC-epsilon delta-overexpressing 32D cells. These results demonstrate that the catalytic domain of PKC-delta contains the primary determinants for its activity in phorbol ester-induced macrophage differentiation. C1 NIH,GENET LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011 NR 31 TC 8 Z9 8 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 JAN 3 PY 1997 VL 272 IS 1 BP 76 EP 82 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400017 ER PT J AU Parrizas, M Saltiel, AR LeRoith, D AF Parrizas, M Saltiel, AR LeRoith, D TI Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IGF-I RECEPTOR; PROGRAMMED CELL-DEATH; HEMATOPOIETIC-CELLS; SIGNAL-TRANSDUCTION; PC12 CELLS; 3-KINASE; NEURONS; PURIFICATION; FIBROBLASTS; STIMULATION AB The role of insulin-like growth factor 1 (IGF-1) in preventing apoptosis was examined in differentiated PC12 cells, Induction of differentiation was achieved using nerve growth factor, and apoptosis was provoked by serum withdrawal. After 4-6 h of serum deprivation, apoptosis was initiated, concomitant with a 30% decrease in cell number and a 75% decrease in MTT activity, IGF-1 was capable of preventing apoptosis at concentrations as low as 10(-9) M and as early as 4 h. The phosphatidylinositol 3' (PI3')-kinase inhibitors wortmannin (at concentrations of 10(-8) M) and LY294002 (10(-6) M) blocked the effect of IGF-1. The pp70 S6 kinase (pp70(S6K)) inhibitor rapamycin (10(-8) M) was, however, less effective in blocking IGF-1 action. Moreover, stable transfection of a dominant-negative p85 (subunit of PI3'-kinase) construct in PC12 cells enhanced apoptosis provoked by serum deprivation. Interestingly, in the cells overexpressing the dominant-negative p85 protein, IGF-1 was still capable of inhibiting apoptosis, suggesting the existence of a second pathway involved in the IGF-1 effect. Blocking the mitogen-activated protein kinase pathway with the specific mitogen-activated protein kinase/extracellular-response kinase kinase inhibitor PD098059 (10(-5) M) inhibited the IGF-1 effect, When wortmannin and PD098059 mere given together, the effect was synergistic. The results presented here suggest that IGF-1 is capable of preventing apoptosis by activation of multiple signal transduction pathways. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT SIGNAL TRANSDUCT,ANN ARBOR,MI 48105. UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48105. OI Saltiel, Alan/0000-0002-9726-9828 NR 44 TC 531 Z9 543 U1 0 U2 7 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 JAN 3 PY 1997 VL 272 IS 1 BP 154 EP 161 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400028 PM 8995241 ER PT J AU Bae, YS Kang, SW Seo, MS Baines, IC Tekle, E Chock, PB Rhee, SG AF Bae, YS Kang, SW Seo, MS Baines, IC Tekle, E Chock, PB Rhee, SG TI Epidermal growth factor (EGF)-induced generation of hydrogen peroxide - Role in EGF receptor-mediated tyrosine phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; PHOSPHOLIPASE C-II; SIGNAL-TRANSDUCTION; AUTOPHOSPHORYLATION SITES; HUMAN-FIBROBLASTS; POINT MUTATION; BINDING-SITES; OXYGEN; H2O2 AB Recent evidence indicates that reactive oxygen species (ROS) may function as intracellular messengers in receptor signaling pathways. The possible role of ROS in epidermal growth factor (EGF) signaling was therefore investigated. Stimulation of A431 human epidermoid carcinoma cells with EGF resulted in a transient increase in the intracellular concentration of ROS, measured with the oxidation-sensitive fluorescent probe 2',7'-dichlorofluorescin diacetate and laser-scanning confocal microscopy. The predominant ROS produced appeared to be H2O2, because the EGF-induced increase in fluorescence was completely abolished by incorporation of catalase into the cells by electroporation. The elimination of H2O2 by catalase also inhibited the EGF-induced tyrosine phosphorylation of various cellular proteins including the EGF receptor and phospholipase C-gamma 1. The dependence of H2O2 production on the intrinsic tyrosine kinase activity of the EGF receptor and the autophosphorylation sites located in its COOH-terminal tail was investigated. EGF failed to induce H2O2 generation in cells expressing a kinase-inactive EGF receptor. However, normal H2O2 generation was observed in cells expressing a mutant receptor from which the 126 COOH-terminal amino acids had been deleted to remove four (out of the total of five) autophosphorylation sites. These results suggest that EGF-induced H2O2 formation requires the kinase activity but probably not the autophosphorylation sites of the EGF receptor and that inhibition of protein tyrosine phosphatase activity by H2O2 may be required for EGF-induced protein tyrosine phosphorylation to be manifested. C1 NHLBI,CELL SIGNALING LAB,NIH,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 50 TC 878 Z9 897 U1 3 U2 45 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 JAN 3 PY 1997 VL 272 IS 1 BP 217 EP 221 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400037 PM 8995250 ER PT J AU Hirschman, JE DeZutter, GS Simonds, WF Jenness, DD AF Hirschman, JE DeZutter, GS Simonds, WF Jenness, DD TI The G beta gamma complex of the yeast pheromone response pathway - Subcellular fractionation and protein-protein interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; SIGNAL TRANSDUCTION PATHWAY; ALPHA-FACTOR PHEROMONE; TRIMERIC-G-PROTEINS; SACCHAROMYCES-CEREVISIAE; MATING-PHEROMONE; ADAPTIVE RESPONSE; BINDING PROTEIN; SUBUNIT; GENE AB Genetic evidence suggests that the yeast STE4 and STE18 genes encode G beta and G gamma subunits, respectively, that the G beta gamma complex plays a positive role in the pheromone response pathway, and that its activity is subject to negative regulation by the G alpha subunit (product of the GPA1 gene) and to positive regulation by cell-surface pheromone receptors, However, as yet there is no direct biochemical evidence for a G beta gamma protein complex associated with the plasma membrane, We found that the products of the STE4 and STE18 genes are stably associated with plasma membrane as well as with internal membranes and that 30% of the protein pool is not tightly associated with either membrane fraction, A slower-migrating, presumably phosphorylated, form of Ste4p is enriched in the non-membrane fraction, The Ste4p and Ste18p proteins that had been extracted from plasma membranes with detergent were found to cosediment as an 8 S particle under low salt conditions and as a 6 S particle in the presence of 0.25 M NaCl; the Ste18p in these fractions was precipitated with anti-Ste4p antiserum, Under the conditions of our assay, Gpa1p was not associated with either particle. The levels of Ste4p and Ste18p accumulation in mutant cells provided additional evidence for a G beta gamma complex. Ste18p failed to accumulate in ste4 mutant cells, and Ste4p showed reduced levels of accumulation and an increased rate of turnover in ste18 mutant cells. The gpa1 mutant blocked stable association of Ste4p with the plasma membrane, and the ste18 mutant blocked stable association of Ste4p with both plasma membranes and internal membranes, The membrane distribution of Ste4p was unaffected by the ste2 mutation or by down-regulation of the cell-surface receptors, These results indicate that at least 40% of Ste4p and Ste18p are part of a G beta gamma complex at the plasma membrane and that stable association of this complex with the plasma membrane requires the presence of G alpha. C1 UNIV MASSACHUSETTS,SCH MED,DEPT MOL GENET & MICROBIOL,WORCESTER,MA 01655. NIDDK,MDB,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM34719] NR 68 TC 36 Z9 36 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 JAN 3 PY 1997 VL 272 IS 1 BP 240 EP 248 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400041 PM 8995254 ER PT J AU Kim, DH Chang, JH Lee, KH Lee, HY Kim, SJ AF Kim, DH Chang, JH Lee, KH Lee, HY Kim, SJ TI Mechanism of E1A-induced transforming growth factor-beta (TGF-beta) resistance in mouse keratinocytes involves repression of TGF-beta type II receptor transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CYCLIN-A; MICROSATELLITE INSTABILITY; PROMOTER REGION; CANCER CELLS; E1A PROTEINS; GENE; EXPRESSION; FACTOR-BETA-1; INHIBITION; DIFFERENTIATION AB Cellular transformation driven by the E1A oncogene is associated with the development of cellular resistance to the growth inhibitory effects of transforming growth factor-beta (TGF-beta). We demonstrate that development of resistance occurs simultaneously with decreased expression of TGF-beta type II receptor (TGF-beta RII) mRNA and protein, To determine whether changes in transcriptional regulation are responsible for the decreased receptor expression in E1A-transformed cells, a series of mobility shift assays was performed utilizing nuclear extracts from E1A-transformed and untransformed murine keratinocytes using radiolabeled positive regulatory elements (PRE1 and PRE2) of the TGF-beta RII promoter. The results from these assays suggest that E1A-transformed cells express markedly lower levels of nuclear proteins that bind specifically to PRE1 and PRE2, Transfection of both E1A-transformed and untransformed cell lines with a series of mutant promoter constructs confirmed that both PREs contribute significantly to basal expression of TGF-beta RII and that inactivation of either element leads to markedly reduced promoter activity. We conclude that development of TGF-beta resistance in E1A-transformed cells is achieved in part through transcriptional down-regulation of the TGF-beta RII gene and that this down-regulation is the result of decreased expression of unidentified transcription factor complexes that interact with PRE1 and PRE2. C1 NCI, CHEMOPREVENT LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. NR 39 TC 36 Z9 36 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 JAN 3 PY 1997 VL 272 IS 1 BP 688 EP 694 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WA564 UT WOS:A1997WA56400100 PM 8995313 ER PT J AU WatanabeAkanuma, M Woodgate, R Ohta, T AF WatanabeAkanuma, M Woodgate, R Ohta, T TI Enhanced generation of A:T->T:A transversions in a recA730 lexA51(Def) mutant of Escherichia coli SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE A:T->T:A transversion; mutational specificity; mutA; mutC; mutD; umuDC ID ALLOW RAPID DETECTION; DNA POLYMERASE-III; MUTATIONAL SPECIFICITY; CHEMICAL MUTAGENESIS; SOS MUTAGENESIS; MISMATCH REPAIR; LACZ MUTATIONS; SAMAB OPERONS; PROTEIN; CLEAVAGE AB RecA730 belongs to a class of mutant RecA protein that is often referred to as RecA*, since it is constitutively activated for coprotease functions in the absence of exogenous DNA-damage. Escherichia coli strains carrying recA730 (or other recA* alleles) exhibit dramatic increases in SOS-dependent spontaneous mutator activity. We have analyzed the specificity of this mutator phenotype by employing F'-plasmids carrying a set of mutant lacZ genes that can individually detect two types of transitions, four types of transversions, and four kinds of specific frameshift events. Analysis revealed that most of the spontaneous mutagenesis in a recA730 lexA5I(Def) strain (which expresses derepressed levels of all LexA-regulated proteins) can be attributed to a specific increase in A:T --> T:A, A:T --> C:G and G:C --> T:A transversions, with the A:T --> T:A transversions occurring most frequently. These transversion events were completely abolished in a Delta umuDC strain, indicating that the functionally active UmuD'C proteins are normally required for their generation. The spectrum obtained was similar to that of strains with a defect in the epsilon (3' --> 5' proofreading) subunit of DNA polymerase III. Such an observation raises the possibility that the wild-type epsilon protein is in activated in strains expressing the RecA730 and UmuD'C proteins. C1 NICHHD,BETHESDA,MD 20892. TOKYO UNIV PHARM & LIFE SCI,SCH LIFE SCI,HACHIOJI,TOKYO 19203,JAPAN. RP WatanabeAkanuma, M (reprint author), INST ENVIRONM TOXICOL,SUZUKI CHO 2-772,KODAIRA,TOKYO 187,JAPAN. NR 28 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JAN 3 PY 1997 VL 373 IS 1 BP 61 EP 66 DI 10.1016/S0027-5107(96)00189-3 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WD742 UT WOS:A1997WD74200008 PM 9015154 ER PT J AU Tsutsui, T Hayashi, N Maizumi, H Huff, J Barrett, JC AF Tsutsui, T Hayashi, N Maizumi, H Huff, J Barrett, JC TI Benzene-, catechol-, hydroquinone- and phenol-induced cell transformation, gene mutations, chromosome aberrations, aneuploidy, sister chromatid exchanges and unscheduled DNA synthesis in Syrian hamster embryo cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE benzene; benzene metabolite; cell transformation; genetic effect; Syrian hamster embryo cell ID NEOPLASTIC TRANSFORMATION; B6C3F1 MICE; MORPHOLOGICAL TRANSFORMATION; HUMAN-LYMPHOCYTES; RISK ASSESSMENT; POTENTIAL ROLE; METABOLISM; TOXICITY; CARCINOGENICITY; EXPOSURE AB Benzene is a human carcinogen present naturally in petroleum and gasoline. For the simultaneous assessment of benzene-induced carcinogenicity and mutagenicity, benzene and its principal metabolites, phenol, catechol and hydroquinone were examined for their ability to induce cell transformation and genotoxic effects using the same mammalian cells in culture. Each of the four compounds induced morphological transformation of Syrian hamster embryo (SHE) cells. Catechol was the most potent, inducing transformation at concentrations of 1-30 mu M, followed by hydroquinone (3-30 mu M), phenol (10-100 mu M) and benzene (only at 100 mu M). Gene mutations at two loci in SHE cells were induced by all four compounds, with catechol being the most potent; both ouabain-resistant and 6-thioguanine-resistant mutant frequencies were increased. Chromosomal aberrations in SHE cells were especially induced by catechol, lesser by hydroquinone, and to a marginal extent by phenol at only the 100 mu M concentration, whereas sister chromatid exchanges in SHE cells occurred with hydroquinone (1-30 mu M), catechol (10-30 mu M) and phenol (1000-3000 mu M). Aneuploidy in the near diploid range of SHE cells was significantly induced by benzene and catechol. All three metabolites induced unscheduled DNA synthesis in SHE cells, whereas benzene did not. This is the first report that the cell transforming activity and mutagenicity of benzene and its metabolites were assessed with the same mammalian cells in culture. The results provide evidence that benzene and several of its metabolites art: cell transforming and genotoxic to cultured mammalian cells. C1 NIEHS, ENVIRONM CARCINOGENESIS PROGRAM, NIH, RES TRIANGLE PK, NC 27709 USA. NIPPON DENT UNIV TOKYO, SCH DENT, DEPT PHARMACOL, CHIYODA KU, TOKYO 102, JAPAN. NR 57 TC 103 Z9 106 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JAN 3 PY 1997 VL 373 IS 1 BP 113 EP 123 DI 10.1016/S0027-5107(96)00196-0 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WD742 UT WOS:A1997WD74200014 PM 9015160 ER PT J AU Bernstein, SL Borst, DE Wong, P AF Bernstein, SL Borst, DE Wong, P TI Region specific mitochondrial gene expression in the human retina SO BRAIN RESEARCH LA English DT Article DE mitochondria; differential gene expression; fovea; retina ID HEREDITARY OPTIC NEUROPATHY; OXYGEN DISTRIBUTION; CONSUMPTION; DNA; RAT; CEREBELLUM; GENOTYPE; GENOME; CAT AB The human mitochondrial genome has not been previously known to differentially express specific mRNA transcripts. Results of northern analysis, using total RNA from two different retinal regions, demonstrate that there is differential expression of five mitochondrial genes. There is a correlation of regional expression of one of these differentially expressed genes with the gene responsible for the majority of cases of foveo-macular mitochondropathy. These findings suggest that there is selective control over specific mitochondrial messenger steady state levels. C1 NEI,NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. RP Bernstein, SL (reprint author), UNIV MARYLAND,DEPT OPHTHALMOL,22 S GREENE ST,BALTIMORE,MD 21201, USA. NR 21 TC 1 Z9 1 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 JAN 2 PY 1997 VL 744 IS 1 BP 143 EP 146 DI 10.1016/S0006-8993(96)00947-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA WD518 UT WOS:A1997WD51800018 PM 9030423 ER PT J AU Rekharsky, MV Mayhew, MP Goldberg, RN Ross, PD Yamashoji, Y Inoue, Y AF Rekharsky, MV Mayhew, MP Goldberg, RN Ross, PD Yamashoji, Y Inoue, Y TI Thermodynamic and nuclear magnetic resonance study of the reactions of alpha- and beta-cyclodextrin with acids, aliphatic amines, and cyclic alcohols SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID INCLUSION COMPLEXES; AQUEOUS-SOLUTION; BENZOIC-ACIDS; BINDING; TITRATION; WATER; CYCLOMALTOHEXAOSE; CYCLOHEXAAMYLOSE; RECOGNITION; MECHANISMS AB Titration calorimetry was used to determine equilibrium constants and standard molar enthalpy, Gibbs energy, and entropy changes for the reactions of a series of acids, amines, and cyclic alcohols with alpha- and beta-cyclodextrin. The results have been examined in terms of structural features in the ligands such as the number of alkyl groups, the charge number, the presence of a double bond, branching, and the presence of methyl and methoxy groups. The values of thermodynamic quantities, in particular the standard molar Gibbs energy, correlate well with the structural features in the ligands. These structural correlations can be used for the estimation of thermodynamic quantities for related reactions. Enthalpy-entropy compensation is evident when the individual classes of substances studied herein are considered, but does not hold when these various classes of ligands are considered collectively. The NMR results indicate that the mode of accommodation of the acids and amines in the alpha-cyclodextrin cavity is very similar, but that the 1-methyl groups in 1-methylhexylamine and in 1-methylheptylamine and the N-methyl group in N-methylhexylamine lie outside the alpha-cyclodextrin cavity. This latter finding is consistent with the calorimetric results. Many of the thermodynamic and NMR results can be qualitatively understood in terms of van der Waals forces and hydrophobic effects. C1 NIST,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. NIH,MOL BIOL LAB,BETHESDA,MD 20892. OSAKA UNIV,FAC ENGN,DEPT MOL CHEM,SUITA,OSAKA 565,JAPAN. NR 46 TC 145 Z9 145 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 2 PY 1997 VL 101 IS 1 BP 87 EP 100 DI 10.1021/jp962715n PG 14 WC Chemistry, Physical SC Chemistry GA WL102 UT WOS:A1997WL10200014 ER PT B AU Doszkocs, TE AF Doszkocs, TE BE Nixon, C Dengler, H Yersak, J TI Real virtual libraries: the technology SO 12TH ANNUAL COMPUTERS IN LIBRARIES '97, PROCEEDINGS LA English DT Proceedings Paper CT 12th Computers in Libraries Conference (CIL 97) CY MAR 10-12, 1997 CL ARLINGTON, VA SP Informat Today Inc C1 NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 BN 1-57387-040-4 PY 1997 BP 23 EP 29 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA BJ45V UT WOS:A1997BJ45V00009 ER PT B AU Thoma, GR Hauser, SE Ford, G Stroman, R AF Thoma, GR Hauser, SE Ford, G Stroman, R BE Nixon, C Dengler, H Yersak, J TI Automating document delivery: A case study SO 12TH ANNUAL COMPUTERS IN LIBRARIES '97, PROCEEDINGS LA English DT Proceedings Paper CT 12th Computers in Libraries Conference (CIL 97) CY MAR 10-12, 1997 CL ARLINGTON, VA SP Informat Today Inc C1 NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,COMMUN ENGN BRANCH,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 BN 1-57387-040-4 PY 1997 BP 137 EP 139 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA BJ45V UT WOS:A1997BJ45V00032 ER PT S AU Johnson, CA Seidel, J Carson, RE Gandler, WR Sofer, A Green, MV DaubeWitherspoon, ME AF Johnson, CA Seidel, J Carson, RE Gandler, WR Sofer, A Green, MV DaubeWitherspoon, ME BE DelGuerra, A TI Evaluation of 3D reconstruction algorithms for a small animal PET camera SO 1996 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT 1996 IEEE Nuclear Science Symposium and Medical Imaging Conference CY NOV 02-09, 1996 CL ANAHEIM, CA SP IEEE AB The use of paired, opposing position-sensitive phototube scintillation cameras (SCs) operating in coincidence for small animal imaging with positron emitters is currently under study. Because of the low sensitivity of the system even in 3D mode and the need to produce images with high resolution, it was postulated that a 3D expectation maximization (EM) reconstruction algorithm might be well suited for this application. We investigated four reconstruction algorithms for the 3D SC PET camera: 2D filtered back-projection (FBP), 2D ordered subset EM (OSEM), 3D reprojection (3DRP), and 3D OSEM. Noise was assessed for all slices by the coefficient of variation in a simulated uniform cylinder. Resolution was assessed from a simulation of 15 point sources in the warm background of the uniform cylinder. At comparable noise levels, the resolution achieved with OSEM (0.9-mm to 1.2-mm) is significantly better than that obtained with FBP or 3DRP (1.5-mm to 2.0-mm.) Images of a rat skull labeled with F-18-fluoride suggest that 3D OSEM can improve image quality of a small animal PET camera. RP Johnson, CA (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 1082-3654 BN 0-7803-3535-X J9 IEEE NUCL SCI CONF R PY 1997 BP 1481 EP 1485 PG 5 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BH59W UT WOS:A1997BH59W00319 ER PT S AU DaubeWitherspoon, ME Carson, RE AF DaubeWitherspoon, ME Carson, RE BE DelGuerra, A TI Investigation of angular and axial smoothing of PET data SO 1996 IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT 1996 IEEE Nuclear Science Symposium and Medical Imaging Conference CY NOV 02-09, 1996 CL ANAHEIM, CA SP IEEE AB Radial filtering of emission and transmission data is routinely performed in PET during reconstruction in order to reduce image noise. Angular smoothing is not typically done, due to the introduction of a non-uniform resolution loss; axial filtering is also not usually performed on data acquired in 2D mode. The goal of this paper was to assess the effects of angular and axial smoothing on noise and resolution. Angular and axial smoothing was incorporated into the reconstruction process on the Scanditronix PC2048-15B brain PET scanner. In-plane spatial resolution and noise reduction were measured for different amounts of radial and angular smoothing. For radial positions away from the center of the scanner, noise reduction and degraded tangential resolution with no loss of radial resolution were seen. Near the center, no resolution loss was observed, but there was also no reduction in noise for angular filters up to a 70 FWHM. These results can be understood by considering the combined effects of smoothing projections across rows (angles) and then summing (back-projecting). Thus, angular smoothing is not optimal due to its anisotropic noise reduction and resolution degradation properties. However, uniform noise reduction comparable to that seen with radial filtering can be achieved with axial smoothing of transmission data. The axial results suggest that combined radial and axial transmission smoothing could lead to improved noise characteristics with more isotropic resolution degradation. RP DaubeWitherspoon, ME (reprint author), NIH,POSITRON EMISS TOMOG DEPT,BLDG 10-1C497,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 1082-3654 BN 0-7803-3535-X J9 IEEE NUCL SCI CONF R PY 1997 BP 1557 EP 1561 PG 5 WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BH59W UT WOS:A1997BH59W00334 ER PT B AU Aldroubi, A Feichtinger, H AF Aldroubi, A Feichtinger, H GP IEEE COMP SOC TI Complete iterative reconstruction algorithms for irregularly sampled data in spline-like spaces SO 1997 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS I - V: VOL I: PLENARY, EXPERT SUMMARIES, SPECIAL, AUDIO, UNDERWATER ACOUSTICS, VLSI; VOL II: SPEECH PROCESSING; VOL III: SPEECH PROCESSING, DIGITAL SIGNAL PROCESSING; VOL IV: MULTIDIMENSIONAL SIGNAL PROCESSING, NEURAL NETWORKS - VOL V: STATISTICAL SIGNAL AND ARRAY PROCESSING, APPLICATIONS LA English DT Proceedings Paper CT 1997 IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP 97) CY APR 21-24, 1997 CL MUNICH, GERMANY SP IEEE Signal Proc Soc, DPG, GI, ITG, TUM AB We prove that the exact reconstruction of a function s from its samples s(x(i)) on any ''sufficiently dense'' sampling set {x(i)}(i is an element of I) subset of R-n, where I is a countable indexing set, can be obtained for a large class of spline-like spaces that belong to L-p(R-n). Moreover, The reconstruction can be implemented using fast algorithms. Since, a special case is the space of bandlimited functions, our result generalizes the classical Shannon-whittacker sampling theorem on regular sampling and the Paley-Wiener theorem on nonuniform sampling. RP Aldroubi, A (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU I E E E, COMPUTER SOC PRESS PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, LOS ALAMITOS, CA 90720 BN 0-8186-7920-4 J9 INT CONF ACOUST SPEE PY 1997 BP 1857 EP 1860 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BH95E UT WOS:A1997BH95E00466 ER PT B AU Vrhel, MJ Aldroubi, A AF Vrhel, MJ Aldroubi, A GP IEEE COMP SOC TI Pre-filtering for the initialization of multi-wavelet transforms SO 1997 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS I - V: VOL I: PLENARY, EXPERT SUMMARIES, SPECIAL, AUDIO, UNDERWATER ACOUSTICS, VLSI; VOL II: SPEECH PROCESSING; VOL III: SPEECH PROCESSING, DIGITAL SIGNAL PROCESSING; VOL IV: MULTIDIMENSIONAL SIGNAL PROCESSING, NEURAL NETWORKS - VOL V: STATISTICAL SIGNAL AND ARRAY PROCESSING, APPLICATIONS LA English DT Proceedings Paper CT 1997 IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP 97) CY APR 21-24, 1997 CL MUNICH, GERMANY SP IEEE Signal Proc Soc, DPG, GI, ITG, TUM AB We introduce a new method for initializing the multi-wavelet decomposition algorithm. The approach assumes that the input signal is contained within some well-defined subspace of L-2 (e.g. space of bandlimited functions). The initialization algorithm is the orthogonal projection of the input signal into the space defined by the multi-scaling function. Unlike an interpolation approach, the projection method will always have a solution. We provide examples and implementation details. RP Vrhel, MJ (reprint author), NATL INST HLTH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NCRR,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E, COMPUTER SOC PRESS PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, LOS ALAMITOS, CA 90720 BN 0-8186-7920-4 J9 INT CONF ACOUST SPEE PY 1997 BP 2033 EP 2036 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BH95E UT WOS:A1997BH95E00510 ER PT B AU Unser, M Zerubia, J AF Unser, M Zerubia, J GP IEEE COMP SOC TI Generalized sampling without bandlimiting constraints SO 1997 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS I - V: VOL I: PLENARY, EXPERT SUMMARIES, SPECIAL, AUDIO, UNDERWATER ACOUSTICS, VLSI; VOL II: SPEECH PROCESSING; VOL III: SPEECH PROCESSING, DIGITAL SIGNAL PROCESSING; VOL IV: MULTIDIMENSIONAL SIGNAL PROCESSING, NEURAL NETWORKS - VOL V: STATISTICAL SIGNAL AND ARRAY PROCESSING, APPLICATIONS LA English DT Proceedings Paper CT 1997 IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP 97) CY APR 21-24, 1997 CL MUNICH, GERMANY SP IEEE Signal Proc Soc, DPG, GI, ITG, TUM AB We investigate the problem of the reconstruction of a continuous-time function f(x) is an element of H from the responses of m linear shift-invariant systems sampled at 1/m the reconstruction rate, extending Papoulis' generalized sampling theory in two important respects. First, we allow for arbitrary (non-bandlimited) input signals (typ. H = L-2). Second, we use a more general specification of the reconstruction subspace V(phi), so that the output of the system can take the form of a bandlimited function, a spline, or a wavelet expansion. The system that we describe-yields an approximation (f) over tilde is an element of V(phi) that is consistent with the input f(x) in the sense that it produces exactly the same measurements. We show that this solution can be computed by multivariate filtering. We also characterize the stability of the system (condition number). Finally, we illustrate the theory by presenting a new example of interlaced sampling using splines. RP Unser, M (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E, COMPUTER SOC PRESS PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, LOS ALAMITOS, CA 90720 BN 0-8186-7920-4 J9 INT CONF ACOUST SPEE PY 1997 BP 2113 EP 2116 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BH95E UT WOS:A1997BH95E00530 ER PT B AU Shi, LMM Fan, Y Myers, TG Weinstein, JN AF Shi, LMM Fan, Y Myers, TG Weinstein, JN GP IEEE TI Genetic function approximation in the molecular pharmacology of cancer SO 1997 IEEE INTERNATIONAL CONFERENCE ON NEURAL NETWORKS, VOLS 1-4 LA English DT Proceedings Paper CT 1997 IEEE International Conference on Neural Networks (ICNN 97) CY JUN 09-12, 1997 CL HOUSTON, TX SP IEEE, Neural Networks Council AB The National Cancer Institute's Developmental Therapeutics Program screens more than 10,000 compounds per year for their ability to inhibit growth of 60 human cancer cell lines. Using a combination of cross-validated back-propagation neural networks and multivariate statistical methods, we found that a compound's mechanism of action could be predicted with considerable accuracy solely on the basis of its pattern of growth inhibitory activity against the 60 cell lines (Weinstein, et al., Science 258: 447, 1992, Weinstein, et al., Science 275: 343, 1997). Over the last several years, the developments, in terms of different mathamatical approaches, led to formulation of a general ''information-intensive'' strategy for drug discovery that integrates data on a compound's molecular structure, pattern of growth inhibitory activity, and possible molecular targets in the cell. Here we will summarize our recent investigations of a new approach to the regression problem, ''genetic function approximation'' (GFA). RP Shi, LMM (reprint author), NCI,DIV BASIC SCI,MOL PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-4123-6 PY 1997 BP 2490 EP 2493 PG 4 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BJ42Y UT WOS:A1997BJ42Y00473 ER PT B AU Wen, H Bennett, E Shah, J Balaban, RS AF Wen, H Bennett, E Shah, J Balaban, RS BE Schneider, SC Levy, M McAvoy, BR TI An imaging method using the interaction between ultrasound and magnetic field SO 1997 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 & 2 LA English DT Proceedings Paper CT 1997 IEEE Ultrasonics Symposium CY OCT 05-08, 1997 CL TORONTO MARRIOTT EATON CTR, TORONTO, CANADA SP IEEE, Ultrason Ferroelect & Frequency Control Soc HO TORONTO MARRIOTT EATON CTR AB A new imaging method using the classical Hall effect has been developed in the context of diagnostic applications. "Hall effect imaging" (HET) relies on ultrasonic signal generated by a pulsed current through the sample in a strong magnetic field. Hall effect images reflect the dielectric distribution of the sample. Phantom images have been collected. with a single crystal sensor. Since dielectric parameters vary greatly among soft tissues and between normal and pathological states, HEI holds promises for human imaging. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Wen, H (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-4153-8 PY 1997 BP 1407 EP 1410 PG 4 WC Acoustics; Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BK64T UT WOS:000072927100302 ER PT B AU Fuhrer, M Rintala, D Hart, K AF Fuhrer, M Rintala, D Hart, K BE Ueda, S Nakamura, R Ishigami, S TI Interrelationships among psychological stress and the components of disablement for people with spinal-cord injury SO 8TH WORLD CONGRESS OF THE INTERNATIONAL REHABILITATION MEDICINE ASSOCIATION (IRMA VIII), PTS 1-2 LA English DT Proceedings Paper CT 8th World Congress of the International-Rehabilitation-Medicine-Association (IRMA VIII) CY AUG 31-SEP 04, 1997 CL KYOTO, JAPAN SP Int Rehab Med Assoc AB The hypothesis was confirmed that the average level of psychological stress for people with spinal cord injuries (SCI) who are living in the community is higher than the average for people in the general population. Stress levels are particularly higher for women with SCI. Individual differences in stress levels were not correlated significantly with either the extent of participants' paralytic impairment or their degree of disability, objectively assessed. Stress levels were generally unrelated to several objectively assessed dimensions of handicap, but they were related in several instances to participants' subjective appraisals of various handicap-related domains of living. Those relationships, too, reflected the influence of gender. RP Fuhrer, M (reprint author), NIH,NATL CTR MED REHABIL RES,ROCKVILLE,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY BN 88-323-0831-2 PY 1997 BP 693 EP 697 PG 5 WC Rehabilitation SC Rehabilitation GA BJ98X UT WOS:A1997BJ98X00115 ER PT B AU Fuhrer, M AF Fuhrer, M BE Ueda, S Nakamura, R Ishigami, S TI Subjective quality of life: conceptual and empirical relationships with the components of disablement SO 8TH WORLD CONGRESS OF THE INTERNATIONAL REHABILITATION MEDICINE ASSOCIATION (IRMA VIII), PTS 1-2 LA English DT Proceedings Paper CT 8th World Congress of the International-Rehabilitation-Medicine-Association (IRMA VIII) CY AUG 31-SEP 04, 1997 CL KYOTO, JAPAN SP Int Rehab Med Assoc AB Ten published studies based an 11 distinct samples of people with various physically disabling conditions were reviewed from the standpoint of reported relationships between subjective well-being (subjective quality of life) and specific aspects of impairment, disability, and handicap. In general, subjective well-being was consistently related to various aspects of handicap and almost as consistently to aspects of disability. Directionally, the relationships indicated that more severe handicap and disability were associated with lower levels of subjective well-being. Insufficient data were available to assess relationships involving impairments. RP Fuhrer, M (reprint author), NIH,NATL CTR MED REHABIL RES,ROCKVILLE,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY BN 88-323-0831-2 PY 1997 BP 701 EP 705 PG 5 WC Rehabilitation SC Rehabilitation GA BJ98X UT WOS:A1997BJ98X00116 ER PT J AU Pinn, VW Chunko, MT AF Pinn, VW Chunko, MT TI The diverse faces of violence: Minority women and domestic abuse SO ACADEMIC MEDICINE LA English DT Article ID POPULATION AB In research and clinical practice, the failure to detect and/or elicit information about domestic abuse is exacerbated by social, economic, and cultural factors. Because domestic violence cannot be separated from the cultural and social context in which it occurs, such factors must be integrated into research studies and the development of interventions. The National Institutes of Health's expanded guidelines on the inclusion in its clinical trials of women from all ethnic and racial backgrounds, along with an increased recognition of the importance of socioeconomic and psychosocial factors in health and disease, has strengthened efforts to improve prove understanding of domestic violence in diverse communities. The involvement of researchers from minority communities is crucial to the success of such efforts. Study of the relationships among race, ethnicity, culture, and domestic violence must be fully incorporated into medical school curricula to sensitize students and enable them to develop the skills needed to detect more effectively deal with, and ultimately prevent, family and intimate violence. C1 NIH,OFF WOMENS HLTH,BETHESDA,MD 20892. NR 31 TC 14 Z9 14 U1 1 U2 7 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 1997 VL 72 IS 1 SU S BP S65 EP S71 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA WE235 UT WOS:A1997WE23500011 PM 9008589 ER PT B AU Wenthold, RJ Wang, YX Petralia, RS Rubio, ME AF Wenthold, RJ Wang, YX Petralia, RS Rubio, ME BE Syka, J TI Distribution and targeting of glutamate receptors in the cochlear nucleus SO ACOUSTICAL SIGNAL PROCESSING IN THE CENTRAL AUDITORY SYSTEM LA English DT Proceedings Paper CT International Symposium on Acoustical Signal Processing in the Central Auditory System CY SEP 04-07, 1996 CL PRAGUE, CZECH REPUBLIC RP Wenthold, RJ (reprint author), NATL INST DEAFNESS OTHER COMMUN DISORDERS,LAB NEUROCHEM,NIH,36 COVENT DR,BLDG 36,ROOM 5D08,BETHESDA,MD 20892, USA. RI Syka, Josef/H-3103-2014 NR 0 TC 10 Z9 10 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45608-7 PY 1997 BP 93 EP 107 DI 10.1007/978-1-4419-8712-9_10 PG 15 WC Engineering, Biomedical; Neurosciences; Otorhinolaryngology SC Engineering; Neurosciences & Neurology; Otorhinolaryngology GA BJ70G UT WOS:A1997BJ70G00010 ER PT J AU Aneman, A Ponten, J Fandriks, L Eisenhofer, G Friberg, P Biber, B AF Aneman, A Ponten, J Fandriks, L Eisenhofer, G Friberg, P Biber, B TI Hemodynamic, sympathetic and angiotensin II responses to PEEP ventilation before and during administration of isoflurane SO ACTA ANAESTHESIOLOGICA SCANDINAVICA LA English DT Article DE angiotensin II; hemodynamics; isoflurane; norepinephrine; PEEP-ventilation ID END-EXPIRATORY PRESSURE; SPLANCHNIC HEMODYNAMICS; INDUCED HYPOTENSION; NERVE ACTIVITY; RENAL-FUNCTION; LUNG INJURY; BLOOD-FLOW; PIGS; CAPACITANCE; ANESTHESIA AB Background: Positive end-expiratory pressure (PEEP) ventilation and isoflurane anesthesia may opposingly affect the sympathetic nervous and renin-angiotensin systems. This study was performed to elucidate the modulatory effects of isoflurane anesthesia on the neurohumoral and cardiovascular responses to PEEP. Methods: Renin-angiotensin and sympathetic nervous activity were investigated in mechanically ventilated, normovolemic, chloralose anesthetized pigs before and during administration of 1.4% isoflurane. Arterial angiotensin II (AII) concentrations were measured and systemic, mesenteric, hepatic and renal spillover of norepinephrine (NE-SO) were calculated using isotope dilution. Regional hemodynamic variables were investigated in parallel. Results: PEEP10 alone moderately elevated AII levels (+12.5 +/-4.9 pg/ml, P<0.05) and increased systemic (+22+/-2.9 pmol . min . 100g(-1), P<0.05) and notably mesenteric (+32+/-9.6 pmol . min . 100g(-1), P<0.05) NE-SO. Blood flow decreased in all vascular beds studied. Except for in the liver, isoflurane generally reduced NE-SO compared to baseline but did not change AII concentrations, Strikingly, the sympathoexcitatory response to PEEP10 was inhibited, whereas AII increased markedly (+284+/-64 pg/ml, P<0.05) during PEEP10 and isoflurane. renal blood flow was significantly more reduced during PEEP10 and isoflurane compared to PEEP10 alone, whereas the magnitude of reductions were similar in the other vascular beds. Conclusion: The data suggest that renin-angiotensin activation is important to attenuate the impact of PEEP ventilation on cardiovascular performance during administration of the sympathodepressant isoflurane. Interference with the renin-angiotensin system may cause cardiovascular decompensation in isoflurane anesthetized patients subjected to PEEP-ventilation. C1 GOTHENBURG UNIV,DEPT CLIN PHYSIOL,S-41345 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT PHYSIOL,S-41345 GOTHENBURG,SWEDEN. UMEA UNIV HOSP,DEPT ANESTHESIOL,S-90185 UMEA,SWEDEN. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Aneman, A (reprint author), GOTHENBURG UNIV,DEPT ANESTHESIOL & INTENS CARE,S-41345 GOTHENBURG,SWEDEN. NR 32 TC 16 Z9 16 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-5172 J9 ACTA ANAESTH SCAND JI Acta Anaesthesiol. Scand. PD JAN PY 1997 VL 41 IS 1 BP 41 EP 48 PN 1 PG 8 WC Anesthesiology SC Anesthesiology GA WH413 UT WOS:A1997WH41300008 PM 9061113 ER PT J AU Rosenfeld, SJ Gralnick, HR AF Rosenfeld, SJ Gralnick, HR TI Adhesive interactions in hemostasis SO ACTA HAEMATOLOGICA LA English DT Review DE integrins; von Willebrand factor; fibrinogen; collagen; GPIIb/IIIa; GPIb/IX ID GLYCOPROTEIN-IIB-IIIA; BERNARD-SOULIER-SYNDROME; COMPLEMENTARY DEOXYRIBONUCLEIC-ACID; COLLAGEN-INDUCED AGGREGATION; VIII-VONWILLEBRAND-FACTOR; LEUCINE-RICH REPEAT; GAMMA-CHAIN; HUMAN-FIBRINOGEN; PLATELET RECEPTOR; ALPHA-CHAIN AB Adhesion molecules and adhesive interactions play a critical role in the process of hemostasis. A vascular rent requires a patch, and this patch must be provided from constituents of the cellular and fluid phases of flowing blood, constituents that must not interfere with this flow under unperturbed conditions. Platelets, the cellular elements of the parch, are inert until they encounter conditions that trigger their activation. In response to injury they undergo a rapid and dramatic change both in shape and in their surface characteristics, a change that allows them to become both the nidus and the stimulus for the precipitation of a meshwork of fibrin. The interactions between platelets and exposed collagen in the damaged vessel wall, plasma and platelet von Willebrand factor, and plasma and platelet fibrinogen can all be considered 'adhesive interactions'. RP Rosenfeld, SJ (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,BLDG 10,RM 2C390,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 111 TC 10 Z9 10 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1997 VL 97 IS 1-2 BP 118 EP 125 PG 8 WC Hematology SC Hematology GA VY778 UT WOS:A1997VY77800016 PM 8980617 ER PT J AU Qazilbash, MH Liu, JM Vlachos, A Fruchtman, S Messner, H Zipursky, A Alter, BP Young, NS AF Qazilbash, MH Liu, JM Vlachos, A Fruchtman, S Messner, H Zipursky, A Alter, BP Young, NS TI A new syndrome of familial aplastic anemia and chronic liver disease SO ACTA HAEMATOLOGICA LA English DT Article DE activated cytotoxic T lymphocytes; bone marrow failure; chronic liver disease; gamma-interferon ID BONE-MARROW FAILURE; STRATEGIES; THERAPY AB This report describes a new familial syndrome characterized by a combination of bone marrow failure and chronic liver disease. This disorder appears to be genetic in origin with an autosomal dominant inheritance and was characterized by hyperactivity of the immune system with increased activated cytotoxic T lymphocytes in peripheral blood and bone marrow and the presence of gamma-interferon messenger RNA in bone marrow of several cases. C1 NHLBI,NIH,HEMATOL BRANCH,BETHESDA,MD 20892. MT SINAI SCH MED,DIV PEDIAT HEMATOL ONCOL,NEW YORK,NY. PRINCESS MARGARET HOSP,ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. HOSP SICK CHILDREN,DIV PEDIAT HEMATOL ONCOL,TORONTO,ON,CANADA. UNIV TEXAS,MED BRANCH,DIV PEDIAT HEMATOL ONCOL,CHILDRENS HOSP,GALVESTON,TX 77550. NR 11 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5792 J9 ACTA HAEMATOL-BASEL JI Acta Haematol. PY 1997 VL 97 IS 3 BP 164 EP 167 PG 4 WC Hematology SC Hematology GA WJ222 UT WOS:A1997WJ22200006 PM 9066711 ER PT J AU Kordek, R Liberski, PP Yanagihara, R Isaacson, S Gajdusek, DC AF Kordek, R Liberski, PP Yanagihara, R Isaacson, S Gajdusek, DC TI Molecular analysis of prion protein (PrP) and glial fibrillary acidic protein (GFAP) transcripts in experimental Creutzfeldt-Jakob disease in mice SO ACTA NEUROBIOLOGIAE EXPERIMENTALIS LA English DT Article DE prion protein; glial fibrillary acidic ID NECROSIS-FACTOR-ALPHA; ASTROGLIAL PROLIFERATION; GENE-EXPRESSION; TRANSGENIC MICE; SCRAPIE; ASTROCYTES; BRAIN; INTERLEUKIN-1; NEURODEGENERATION; PROPAGATION AB Prion protein (PrPSC) which accumulates in the brains affected with subacute spongiform encephalopathies (SSE) is altered isoform of normal, cellular isoform (PrPC), and PrP deposition is accompanied with spongiosis and astrogliosis. To find the amounts of PrP and GFAP transcripts during progression of experimental Creutzfeldt-Jakob disease we performed comparative RT-PCR on the terminally sick mice brains, 22 weeks following inoculation with Fujisaki strain of CJD agent, and on control brains. The intensity of bands for PrP-mRNA and control beta-actin were similar for infected and uninfected brains, while amounts of transcripts for GFAP increased as for cytokines released by glial cells - TNF-alpha and IL-1 alpha. This study supports thesis that PrPC to PrPSC conversion is post-translational process not related to PrP overproduction. Increased amounts of GFAP-mRNA during the course of the disease correlated with astrocytosis estimated by immunohistochemistry with anti-GFAP antibody. C1 MED ACAD,CHAIR ONCOL,LAB TUMOR BIOL,PL-93509 LODZ,POLAND. MED ACAD,CHAIR ONCOL,DEPT TUMOR PATHOL,PL-93509 LODZ,POLAND. RP Kordek, R (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. RI Kordek, Radzislaw/S-9616-2016 NR 38 TC 17 Z9 17 U1 1 U2 1 PU NENCKI INST EXPERIMENTAL BIOLOGY PI WARSAW PA UL PASTEURA 3, 02-093 WARSAW, POLAND SN 0065-1400 J9 ACTA NEUROBIOL EXP JI Acta Neurobiol. Exp. PY 1997 VL 57 IS 2 BP 85 EP 90 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XA580 UT WOS:A1997XA58000001 PM 9407695 ER PT J AU Bakketeig, LS Hoffman, HJ Jacobsen, G Hagen, JA Storvik, BE AF Bakketeig, LS Hoffman, HJ Jacobsen, G Hagen, JA Storvik, BE TI Intrauterine growth pattern by the tendency to repeat small-for-gestational-age births in successive pregnancies SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE intrauterine growth retardation; small-for-gestational-age ID WEIGHT; RISK AB Background. Fetuses of women who repeat small-for-gestational-age births in successive pregnancies may have a different intrauterine growth pattern than SGA birth of non-repeater mothers. Also repeated SGA births may grow differently depending on whether the tendency to repeat is due to some external factors such as cigarette smoking (''false repeaters'') or due to genetic or intrinsic factors (''true repeaters''). Material and methods. Fetal growth were compared in a ''nested case-control'' study within a longitudinal. (cohort) study, comparing three types of SGA births, 23 of ''true repeater'' mothers, 46 of ''false repeater'' mothers and 65 of non-repeater mothers, and these were compared with 1017 non-SGA births. Fetal growth was compared using a regression analysis based on repeated measurements (four for each woman). Results. For mean abdominal diameter the ''true repeater'' SGA births grew more slowly towards the end of pregnancy. However, the growth curves show only minor differences between the three types of SGA births, but the patterns are grossly different from the growth of non-SGA births (controls). Conclusion. The intrauterine growth retardation starts early in pregnancy, and is not strikingly different between births of repeater and non-repealer mothers. C1 NATL INST DEAFNESS & COMMUN DISORDERS,NIH,BETHESDA,MD. NORWEGIAN UNIV SCI & TECHNOL,DEPT GEN PRACTICE & COMMUNITY MED,N-7034 TRONDHEIM,NORWAY. UNIV OSLO,DEPT STAT,OSLO,NORWAY. RP Bakketeig, LS (reprint author), NATL INST PUBL HLTH,DEPT POPULAT HLTH SCI,POSTBOKS 4404 TORSHOV,N-6403 OSLO,NORWAY. NR 9 TC 4 Z9 4 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 3 EP 7 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200002 ER PT J AU Goldenberg, RL Cliver, SP Neggers, Y Copper, RL DuBard, MD Davis, RO Hoffman, HJ AF Goldenberg, RL Cliver, SP Neggers, Y Copper, RL DuBard, MD Davis, RO Hoffman, HJ TI The relationship between maternal characteristics and fetal and neonatal anthropometric measurements in women delivering at term: A summary SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE birthweight; ultrasound biometry; risk factors; neonatal anthropometric measurements ID LOW-BIRTH-WEIGHT; GESTATIONAL-AGE; RISK-FACTORS; INTRAUTERINE GROWTH; SIZE; SEX; DETERMINANTS; RETARDATION; POPULATION; PREGNANCY AB Background We wanted to determine the relationship between a number of maternal characteristics and various fetal and neonatal anthropometric measurements determined by ultrasound and at birth. Methods. A total of 1205 term singleton maternal-infant pairs were studied, Various ultrasound measurements obtained at 18, 24, 30 and 36 weeks' gestation and neonatal anthropometric measurements obtained at birth were studied in relationship to various maternal characteristics using univariate and multivariate techniques. Results. Black race, female sex, cigarette smoking, drug use, having a previous low birthweight infant, maternal hypertension and being short or thin or failing to gain weight each resulted in a birthweight decrease of 100 to 300 g. The effect of each of these characteristics on each ultrasound measurement, the timing of the effect, and its ultimate effect on neonatal anthropometric measurements are described. Conclusion. The data presented in this paper provide a more complete understanding of the relationship between maternal characteristics, infant sex, and various fetal ultrasound and neonatal measurements. C1 UNIV ALABAMA,DEPT HUMAN NUTR,TUSCALOOSA,AL. NICHHD,PREVENT RES PROGRAM,NIH,BETHESDA,MD 20892. RP Goldenberg, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,CTR OBSTET RES,618 S 20TH ST,OHB 560,BIRMINGHAM,AL 35233, USA. FU NICHD NIH HHS [N01-HD-4-2811]; PHS HHS [282-92-0055] NR 21 TC 7 Z9 9 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 8 EP 13 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200003 PM 9219450 ER PT J AU Jacobsen, G Schei, B Hoffman, HJ AF Jacobsen, G Schei, B Hoffman, HJ TI Psychosocial factors and small-for-gestational-age infants among parous Scandinavian women SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE psychosocial factors; small-for-gestational-age; parous women; Scandinavia ID LOW-BIRTH-WEIGHT; PRETERM DELIVERY; PREGNANCY; STRESS AB Background. We wanted to analyze the association between small-for-gestational-age (SGA) births, defined as a newborn with a birthweight below the 15th percentile-for-gestational age, and socioeconomic and psychosocial risk factors. Methods. Information on social background, psychological status, and life events was collected prospectively by use of questionnaires in the second and third trimester of pregnancy. The respondents were 1552 women who expected their second or third child and took part in a Scandinavian multicenter study of fetal growth and perinatal outcome. Results. No significant differences were found in relational stress, state and trait anxiety, depression, and physical strain between SGA and non-SGA births, whereas smoking around time of conception and low prepregnant body mass were significant SGA birth predictors. Maternal and paternal education of nine years or less increased the SGA birth risk (RR 1.46 (95% CL 1.12; 1.92) and RR 1.34 (95% CL 1.01; 1.79), respectively. The increased risk from a low maternal education was still significant when body mass and low paternal education were controlled, but not after adjustment for maternal smoking. A protective effect of paternal, but not maternal, education of 12 years or more was also observed and retained its effect when maternal smoking and body mass were controlled. Conclusion. In this seemingly homogeneous Scandinavian population, parental education and maternal body proportion and life style influenced the prevalence of small-for-gestational-age births. Relational stress, anxiety depression, and physical strain did not influence birth outcome. C1 NORWEGIAN UNIV SCI & TECHNOL,DEPT COMMUNITY MED & GEN PRACTICE,N-7034 TRONDHEIM,NORWAY. NATL INST DEAFNESS & COMMUN DISORDERS,NIH,BETHESDA,MD. NR 20 TC 7 Z9 7 U1 1 U2 8 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 14 EP 18 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200004 ER PT J AU Goldenberg, RL Hickey, CA Cliver, SP Gotlieb, S Woolley, TW Hoffman, HJ AF Goldenberg, RL Hickey, CA Cliver, SP Gotlieb, S Woolley, TW Hoffman, HJ TI Abbreviated scale for the assessment of psychosocial status in pregnancy: Development and evaluation SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE pregnancy; psychosocial status; abbreviated psychosocial scale ID PRETERM DELIVERY; BIRTH-WEIGHT; STRESS; OUTCOMES; GROWTH; WOMEN AB Background. Data from five existing psychosocial scales were used to develop an abbreviated scale for the assessment of psychosocial status during pregnancy. Methods. Scales were self-administered by 842 black and 381 white low-income multiparous women at risk for poor pregnancy outcome. Trait anxiety (Speilberger), self-esteem (Rosenberg), mastery (Pearlin), and depression (CES-D) were assessed at 24-26 weeks' gestation; subjective stress (Schar) was assessed at 30-32 weeks' gestation. The 59 pooled items were examined for redundancy and the discernment of primary factors using principal factor analysis. Regression analysis was used to determine if the resulting abbreviated scale (28 items) would provide information similar to that obtained with the 59 item pool (full scale) in predicting gestational age (GA), birth weight (BW), fetal growth restriction (FGR), and preterm delivery (PTD). Results. The abbreviated scale was highly correlated (r = 0.97) with the 59-item pool and the six factors isolated were generally compatible with the major characteristics assessed by the five original scales. The distribution of FGR and PTD by scale quartile was similar for the abbreviated and the combined scales. Logistic regression analysis of scores for all women revealed that poor (high) scores on both the full (p = 0.0151) and the abbreviated scales (p = 0.0131) were positively associated with FGR, but not with PTD. In linear regression analysis poor (high) scores on both the full (p = 0.0024) and the abbreviated scale (p = 0.0019) were negatively related to BW, but not to GA. When data for black and white women were examined separately, the two scares provided comparable information. Conclusions. The abbreviated psychosocial. scale provided information similar to that obtained with 59 pooled items in predicting GA, BW, FGR, and PTD. C1 UNIV ALABAMA,SCH PUBL HLTH,DEPT MATERNAL & CHILD HLTH,BIRMINGHAM,AL 35294. SAMFORD UNIV,SCH BUSINESS,BIRMINGHAM,AL. NATL INST DEAFNESS & COMMUN DISORDERS,EPIDEMIOL STAT & DATA SYST BRANCH,NIH,BETHESDA,MD. RP Goldenberg, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,SCH MED,CTR OBSTET RES,618 SO 20TH ST,OHB 560,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [1-HD-4-2811]; PHS HHS [282-92-0055, MCJ-9040] NR 20 TC 12 Z9 12 U1 1 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 19 EP 29 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200005 PM 9219452 ER PT J AU Magnus, P Bakketeig, LS Hoffman, H AF Magnus, P Bakketeig, LS Hoffman, H TI Birth weight of relatives by maternal tendency to repeat small-for-gestational-age (SGA) births in successive pregnancies SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE small-for-gestational-age; birth weight; parents AB Background and method. Small-for-gestational-age (SGA) infants represent a heterogeneous group of normal and growth-retarded children. To assess the familial aggregation of reduced fetal growth, birth weights in both maternal and paternal relatives of 1246 index children in the Scandinavian SGA Study were compared across groups defined by the SGA outcome of the index child as well as that of earlier siblings. Results. Mean maternal birth weight +/- SEM was 3127 +/- 54 g for mothers who had experienced two SGA births as opposed to 3424 +/- 22 for mothers with no SGA births. Mean paternal birth weight was 3497 +/- 88 g and 3665 +/- 24 in the same two groups. The odds ratio (with 95% confidence interval) for having a mother with birth weight below the 10th percentile was 1.74 (0.85-3.58) for the group where two SGA births had occurred compared to no SGA births and it was 2.49 (1.22-5.07) for having a father with birth weight below the 10th percentile. There was no correlation between maternal and paternal birth weights. Conclusions. The association also to paternal birth weight suggests the presence of genetic or common environmental factors in explaining the tendency to have SGA children. Although taking parental birth weights into consideration will aid in diagnosing growth-retardation in a SGA child, SGA remains a heterogeneous group where familial and non-familial cases will be difficult to separate. C1 NATL INST PUBL HLTH,DEPT EPIDEMIOL,N-0462 OSLO,NORWAY. NICHHD,NIH,BETHESDA,MD 20892. NR 12 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 35 EP 38 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200007 ER PT J AU Markestad, T Bergsjo, P Aakvaag, A Lie, RT Jacobsen, G Hoffman, HJ Bakketeig, LS AF Markestad, T Bergsjo, P Aakvaag, A Lie, RT Jacobsen, G Hoffman, HJ Bakketeig, LS TI Prediction of fetal growth based on maternal serum concentrations of human chorionic gonadotropin, human placental lactogen and estriol SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE human chorionic gonadotropin; human placental lactogen; estriol; fetal growth; small for gestational age ID BIRTH-WEIGHT; PREGNANCIES; RETARDATION; MANAGEMENT; INFANTS; HPL AB Background. The purpose was to determine the usefulness of maternal serum concentrations of human chorionic gonadotropin (hCG), human placental lactogen (hPL) and estriol as predictors of fetal growth. Method. From a large cohort serum obtained serially at 17, 25, 33 and 37 weeks of gestation were analyzed for randomly selected pregnancies resulting in small for gestational age (SGA, n = 102) and non-SGA (n = 112) infants. Results. There were no significant correlations between birthweight ratio (ratio of birthweight to mean weight for gestational age) and hCG, but between birthweight ratio on one hand and estriol for all stages of pregnancy (r = 0.19-0.38, p < 0.01 - p < 0.001) and hCL except at 33 weeks (r = 0.11 - 0.40, p ns - p < 0.001) on the other. There were statistically significant, but small median differences and substantial overlaps between the SGA and non-SGA infants for hCG at 17 and 37 weeks, for hPL at 17, 33 and 37 weeks, and for estriol at all the stages of pregnancy. The sensitivity and positive predictive value of low hormone concentrations (below the 10th percentile) in predicting the birth of an SGA infant were in the range of 6 - 26% and 17 - 39%, respectively. The corresponding specificity and prediction of a non-SGA infant from normal levels were 91 - 93% and 85 - 88%. Conclusions. HPL and estriol, but not hCG concentrations, are positively related to the size of the fetus, but the relationships are too weak to be of predictive value in an unselected population. C1 UNIV BERGEN,DEPT PEDIAT,N-5014 BERGEN,NORWAY. UNIV BERGEN,DEPT ENDOCRINE STUDIES,BERGEN,NORWAY. UNIV BERGEN,DEPT OBSTET & GYNECOL,BERGEN,NORWAY. UNIV BERGEN,DEPT MED BIRTH REGISTRY,BERGEN,NORWAY. UNIV TRONDHEIM,DEPT COMMUNITY MED & GEN PRACTICE,TRONDHEIM,NORWAY. NIH,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. NR 24 TC 1 Z9 1 U1 1 U2 7 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 50 EP 55 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200010 ER PT J AU Gardner, MO Goldenberg, RL Cliver, SP Boots, LR Hoffman, HJ AF Gardner, MO Goldenberg, RL Cliver, SP Boots, LR Hoffman, HJ TI Maternal serum concentrations of human placental lactogen, estradiol and pregnancy specific beta(1)-glycoprotein and fetal growth retardation SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE fetal growth retardation; human placental lactogen; estradiol; pregnancy; specific beta(1)-glycoprotein ID INTRAUTERINE AB Background. To determine if maternal serum levels of human placental lactogen (hPL), estradiol, and pregnancy-specific beta(1)-glycoprotein (SP1) measured at approximately 18 weeks' gestation were associated with fetal growth retardation (FGR) in infants delivered at or after 37 weeks. Method's. Serum samples were obtained at a mean of 18 weeks' gestational age from 200 multiparous women with risk factors for FGR. Maternal serum concentrations of hPL, estradiol and SP1 were correlated with FGR. Results. A total of 59 (29.5%) of the 200 infants were diagnosed postnatally with FGR. There were no significant differences in the prevalence of FGR among the lowest quartiles of estradiol, hPL or SP1. However, pregnancies in the highest quartile of estradiol levels at 18 weeks' (>580 pg/ml) were associated with a significantly lower risk of FGR than those in the lower three quartiles, 8 out of 50 (16%) vs 51 of 150 (34%) (p = <0.05). The prevalence of FGR associated with the highest quartile of hPL (>1.73 mu g/ml) was 12.2% compared to 35% in the lower three quartiles (p = 0.025) and the prevalence of FGR associated with the highest quartile of SP1 (>43 ng/ml) was 14% compared to 34.7% in the lower three quartiles (p = 0.018). Only one out of 21 infants (4.5%) whose mothers had each value in the highest quartile of hPL, estradiol, and SP1 was diagnosed with FGR compared to 58 out of 178 (32.6%) of the remaining infants (p = 0.007). Conclusions. In pregnancies of women at high risk for FGR, higher levels of estradiol, hPL, and SP1 at 18 weeks are associated with a decreased prevalence of FGR. This finding indicates that high levels of these hormones are related to a lower risk of FGR, but that low levels do not predict FGR. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,CTR OBSTET RES,BIRMINGHAM,AL 35233. NICHHD,PREVENT RES PROGRAM,NIH,BETHESDA,MD 20892. NR 11 TC 1 Z9 1 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 56 EP 58 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200011 ER PT J AU Markestad, T Lossius, P MaartmannMoe, H Iversen, OE Lie, RT Bergsjo, P Jacobsen, G Hoffman, HJ Bakketeig, LS AF Markestad, T Lossius, P MaartmannMoe, H Iversen, OE Lie, RT Bergsjo, P Jacobsen, G Hoffman, HJ Bakketeig, LS TI Cell division in placentas of appropriate and small-for-gestational-age infants - A flow cytometry study SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE flow cytometry; placenta; pregnancy; intrauterine growth retardation; small for gestational age (SGA) ID GROWTH AB Background. The purpose of this study was to examine if placentas of small- for-gestational-age (SGA) and non-SGA infants differ with respect to proliferative cell activity. Method. Cell cycle distribution was studied in placentas from 181 SGA (birthweight <10th percentile) and 528 non-SGA births by flow cytometry measurements of relative DNA content. Results. The fraction of cells in various cell cycle phases (G(1)-, S- and G(2)-phases) did not differ with gestational age from 30 to 43 weeks in either of the groups. The placentas of the SGA infants had a significantly lower mean (+/-1 SEM) growth fraction than placentas of non-SGA infants (S-phase 5.2 +/- 0.2 vs 5.5 +/- 0.1, p = 0.05, and G(2)-fraction 5.4 +/- 0.2 vs 6.3 +/- 0.1, p < 0.001), but the overlaps of the distributions were large. Thus sensitivity, specificity and predictive values of low fractions did not differ substantially from a purely random prediction of SGA. Conclusions. Cell division in the placenta is maintained until and beyond term. Placentas of SGA infants have, on average, lower proliferative activity than placentas of non-SGA infants, but the difference is too small to be of predictive value in identifying intrauterine growth retardation. C1 UNIV BERGEN,DEPT PEDIAT,N-5014 BERGEN,NORWAY. UNIV BERGEN,DEPT OBSTET & GYNECOL,BERGEN,NORWAY. UNIV BERGEN,DEPT PATHOL,BERGEN,NORWAY. UNIV BERGEN,DEPT MED BIRTH REGISTRY,BERGEN,NORWAY. NORWEGIAN UNIV SCI & TECHNOL,DEPT COMMUNITY MED & GEN PRACTICE,N-7034 TRONDHEIM,NORWAY. NICHHD,BETHESDA,MD 20892. NR 14 TC 0 Z9 0 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 59 EP 62 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200012 ER PT J AU Tamura, T Goldenberg, RL Johnston, KE Cliver, SP Hoffman, HJ AF Tamura, T Goldenberg, RL Johnston, KE Cliver, SP Hoffman, HJ TI Serum concentrations of zinc, folate, vitamins A and E, and proteins, and their relationships to pregnancy outcome SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE folate; zinc; vitamin A; serum proteins; pregnancy outcome ID MATERNAL NUTRITIONAL-STATUS; FETAL GROWTH-RETARDATION; FOLIC-ACID SUPPLEMENT; BIRTH-WEIGHT; GESTATIONAL-AGE; CORD SERUM; ANTIOXIDANT FUNCTION; LIPID-PEROXIDATION; BLOOD-SAMPLES; A STATUS AB Objective. To review the relationships between various laboratory measures relating to nutrition and pregnancy outcome. The data were obtained during the investigation entitled ''Successive small-for-gestational-age births study''. Methods. A total of 289 pregnant women of the 1545 who participated in the study between 1986 and 1988 in Birmingham, Alabama, USA. The following determinations were done using the serum samples obtained at 18 and 30 weeks of gestation: zinc, folate, vitamins A and E, and proteins (alpha-2-macroglobulin, retinol-binding protein, prealbumin, and albumin). These laboratory values were correlated with various measures of pregnancy outcome including the incidence of Fetal-growth retardation and maternal infections during the perinatal period, and birth weight and Apgar score of infants. Results. Serum folate concentrations showed positive relationships with the incidence of fetal-growth retardation as well as birth weight of infants, and alpha-2-macroglobulin was negatively correlated with birth weight. These relationships were significant after adjusting for factors previously known to affect the birth weight of infants. The concentrations of serum zinc, vitamins A and E, and proteins did not show significant correlation with measures of pregnancy outcome. Conclusion. Among the laboratory measures evaluated in this study, serum folate and alpha-2-macroglobulin concentrations correlated with pregnancy outcome. Further research is warranted to investigate the mechanism(s) of the relationship between serum alpha-2-macroglobulin and birth weight of infants. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35294. NIH,BETHESDA,MD 20892. RP Tamura, T (reprint author), UNIV ALABAMA,DEPT NUTR SCI,218 WEBB BLDG,UAB STN,BIRMINGHAM,AL 35294, USA. NR 76 TC 6 Z9 7 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 63 EP 70 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200013 ER PT J AU Neggers, YH Goldenberg, RL Tamura, T Cliver, SP Hoffman, HJ AF Neggers, YH Goldenberg, RL Tamura, T Cliver, SP Hoffman, HJ TI The relationship between maternal dietary intake and infant birthweight SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE zinc; folate; dietary intake; birthweight ID LOW-BIRTH-WEIGHT; PREGNANCY; ZINC; ASSOCIATION AB Background. Zinc and folate are important far fetal growth. However, the relationship between the dietary intake of these nutrients and pregnancy outcome is not settled. Methods. A prospective study was conducted to ascertain the relationship between maternal dietary zinc and folate intake (n = 1398), serum zinc and folate levels (n = 289), and infant birthweight. Twenty-four hour recalls were used to measure energy, zinc, folate and other nutrient intakes at 18 and 30 weeks of gestation. Subjects in the study were offered daily folic acid (1.0 mg) and iron (60 mg as ferrous sulfate) at enrollment. Results. Maternal zinc nutriture as assessed by serum and dietary intake was not associated with birthweight or length of gestation. There was a small but significant positive association between maternal folate intake and adjusted infant birthweight (beta = 0.05, p = 0.03). The indirect measures of maternal nutritional status including maternal pre-pregnancy weight (beta = 8.0, p = 0.0001) and weight gain during pregnancy (beta = 18.1, p = 0.0001) were stronger predictors of adjusted infant birthweight as compared to energy intake and intakes of zinc and folate. An increase of 320, 290, and 48 g in infant birthweight was associated with the 90th-10th percentile difference for pre-pregnancy weight, weight gain during pregnancy, and folate intake respectively. Conclusions. These results indicate that pre-pregnancy weight and weight gain during pregnancy are both strong predictors of infant birthweight. Folate intake, although significantly associated with birthweight, was a weak predictor while maternal intake of zinc and other nutrients was not associated with birthweight. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35294. NICHHD,PREVENT RES PROGRAM,NIH,BETHESDA,MD 20892. RP Neggers, YH (reprint author), UNIV ALABAMA,DEPT HUMAN NUTR,BOX 870158,TUSCALOOSA,AL 35487, USA. FU NICHD NIH HHS [N01-HD-4-2811]; PHS HHS [282-92-0055] NR 25 TC 17 Z9 20 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 71 EP 75 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200014 PM 9219461 ER PT J AU Vik, T Markestad, T Ahlsten, G GebreMedhin, M Jacobsen, G Hoffman, HJ Bakketeig, LS AF Vik, T Markestad, T Ahlsten, G GebreMedhin, M Jacobsen, G Hoffman, HJ Bakketeig, LS TI Body proportions and early neonatal morbidity in small-for-gestational-age infants of successive births SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE small for gestational age; newborn infant; neonatal morbidity; perinatal mortality; ponderal index ID INTRAUTERINE GROWTH-RETARDATION AB Background. We wanted to examine if infants who were small for gestational age (SGA) at term had increased perinatal mortality or morbidity compared to non-SGA infants, and if this could be related to the infant's body proportions, or to whether the mother previously had delivered a low-birthweight infant (''repeater'') or not (''non-repeater''). Methods. From a cohort of 5722 para 1 and para 2 women, we compared perinatal mortality in 541 SGA (birthweight <10th percentile) and 4737 non-SGA infants. From the same cohort, early neonatal morbidity was studied in 368 SGA and 462 control infants without congenital malformations, Results. SGA infants had a 6.4 (95% CI: 2.6-15.7) higher risk of perinatal death than controls, but when infants who died with congenital malformations were excluded, this risk was not significantly increased. SGA infants were more often transferred to an intensive care unit than controls (1.7, 95% CI: 1.0-2.9). Among SGA births, infants with asymmetric body proportions (i.e. low ponderal index) more often had symptoms in the neonatal period (RR: 2.5; 95% CI: 1.4-4.3) and were more often transferred to an intensive care unit (3.4; 95% CI: 1.6-7.4) than symmetric SGA infants, whereas there were no differences between SGA infants of repeaters and non-repeaters. Conclusions. We found that SGA infants had higher perinatal mortality than controls, but this was due to a higher prevalence of congenital malformations. Among SGA infants without malformations, our results indicated increased neonatal morbidity in infants with asymmetric body proportions. C1 NORWEGIAN UNIV SCI & TECHNOL,DEPT PEDIAT,N-7034 TRONDHEIM,NORWAY. NORWEGIAN UNIV SCI & TECHNOL,DEPT COMMUNITY MED & GEN PRACTICE,N-7034 TRONDHEIM,NORWAY. UNIV BERGEN,DEPT PEDIAT,N-5014 BERGEN,NORWAY. DEPT PEDIAT,UPPSALA,SWEDEN. NICHHD,NIH,BETHESDA,MD 20892. NR 22 TC 4 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 76 EP 81 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200015 ER PT J AU Nelson, KG Goldenberg, RL Hoffman, HJ Cliver, SP AF Nelson, KG Goldenberg, RL Hoffman, HJ Cliver, SP TI Growth and development during the first year in a cohort of low income term-born American children SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE small for gestational age; intrauterine growth retardation; low income; growth; child development ID FOR-GESTATIONAL-AGE; LOW-BIRTH-WEIGHT; 1ST 3 YEARS; FOLLOW-UP; INFANTS; DIAGNOSIS; PRETERM; DATES AB Background. Infants born small for gestational age (SGA) are at risk for poor postnatal growth and development. This study evaluates biologic and environmental determinants of outcome during the first year of life in a cohort of low income term-born American infants. Methods. Seven hundred and seventeen of 949 (76%) singleton births to women followed from early pregnancy were studied over their first year of life and measures of growth, home environment, physical and cognitive development were obtained. Infants were categorized as SGA or non-SGA based on birthweight <15th percentile for gestational age. SGA and non-SGA children's outcomes were analyzed by race, gender and symmetry. Results. SGA infants were demographically similar to non-SGA infants but significantly lower in mean maternal height, weight and education. Birthweight, crownheel length and head circumference were all significantly smaller in SGA infants. By age I year, the SGA children were still shorter, lighter and had smaller head circumferences than the non-SGA children though their rate of growth during the first year was significantly greater for length and head circumference. Cognitive functioning as measured by the Bayley Scales of Infant Development and the Fagan Test of Infant Intelligence did not differ significantly except for a lower Bayley Psychomotor Development Index (PDI) in SGA infants. Since most of these children live in economically disadvantaged households, any negative consequences of poor intrauterine growth may be influenced by postnatal environment and longer term follow-up will be necessary to assess this relationship. C1 UNIV ALABAMA, DEPT OBSTET & GYNECOL, BIRMINGHAM, AL 35233 USA. NICHHD, DIV BIOMETRY, NIH, BETHESDA, MD 20892 USA. RP Nelson, KG (reprint author), UNIV ALABAMA, DEPT PEDIAT, P100 VOLKER HALL, 1670 UNIV BLVD, BIRMINGHAM, AL 35233 USA. NR 23 TC 6 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-6349 EI 1600-0412 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 87 EP 92 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200017 ER PT J AU Markestad, T Vik, T Ahlsten, G GebreMedhin, M Skjaerven, R Jacobsen, G Hoffman, HJ Bakketeig, LS AF Markestad, T Vik, T Ahlsten, G GebreMedhin, M Skjaerven, R Jacobsen, G Hoffman, HJ Bakketeig, LS TI Small-for-gestational-age (SGA) infants born at term: Growth and development during the first year of life SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE intrauterine growth retardation (IUGR); small for gestational age (SGA); growth; development; cigarette smoking ID LOW-BIRTHWEIGHT CHILDREN; DEVIANT BIRTH-WEIGHT; 1ST 3 YEARS; RISK-FACTORS; FOLLOW-UP; MENTAL-DEVELOPMENT; DATES INFANTS; BABIES; SIZE; INTELLIGENCE AB Background. The purpose was to compare growth patterns and psychomotor development of healthy small-for-gestational-age (SGA) and non-SGA infants, and identify factors predictive of outcome at 13 months of age. Method. A total of 265 SGA infants and 329 non-SGA controls were identified from a multicenter cohort of 5722 para 1 and 2 women who had been followed during pregnancy. The infants were examined at 2 days and at 13 months of age. Psychomotor development at 13 months was assessed with The Bayley Scale of Infant Development. Results. The SGA infants showed partial catch-up growth, but had still lower (mean +/- SEM, p < 0.0001) weight (9750 +/- 65 vs 10505 +/- 67 g), crown-heel length (75.9 +/- 0.2 vs 77.5 +/- 0.2 cm) and head circumference (46.9 +/- 0.1 vs 47.7 +/- 0.1 cm) than the non-SGA infants at 13 months. The SGA children scored equally well on the motor (PDI 106.8 +/- 1.0 vs 107.2 +/- 0.8) but lower on the mental scale (MDI 112.1 +/- 0.8 vs 116.5 +/- 0.7, p < 0.0001) of the Bayley Scale, and the asymmetric SGA scored lower than the symmetric SGA infants (MDI 110.2 +/- 1.3 vs 113.3 +/- 0.9, p = 0.05). In a multivariate regression analysis the parents' growth parameters had the greatest effect on growth measures at 13 months while education and maternal smoking had no significant effect. SGA vs non-SGA status had the greatest effect on growth velocities during infancy. For mental development only SGA vs non-SGA status and the mothers' education made significant contributions, but only accounted for 6% of the variance. Conclusion. The negative impact of intrauterine factors on growth are partly abolished by catch-up growth during infancy, and growth parameters at one year of age are mostly determined by genetic factors even in SGA infants. Decreased intrauterine growth may possibly have a negative effect on brain growth and mental developmental potential. C1 UNIV BERGEN,DEPT PEDIAT,N-5014 BERGEN,NORWAY. UNIV BERGEN,DEPT MED STAT,N-5014 BERGEN,NORWAY. NORWEGIAN UNIV SCI & TECHNOL,DEPT PEDIAT,N-7034 TRONDHEIM,NORWAY. NORWEGIAN UNIV SCI & TECHNOL,DEPT COMMUNITY MED & GEN PRACTICE,N-7034 TRONDHEIM,NORWAY. UPPSALA UNIV,DEPT PEDIAT,UPPSALA,SWEDEN. NICHHD,NIH,BETHESDA,MD 20892. NR 47 TC 8 Z9 9 U1 3 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 93 EP 101 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200018 ER PT J AU Bakketeig, LS Goldenberg, RL Hoffman, HJ AF Bakketeig, LS Goldenberg, RL Hoffman, HJ TI Prospects of the collaborative small-for-gestational-age birth study for the five year old follow-up study SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article ID WEIGHT C1 NORWEGIAN UNIV SCI & TECHNOL,DEPT COMMUNITY MED & GEN PRACTICE,TRONDHEIM,NORWAY. UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL. NICHHD,NIH,BETHESDA,MD 20892. NR 7 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 1997 VL 76 SU 165 BP 102 EP 103 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XJ352 UT WOS:A1997XJ35200019 ER PT J AU Ding, I Huang, KD Wang, X Greig, JR Miller, RW Okunieff, P AF Ding, I Huang, KD Wang, X Greig, JR Miller, RW Okunieff, P TI Radioprotection of hematopoietic tissue by fibroblast growth factors in fractionated radiation experiments SO ACTA ONCOLOGICA LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; SUPEROXIDE-DISMUTASE; PROGENITOR CELLS; BONE-MARROW; MEGAKARYOCYTOPOIESIS; MICE; PROLIFERATION; APOPTOSIS; INDUCTION AB Acidic and basic fibroblast growth factors (FGF(1/2)) myeloprotect mice in single dose total body irradiation (TBI) experiments with a dose modification factor (DMF) of approximate to 1.15. CFU-C assay suggests that one of the mechanisms is augmentation of the shoulder of the radiation dose response curve, and thus protection could be greater with fractionation. Four equal fractions of TBI were delivered to C3H/He mice at times 0 h, 8 h, 24 h, and 32 h. FGF(1/2) dose was 3 mu g per iv injection given 24 and 4 hrs before the first radiation dose. FGF(2) treated mice had a significant survival advantage over saline-treated mice with a DMF of 1.22 +/- 0.07 (p < 0.01). Adding a third dose of FGF(2), had no additional benefit on LD50/30 (dose of radiation lethal to 50% of animals measured at day 30) (DMF = 1.23 +/- 0.06, p < 0.01). FGF(1) was not as effective with fractionation (DMF = 1.04 +/- 0.03). Increased survival in FGF2 treated mice was due to the a more rapid recovery of bone marrow hematopoietic cells and peripheral WBC, RBC and platelets. FGF(2) may prove a useful treatment response modifier in clinical fractionated irradiation. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 19 TC 11 Z9 11 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1997 VL 36 IS 3 BP 337 EP 340 PG 4 WC Oncology SC Oncology GA XD553 UT WOS:A1997XD55300016 PM 9208907 ER PT J AU Kahan, E Ibrahim, AS ElNajjar, K Ron, E AlAgha, H Polliack, A ElBolkainy, MN AF Kahan, E Ibrahim, AS ElNajjar, K Ron, E AlAgha, H Polliack, A ElBolkainy, MN TI Cancer patterns in the Middle East - Special report from the Middle East Cancer Society SO ACTA ONCOLOGICA LA English DT Article AB To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access. C1 RABIN MED CTR,DEPT FAMILY MED,PETAH TIQWA,ISRAEL. CAIRO UNIV,NATL CANC INST,CAIRO,EGYPT. PALESTINIAN NATL AUTHOR,MINIST HLTH,KHAN YUNIS,GAZA STRIP,MOZAMBIQUE. NCI,NIH,BETHESDA,MD 20892. PALESTINE HOSP,CAIRO,EGYPT. HADASSAH UNIV HOSP,IL-91120 JERUSALEM,ISRAEL. RP Kahan, E (reprint author), TEL AVIV UNIV,INST OCCUPAT HLTH,EPIDEMIOL UNIT,IL-69978 TEL AVIV,ISRAEL. NR 10 TC 33 Z9 33 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1997 VL 36 IS 6 BP 631 EP 636 PG 6 WC Oncology SC Oncology GA YH936 UT WOS:A1997YH93600014 PM 9408155 ER PT J AU Dawson, DA AF Dawson, DA TI Alcohol, drugs, fighting and suicide attempt/ideation SO ADDICTION RESEARCH LA English DT Article ID JAIL DETAINEES; SUBSTANCE USE; DISORDERS; PATTERNS; AGGRESSION; OFFENDERS; HOMICIDE; ETHANOL; WOMEN AB In a representative U.S. sample of 18,352 current drinkers 18 years of age and over, past-year alcohol-or other drug-related fighting and suicide attempt/ideation both showed strong positive bivariate associations with volume of alcohol intake, proportion of drinking days resulting in intoxication (the intoxication index) and past-year drug use, especially multiple drug use. After adjusting for potential confounders in a series of multiple logistic regression models, average daily ethanol intake retained a significant positive association with the odds of alcohol-and other drug-related fighting, as did the intoxication index-except among drinkers who used marijuana only (i.e., no other drugs). The odds of this outcome also were increased by use of simulants or cocaine only, use of multiple drugs and use of marijuana-the latter primarily among women. The odds of past-year suicide attempt/ideation were positively associated with the intoxication index but were not significantly associated with average daily ethanol intake. Suicide attempt/ideation also was positively associated with the use of marijuana only, sedatives/tranquilizers only, cocaine/stimulants only and multiple drugs. Because drug use was positively associated with alcohol use, models restricted to only alcohol or only drug use measures overestimated some of their associations with the two outcome measures. Simultaneous use of alcohol and drugs was not significantly associated with the odds of either of the outcomes considered in this analysis, but the data were suggestive of a positive effect of simultaneous use on alcohol-and drug-related fighting. C1 NIAAA, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Div Biometry & Epidemiol, Willco Bldg,Suite 514,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 45 TC 24 Z9 24 U1 3 U2 5 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1058-6989 J9 ADDICT RES JI Addict. Res. PY 1997 VL 5 IS 6 BP 451 EP 472 DI 10.3109/16066359709004360 PG 22 WC Substance Abuse; Social Issues SC Substance Abuse; Social Issues GA ZL632 UT WOS:000073454600003 ER PT S AU Fisher, B Dignam, J AF Fisher, B Dignam, J BE Salmon, SE TI Recent findings from three NSABP clinical trials evaluating systemic adjuvant therapy in patients with primary breast cancer and negative axillary nodes SO ADJUVANT THERAPY OF CANCER VIII SE ADJUVANT THERAPY OF CANCER LA English DT Proceedings Paper CT 8th International Conference on the Adjuvant Therapy of Cancer CY MAR, 1996 CL SCOTTSDALE, AZ SP Arizona Canc Ctr RP Fisher, B (reprint author), NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 SN 1040-5089 BN 0-397-58443-1 J9 ADJ THER CANC PY 1997 VL 8 BP 83 EP 91 PG 9 WC Oncology SC Oncology GA BJ91R UT WOS:A1997BJ91R00009 ER PT S AU Chrousos, GP AF Chrousos, GP BE Creatsas, G Mastorakos, G Chrousos, GP TI The future of pediatric and adolescent endocrinology SO ADOLESCENT GYNECOLOGY AND ENDOCRINOLOGY: BASIC AND CLINICAL ASPECTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Congress on Update on Adolescent Gynecology and Endocrinology CY DEC 06-09, 1995 CL ATHENS, GREECE SP Hellenic Soc Pediat & Adolescent Gynecol, Int Federat Pediat & Adolescent Gynecol, NICHHD ID STRESS SYSTEM DISORDERS; MAJOR DEPRESSION; WOMEN RP Chrousos, GP (reprint author), NICHHD, PEDIAT ENDOCRINOL SECT, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 12 TC 3 Z9 3 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-039-5; 1-57331-038-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 816 BP 4 EP 8 DI 10.1111/j.1749-6632.1997.tb52124.x PG 5 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Obstetrics & Gynecology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Obstetrics & Gynecology GA BJ18G UT WOS:A1997BJ18G00002 PM 9238250 ER PT S AU Mastorakos, G Ghizzoni, L Webster, EL Chrousos, GP AF Mastorakos, G Ghizzoni, L Webster, EL Chrousos, GP BE Creatsas, G Mastorakos, G Chrousos, GP TI Autocrine-paracrine role of ovarian corticotropin-releasing hormone SO ADOLESCENT GYNECOLOGY AND ENDOCRINOLOGY: BASIC AND CLINICAL ASPECTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Congress on Update on Adolescent Gynecology and Endocrinology CY DEC 06-09, 1995 CL ATHENS, GREECE SP Hellenic Soc Pediat & Adolescent Gynecol, Int Federat Pediat & Adolescent Gynecol, NICHHD ID CYTOKINE-MEDIATED REGULATION; SYMPATHETIC NERVOUS-SYSTEM; RAT LEYDIG-CELLS; FACTOR RECEPTORS; INFLAMMATORY REACTION; BETA-ENDORPHIN; IN-VIVO; LOCALIZATION; SECRETION; STRESS C1 NICHHD, DEB, NIH, BETHESDA, MD 20892 USA. UNIV PARMA, DEPT PEDIAT, I-43100 PARMA, ITALY. RP Mastorakos, G (reprint author), UNIV ATHENS, EVGENIDION HOSP, ENDOCRINE UNIT, PAPADIAMANTOPOULOU 20, ATHENS 11528, GREECE. NR 47 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-039-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 816 BP 27 EP 41 DI 10.1111/j.1749-6632.1997.tb52127.x PG 15 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Obstetrics & Gynecology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Obstetrics & Gynecology GA BJ18G UT WOS:A1997BJ18G00005 PM 9238253 ER PT S AU Magiakou, MA Mastorakos, G Webster, E Chrousos, GP AF Magiakou, MA Mastorakos, G Webster, E Chrousos, GP BE Creatsas, G Mastorakos, G Chrousos, GP TI The hypothalamic-pituitary-adrenal axis and the female reproductive system SO ADOLESCENT GYNECOLOGY AND ENDOCRINOLOGY: BASIC AND CLINICAL ASPECTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Congress on Update on Adolescent Gynecology and Endocrinology CY DEC 06-09, 1995 CL ATHENS, GREECE SP Hellenic Soc Pediat & Adolescent Gynecol, Int Federat Pediat & Adolescent Gynecol, NICHHD ID CORTICOTROPIN-RELEASING HORMONE; STRESS-INDUCED INHIBITION; CENTRAL NERVOUS-SYSTEM; BIOCHEMICAL MANIFESTATIONS; RECOMBINANT INTERLEUKIN-6; POTENTIAL IMPLICATIONS; SEXUAL DIMORPHISM; CUSHINGS-SYNDROME; FACTOR RECEPTORS; BINDING-PROTEIN C1 UNIV ATHENS, EVGENIDION HOSP, ENDOCRINE UNIT, ATHENS 11527, GREECE. NICHHD, PEDIAT ENDORCRINOL SECT, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Magiakou, MA (reprint author), UNIV ATHENS, P&A KYRIAKOU CHILDRENS HOSP, DEPT PEDIAT 2, ATHENS 11527, GREECE. NR 69 TC 105 Z9 108 U1 1 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-039-5; 1-57331-038-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 816 BP 42 EP 56 DI 10.1111/j.1749-6632.1997.tb52128.x PG 15 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Obstetrics & Gynecology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Obstetrics & Gynecology GA BJ18G UT WOS:A1997BJ18G00006 PM 9238254 ER PT S AU Tsigos, C Latronico, AC Chrousos, GP AF Tsigos, C Latronico, AC Chrousos, GP BE Creatsas, G Mastorakos, G Chrousos, GP TI Luteinizing hormone resistance syndromes SO ADOLESCENT GYNECOLOGY AND ENDOCRINOLOGY: BASIC AND CLINICAL ASPECTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd International Congress on Update on Adolescent Gynecology and Endocrinology CY DEC 06-09, 1995 CL ATHENS, GREECE SP Hellenic Soc Pediat & Adolescent Gynecol, Int Federat Pediat & Adolescent Gynecol, NICHHD ID ISOLATED GLUCOCORTICOID DEFICIENCY; CHORIONIC-GONADOTROPIN RECEPTOR; LIMITED PRECOCIOUS PUBERTY; LEYDIG-CELL HYPOPLASIA; MALE PSEUDOHERMAPHRODITISM; CHORIOGONADOTROPIN RECEPTOR; GENE; MUTATION; ABNORMALITIES C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X NR 28 TC 5 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-039-5; 1-57331-038-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 816 BP 263 EP 273 DI 10.1111/j.1749-6632.1997.tb52150.x PG 11 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Obstetrics & Gynecology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Obstetrics & Gynecology GA BJ18G UT WOS:A1997BJ18G00028 PM 9238276 ER PT S AU Moss, J Zolkiewska, A Okazaki, I AF Moss, J Zolkiewska, A Okazaki, I BE Haag, F KochNolte, F TI ADP-ribosylarginine hydrolases and ADP-ribosyltransferases - Partners in ADP-ribosylation cycles SO ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Workshop on the Biological Significance of Mono-ADP-Ribosylation in Animal Tissues CY MAY 19-23, 1996 CL HAMBURG, GERMANY SP Deut Forschungsgemeinsch ID TURKEY ERYTHROCYTES; SKELETAL-MUSCLE; SUBSTRATE-SPECIFICITY; CATALYZED REACTION; PROTEIN; RIBOSE; NAD; CYSTEINE; IDENTIFICATION; PURIFICATION AB Mono-ADP-ribosylation is a reversible modification of arginine residues in proteins, with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases constituting opposing arms of a putative ADP-ribosylation cycle. The enzymatic components of an ADP-ribosylation cycle have been identified in both prokaryotic and eukaryotic systems. The regulatory significance of the cycle has been best documented in prokaryotes. As shown by Ludden and coworkers, ADP-ribosylation controls the activity of dinitrogenase reductase in the phototropic bacterium Rhodospirillum rubrum. ADP-ribosylation of other amino acids, such as cysteine, has also been demonstrated, lending credence to the hypothesis that this modification is heterogeneous. In eukaryotes, the functional relationship between ADP-ribosyltransferases and ADP-ribosylarginine hydrolases is less well documented. The transferase-catalyzed reaction results in stereospecific formation of alpha-ADP-ribosylarginine from beta-NAD; ADP-ribosylarginine hydrolases specifically cleave the alpha-anomer, leading to release of ADP-ribose and regeneration of the free guanidino group of arginine. The two reactions can thus be coupled in vitro. Coupling in vivo is dependent on cellular localization. The deduced amino acid sequences of ADP-ribosyltransferases from avian and mammalian tissues have common consensus sequences involved in catalytic activity but, in some instances, enzyme-specific cellular localization signals. The presence of amino- and carboxy-terminal signal sequences is consistent with the glycosylphosphatidylinositol(GPI)-anchoring to the cell surface. The muscle and lymphocyte transferases ADP-ribosylate integrins. Some transferases lack the carboxy- terminal signal sequence needed for GPI-anchoring. Most ADP-ribosylarginine hydrolase activity is cytosolic, although perhaps some is located at the cell surface. Deduced amino acid sequences of hydrolases from a number of mammallan species are consistent with their cytoplasmic localization. Katada and coworkers have determined, however, that auto-ADP-ribooylated RT6, a GPI-linked protein, is metabolized by a hydrolase-like activity, consistent with the existence of an ADP-ribosylation cycle. ADP-ribosyl RT6 may be internalized, thereby coming in contact with the cytosolic hydrolase; alternatively, a novel form of the hydrolase may be located at the surface. The mechanism of coupling of ADP-ribosyltransferases and hydrolases in eukaryotic ADP-ribosylation cycles has yet to be clarified. RP Moss, J (reprint author), NHLBI, PULM CRIT CARE MED BRANCH, NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 39 TC 29 Z9 29 U1 0 U2 3 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45510-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 419 BP 25 EP 33 PG 9 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BH84G UT WOS:A1997BH84G00003 PM 9193633 ER PT S AU Okazaki, IJ Kim, HJ Moss, J AF Okazaki, IJ Kim, HJ Moss, J BE Haag, F KochNolte, F TI Molecular cloning and characterization of lymphocyte and muscle ADP-ribosyltransferases SO ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Workshop on the Biological Significance of Mono-ADP-Ribosylation in Animal Tissues CY MAY 19-23, 1996 CL HAMBURG, GERMANY SP Deut Forschungsgemeinsch ID HEAT-LABILE ENTEROTOXIN; AERUGINOSA EXOTOXIN-A; ACTIVE-SITE MUTATIONS; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; PERTUSSIS TOXIN; PSEUDOMONAS-AERUGINOSA; SKELETAL-MUSCLE; CHOLERA-TOXIN; GLUTAMIC ACID-553 AB Mono-ADP-ribosylation, catalyzed by ADP-ribosyltransferases, is a posttranslational modification of proteins in which the ADP-ribose moiety of NAD is transferred to an acceptor protein(arginine). Several of the bacterial toxin ADP-ribosyltransferases have been well characterized in their ability to alter cellular metabolism. It has been postulated that these bacterial toxins mimic the actions of transferases from mammalian cells. We have cloned and characterized ADP-ribosyltransferases from rabbit and human skeletal muscle, and mouse lymphocytes. The muscle transferases are glycosylphosphatidylinositol (GPI)-anchored proteins that are conserved among species. Two distinct transferases, termed Yac-l and Yac-2 were cloned from mouse lymphoma (Yac-l) cells. The Yac-l transferase, like the muscle enzymes, is a GPI-linked exoenzyme. The Yac-2 transferase, on the other hand, is membrane-associated but appears not to be GPI-linked. In contrast to Yac-l, the Yac-2 enzyme had significant NAD glycohydrolase activity and may preferentially hydrolyze NAD. The bacterial toxin ADP-ribosyltransferases contain three noncontiguous regions of sequence similarity, which are involved in formation of the catalytic site. Alignment of the deduced amino acid sequences of the mammalian transferases and the rodent RT6 enzymes, along with results from site-directed mutagenesis of the muscle enzyme, are consistent with the notion of a common mechanism of NAD binding and catalysis among ADP-ribosyltransferases. RP NHLBI, PULM CRIT CARE MED BRANCH, NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 46 TC 2 Z9 2 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45510-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 419 BP 129 EP 136 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BH84G UT WOS:A1997BH84G00015 PM 9193645 ER PT S AU Bortell, R Rigby, M Stevens, L Moss, J Kanaitsuka, T Mordes, J Greiner, D Rossini, A AF Bortell, R Rigby, M Stevens, L Moss, J Kanaitsuka, T Mordes, J Greiner, D Rossini, A BE Haag, F KochNolte, F TI Mouse RT6 locus 1 and rat RT6.2 are NAD+ - Arginine ADP-ribosyltransferases with auto-ADP-ribosylation activity SO ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Workshop on the Biological Significance of Mono-ADP-Ribosylation in Animal Tissues CY MAY 19-23, 1996 CL HAMBURG, GERMANY SP Deut Forschungsgemeinsch ID DIFFERENTIATION MARKER RT6; EXPRESSION AB We report that rat RT6.2 and recombinant mouse Rt6 locus 1 proteins possess auto-ADP-ribosyltransferase activity and that Rt6, but not RT6, catalyzes the ADP-ribosylation of exogenous histones. Based on NH2OH sensitivity, it appeared that the ADP-ribose was attached to arginine residues on proteins. We also observed that the NAD(+) concentration in culture medium correlates inversely with the proliferation of rat RT6(+) T cells. The data suggest that lymphocyte surface ADP-ribosyltransferases could be involved in signaling and immunoregulatory processes. C1 NHLBI, PULM CRIT CARE MED BRANCH, NIH, BETHESDA, MD 20892 USA. RP Bortell, R (reprint author), UNIV MASSACHUSETTS, SCH MED, DIABET DIV, 373 PLANTAT ST, WORCESTER, MA 01605 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45510-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 419 BP 169 EP 173 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BH84G UT WOS:A1997BH84G00020 PM 9193650 ER PT S AU Greiner, DL Malkani, S Kanaitsuka, T Bortell, R Doukas, J Rigby, M Whalen, B Stevens, LA Moss, J Mordes, JP Rossini, AA AF Greiner, DL Malkani, S Kanaitsuka, T Bortell, R Doukas, J Rigby, M Whalen, B Stevens, LA Moss, J Mordes, JP Rossini, AA BE Haag, F KochNolte, F TI The T cell marker RT6 in a rat model of autoimmune diabetes SO ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Workshop on the Biological Significance of Mono-ADP-Ribosylation in Animal Tissues CY MAY 19-23, 1996 CL HAMBURG, GERMANY SP Deut Forschungsgemeinsch ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; AMINO-ACID-SEQUENCE; PRONE BB RATS; MOUSE HOMOLOG; ALLOANTIGEN; EXPRESSION; MELLITUS; SUBSET; NUCLEOTIDE; PHENOTYPE C1 NHLBI, PULM CRIT CARE MED BRANCH, NIH, BETHESDA, MD 20892 USA. RP Greiner, DL (reprint author), UNIV MASSACHUSETTS, SCH MED, DIABET DIV, 373 PLANTAT ST, SUITE 218, WORCESTER, MA 01605 USA. NR 42 TC 15 Z9 15 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45510-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 419 BP 209 EP 216 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BH84G UT WOS:A1997BH84G00026 PM 9193656 ER PT S AU Zolkiewska, A Moss, J AF Zolkiewska, A Moss, J BE Haag, F KochNolte, F TI The alpha 7 integrin as a target protein for cell surface mono-ADP-ribosylation in muscle cells SO ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Workshop on the Biological Significance of Mono-ADP-Ribosylation in Animal Tissues CY MAY 19-23, 1996 CL HAMBURG, GERMANY SP Deut Forschungsgemeinsch ID SKELETAL-MUSCLE; CYTOPLASMIC DOMAINS; RIBOSYLTRANSFERASE; EXPRESSION; LAMININ AB A membrane-associated arginine-specific mono-ADP-ribosyltransferase was purified 215,000-fold from rabbit skeletal muscle and its gene was isolated from a skeletal muscle cDNA library. The enzyme was a glycosylphosphatidyl-inositol-linked protein, present on the surface of differentiated skeletal muscle myoblasts (myotubes). Following incubation of cultured, intact myotubes with [adenylate-P-32]NAD and analysis by SDS-PAGE, a major radiolabeled protein of 97/140 kDa (reduced/nonreduced conditions) was observed. It was identified as integrin alpha 7 based on its size, binding to a laminin affinity column, immunoprecipitation with a monoclonal antibody, and partial amino acid sequencing. Since ADP-ribosylarginine hydrolase, the enzyme responsible for cleavage of the ADP-ribosylarginine bond and a component with the transferase of a putative ADP-ribosylation cycle, is cytosolic, whereas the transferase is attached via a GPI-anchor to the cell surface, the processing of ADP-ribosylated integrin alpha 7 was investigated. P-32 label was rapidly removed from [P-32] ADP-ribosylated integrin alpha 7, a process inhibited by free ADP-ribose or p-nitrophenylthymidine-5'-monophosphate, alternative substrates for 5'-nucleotide phosphodiesterase. The processed integrin alpha 7 was not susceptible to subsequent ADP-ribosylation, although the amount of surface integrin alpha 7 remained constant. During the processing, no loss of label was observed from integrin alpha 7 radiolabeled with [C-14]NAD, containing C-14 in the nicotinamide-proximal ribose, consistent with a degradation of the ADP-ribose moiety by a cell surface 5'-nucleotide phosphodiesterase. Thus, cell surface ADP-ribosylation, in contrast to intracellular ADP-ribosylation, is not readily reversed by the presently known ADP-ribosylarginine hydrolase and seems to operate outside the postulated ADP-ribosylation cycle. RP Zolkiewska, A (reprint author), NHLBI, PULM CRIT CARE MED BRANCH, NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 20 TC 8 Z9 8 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45510-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 419 BP 297 EP 303 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BH84G UT WOS:A1997BH84G00039 PM 9193669 ER PT S AU Vaughan, M Moss, J AF Vaughan, M Moss, J BE Haag, F KochNolte, F TI Activation of toxin ADP-ribosyltransferases by the family of ADP-ribosylation factors SO ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Workshop on the Biological Significance of Mono-ADP-Ribosylation in Animal Tissues CY MAY 19-23, 1996 CL HAMBURG, GERMANY SP Deut Forschungsgemeinsch ID PHOSPHOLIPASE-D; CHOLERA-TOXIN; BINDING PROTEINS; BOVINE BRAIN; GTP; ARF; PURIFICATION; DROSOPHILA; MECHANISM; COFACTOR AB ADP-ribosylation factors or ARFs are 20-kDa guanine nucleotide-binding proteins, initially identified as stimulators of cholera toxin-catalyzed ADP-ribosylation of Gsa. We now know that ARFs play a critical role in many vesicular trafficking events and ARF activation of a membrane-associated phospholipase D (PLD) has been recognized. ARF is active and associates with membranes when GTP is bound. The active state is terminated by hydrolysis of bound GTP, producing inactive ARF.GDP. The nucleotide effect on ARF association with membranes is related to alteration in orientation of the N-terminal myristoyl moiety that is important for ARF function. Cycling of ARF between active and inactive states involves guanine nucleotide-exchange proteins (GEPs) that accelerate replacement of bound GDP with GTP and GTPase-activating proteins (GAPS) that are responsible for ARF inactivation. Six mammalian ARFs have been identified by cDNA cloning. Class I ARFs 1 and 3 have been studied most extensively. Their activation (GTP binding) is catalyzed by a GEP now purified from spleen cytosol. In crude preparations, GEP was inhibited by brefeldin A (BFA), which in cells causes apparent disintegration of Golgi. Demonstration that the similar to 60 kDa purified GEP was not inhibited by BFA means that contrary to earlier belief, there must be another protein to mediate BFA inhibition. GEP activity was greatly enhanced by phosphatidyl serine. The purified GEP, equally active with ARFs 1 and 3, was inactive with ARFs 5 and 6 (Classes II and III); myristoylated ARFs were better substrates than were their non-myristoylated counterparts. ARF GAP purified from bovine spleen cytosol in our laboratory had much broader substrate specificity than the GEP. It used both ARFs 5 and 6 at least as well as ARFs 1 and 3; myristoylation was without effect. It also accelerated GTP hydrolysis by certain ARF mutants and an ARF-like protein (ARL1) that does not have ARF activity. The purified GAP also differed from the GEP in its rather specific requirement for phosphatidylinositol bisphosphate. This was also observed with a seemingly different ARF GAP that was purified and subsequently cloned in Cassel's laboratory. Activation and inactivation of ARFs present many potential sites for physiological regulation and, therefore, for pathological disruption of ARF function. RP Vaughan, M (reprint author), NHLBI, PULM CRIT CARE MED BRANCH, NIH, BLDG 10, ROOM 5N307, BETHESDA, MD USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45510-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 419 BP 315 EP 320 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BH84G UT WOS:A1997BH84G00041 PM 9193671 ER PT S AU Pace, M Agnellini, D Lippoli, G Berger, RL AF Pace, M Agnellini, D Lippoli, G Berger, RL BE Haag, F KochNolte, F TI Hydrophobic properties of nad glycohydrolase from neurospora crassa conidia and interaction with dioxane SO ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Workshop on the Biological Significance of Mono-ADP-Ribosylation in Animal Tissues CY MAY 19-23, 1996 CL HAMBURG, GERMANY SP Deut Forschungsgemeinsch ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PURIFICATION AB NAD glycohydrolase (NADase, EC 3.2.2.5) from Neurospora crassa conidia shows marked hydrophobic properties which are related to the self inhibition of the enzyme. Both aliphatic amines and carboxylic acids are able to inhibit noncompetitively the catalytic activity of the enzyme and the inhibition depends on the non-polar moiety of the substances. Also dioxane is an inhibitor of NAD glycohydrolase even though it apparently increases the specific activity of the enzyme. This effect can be explained by the fact that NADase is present as a dimer when the enzyme is concentrated or at high temperature, and dioxane binds the enzyme breaking the hydrophobic bonds in the dimeric enzyme and yielding the most active monomeric form which is only slightly inhibited by the organic solvent. C1 NHLBI, BIOPHYS CHEM LAB, IR, NIH, BETHESDA, MD 20892 USA. RP Pace, M (reprint author), UNIV MILAN, INST VET PHYSIOL & BIOCHEM, VIA CELORIA 10, I-20133 MILAN, ITALY. NR 23 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45510-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 419 BP 389 EP 397 PG 9 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BH84G UT WOS:A1997BH84G00051 PM 9193681 ER PT B AU Fuhrer, MJ AF Fuhrer, MJ BE Anogianakis, G Buhler, C Soede, M TI Evaluating the outcomes of assistive technologies and related services: The roles of program management-oriented and rehabilitation science-oriented outcomes research SO ADVANCEMENT OF ASSISTIVE TECHNOLOGY SE ASSISTIVE TECHNOLOGY RESEARCH SERIES LA English DT Proceedings Paper CT AAATE 97 Conference / 4th European Conference for the Advancement of Assistive Technology CY 1997 CL PORTO CARRAS, GREECE SP Assoc Adv Assist Technol Europe DE assistive technology; evaluation research; outcomes AB Two different approaches to outcomes research are advanced: program management-oriented and rehabilitation science-oriented. For purposes of evaluating the outcomes of assistive technologies and the related services, the two kinds of studies are considered in terms of their aims, audiences, choice of outcome criteria, characteristic strategies, financial support and information dissemination practices, as well as their concern with treatment theory, cost considerations, and issues of internal and external validity. RP Fuhrer, MJ (reprint author), NICHHD,NATL CTR MED REHABIL RES,NIH,6100 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-361-7 J9 ASSIST TECHN RES SER PY 1997 VL 3 BP 44 EP 47 PG 4 WC Computer Science, Cybernetics; Computer Science, Interdisciplinary Applications; Health Policy & Services; Rehabilitation SC Computer Science; Health Care Sciences & Services; Rehabilitation GA BJ94E UT WOS:A1997BJ94E00010 ER PT S AU Ha, JH Knauer, S Moody, E Jones, EA Basile, AS AF Ha, JH Knauer, S Moody, E Jones, EA Basile, AS BE Felipo, V Grisolia, S TI Direct enhancement of GABA-ergic neurotransmission by ammonia SO ADVANCES IN CIRRHOSIS, HYPERAMMONEMIA, AND HEPATIC ENCEPHALOPATHY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Symposium on Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy CY DEC 02-04, 1996 CL VALENCIA, SPAIN SP Minist Sanidad & Consumo, Minist Educac & Cienc, Conseller Sanidad & Educac Generalitat Valenciana, Sigma Tau Labs ID SPINAL MOTONEURONS; A RECEPTORS; INHIBITION; MODULATION; NEURONS; BINDING; BRAIN C1 NIDDK, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. NR 23 TC 4 Z9 4 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45598-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 420 BP 85 EP 94 PG 10 WC Gastroenterology & Hepatology; Medicine, Research & Experimental SC Gastroenterology & Hepatology; Research & Experimental Medicine GA BJ40G UT WOS:A1997BJ40G00006 PM 9286428 ER PT S AU Stracke, ML Clair, T Liotta, LA AF Stracke, ML Clair, T Liotta, LA BE Weber, G TI Autotaxin, tumor motility-stimulating exophosphodiesterase SO ADVANCES IN ENZYME REGULATION, VOL 37 SE Advances in Enzyme Regulation LA English DT Review CT 37th Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY SEP 30-OCT 01, 1996 CL INDIANA UNIV SCH MED, INDIANAPOLIS, IN HO INDIANA UNIV SCH MED ID CELL MEMBRANE GLYCOPROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR; FIBROBLAST GROWTH-FACTOR; SOMATOMEDIN-B DOMAIN; AMINO-ACID-SEQUENCE; NUCLEOTIDE PYROPHOSPHATASE; CDNA CLONING; RAT-BRAIN; 5'-NUCLEOTIDE PHOSPHODIESTERASE; MOLECULAR-CLONING RP Stracke, ML (reprint author), NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NR 38 TC 72 Z9 72 U1 0 U2 2 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0065-2571 BN 0-08-043095-3 J9 ADV ENZYME REGUL JI Adv. Enzym. Regul. PY 1997 VL 37 BP 135 EP 144 DI 10.1016/S0065-2571(96)00017-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BJ54D UT WOS:A1997BJ54D00009 PM 9381968 ER PT S AU Rodbell, M AF Rodbell, M BE Weber, G TI The complex regulation of receptor-coupled G-proteins SO ADVANCES IN ENZYME REGULATION, VOL 37 SE Advances in Enzyme Regulation LA English DT Review CT 37th Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY SEP 30-OCT 01, 1996 CL INDIANA UNIV SCH MED, INDIANAPOLIS, IN HO INDIANA UNIV SCH MED ID BETA-ADRENERGIC-RECEPTOR; GTP-BINDING PROTEINS; SIGNAL-TRANSDUCTION; ADENYLYL CYCLASE; HUMAN-NEUTROPHILS; PLASMA-MEMBRANES; ACTIN-FILAMENTS; ALPHA-SUBUNITS; GAMMA-SUBUNITS; CELLS RP Rodbell, M (reprint author), NIEHS, CELLULAR & MOL PHARMACOL LAB, SIGNAL TRANSDUCT SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 45 TC 36 Z9 36 U1 2 U2 4 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0065-2571 BN 0-08-043095-3 J9 ADV ENZYME REGUL JI Adv. Enzym. Regul. PY 1997 VL 37 BP 427 EP 435 DI 10.1016/S0065-2571(96)00020-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BJ54D UT WOS:A1997BJ54D00022 PM 9381985 ER PT S AU Gellert, M AF Gellert, M BE Dixon, FJ TI Recent advances in understanding V(D)J recombination SO ADVANCES IN IMMUNOLOGY, VOL 64 SE Advances in Immunology LA English DT Review ID DEPENDENT PROTEIN-KINASE; STRAND-BREAK-REPAIR; T-CELL RECEPTOR; SEVERE COMBINED IMMUNODEFICIENCY; IMMUNOGLOBULIN GENE CONVERSION; SITE-SPECIFIC RECOMBINATION; COMBINED IMMUNE-DEFICIENCY; BROKEN DNA-MOLECULES; SCID MUTATION; CATALYTIC SUBUNIT RP Gellert, M (reprint author), NIDDKD, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 107 TC 164 Z9 167 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022464-X J9 ADV IMMUNOL JI Adv.Immunol. PY 1997 VL 64 BP 39 EP 64 DI 10.1016/S0065-2776(08)60886-X PG 26 WC Immunology SC Immunology GA BH71W UT WOS:A1997BH71W00002 PM 9100979 ER PT J AU Kannel, WB Wilson, PWF AF Kannel, WB Wilson, PWF TI Comparison of risk profiles for cardiovascular events implications for prevention SO ADVANCES IN INTERNAL MEDICINE, VOL 42 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID CORONARY HEART-DISEASE; VITAMIN-E CONSUMPTION; MYOCARDIAL-INFARCTION; ARTERY DISEASE; PLASMA HOMOCYST(E)INE; PHYSICAL-ACTIVITY; MEDICAL PROGRESS; BLOOD-PRESSURE; WOMEN; MEN C1 NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. RP Kannel, WB (reprint author), BOSTON UNIV,SCH MED,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA 01701, USA. NR 67 TC 13 Z9 16 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1997 VL 42 BP 39 EP 66 PG 28 WC Medicine, General & Internal SC General & Internal Medicine GA BH96D UT WOS:A1997BH96D00002 PM 9048116 ER PT J AU Hoak, JC AF Hoak, JC TI Evaluation and management of the thrombosis-prone patient SO ADVANCES IN INTERNAL MEDICINE, VOL 42 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID PROTEIN-C DEFICIENCY; HEPARIN-INDUCED THROMBOCYTOPENIA; MOLECULAR-WEIGHT HEPARIN; COAGULATION-FACTOR-V; POOR ANTICOAGULANT RESPONSE; LINKED-IMMUNOSORBENT-ASSAY; DEEP VENOUS THROMBOSIS; TOTAL HIP-REPLACEMENT; ESSENTIAL THROMBOCYTHEMIA; UNFRACTIONATED HEPARIN C1 UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DIV HEMATOL ONCOL,IOWA CITY,IA 52242. UNIV VERMONT,COLL MED,DEPT MED,BURLINGTON,VT 05405. RP Hoak, JC (reprint author), NHLBI,DIV BLOOD DIS & RESOURCES,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 121 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 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1997 VL 42 BP 105 EP 137 PG 33 WC Medicine, General & Internal SC General & Internal Medicine GA BH96D UT WOS:A1997BH96D00004 PM 9048118 ER PT J AU Ognibene, FP AF Ognibene, FP TI Pathogenesis and innovative treatment of septic shock SO ADVANCES IN INTERNAL MEDICINE, VOL 42 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID TUMOR-NECROSIS-FACTOR; CRITICALLY ILL PATIENTS; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NITRIC-OXIDE SYNTHASE; LEFT-VENTRICULAR PERFORMANCE; HUMAN MONOCLONAL-ANTIBODY; GRAM-NEGATIVE BACTEREMIA; PLACEBO-CONTROLLED TRIAL; INTENSIVE-CARE UNIT; LOW-DOSE DOPAMINE RP Ognibene, FP (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 89 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1997 VL 42 BP 313 EP 338 PG 26 WC Medicine, General & Internal SC General & Internal Medicine GA BH96D UT WOS:A1997BH96D00009 PM 9048123 ER PT S AU Striker, GE Klahr, S AF Striker, GE Klahr, S BE Schrier, RW TI Clinical trials in progression of chronic renal failure SO ADVANCES IN INTERNAL MEDICINE, VOL 42 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID CONVERTING ENZYME-INHIBITION; DIABETIC NEPHROPATHY; PROTEIN RESTRICTION; BLOOD-PRESSURE; DISEASE; MICROALBUMINURIA; MELLITUS; DIET; MANAGEMENT; RECOMMENDATIONS C1 WASHINGTON UNIV, JEWISH HOSP ST LOUIS, SCH MED, DEPT MED, ST LOUIS, MO 63110 USA. RP Striker, GE (reprint author), NIDDKD, DIV KIDNEY UROL & HEMATOL DIS, NIH, BETHESDA, MD 20892 USA. NR 53 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 USA SN 0065-2822 BN 0-8151-8315-1 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1997 VL 42 BP 555 EP 595 PG 41 WC Medicine, General & Internal SC General & Internal Medicine GA BH96D UT WOS:A1997BH96D00016 PM 9048130 ER PT J AU Lane, MA Ingram, DK Roth, GS AF Lane, MA Ingram, DK Roth, GS TI Beyond the rodent model: Calorie restriction in rhesus monkeys SO AGE LA English DT Article ID TERM DIETARY RESTRICTION; HIGH-DENSITY-LIPOPROTEIN; ISCHEMIC-HEART-DISEASE; AGE-RELATED-CHANGES; FOOD RESTRICTION; FISCHER-344 RATS; MYOCARDIAL-INFARCTION; METABOLIC-RATE; DEHYDROEPIANDROSTERONE-SULFATE; INSULIN SENSITIVITY AB Lifespan extension and reduction of age-related disease by calorie restriction (CR) are among the most consistent findings in gerontological research. The well known effects of CR have been demonstrated many times in rodents and other short-lived species. However, effects of CR on aging in longer-lived species, more closely related to humans, were unknown until recently. Studies of CR and aging using nonhuman primates (rhesus monkeys) were begun several years ago at the National Institute on Aging, the University of Wisconsin-Madison, and the University of Maryland. These studies are beginning to yield useful data regarding the effects of this nutritional intervention in primates. Several studies from these ongoing investigations have shown that rhesus monkeys on CR exhibit physiological responses to CR that parallel findings in rodents. In addition, several potential biomarkers of aging are being evaluated and preliminary findings suggest the possibility that CR in rhesus monkeys could slow the rate of aging and reduce age-related disease, specifically diabetes and cardiovascular disease. It will be several years before conclusive proof that CR slows aging and extends life span in primates is established, however, results from these exciting studies suggest the possibility that the anti-aging effects of CR reported in rodents also occur in longer-lived species such as nonhuman primates, strenghtening the possibility that this nutritional intervention will also prove beneficial in longer-lived species, including humans. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave,Hopkins Bayview Res Campus, Baltimore, MD 21224 USA. EM MLANE@vax.grc.nia.nih.gov NR 75 TC 49 Z9 52 U1 0 U2 1 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 AGE JI Age PD JAN PY 1997 VL 20 IS 1 BP 45 EP 56 DI 10.1007/s11357-997-0004-2 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ZB179 UT WOS:000072444300004 PM 23604290 ER PT J AU Sunila, I Vaccarezza, M Pantaleo, G Fauci, AS Orenstein, JM AF Sunila, I Vaccarezza, M Pantaleo, G Fauci, AS Orenstein, JM TI Gp120 is present on the plasma membrane of apoptotic CD4 cells prepared from lymph nodes of HIV-1-infected individuals: An immunoelectron microscopic study SO AIDS LA English DT Article DE gp120; apoptosis; CD4+ cells; lymph node; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; HIV-INFECTED PERSONS; T-CELLS; MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; PROGRAMMED DEATH; ACTIVATION; DISEASE; AIDS AB Objective: To study whether free gp120 can be detected on the plasma membranes of apoptotic CD4+ T lymphocytes in lymph nodes from HIV-positive patients. Methods: Lymph-node cell suspensions prepared from three HIV-positive patients were studied by pre-embedding, double-immunogold-labeling to identify cell type, determine cell morphology, and detect the presence of bound gp120 molecules. Cells were classified by their surface antigens as helper/inducer T lymphocytes (CD4+), cytotoxic/suppressor T lymphocytes (CD8+), B cells (CD20+), and total lymphocytes [CD45+, leukocyte common antigen (LCA)+]. Results: gp120 colabeled with both apoptotic and normal CD4+ T lymphocytes and LCA+ cells, but not with either apoptotic or normal CD8+ T lymphocytes or B cells. gp120 was more often identified on apoptotic than on normal CD4+ T lymphocytes. The gp120 and CD45 label were often colocalized. HIV particles were not identified to be associated with or budding from either normal or apoptotic lymphocytes. Conclusions: Free gp120 is found bound to CD4+ T cells in lymph nodes of HIV-infected individuals and potentially mark them for premature death by apoptosis. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. RP Sunila, I (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,2300 EYE ST NW,WASHINGTON,DC 20037, USA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X FU NIAID NIH HHS [NIAID 263-94-D-0217] NR 38 TC 28 Z9 31 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JAN PY 1997 VL 11 IS 1 BP 27 EP 32 DI 10.1097/00002030-199701000-00005 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WB212 UT WOS:A1997WB21200005 PM 9110072 ER PT J AU Brouwers, P Hendricks, M Lietzau, JA Pluda, JM Mitsuya, H Broder, S Yarchoan, R AF Brouwers, P Hendricks, M Lietzau, JA Pluda, JM Mitsuya, H Broder, S Yarchoan, R TI Effect of combination therapy with zidovudine and didanosine on neuropsychological functioning in patients with symptomatic HIV disease: A comparison of simultaneous and alternating regimens SO AIDS LA English DT Article DE HIV dementia; antiviral therapy; macrophages; neuropsychological ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; DEMENTIA COMPLEX; INFECTION; CHILDREN; REPLICATION; AZT; ENCEPHALOPATHY; DIDEOXYINOSINE; MACROPHAGES AB Objective: To evaluate the effects of treatment with alternating and simultaneous regimens of zidovudine and didanosine on neuropsychological Function in patients with symptomatic HIV-1 disease, focusing on patients with possible HIV-1-associated central nervous system (CNS) compromise at entry. Design: Randomized non-blinded clinical trial. Setting: Government medical research center. Patients: Thirty-eight patients with symptomatic HIV-1 disease, of whom 21 had evidence of CNS compromise at entry. Results: After 12 weeks of therapy, overall significant improvements in memory (P < 0.01) and focused attention (P < 0.001) were seen on both regimens. These gains, however, were largely limited to those patients with HIV-1-associated CNS compromise at entry (P < 0.05). Improvements were also noted in receptive vocabulary, reading, perceptual discrimination and reasoning, divided attention, motor strength, and in mood and affect. Improvements in those latter functions were generally of limited magnitude and were of comparable size for both compromised and non-compromised patients. There was no overall difference between the two drug regimens in the effects on CNS parameters. Conclusions: Therapy-related improvements were noted particularly for patients with HIV-1-associated CNS compromise. Neuropsychological functions that have been implicated in AIDS dementia - memory and attention - showed the greatest gains. In contrast to the previously described superiority of the simultaneous regimen with regard to immunologic and virologic parameters, there was no difference between the regimens with regard to CNS measures. This supports the contention that the CNS constitutes a relatively independent compartment in terms of HIV disease and treatment. C1 NCI,NIH,MED BRANCH,BETHESDA,MD 20892. NCI,NIH,OFF DIRECTOR,BETHESDA,MD 20892. RP Brouwers, P (reprint author), NCI,NIH,HIV & AIDS MALIGNANCY BRANCH,BLDG 10,RM 13N240,BETHESDA,MD 20892, USA. NR 42 TC 36 Z9 36 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JAN PY 1997 VL 11 IS 1 BP 59 EP 66 DI 10.1097/00002030-199701000-00009 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WB212 UT WOS:A1997WB21200009 PM 9110076 ER PT J AU Berger, EA AF Berger, EA TI HIV entry and tropism: the chemokine receptor connection SO AIDS LA English DT Review DE fusion; tropism; chemokine receptors; transmission; pathogenesis; therapy; vaccines ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL-LINE; 7-TRANSMEMBRANE DOMAIN RECEPTOR; TISSUE-SPECIFIC EXPRESSION; AMINO-ACID SUBSTITUTIONS; ENVELOPE GLYCOPROTEIN; HUMAN CD4; V3 LOOP; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION RP Berger, EA (reprint author), NIAID,VIRAL DIS LAB,NIH,BLDG 4,ROOM 236,BETHESDA,MD 20892, USA. NR 141 TC 236 Z9 238 U1 1 U2 7 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PY 1997 VL 11 SU A BP S3 EP S16 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YJ012 UT WOS:A1997YJ01200002 PM 9451961 ER PT J AU Rubbert, A Weissman, D Combadiere, C Pettrone, KA Daucher, JA Murphy, PM Fauci, AS AF Rubbert, A Weissman, D Combadiere, C Pettrone, KA Daucher, JA Murphy, PM Fauci, AS TI Multifactorial nature of noncytolytic CD8(+) T cell-mediated suppression of HIV replication: beta-Chemokine-dependent and -independent effects SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS-REPLICATION; DENDRITIC CELLS; INFECTION; LYMPHOCYTES; CYTOKINES; RANTES; INTERLEUKIN-8; EXPRESSION; DISEASE AB Chemokines were originally characterized by their ability to direct migration and induce activation of selected leukocyte populations. The beta-chemokines MIP-1 alpha, MIP-beta, and RANTES have been implicated in the suppression of viral replication by CD8(+) T cells from HIV-infected individuals. The present study was undertaken to evaluate the effect of beta-chemokines on HIV replication in cocultures of dendritic cells (DCs) and CD4(+) T cells, an in vitro model of the lymphoid microenvironment. In the acute infection system, where DCs from uninfected individuals are pulsed with HIV and cocultured with autologous CD4(+) T cells, no inhibition of replication of monocytotropic or T cell tropic viral isolates by MIP-1 alpha, MIP-1 beta, and RANTES, alone or in combination, was observed. In contrast, in an endogenous infection system, where the DCs and CD4(+) T cells were obtained from HIV-infected subjects, addition of recombinant beta-chemokines suppressed HIV replication. However, neutralizing antibodies to beta-chemokines did not affect the suppressive activity of CD8(+) T cells from HIV-infected donors in either system, suggesting that CD8(+) T cell-mediated suppression is not due exclusively to beta-chemokines. Furthermore, no significant differences in secretion of MIP-1 alpha; MIP-1 beta, and RANTES by purified CD8(+) T cells were noted in uninfected versus HIV-infected donors, regardless of the stage of disease. These results indicate that EW suppression by CD8(+) T cells derived from HIV-infected donors is a multifactorial phenomenon and not limited to the action of MIP-1 alpha, MIP-1 beta, and RANTES. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 26 TC 52 Z9 52 U1 1 U2 1 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 JAN 1 PY 1997 VL 13 IS 1 BP 63 EP 69 DI 10.1089/aid.1997.13.63 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WA167 UT WOS:A1997WA16700009 PM 8989428 ER PT J AU Dong, QS Karanian, JW Wesely, L Myers, AK AF Dong, QS Karanian, JW Wesely, L Myers, AK TI Inhibition of platelet aggregation in whole blood after exposure of rats to alcohol by inhalation SO ALCOHOL LA English DT Article DE platelet aggregation; blood alcohol concentration; inhalation ID HEART-DISEASE; ETHANOL; MORTALITY; CONSUMPTION; ACTIVATION; INVITRO AB The dose-effect relationship between blood alcohol concentration (BAG) and altered platelet function was examined in whole blood in a rat model of alcohol exposure by inhalation, using the impedance method of ex vivo whole blood platelet aggregation. With rates of alcohol addition to the chamber air inflow from 29 to 56 mg ethanoyl/l air/min, BAC was dependent on duration of exposure and concentration of alcohol in the air. Next, 3, 6, and 9 h exposures to the highest delivery rate were used, and platelet aggregability was tested. After 9 h, BAC reached 453 +/- 16 mg% and aggregation responses to three doses of collagen were significantly lower than in control blood (p < 0.01). Less consistent inhibition was observed with arachidonic acid and ADP, and also when exposure duration was reduced. However, some significant inhibition of collagen-induced aggregation (p < 0.05) was observed with BAC as low as 127 +/- 15 mg%. These experiments demonstrate that in vivo alcohol exposure inhibits, in a concentration-dependent manner, ex vivo rat whole blood platelet aggregation, at BACs readily attained in humans by ingestion. Copyright (C) 1997 Elsevier Science Inc. C1 GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,NIH,BETHESDA,MD 20892. FU NIAAA NIH HHS [AA 09586] NR 21 TC 2 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD JAN-FEB PY 1997 VL 14 IS 1 BP 49 EP 54 DI 10.1016/S0741-8329(96)00105-X PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA WD854 UT WOS:A1997WD85400008 PM 9014024 ER PT J AU Zakhari, S AF Zakhari, S TI Alcohol and the cardiovascular system - Molecular mechanisms for beneficial and harmful action SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE chronic AODE (alcohol and other drug effects); molecular interaction; biochemical mechanism; lipoproteins; platelets; blood coagulation; moderate AOD use; heavy AOD use; therapeutic drug effect; AODR (alcohol and other drug related) disorder; alcoholic cardiomyopathy; cardiac arrhythmia; hypertensive disorder; stroke; literature review; cell signaling ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; ESTER TRANSFER PROTEIN; PLASMINOGEN-ACTIVATOR; INDUCED HYPERTENSION; RISK-FACTORS; CONSUMPTION; ETHANOL; WOMEN; JAPANESE AB Alcohol can be beneficial or harmful to the cardiovascular system, depending on the amount consumed and the characteristics of the consumer, Of the numerous cellular and molecular mechanisms that are thought to explain the beneficial effects of moderate drinking, this article discusses four, involving (1) high density lipoproteins, (2) cellular signaling, (3) platelet function in blood clot formation, and (4) stimulation of blood clot dissolution, Although light-to-moderate drinking can protect against coronary artery disease, heavy alcohol consumption can damage the cardiovascular system, resulting in maladies such as heart muscle disorders, irregular heart rhythms, high blood pressure, and strokes, This article summarizes representative epidemiological and animal studies on these cardiovascular consequences of chronic heavy alcohol consumption and reviews mechanisms that have been suggested to explain alcohol's effects. RP Zakhari, S (reprint author), NIAAA,BIOMED RES BRANCH,BETHESDA,MD 20205, USA. NR 47 TC 49 Z9 51 U1 2 U2 5 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1997 VL 21 IS 1 BP 21 EP 29 PG 9 WC Substance Abuse SC Substance Abuse GA XP598 UT WOS:A1997XP59800003 PM 15706760 ER PT S AU Kosaraju, SR Schaffer, AA Biesecker, LG AF Kosaraju, SR Schaffer, AA Biesecker, LG BE Dehne, F RauChaplin, A Sack, JR Tamassia, R TI Approximation algorithms for a genetic diagnostics problem SO ALGORITHMS AND DATA STRUCTURES SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 5th International Workshop on Algorithms and Data Structures (WADS 97) CY AUG 06-08, 1997 CL TUNS DALHOUSIE UNIV, HALIFAX, CANADA SP Carleton Univ, TUNS Dalhousie Univ HO TUNS DALHOUSIE UNIV ID POLYMERASE CHAIN-REACTION; MENTAL-RETARDATION; DNA POLYMORPHISMS; REARRANGEMENTS; PCR AB We define and study a combinatorial problem called WEIGHTED DIAGNOSTIC COVER (WDC) that models the use of a laboratory technique called genotyping in the diagnosis of a important class of chromosomal aberrations. An optimal solution to WDC would enable us to define a genetic assay that maximizes the diagnostic power for a specified cost of laboratory work. We develop approximation algorithms for WDC by making use of the well-known problem SET COVER for which the greedy heuristic has been extensively studied. We prove worst-case performance bounds on the greedy heuristic for WDC and for another heuristic we call directional greedy. We implemented both heuristics. We also implemented a local search heuristic that takes the solutions obtained by greedy and dir-greedy and applies swaps until they are locally optimal. We report their performance on a real data set that is representative of the options that a clinical geneticist faces for the real diagnostic problem. Many open problems related to WDC remain, both of theoretical interest and practical importance. C1 Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. RP Kosaraju, SR (reprint author), Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. RI Schaffer, Alejandro/F-2902-2012 NR 23 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0302-9743 BN 3-540-63307-3 J9 LECT NOTES COMPUT SC PY 1997 VL 1272 BP 69 EP 92 PG 24 WC Computer Science, Theory & Methods SC Computer Science GA BL01E UT WOS:000074043700007 ER PT J AU Fortinsky, RH Hazuda, HP Larson, EB Lindeman, DA Mullican, CA Tetzloff, I Wetle, T AF Fortinsky, RH Hazuda, HP Larson, EB Lindeman, DA Mullican, CA Tetzloff, I Wetle, T TI Principles underlying selection of outcomes in Alzheimer disease research SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT Conference on Defining and Measuring Outcomes in Alzheimers Disease - Do We Agree CY SEP 11-12, 1996 CL WASHINGTON, D.C. SP Alzheimers Assoc, Advisory Panel Alzheimers Dis, Agcy Hlth Care Policy & Res, Dept Vet Affairs, NIA, NIMH, NINR, Univ Hosp Cleveland C1 Case Western Reserve Univ, Sch Med WG37C, Dept Med, Cleveland, OH 44106 USA. Univ Texas, Dept Med, San Antonio, TX 78285 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Rush Presbyterian St Lukes Med Ctr, Rush Inst Aging, Chicago, IL 60612 USA. US Dept HHS, Agcy Hlth Care Policy & Res, Rockville, MD 20852 USA. US Adm Aging, Washington, DC USA. NIA, Bethesda, MD 20892 USA. RP Fortinsky, RH (reprint author), Case Western Reserve Univ, Sch Med WG37C, Dept Med, 10900 Euclid Ave, Cleveland, OH 44106 USA. NR 0 TC 2 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PY 1997 VL 11 SU 6 BP 184 EP 185 PG 2 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA YN768 UT WOS:000071204600026 PM 9437466 ER PT J AU Sunderland, T Molchan, SE Little, JT Bahro, M Putnam, KT Weingartner, H AF Sunderland, T Molchan, SE Little, JT Bahro, M Putnam, KT Weingartner, H TI Pharmacologic challenges in Alzheimer disease and normal controls: Cognitive modeling in humans SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT Symposium on Alzheimer Disease Therapy - Behavior as an Efficacy Outcome, at the 5th International Conference on Alzheimers Disease and Related Disorders CY JUL 24-29, 1996 CL OSAKA, JAPAN SP Eli Lilly & Co DE pharmacomodeling; cholinergic; nicotinic; serotonergic; combination; deficit ID META-CHLOROPHENYLPIPERAZINE; SEROTONIN AGONIST; DYSFUNCTION; INHIBITION; MOOD AB Alzheimer disease (AD) is a progressive disorder characterized by cognitive and behavioral dysfunction, central to which are deficits in the cholinergic and other neurotransmitter systems. These result in the essential symptoms of dementia, including impairment of memory, judgment, and abstract thinking. The pharmacologic relationships among the various neurotransmitters (e.g., cholinergic, serotonergic, nicotinic, and dopaminergic) an highly complex and are still being investigated. information on the pharmacologic basis of cognitive and behavioral dysfunction in AD has applications to drug therapy. One method of obtaining this information is by pharmacomodeling, using individual or combined drugs. Joint cholinergic antagonism with both muscarinic and nicotinic blockade combines to produce short-term memory impairment, which approximates to mild AD in normal elderly people. This effect is better than that achieved with either agent alone. Mixed cholinergic and serotonergic antagonism has an effect on the cognitive function of AD patients and on depression-related behavior. Dopaminergic dysfunction is linked with the development of hallucinatory and psychotic symptoms and may also be involved in dysfunction of verbal fluency. Combination pharmacomodeling allows the various behavioral and cognitive deficits in AD to be studied and allows models for drug trials to be developed. RP Sunderland, T (reprint author), NIMH,SECT GERIATR PSYCHIAT,GERIATR PSYCHIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 3D41,BETHESDA,MD 20892, USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PY 1997 VL 11 SU 4 BP S23 EP S26 PG 4 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA YC126 UT WOS:A1997YC12600005 PM 9339269 ER PT J AU Lee, M Gardin, JM Lynch, JC Smith, VE Tracy, RP Savage, PJ Szklo, M Ward, BJ AF Lee, M Gardin, JM Lynch, JC Smith, VE Tracy, RP Savage, PJ Szklo, M Ward, BJ TI Diabetes mellitus and echocardiographic left ventricular function in free-living elderly men and women: The cardiovascular health study SO AMERICAN HEART JOURNAL LA English DT Article ID DIASTOLIC FUNCTION; DOPPLER ECHOCARDIOGRAPHY; TRANSMITRAL FLOW; HEART; MASS; DISEASE; CARDIOMYOPATHY; AGE AB This report describes the relation among diabetes, blood pressure, and prevalent cardiovascular disease, and echocardiographically measured left ventricular mass and filling (transmitral valve flow) velocities in the Cardiovascular Health Study, a cohort of 5201 men and women greater than or equal to 65 years of age. Ventricular septal and left posterior wall thicknesses were greater in diabetic than in nondiabetic subjects, showing a significant linear trend (p = 0.025 for ventricular septal thickness in both sexes combined, p = 0.002 for posterior wall thickness) with increased duration of diabetes. Increased wall thickness of the ventricular septum or the left posterior wall was not associated with prevalent coronary heart disease (CHD) in the cohort. Increased left ventricular mass was associated with diabetic persons not reporting CHD and with all subjects with CHD regardless of glucose tolerance status. After adjusting for body weight, blood pressure, heart rate, and prevalent coronary or cerebrovascular disease, diabetes (as measured by glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination) remained an independent predictor of increased left ventricular mass among men and women (174.2 gm in diabetic men vs 169.8 gm in normal men, 138.2 gm in diabetic women vs 134.0 gm in normal women, p = 0.043 for both sexes combined). Both early and late diastolic transmitral peak Row velocities were higher with increased duration of diabetes, but the calculated ratio of the early peak flow velocity to the late velocity (E/A ratio) did not differ significantly between subjects with historical diabetes and those with normal fasting glucose (both genders combined, p = 0.190). Glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination were significant independent predictors of the late transmitral peak flow velocity and its integrated Row-velocity curve but not for the integral of the early peak Row velocity or the E/A ratio. Diabetes is associated with abnormal left ventricular structure and function in elderly persons. This association persists after adjustment for body weight, blood pressure, heart rate, and reported coronary or cerebrovascular disease. C1 UNIV CALIF DAVIS, DEPT GEN MED, DAVIS, CA 95616 USA. UNIV CALIF IRVINE, DEPT MED, DIV CARDIOL, IRVINE, CA 92717 USA. UNIV WASHINGTON, DEPT BIOSTAT, SEATTLE, WA 98195 USA. ALBANY MED COLL, DIV CARDIOL, ALBANY, NY 12208 USA. UNIV VERMONT, SCH MED, DEPT PATHOL, BURLINGTON, VT 05405 USA. UNIV VERMONT, SCH MED, DEPT BIOCHEM, BURLINGTON, VT 05405 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, BALTIMORE, MD USA. FU NHLBI NIH HHS [N01-HC85079, HC-85086] NR 31 TC 89 Z9 91 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD JAN PY 1997 VL 133 IS 1 BP 36 EP 43 DI 10.1016/S0002-8703(97)70245-X PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WC589 UT WOS:A1997WC58900005 PM 9006288 ER PT J AU Cutler, JA Stamler, J AF Cutler, JA Stamler, J TI Introduction and summary of the dietary and nutritional methods and findings in the Multiple Risk Factor Intervention Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article C1 NHLBI, PREVENT & DEMONSTRAT RES BRANCH, NIH, BETHESDA, MD 20892 USA. NORTHWESTERN UNIV, DEPT PREVENT MED, CHICAGO, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 1997 VL 65 SU 1 BP 184 EP 190 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WB202 UT WOS:A1997WB20200002 ER PT J AU Kjelsberg, MO Cutler, JA Dolecek, TA AF Kjelsberg, MO Cutler, JA Dolecek, TA TI Brief description of the Multiple Risk Factor Intervention Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE nutrition; clinical trial; MRFIT description ID BLOOD-PRESSURE; MRFIT; SMOKING AB The Multiple Risk Factor Intervention Trial (MRFIT) was one of the coronary heart disease prevention trials recommended to the National Heart and Lung Institute in 1971 as an alternative to a national single-factor dietary trial, which was judged to be infeasible. MRFIT was a randomized, primary prevention trial, conducted at 22 US clinical centers from 1973 to 1982 to test whether lowering elevated serum cholesterol and diastolic blood pressure and ceasing cigarette smoking would reduce coronary heart disease mortality. Men 35-57 y of age (n = 12 866) with one or more of these risk factors were randomly assigned to the special intervention (SI) or usual care (UC) group and followed for 6-8 y. UC men were given information on risk factors, referred to their usual sources of care, and reexamined annually. SI participants received group and individual counseling on a fat-modified diet, a stepped-care drug treatment program for diastolic hypertension (after an initial attempt at blood pressure control by weight reduction, if indicated), and, for cigarette smokers, counseling aimed at cessation. SI men had risk factor assessments every 4 mo and annual examinations that were generally identical to those given to UC men and that always included measurement of blood cholesterol concentration. A listing of variables measured at each visit along with the design and major mortality results of MRFIT are included in this chapter. C1 NHLBI, PREVENT & DEMONSTRAT RES BRANCH, NIH, BETHESDA, MD 20892 USA. ILLINOIS DEPT PUBL HLTH, DIV EPIDEMIOL STUDIES, SPRINGFIELD, IL 62761 USA. RP UNIV MINNESOTA, SCH PUBL HLTH, DIV BIOSTAT, 2221 UNIV AVE SE, MINNEAPOLIS, MN 55414 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 1997 VL 65 SU 1 BP 191 EP 195 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WB202 UT WOS:A1997WB20200003 ER PT J AU Dolecek, TA Johnson, RL Grandits, GA FarrandZukel, M Caggiula, AW AF Dolecek, TA Johnson, RL Grandits, GA FarrandZukel, M Caggiula, AW TI Nutritional adequacy of diets reported at baseline and during trial years 1-6 by the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE nutrition intervention; nutritional adequacy assessment ID UNITED-STATES; NUTRIENT AB This chapter addresses whether a fat-modified diet as implemented by special intervention participants in the Multiple Risk Factor Intervention Trial affected intake of vitamins and minerals, and whether nutritional adequacy was altered by this dietary intervention. Despite likely underreporting of intake, for men in the special intervention group, most mean intakes of 15 micronutrients estimated from 24-h recalls were above established recommended dietary allowances. A few means were slightly below; lowest was zinc at 77% (from 98% at baseline) followed by calcium at 79% (from 102% at baseline). Calculated as nutrient densities (per 1000 kcal), nutrients that were below indexes of nutritional quality (the corresponding standard based on nutrient density) during follow-up, although not reduced below baseline by this measure, were vitamin D, calcium, iron (marginally), and zinc. Analyses by food groups indicated that intake of these nutrients might have been improved by greater replacement of high- and medium-fat dairy products with low-fat dairy products (for vitamin D and calcium) and of high-fat meats with low-fat meats, fish, or poultry (for iron and zinc), or (because iron was adequate) by increasing consumption of vegetables and whole-grain products. The safety of the eating pattern was further confirmed by more favorable micronutrient profiles in men who adhered best to the intervention program, as measured by degree of serum cholesterol reduction and weight loss. C1 UNIV MINNESOTA, SCH PUBL HLTH, DIV BIOSTAT, MINNEAPOLIS, MN 55414 USA. ILLINOIS DEPT PUBL HLTH, DIV EPIDEMIOL STUDIES, SPRINGFIELD, IL 62761 USA. UNIV SO CALIF, DEPT MED, LOS ANGELES, CA USA. NHLBI, BETHESDA, MD 20892 USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, PITTSBURGH, PA 15260 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 1997 VL 65 SU 1 BP 305 EP 313 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WB202 UT WOS:A1997WB20200011 ER PT J AU ElenitobaJohnson, KSJ Kumar, S Lim, MS Kingma, DW Raffeld, M Jaffe, ES AF ElenitobaJohnson, KSJ Kumar, S Lim, MS Kingma, DW Raffeld, M Jaffe, ES TI Marginal zone B-cell lymphoma with monocytoid B-cell lymphocytes in pediatric patients without immunodeficiency - A report of two cases SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE malignant lymphoma; marginal zone B-cell lymphoma; monocytoid B-cells ID MALIGNANT-LYMPHOMA; TISSUE; DIAGNOSIS; TOXOPLASMOSIS; FEATURES; BIOPSY AB We report two cases of marginal zone B-cell lymphoma in two patients 6 and 18 years of age, respectively (cases 1 and 2) who had no clinical evidence of immunodeficiency or risk factors for human immunodeficiency virus (HIV) infection. Histologic analysis in both cases revealed diffuse nodal effacement by a monotonous population of atypical lymphoid cells with abundant pale cytoplasm and round to oval nuclei, with very infrequent mitotic activity. The neoplastic cells in both cases were of B-cell Lineage (CD20 and CD79a positive), with CD43 coexpression. One case showed monoclonal light chain expression, and polymerase chain reaction analysis demonstrated clonal rearrangements of the immunoglobulin heavy chain gene in both eases. Abnormal cytogenetic findings were detected in case 2, in which metaphase spreads revealed trisomy 13 (karyotype 47, XY,+13). Although trisomy 13 has been described in association with acute nonlymphocytic leukemias and myelodysplastic syndromes, this case represents the first documented association of trisomy 13 with marginal zone B-cell lymphoma. Interphase cytogenetics analysis for trisomy 3, reported to be associated with mucosa-associated lymphoid tissue (MALT) lymphomas, was negative in both cases. Although low-grade lymphomas of the MALT type have been reported in HIV-positive patients, the two cases reported here are unique in that they occurred in young patients without HIV infection or any other evidence of immunodeficiency. C1 NCI,NIH,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. NR 26 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1997 VL 107 IS 1 BP 92 EP 98 PG 7 WC Pathology SC Pathology GA VZ155 UT WOS:A1997VZ15500017 PM 8980374 ER PT J AU Robertson, EB Donnermeyer, JF AF Robertson, EB Donnermeyer, JF TI Illegal drug use among rural adults: Mental health consequences and treatment utilization SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article ID PREVALENCE; DISORDERS; AMERICA AB This study uses the National Household Survey on Drug Abuse to examine mental health consequences and treatment utilization among nonmetropolitan and rural adults. The study employs an ecological systems perspective, dividing the study population into three groups: nonmetropolitan-rural, nonmetropolitan-urban, and metropolitan-rural, Logistic regression analysis is used to examine four sets of factors related to self-report of mental health problems among drug-using adults, including community level features, family characteristics, personal characteristics, and stress factors. Perceived ease of purchasing cocaine, number of moves in last five years, employment in blue-collar occupations, number of jobs in last five years, and residence in neighborhoods with a low rate (< 10%) of minority households were significantly related to self-report problems. Results of the analysis are discussed in terms of barriers to utilization of treatment and rehabilitation services among nonmetropolitan and rural adults, such as availability and access to facilities and professional services, social stigma, ability to afford services, and the difficulty for rural communities to support in-hospital and outpatient services. C1 OHIO STATE UNIV,COLUMBUS,OH 43210. RP Robertson, EB (reprint author), NIDA,ROCKVILLE,MD, USA. NR 28 TC 28 Z9 28 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 1997 VL 23 IS 3 BP 467 EP 484 DI 10.3109/00952999709016890 PG 18 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA XN734 UT WOS:A1997XN73400010 PM 9261493 ER PT J AU Kosten, TR Rosen, MI McMahon, TL Bridge, TP OMalley, SS Pearsall, R OConnor, PG AF Kosten, TR Rosen, MI McMahon, TL Bridge, TP OMalley, SS Pearsall, R OConnor, PG TI Treatment of early AIDS dementia in intravenous drug users: High versus low dose peptide T SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article ID COMPLEX; INFECTION AB This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four weeks. Neuropsychological performance improved in four of five patients treated with the high dose, but at the lower dose, three of four patients showed no improvement on Peptide T when compared with placebo. When subjects who received the high dose were compared with those who received the low dose, a significant dose effect was found only during the active phase of the trial even after correction for differences in level of functioning at baseline. C1 DEPT PSYCHIAT,DIV SUBST ABUSE,W HAVEN,CT. YALE UNIV,SCH MED,DEPT MED,NEW HAVEN,CT 06510. NIDA,MEDICAT DEV DIV,ROCKVILLE,MD. FU NIDA NIH HHS [KO2-DAO112, P50-DAO4060, R18-DAO7190] NR 38 TC 11 Z9 11 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 1997 VL 23 IS 4 BP 543 EP 553 DI 10.3109/00952999709016894 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA YF126 UT WOS:A1997YF12600004 PM 9366972 ER PT J AU Korn, EL Graubard, BI Midthune, D AF Korn, EL Graubard, BI Midthune, D TI Time-to-event analysis of longitudinal follow-up of a survey: Choice of the time-scale SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; epidemiologic methods; proportional hazards models; statistics; survey methods; survival analysis ID CORONARY HEART-DISEASE; NHANES-I; NATIONAL COHORT; WEIGHT-LOSS; MORTALITY; RISK; HEALTH; MODELS; DEATH; WOMEN AB Following individuals sampled in a large-scale health survey for the development of diseases and/or death offers the opportunity to assess the prognostic significance of various risk factors, The proportional hazards regression model, which allows for the control of covariates, is frequently used for the analysis of such data, The authors discuss the appropriate time-scale for such regression models, and they recommend that age rather than time since the baseline survey (time-on-study) be used. Additionally, with age as the time-scale, control for calendar-period and/or birth cohort effects can be achieved by stratifying the model on birth cohort. Because, as discussed by the authors, many published analyses have used regression models with time-on-study as the time-scale, it is important to assess the magnitude of the error incurred from this type of incorrect modeling. The authors provide simple conditions for when incorrect use of time-on-study as the time-scale will nevertheless yield approximately unbiased proportional hazards regression coefficients. Examples are given using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Followup Study. Additional issues concerning the analysis of longitudinal follow-up of survey data are briefly discussed. C1 NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Korn, EL (reprint author), NCI,BIOMETR RES BRANCH EPN 739,BETHESDA,MD 20892, USA. NR 32 TC 517 Z9 518 U1 0 U2 19 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 1997 VL 145 IS 1 BP 72 EP 80 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WA787 UT WOS:A1997WA78700010 PM 8982025 ER PT J AU Zhou, HB Weinberg, CR AF Zhou, HB Weinberg, CR TI Smoking reduces fecundity: A European Multicenter Study on infertility and subfecundity SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID PREGNANCY; TIME RP Zhou, HB (reprint author), NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 1997 VL 145 IS 1 BP 81 EP 81 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WA787 UT WOS:A1997WA78700011 PM 8982026 ER PT J AU Fox, KM Durham, N Garruto, RM Plato, CC AF Fox, KM Durham, N Garruto, RM Plato, CC TI The history and future of dermatoglyphics. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 UNIV NO IOWA,CEDAR FALLS,IA 50614. NIH,BALTIMORE,MD. NR 0 TC 0 Z9 0 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 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1997 VL 9 IS 1 BP 116 EP 116 PG 2 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA WG242 UT WOS:A1997WG24200032 ER PT J AU Garruto, RM Weitz, CA Chin, CT Liu, JZ Liu, RL He, X AF Garruto, RM Weitz, CA Chin, CT Liu, JZ Liu, RL He, X TI Arterial oxygen saturation and hematological characteristics among Han born and raised near sea level and at high altitude in western China. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. TEMPLE UNIV,PHILADELPHIA,PA 19122. BEIJING MED UNIV,MATERNAL & CHILDRENS HOSP,BEIJING 100083,PEOPLES R CHINA. QINGHAI BUR PUBL HLTH,DEPT MATERNA & CHILD HLTH,XINING,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1997 VL 9 IS 1 BP 122 EP 122 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA WG242 UT WOS:A1997WG24200038 ER PT J AU LethbridgeCejku, M Plato, CC Rudan, P AF LethbridgeCejku, M Plato, CC Rudan, P TI Gender differences in effect of occupation on hand osteoarthritis: Data from the population isolate of Brac Island, Croatia. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. INST ANTHROPOL RES,ZAGREB,CROATIA. NIA,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1997 VL 9 IS 1 BP 136 EP 136 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA WG242 UT WOS:A1997WG24200052 ER PT J AU Pearson, JD Landis, PK Metter, EJ Fozard, JL Cadeddu, JA Partin, AW Epstein, JI Carter, HB AF Pearson, JD Landis, PK Metter, EJ Fozard, JL Cadeddu, JA Partin, AW Epstein, JI Carter, HB TI Free/total prostate-specific antigen ratio and prostate composition in men with benign prostatic hyperplasia. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 MERCK RES LABS,BLUE BELL,PA. NIA,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. RI Fozard, James Leonard/B-3660-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1997 VL 9 IS 1 BP 152 EP 152 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA WG242 UT WOS:A1997WG24200068 ER PT J AU Plato, CC Roy, TA LethbridgeCejku, M Tobin, JD AF Plato, CC Roy, TA LethbridgeCejku, M Tobin, JD TI Bone loss with age: Cross-sectional, longitudinal and cross-cultural considerations. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NIA, LAB CLIN PHYSIOL, GRC, NIH, BALTIMORE, MD 21224 USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1042-0533 EI 1520-6300 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1997 VL 9 IS 1 BP 153 EP 153 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA WG242 UT WOS:A1997WG24200069 ER PT J AU Weitz, CA Garruto, RM Chin, CT Liu, JZ Liu, RL He, X AF Weitz, CA Garruto, RM Chin, CT Liu, JZ Liu, RL He, X TI Morphology and pulmonary function among Han boys and girls born and raised near sea level and at high altitude in western China. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 TEMPLE UNIV,PHILADELPHIA,PA 19122. NIH,BETHESDA,MD 20892. BEIJING MED UNIV,MATERNAL & CHILDRENS HOSP,BEIJING 100083,PEOPLES R CHINA. QUIGHAI BUR PUBL HLTH,DEPT MATERNAL & CHILD HLTH,XINING,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1997 VL 9 IS 1 BP 170 EP 170 PG 2 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA WG242 UT WOS:A1997WG24200086 ER PT J AU Wong, ACC Ning, Y Flint, J Clark, K Dumanski, JP Ledbetter, DH McDermid, HE AF Wong, ACC Ning, Y Flint, J Clark, K Dumanski, JP Ledbetter, DH McDermid, HE TI Molecular characterization of a 130-kb terminal microdeletion at 22q in a child with mild mental retardation SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INSITU HYBRIDIZATION; ALPHA-THALASSEMIA; HUMAN PROACROSIN; ACROSIN ACTIVITY; HUMAN GENOME; CLONING; CHROMOSOMES; INFERTILITY; BREAKPOINT; LIBRARIES AB We have analyzed a recently described 22q13.3 microdeletion in a child with some overlapping features of the cytologically visible 22q13.3 deletion syndrome. Patient NT, who shows mild mental retardation and delay of expressive speech, was previously found to have a paternal microdeletion in the subtelomeric region of 22q. In order to characterize this abnormality further, we have constructed a cosmid/P1 contig covering the terminal 150 kb of 22q, which encompasses the 130-kb microdeletion. The microdeletion breakpoint is within the VNTR locus D22S163. The cloning of the breakpoint sequence revealed that the broken chromosome end was healed by the addition of telomeric repeats, indicating that the microdeletion is terminal. This is the first cloned terminal deletion breakpoint on a human chromosome other than 16p. The cosmid/P1 contig was mapped by pulsed-field gel electrophoresis analysis to within 120 kb of the arylsulfatase A gene, which places the contig in relation to genetic and physical maps of the chromosome. The acrosin gene maps within the microdeletion, similar to 70 kb from the telomere. With the distal end of chromosome 22q cloned, it is now possible to isolate genes that may be involved in the overlapping phenotype of this microdeletion and 22q13.3 deletion syndrome. C1 UNIV ALBERTA,DEPT BIOL SCI,BIOL SCI CTR CW405,EDMONTON,AB T6G 2E9,CANADA. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9DU,ENGLAND. KAROLINSKA INST,DEPT MOL MED,CLIN GENET UNIT,STOCKHOLM,SWEDEN. NR 30 TC 100 Z9 103 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1997 VL 60 IS 1 BP 113 EP 120 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WA818 UT WOS:A1997WA81800017 PM 8981954 ER PT J AU McIntosh, I Clough, MV Schaffer, AA Puffenberger, EG Horton, VK Peters, K Abbott, MH Roig, CM Cutone, S Ozelius, L Kwiatkowski, DJ Pyeritz, RE Brown, LJ Pauli, RM McCormick, MK Francomano, CA AF McIntosh, I Clough, MV Schaffer, AA Puffenberger, EG Horton, VK Peters, K Abbott, MH Roig, CM Cutone, S Ozelius, L Kwiatkowski, DJ Pyeritz, RE Brown, LJ Pauli, RM McCormick, MK Francomano, CA TI Fine mapping of the nail-patella syndrome locus at 9q34 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; LINKAGE ANALYSIS; CHROMOSOME-9; ASSIGNMENT; 9Q31-34; MAP; ACHONDROPLASIA; LOCALIZATION; STRATEGIES; GENES AB Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant, pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and nephropathy. Previous studies have demonstrated linkage of the nail-patella locus to the ABO and adenylate kinase loci on human chromosome 9q34. As a first step toward isolating the NPS gene, we present linkage analysis with 13 polymorphic markers in five families with a total of 69 affected persons. Two-point linkage analysis with the program MLINK showed tight linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1). C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. NIH, NATL CTR HUMAN GENOME RES, MED GENET BRANCH, BETHESDA, MD 20892 USA. NIH, NATL CTR HUMAN GENOME RES, LAB GENET DIS RES, BETHESDA, MD 20892 USA. UNIV WISCONSIN, DEPT PEDIAT, MADISON, WI USA. UNIV WISCONSIN, DEPT MED GENET, MADISON, WI 53706 USA. SO CALIF PERMANENTE MED GRP, DEPT MED GENET, SACRAMENTO, CA USA. MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, CHARLESTOWN, MA USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DIV EXPT MED, BOSTON, MA 02115 USA. RP McIntosh, I (reprint author), JOHNS HOPKINS UNIV, SCH MED, CTR MED GENET, 600 N WOLFE ST, BLALOCK 1012G, BALTIMORE, MD 21287 USA. RI Pyeritz, Reed/A-1364-2010; Schaffer, Alejandro/F-2902-2012 FU NIAMS NIH HHS [AR41135]; NIDCR NIH HHS [DE10293]; NIGMS NIH HHS [GM46846] NR 42 TC 32 Z9 33 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1997 VL 60 IS 1 BP 133 EP 142 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA WA818 UT WOS:A1997WA81800019 PM 8981956 ER PT J AU Norman, RA Thompson, DB Foroud, T Garvey, WT Bennett, PH Bogardus, C Ravussin, E AF Norman, RA Thompson, DB Foroud, T Garvey, WT Bennett, PH Bogardus, C Ravussin, E TI Genomewide search for genes influencing percent body fat in Pima Indians: Suggestive linkage at chromosome 11q21-q22 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID X-RAY ABSORPTIOMETRY; MASS INDEX; MAJOR GENE; SEGREGATION ANALYSIS; QUANTITATIVE TRAIT; COMPLEX TRAITS; MALE TWINS; OBESITY; PREVALENCE; LOCI AB On the basis of accumulating evidence that obesity has a substantial genetic component, a genomewide search fur linkages of DNA markers to percent body fat is ongoing in Pima Indians, a population with a very high prevalence of obesity, An initial screen oi: the genome (>600 markers in 874 individuals) has been completed using highly polymorphic markers (mean heterozygosity = .67), Reported here are the sib-pair linkage results for percent body fat (277 siblings), the best available indicator of overall obesity, Single-marker linkages to percent body fat were evaluated by sib-pair analysis for quantitative traits, From these analyses, the best evidence of genes influencing body fat came from markers at chromosome 11q21-q22 and 3p24.2-p22 (P = .001; LOD = 2.0), Regions flanking these markers were further investigated by multipoint linkage. The evidence for linkage at 11q21-q22 increased to P = .0002 (LOD = 2.8), peaking between markers D11S2000 and D11S2366, Evidence for linkage at 3p24.2-p22 did nor change, No association was detected for any marker in the region, Although several genes are known in the 11q21-q22 region, none have been implicated as candidate genes for obesity. C1 INDIANA UNIV,DEPT MOL & MED GENET,INDIANAPOLIS,IN 46204. MED UNIV S CAROLINA,DIV ENDOCRINOL DIABET & MED GENET,CHARLESTON,SC 29425. RP Norman, RA (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,ROOM 541,4212 N 16TH ST,PHOENIX,AZ 85016, USA. FU NCRR NIH HHS [1 P41 RR03655] NR 43 TC 115 Z9 119 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1997 VL 60 IS 1 BP 166 EP 173 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WA818 UT WOS:A1997WA81800023 PM 8981960 ER PT J AU Proschan, M Davis, B Cutler, J Ford, C Furberg, C Grimm, R Oparil, S AF Proschan, M Davis, B Cutler, J Ford, C Furberg, C Grimm, R Oparil, S TI ALLHAT and calcium channel blockers SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Letter ID MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; ANGINA C1 NHLBI,BETHESDA,MD 20892. NR 10 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 1997 VL 10 IS 1 BP 142 EP 143 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WB877 UT WOS:A1997WB87700021 PM 9008261 ER PT S AU Lee, YJ AF Lee, YJ BE Hayakawa, T Aoshima, M Shimizu, K TI A two-sample nonparametric test with missing observations SO AMERICAN JOURNAL OF MATHEMATICAL AND MANAGEMENT SCIENCES, VOL 17, NOS 1 AND 2, 1997: MULTIVARIATE STATISTICAL INFERENCE - MSI-2000L MULTIVARIATE STATISTICAL ANALYSIS IN HONOR OF PROFESSOR MINORU SIOTANI ON HIS 70TH BIRTHDAY SE AMERICAN JOURNAL OF MATHEMATICAL AND MANAGEMENT SCIENCES-SERIES LA English DT Proceedings Paper CT Multivariate Statistical Inference 2000 Conference (MSI-2000), in Honor of Professor Minoru Siotani on His 70th Birthday CY AUG 07-11, 1995 CL UNIV HAWAII, EAST & WEST CTR, HONOLULU, HI HO UNIV HAWAII, EAST & WEST CTR DE nonparametric test; two sample test; missing observations; propensity score; clinical trial AB The Wilcoxon two sample nonparametric test is modified to analyze the data with missing observations. The approach is to weigh each complete observation with its own estimated weight score, which is the inverse of probability of completing the observation. The proposed modified method is applied to a recently conducted clinical trial data. A small simulation study shows that the modified method is unbiased under the null hypothesis, while the Wilcoxon two sample test is biased when applied only to complete observations. RP Lee, YJ (reprint author), NICHHD,BIOMETRY & MATH STAT BRANCH,6100 EXECUT BLVD,ROOM 7B13,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SCIENCES PR PI SYRACUSE PA 20 CROSS RD, SYRACUSE, NY 13224-2144 SN 0196-6324 BN 0-935950-40-0 J9 AM J MATH-S PY 1997 VL 17 IS 1&2 BP 187 EP 200 PG 14 WC Statistics & Probability SC Mathematics GA BJ31V UT WOS:A1997BJ31V00010 ER PT J AU Stewart, CA Termanini, B Sutliff, VE Corleto, VD Weber, HC Gibril, F Jensen, RT AF Stewart, CA Termanini, B Sutliff, VE Corleto, VD Weber, HC Gibril, F Jensen, RT TI Management of the Zollinger-Ellison syndrome in pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE Zollinger-Ellison syndrome; pregnancy; gastrinoma; pancreatic endocrine tumor ID H2-RECEPTOR ANTAGONISTS; NEONATAL EXPOSURE; LONG-TERM; CIMETIDINE; GASTRINOMAS; RESECTION AB OBJECTIVE: There is almost no information on the management of patients with functional pancreatic endocrine tumors such as Zollinger-Ellison syndrome during pregnancy. The purpose of this study was to develop an approach for the management of such cases during pregnancy on the basis of experience with five recent cases. STUDY DESIGN: Five women with Zollinger-Ellison syndrome who had seven pregnancies were the subject of this study. Each patient had an initial evaluation to confirm the diagnosis and to establish gastrinoma location and for the presence or absence of multiple endocrine neoplasia type I. In patients with Zollinger-Ellison syndrome diagnosed before conception, various medical or surgical treatments were established before conception and were used to control acid secretion throughout the pregnancy. The presence of upper gastrointestinal symptoms during pregnancy, maternal and fetal complications, gender, and weight of the infant were determined in all cases. Acid control was determined in four of the five patients during six pregnancies. RESULTS: The interval between the onset of Zollinger-Ellison syndrome and the subsequent pregnancy varied from 0.6 to 9.9 years (mean 6.9 +/- 1.7 years). Zollinger-Ellison syndrome was unrecognized before pregnancy in two patients (40%); it was diagnosed between 0.2 and 2.4 years after the pregnancy. In three patients the time of diagnosis varied from 2.6 to 9 years before pregnancy. All patients had symptoms from gastric hypersecretion and elevated fasting serum gastrin levels that varied from 20% above normal to 37-fold above normal with mean of 2536 pg/ml (range 124 to 6970 pg/ml). Four of the five patients (80%) had positive secretin and calcium provocative tests. Two patients had multiple endocrine neoplasia type I. The five patients had seven pregnancies. Acid secretion was treated during pregnancy with antacids only (one patient), ranitidine alone (one patient), prior curative gastrinoma resection (one patient, two pregnancies), prior parietal cell vagotomy with incomplete tumor resection (one patient, two pregnancies), and prior parathyroidectomy and use of ranitidine in a patient with multiple endocrine neoplasia type I. In five pregnancies in three of the cases, no gastric antisecretory medications were needed during pregnancy. The mean acid secretion during pregnancy was 11.9 mEq/hr (range 0 to 42 mEq/hr). In the two cases with poor acid control and unrecognized Zollinger-Ellison syndrome mild fetal complications occurred. CONCLUSIONS: It is possible for patients with Zollinger-Ellison syndrome to have pregnancies that are not complicated by gastric acid hypersecretion. If the Zollinger-Ellison syndrome is diagnosed before pregnancy, curative resection or resection with parietal cell vagotomy may obviate the need for gastric antisecretory drugs. If metastases are present or the diagnosis of Zollinger-Ellison syndrome is made after conception, ranitidine in the lowest possible dose should be used to control acid secretion. If acid secretion in uncontrolled, the dose may be increased or omeprazole may be used. C1 NIDDK,DDB,NIH,BETHESDA,MD 20892. NR 25 TC 9 Z9 10 U1 0 U2 0 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 JAN PY 1997 VL 176 IS 1 BP 224 EP 233 DI 10.1016/S0002-9378(97)80041-5 PN 1 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WF178 UT WOS:A1997WF17800039 PM 9024119 ER PT J AU Wellmann, A Krenacs, L Fest, T Scherf, U Pastan, I Raffeld, M Brinkmann, U AF Wellmann, A Krenacs, L Fest, T Scherf, U Pastan, I Raffeld, M Brinkmann, U TI Localization of the cell proliferation and apoptosis-associated CAS protein in lymphoid neoplasms SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID IN-VIVO; C-MYC; LYMPHOMAGENESIS; EXPRESSION; CLONING; BCL-2 AB We have evaluated the expression and distribution of the cellular apoptosis susceptibility (CAS) protein in normal lymphoid tissue and malignant lymphomas. CAS protein, the product of the CAS gene, is associated with microtubules and the mitotic spindle. Immunohistochemistry with an antibody to CAS shows many CAS-positive cells in normal tonsils. The majority of strongly CAS-positive cells were localized to the dark zone of the follicles, whereas the mantle zone and interfollicular areas were essentially negative. Double staining for CAS and Ki-67 revealed co-expression of the two proliferation markers in approximately 85 to 90% of the CAS-positive cells. Different subtypes of lymphomas exhibited varying patterns of CAS expression. Low-grade non-Hodgkin's lymphoma generally revealed weak staining with CAS, with 10 to 60% of all cells being positive. In contrast, highly malignant non-Hodgkin's lymphoma and malignant cells of Hodgkin's disease displayed very strong CAS positivity, with staining pattern of CAS and Ki-67 was superimposable within a particular lymphoma subtype. However, in all lymphomas we observed a significant fraction of CAS-positive normal and malignant lymphocytes that were Ki-67 negative, probably because they were momentarily noncycling cells. We conclude that a high expression of CAS correlates with proliferation of normal and malignant lymphoid cells. The fact that detection of CAS protein identifies a higher portion of proliferating and malignant cells than Ki-67 warrants further evaluation of CAS protein as a marker with a diagnostic potential. C1 NCI,MOL BIOL LAB,NIH,DIV BASIC SCI,BETHESDA,MD 20892. NCI,HEMATOPATHOL SECT,NIH,DIV BASIC SCI,BETHESDA,MD 20892. NCI,PATHOL LAB,DIV CLIN SCI,NIH,BETHESDA,MD 20892. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 15 TC 48 Z9 48 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 JAN PY 1997 VL 150 IS 1 BP 25 EP 30 PG 6 WC Pathology SC Pathology GA WB761 UT WOS:A1997WB76100003 PM 9006318 ER PT J AU Wienecke, R Maize, JC Reed, JA deGunzburg, J Yeung, RS DeClue, JE AF Wienecke, R Maize, JC Reed, JA deGunzburg, J Yeung, RS DeClue, JE TI Expression of the TSC2 product tuberin and its target Rap1 in normal human tissues SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SCLEROSIS; GENE; IDENTIFICATION; ASSOCIATION; COMPLEX AB The tuberous sclerosis-2 (TSC2) gene is linked to tuberous sclerosis (TSC), dominantly inherited genetic syndrome in which inactivation of the normal TSC2 allele is associated with the development of mostly benign tumors and focal dysplasias. TSC2 encodes the protein tuberin, which is a widely expressed 180-kd polypeptide that exhibits specific GTPase activating activity toward Rap1 in vitro and co-localizes with Rap1 in cultured cells. In this study, we have performed immunohistochemical analyses, using affinity-purified anti-tuberin antibodies, to study the distribution of tuberin in a panel of normal human organs that are commonly affected by TSC. Cryosections indicated that tuberin is widely expressed at low levels. More intense staining of tuberin, in the cryosections and in paraffin sections, was observed in the small blood vessels of many organs, including the kidney, skin, and adrenal gland. High levels of tuberin were also detected in cortical neurons and cerebellar Purkinje cells. These findings imply that loss-of-function mutations in TSC2 might lead to the development of highly vascularized tumors, subcortical tubers, and focal atrophy of the cerebellar cortex, which are features commonly associated with TSC. Moreover, Rap1 was also found to be highly expressed in many of the same cells that contained high levels of tuberin, suggesting a functional interaction between tuberin and Rap1 in these tissues. C1 NCI, CELLULAR ONCOL LAB, NIH, BETHESDA, MD 20892 USA. CORNELL UNIV, MED CTR, NEW YORK HOSP, DEPT DERMATOPATHOL, NEW YORK, NY 10021 USA. NCI, CELLULAR ONCOL LAB, BETHESDA, MD 20892 USA. INST CURIE, SECT RECH, PARIS, FRANCE. FOX CHASE CANC CTR, DIV MED SCI, PHILADELPHIA, PA 19111 USA. NR 35 TC 63 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1997 VL 150 IS 1 BP 43 EP 50 PG 8 WC Pathology SC Pathology GA WB761 UT WOS:A1997WB76100005 PM 9006320 ER PT J AU Chuaqui, RF Zhuang, ZP EmmertBuck, MR Liotta, LA Merino, MJ AF Chuaqui, RF Zhuang, ZP EmmertBuck, MR Liotta, LA Merino, MJ TI Analysis of loss of heterozygosity on chromosome 11q13 in atypical ductal hyperplasia and in situ carcinoma of the breast SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID IMMUNOHISTOCHEMICAL EXPRESSION; CANCER EVOLUTION; P53 PROTEIN; IN-SITU; INSITU; POLYMORPHISM; C-ERBB-2; LESIONS; DISEASE; REGIONS AB Identical allelic loss in invasive and adjacent in situ ductal breast carcinoma (DCIS) on chromosome 11q13 has been previously reported, providing molecular evidence for the progression of DCIS to invasive tumor. In this study we analyzed loss of heterozygosity (LOH) on 11q13 (PYGM, INT-2) in atypical ductal hyperplasia (ADN) and various histological types of in situ carcinomas of the breast in patients without invasive cancer Twenty-four cases of in situ carcinoma and twelve cases of ADH were studied. Tissue micro-dissection of normal, hyperplastic, and tumor cells from fixed, paraffin-embedded sections was performed, and DNA was extracted for polymerase chain reaction. In situ tumors included both high- and low-grade DCIS, LOH was identified in six of twenty-two (27.3%) in situ tumors and in one of eleven (9%) ADH cases, within in situ carcinomas, LOH was identified in six of seventeen (35%) high-grade DCIS but in none of six lour-grade DCIS. The present results show that LOH at 11q13 occurs in an appreciable proportion of high-grade DCIS, although the rate is substantially less than in patients with concomitant DCIS and invasive tumor LON was identified less frequently in low-grade in situ tumors and ADH, suggesting that a putative tumor suppressor gene(s) located on chromosome 11q13 may be involved in the transition from early preneoplastic lesions to invasive breast cancer. RP Chuaqui, RF (reprint author), NCI,PATHOL LAB,NIH,9000 ROCKVILLE PIKE,BLDG 10,RM 2N212,BETHESDA,MD 20814, USA. NR 25 TC 57 Z9 61 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 JAN PY 1997 VL 150 IS 1 BP 297 EP 303 PG 7 WC Pathology SC Pathology GA WB761 UT WOS:A1997WB76100029 PM 9006344 ER PT J AU Spatz, M Kawai, N Merkel, N Bembry, J McCarron, RM AF Spatz, M Kawai, N Merkel, N Bembry, J McCarron, RM TI Functional properties of cultured endothelial cells derived from large microvessels of human brain SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE cultures of cerebrovascular endothelium; endothelin-1; potassium uptake; sodium-potassium-adenosinetriphosphatase; sodium-potassium-chloride cotransport ID PROTEIN-KINASE-C; HUMAN CEREBROMICROVASCULAR ENDOTHELIUM; SMOOTH-MUSCLE CELLS; CAPILLARY ENDOTHELIUM; ADENYLATE-CYCLASE; DEPENDENT PATHWAY; GROWTH-FACTOR; RAT-BRAIN; RECEPTORS; SODIUM AB This report describes the fractional separation of microvessels from human brain for establishment of segmentally derived endothelial cell (EC) cultures. The investigation comprised evaluation of media constituents and purity of the cell culture and focused on functional biochemical characterization of endothelium derived from large microvessels (EC). Cells contained endothelial marker factor VIII (von Willebrand antigen), secreted endothelin-l (ET-1) and prostaglandins, and took up Rb-86(+) as a measure of K+. Exogenous ET-1 stimulated phosphatidylinositol hydrolysis and K+ uptake; BQ-123 (selective ET(A) receptor antagonist) but not IRL-1038 or BQ-788 (selective ET(B) receptor antagonists) inhibited both. Ouabain (inhibitor of Na+-K+-ATPase) and bumetanide (inhibitor of Na+-K+-Cl- cotransport) reduced (74-80 and 20-40%, respectively) the ET-1-stimulated K+ uptake. Staurosporine [protein kinase C (PKC) inhibitor] selectively reduced Na+-K+-Cl- cotransport, whereas verapamil but not nifedipine (L-type voltage-dependent Ca2+ channel blockers) decreased Na+-K+-ATPase activity induced by ET-1. Phorbol la-myristate 13-acetate (PMA; activator of PKC) stimulated K+ uptake, which was only decreased with bumetanide. N-ethylisopropylamiloride (inhibitor of Na+/H+ exchange) reduced the ET-1-stimulated but not the PMA-induced K+ uptake. Results indicate that phosphatidylinositol hydrolysis and ion transport systems in large microvascular EC are stimulated by ET-1 through activation of ETA receptors. The findings also suggest that the ET-1-stimulated Na+-K+-ATPase activity, in contrast to Na+-K+-Cl- cotransport, is not mediated by PKC. In addition, the data suggest a linkage between Na+-K+-ATPase activity and Na+/H+ exchange. RP Spatz, M (reprint author), NINCDS, STROKE BRANCH, NIH, 36 CONVENT DR, MSC 4128, BETHESDA, MD 20892 USA. NR 38 TC 48 Z9 50 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 JAN PY 1997 VL 272 IS 1 BP C231 EP C239 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WG820 UT WOS:A1997WG82000024 PM 9038829 ER PT J AU Liu, Y Suchy, FJ Silverman, JA Vore, M AF Liu, Y Suchy, FJ Silverman, JA Vore, M TI Prolactin increases ATP-dependent taurocholate transport in canalicular plasma membrane from rat liver SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE perfused liver; cycloheximide; ecto-adenosinetriphosphatase; postpartum; bile acid transport ID BILE-SALT TRANSPORT; GROWTH-HORMONE; TYROSINE KINASE; MAMMARY-GLAND; ECTO-ATPASE; ACID; RECEPTOR; SYSTEM; HEPATOCYTES; COTRANSPORT AB The tauracholate (TC) maximal secretory rate (SR(m)) in the isolated perfused liver is increased in postpartum rats and ovariectomized rats treated with ovine prolactin (oPRL). The present studies were designed to characterize the mechanism(s) by which oPRL increases TC transport in the liver. oPRL (300 mu g/day iv for 7 days) increased the SR(m) 1.6-fold from 185 to 364 nmol . min(-1). mg protein(-1) in the perfused rat liver and the maximal rate of transport for ATP-dependent transport 1.7-fold from 66 to 109 nmol . min(-1). mg protein(-1) in canalicular liver plasma membrane (cLPM) vesicles without changing the Michaelis constant (5-6 mu M). The oPRL-mediated increases in biliary excretion in the perfused liver and ATP-dependent TC transport in cLPM vesicles were significantly inhibited by cycloheximide treatment (2 mg/kg). oPRL (300 mu g/day iv for 7 days) increased expression of Ca2+-Mg2+-ecto-adenosinetriphosphatase mRNA sixfold and increased protein expression two- to threefold, but had no effect on the expression of P-glycoprotein (mdr1b and mdr2) mRNA. Thus the increase in ATP-dependent transport in cLPM Vesicles due to oPRL treatment accounts for the increased TC SR(m) in the perfused liver. The oPRL-mediated increased TC transport may be associated with increased expression of proteins related to bile acid transport. C1 UNIV KENTUCKY, GRAD CTR TOXICOL, DEPT PHARMACOL, LEXINGTON, KY 40536 USA. YALE UNIV, SCH MED, DEPT PEDIAT, PEDIAT GASTROENTEROL HEPATOL SECT, NEW HAVEN, CT 06510 USA. NCI, EXPT CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. RI Vore, Mary/E-2177-2012 FU NIDDK NIH HHS [DK-46923] NR 40 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 1997 VL 272 IS 1 BP G46 EP G53 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA WG271 UT WOS:A1997WG27100008 PM 9038875 ER PT J AU Korzick, DH Xiao, RP Ziman, BD Koch, WJ Lefkowitz, RJ Lakatta, EG AF Korzick, DH Xiao, RP Ziman, BD Koch, WJ Lefkowitz, RJ Lakatta, EG TI Transgenic manipulation of beta-adrenergic receptor kinase modifies cardiac myocyte contraction to norepinephrine SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE beta(1)-adrenergic receptors; transgenic mice; G proteins; desensitization ID FAILING HUMAN HEART; G-PROTEINS; MICE; DESENSITIZATION; MECHANISMS; MYOCARDIUM; ACTIVATION AB To determine the direct functional significance of the beta-adrenergic receptor (AR) kinase 1 (beta ARK1) on myocardial performance in the absence of tonic sympathoadrenal neural activation and mechanical loading, we measured the contractile responses to acute beta(1)-AR stimulation in left ventricular myocytes isolated from nontransgenic control (NTG) and transgenic mice overexpressing either beta ARK1 (TG beta K12) or a beta ARK1 inhibitor (TGMini27). Contractile response to five concentrations (10-(8)-10(-7) M) of the beta(1)-AR agonist norepinephrine (NE) plus prazosin (10(-6) M) was measured after a 60-s rest, i.e., rested-state contraction (RSC), and during steady-state contraction (SSC) stimulation at 0.5 Hz (23 degrees C). At baseline, resting cell length was significantly greater in TG beta K12 myocytes (P < 0.05); however, there were no significant differences in RSC or SSC among NTG, TG beta K12, or TGMini27 mice. On the other hand, both the dose-response curve and kinetics for the NE-induced SSC response normalized to RSC (SSC/RSC) were significantly different among experimental groups (P < 0.001). Specifically, maximal SSC induced by NE in myocytes isolated from TG beta K12 was only 70% of the response observed in NTG cells and 50% of the response measured in TGMini27. These data suggest that 1) in the absence of circulating catecholamines or basal sympathetic tone, beta ARK1 actions in single myocytes are minimal, and 2) substantial functional beta ARK1 modulation of beta(1)-AR signaling occurs in cardiac myocytes even during short-term beta(1)-AR stimulation. These results are consistent with a role for agonist-induced phosphorylation and desensitization of cardiac beta(1)-ARs by beta ARK1 in single myocytes and highlight the potential functional importance of beta ARK1 as a critical determinant of the cardiac beta(1)-AR contractile response. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Natl Inst Hlth, Baltimore, MD 21224 USA. Duke Univ, Dept Surg, Durham, NC 27710 USA. Duke Univ, Dept Med, Durham, NC 27710 USA. Duke Univ, Howard Hughes Med Inst, Durham, NC 27710 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Natl Inst Hlth, 4940 Eastern Ave,Box 13, Baltimore, MD 21224 USA. NR 31 TC 21 Z9 21 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 1997 VL 272 IS 1 BP H590 EP H596 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WG572 UT WOS:A1997WG57200069 PM 9038983 ER PT J AU Miyashita, Y Sollott, SJ Cheng, L Kinsella, JL Koh, E Lakatta, EG Froehlich, JP AF Miyashita, Y Sollott, SJ Cheng, L Kinsella, JL Koh, E Lakatta, EG Froehlich, JP TI Redistribution of intracellular Ca2+ stores after beta-adrenergic stimulation of rat tail artery SMC SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE beta-adrenergic relaxation; isoproterenol; arterial smooth muscle; sarcoplasmic reticulum; fura 2; intracellular calcium ID SMOOTH-MUSCLE CELLS; RABBIT EAR ARTERY; PIG TAENIA-COLI; CALCIUM CHANNELS; SARCOPLASMIC-RETICULUM; SIGNAL-TRANSDUCTION; VOLTAGE DEPENDENCE; MESENTERIC-ARTERY; RELAXATION; TENSION AB beta-Adrenergic agonists induce the relaxation of vascular smooth muscle by a mechanism that activates the extrusion of Na+ and Ca2+ from the cell. A primary source of contractile Ca2+ resides in the sarcoplasmic reticulum (SR), which releases Ca2+ in response to vasoactive agents through inositol trisphosphate-mediated channels. To determine if smooth muscle relaxation induced by beta(2)-adrenergic agonists involves the redistribution of intracellular Ca2+, we studied the effects of isoproterenol (Iso) on freshly isolated, single rat tail artery smooth muscle cells loaded with fura 2, using digital ratiometric fluorescence imaging. Stimulation with 1 mu M phenylephrine (PE) or norepinephrine produced phasic and tonic increases in cytoplasmic intracellular Ca2+ concentration ([Ca2+](i)) associated with cell shortening. Exposure to caffeine and to Ca2+-free solutions eliminated the phasic and tonic components, respectively, from the Ca2+ signal. Intermittent superfusion with PE or caffeine was used to evaluate SR Ca2+ stores after stimulation by Iso. Exposure to 1 mu M Iso induced a time-dependent decrease in PE-activated peak and tonic [Ca2+](i) without any change in resting [Ca2+](i). Intermittent stimulation with 10 mM caffeine revealed st similar decline in peak [Ca2+](i), indicating Iso-dependent depletion of SR Ca2+ stores. The Ca2+ that remained in the SR after prolonged exposure to Iso (30% of the pre-Iso level by 80 min at 22 degrees C) failed to elicit a contractile response. The cells, perfused with a Na+- and Ca2+-free medium to block Na+/Ca2+ exchange, prevented depletion of the SR Ca2+ stares by Iso. We propose that Iso inhibits agonist-mediated Ca2+ influx through sarcolemmal Ca2+ channels and activates Ca2+ redistribution from storage sites in the SR to the extracellular compartment by a mechanism that involves Na+/Ca2+ exchange. These combined effects of Iso facilitate smooth muscle relaxation (and reduce vascular tonus) by reducing the increase in cytoplasmic Ca2+ evoked by vasoconstrictors. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Froehlich, JP (reprint author), NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 42 TC 4 Z9 4 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 1997 VL 272 IS 1 BP H244 EP H255 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WG572 UT WOS:A1997WG57200029 PM 9038944 ER PT J AU Spencer, RGS Buttrick, PM Ingwall, JS AF Spencer, RGS Buttrick, PM Ingwall, JS TI Function and bioenergetics in isolated perfused trained rat hearts SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE creatine kinase isoenzymes; diastolic dysfunction; high-energy phosphates; phosphorus-31 nuclear magnetic resonance; cardiac rehabilitation ID CREATINE-KINASE ISOENZYMES; MAGNETIC-RESONANCE; METABOLIC RESPONSE; ATP SYNTHESIS; EXERCISE; PERFORMANCE; HYPOXIA; HYPERTROPHY; MYOCARDIUM; SATURATION AB To evaluate the resistance of physiologically hypertrophied hearts to hypoxic insult, we quantified the development of functional deficits during hypoxia and reoxygenation in hypertrophied hearts from swim-trained female rats and we correlated this with assessment of high-energy phosphate (HEP) metabolites from simultaneous P-31 nuclear magnetic resonance (NMR) measurements. Furthermore, in vive enzymatic studies were carried out with saturation transfer NMR under well-oxygenated perfusion conditions for both beating and KCl-arrested hearts. Finally, in vitro enzymatic assays were performed. During hypoxia, the trained hearts exhibited improved systolic and diastolic function compared with hearts from sedentary animals. After 16 min of hypoxia, left ventricular (LV) developed pressure fell to 9% of baseline in control hearts but to only 21% of baseline in trained hearts (P < 0.01). LV diastolic function was also improved by training, increasing during hypoxia from a baseline of 10 to 71.0 +/- 3.3 mmHg in control hearts and to 55.3 +/- 4.8 mmHg in trained hearts (P < 0.05). Trained hearts also showed more rapid and complete recovery of function during reoxygenation and greater coronary flow per gram of heart throughout the entire protocol. Functional differences were not accompanied by differences in HEP at baseline; moreover, ATP and phosphocreatine (PCr) loss during hypoxia was similar between control and trained hearts, as was the recovery of PCr during reoxygenation. Saturation transfer experiments showed an increase in the forward creatine kinase (CrK) rate constant in trained hearts of 18% while beating, whereas in vitro enzymatic analysis revealed a 16% increase in the ratio of mitochondrial CrK to citrate synthase activity in LV tissue. Thus the relative preservation of function in hearts from trained rats could not be accounted for by overall HEP levels but may reflect adaptations in the CrK system. C1 NIA, Nucl Magnet Resonance Unit, NIH, Baltimore, MD 21224 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Spencer, RGS (reprint author), NIA, Nucl Magnet Resonance Unit, NIH, GRC 4D-08, Baltimore, MD 21224 USA. FU NHLBI NIH HHS [HL-43170, HL-15498] NR 46 TC 19 Z9 19 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 1997 VL 272 IS 1 BP H409 EP H417 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WG572 UT WOS:A1997WG57200048 PM 9038963 ER PT J AU OReilly, MA Staversky, RJ Flanders, KC Johnston, CJ Finkelstein, JN AF OReilly, MA Staversky, RJ Flanders, KC Johnston, CJ Finkelstein, JN TI Temporal changes in expression of TGF-beta isoforms in mouse lung exposed to oxygen SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE hyperoxia; lung injury; transforming growth factor-beta ID TRANSFORMING GROWTH-FACTOR; FACTOR-BETA-3 MESSENGER-RNA; INDUCED PULMONARY FIBROSIS; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; PROTEIN; FIBRONECTIN; HYPEROXIA; COLLAGEN; FAMILY AB Oxygen-induced pulmonary injury is associated with cell death and a significant inflammatory response. Because transforming growth factor (TGF)-beta is a potent modulator of the immune response, changes in expression of the three TGF-beta (beta 1, beta 2, beta 3) isoforms was determined in lungs of adult mice exposed to >95% oxygen. TGF-beta 1 immunostaining within cuboidal non-ciliated bronchiolar epithelial cells was increased within 3 h of oxygen exposure and continued to increase for 48 h before decreasing to control levels by 72 h. A similar but less marked change that was morphologically consistent with alveolar type II cells was observed in granulated cells. Immunostaining for TGF-beta 2 and TGF-beta 3 revealed a similar change in bronchiolar epithelium with little change observed in the alveolar epithelium. Immunohistochemical changes in TGF-beta expression were not observed in any other pulmonary cells. Northern blot analysis of total lung RNA revealed that expression of the TGF-beta mRNA was not markedly altered over the 72-h exposure period. Exposure to >95% oxygen resulted in cell type-specific posttranscriptional changes in TGF-beta isoforms in the lung. C1 UNIV ROCHESTER, STRONG MEM HOSP, CHILDRENS HOSP, DEPT PEDIAT, ROCHESTER, NY 14642 USA. NCI, CHEMOPREVENT LAB, NIH, BETHESDA, MD 20892 USA. NR 31 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 1997 VL 272 IS 1 BP L60 EP L67 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA WG569 UT WOS:A1997WG56900009 PM 9038903 ER PT J AU Pohl, J Winder, SJ Allen, BG Walsh, MP Sellers, JR Gerthoffer, WT AF Pohl, J Winder, SJ Allen, BG Walsh, MP Sellers, JR Gerthoffer, WT TI Phosphorylation of calponin in airway smooth muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE actin-binding proteins; carbachol; in vitro motility; trachea ID PROTEIN-KINASE-C; MYOSIN PHOSPHORYLATION; IN-VITRO; CONTRACTION; CALDESMON; ACTIN; DEPHOSPHORYLATION; DISSOCIATION; PHOSPHATASE; INHIBITION AB Calponin is an actin-binding protein known to be a substrate in vitro for several protein kinases and phosphoprotein phosphatases. We tested the hypothesis that calponin is phosphorylated in vivo using canine tracheal smooth muscle strips metabolically labeled with P-32(i). Calponin was gel purified from muscles stimulated with 1 mu M carbachol. Phosphorylation increased to 2.0 times the basal level of 178 +/- 26 counts per minute (cpm)/mu g calponin within 30 s to 350 +/- 64 cpm/mu g. Two-dimensional nonequilibrium pH gradient gel electrophoresis resolved four charge isoforms of calponin in unstimulated muscle. Stimulation with carbachol induced an additional more acidic isoform. Phosphorylation of calponin in vitro with protein kinase C (PKC) also induced formation of additional acidic isoforms. The functional effect of phosphorylation was demonstrated using an in vitro motility assay in which unphosphorylated calponin (2 mu M) caused a profound inhibition of actin sliding. Calponin phosphorylated by PKC did not inhibit actin sliding. The results show that phosphorylation of calponin occurs in intact tracheal smooth muscle and that phosphorylation of calponin in vitro alleviates the inhibitory effect of calponin on actomyosin function. C1 UNIV NEVADA, SCH MED, DEPT PHARMACOL 318, RENO, NV 89557 USA. UNIV CALGARY, FAC MED, SMOOTH MUSCLE RES GRP, CALGARY, AB T2N 4N1, CANADA. NHLBI, MOL CARDIOL LAB, BETHESDA, MD 20892 USA. RI Allen, Bruce/B-4693-2008 OI Allen, Bruce/0000-0001-9000-9495 FU NHLBI NIH HHS [HL-48183] NR 28 TC 33 Z9 34 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 1997 VL 272 IS 1 BP L115 EP L123 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA WG569 UT WOS:A1997WG56900016 PM 9038910 ER PT J AU Knepper, MA AF Knepper, MA TI Molecular physiology of urinary concentrating mechanism: Regulation of aquaporin water channels by vasopressin SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 96 Annual Meeting CY APR 14-18, 1996 CL WASHINGTON, D.C. SP Federat Amer Soc Exptl Biol DE collecting duct; aquaporins ID THICK ASCENDING LIMB; DEPENDENT ADENYLATE-CYCLASE; INTEGRAL MEMBRANE-PROTEIN; KIDNEY COLLECTING DUCT; RAT-KIDNEY; HENLES LOOP; CHLORIDE TRANSPORT; BRATTLEBORO RAT; NACL TRANSPORT; FAMILY AB The purpose of this review is to illustrate the application of molecular methodologies to the investigation of a fundamentally integrative problem in renal physiology, namely, the mechanism of regulation of water excretion by the kidney and the concomitant concentration of solutes in the urine. A new revolution in renal physiology is occurring as new research tools have become available as a result of the cloning of cDNAs for many of the major transporters and receptors in the renal medulla. Among the important renal medullary transporters are the aquaporin water channels, which mediate the osmotic water transport across renal medullary epithelia. One of these water channels, aquaporin-2, has been shown to be the target for short-term regulation of collecting duct water permeability by vasopressin. In addition, two collecting duct water channels, aquaporin-2 and aquaporin-3, are targets for long-term regulation by vasopressin through effects on the absolute expression levels of the water channel proteins. This review focuses on the mechanisms of both short- and long-term regulation of these water channels by vasopressin. RP Knepper, MA (reprint author), NHLBI, KIDNEY & ELECTROLYTE METAB LAB, RENAL MECHANISMS SECT,NIH, BLDG 9, 9 MEM DR MSC 0951, BETHESDA, MD 20892 USA. NR 58 TC 211 Z9 217 U1 4 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 1997 VL 272 IS 1 BP F3 EP F12 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA WP861 UT WOS:A1997WP86100002 PM 9039043 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI Transfer of tools and food between groups of tufted capuchins (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE capuchin; Cebus apella; cooperation; exchange; food-sharing; tool use ID MONKEYS; EVOLUTION; CAPUCINUS AB This research examined tool and food transfer between two groups of tufted capcuhin monkeys (Cebus apella). Subjects in one group transferred stones to subjects in a second group who in turn used the stones as cutting tools and then transferred food to subjects in the first group. Aspects of the capuchins' behavior are similar to those described for food-sharing in Cebus, cooperative tool use in Papio, and tool and food exchange in Pan. We propose that tool use and food-sharing facilitate tool and food transfer between captive groups of Cebus apella. (C) 1997 Wiley-Liss, Inc. C1 NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD. NR 19 TC 23 Z9 24 U1 3 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1997 VL 43 IS 1 BP 33 EP 41 DI 10.1002/(SICI)1098-2345(1997)43:1<33::AID-AJP2>3.3.CO;2-X PG 9 WC Zoology SC Zoology GA XU841 UT WOS:A1997XU84100002 PM 9294639 ER PT J AU Norcross, JL Newman, JD AF Norcross, JL Newman, JD TI Social context affects phee call production by nonreproductive common marmosets (Callithrix jacchus) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE common marmosets; Callithrix jacchus; vocalizations; social environment ID COTTON-TOP TAMARINS; SAGUINUS-OEDIPUS-OEDIPUS; REPRODUCTIVE STATUS; FAMILY GROUPS; HOME-RANGE; MONKEYS; FERTILITY; ONTOGENY; BEHAVIOR; BRAZIL AB Common marmosets produce two variants of their long call (phee call) in different situations. Intergroup calls are produced in territorial situations, and intragroup separation calls are produced by marmosets isolated from group members, Marmoset groups frequently include postpubertal, nonreproductive members; their roles in the spontaneous production of territorial vocalizations is unclear. This study analyzed the production of home cage phee calls by nonreproductive, postpubertal marmosets while they were housed in their natal groups and after pairing with an opposite-sex conspecific, Additionally, the production of the separation phee call variant was assessed in both social conditions, The results indicated that the marmosets rarely produced home cage, or territorial, phee calls while they were naturally housed. In contrast, both males and females produced the territorial phee call at a much higher rate as early as 4 days after pairing. Age-matched females remaining in their natal groups throughout the study produced home cage phee calls infrequently. Most marmosets produced separation phee calls at a high rate after separation from either their natal group or a partner, suggesting that the makeup of a social group has little effect on an animal's motivation to reunite with conspecifics. These results suggest that the social environment has an important influence on the production of territorial phee calls. (C) 1997 Wiley-Liss, Inc. RP Norcross, JL (reprint author), NICHHD,COMPARAT ETHOL LAB,NIH,POB 529,POOLESVILLE,MD 20837, USA. NR 39 TC 18 Z9 19 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1997 VL 43 IS 2 BP 135 EP 146 DI 10.1002/(SICI)1098-2345(1997)43:2<135::AID-AJP3>3.0.CO;2-Y PG 12 WC Zoology SC Zoology GA XY755 UT WOS:A1997XY75500003 PM 9327096 ER PT J AU Erhart, EM Coelho, AM Bramblett, CA AF Erhart, EM Coelho, AM Bramblett, CA TI Kin recognition by paternal half-siblings in captive Papio cynocephalus SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE kin selection; kin recognition; recognition mechanisms; Papio ID MACAQUES MACACA-FUSCATA; RHESUS-MONKEYS; YELLOW BABOONS; KINSHIP; BEHAVIOR; PREFERENCES; INFANT; AGE; AFFILIATION; FAMILIARITY AB Our objective in this study was to evaluate whether a group of paternally related, subadult baboons (Papio cynocephalus) would preferentially interact with kin or nonkin when they had been raised apart from kin other than their mothers. Subjects and their mothers were removed from the breeding group and placed in alternate housing within 24 h after birth to ensure that the subjects would not have a social history with either their sire or their half-siblings. At 90 days of age, the 23 subjects were separated from their mothers and assigned to a peer-peer social group. Behavioral performance was measured using focal animal sampling techniques and 12 molecular behavioral criteria. Analyses of the data indicate that in dyadic interactions kin did not interact more frequently than nonkin in performance of affiliative, sociosexual, and agonistic behaviors. The hypothesis that baboons recognize kin in the absence of maternal associations was not supported by the data; moreover, we suggest that social learning and social history are the most likely mechanisms for kin recognition. (C) 1997 Wiley-Liss, Inc. C1 NHLBI, BETHESDA, MD 20892 USA. RP Erhart, EM (reprint author), UNIV TEXAS, DEPT ANTHROPOL, EP SCHOCH, C3200, AUSTIN, TX 78712 USA. FU NHLBI NIH HHS [HL 19362, HL 15914] NR 59 TC 29 Z9 30 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1997 VL 43 IS 2 BP 147 EP 157 PG 11 WC Zoology SC Zoology GA XY755 UT WOS:A1997XY75500004 PM 9327097 ER PT J AU Jaquish, CE Tardif, SD Cheverud, JM AF Jaquish, CE Tardif, SD Cheverud, JM TI Interactions between infant growth and survival: Evidence for selection on age-specific body weight in captive common marmosets (Callithrix jacchus) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE body weight; callitrichids; infant survival; social environment ID COTTON-TOP TAMARINS; CALLITRICHIDAE; MORTALITY; COLONY AB The objective of this study is to investigate factors influencing infant survival in captive common marmosets, We investigated the influence of age-specific weight, litter size, caging, and the presence of helpers on survival to 6 months of age in 189 Callithrix jacchus infants. Infant survival was analyzed using Cox Proportional Hazards regression, and fitness functions were plotted to explore the relationship between survival and growth. Results indicate that weights at birth and 120 days significantly affect future survival probability. Litter size significantly influences survival prior to 60 days of age with larger litters having poorer survival. Males and females did not have significantly different survival and the presence of helpers in the group did not influence survival probability. Patterns of survival with respect to age-specific weights suggest stabilizing selection on birth weight and directional selection on weight at 120 days of age. (C) 1997 Wiley-Liss, Inc. C1 KENT STATE UNIV,DEPT BIOL,KENT,OH 44242. WASHINGTON UNIV,DEPT ANAT & NEUROBIOL,ST LOUIS,MO. RP Jaquish, CE (reprint author), NHGRI,CTR INHERITED DIS RES,NIH,SUITE 2000,333 CASSELL DR,BALTIMORE,MD 21224, USA. FU NCRR NIH HHS [R01-RR-02022] NR 29 TC 9 Z9 10 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1997 VL 42 IS 4 BP 269 EP 280 DI 10.1002/(SICI)1098-2345(1997)42:4<269::AID-AJP2>3.0.CO;2-V PG 12 WC Zoology SC Zoology GA XP088 UT WOS:A1997XP08800002 PM 9261508 ER PT J AU Tardif, SD Jaquish, CE AF Tardif, SD Jaquish, CE TI Number of ovulations in the marmoset monkey (Callithrix jacchus): Relation to body weight, age and repeatability SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE marmoset; ovulation; body weight ID REPRODUCTION; EVOLUTION; COSTS; SIZE AB The relation between number of ovulations and body weight, age or maternal identity was examined in 69 ovarian cycles from 29 captive-born common marmoset monkeys (Callithrix jacchus). Specifically, we addressed the following questions: was there high repeatability of ovulation number? Most of the variation in ovulation number was within, rather than between subjects. Repeatability in number of ovulations was 0.081 (n = 20 females with 2-6 ovulatory cycles per female); was age related to number of ovulations? There was no relation between age and number of ovulations, either within or between subjects; and was weight related to number of ovulations? Weight was related to number of ovulations. When the relation between number of ovulations (1-2 versus 3-4) and weight was examined through a logistic regression, there was a significant relation. Also, of the 11 subjects which had a variable number of ovulations across cycles, 90.9% were heavier when ovulating 3-4 than when ovulating 2. These results are discussed as the basis for the proposal that callitrichid primates may have been selected for potential variation in reproductive output and that this variation may be related to energy availability. (C) 1997 Wiley-Liss, Inc. C1 NIH,CTR INHERITED DIS RES,NCHGR,TRIAD TECHNOL CTR,BALTIMORE,MD. RP Tardif, SD (reprint author), KENT STATE UNIV,DEPT BIOL SCI,CUNNINGHAM HALL,KENT,OH 44240, USA. FU NCRR NIH HHS [R01-RR02022] NR 28 TC 34 Z9 36 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1997 VL 42 IS 4 BP 323 EP 329 DI 10.1002/(SICI)1098-2345(1997)42:4<323::AID-AJP7>3.3.CO;2-6 PG 7 WC Zoology SC Zoology GA XP088 UT WOS:A1997XP08800007 PM 9261513 ER PT J AU AlaghbandRad, J Hamburger, SD Giedd, JN Frazier, JA Rapoport, JL AF AlaghbandRad, J Hamburger, SD Giedd, JN Frazier, JA Rapoport, JL TI Childhood-onset schizophrenia: Biological markers in relation to clinical characteristics SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEGATIVE SYMPTOMS; VENTRICULAR ENLARGEMENT; PREMORBID ADJUSTMENT; BRAIN STRUCTURE; ABNORMALITIES; GENDER; PSYCHOPATHOLOGY; DIAGNOSIS; DISORDERS; FAMILY AB Objective: The purpose of this study was to examine the relationships between clinical and neurobiological measures of childhood-onset schizophrenia. It was hypothesized that there would be a more striking pattern in the rare cases with very early onset than is seen in subjects with later onset. Method: Premorbid, clinical, prenatal, perinatal, and magnetic resonance imaging brain measures were examined in 29 children and adolescents who met the DSM-III-R criteria for schizophrenia with onset before age 12. Specifically, gender, premorbid adjustment, and clinical symptoms were examined in relation to cerebral volume, ventricular volume, and maternal obstetrical complications. Results: Males were more likely to have had an insidious onset than females. There was a significant negative correlation between score on the Scale for the Assessment of Negative Symptoms and total cerebral volume. Conclusions: These neurobiological associations support the continuity of early-onset schizophrenia with the later-onset disorder; the striking association between small cerebral volume and negative symptoms suggests a more homogeneous or more potent neurobiological basis for very early-onset schizophrenia. RP AlaghbandRad, J (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,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 43 TC 36 Z9 36 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1997 VL 154 IS 1 BP 64 EP 68 PG 5 WC Psychiatry SC Psychiatry GA WA663 UT WOS:A1997WA66300011 PM 8988960 ER PT J AU Jacobsen, LK Frazier, JA Malhotra, AK Karoum, F McKenna, K Gordon, CT Hamburger, SD Lenane, MC Pickar, D Potter, WZ Rapoport, JL AF Jacobsen, LK Frazier, JA Malhotra, AK Karoum, F McKenna, K Gordon, CT Hamburger, SD Lenane, MC Pickar, D Potter, WZ Rapoport, JL TI Cerebrospinal fluid monoamine metabolites in childhood-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HOMOVANILLIC-ACID; NEUROLEPTIC TREATMENT; PSYCHIATRIC-PATIENTS; CLOZAPINE; PROLACTIN; SEROTONIN; CHLORPROMAZINE; NOREPINEPHRINE; IMMUNOGLOBULIN; PATTERNS AB Objective: Pediatric studies of cerebrospinal fluid (CSF) monoamine metabolites in childhood-onset schizophrenia may help to elucidate both pathophysiology and treatment response in early-onset psychosis. Method: CSF homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) and serum prolactin were measured during drug-free and antipsychotic medication conditions in 18 patients (mean age=14.2 years, SD=1.7) who had onset of schizophrenia by age 12 (mean age at onset=9.9 years, SD=1.8). Relationships between changes in CSF monoamines and serum prolactin and clinical outcome were examined, and the degree of change in CSF monoamines in response to clozapine treatment was compared with that for 16 patients with later-onset schizophrenia. Results: Despite patients' significant clinical improvement with treatment, CSF monoamine concentrations and ratios of HVA/5-HIAA and HVA/MHPG did not significantly change with 6 weeks of either haloperidol or clozapine treatment. Serum prolactin levels increased during haloperidol treatment. Clozapine had similar effects on CSF monoamines inpatients with childhood- and later-onset schizophrenia. Conclusions: While these data are compatible with continuity between childhood- and later-onset schizophrenia, they also highlight the complexity of the biochemical events mediating clinical changes in schizophrenia. C1 NIMH,ANALYT BIOCHEM LAB,WASHINGTON,DC. NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. RP Jacobsen, LK (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 12 Z9 12 U1 2 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1997 VL 154 IS 1 BP 69 EP 74 PG 6 WC Psychiatry SC Psychiatry GA WA663 UT WOS:A1997WA66300012 PM 8988961 ER PT J AU George, DT Benkelfat, C Rawlings, RR Eckardt, MJ Phillips, MJ Nutt, DJ Wynne, D Murphy, DL Linnoila, M AF George, DT Benkelfat, C Rawlings, RR Eckardt, MJ Phillips, MJ Nutt, DJ Wynne, D Murphy, DL Linnoila, M TI Behavioral and neuroendocrine responses to m-chlorophenylpiperazine in subtypes of alcoholics and in healthy comparison subjects SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID 5-HT1C RECEPTOR ANTAGONISTS; PANIC DISORDER PATIENTS; META-CHLOROPHENYLPIPERAZINE; SEROTONIN FUNCTION; PREFERRING P; ETHANOL; MCPP; RAT; ONSET; AGE AB Objective: The purpose of this study was to explore central serotonergic functions in subgroups of alcoholics and in health comparison subjects. Method: The mixed serotonin (5-HT) agonist/antagonist m-chlorophenylpiperazine (m-CPP) was administered to male alcoholic patients who were classified according to the criteria of von Knorring et al. as type I alcoholics (late onset) (N=16) or type II alcoholics (early onset with antisocial traits) (N=24) and to 22 healthy comparison subjects. Psychological, physiological, and neuroendocrine measures were obtained before and after the m-CPP infusion. Results: m-CPP elicited subtype-related differential effects among the alcoholics; the type I alcoholics reported more anger and anxiety, and the type II alcoholics reported increased euphoria and a greater likelihood of drinking. The healthy comparison subjects exhibited a greater increase in plasma ACTH response to the m-CPP infusion than the alcoholics regardless of subtype. Conclusions: Differences in certain 5-HT receptor functions may explain some of the clinical characteristics that differentiate the type II and type I subgroups of alcoholic patients. Furthermore, alcoholics may have reduced sensitivity of 5-HT2C receptors in comparison with healthy subjects. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,SCHIZOPHRENIA RES BRANCH,ROCKVILLE,MD 20857. MCGILL UNIV,DEPT PSYCHIAT,MONTREAL,PQ,CANADA. UNIV BRISTOL,SCH MED,PSYCHOPHARMACOL UNIT,BRISTOL,AVON,ENGLAND. RP George, DT (reprint author), NIAAA,CLIN STUDIES LAB,BLDG 10,ROOM 3B19,10 CTR DR MSC-1250,BETHESDA,MD 20892, USA. NR 52 TC 46 Z9 46 U1 4 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1997 VL 154 IS 1 BP 81 EP 87 PG 7 WC Psychiatry SC Psychiatry GA WA663 UT WOS:A1997WA66300014 PM 8988963 ER PT J AU Swedo, SE Leonard, HL Mittleman, BB Allen, AJ Rapoport, JL Dow, SP Kanter, ME Chapman, F Zabriskie, J AF Swedo, SE Leonard, HL Mittleman, BB Allen, AJ Rapoport, JL Dow, SP Kanter, ME Chapman, F Zabriskie, J TI Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ADOLESCENTS; ANTIBODIES; CHILDHOOD; CHOREA AB Objective: The authors' goal was to determine whether a trait marker of rheumatic fever susceptibility (labeled D8/17) could identify children with pediatric autoimmune neuropsychiatric disorders (obsessive-compulsive disorder and tic disorders) associated with streptococcal infections (PANDAS). Method: Blood samples obtained from 27 children with PANDAS, nine children with Sydenham's chorea, and 24 healthy children were evaluated for D8/17 reactivity. Individuals were defined as D8/17 positive if they had 12% or more D8/17+ cells. Results: The frequency of D8/17-positive individuals was significantly higher in both patient groups than it was among the healthy volunteers: 85% of the children with PANDAS and 89% of the children with Sydenham's chorea, compared with 17% of the healthy children, were D8/17 positive. Further, the mean number od D8/17+ cells was similar in the two patient groups and was significantly higher in these groups than in the group of healthy children. Conclusions: These results suggest that there may be a subgroup of D8/17-positive children who present with clinical symptoms of obsessive-compulsive disorder and Tourette's syndrome, rather than Sydenham's chorea, but who have similar poststreptococcal autoimmunity. C1 NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. ROCKEFELLER UNIV,NEW YORK,NY 10021. RP Swedo, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT SECT,10 CTR DR,MSC 1381,BETHESDA,MD 20892, USA. NR 16 TC 220 Z9 233 U1 1 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1997 VL 154 IS 1 BP 110 EP 112 PG 3 WC Psychiatry SC Psychiatry GA WA663 UT WOS:A1997WA66300020 PM 8988969 ER PT J AU SimonsMorton, BG McKenzie, TJ Stone, E Mitchell, P Osganian, V Strikmiller, PK Ehlinger, S Cribb, P Nader, PR AF SimonsMorton, BG McKenzie, TJ Stone, E Mitchell, P Osganian, V Strikmiller, PK Ehlinger, S Cribb, P Nader, PR TI Physical activity in a multiethnic population of third graders in four states SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SELF-REPORT; CHILDREN; FITNESS; ADOLESCENTS; VALIDITY; RELIABILITY; FREQUENCY; EXERCISE; ISSUES; YOUTH AB Objectives. This research assessed the amount of daily physical activity in a multiethnic sample of US third-grade students. Methods. Physical activity interviews were conducted with 2410 third graders from 96 schools in four states. Blood pressure, cholesterol, body mass index, timed run for distance, physical-activity self-efficacy, and perceived support for physical activity were also assessed. Results. Students reported a daily average of 89.9 minutes of moderate to vigorous physical activity, 34.7 minutes of vigorous activity, and 120.4 minutes of sedentary behavior; however, 36.6% obtained less than 60 minutes of moderate to vigorous physical activity daily, and 12.8% reported less than 30 minutes. Boys reported more physical and sedentary activity than girls; White children reported more activity than Black or Hispanic children; California children reported the most activity and Louisiana children the least. Geographic location, male gender, lower cholesterol, higher perceived efficacy in physical activity, and higher social Support were associated with more physical activity. Conclusions. Average reported activity met the Year 2000 objectives; however, many students reported less than recommended amounts of activity. These findings support the need for health promotion programs that increase the number of physically active children. C1 NICHHD,NIH,ROCKVILLE,MD. NHLBI,NIH,ROCKVILLE,MD. SAN DIEGO STATE UNIV,SAN DIEGO,CA 92182. NEW ENGLAND RES INST,WATERTOWN,MA 02172. TULANE SCH PUBL HLTH & TROP MED,BATON ROUGE,LA. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV TEXAS,AUSTIN,TX 78712. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NHLBI NIH HHS [U01 HL 39852, U01 HL 39880, U01 HL 39927] NR 36 TC 31 Z9 31 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC 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 JAN PY 1997 VL 87 IS 1 BP 45 EP 50 DI 10.2105/AJPH.87.1.45 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WG315 UT WOS:A1997WG31500010 PM 9065225 ER PT J AU McClure, ME AF McClure, ME TI NIH funding opportunities: Tempora mutantur et nos mutamur in illis! (Times are changing and we are changing with them) SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article AB The study of Latin, including the memorizing of many classical quotations, was a standard requirement for a high school education in most European countries in the early decades of my youth. So it was also at the small country high school that I attended in the 1950s. At that time, studying a dead language seemed a. meaningless and outdated exercise since no one at the malt shop spoke it and not one of my comic books had Latin print in it. Throughout my adult life, however, the eternal wisdom and validity of those memorized age-old adages have proven useful and correct time and time again. This manuscript embraces one of those old adages fully-''times are changing and we are changing with them.'' There are and have been great ongoing changes at the NIH in regard to the NIH Extramural Program and the manner of its providing grants to research scientists. Within that context, I would like to present here an overview of three aspects of these changes that our extramural colleagues may find useful: 1) what's going on at the NICHD? 2) what's the future of grant support for reproduction research? and 3) what can the society and its members do to promote the continued availability of such grants? As a background for orientation, permit me to describe for you the nature of the NICHD's Extramural Program and that of our Reproductive Sciences Research Program. While similar in its operational structure to other NIH institutes, the NICHD differs from nearly all of them in that its mission is not categorically focused on one or a few human diseases or disorders. The NICHD's scientific mission spans a broad expanse of human experience from conception through early maturity. Through its research programs, it seeks to develop new knowledge that can be applied in resolving reproductive and developmental problems encountered in starting and growing healthy, wanted children. Functionally, the extramural programs at the NICHD are organized within three separate centers: the Center for Population Research (CPR), the Center for Research for Mothers and Children (CRMC), and the National Center for Medical Rehabilitation Research (NCMRR). All three centers support reproduction research relevant to their specific program priorities. Two of the centers, CPR and CRMC, support program relevant aspects of reproductive immunology research. RP McClure, ME (reprint author), NICHHD,REPROD SCI BRANCH,POPULAT RES CTR,BLDG 61E,RM 8B01,BETHESDA,MD 20892, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JAN PY 1997 VL 37 IS 1 BP 144 EP 148 PG 5 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA WG564 UT WOS:A1997WG56400018 PM 9138448 ER EF