FN Thomson Reuters Web of Science™ VR 1.0 PT J AU LOU, JS GOLDFARB, L MCSHANE, L GATEV, P HALLETT, M AF LOU, JS GOLDFARB, L MCSHANE, L GATEV, P HALLETT, M TI USE OF BUSPIRONE FOR TREATMENT OF CEREBELLAR-ATAXIA - AN OPEN-LABEL STUDY SO ARCHIVES OF NEUROLOGY LA English DT Article ID SEROTONIN RECEPTORS; HUMAN-BRAIN AB Objective: To evaluate the efficacy of buspirone hydrochloride, a serotonin (5-hydroxytryptamine(1A)) agonist, in treating patients with cerebellar ataxia. Design: Open-label study in which 20 patients (14 with cerebellar cortical atrophy and six with olivopontocerebellar atrophy) received buspirone hydrochloride, up to 60 mg/d, for 8 weeks. Setting: Research hospital. Main Outcome Measures: Clinical, physiological, and psychological assessment. Results: Nine patients with mild or moderate cerebellar dysfunction who completed the study showed significant improvement in clinical and self-assessment ratings, but not in a motor performance test, posturography (data were incomplete), State-Trait Anxiety Inventory, and Beck Depression Inventory. Seven patients with severe cerebellar dysfunction who completed the study had no improvement on any measure. Conclusions: Buspirone may be effective in treating mild to moderate cerebellar ataxia. A double-blind study of the efficacy of buspirone in cerebellar ataxia is warranted. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. NR 21 TC 49 Z9 51 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 1995 VL 52 IS 10 BP 982 EP 988 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA RY609 UT WOS:A1995RY60900008 PM 7575226 ER PT J AU HOOKS, JJ KUPFER, C AF HOOKS, JJ KUPFER, C TI HERPES-SIMPLEX VIRUS IN IRIDOCORNEAL ENDOTHELIAL SYNDROME SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter RP HOOKS, JJ (reprint author), NEI,BLDG 10,ROOM 6N228,BETHESDA,MD 20892, USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 1995 VL 113 IS 10 BP 1226 EP 1227 PG 2 WC Ophthalmology SC Ophthalmology GA RY945 UT WOS:A1995RY94500005 PM 7575245 ER PT J AU MUKHIN, DN CHAO, FF KRUTH, HS AF MUKHIN, DN CHAO, FF KRUTH, HS TI GLYCOSPHINGOLIPID ACCUMULATION IN THE AORTIC-WALL IS ANOTHER FEATURE OF HUMAN ATHEROSCLEROSIS SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE ATHEROSCLEROSIS; AORTA; GLYCOSPHINGOLIPIDS; EXTRACELLULAR LIPID PARTICLES; GANGLIOSIDES ID ALTERNATIVE COMPLEMENT PATHWAY; PROMOTE CHOLESTEROL EFFLUX; RICH LIPID PARTICLES; UNESTERIFIED CHOLESTEROL; HYPERLIPIDEMIC RABBIT; PLASMA-LIPOPROTEINS; NEUTRAL GLYCOSPHINGOLIPIDS; DIFFERENT MECHANISMS; CELL-PROLIFERATION; HUMAN-FIBROBLASTS AB High accumulation of lipids is a typical feature of an atherosclerotic lesion. We have previously identified the chemical structure of the major glycosphingolipids (GSLs) of human aorta; however, quantification of the absolute concentration of GSLs was not carried out. In the present study, for the first time we have performed a quantitative comparative analysis of GSL composition in the media and two sublayers of the intima taken from normal regions, fatty streaks, and atherosclerotic plaques of the human aorta. The intimal tissue containing fatty streaks and atherosclerotic plaques accumulated GSLs, predominantly glucosylceramide (GlcCer), lactosylceramide (LacCer), and ganglioside G(M3). GSL levels in plaques were highest: GlcCer was 18- and 8-fold, LacCer was 8- and 7-fold, and G(M3) was 2.5- and 12-fold higher than in musculoelastic and elastic-hyperplastic intimal layers of normal regions, respectively. We did not observe a significant increase in other GSLs. An increase in the content of gangliosides G(D3) and G(D1a) was detected in the media underlying atherosclerotic lesions. On the basis of an analysis of the ratio of GlcCer, LacCer, and G(M3); accumulated in the tissue and cells of the elastic-hyperplastic layer of intima, we have concluded that the accumulation of the above-mentioned GSLs occurs mainly in the extracellular space of the intima. In this study, we have also demonstrated that extracellular lipid liposomes, which appear in the early stages of atherogenesis, are one locus of GSL accumulation in the extracellular space of the intima. The findings suggest that the GSL concentration and distribution within the normal and atherosclerotic aorta reflects a number of factors that include (1) synthesis of GSLs within the vessel wall, (2) deposition of GSLs within the vessel wall from plasma-derived lipoproteins, (3) the degree of association of the various GSLs with intimal cells as well as extracellular lipid particles, and (4) metabolic relationships between cholesterol and GSL accumulation. C1 NHLBI,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892. RUSSIAN ACAD MED SCI,CARDIOL RES CTR,INST EXPTL CARDIOL,MOSCOW 121552,RUSSIA. NR 67 TC 48 Z9 48 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscl. Thromb. Vasc. Biol. PD OCT PY 1995 VL 15 IS 10 BP 1607 EP 1615 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RZ865 UT WOS:A1995RZ86500011 PM 7583534 ER PT J AU SNELLER, MC POLIS, MA AF SNELLER, MC POLIS, MA TI DIAGNOSING CYTOMEGALOVIRUS PNEUMONIA - COMMENT ON THE CONCISE COMMUNICATION BY AGLAS ET-AL SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID RHEUMATOID-ARTHRITIS; METHOTREXATE; THERAPY RP SNELLER, MC (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1995 VL 38 IS 10 BP 1528 EP 1528 DI 10.1002/art.1780381024 PG 1 WC Rheumatology SC Rheumatology GA TA574 UT WOS:A1995TA57400023 PM 7575707 ER PT J AU HALULA, M AF HALULA, M TI GIVE CREDIT WHERE CREDIT IS DUE SO ASM NEWS LA English DT Letter C1 NIAID,DIV EXTRANURAL ACT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD OCT PY 1995 VL 61 IS 10 BP 500 EP 500 PG 1 WC Microbiology SC Microbiology GA RZ270 UT WOS:A1995RZ27000005 ER PT J AU BURKHART, JG ARMSTRONG, FB EISEN, EJ AF BURKHART, JG ARMSTRONG, FB EISEN, EJ TI A UNIQUE BILIRUBIN-UDP-GLUCURONOSYLTRANSFERASE DEFICIENCY RELATED TO NEONATAL JAUNDICE IN MICE SO BIOCHEMICAL GENETICS LA English DT Article DE BILIRUBIN-UDP-GLUCURONOSYLTRANSFERASE DEFICIENCY; JAUNDICE; MICE ID GILBERTS SYNDROME; HUMAN-LIVER; MOUSE; RAT; GLUCURONYLTRANSFERASE; HETEROGENEITY; METABOLISM; SEPARATION; CLONING; CDNAS AB This report describes biochemical and cellular characterization of a spontaneous mutation in ICR mice; the mutation has been phenotypically characterized as autosomal recessive jaundice in neonates and juveniles and given the gene symbol hub (J. Hered. 76:441-446, 1985; Mouse Newslett. 73:28, 1985). The results obtained demonstrate that (1) mice homozygous for the mutation are deficient in bilirubin-UDP-glucuronosyltransferase activity, and there is no deficiency in heterozygous mice, (2) the deficiency is lifelong, even though the clinical symptom of jaundice is transitory and restricted to neonates or juveniles, (3) bilirubin-UDP-glucuronosyltransferase activity in mutant and nonmutant mice is similarly induced by triiodothyronine, (4) glucuronidation and xylodation of bilirubin probably occur as the result of separate enzyme forms in mice, and (5) Western analysis using antibody to rat bilirubin-UDP-glucuronosyltransferase indicates that although there is no electrophoretic mobility difference, there is a diffuse band missing in mutant mice. Hepatic hyperplasia, cytomegaly, single-cell necrosis, and eosinophilic foci are also pleiotropic traits associated with homozygous but not heterozygous hub. The hub/hub mouse will be useful in the study of substrate specificity and regulation within a complex gene family and, perhaps, provide a new and useful animal model for the long-term health effects of deficiency in the metabolism of xenobiotics cleared via UDP-glucuronosyltransferase. C1 N CAROLINA STATE UNIV,DEPT BIOCHEM,RALEIGH,NC 27695. N CAROLINA STATE UNIV,DEPT ANIM SCI,RALEIGH,NC 27695. RP BURKHART, JG (reprint author), NATL INST ENVIRONM HLTH SCI,ENVIRONM TOXICOL PROGRAM,MD C4-07,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0006-2928 J9 BIOCHEM GENET JI Biochem. Genet. PD OCT PY 1995 VL 33 IS 9-10 BP 307 EP 326 DI 10.1007/BF02399930 PG 20 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TK388 UT WOS:A1995TK38800003 PM 8748456 ER PT J AU Zang, LY Shi, XL AF Zang, LY Shi, XL TI Evidence for superoxide radical production in peroxynitrite decomposition SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE peroxynitrite decomposition; ESR spin trapping; O-2(.-); generation ID NITRIC-OXIDE; HYDROXYL; INJURY AB Peroxynitrite decomposition was investigated by ESR spin trapping. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). A mixture of peroxynitrite and DMPO generated predominantly DMPO-O-2(-) adduct. A combination of SOD and catalase suppressed the formation of DMPO-O-2(-). The DMPO-O-2(-) signal reached its maximum at pH lower than 7 and decreased as pH increased. The DMPO-O-2(-) signal also depended on peroxynitrite concentration with maximum signal intensity appearing at 4.2 mM. The results demonstrate that peroxynitrite decomposition generates O2(.-). Since reaction of H2O2 with NO2- generates peroxynitrite, the results point out a pathway for conversion of H2O2 to O-2(.-) via peroxynitrite as an intermediate. C1 NCI,LAB EXPT PATHOL,NIH,BETHESDA,MD 20892. RI Shi, Xianglin/B-8588-2012 NR 18 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD OCT PY 1995 VL 37 IS 2 BP 355 EP 360 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG873 UT WOS:A1995VG87300018 PM 8673019 ER PT J AU MENTIS, MJ WEINSTEIN, EA HORWITZ, B MCINTOSH, AR PIETRINI, P ALEXANDER, GE FUREY, M MURPHY, DGM AF MENTIS, MJ WEINSTEIN, EA HORWITZ, B MCINTOSH, AR PIETRINI, P ALEXANDER, GE FUREY, M MURPHY, DGM TI ABNORMAL BRAIN GLUCOSE-METABOLISM IN THE DELUSIONAL MISIDENTIFICATION SYNDROMES - A POSITRON EMISSION TOMOGRAPHY STUDY IN ALZHEIMER-DISEASE SO BIOLOGICAL PSYCHIATRY LA English DT Article DE GLUCOSE BRAIN METABOLISM; DELUSION; DEMENTIA; FRONTAL LOBE; PARALIMBIC SYSTEM; LIMBIC SYSTEM ID CAPGRAS SYNDROME; REDUPLICATIVE PARAMNESIA; HEMORRHAGE; DISORDERS; PATIENT; MEMORY; PET AB Brain lesions have been reported with increasing frequency in the delusional misidentification syndromes (DMS). This is the first controlled study to describe DMS regional cerebral metabolic rates of glucose (rCMRglc). We compared rCMPglc (using positron emission tomography) and neuropsychological data in 9 patients with DMS and Alzheimer dementia (AD), 15AD patients without DMS, and 17 healthy controls. The DMS group differed from the AD group without DMS in having significant hypometabolism in paralimbic (orbitofrontal and cingulate areas bilaterally) and left medial temporal areas, and significant bilateral normalized hypermetabolism in sensory association cortices (superior temporal and inferior parietal) without right left asymmetry. Compared to healthy controls, both AD groups had significant dorsolateral frontal hypometabolism bilaterally. No specific DMS neuropsychological profile was identified. Dysfunctional connections among multimodal association areas, paralimbic structures, and dorsolateral frontal cortex are proposed as the predisposing neural deficit underlying DMS, causing cognitive-perceptual-affective dissonance, which under specific conditions result in ''positive'' delusion formation. RP MENTIS, MJ (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C414,BETHESDA,MD 20892, USA. RI McIntosh, Anthony/G-4955-2011; Furey, Maura/H-5273-2013 NR 62 TC 87 Z9 87 U1 2 U2 6 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD OCT 1 PY 1995 VL 38 IS 7 BP 438 EP & DI 10.1016/0006-3223(94)00326-X PG 0 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RY993 UT WOS:A1995RY99300004 PM 8672604 ER PT J AU KADOR, PF LEE, YS RODRIGUEZ, L SATO, S BARTOSZKOMALIK, A ABDELGHANY, YS MILLER, DD AF KADOR, PF LEE, YS RODRIGUEZ, L SATO, S BARTOSZKOMALIK, A ABDELGHANY, YS MILLER, DD TI IDENTIFICATION OF AN ALDOSE REDUCTASE INHIBITOR SITE BY AFFINITY LABELING SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID DIABETIC COMPLICATIONS; IRREVERSIBLE INHIBITORS; KIDNEY ALDOSE; RAT LENS; DEHYDROGENASE; KINETICS; BINDING AB Animal studies indicate that aldose reductase inhibitors represent a pharmacological method for inhibiting the onset of diabetic complications that is independent of blood sugar control. This has spurred the development of aldose reductase inhibitors (ARIs). To facilitate the rational development of more potent and direct ARIs, more specific knowledge of the structural and pharmacophoric requirements of the site at which ARIs interact are required. Go-crystallization of human placental aldose reductase with the inhibitor zopolrestat has been reported to result in a complex where the inhibitor is almost completely sequestered in the hydrophobic pocket which forms the substrate site. Zopolrestat's observed location, which makes the active site pocket inaccessible to solvent or further productive binding of substrate, is not supported by published inhibitor structure-activity relationships (SAR) studies or kinetic results which indicate that aldose reductase inhibitors such as zopolrestat are either non-competitive or uncompetitive inhibitors. Using a 5-iodoacetamido analog of alrestatin as an affinity labeled aldose reductase inhibitor, an inhibitor binding site on aldose reductase has been located. This inhibitor binding site contains a number of pharmacophoric elements previously proposed for the inhibitor site. Its location and composition is consistent with reported kinetic data, SAR observations, stereochemical requirements, and quantum chemical calculations. C1 NEI, OCULAR THERAPEUT LAB, BETHESDA, MD 20892 USA. OHIO STATE UNIV, COLL PHARM, DIV MED CHEM & NAT PROD, COLUMBUS, OH 43210 USA. NR 41 TC 16 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1995 VL 3 IS 10 BP 1313 EP 1324 DI 10.1016/0968-0896(95)00118-Z PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA TB494 UT WOS:A1995TB49400003 PM 8564397 ER PT J AU SIDDIQI, SM PEARLSTEIN, RA SANDERS, LH JACOBSON, KA AF SIDDIQI, SM PEARLSTEIN, RA SANDERS, LH JACOBSON, KA TI COMPARATIVE MOLECULAR-FIELD ANALYSIS OF SELECTIVE A(3) ADENOSINE RECEPTOR AGONISTS SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID RAT-BRAIN; CLONING; CELLS; AM1 AB A series of 48 N-6-benzyladenosine 5'-uronamide derivatives has been described recently as moderately selective A(3) adenosine receptor agonists of nanomolar potency (Gallo-Rodriguez, C. et al. J. Med. Chem. 1994, 37, 636). Quantitative structure activity relationships in this series, including some novel derivatives, have been investigated using a Comparative Molecular Field Analysis (CoMFA), with emphasis on the N-6-substituent. The resulting three dimensional pharmacophore model defines the steric and electronic factors which modulate in vitro affinities in binding to rat brain A(3) adenosine receptors. The model indicates a positive correlation of affinity with the steric characteristics of the compounds (major factor), particularly toward the 3-position of the benzyl ring of N-6-benzyl NECA, and a weak correlation with the electrostatic effects of the N-6-substituent. A comparison of active and inactive compounds using volume maps showed that bulk at the 3-position of the benzyl ring of the molecule is conducive to high affinity at A(3) receptors, while steric bulk at other positions of the benzyl ring leads to poor binding. t-Boc-amino acid conjugates of a 3-aminobenzyl derivative were synthesized to probe the steric and hydrophobic limitations at that position. We have discovered a subregion of the N-6-benzyl binding pocket occupied by a 3-(L-prolylamino) group that is sterically disallowed at A(3) receptors and allowed in A(1) and A(2), receptors. 6-N-Phenylhydrazino and 6-O-phenylhydroxylamino derivatives, incorporating major changes in electrostatic character of the ligand proximal to the purine, were predicted by the CoMFA model to have high A(3) affinity. Such analogs were synthesized and found to be well tolerated at the A(3) receptor binding site. C1 NIDR,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 31 TC 22 Z9 22 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1995 VL 3 IS 10 BP 1331 EP 1343 DI 10.1016/0968-0896(95)00116-X PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA TB494 UT WOS:A1995TB49400005 PM 8564399 ER PT J AU VERGARA, LA STOJILKOVIC, SS ROJAS, E AF VERGARA, LA STOJILKOVIC, SS ROJAS, E TI GNRH-INDUCED CYTOSOLIC CALCIUM OSCILLATIONS IN PITUITARY GONADOTROPHS - PHASE RESETTING BY MEMBRANE DEPOLARIZATION SO BIOPHYSICAL JOURNAL LA English DT Article ID INOSITOL TRISPHOSPHATE; CA2+ OSCILLATIONS; PLASMA-MEMBRANE; ACINAR-CELLS; HORMONE; MOBILIZATION; ACTIVATION; SECRETION; CHANNELS; CA-2+ AB Cultured rat pituitary gonadotrophs under whole-cell voltage clamp conditions respond to the hypothalamic hormone GnRH with synchronized oscillatory changes in both cytosolic Ca2+ concentration ([Ca2+](i)) and [Ca2+](i)-activated, apamin-sensitive K+ current (I-K(Ca)). We found, and report here for the first time, that in GnRH-stimulated cells a brief depolarizing pulse can elicit a transient [Ca2+](i) rise similar to the endogenous cycle. Furthermore, Ca2+ entry during a single depolarizing pulse was found to shift the phase of subsequent endogenous [Ca2+](i) oscillations, which thereafter continue to occur at their previous frequency before the pulse. Application of two consecutive depolarizing pulses showed that the size of the [Ca2+](i) rise evoked by the second pulse depended on the time lapsed between two consecutive pulses, indicating that each endogenous or evoked [Ca2+](i) rise cycle leaves the Ca2+ release mechanism of the gonadotroph in a refractory state. Recovery from this condition can be described by an exponential function of the time lapsed between the pulses (time constant of ca. 1 s). We propose that the underlying mechanism in both refractoriness after endogenous cycles and phase resetting by a brief pulse of Ca2+ entry involves the InsP(3) receptor-channel molecule presumed to be located on the cytosolic aspect of the endoplasmic reticulum membrane. C1 NIDDK,LCBG,BETHESDA,MD 20892. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD. NR 40 TC 10 Z9 10 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1995 VL 69 IS 4 BP 1606 EP 1614 PG 9 WC Biophysics SC Biophysics GA TJ021 UT WOS:A1995TJ02100040 PM 8534831 ER PT J AU DYER, KD ROSENBERG, HF AF DYER, KD ROSENBERG, HF TI ISOLATION OF HOMOLOGOUS GENE-SEQUENCES BY VECTORETTE CLONING SO BIOTECHNIQUES LA English DT Note ID CHROMOSOME RP DYER, KD (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N104,10 CTR DR MSC 1886,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1995 VL 19 IS 4 BP 550 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY991 UT WOS:A1995RY99100006 PM 8777041 ER PT J AU CHAN, CH BLAZAR, BR EIDE, CR KREITMAN, RJ VALLERA, DA AF CHAN, CH BLAZAR, BR EIDE, CR KREITMAN, RJ VALLERA, DA TI A MURINE CYTOKINE FUSION TOXIN SPECIFICALLY TARGETING THE MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) RECEPTOR ON NORMAL COMMITTED BONE-MARROW PROGENITOR CELLS AND GM-CSF-DEPENDENT TUMOR-CELLS SO BLOOD LA English DT Article ID ACUTE MYELOBLASTIC-LEUKEMIA; BINDING DOMAIN SUBSTITUTION; HUMAN MYELOID CELLS; DIPHTHERIA-TOXIN; GENETIC CONSTRUCTION; BLAST CELLS; PROLIFERATIVE RESPONSE; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING; FRAGMENT-B AB A fusion protein was synthesized consisting of the murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mGM-CSF hybrid gene was cloned into a vector under the control of an inducible promoter and the protein expressed in Escherichia coli. After induction, a protein was purified from inclusion bodies in accord with the deduced molecular weight of DT390 mGM-CSF, Cell-free studies of the adenosine diphosphate-ribosylating activity of DT390 mGM-CSF showed results that were similar to those of native DT. The DT390 mGM-CSF immunotoxin inhibited FDCP2.1d, a murine myelomonocytic tumor line expressing the GMCSF receptor with an IC50 (concentration inhibiting 50% activity) of 5 x 10(-11) mol/L. The fusion toxin was specifically cytotoxic and directed by the GM-CSF portion of the molecule because addition of a monoclonal antibody directed against GM-CSF inhibited its ability to kill the cell line. Cell lines that do not express GM-CSF receptor were not inhibited by the fusion toxin. DT390 mGM-CSF was also able to specifically inhibit normal committed bone marrow (BM) progenitor cells as measured in clonal colony-forming unit granulocyte-macrophage assays. Together, these findings indicate that DT390 mGM-CSF may be useful as a novel tool for purging BM of contaminating leukemia cells or in vivo for eliminating residual leukemia cells. Also, it can be used to determine whether committed and/or noncommitted BM progenitor cells express the GM-CSF receptor. (C) 1995 by The American Society of Hematology. C1 UNIV MINNESOTA HOSP & CLIN,DEPT THERAPEUT RADIOL,EXPTL CANC IMMUNOL SECT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA HOSP & CLIN,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN. UNIV MINNESOTA HOSP & CLIN,DEPT PEDIAT,DIV BONE MARROW TRANSPLANTAT,MINNEAPOLIS,MN. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [R01-CA36725, R01-CA31618] NR 53 TC 31 Z9 32 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 OCT 1 PY 1995 VL 86 IS 7 BP 2732 EP 2740 PG 9 WC Hematology SC Hematology GA RW497 UT WOS:A1995RW49700032 PM 7670112 ER PT J AU IBANEZ, V DEIBER, MP SADATO, N TORO, C GRISSOM, J WOODS, RP MAZZIOTTA, JC HALLETT, M AF IBANEZ, V DEIBER, MP SADATO, N TORO, C GRISSOM, J WOODS, RP MAZZIOTTA, JC HALLETT, M TI EFFECTS OF STIMULUS RATE ON REGIONAL CEREBRAL BLOOD-FLOW AFTER MEDIAN NERVE-STIMULATION SO BRAIN LA English DT Article DE SOMATOSENSORY EVOKED POTENTIALS; PET; MOVEMENT DISORDERS; PRIMARY SOMATOSENSORY AREA ID SOMATOSENSORY-EVOKED-POTENTIALS; POSITRON EMISSION TOMOGRAPHY; PET IMAGES; ELECTRICAL-STIMULATION; HUNTINGTONS-DISEASE; AUTOMATED ALGORITHM; FINGER STIMULATION; CORTICAL DYNAMICS; ACTIVE MOVEMENT; DORSAL HORN AB The primary motor cortex and supplementary motor area (SMA) are purportedly involved in the generation of the P22 and N30 components of somatosensory evoked potentials (SEPs) evoked by electrical stimulation of the median nerve at the wrist. We used regional cerebral blood flow (rCBF) measurements and PET in 10 normal subjects to study the cerebral areas activated by median nerve electrical stimulation. PET scans were performed with the subjects at rest and during stimulation of the right median nerve at frequencies of up to 20 Hz. Stimulation evoked a single focus of activation in the primary somatosensory area (SI). An increase of rCBF in this area was linearly correlated with stimulus frequencies of up to 4 Hz and then reached a plateau. The SMA was not significantly activated by stimulation at arty of the frequencies tested. In contrast to the SI, the SMA showed no trend toward a correlation between the rCBF changes and the stimulus repetition rate. In order to achieve maximal resolution in the sensorimotor cortex, regions of interest were placed in individual co-registered MRI-PET images on both sides of the central sulcus. There was no significant increase of rCBF in the crown of the precentral gyrus. These results suggest that a contribution of the primary motor cortex and the SMA to the generation of the P22 and N30 components of SEPs is unlikely. Consequently, functional clinical interpretations derived from P22 or N30 abnormalities must be reconsidered. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. RI Deiber, Marie-Pierre/M-5949-2014 NR 78 TC 85 Z9 85 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 1995 VL 118 BP 1339 EP 1351 DI 10.1093/brain/118.5.1339 PN 5 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TH864 UT WOS:A1995TH86400022 PM 7496791 ER PT J AU BUDKA, H AGUZZI, A BROWN, P BRUCHER, JM BUGIANI, O GULLOTTA, F HALTIA, M HAUW, JJ IRONSIDE, JW JELLINGER, K KRETZSCHMAR, HA LANTOS, PL MASULLO, C SCHLOTE, W TATEISHI, J WELLER, RO AF BUDKA, H AGUZZI, A BROWN, P BRUCHER, JM BUGIANI, O GULLOTTA, F HALTIA, M HAUW, JJ IRONSIDE, JW JELLINGER, K KRETZSCHMAR, HA LANTOS, PL MASULLO, C SCHLOTE, W TATEISHI, J WELLER, RO TI NEUROPATHOLOGICAL DIAGNOSTIC-CRITERIA FOR CREUTZFELDT-JAKOB-DISEASE (CJD) AND OTHER HUMAN SPONGIFORM ENCEPHALOPATHIES (PRION DISEASES) SO BRAIN PATHOLOGY LA English DT Article ID GERSTMANN-STRAUSSLER SYNDROME; ALZHEIMERS-DISEASE; AMYLOID PLAQUES; PROTEIN; DEMENTIA; PATHOLOGY; SCHEINKER; VARIANT; FAMILY AB Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD - sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immunoreactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Straussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spongiosis. This includes status spongiosus (''spongiform state''), comprising irregular cavities in gliotic neuropil following extensive neuronal (including also lesions of ''burnt-out'' ''spongy'' changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission. C1 UNIV ZURICH, INST NEUROPATHOL, ZURICH, SWITZERLAND. NIH, NINDS, CENT NERVOUS SYST STUDIES LAB, BETHESDA, MD 20892 USA. UNIV CATHOLIQUE LOUVAIN, NEUROPATHOL UNIT, B-1200 BRUSSELS, BELGIUM. NATL INST NEUROL C BESTA, MILAN, ITALY. UNIV MUNSTER, INST NEUROPATHOL, W-4400 MUNSTER, GERMANY. UNIV HELSINKI, INST PATHOL, HELSINKI, FINLAND. HOP LA PITIE SALPETRIERE, LAB NEUROPATHOL R ESCOUROLLE, F-75651 PARIS, FRANCE. WESTERN GEN HOSP, DEPT PATHOL, NEUROPATHOL LAB, EDINBURGH EH4 2XU, MIDLOTHIAN, SCOTLAND. LAINZ HOSP, DEPT NEUROL, NEUROPATHOL LAB, VIENNA, AUSTRIA. UNIV GOTTINGEN, INST NEUROPATHOL, W-3400 GOTTINGEN, GERMANY. UNIV LONDON, INST PSYCHIAT, DEPT NEUROPATHOL, LONDON SE5 8AF, ENGLAND. UNIV CATTOLICA SACRO CUORE, INST NEUROL, I-00168 ROME, ITALY. UNIV FRANKFURT, INST NEUROL, W-6000 FRANKFURT, GERMANY. KYUSHU UNIV, INST NEUROL, DEPT NEUROPATHOL, FUKUOKA 812, JAPAN. SOUTHAMPTON UNIV HOSP, SOUTHAMPTON, HANTS, ENGLAND. RP BUDKA, H (reprint author), UNIV VIENNA, NEUES AKA, INST NEUROL, POB 48, A-1097 VIENNA, AUSTRIA. RI Aguzzi, Adriano/A-3351-2008; OI Budka, Herbert/0000-0002-1933-1577; Aguzzi, Adriano/0000-0002-0344-6708 NR 38 TC 284 Z9 290 U1 3 U2 14 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 1995 VL 5 IS 4 BP 459 EP 466 DI 10.1111/j.1750-3639.1995.tb00625.x PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA TK374 UT WOS:A1995TK37400013 PM 8974629 ER PT J AU DALY, JW AF DALY, JW TI ALKALOIDS FROM FROG SKINS - SELECTIVE PROBES FOR ION CHANNELS AND NICOTINIC RECEPTORS SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE ALKALOIDS; AMPHIBIANS; BIRDS; BATRACHOTOXIN; HISTRIONICOTOXINS; PUMILIOTOXINS; EPIBATIDINE ID MYOBATRACHIDAE; PUMILIOTOXINS; QUINOLIZIDINES; PYRROLIZIDINES; DENDROBATIDAE; INDOLIZIDINES AB Amphibian skin has provided a wide range of biologically active alkaloids: many of which have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified and structures of over a dozen different classes of alkaloids have been elucidated. These include the batrachotoxins, which were shown to be potent and selective activators and ligands for sodium channels, the histrionicotoxins, which were shown to be potent non-competitive blockers and ligands for nicotinic receptor channel complexes, the pumiliotoxins and related allo- and homo-pumiliotoxins, which were shown to have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, which was shown to have potent antinociceptive activity due to selective agonist activity at nicotinic receptors. These alkaloids are known in nature only in amphibian skin, except for homobatrachotoxin, which was recently identified in feathers and skill of a bird. Further classes of alkaloids from amphibian skin include monocyclic pyrrolidines and piperidines, bicyclic decahydroquinolines, pyrrolizidines: indolizidines, and quinolizidines and tricyclic gephyrotoxins, pyrrolizidine oximes: pseudophrynamines, and coccinellines. These alkaloids also have activity at ion channels. It appears likely that all of the frog skin alkaloids are taken up and sequestered into the skin from the diet, which for such amphibians consists mainly of small arthropods. The pyrrolidines, piperidines, 3,5-disubstituted pyrrolizidines and 3,5-disubstituted indolizidines appear likely to be derived from ants? the coccinellines and related tricyclics from beetles and the pyrrolizidine oximes from millipedes. The origins of the batrachotoxins, histrionicotoxins, pumiliotoxins and epibatidine are of particular interest in view of their remarkable biological activities. RP DALY, JW (reprint author), NIDDK,BIOORGAN CHEM LAB,BLDG 8,RM 1A17,BETHESDA,MD 20892, USA. NR 28 TC 17 Z9 19 U1 1 U2 14 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD OCT PY 1995 VL 28 IS 10 BP 1033 EP 1042 PG 10 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA TD308 UT WOS:A1995TD30800002 PM 8634674 ER PT J AU RODGERS, GP RACHMILEWITZ, EA AF RODGERS, GP RACHMILEWITZ, EA TI NOVEL TREATMENT OPTIONS IN THE SEVERE BETA-GLOBIN DISORDERS SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE GLOBIN GENE EXPRESSION; SEVERE BETA-GLOBIN DISORDERS; GENETIC CONTROL ID SICKLE-CELL-ANEMIA; FETAL HEMOGLOBIN PRODUCTION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; THALASSEMIA-INTERMEDIA; GENE-EXPRESSION; ERYTHROID-CELLS; HYDROXYUREA; DISEASE; BUTYRATE; STIMULATION C1 NIDDK,BETHESDA,MD. HEBREW UNIV JERUSALEM,HADASSAH UNIV HOSP,HADASSAH MED SCH,DEPT HAEMATOL,JERUSALEM,ISRAEL. NR 63 TC 61 Z9 61 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 1995 VL 91 IS 2 BP 263 EP 268 DI 10.1111/j.1365-2141.1995.tb05288.x PG 6 WC Hematology SC Hematology GA TA931 UT WOS:A1995TA93100001 PM 8547060 ER PT J AU SUGDEN, D ANWAR, N KLEIN, DC AF SUGDEN, D ANWAR, N KLEIN, DC TI CHARACTERIZATION OF THE ALPHA(1)-ADRENOCEPTOR SUBTYPE IN THE RAT PINEAL-GLAND SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 NATL INST HLTH,BETHESDA,MD 20892. UNIV LONDON KINGS COLL,DIV BIOMED SCI,PHYSIOL GRP,LONDON W8 7AH,ENGLAND. NR 2 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 1995 VL 116 SU S BP P206 EP P206 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RZ545 UT WOS:A1995RZ54500206 ER PT J AU Clemens, J Rao, M Naficy, A AF Clemens, J Rao, M Naficy, A TI Selection of outcomes for assessing vaccine protection in cholera vaccine trials: The need for suitable breadth and depth SO BULLETIN DE L INSTITUT PASTEUR LA English DT Article ID FIELD TRIAL; BREAST-MILK; CHILDREN RP Clemens, J (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD OCT-DEC PY 1995 VL 93 IS 4 BP 237 EP 241 DI 10.1016/0020-2452(96)85757-5 PG 5 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA TW006 UT WOS:A1995TW00600003 ER PT J AU Szu, SC Gupta, R Kovac, P Taylor, DN Robbins, JB AF Szu, SC Gupta, R Kovac, P Taylor, DN Robbins, JB TI Development of O-specific polysaccharide-protein conjugates is based upon the protective effect of serum vibriocidal antibodies against cholera SO BULLETIN DE L INSTITUT PASTEUR LA English DT Article ID FIELD TRIAL; BANGLADESH; VACCINES; IMMUNITY; LIPOPOLYSACCHARIDES; IMMUNIZATION; INFECTION C1 NIH,BETHESDA,MD 20892. WALTER REED ARMY INST RES,WASHINGTON,DC 20014. NR 31 TC 3 Z9 3 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0020-2452 J9 B I PASTEUR JI Bull. Inst. Pasteur PD OCT-DEC PY 1995 VL 93 IS 4 BP 269 EP 272 DI 10.1016/0020-2452(96)85761-7 PG 4 WC Immunology; Microbiology; Virology SC Immunology; Microbiology; Virology GA TW006 UT WOS:A1995TW00600007 ER PT J AU RIMINUCCI, M SILVESTRINI, G BONUCCI, E FISHER, LW ROBEY, PG BIANCO, P AF RIMINUCCI, M SILVESTRINI, G BONUCCI, E FISHER, LW ROBEY, PG BIANCO, P TI THE ANATOMY OF BONE SIALOPROTEIN IMMUNOREACTIVE SITES IN BONE AS REVEALED BY COMBINED ULTRASTRUCTURAL HISTOCHEMISTRY AND IMMUNOHISTOCHEMISTRY SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE BONE SIALOPROTEIN; OSTEOBLAST; BONE MATRIX; ELECTRON MICROSCOPY; IMMUNOLOCALIZATION; NONCOLLAGENOUS PROTEIN ID CARTILAGE FIXATION; RAT OSTEOCLASTS; MATRIX PROTEINS; MALACHITE GREEN; OSTEOPONTIN; IMMUNOLOCALIZATION; ATTACHMENT; BSP; PURIFICATION; LOCALIZATION AB Bone sialoprotein was immunolocalized at the EM level in thin Lowicryl K4M sections of rat bone. Because of the unconventional EM morphology of the bone matrix seen in thin demineralized acrylate sections, the pattern of immunolabeling was compared with detailed structural images of demineralized bone obtained using an en bloc treatment of tissue samples with the cationic electron 'dye,' Malachite Green (MG), which provides stabilization and retention of anionic material throughout specimen processing. A system of structures corresponding to the sites of bone sialoprotein (BSP) immunoreactivity, as seen in Lowicryl K4M thin sections, could be readily identified in the MG-treated, epoxy thin sections. This system includes the cement lines, and aggregates of similar material within mineralized bone and mineralizing osteoid. The virtual identity of BSP distribution with the arrangement of the MG-visualized material indicates that a BSP-enriched, noncollagenous phase can be demonstrated using different, unrelated tissue preparation and imaging protocols for EM. Besides improving our understanding of the distribution of bone sialoprotein in bone, these data assign a previously unrecognized structural dimension to noncollagenous material in the bone matrix. C1 UNIV ROMA LA SAPIENZA,DEPT EXPTL MED,I-00161 ROME,ITALY. UNIV LAQUILA,LAQUILA,ITALY. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 29 TC 27 Z9 27 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD OCT PY 1995 VL 57 IS 4 BP 277 EP 284 DI 10.1007/BF00298883 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RV814 UT WOS:A1995RV81400007 PM 8673865 ER PT J AU COLWELL, RR HUQ, A CHOWDHURY, MAR BRAYTON, PR XU, B AF COLWELL, RR HUQ, A CHOWDHURY, MAR BRAYTON, PR XU, B TI SEROGROUP CONVERSION OF VIBRIO-CHOLERAE SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Note DE SEROGROUP CONVERSION; VIBRIO CHOLERAE O1; VIBRIO CHOLERAE NON-O1; CHOLERA ID SEROTYPE CONVERSION; CHESAPEAKE BAY; ENVIRONMENT; O1; VIBRIO-CHOLERAE-01; ANTIBODY; BACTERIA; SURVIVAL; ECOLOGY AB Vibrio choler ae serogroup O1 can be detected in the environment in a viable but nonculturable form, whereas V. cholerae non-Ol cells can be readily cultured during interepidemic periods in geographical regions where cholera is endemic. In the present study, pure cultures of V. cholerae non-Ol cells contained O1 cells when examined by immune-fluorescence microscopy. Laboratory microcosms were used to examine the outgrowth of the O1 cells in cultures of non-Ol V. choler ae. One O1 cell per 10(6) non-O1 cells could be detected by direct fluorescent-monoclonal antibody staining but only after incubation of the non-O1 culture for 48 h. Individual O1 cells were not detected in cultures incubated less than 48 h. Hybridization study, using a polymerase chain reaction (PCR) amplified fragment of the O-antigen of V. cholerae O1 as a probe, revealed the existence of a homologous gene in a microcosm sample of V. cholerae non-O1 containing serogroup-converted cells. The mechanism by which O1 cells can occur in cultures of non-O1 V. cholerae most likely resulted from spontaneous mutation of gene(s) encoding the O-somatic properties and (or) chemical, physical, or biological changes in the environment inducing expression or repression of the controlling gene(s). These findings have important implications for the epidemiology of cholera and the environmental source(s) of toxin producing V. cholerae O1. C1 UNIV MARYLAND,DEPT MICROBIOL,COLLEGE PK,MD 20740. NEI,BETHESDA,MD 20892. RP COLWELL, RR (reprint author), UNIV MARYLAND,INST BIOTECHNOL,4321 HARTWICK RD,SUITE 550,COLLEGE PK,MD 20740, USA. NR 28 TC 30 Z9 34 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD OCT PY 1995 VL 41 IS 10 BP 946 EP 950 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA TA465 UT WOS:A1995TA46500014 PM 8590409 ER PT J AU ESTEVALORENZO, F JANIK, JE FENTON, RG EMSLIESMITH, A ENGEL, AG LONGO, DL AF ESTEVALORENZO, F JANIK, JE FENTON, RG EMSLIESMITH, A ENGEL, AG LONGO, DL TI MYOSITIS ASSOCIATED WITH INTERLEUKIN-2 THERAPY IN A PATIENT WITH METASTATIC RENAL-CELL CARCINOMA SO CANCER LA English DT Article DE INTERLEUKIN-2; RENAL CELL CANCER; IMMUNOTHERAPY; MYOSITIS; TUMOR VACCINE ID ACTIVATED KILLER CELLS; HIGH-DOSE INTERLEUKIN-2; CLASS-I; POLYMYOSITIS; EXPRESSION; CANCER; MYOPATHIES; CIMETIDINE; COMPLEX AB Background. Interleukin-2 (IL-2) has been used successfully in the treatment of some patients with metastatic renal cell carcinoma and melanoma, with a partial response rate of 15%-20%. It produces a well documented spectrum of side effects. Autoimmune diseases have been associated with IL-2 immunotherapy and the development of autoimmune thyroiditis may correlate with antitumor clinical response. Methods. A patient with metastatic renal cell carcinoma is described who developed a polymyositis-like myopathy after an autologous tumor vaccine and IL-2 therapy. Results. The patient had a delayed response for 15 months after developing this previously unreported toxicity. Conclusions. To the authors' knowledge, this represents the first reported case of necrotizing myositis in association with IL-2 therapy. Subsequent continuous partial response of the advanced malignancy was observed for 15 months. In this case, IL-2 may have broken tolerance to both normal muscle cells and tumor cells. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. MAYO CLIN,NEUROMUSCULAR RES LAB,ROCHESTER,MN. RP ESTEVALORENZO, F (reprint author), GEORGETOWN UNIV,MED CTR,LOMBARDI CANC CTR,DIV HEMATOL ONCOL,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. FU NINDS NIH HHS [NS6277] NR 26 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1995 VL 76 IS 7 BP 1219 EP 1223 DI 10.1002/1097-0142(19951001)76:7<1219::AID-CNCR2820760719>3.0.CO;2-O PG 5 WC Oncology SC Oncology GA RV692 UT WOS:A1995RV69200018 PM 8630901 ER PT J AU ANWAR, N KINGMA, DW BLOCH, AR MOURAD, M RAFFELD, M FRANKLIN, J MAGRATH, I ELBOLKAINY, N JAFFE, ES AF ANWAR, N KINGMA, DW BLOCH, AR MOURAD, M RAFFELD, M FRANKLIN, J MAGRATH, I ELBOLKAINY, N JAFFE, ES TI THE INVESTIGATION OF EPSTEIN-BARR VIRAL SEQUENCES IN 41 CASES OF BURKITTS-LYMPHOMA FROM EGYPT - EPIDEMIOLOGIC CORRELATIONS SO CANCER LA English DT Article DE BURKITTS LYMPHOMA; EPSTEIN-BARR VIRUS (EBV); EBER1; IN SITU HYBRIDIZATION; P53; IMMUNOSUPPRESSION ID HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; ASSOCIATION; AFRICAN; INDIVIDUALS; RELEVANCE; CHILDREN; SUBTYPES; DISEASE; TUMORS AB Background. Epstein-Barr virus (EBV) is associated with many human neoplasms, including Burkitt's lymphoma (BL). Endemic BL in central Africa is more often EBV-associated than BL in the United States, where seroconversion for EBV occurs somewhat later than in Africa. Therefore, the EBV association rate in BL may correlate more with the socioeconomic status of the population studied, which influences the age of EBV seroconversion, than with such factors as malaria, which may relate to the overall higher incidence rate in endemic regions. Methods. Forty-one patients with BL in Egypt, which differs both climatically and racially from central African countries (i.e., Kenya, Uganda) where BL is endemic, were analyzed. All biopsies were evaluated for EBV-encoded RNAs (EBER1) by RNA in situ hybridization, analyzed for p53 protein expression using the monoclonal antibody D07, and immunophenotyped using a panel of monoclonal antibodies that included L26 (CD20), Leu 22 (CD43), and A6 (CD45RO). Twelve cases were evaluable for EBV subtype by polymerase chain reaction with EBV-specific primers. Results. The median age at diagnosis was 9 years (range, 2-22 years). The biopsy site was extranodal in 29 patients and nodal in 12 patients. All 41 cases were documented as B-cell neoplasms. A hybridization signal for EBER1 RNA was identified in greater than 95% of the neoplastic cells in 30 of 41 cases (73%), whereas no signal was observed in 11 cases (27%). Epstein-Barr virus subtype 1 was found in 10 patients, subtype 2 in two patients. Immunostaining for p53 was observed in greater than 5% of the neoplastic cells in 9 of 37 cases (24%). No significant correlation was observed between EBV positivity and sex, biopsy site, or p53 immunostaining. Conclusions. The prevalence of EBV in BL from Egypt is slightly lower than in BL in endemic regions, but significantly higher than in sporadic BL. Epstein-Barr virus positivity probably reflects the socioeconomic status of the patient population, and age at seroconversion. The prevalence of EBV subtype 1 suggests that immunodeficiency does not play a role in Egyptian Burkitt's lymphoma, in contrast to endemic Burkitt's lymphoma, in which holoendemic malaria is thought to contribute to immunodeficiency, a higher incidence rate, and the observed prevalence of subtype 2. C1 NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. NATL CANC INST,CAIRO,EGYPT. NR 30 TC 44 Z9 45 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1995 VL 76 IS 7 BP 1245 EP 1252 DI 10.1002/1097-0142(19951001)76:7<1245::AID-CNCR2820760723>3.0.CO;2-D PG 8 WC Oncology SC Oncology GA RV692 UT WOS:A1995RV69200022 PM 8630905 ER PT J AU POLITI, PM XIE, F DAHUT, W FORD, H KELLEY, JA BASTIAN, A SETSER, A ALLEGRA, CJ CHEN, AP HAMILTON, JM ARBUCK, SF LINZ, P BRAMMER, H GREM, JL AF POLITI, PM XIE, F DAHUT, W FORD, H KELLEY, JA BASTIAN, A SETSER, A ALLEGRA, CJ CHEN, AP HAMILTON, JM ARBUCK, SF LINZ, P BRAMMER, H GREM, JL TI PHASE-I CLINICAL-TRIAL OF CONTINUOUS-INFUSION CYCLOPENTENYL CYTOSINE SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE CYCLOPENTENYL CYTOSINE; PHASE I TRIALS; CTP SYNTHASE; PHARMACOKINETICS; HYPOTENSION ID METABOLISM; CYTIDINE; ANALOG; TRIPHOSPHATE; ANTITUMOR; ACIVICIN; CELLS; ACID AB Cyclopentenyl cytosine (CPE-C) is an investigational drug that is active against human solid tumor xenografts. The 5'-triphosphate of CPE-C inhibits CTP synthase, and depletes CTP and dCTP pools. We conducted a phase I clinical trial of CPE-C given as a 24-h continuous i.v. infusion every 3 weeks in 26 adults with solid tumors. The starting dose rate, 1 mg/m(2) per h, was selected on the basis of both preclinical studies and pharmacokinetic data from two patients obtained after a test dose of 24 mg/m(2) CPE-C as an i.v. bolus. Dose escalation was guided by clinical toxicity. A total of 87 cycles were given, and ten patients received four or more cycles. The mean CPE-C steady-state plasma levels (Cpss) increased linearly from 0.4 mu M to 3.1 mu M at dose levels ranging from 1 to 5.9 mg/m(2) per h (actual body weight); the mean total body clearance was 146 +/- 38 ml/min per m(2). CPE-C was eliminated by both renal excretion of intact drug and deamination to cyclopentenyl uracil in an apparent 2:1 ratio. CTP synthase activity in intact bone marrow mononuclear cells was inhibited by 58% to 100% at 22 h compared to matched pretreatment samples at all CPE-C dose levels. When all data were combined, flux through CTP synthase was decreased by 89.6% +/- 3.1% at 22 h (mean +/- SE, n = 16), and remained inhibited by 67.6% +/- 7.7% (n = 10) for at least 24 h post-CPE-C infusion. Granulocyte and platelet toxicities were dose-dependent, and dose-limiting myelosuppression occurred during the initial cycle in two of three patients treated with 5.9 mg/m(2) per h. Four of 11 patients (4 of 20 cycles) who received 4.7 mg/m(2) per h CPE-C experienced hypotension 24-48 h after completion of the CPE-C infusion during their first (n = 2), third (n = 1) and sixth cycles (n = 1): respectively. Two of these patients died with refractory hypotension despite aggressive hydration and cardiopulmonary resuscitation. One of 12 patients (28 total cycles) treated with 3.5 mg/m(2) per h CPE-C experienced orthostatic hypotension during cycle 1; and this patient had a second episode of orthostatic hypotension at a lower dose (3.0 mg/m(2)per h). Hypotension was not seen in patients receiving less than or equal to 2.5 mg/m(2) per h CPE-C. The occurrence of hypotension did not directly correlate with either CPE-C Cpss, CPE-U plasma levels, pretreatment cytidine plasma levels, baseline CTP synthase activity, or with the degree of enzyme inhibition during treatment. While the hypotension appeared to be dose-related, its unpredictable occurrence and the uncertainty concerning the mechanism preclude a recommendation of a tolerable dose for future studies. C1 NCI, DIV CANC TREATMENT, CLIN ONCOL PROGRAM, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NCI, DIV CANC TREATMENT, MED CHEM LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT INTERNAL MED, DIV CARDIOL, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT RADIOL, BETHESDA, MD 20892 USA. NR 27 TC 36 Z9 36 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 1995 VL 36 IS 6 BP 513 EP 523 DI 10.1007/BF00685802 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA RW211 UT WOS:A1995RW21100010 PM 7554044 ER PT J AU GREENWALD, P KELLOFF, GJ BOONE, CW MCDONALD, SS AF GREENWALD, P KELLOFF, GJ BOONE, CW MCDONALD, SS TI GENETIC AND CELLULAR-CHANGES IN COLORECTAL-CANCER - PROPOSED TARGETS OF CHEMOPREVENTIVE AGENTS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; PROSTAGLANDIN-H-SYNTHASE; K-RAS MUTATIONS; MALE F344 RATS; COLON-CANCER; CHEMICAL CARCINOGENESIS; N-ACETYLCYSTEINE; TUMOR PROMOTION; ELLAGIC ACID; REDUCED RISK AB Progress in development of a genetic model for colorectal tumorigenesis and human chemoprevention research may allow the mechanism-based identification of targets and chemopreventive agents that will protect against colorectal cancer, For example, numerous mutagenic events can occur throughout colorectal carcinogenesis, including loss of heterozygosity in tumor suppressor genes such as APC, MCC, DCC, and p53, as well as in oncogenes such as K-ras, Chemopreventive agents that inhibit mutagenic activity such as N-acetyl-l-cysteine, oltipraz, and nonsteroidal anti-inflammatory drugs may protect against these mutations, Also, agents such as perillyl alcohol and lovastatin that interfere,vith protein isoprenylation and, hence, inhibit oncogene activation may protect against aberrant K-ras expression, Hyperproliferation in normal mucosa, leading to early adenomas, and cellular proliferation, leading to growth and progression of neoplasia, are also aspects of colorectal carcinogenesis that can be controlled by chemopreventive agents, Calcium is a chemopreventive agent for which there is both clinical and experimental evidence of inhibition of cell proliferation in colon mucosa, Other examples of antiproliferative agents with potential chemopreventive efficacy in colon are 2-difluoromethylornithine, dehydroepiandrosterone, and selenium, Differentiating agents such as retinoids and deltanoids also may slow proliferation and progression, Antioxidants have potential for interfering with both mutagenicity and proliferation (e,g,, by preventing oxidative activation of carcinogens and scavenging activated oxygen species generated during inflammation), The same mechanistic principles apply to identification of dietary chemopreventive intervention for colorectal carcinogenesis, For example, lowering dietary fat and increasing dietary fiber lead to lower colorectal mucosal proliferation, and cruciferous vegetables contain agents such as indoles and dithiolthiones that have shown antimutagenic activity. C1 SCI CONSULTING GRP INC,GAITHERSBURG,MD 20878. RP GREENWALD, P (reprint author), NCI,DIV CANC PREVENT & CONTROL,BLDG 31,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 173 TC 56 Z9 58 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT-NOV PY 1995 VL 4 IS 7 BP 691 EP 702 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RZ110 UT WOS:A1995RZ11000001 PM 8672984 ER PT J AU KLABUNDE, C KALUZNY, A FORD, L AF KLABUNDE, C KALUZNY, A FORD, L TI COMMUNITY CLINICAL ONCOLOGY PROGRAM PARTICIPATION IN THE BREAST-CANCER PREVENTION TRIAL - FACTORS AFFECTING ACCRUAL SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SIZE AB Cancer prevention and control involves a diverse spectrum of activities that range from preventing the disease to providing rehabilitation to its survivors. The range of activities included within the definition of cancer prevention and control makes it difficult to determine factors that would predict accrual to specific cancer prevention and control trials, The participation of 36 CCOP organizations in the National Cancer Institute-sponsored Breast Cancer Prevention Trial (BCPT) presented the opportunity to assess the ability of Community Clinical Oncology Program (CCOPs) to enroll subjects in one of the nation's first large-scale cancer prevention trials and to compare characteristics of CCOP accrual to the BCPT with factors associated with accrual by CCOPs to cancer treatment and other cancer prevention and control clinical trials, Although representing only 13% of participating health care organizations, CCOPs presently contribute nearly 30% of total BCPT accrual, Comparison of regression models representing accrual to treatment, cancer control, and chemoprevention (i,e,, BCPT) protocols shows similar predictors between treatment and chemoprevention models, Cancer control models, however, did not share similar predictors, Thus, accrual to chemoprevention trials is associated, to a greater extent, with the characteristics that facilitate accrual to treatment trials rather than to cancer control trials, Results have implications for the planning and ongoing management of cancer treatment, control, and chemoprevention clinical trials. C1 UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH PUBL HLTH,CHAPEL HILL,NC 27599. NCI,DIV CANC PREVENT & CONTROL,COMMUNITY ONCOL & REHABIL BRANCH,BETHESDA,MD 20892. RP KLABUNDE, C (reprint author), UNIV N CAROLINA,CECIL G SHEPS CTR HLTH SERV RES,725 AIRPORT RD,BLDG CB 7590,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [5-P50-CA58223] NR 21 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT-NOV PY 1995 VL 4 IS 7 BP 783 EP 789 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RZ110 UT WOS:A1995RZ11000014 PM 8672997 ER PT J AU MCDONALD, JW TAYLOR, JA WATSON, MA SACCOMANNO, G DEVEREUX, TR AF MCDONALD, JW TAYLOR, JA WATSON, MA SACCOMANNO, G DEVEREUX, TR TI P53 AND K-RAS IN RADON-ASSOCIATED LUNG ADENOCARCINOMA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Note ID URANIUM MINERS; MUTATIONS; RADIATION; CANCER AB Mutations in the p53 tumor suppressor gene and the K-ras proto-oncogene are common genetic defects in lung cancer, Analysis of the patterns of damage in these genes may provide important insights into the mechanisms by which environmental mutagens initiate cancer, Previously, our laboratory found that a rare p53 codon 249 mutation (AGG(ARG) to ATG(MET) transversion) was present in 31% of a series of 52 large and squamous cell lung cancers from uranium miners, suggesting that this mutation might be a marker for radon exposure, In the current study, we analyzed 23 lung adenocarcinomas from the same cohort of highly exposed uranium miners. These tumors failed to show the codon 249 transversion, but 9 (39%) of 23 contained 1 or more mutations within hotspots in the K-ras gene, The results suggest that there is histological tissue-type specificity for the codon 249 mutation; although this mutation was common in squamous and large cell tumors from very highly exposed uranium miners, it is rare in adenocarcinomas from the same cohort of miners. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. ST MARYS HOSP,GRAND JCT,CO. OI taylor, jack/0000-0001-5303-6398 NR 11 TC 36 Z9 42 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT-NOV PY 1995 VL 4 IS 7 BP 791 EP 793 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RZ110 UT WOS:A1995RZ11000015 PM 8672998 ER PT J AU TOMASZEWSKI, JG DELAPENA, L MOLENDA, J GANTZ, S BERNATO, DL FOLTS, S AF TOMASZEWSKI, JG DELAPENA, L MOLENDA, J GANTZ, S BERNATO, DL FOLTS, S TI PROGRAMMED-INSTRUCTION - BIOTHERAPY MODULE .2. OVERVIEW OF BIOTHERAPY SO CANCER NURSING LA English DT Article RP TOMASZEWSKI, JG (reprint author), NIH,CTR CLIN,CANC HUMAN GENOME NURSING SERV,BETHESDA,MD 20892, USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD OCT PY 1995 VL 18 IS 5 BP 397 EP 412 PG 16 WC Oncology; Nursing SC Oncology; Nursing GA TA468 UT WOS:A1995TA46800009 PM 7585495 ER PT J AU YANG, CL CIRIELLI, C CAPOGROSSI, MC PASSANITI, A AF YANG, CL CIRIELLI, C CAPOGROSSI, MC PASSANITI, A TI ADENOVIRUS-MEDIATED WILD-TYPE P53 EXPRESSION INDUCES APOPTOSIS AND SUPPRESSES TUMORIGENESIS OF PROSTATIC TUMOR-CELLS SO CANCER RESEARCH LA English DT Note ID GROWTH AB The use of replication-deficient adenoviral vectors in gene therapy may become a powerful method to achieve efficient but safe transfer of antitumor agents. Introduction of the wild-type p53 gene into tumor cells has, in general, been associated with growth suppression, In this study, infection of androgen-independent human prostate Tsu-pr1 cells lacking functional p53 alleles resulted in high levels of p53 protein within 10-15 h. Cells infected with AdCMV.p53 detached from the substratum, condensed, and exhibited fragmentation of nuclear DNA into nucleosomal units consistent with the process of apoptosis. These effects were evident within 24 h after infection, and the majority of cells had undergone apoptosis by 48 h, whereas cells infected with AdCMV.NLS beta Gal continued to proliferate, Uninfected or AdCMV.NLS beta Gal-infected Tsu-pr1 cells formed tumors in nude mice within 3 weeks after implantation, whereas AdCMV.p53-infected cells failed to form tumors during this period, Therefore, adenoviral-mediated antitumor therapy using the p53 gene is an efficient method to inhibit prostate tumor growth, and agents that target the cellular programmed cell death pathway may be useful in clinical applications. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,GENE THERAPY UNIT,BALTIMORE,MD 21224. IST DERMOPATICO IMMACOLTA,PATOL VASC LAB,I-00167 ROME,ITALY. NR 24 TC 140 Z9 145 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 OCT 1 PY 1995 VL 55 IS 19 BP 4210 EP 4213 PG 4 WC Oncology SC Oncology GA RX114 UT WOS:A1995RX11400002 PM 7671222 ER PT J AU RAO, CV RIVENSON, A SIMI, B ZANG, E HAMID, R KELLOFF, GJ STEELE, V REDDY, BS AF RAO, CV RIVENSON, A SIMI, B ZANG, E HAMID, R KELLOFF, GJ STEELE, V REDDY, BS TI ENHANCEMENT OF EXPERIMENTAL COLON CARCINOGENESIS BY DIETARY 6-PHENYLHEXYL ISOTHIOCYANATE SO CANCER RESEARCH LA English DT Article ID MALE F344 RATS; PHENETHYL ISOTHIOCYANATE; BENZYL ISOTHIOCYANATE; ARYLALKYL ISOTHIOCYANATES; A/J MICE; PROSTAGLANDIN SYNTHESIS; N-NITROSODIMETHYLAMINE; SIGNAL TRANSDUCTION; 2ND MESSENGERS; PROTEIN-KINASE AB Naturally occurring and related synthetic isothiocyanates are known to exert chemopreventive effects in several organs in rodent models. The present study was designed to investigate the efficacy of 6-phenylhexyl isothiocyanate (PHITC), a potent chemopreventive agent in the lung tumor model in strain A mice, on azoxymethane-induced colon tumorigenesis, Another aim was to study the modulating effect of PHITC on colonic mucosal and tumor phospholipase A(2) (PLA(2)), phosphatidylinositol-specific phospholipase C (PI-PLC), lipoxygenase (LOX), and cyclooxygenase (COX) activities. At 5 weeks of age, groups of male F344 rats were fed control diet or diets containing 320 or 640 ppm of PHITC representing 40 and 80% maximum tolerated dose levels, respectively. At 7 weeks of age, all animals except those in the vehicle-treated groups were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight/week. All animals continued on their respective dietary regimen for 52 weeks after the carcinogen treatment; then the study was terminated. Colonic mucosa and tumors were analyzed for PLA(2), PI-PLC, prostaglandin (PG) E(2), COX, and LOX activities. Intestinal tumors were evaluated histopathologically and classified as invasive or noninvasive adenocarcinomas. Intestinal tumor incidence (percentage of animals with tumors) and tumor multiplicity (tumors/animal; tumors/tumor-bearing animal) were compared among the dietary groups. At the 640-ppm dose level, dietary PHITC significantly increased the incidence of intestinal (small intestine plus colon) adenocarcinomas (P < 0.05) as well as the multiplicities of invasive and noninvasive adenocarcinomas of the colon (P < 0.05 to 0.01). At the 320-ppm dose level, PHITC increased the multiplicity (tumors/animal) of noninvasive adenocarcinomas and total (invasive plus noninvasive) adenocarcinomas of the colon (P < 0.05). Dietary PHITC also increased the colon tumor volume (2- to 4.3-fold) in a dose-dependent manner. Moreover, PHITC significantly enhanced the activities of PLA(2) (50-100%) and levels of PGE(2) (2-fold) in the colonic mucosa and in tumors, but it had no significant effect (P > 0.05) on PI-PLC activity. The formation of COX metabolites, particularly PGE(2), PGF(2 alpha), PGD(2), 6-keto PGF(1 alpha), and thromboxane B-2, as well as LOX metabolites such as 8(S)-, 12(S)- and 15 (S)-hydroxyeicosatetraenoic acids, were significantly increased in the colonic mucosa and tumors of animals that were fed 640 ppm of PHITC. Although the exact mechanism by which PHITC promotes colon tumorigenesis remains to be elucidated, it is likely that the tumor-promoting effects of PHITC may, at least in part, be related to increased eicosanoid metabolism in the colon. C1 AMER HLTH FDN, DIV NUTR CARCINOGENESIS, VALHALLA, NY 10595 USA. AMER HLTH FDN, DIV PATHOL & TOXICOL, VALHALLA, NY 10595 USA. AMER HLTH FDN, RES ANIM FACIL, VALHALLA, NY 10595 USA. AMER HLTH FDN, BIOSTAT & COMP FACIL, VALHALLA, NY 10595 USA. NCI, CHEMOPREVENT BRANCH, BETHESDA, MD 20892 USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CA17613, CN85095-05] NR 57 TC 49 Z9 49 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1995 VL 55 IS 19 BP 4311 EP 4318 PG 8 WC Oncology SC Oncology GA RX114 UT WOS:A1995RX11400023 PM 7671241 ER PT J AU PRIMIANO, T EGNER, PA SUTTER, TR KELLOFF, GJ ROEBUCK, BD KENSLER, TW AF PRIMIANO, T EGNER, PA SUTTER, TR KELLOFF, GJ ROEBUCK, BD KENSLER, TW TI INTERMITTENT DOSING WITH OLTIPRAZ - RELATIONSHIP BETWEEN CHEMOPREVENTION OF AFLATOXIN-INDUCED TUMORIGENESIS AND INDUCTION OF GLUTATHIONE S-TRANSFERASES SO CANCER RESEARCH LA English DT Article ID RAT-LIVER; 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOLE-3-THIONE OLTIPRAZ; MOLECULAR DOSIMETRY; NUCLEOTIDE-SEQUENCE; SULFUR-COMPOUNDS; GENE-EXPRESSION; MESSENGER-RNAS; CDNA CLONE; CANCER; CHROMATOGRAPHY AB Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione] protects against chemical carcinogenesis in several animal models and is currently under evaluation as a possible chemopreventive agent in humans. Ideally, clinical chemopreventive interventions use dosing regimens that maximize efficacy while minimizing toxicity. Toward this end, the chemopreventive efficacy achieved by administration of intermittent doses of oltipraz was evaluated in rats. F344 rats were treated with oltipraz (0.5 mmol/kg, p.o.) once weekly, twice weekly, or daily over a 5-week period. After the first week, all rats were gavaged with 20 mu g/kg of aflatoxin B-1 for 28 consecutive days. Livers were analyzed 2 months after the last aflatoxin B-1 dose, and the volume of liver occupied by glutathione S-transferase (GST)-P positive foci, a presumptive marker of neoplasia, was observed to be decreased >95%, >97%, or >99% in livers of rats receiving once-, twice-weekly or daily oltipraz treatments, respectively. The chemopreventive actions of oltipraz have been associated with increases in the levels of phase 2 detoxifying enzymes, such as the glutathione S-transferase isozymes. Accordingly, GST conjugation activity measured with 1-chloro-2,4-dinitrobenzene as substrate increased 1.5-, 1.8-, or 2.4-fold for the once-weekly, twice-weekly or daily treatments, respectively, throughout a 7-day period. Quantitative HPLC analyses of GST subunits 24 h after 2 or 7 daily administrations of oltipraz showed that the levels of subunits Yb-1, Yp, Yc(2), and Ya(2) were increased with maximum elevations of 5.6-, 11.1-, 6.4-, and 10.4-fold, respectively. In comparison, levels of subunits Yb-2 and Yc(1) were modestly elevated 1.8- to 2.6-fold, respectively, whereas subunit Ya, was not induced. Remarkably, the levels of subunit Yp and Ya, remained elevated approximate to 2.3-fold 7 days after a single dose of oltipraz. In contrast, the levels of subunits Yb-1 and Yc(2) diminished to approximate control levels within 7 days after a single dose of oltipraz. GST mRNA levels for Ya, Yb, and Yp were measured by Northern blot analysis and were found to be elevated maximally to 13.7-, 13.5-, and 3.9-fold, respectively, after two daily oltipraz doses. Interestingly, GST Ya and Yb mRNA diminished to constitutive levels after 7 daily doses of oltipraz, with no corresponding decreases in GST subunit or activity levels. The levels of GST Ya and Yb mRNA decreased to constitutive levels within 4 days after a single oltipraz administration, whereas GST Yp mRNA levels remained elevated throughout the 7-day follow-up period. These results suggest that the protracted pharmacodynamic actions of oltipraz on enzyme induction may account for the marked reduction in the hepatic burden of aflatoxin B-1-induced putative preneoplastic tumors after intermittent dosing. Consequently, scheduling of intermittent dosing protocols may sustain efficacy while improving drug tolerance and patient compliance over long-term treatments. These properties of oltipraz increase its attractiveness for clinical chemopreventive interventions. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. DARTMOUTH COLL,SCH MED,DEPT PHARMACOL & TOXICOL,HANOVER,NH 03755. RI Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU NCI NIH HHS [CA 39416]; NIEHS NIH HHS [ES 03819, ES 06052] NR 43 TC 81 Z9 82 U1 1 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 OCT 1 PY 1995 VL 55 IS 19 BP 4319 EP 4324 PG 6 WC Oncology SC Oncology GA RX114 UT WOS:A1995RX11400024 PM 7671242 ER PT J AU SALEH, MN KHAZAELI, MB WHEELER, RH BUCY, RP LIU, TP EVERSON, MP MUNN, DH SCHLOM, J LOBUGLIO, AF AF SALEH, MN KHAZAELI, MB WHEELER, RH BUCY, RP LIU, TP EVERSON, MP MUNN, DH SCHLOM, J LOBUGLIO, AF TI PHASE-II TRIAL OF MURINE MONOCLONAL-ANTIBODY D612 COMBINED WITH RECOMBINANT HUMAN MONOCYTE COLONY-STIMULATING FACTOR (RHM-CSF) IN PATIENTS WITH METASTATIC GASTROINTESTINAL CANCER SO CANCER RESEARCH LA English DT Article ID RAPID INTRAVENOUS-INFUSION; TUMOR-ASSOCIATED ANTIGENS; GAMMA-INTERFERON; CELLS; CYTOTOXICITY; IMMUNOTHERAPY; INTERLEUKIN-2; ENHANCEMENT; XENOGRAFTS; PHENOTYPE AB In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m(2), days 4, 7, and 11) in combination with recombinant human monocyte colony stimulating factor [(rhM-CSF) 80 mu g/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral monocytosis (peak absolute monocyte count, 1444 +/- 394/mm(3)) and thrombocytopenia (nadir count, 78 +/- 10/mm(3)). Monocyte surface marker analysis revealed a high baseline expression of CD16(+) cells in our patient population with an additional increase with rhM-CSF therapy. We observed a correlation between the degree of thrombocytopenia and the pretreatment CD16(+) monocyte count. Of the plasma cytokines assayed, serum Neopterin demonstrated the most consistent increase during rhM-CSF therapy. There was a significant difference in the half-life of the first and last dose of D612 (35.8 +/- 2 versus 27 +/- 2.9 h; P < 0.05). Eleven of fourteen patients developed low-moderate levels of anti-D612 antibody. Despite the observed biological activity of both rhM-CSF and D612 and the previously described in vitro synergy, no clinical antitumor responses were observed in this Phase II study. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. MED COLL GEORGIA,AUGUSTA,GA 30912. NCI,BETHESDA,MD 20982. RP SALEH, MN (reprint author), UNIV ALABAMA,DEPT MED,263 WALLACE TUMOR INST,1824 6TH AVE S,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [R01 CA45232-05, N01 CM97611] NR 46 TC 10 Z9 10 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 OCT 1 PY 1995 VL 55 IS 19 BP 4339 EP 4346 PG 8 WC Oncology SC Oncology GA RX114 UT WOS:A1995RX11400027 PM 7671245 ER PT J AU LIEBMANN, J FISHER, J LIPSCHULTZ, C KUNO, R KAUFMAN, DC AF LIEBMANN, J FISHER, J LIPSCHULTZ, C KUNO, R KAUFMAN, DC TI ENHANCED GLUTATHIONE-PEROXIDASE EXPRESSION PROTECTS CELLS FROM HYDROPEROXIDES BUT NOT FROM RADIATION OR DOXORUBICIN SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER-CELLS; ANTICANCER QUINONES; HYDROGEN-PEROXIDE; TUMOR-CELLS; DNA; METALLOTHIONEIN; OVEREXPRESSION; TRANSFERASE; ADRIAMYCIN; GENE AB Both radiation and anthracycline antibiotics may produce reactive oxygen species to cause cytotoxicity, and it has been suggested that some cellular antioxidant enzymes may be important for resistance to these agents. The human breast adenocarcinoma cell line MCF-7(WT) has a low level of glutathione peroxidase (GPX) activity, We have transfected MCF-7(WT) cells with a plasmid that contains the cDNA for human GPX under the transcriptional control of the human metallothionein IIA promoter, One transfected clone, MCF-GPX-6, contained multiple copies of GPX cDNA/cell and, after exposure to heavy metals, expressed a level of GPX enzyme activity that was 40-fold higher than that present in MCF-7(WT) cells and comparable to the GPX activity contained in the doxorubicin-resistant MCF-7(DOX) cell line, No differences in levels of glutathione, catalase, superoxide dismutase, glutathione S-transferase, or glutathione reductase were noted in MCF-GPX-6 cells compared to MCF-7(WT) cells, MCF-GPX-6 cells were relatively resistant to hydrogen peroxide and tert-butylhydroperoxide compared to MCF-7(WT) cells, e.g., exposure of both cell Lines to 750 mu M H2O2 for 1 h resulted in a relative surviving fraction of 0.07 for MCF-7(WT) and 0.35 for MCF-GPX-6 cells, However, no difference in sensitivity to either radiation or doxorubicin was noted between MCF-7(WT) and MCF-GPX-6 cells. These results suggest that GPX is not important for the development of cellular resistance to either radiation or doxorubicin. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. NR 34 TC 26 Z9 26 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 OCT 1 PY 1995 VL 55 IS 19 BP 4465 EP 4470 PG 6 WC Oncology SC Oncology GA RX114 UT WOS:A1995RX11400046 PM 7671261 ER PT J AU CLARKSON, B CHABNER, BA WEINBERG, RA AF CLARKSON, B CHABNER, BA WEINBERG, RA TI TARGETS FOR SPECIFIC THERAPIES IN LEUKEMIA SO CANCER RESEARCH LA English DT Editorial Material ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; HUMAN B-CELLS; PHILADELPHIA-CHROMOSOME; GENE-PRODUCT; SH2 DOMAIN; PROTEIN; BINDING; INVITRO; BCR C1 NCI,BETHESDA,MD 20892. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. RP CLARKSON, B (reprint author), MEM SLOAN KETTERING CANC CTR,1275 YORK AVE,BOX 96,NEW YORK,NY 10021, USA. NR 76 TC 2 Z9 2 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 OCT 1 PY 1995 VL 55 IS 19 BP 4488 EP 4498 PG 11 WC Oncology SC Oncology GA RX114 UT WOS:A1995RX11400051 PM 7545542 ER PT J AU SOULIOTIS, VL CHHABRA, S ANDERSON, LM KYRTOPOULOS, SA AF SOULIOTIS, VL CHHABRA, S ANDERSON, LM KYRTOPOULOS, SA TI DOSIMETRY OF O-6-METHYLGUANINE IN RAT DNA AFTER LOW-DOSE, CHRONIC EXPOSURE TO N-NITROSODIMETHYLAMINE (NDMA) - IMPLICATIONS FOR THE MECHANISM OF NDMA HEPATOCARCINOGENESIS SO CARCINOGENESIS LA English DT Article ID HUMAN CANCER; DEOXYRIBONUCLEIC-ACID; ALKYLATION ADDUCTS; NITROSO-COMPOUNDS; CHRONIC INGESTION; HAMSTER LIVER; DIMETHYLNITROSAMINE; NITROSODIETHYLAMINE; O6-METHYLGUANINE; REPAIR AB Groups of female Wistar Furth/NCr rats, aged 6 weeks or 7 months at the start of the experiment, were administered drinking water containing N-nitrosodimethylamine (NDMA) for up to 28 days at concentrations in the range 0.2-2.54 p.p.m., resulting in daily intakes in the range 28-372 mu g/kg/day at age 10 weeks. The levels of the premutagenic DNA adduct O-6-methylguanine (O-6-meG) in liver and blood leukocyte DNA were measured at different times during this exposure as well as on the days immediately following cessation of exposure. The adduct was found to accumulate rapidly in both tissues, reaching within 2-7 days steady states in the range 0.08-0.45 mu mol/molG, similar in young and adult animals. Accumulation of O-6-meG in blood leukocytes was similar to 30% lower than in the liver. Following cessation of NDMA treatment, adducts were lost rapidly from the DNA of both tissues, with an apparent t(1/2) of similar to 19-23 h for the liver and 30-35 h for blood leukocytes, No change in liver O-6-alkylguanine-DNA alkyltransferase (AGT) took place throughout this treatment. The steady-state adduct levels were approximately linearly related to NDMA dose-rate, except that a clear break (corresponding to a 2.6-fold lower slope) was observed at dose rates >0.4 p.p.m. (similar to 56 mu g/kg/day). This dose - response relationship is in contrast to the sharp increase in the liver tumour induction in rats chronically treated with similar concentrations of NDMA reported by Pete et al. (Cancer Res., 51, 6415-6451) and suggests that accumulation of O-6-meG cannot by itself account for the hepatocarcinogenic efficacy of NDMA in the rat. Following i.g. administration of single doses of NDMA in a range approximately corresponding to the daily intake during the above mentioned chronic exposure study (25, 50 or 100 mu g/kg), repair of O-6-meG followed sharply biphasic kinetics in both liver and blood leukocytes. In the liver, an initial rapid phase (t(1/2) similar to 1.5-1.7 h) was followed by much slower repair (t(1/2) similar to 20.7-24.9 h) despite the absence of any change in AGT. Extrapolation of the two segments of the repair kinetics plots back to 0 time suggests that similar to 52-61% of the adducts originally formed in the liver and 33-35% of those formed in blood leukocytes belonged to the rapidly repaired category, The observation of biphasic repair under conditions of full AGT activity implies the existence of adduct populations with different susceptibility to repair, possibly reflecting adducts in different cell types or in different chromatin regions. The rate of loss of O-6-meG from DNA following cessation of chronic treatment was similar to that of the slowly repaired category of adducts, confirming that only adducts of this category accumulate during chronic exposure. C1 NATL HELLEN RES FDN, INST BIOL RES & BIOTECHNOL, CHEM CARCINOGENESIS LAB, GR-11635 ATHENS, GREECE. NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NR 53 TC 31 Z9 31 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1995 VL 16 IS 10 BP 2381 EP 2387 DI 10.1093/carcin/16.10.2381 PG 7 WC Oncology SC Oncology GA TA476 UT WOS:A1995TA47600016 PM 7586139 ER PT J AU YE, JP ZHANG, XY YOUNG, HA MAO, Y SHI, XL AF YE, JP ZHANG, XY YOUNG, HA MAO, Y SHI, XL TI CHROMIUM(VI)-INDUCED NUCLEAR FACTOR-KAPPA-B ACTIVATION IN INTACT-CELLS VIA FREE-RADICAL REACTIONS SO CARCINOGENESIS LA English DT Article ID SINGLE-STRAND BREAKS; DNA DAMAGE; GLUTATHIONE-REDUCTASE; TRANSCRIPTION FACTOR; SODIUM CHROMATE(VI); CHROMIUM COMPOUNDS; HYDROGEN-PEROXIDE; CARCINOGENICITY; FIBROBLASTS; MECHANISM AB Incubation of chromium(VI) [Cr(VI)] with cultured Jurkat cells resulted in activation of DNA binding activity of the nuclear factor (N kappa)-kappa B. In a combination with glutathione reductase, a Cr(VI) reducing agent, Cr(VI) expressed an enhanced activity in induction of NF-kappa B. This activation of NF-kappa B was decreased by a metal chelator, diethylenetriaminepentaacetic acid or catalase, but increased by superoxide dismutase. Addition of Mn2+, which reacts with Cr(IV) and inhibits Cr(IV)-mediated hydroxyl radical ((OH)-O-.) generation via Fenton-like reaction, attenuated the activation of NF-kappa B. Sodium formate, an (OH)-O-. radical scavenger, also inhibited the activation. Electron spin resonance measurements showed that the incubation of Cr(VI) with intact Jurkat cells generated reactive Cr(V) intermediate. Glutathione reductase and NADPH enhanced Cr(V) generation. Electron spin resonance spin trapping measurements using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent provided evidence that the incubation of Cr(VI) with the Jurkat cells in the presence of glutathione reductase generated (OH)-O-. radicals, H2O2 enhanced (OH)-O-. radical generation and also enhanced Cr(V) formation, indicating the role of Cr(IV) in (OH)-O-. radical generation. We conclude that Cr(VI) can activate MF-kappa B in vitro via Cr(IV)-mediated free radical reactions, We hypothesize that Cr(VI)-mediated NF-kappa B activation may be involved in the mechanism of Cr(VI)-induced carcinogenicity. C1 NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RI Shi, Xianglin/B-8588-2012 NR 43 TC 100 Z9 101 U1 0 U2 8 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1995 VL 16 IS 10 BP 2401 EP 2405 DI 10.1093/carcin/16.10.2401 PG 5 WC Oncology SC Oncology GA TA476 UT WOS:A1995TA47600019 PM 7586142 ER PT J AU HAYWARD, JJ SHANE, BS TINDALL, KR CUNNINGHAM, ML AF HAYWARD, JJ SHANE, BS TINDALL, KR CUNNINGHAM, ML TI DIFFERENTIAL IN-VIVO MUTAGENICITY OF THE CARCINOGEN/NON-CARCINOGEN PAIR 2,4-DIAMINOTOLUENE AND 2,6-DIAMINOTOLUENE SO CARCINOGENESIS LA English DT Article ID LACI TRANSGENIC MICE; MUTATIONS; NONCARCINOGEN; DNA AB The aromatic amines a,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are structural isomers that have been extensively studied for their mutagenic and carcinogenic characteristics. Both compounds are equally mutagenic in the Ames/Salmonella assay in the presence of S9. However, the differences in the results of chronic rodent carcinogen bioassays using these two compounds are significant, in that 2,4-DAT is a potent hepatocarcinogen, whereas 2,S-DAT does not produce an increased incidence of tumors in rats or mice at similar doses. The Big Blue(R) transgenic B6C3F1 mouse carries multiple copies of bacteriophage lambda, each with a lad mutational target gene, integrated into mouse chromosome 4. Our studies were designed to determine whether the Big Blue(R) system could be used to detect differences in the in vivo mutagenic activity between the carcinogen/non-carcinogen pair 2,4- and 2,6-DAT and to determine whether the in vivo mutagenesis assay results correspond to the rodent carcinogen bioassay results. Male B6C3F1 transgenic mice were exposed to 2,4- or 2,6-DAT at 0 or 1000 p.p.m. in the diet for 30 and 90 days. Mice serving as positive controls were administered five daily i.p. injections of 6 mg/kg dimethylnitrosamine (DMN) in saline and were sacrificed 15 days following the last injection. Mutant frequencies at lad were determined by recovering the genomically integrated lambda phage using an in vitro packaging reaction followed by infection of an appropriate Escherichia coli host. Complete non-sectored blue mutant plaques were scored against a background of clear non-mutant plaques, Mutant frequencies were nearly identical for all three groups at 30 days, while at 90 days the mutant frequency for the hepatocarcinogen 2,4-DAT (12.1 +/- 1.4 X 10(-5)) was significantly higher (P < 0.01) as compared with both age-matched (spontaneous) controls (5.7 +/- 2.9 X 10(-5)) and the 2,6-DAT-exposed group (5.7 +/- 2.4 X 10(-5)). Mutations at loci arising ex vivo during replication in E. coli are observed in this system as sectored blue plaques. The sectored plaque frequency in this study was constant across all groups at similar to 9.0 X 10(-5). Results from this study demonstrate that the Big Blue(R) transgenic mutation assay: (i) can distinguish differences in vivo between the mutagenic responses of a carcinogen and a non-carcinogen which elicited comparable mutagenic activity in S.typhimurium; (ii) is sensitive to mutagens through subchronic dietary exposure; and (iii) yields a differential response depending upon the length of time mice are exposed to a mutagen. C1 NIEHS, ENVIRONM TOXICOL PROGRAM, RES TRIANGLE PK, NC 27709 USA. NIEHS, ENVIRONM CARCINOGENESIS PROGRAM, RES TRIANGLE PK, NC 27709 USA. LOUISIANA STATE UNIV, INST ENVIRONM STUDIES, BATON ROUGE, LA 70803 USA. NR 18 TC 33 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1995 VL 16 IS 10 BP 2429 EP 2433 DI 10.1093/carcin/16.10.2429 PG 5 WC Oncology SC Oncology GA TA476 UT WOS:A1995TA47600024 PM 7586147 ER PT J AU MATZINGER, SA CRIST, KA STONER, GD ANDERSON, MW PEREIRA, MA STEELE, VE KELLOFF, GJ LUBET, RA YOU, M AF MATZINGER, SA CRIST, KA STONER, GD ANDERSON, MW PEREIRA, MA STEELE, VE KELLOFF, GJ LUBET, RA YOU, M TI K-RAS MUTATIONS IN LUNG-TUMORS FROM A/J AND A/JXTSG-P53 F1-MICE TREATED WITH 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE AND PHENETHYL ISOTHIOCYANATE SO CARCINOGENESIS LA English DT Article ID POLYMERASE CHAIN-REACTION; CONFORMATION POLYMORPHISM ANALYSIS; XENOBIOTIC-METABOLIZING ENZYMES; TOBACCO-SPECIFIC NITROSAMINES; CHEMICAL CARCINOGENESIS; P53 MUTATIONS; ARYLALKYL ISOTHIOCYANATES; MOUSE LUNG; AROMATIC ISOTHIOCYANATES; MOLECULAR ANALYSIS AB The purpose of this study was to evaluate the effects of the loss of a p53 allele and phenethyl isothiocyanate (PEITC) pre-treatment on the tumorigenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and K-ras mutation frequency in a hybrid mouse model. Male TSG-p53 'knock-out' mice were bred with A/J female mice to produce (A/J X TSG-p53) F-1 mice either homozygous (p53 +/+) or heterozygous (p53 +/-) for p53 alleles. These mice, together with female A/J mice, were treated at 6-8 weeks of age with NNK or dosed with PEITC prior to administration of NNK. The A/J mice treated with NNK had a 100% incidence of lung tumors, with 9.7 +/- 3.4 tumors/mouse. A/J mice pre-treated with PEITC prior to NNK administration had 3.5 +/- 2.1 lung tumors/animal, although the incidence remained at 100%. In (A/J X TSG-p53) F-1 mice with either the p53(+/-) or p53(+/+) genotype PEITC pre-treatment significantly decreased tumor incidence (100 to 40 and 36%, respectively) and multiplicity (2.0 +/- 0.5 to 0.5 +/- 0.4 and 2.1 +/- 0.5 to 0.5 +/- 0.4, respectively), indicating that PEITC is an effective chemopreventive agent in both A/J mice and (A/J X TSG-p53) F-1 mice. Analysis of lung tumor DNA from A/J mice treated with NNK or NNK/PEITC indicated that 15 of 17 (88%) and 20 of 23 (87%) of the tumors, respectively, contained G-->A transitions at the second base of codon 12 in the K-ras gene. Similarly, in lung tumors from (A/J X TSG-p53) F-1 mice treated with NNK or NNK/PEITC 29 of 30 (96%) and 9 of 10 (90%), respectively contained G-->A transitions at the second base of codon 12 of the K-ras gene. No mutations of the p53 gene were found in any of the tumors analyzed, suggesting minimal involvement of this gene in the development of lung adenomas. These data indicate that absence of a p53 allele in (A/J x TSG-p53) F-1 mice does not alter the incidence or multiplicity of NNK-induced lung tumors and that PEITC inhibition of NNK tumorigenesis does not affect the frequency or spectrum of K-ras gene mutations found consistently with NNK carcinogenesis. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. OHIO STATE UNIV,COLUMBUS,OH 43210. ST MARYS HOSP,GRAND JCT,CO 81501. ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY 40503. NCI,ROCKVILLE,MD 20892. FU NCI NIH HHS [N01-CN-25495-02, N01-CN-25495-01, CA-58554] NR 64 TC 46 Z9 46 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1995 VL 16 IS 10 BP 2487 EP 2492 DI 10.1093/carcin/16.10.2487 PG 6 WC Oncology SC Oncology GA TA476 UT WOS:A1995TA47600033 PM 7586156 ER PT J AU SHERMAN, CD PORTIER, CJ AF SHERMAN, CD PORTIER, CJ TI QUANTITATIVE-ANALYSIS OF MULTIPLE PHENOTYPE ENZYME-ALTERED FOCI IN RAT HEPATOCARCINOGENESIS EXPERIMENTS - THE MULTIPATH MULTISTAGE MODEL SO CARCINOGENESIS LA English DT Article ID LIVER; CARCINOGENESIS; LESIONS; SIZE AB The promotional effect of phenobarbital and 1-hydroxymethyl-pyren on enzyme altered lesions in the rat liver were quantified within the framework of two separate multipath/multistage multistage models. The experiment analyzed followed an initiation-promotion protocol in which female Wistar rats were initiated with a single dose of diethylnitrosamine at 0.15 mu mol/g body wt followed by a 3 week treatment-free period. A promotor, 1-hydroxymethyl-pyren or phenobarbital was then administered continuously in the diet for 120 days. All animals were sacrificed 3 weeks after treatment and their livers were examined for enzyme histological changes. Focal lesions were classified into three phenotype categories: adenosine triphosphatase altered (ATPase), sulfotransferase altered (ST) and jointly altered lesions (ATPase and ST). Quantitative methods were used to analyze the data, which consisted of the number and sizes of these enzyme-altered lesions. Both multipath/multistage models fitted to the data clearly demonstrate that phenobarbital promotion produced more observable and larger foci than promotion via 1-hydroxymethyl-pyren and that the growth kinetics of the jointly altered lesions were elevated relative to the lesions expressing a single marker. It was not possible with these data to determine if there was a predominant sequence in the formation of jointly altered lesions. RP SHERMAN, CD (reprint author), NIEHS,QUALITAT & COMPUTAT BIOL LAB,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 17 TC 9 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1995 VL 16 IS 10 BP 2499 EP 2506 DI 10.1093/carcin/16.10.2499 PG 8 WC Oncology SC Oncology GA TA476 UT WOS:A1995TA47600035 PM 7586158 ER PT J AU KATAYOSE, D WERSTO, R COWAN, KH SETH, P AF KATAYOSE, D WERSTO, R COWAN, KH SETH, P TI EFFECTS OF A RECOMBINANT ADENOVIRUS EXPRESSING WAF1/CIP1 ON CELL-GROWTH, CELL-CYCLE, AND APOPTOSIS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID WILD-TYPE P53; PROTEIN; TRANSFORMATION AB To evaluate the effects of a p53-inducible gene WAF1/Cip1 on cell proliferation and apoptosis, a recombinant adenovirus vector (E1 minus) expressing WAF1/Cip1 cDNA (AdWAF1) was constructed and compared with a previously studied recombinant adenovirus vector expressing wild-type p53 (AdWTp53). Infection of normal and tumor cells of lung and mammary epithelial origin with AdWAF1 resulted in high levels of WAF1/Cip1 gene expression, which was comparable to that induced by AdWTp53. AdWAF1 and AdWTp53 inhibited growth of all cells studied; tumor cells devoid of endogenous p53 (H-358) or cells expressing endogenous mutant p53 (MDA-MB-231) were more sensitive to the inhibitory effect than tumor (MCF-7) or normal mammary epithelial cells expressing endogenous wild-type p53. Cell cycle analysis of AdWTp53-infected cells indicated a decline in the cell number in S phase and a significant increase in cell number in G(1)-M phase. AdWAF1 infection also led to a decline in the percentage of cells in S phase and a significant accumulation of cells in G(1). AdWAF1 failed to induce apoptosis in any of the cells tested. In contrast, AdWTp53 induced apoptosis in H-358 and in MDA-MB231 cells. These data suggest that AdWTp53-mediated WAF1/Cip1 induction and cytotoxicity are likely to be associated with WAF1/Cip1-mediated cell cycle arrest. However, because overexpression of WAF1/Cip1 protein failed to induce apoptosis, AdWTp53 effects on apoptosis apparently require cellular factors in addition to WAF1/Cip1 induction. C1 NCI,MED BRANCH,MED BREAST CANC SECT,BETHESDA,MD 20892. NCI,PATHOL BRANCH,BETHESDA,MD 20892. NR 39 TC 94 Z9 95 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1995 VL 6 IS 10 BP 1207 EP 1212 PG 6 WC Cell Biology SC Cell Biology GA RZ082 UT WOS:A1995RZ08200002 PM 8845297 ER PT J AU SCHUETZ, JD SILVERMAN, JA THOTTASSERY, JV FURUYA, KN SCHUETZ, EG AF SCHUETZ, JD SILVERMAN, JA THOTTASSERY, JV FURUYA, KN SCHUETZ, EG TI DIVERGENT REGULATION OF THE CLASS-II P-GLYCOPROTEIN GENE IN PRIMARY CULTURES OF HEPATOCYTES VERSUS H35 HEPATOMA BY GLUCOCORTICOIDS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MULTIDRUG-RESISTANCE GENE; ADULT-RAT HEPATOCYTES; HUMAN MDR1 GENE; PRIMARY MONOLAYER-CULTURES; MESSENGER-RNA; PREGNENOLONE 16-ALPHA-CARBONITRILE; CDNA CLONE; EXPRESSION; CELLS; LIVER AB We investigated whether the glucocorticoid-mediated mechanisms controlling P-glycoprotein (pgp2 or mdr1b) are similar in normal hepatocytes compared with the H35 hepatoma cell line. In primary rat hepatocytes, dexamethasone (DEX) caused a dose- and time-dependent decrease in the amount of the pgp2 mRNA, which correlated with functional pgp2 expression (intracellular accumulation of [H-3]vincristine). The suppression of pgp2 mRNA was specific for glucocorticoids because a representative estrogen and progestin were without effect, and DEX suppression of pgp2 mRNA could be reversed by cotreatment with an anti-glucocorticoid. DEX suppression of pgp2 mRNA appears to be posttranscriptional because following actinomycin D inhibition of new RNA synthesis, the pgp2 transcript disappeared at a faster rate in DEX treated versus untreated hepatocytes. Moreover, transcriptional activity of chloramphenicol acetyltransferase plasmids containing the pgp2 promoter in primary rat hepatocytes was unaffected by DEX treatment. Thus, suppression of pgp2 mRNA by glucocorticoids in primary hepatocytes is due to a decrease in pgp2 mRNA stability. In contrast, in the H35 hepatoma cell line, DEX dose dependently increased pgp protein and pgp2 mRNA, effects which parallel transcriptional activation of the pgp2 promoter. Activation of the pgp2 promoter was specific for glucocorticoids since a representative estrogen had no significant effect on transcription of the pgp2 promoter and RU486 blocked DEX activation of pgp2 transcription. Transcriptional activation of the pgp2 promoter was not due to a global up-regulation of basal transcription factors because DEX treatment did not activate either a herpes simplex virus thymidine kinase promoter or the SV40 early gene promoter. Further studies with a panel of pgp2 5' sequence deletion plasmids revealed that the minimal promoter (-66 bp) was not activated by DEX. In contrast, inclusion of sequences up to -177 bp restored DEX-dependent transcriptional activation. These are the first studies to demonstrate that glucocorticoids regulate pgp2 by different mechanisms in normal rat hepatoctyes compared to the H35 hepatoma cell line. C1 UNIV TENNESSEE, CTR PEDIAT PHARMACOKINET & THERAPEUT, DEPT PEDIAT, MEMPHIS, TN 38105 USA. NCI, EXPTL CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RP ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT SCI, 332 N LAUDERDALE AVE, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [CA21765]; NIEHS NIH HHS [ES05851] NR 60 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1995 VL 6 IS 10 BP 1321 EP 1332 PG 12 WC Cell Biology SC Cell Biology GA RZ082 UT WOS:A1995RZ08200015 PM 8845310 ER PT J AU Burbach, JPH Adan, RAH Lolait, SJ vanLeeuwen, FW Mezey, E Palkovits, M Barberis, C AF Burbach, JPH Adan, RAH Lolait, SJ vanLeeuwen, FW Mezey, E Palkovits, M Barberis, C TI Molecular neurobiology and pharmacology of the vasopressin oxytocin receptor family SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE vasopressin; oxytocin; G-protein coupled receptors ID CORTICOTROPIN-RELEASING FACTOR; SENSITIVE ADENYLATE-CYCLASE; BINDING-SITES; ARGININE-VASOPRESSIN; RAT-BRAIN; AUTORADIOGRAPHIC LOCALIZATION; NEUROHYPOPHYSEAL HORMONES; STRUCTURAL REQUIREMENTS; DIRECT IDENTIFICATION; MEMBRANE-RECEPTORS AB 1. VP and OT mediate their wealth of effects via 4 receptor subtypes V-1a, V-1b, V-2, and OT receptors. 2. We here review recent insights in the pharmacological properties, structure activity relationships, species differences in ligand specificity, expression patterns, and signal transduction of VP/OT receptor. 3. Furthermore, the existence of additional VP/OT receptor subtypes is discussed. C1 NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. NETHERLANDS INST BRAIN RES, 1105 AZ AMSTERDAM, NETHERLANDS. NINCDS, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. CNRS, INSERM, CTR PHARMACOL ENDOCRINOL, F-34094 MONTPELLIER 05, FRANCE. RP Burbach, JPH (reprint author), UNIV UTRECHT, DEPT MED PHARMACOL, RUDOLF MAGNUS INST NEUROSCI, UNIV WEG 100, 3584 CG UTRECHT, NETHERLANDS. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 95 TC 35 Z9 35 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 EI 1573-6830 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD OCT PY 1995 VL 15 IS 5 BP 573 EP 595 PG 23 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA TP925 UT WOS:A1995TP92500006 ER PT J AU TANG, Y KIM, WK HOLMES, KL HUGIN, AW KENNY, JJ CHATTOPADHYAY, SK HARTLEY, JW MORSE, HC AF TANG, Y KIM, WK HOLMES, KL HUGIN, AW KENNY, JJ CHATTOPADHYAY, SK HARTLEY, JW MORSE, HC TI CONTRIBUTION OF B-CELL SUBSETS TO DELAYED DEVELOPMENT OF MAIDS IN XID MICE SO CELLULAR IMMUNOLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; MURINE LEUKEMIA VIRUSES; X-LINKED IMMUNODEFICIENCY; MLS DETERMINANTS; AIDS; INDUCTION; DISEASE; INVIVO; SUPERANTIGEN; PROGRESSION AB C57BL/6 (B6) mice develop a syndrome of progressive lymphoproliferation and immunodeficiency, murine AIDS (MAIDS), when infected with an etiologic replication-defective virus termed BM5def. Induction of MAIDS requires the presence of CD4(+) T cells and B cells. B6 mice with altered conventional B cell function and a deficit in CD5(+) B cells due to the rid mutation develop disease with a greatly prolonged latency. The association of this mutation with resistance to MAIDS was confirmed in studies of P .xid mice. To test the hypothesis that conventional B cells are required for rapid induction of disease, B6 .xid mice were injected with spleen cells from nude mice or were given bone marrow from aged donors. Both sets of recipients developed advanced disease by 10 weeks post infection, suggesting that resistance to MAIDS in rid mutants may be due to effects of B cells other than the CD5(+) subset. (C) 1995 Academic Press, Inc. C1 UNIV HOSP GENEVA,DEPT DERMATOL,CH-1211 GENEVA 4,SWITZERLAND. SAIC,FREDERICK,MD 21702. RP TANG, Y (reprint author), NIAID,IMMUNOPATHOL LAB,7 CTR DR,MSC 0760,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 37 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 1 PY 1995 VL 165 IS 1 BP 1 EP 6 DI 10.1006/cimm.1995.1179 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA RX039 UT WOS:A1995RX03900001 PM 7545546 ER PT J AU Brouwers, P vanderVlugt, H Moss, H Wolters, P Pizzo, P AF Brouwers, P vanderVlugt, H Moss, H Wolters, P Pizzo, P TI White matter changes on CT brain scan are associated with neurobehavioral dysfunction in children with symptomatic HIV disease SO CHILD NEUROPSYCHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBROSPINAL-FLUID; PEDIATRIC AIDS; MR EVALUATION; INFECTION; MYELINATION; ZIDOVUDINE; INFANTS; ENCEPHALOPATHY; INFUSION AB The effect of white matter abnormalities on neurobehavioral dysfunction was investigated in 58 children with symptomatic HIV-1 disease, 28 with CT white matter abnormalities and 30 matched (for age, gender, route of infection, and stage of disease) control patients with comparable levels of cortical atrophy, but no white matter abnormalities. Children with white matter abnormalities were more impaired on measures of general level of mental functioning (standard scores of 70.3 vs. 86.1; (p < .05). They also scored lower than the group without white matter abnormalities on activities of daily living (76.9 vs. 87.4; p < 0.5), particularly those requiring self-help skills, and in socialization (79.5 vs. 89.3; p < .05). Furthermore, patients with white matter abnormalities exhibited higher levels of attention deficit/hyperactive behaviors (p < .05) and more severe autistic symptoms (p < .05). White matter abnormalities by themselves were, thus, associated with deficits in cognitive function and socio-emotional behavior. These findings are in partial agreement with the nonverbal learning disabilities (NLD) model. Although NLD profiles; in general, have been described in older children, the current results seem to suggest that antecedents for these behavior patterns can be found in much younger children with white matter abnormalities. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. TILBURG UNIV,DEPT PSYCHOL,TILBURG,NETHERLANDS. MED ILLNESS COUNSELING CTR,CHEVY CHASE,MD. NR 53 TC 14 Z9 15 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD OCT PY 1995 VL 1 IS 2 BP 93 EP 105 DI 10.1080/09297049508402241 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA TY624 UT WOS:A1995TY62400001 ER PT J AU LI, JY LI, B BLOT, WJ TAYLOR, PR AF LI, JY LI, B BLOT, WJ TAYLOR, PR TI PRELIMINARY-REPORT ON THE RESULTS OF NUTRITION PREVENTION TRIALS OF CANCER AND OTHER COMMON DISEASES AMONG RESIDENTS IN LINXIAN, CHINA SO CHINESE MEDICAL JOURNAL LA English DT Note C1 NCI,BETHESDA,MD 20892. RP LI, JY (reprint author), CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CHINESE MEDICAL ASSOCIATION PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD OCT PY 1995 VL 108 IS 10 BP 780 EP 780 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TF113 UT WOS:A1995TF11300014 PM 8565666 ER PT J AU DORN, LD BURGESS, ES DUBBERT, B SIMPSON, SE FRIEDMAN, T KLING, M GOLD, PW CHROUSOS, GP AF DORN, LD BURGESS, ES DUBBERT, B SIMPSON, SE FRIEDMAN, T KLING, M GOLD, PW CHROUSOS, GP TI PSYCHOPATHOLOGY IN PATIENTS WITH ENDOGENOUS CUSHINGS-SYNDROME - ATYPICAL OR MELANCHOLIC FEATURES SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; CUSHINGS-SYNDROME; BIOCHEMICAL MANIFESTATIONS; PSYCHIATRIC MANIFESTATIONS; BEHAVIORAL HOMEOSTASIS; RAT-BRAIN; DEPRESSION; STRESS; DISEASE AB OBJECTIVE Prolonged elevations of glucocorticoids have been linked to the affective disturbances experienced by patients with Cushing's syndrome. Major depression has been most commonly reported in patients with endogenous Cushing's syndrome. The purpose of this study was to determine whether these patients experience melancholic or 'atypical' subtype depression and to determine relations between current psychological functioning and factors such as duration and severity of Cushing's syndrome. DESIGN AND PATIENTS We examined 33 adult patients with documented Cushing's syndrome and 17 hospitalized, matched controls, using standardized structured interviews and tests. RESULTS During the active phase of Cushing's syndrome (prior to and/or on admission), 66.7% of all patients reported histories meeting criteria for a psychiatric diagnosis. Of those with a diagnosis during Cushing's syndrome, 50% reported major depression. Upon presentation to this institution, atypical depression was the most common diagnosis involving 51.5% (n = 17) of all enrolled patients. Of the 17 with atypical depression, 8 reported a co-morbid psychiatric disorder. The duration of Cushing's syndrome was an important factor in predicting whether patients sought psychological intervention or met criteria for psychiatric diagnosis. CONCLUSION Patients with active endogenous Cushing's syndrome exhibit significant psychopathology expressed primarily by atypical depression. Longer duration of Cushing's syndrome may place them at increased risk of such psychopathology. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD USA. AMERICAN UNIV, DEPT PSYCHOL, WASHINGTON, DC USA. UNIV VIRGINIA, COLL NURSING, CHARLOTTESVILLE, VA 22903 USA. NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD USA. RP DORN, LD (reprint author), UNIV PITTSBURGH, VICTORIA BLDG, RM 440, PITTSBURGH, PA 15261 USA. NR 58 TC 96 Z9 98 U1 3 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 1995 VL 43 IS 4 BP 433 EP 442 DI 10.1111/j.1365-2265.1995.tb02614.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RZ090 UT WOS:A1995RZ09000006 PM 7586617 ER PT J AU KELEN, GD HEXTER, DA HANSEN, KN TANG, N PRETORIUS, S QUINN, TC AF KELEN, GD HEXTER, DA HANSEN, KN TANG, N PRETORIUS, S QUINN, TC TI TRENDS IN HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTION AMONG A PATIENT POPULATION OF AN INNER-CITY EMERGENCY DEPARTMENT - IMPLICATIONS FOR EMERGENCY DEPARTMENT-BASED SCREENING PROGRAMS FOR HIV-INFECTION SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; PREVALENCE; ANTIBODY; RISK; WORKERS; WOMEN AB Personnel of inner-city emergency departments (EDs), which are frequently the only source of medical care for many patients, may be in a unique position to detect human immunodeficiency virus (HIV) infection earlier than personnel at other recommended screening sites. To assist development of ED-based screening strategies for HIV infection, we undertook a serosurvey of HIV infection in adult patients attending an ED during a 6-week period in 1992 using an identity-unlinked technique and compared our findings with data collected similarly in 1988. Of 1,606 patients, 183 (11.4%) were HIV-positive, compared with 6.0% in 1988. Seroprevalence rates of HIV infection among patients only at risk of heterosexual transmission increased more than fourfold (7% to 30.3%). CD4(+) cell counts were higher in those patients with undiagnosed HIV infection than in those with known HIV infection. Targeting minority patients aged 25-44 years, intravenous drug users, and those patients at heterosexual risk would have identified 87% of patients with new HIV infection, while requiring screening of 41% of the study sample. Targeted voluntary screening programs in certain EDs would likely detect significant numbers of new early HIV infections. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT EMERGENCY MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,BETHESDA,MD 20892. OI Kelen, Gabor/0000-0002-3236-8286 NR 25 TC 46 Z9 46 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1995 VL 21 IS 4 BP 867 EP 875 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RZ139 UT WOS:A1995RZ13900005 PM 8645832 ER PT J AU REX, JH BENNETT, JE SUGAR, AM PAPPAS, PG SERODY, J EDWARDS, JE WASHBURN, RG AF REX, JH BENNETT, JE SUGAR, AM PAPPAS, PG SERODY, J EDWARDS, JE WASHBURN, RG TI INTRAVASCULAR CATHETER EXCHANGE AND DURATION OF CANDIDEMIA SO CLINICAL INFECTIOUS DISEASES LA English DT Note ID FUNGEMIA AB During a comparative trial of amphotericin B vs, fluconazole for treatment of candidemia in nonneutropenic patients, data on the management of intravascular catheters were collected, Complete records were available for 91% of the 206 study patients, For the subset of patients with a catheter in place at the time of their first positive blood culture, removal and replacement of all intravascular catheters without exchange over a guidewire from a preexisting line on or before the first day the study drug was administered were associated with a reduction in the subsequent mean duration (+/- SE) of candidemia, from 5.6 +/- 0.8 days to 2.6 +/- 0.5 days (P < .001). C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. BOSTON UNIV,HOSP MED CTR,BOSTON,MA 02215. UNIV ALABAMA,BIRMINGHAM,AL. UNIV N CAROLINA,CHAPEL HILL,NC. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CALIF LOS ANGELES,HARBOR MED CTR,TORRANCE,CA 90509. RP REX, JH (reprint author), UNIV TEXAS,SCH MED,6431 FANNIN 1728 JFB,HOUSTON,TX 77030, USA. OI Serody, Jonathan/0000-0003-4568-1092 FU NIAID NIH HHS [N01-AI-15082] NR 8 TC 168 Z9 171 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT PY 1995 VL 21 IS 4 BP 994 EP 996 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RZ139 UT WOS:A1995RZ13900028 PM 8645855 ER PT J AU DEMORAIS, SMF GOLDSTEIN, JA XIE, HG HUANG, SL LU, YQ XIA, H XIAO, ZS ILE, N ZHOU, HH AF DEMORAIS, SMF GOLDSTEIN, JA XIE, HG HUANG, SL LU, YQ XIA, H XIAO, ZS ILE, N ZHOU, HH TI GENETIC-ANALYSIS OF THE S-MEPHENYTOIN POLYMORPHISM IN A CHINESE POPULATION SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HYDROXYLATION DEFICIENCY; OXIDATION POLYMORPHISMS; DIAZEPAM METABOLISM; DEBRISOQUIN; PHARMACOKINETICS; JAPANESE AB The 4'-hydroxylation of S-mephenytoin exhibits a polymorphism in humans, with the poor metabolizer phenotype exhibiting a lower frequency in white (3% to 5%) than in Oriental populations (13% to 23%). Two mutations in CYP2C19 (CYP2C19(m1) and CYP2C19(m2) have recently been described that account for similar to 85% of white and 100% of Japanese poor metabolizers. This study examines whether these mutations account for the poor metabolizer phenotype in the Chinese population. The metabolism of S-mephenytoin exhibited a bimodal distribution in 244 unrelated Chinese subjects, although the distribution of the two phenotypes overlapped. In 75 selected Chinese subjects, CYP2C19 genotype analysis predicted the phenotype with 100% accuracy. The frequency of the poor metabolizer phenotype was similar to 11% (95% confidence interval 7% to 15%). The frequency of the CYP2C19(m1) allele was 0.289, whereas that of CYP2C19(m2) was 0.044. Homozygous extensive metabolizers had slightly lower ratios of S/R-mephenytoin compared with heterozygous extensive metabolizers, showing a gene-dosage effect. These data show the advantages of genotype analysis in investigations of the mephenytoin phenotype in Oriental subjects. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. HUNAN MED UNIV,DEPT PHARMACOL,CHANGSHA,PEOPLES R CHINA. RI Goldstein, Joyce/A-6681-2012 NR 31 TC 130 Z9 133 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 1995 VL 58 IS 4 BP 404 EP 411 DI 10.1016/0009-9236(95)90053-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TF122 UT WOS:A1995TF12200006 PM 7586932 ER PT J AU FREEDMAN, LS SIMON, R FOULKES, MA FRIEDMAN, L GELLER, NL GORDON, DJ MOWERY, R AF FREEDMAN, LS SIMON, R FOULKES, MA FRIEDMAN, L GELLER, NL GORDON, DJ MOWERY, R TI INCLUSION OF WOMEN AND MINORITIES IN CLINICAL-TRIALS AND THE NIH-REVITALIZATION-ACT OF 1993 - THE PERSPECTIVE OF NIH CLINICAL TRIALISTS SO CONTROLLED CLINICAL TRIALS LA English DT Article C1 NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. NIAID,DIV AIDS,BETHESDA,MD 20892. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. NHLBI,DIV HEART & VASC DIS,BETHESDA,MD 20892. NEI,DIV COLLABORAT RES,BETHESDA,MD 20892. RP FREEDMAN, LS (reprint author), NCI,DCPC,BIOMETRY BRANCH,EXECUT PLAZA N,SUITE 344,BETHESDA,MD 20892, USA. NR 4 TC 95 Z9 96 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 1995 VL 16 IS 5 BP 277 EP 285 DI 10.1016/0197-2456(95)00048-8 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TG799 UT WOS:A1995TG79900001 PM 8582146 ER PT J AU BRAWLEY, OW AF BRAWLEY, OW TI INCLUSION OF WOMEN AND MINORITIES IN CLINICAL-TRIALS AND THE NIH-REVITALIZATION-ACT OF 1993 - THE PERSPECTIVE OF NIH CLINICAL TRIALISTS SO CONTROLLED CLINICAL TRIALS LA English DT Article C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD. NR 3 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 1995 VL 16 IS 5 BP 293 EP 295 DI 10.1016/0197-2456(95)00131-X PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TG799 UT WOS:A1995TG79900005 ER PT J AU BALDWIN, W AF BALDWIN, W TI IMPACT OF THE NM INCLUSION GUIDELINES SO CONTROLLED CLINICAL TRIALS LA English DT Article RP BALDWIN, W (reprint author), NIH,ROCKVILLE,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 1995 VL 16 IS 5 BP 300 EP 300 DI 10.1016/0197-2456(95)00121-2 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TG799 UT WOS:A1995TG79900008 ER PT J AU FREEDMAN, LS SIMON, R FOULKES, MA FRIEDMAN, L GELLER, NL GORDON, DJ MOWERY, R AF FREEDMAN, LS SIMON, R FOULKES, MA FRIEDMAN, L GELLER, NL GORDON, DJ MOWERY, R TI INCLUSION OF WOMEN AND MINORITIES IN CLINICAL-TRIALS AND THE NIH-REVITALIZATION-ACT OF 1993 - THE PERSPECTIVE OF NIH CLINICAL TRIALISTS - RESPONSE SO CONTROLLED CLINICAL TRIALS LA English DT Article RP FREEDMAN, LS (reprint author), NCI,BIOMETRY BRANCH,EXECUT PLAZA N,SUITE 344,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 1995 VL 16 IS 5 BP 310 EP 312 DI 10.1016/0197-2456(95)00133-6 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TG799 UT WOS:A1995TG79900012 ER PT J AU NGUYEN, B KEANE, MM JOHNSTON, PG AF NGUYEN, B KEANE, MM JOHNSTON, PG TI THE BIOLOGY OF GROWTH-REGULATION IN NORMAL AND MALIGNANT BREAST EPITHELIUM - FROM BENCH TO CLINIC SO CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY LA English DT Review ID MOUSE MAMMARY-GLAND; FACTOR-BINDING-PROTEINS; FACTOR-I RECEPTORS; MESSENGER RIBONUCLEIC-ACID; CANCER-CELLS INVITRO; RESTING HUMAN-BREAST; TUMOR EFFECTS INVIVO; TERM TISSUE-CULTURE; C-MYC AMPLIFICATION; HER-2 NEU ONCOGENE C1 USN,NCI,MED ONCOL BRANCH,DIV CANC TREATMENT,BETHESDA,MD. NR 168 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD OCT PY 1995 VL 20 IS 3 BP 223 EP 236 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA TJ541 UT WOS:A1995TJ54100003 PM 8748011 ER PT J AU KUNKEL, TA AF KUNKEL, TA TI DNA-MISMATCH REPAIR - THE INTRICACIES OF EUKARYOTIC SPELL-CHECKING SO CURRENT BIOLOGY LA English DT Note AB Recent work suggests that the eukaryotic system responsible fdr repairing DNA mismatches, and so correcting replication errors, is more complex than was thought; its multiple components have many cellular functions. RP KUNKEL, TA (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 32 Z9 32 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1995 VL 5 IS 10 BP 1091 EP 1094 DI 10.1016/S0960-9822(95)00218-1 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TA464 UT WOS:A1995TA46400004 PM 8548274 ER PT J AU YANCEYWRONA, JE CAMERINIOTERO, RD AF YANCEYWRONA, JE CAMERINIOTERO, RD TI THE SEARCH FOR DNA HOMOLOGY DOES NOT LIMIT STABLE HOMOLOGOUS PAIRING PROMOTED BY RECA PROTEIN SO CURRENT BIOLOGY LA English DT Article ID ESCHERICHIA-COLI; STRAND EXCHANGE; SACCHAROMYCES-CEREVISIAE; DUPLEX DNA; RECOMBINATION; MECHANISM; PURIFICATION; MEIOSIS; SPECIFICITY; INITIATION AB Background: The basic molecular mechanisms that govern the search for DNA homology and subsequent homologous pairing during genetic recombination are not understood. RecA is the central homologous recombination protein of Escherichia call; because several RecA homologues have been identified in eukaryotic cells, it is likely that the mechanisms employed by RecA are conserved throughout evolution. Analysis of the kinetics of the homologous search and pairing reactions catalyzed by RecA should therefore provide insights of general relevance into the mechanisms by which macromolecules locate, and interact with, specific DNA targets. Results: RecA forms three-stranded synaptic complexes with a single-stranded oligonucleotide and a homologous region in duplex DNA. The kinetics of this initial pairing reaction were characterized using duplex DNA molecules of various concentrations and complexities containing a single target site, as well as various concentrations of homologous single-stranded oligonucleotides. The formation of the synaptic complex follows apparent second-order reaction kinetics with a rate proportional to the concentrations of both the homologous single-stranded oligonucleotide and the target sites within the duplex DNA. The reaction rate is independent of the complexity of duplex DNA in the reaction. We propose a kinetic scheme in which the RecA-single-stranded DNA filament interacts with duplex DNA and locates its target in a relatively fast reaction. We also suggest that complex conformational changes occur during the subsequent rate-limiting step. Conclusions: We conclude that, during the formation of synaptic complexes by RecA, the search for homology is not rate-limiting and that the iteration frequency of the search is around 10(2)-10(3) s(-1). This value agrees well with what has been calculated as the minimum number for such a frequency in genome-wide searches, and limits the possible structures involved in the search for homology to those involving very soft (low energy) interactions. Furthermore, from the order of the reaction at the DNA concentrations found in eukaryotic nuclei, and the rate constant of the overall reaction, we predict that the search for homology is also not the rate-limiting step in the genome-wide searches implicated in meiosis and in gene targeting. C1 NIDDK,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 53 TC 38 Z9 40 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1995 VL 5 IS 10 BP 1149 EP 1158 DI 10.1016/S0960-9822(95)00231-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TA464 UT WOS:A1995TA46400017 PM 8548287 ER PT J AU GAUDET, SJ RAZAVI, P CAIAFA, GJ CHADER, GJ AF GAUDET, SJ RAZAVI, P CAIAFA, GJ CHADER, GJ TI IDENTIFICATION OF ARYLAMINE N-ACETYLTRANSFERASE ACTIVITY IN THE BOVINE LENS SO CURRENT EYE RESEARCH LA English DT Article DE N-ACETYLTRANSFERASE; LENS; ARYLAMINE; DETOXIFICATION; BOVINE ID ACETYLATION; PINEAL; LIVER AB Arylamine N-acetyltransferase (NAT) activity was identified and partially characterized in the bovine lens. According to size-exclusion HPLC, the molecular mass of the arylamine NAT is approximately 30-kDa. Based upon substrate specificity analysis, it is best described as an arylamine NAT which has some ability to N-acetylate arylalkylamines. This arylamine NAT acetylates para-aminobenzoic acid thereby demonstrating a monomorphic pattern of N-acetylation. It demonstrates low sensitivity to methotrexate inhibition as indicated by the relatively high IC50 value (470 mu M). NAT could be involved in lenticular detoxification of both endogenous amines and exogenous drugs. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 17 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 1995 VL 14 IS 10 BP 873 EP 877 DI 10.3109/02713689508995126 PG 5 WC Ophthalmology SC Ophthalmology GA TB389 UT WOS:A1995TB38900002 PM 8549152 ER PT J AU SARTANI, G SILVER, PB STRASSMANN, G CHAN, CC CASPI, RR AF SARTANI, G SILVER, PB STRASSMANN, G CHAN, CC CASPI, RR TI SURAMIN TREATMENT SUPPRESSES INDUCTION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU) IN RODENTS SO CURRENT EYE RESEARCH LA English DT Article DE AUTOIMMUNE DISEASE; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU); MOUSE; RAT; SURAMIN; UVEITIS ID IN-VITRO; CELLS; BINDING; GROWTH; MECHANISM; RECEPTOR; UVEITIS; DISEASE; MODEL; MICE AB The experimental drug suramin has been shown to possess several immunosuppressive properties. In this study we investigated the effect of suramin on the development of experimental autoimmune uveoretinitis (EAU) in mice and in rats. EAU was induced either by active immunization with a uveitogenic protein or peptide, or by the adoptive transfer of a uveitogenic T cell line. The development of EAU was assessed by clinical evaluation as well as by histopathology. Immunological responses were measured by delayed type hypersensitivity (DTH), lymphocyte proliferation, and serum antibody levels to the immunizing antigen. Suramin treatment was most effective in suppressing EAU when started concurrently with immunization (afferent). Treatment was less effective in suppressing disease when first administered 7 days after immunization or when given to animals that received an adoptive transfer of uveitogenic T cells (efferent). The effect of suramin on DTH and lymphocyte proliferation roughly paralleled its effect on EAU. Afferent treatment of mice with suramin completely suppressed anti-IRBP antibody titers. Interestingly, animals receiving efferent treatment had unreduced IgM levels but little or no IgG, suggesting prevention of the IgM-to-IgG switch. Depressed in vitro lymphocyte proliferative responses in animals treated with suramin during the afferent stage suggested that the suppressive effect on disease was due at least in part to an inhibition of antigen priming. Our results suggest that suramin merits further investigation as a potential treatment for some types of uveitis. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD. NR 31 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 1995 VL 14 IS 10 BP 887 EP 896 DI 10.3109/02713689508995128 PG 10 WC Ophthalmology SC Ophthalmology GA TB389 UT WOS:A1995TB38900004 PM 8549154 ER PT J AU GUMBINER, BM YAMADA, KM AF GUMBINER, BM YAMADA, KM TI CELL-TO-CELL CONTACT AND EXTRACELLULAR-MATRIX SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP GUMBINER, BM (reprint author), MEM SLOAN KETTERING CANC CTR,CELLULAR BIOCHEM & BIOPHYS PROGRAM,BOX 564,1275 YORK AVE,NEW YORK,NY 10021, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 2 TC 28 Z9 29 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 1995 VL 7 IS 5 BP 615 EP 618 DI 10.1016/0955-0674(95)80101-4 PG 4 WC Cell Biology SC Cell Biology GA RX302 UT WOS:A1995RX30200001 PM 8573334 ER PT J AU YAMADA, KM MIYAMOTO, S AF YAMADA, KM MIYAMOTO, S TI INTEGRIN TRANSMEMBRANE SIGNALING AND CYTOSKELETAL CONTROL SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID CELL-CELL; ADHESION; RECEPTOR; PROTEIN; SURFACE; MATRIX AB Integrins are remarkably multifunctional: they mediate cell adhesion and migration, orchestrate organization of the actin-based cytoskeleton, and activate signal transduction pathways. Recent studies have identified a variety of steps and hierarchies in these intracellular cytoskeletal and signaling responses, laying the groundwork for future studies on specificity and coordination with responses to growth factors. RP YAMADA, KM (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 421,30 CONVENT DR,MSC 4370,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 84 TC 536 Z9 541 U1 0 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 1995 VL 7 IS 5 BP 681 EP 689 DI 10.1016/0955-0674(95)80110-3 PG 9 WC Cell Biology SC Cell Biology GA RX302 UT WOS:A1995RX30200010 PM 8573343 ER PT J AU BIRKEDALHANSEN, H AF BIRKEDALHANSEN, H TI PROTEOLYTIC REMODELING OF EXTRACELLULAR-MATRIX SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID C-TERMINAL DOMAIN; TISSUE INHIBITOR; IV COLLAGENASE; GROWTH-FACTOR; ACTIVATION; METALLOPROTEINASE; PROCOLLAGENASE; STROMELYSIN; GENE; IDENTIFICATION AB Matrix metalloproteinases and their natural inhibitors are ingredients of a fundamental cellular toolbox for effecting environmental change. These enzymes enable cells to alter their relationship to the environment by directly cleaving structural macromolecules of the extracellular matrix. In addition, evidence is emerging that they also play an important regulatory role in matrix remodeling by catalyzing the processing of inactive matrix metalloproteinase and cytokine precursors. RP BIRKEDALHANSEN, H (reprint author), NIDR,BLDG 30,ROOM 132,30 CONVENT DR,MSC 4326,BETHESDA,MD 20894, USA. NR 61 TC 845 Z9 855 U1 1 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 1995 VL 7 IS 5 BP 728 EP 735 DI 10.1016/0955-0674(95)80116-2 PG 8 WC Cell Biology SC Cell Biology GA RX302 UT WOS:A1995RX30200016 PM 8573349 ER PT J AU JAMES, S COLLEY, D AF JAMES, S COLLEY, D TI SCHISTOSOMIASIS SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Article AB Despite the existence of effective chemotherapy, the global disease burden inflicted by helminth parasites of the genus Schistosoma remains unabated. Arguably, the most exciting advances made in this field over the past year lie in the elucidation of the pathogenetic immune mechanisms, especially in terms of cytokine function. Research on the biochemical and immunologic resistance mechanisms to infection, disease development, and drug action is yielding insights which should contribute to the design of more efficacious integrated control strategies. RP JAMES, S (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD OCT PY 1995 VL 8 IS 5 BP 351 EP 355 DI 10.1097/00001432-199510000-00006 PG 5 WC Infectious Diseases SC Infectious Diseases GA RX035 UT WOS:A1995RX03500006 ER PT J AU GREENE, LA KAPLAN, DR AF GREENE, LA KAPLAN, DR TI EARLY EVENTS IN NEUROTROPHIN SIGNALING VIA TRK AND P75 RECEPTORS SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; FACTOR-INDUCED DIFFERENTIATION; AFFINITY NGF RECEPTOR; PC12 CELLS; NEURONAL DIFFERENTIATION; RAS P21; BINDING; TRANSDUCTION; LEADS; ACTIVATION AB Biological responses to neurotrophins appear to be mediated by multiple signalling pathways. These emanate from, and are regulated by, the contributions of both Trk and p75 receptors. Early events in Trk signalling are becoming more clearly defined and point to cooperative interaction of both Ras-dependent and Ras-independent pathways. Work over the past year has clarified the steps by which Trk receptor occupation leads to Ras activation and has highlighted the required roles of Ras and extracellular signal regulated kinases in certain neurotrophin responses, including neurite outgrowth. Pharmacologic and mutagenesis studies have additionally supported the importance of the phosphatidylinositol-3' kinase and SNT protein pathways in neurotrophin signalling. Although many findings point to clear involvement for p75 in neurotrophin signalling, the molecular mechanisms by which these occur are just beginning to be identified. Recent studies indicate that p75 dramatically influences Trk activity and ligand interactions, and may mediate signals through the ceramide second-messenger pathway. C1 COLUMBIA UNIV COLL PHYS & SURG,CTR NEUROBIOL & BEHAV,NEW YORK,NY 10032. NCI,FREDERICK CANC RES & DEV FACIL,EUKARYOT SIGNAL TRANSDUCT SECT,ALB BASIC RES PROGRAM,FREDERICK,MD 21702. RP GREENE, LA (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,630 W 168TH ST,NEW YORK,NY 10032, USA. NR 72 TC 262 Z9 266 U1 2 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 1995 VL 5 IS 5 BP 579 EP 587 DI 10.1016/0959-4388(95)80062-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA TG858 UT WOS:A1995TG85800006 PM 8580709 ER PT J AU KIRKEN, RA RUI, H MALABARBA, MG HOWARD, OMZ KAWAMURA, M OSHEA, JJ FARRAR, WL AF KIRKEN, RA RUI, H MALABARBA, MG HOWARD, OMZ KAWAMURA, M OSHEA, JJ FARRAR, WL TI ACTIVATION OF JAK3, BUT NOT JAK1, IS CRITICAL FOR IL-2-INDUCED PROLIFERATION AND STAT5 RECRUITMENT BY A COOH-TERMINAL REGION OF THE IL,-2 RECEPTOR BETA-CHAIN SO CYTOKINE LA English DT Article ID HUMAN INTERLEUKIN-2 RECEPTOR; GAMMA SIGNAL-TRANSDUCTION; TYROSINE KINASE; IL-2 RECEPTOR; FUNCTIONAL COMPONENT; MOLECULAR-CLONING; EXPRESSION; CDNAS; CELLS AB A number of cytokines and growth factors use the JAR-STAT pathway to signal from the cell membrane to the nucleus, While homodimerizing cytokine receptors may transmit signal via a single form of JAK (i.e. growth hormone receptors), several multicomponent cytokine receptors have been shown to require simultaneous activation of pairs of different JAR kinases (i.e. interferon receptors). Recent evidence for a preferential coupling of JAK3 to interleukin-2 receptor-gamma (IL-2R gamma) and JAK1 to IL-2R beta supports the concept of heterotrans-activation of JAK1 and JAK3 caused by IL-2-induced heterodimerization of their receptor partners, The present study verified the ability of IL-2 to cause tyrosine phosphorylation and activation of JAK1 and JAK3, but demonstrated that IL-2 stimulated JAK3 to a significantly larger extent than JAK1 in human T lymphocytes and the YT cell line, This conclusion was based upon several independent criteria, including more vigorous tyrosine phosphorylation of JAK3, more marked enzymatic activation of JAK3 as well as higher abundance of JAK3 in activated IL-2 receptor complexes, Furthermore, when human IL-2R beta was stably expressed in murine BA/F3 cells, robust IL-2-induced proliferation and JAK3 activation occurred without detectable involvement of either JAK1, JAK2 or TYK2, We therefore propose that IL-2 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL-2-induced heterodimerization of IL-2R beta and IL-2R gamma. Nonetheless, a membrane-proximal region of human IL-2R beta (Asn(240)-Leu(335)) was critical for JAK3 activation, and the amount of JAK3 present in activated IL-2 receptor complexes increased with time, suggesting that stabilization of JAK3 binding to the receptor complex relies on both IL-2R beta and IL-2R gamma, Moreover, STAT5 was found to be the predominant STAT transcription factor used by IL-2 in human T cells, and specifically required a COOH-terminal region of IL-2R beta (Ser(386)-Val(525)), while STAT5 recruitment was not correlated to activation of IL-2R gamma or JAK3. (C) 1995 Academic Press Limited. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NIAMS,ARTHRIT & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20892. RP KIRKEN, RA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DEPT CYTOKINE MOLEC MECHANISMS SECT,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012; Malabarba, Maria Grazia/L-4805-2015 OI Howard, O M Zack/0000-0002-0505-7052; Malabarba, Maria Grazia/0000-0002-9457-2047 FU FIC NIH HHS [5FO5 TWO4300-02] NR 34 TC 63 Z9 64 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 1995 VL 7 IS 7 BP 689 EP 700 DI 10.1006/cyto.1995.0081 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA TC162 UT WOS:A1995TC16200002 PM 8580378 ER PT J AU MELLERICK, DM NIRENBERG, M AF MELLERICK, DM NIRENBERG, M TI DORSAL-VENTRAL PATTERNING GENES RESTRICT NK-2 HOMEOBOX GENE-EXPRESSION TO THE VENTRAL HALF OF THE CENTRAL-NERVOUS-SYSTEM OF DROSOPHILA EMBRYOS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID SINGLE-MINDED GENE; CNS MIDLINE CELLS; NUCLEAR-LOCALIZATION; GRADIENT MORPHOGEN; TWIST GENE; PROTEIN; MELANOGASTER; MESODERM; NEUROECTODERM; SEQUENCE AB Genes that affect the expression of the NK-2 homeobox gene were identified by comparing the patterns of NK-2 mRNA in wild-type Drosophila embryos with patterns in mutant embryos that have defects in genes that are required to establish the ventral-dorsal pattern of primordia in the early embryo. The NK-2 gene was shown to be activated by dorsal in the ventral half of the embryo during the syncytial blastoderm stage of development. However, expression of the NK-2 gene is restricted to the ventral half of the ventrolateral neurogenic anlagen and part of the procephalic region. The NK-2 gene is not expressed in the mesodermal anlage due to repression by snail, in mesectodermal cells due to repression by singleminded, or in the lateral neuroectodermal and/or dorsal. epidermal anlagen due to repression mediated indirectly by decapentaplegic. Twist activates the NK-2 gene in the posterior portion of the embryo or is a coactivator with dorsal. The stripes of medial neuroectodermal cells that synthesize NK-2 mRNA are converted into clusters of neuroectodermal cells that contain NK-2 mRNA by segmentally repeated decreases in NK-2 mRNA. Medial neuroblasts, neuroblasts in the posterior portion of segments, and some ganglion mother cells and neurons express the Nk-2 gene. These results suggest that the NK-2 gene receives and integrates information from ventral-dorsal and anterior-posterior gradients of gene regulators and that ventral, dorsal, anterior, and posterior boundaries of each cluster of neuroectodermal cells that express NK-2 are determined independently. (C) 1995 Academic Press, Inc. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 47 TC 90 Z9 91 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT PY 1995 VL 171 IS 2 BP 306 EP 316 DI 10.1006/dbio.1995.1283 PG 11 WC Developmental Biology SC Developmental Biology GA RY528 UT WOS:A1995RY52800004 PM 7556915 ER PT J AU KNEZEVIC, V RANSON, M MACKEM, S AF KNEZEVIC, V RANSON, M MACKEM, S TI THE ORGANIZER-ASSOCIATED CHICK HOMEOBOX GENE, GNOT1, IS EXPRESSED BEFORE GASTRULATION AND REGULATED SYNERGISTICALLY BY ACTIVIN AND RETINOIC ACID SO DEVELOPMENTAL BIOLOGY LA English DT Article ID MESODERM INDUCTION; PRIMITIVE STREAK; AXIAL STRUCTURES; BOX GENE; EMBRYOS; CELLS; BLASTODERM; HYPOBLAST; DOMAIN; REGION AB Gnot1, a Not (for notochord) family homeobox gene, is expressed in the chick pregastrulation blastoderm. Gnot1 expression in the epiblast is upregulated as the posteriorly derived hypoblast moves forward anteriorly to form a layer beneath it, which is of particular interest considering the known inductive role of the hypoblast in axis formation in the chick. Both activin and retinoic acid are able to activate Gnot1 expression in cultured blastodermal cells and show a strong synergistic effect when applied in combination. Strong superinduction of Gnot1 transcripts in the presence of cycloheximide also indicates the presence of a potent and labile intracellular inhibitor capable of modulating Gnot1 expression. During gastrulation, Gnot1 transcripts become localized specifically to tissues associated with ''organizer'' function (Hensen's node, head process, notochord). The expression data and the response to mesoderm inducing factors and axial ''caudalizing'' signals suggest that Gnot1 may be involved in specification of the embryonic body axis and could play a part in regulating features of the trunk/tail organizer in the chick embryo. (C) 1995 Academic Press, Inc. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. OI Ranson, Marie/0000-0002-5570-9645 NR 55 TC 44 Z9 44 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT PY 1995 VL 171 IS 2 BP 458 EP 470 DI 10.1006/dbio.1995.1296 PG 13 WC Developmental Biology SC Developmental Biology GA RY528 UT WOS:A1995RY52800017 PM 7556928 ER PT J AU MCALEER, MA REIFSNYDER, P PALMER, SM PROCHAZKA, M LOVE, JM COPEMAN, JB POWELL, EE RODRIGUES, NR PRINS, JB SERREZE, DV DELARATO, NH WICKER, LS PETERSON, LB SCHORK, NJ TODD, JA LEITER, EH AF MCALEER, MA REIFSNYDER, P PALMER, SM PROCHAZKA, M LOVE, JM COPEMAN, JB POWELL, EE RODRIGUES, NR PRINS, JB SERREZE, DV DELARATO, NH WICKER, LS PETERSON, LB SCHORK, NJ TODD, JA LEITER, EH TI CROSSES OF NOD MICE WITH THE RELATED NON STRAIN - A POLYGENIC MODEL FOR IDDM SO DIABETES LA English DT Article ID NONOBESE DIABETIC MICE; GENETIC-CONTROL; MOUSE; MELLITUS; RELEVANCE; CANDIDATE; RECEPTOR; LINKAGE AB Chromosome locations of non-major histocompatibility complex (MHC) genes contributing to insulin-dependent diabetes mellitus (IDDM) in mice have been determined by outcrossing NOD mice to other inbred strains congenic for the NOD MHC haplotype (H2(g7)). At least nine non-MHC IDDM susceptibility genes (Idd) were previously identified at first backcross (BC1) after outcross of NOD to C57BL/10.H2(g7) congenic mice (B10.H2(g7)). We investigated whether the same set of Idd loci segregated with IDDM susceptibility after outcross of NOD to NON.H2(g7) congenic mice, Since the outcrosses to NON.H2(g7) and B10.H2(g7) were performed in the same vivarium, direct comparisons were made of the chromosomal locations and relative strengths of Idd alleles in diabetic progeny from the two different outcrosses, In comparison with the NOD x B10.H2(g7) outcross, the NOD x NON.H2(g7) outcross produced significantly higher IDDM: frequencies in Fl, F2, and BC1 generations, The high F2 diabetes frequency allowed evaluation of the effects of homozygous expression of both the susceptibility and the resistance allele at Idd loci, This analysis demonstrated that no single non-MHC Idd locus was essential for the onset of diabetes in this cross, After outcross to NON.H2(g7), Idd4 (chromosome [Chr] 11), Idd5 (Chr 1), and Idd8 (Chr 14) did not segregate with IDDM in either the BC1 or the F2 generation, Diabetogenic NOD-derived alleles at Idd2 (Chr 9), Idd3 (Chr 3), and Idd10 (Chr 3) were segregating in the BC1, An NON-derived allele contributing to susceptibility on Chr 7 (Idd7) was also detected, Dominant traits, detectable only in the F2 cross, were encoded by Chr 4 (Idd9) and two newly mapped loci on Chr 13 (Idd14) and 5 (Idd15). A third dominant trait was encoded by Chr 6 (possibly Idd6), but here, in contrast to Idd9, Idd14, and Idd15, the NON allele was diabetogenic, Stepwise logistic regression analysis of the BC1 and F2 data confirmed that the ability to identify certainty of the non-MHC Idd loci was contingent on the extent of homozygosity for NOD background genes, This study shows that the diabetogenic phenotype can be achieved through the actions of variable combinations of MHC-unlinked genes and a diabetogenic MHC haplotype. C1 JACKSON LAB,BAR HARBOR,ME 04609. UNIV OXFORD,WELLCOME TRUST CTR HUMAN GENET,NUFFIELD DEPT SURG,OXFORD,ENGLAND. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. MERCK & CO INC,MERCK SHARP & DOHME RES LABS,DEPT MOLEC & CELLULAR PHARMACOL,RAHWAY,NJ 07065. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. RI Wicker, Linda/F-7384-2010; Powell, Elizabeth/B-4455-2011; Todd, John/A-3542-2010 OI Powell, Elizabeth/0000-0001-5008-8061; FU NCI NIH HHS [CA-34196]; NIDDK NIH HHS [DK-27722, DK-36175]; Wellcome Trust NR 39 TC 118 Z9 118 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1995 VL 44 IS 10 BP 1186 EP 1195 DI 10.2337/diabetes.44.10.1186 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD624 UT WOS:A1995TD62400009 PM 7556956 ER PT J AU PAOLISSO, G TATARANNI, PA FOLEY, JE BOGARDUS, C HOWARD, BV RAVUSSIN, E AF PAOLISSO, G TATARANNI, PA FOLEY, JE BOGARDUS, C HOWARD, BV RAVUSSIN, E TI A HIGH-CONCENTRATION OF FASTING PLASMA NONESTERIFIED FATTY-ACIDS IS A RISK FACTOR FOR THE DEVELOPMENT OF NIDDM SO DIABETOLOGIA LA English DT Article DE NONESTERIFIED FATTY ACIDS; NON-INSULIN-DEPENDENT DIABETES MELLITUS; OBESITY; INSULIN ACTION; IN VITRO LIPOLYSIS ID DEPENDENT DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; PIMA-INDIANS; GLYCOGEN-SYNTHASE; METABOLISM; OXIDATION; OBESITY; ADIPOCYTES AB To assess the role of fasting plasma non-esterified fatty acids (NEFA) in the development of non-insulin-dependent diabetes mellitus (NIDDM), data were analysed from annual examinations of 190 non-diabetic Pima Indians, Glucose tolerance was measured by a 75-g oral glucose tolerance test, insulin action by a euglycaemic hyperinsulinaemic (40 mU . m(-2). min(-1)) clamp and in vitro lipolysis using isolated abdominal fat cells. After a mean follow-up period of 4.0+/-2.4 years (mean+/-SD), 47 subjects developed NIDDM. Risk factors for NIDDM were estimated by proportional-hazards analysis and risk ratios (RR) with 95% confidence intervals (95% CI) calculated at the 90th and 10th percentile of the predictor variables. A large average fat-cell volume was predictive of NIDDM (RR = 2.4; 95% CI = 1.2-4.8) independent of age, sex, percent body fat and body fat distribution. A high fasting plasma NEFA concentration was also a risk factor for NIDDM (RR = 2.3; 95% CI = 1.1-4.7) independent of sex, percent body fat, waist/thigh ratio, insulin-mediated glucose uptake and fasting triglyceride concentration. We conclude that large fat cells and the resulting increased plasma NEFA concentrations are risk factors for the development of NIDDM. C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. SANDOZ INC,RES INST,DEPT DIABET,E HANOVER,NJ. MEDLANTIC RES INST,WASHINGTON,DC. OI Paolisso, Giuseppe/0000-0002-2137-455X NR 37 TC 247 Z9 254 U1 0 U2 13 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1995 VL 38 IS 10 BP 1213 EP 1217 DI 10.1007/BF00422371 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RY232 UT WOS:A1995RY23200011 PM 8690174 ER PT J AU GRANT, BF HARFORD, TC AF GRANT, BF HARFORD, TC TI COMORBIDITY BETWEEN DSM-IV ALCOHOL-USE DISORDERS AND MAJOR DEPRESSION - RESULTS OF A NATIONAL SURVEY SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE COMORBIDITY; ALCOHOL USE DISORDERS; MAJOR DEPRESSION; COMORBID DISORDER ID PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS AB The purpose of this study was to describe detailed patterns of comorbidity between Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) alcohol use disorders and major depression using a representative sample of the United States. Comorbidity rates and associations between DSM-IV alcohol use disorders and major depression were expressed as odds ratios with confidence intervals adjusted for the complex design characteristics of the NLAES. Comorbidity analyses were presented by sex, ethnicity and age for past year, prior to past year and lifetime diagnoses. Virtually all odds ratios were significantly greater than 1.0, demonstrating that comorbidity of alcohol use disorders and major depression is pervasive in the general population. The magnitude of the association remained stable across the three time frames but diagnostic and subgroup variations in comorbidity were noted. The association between alcohol dependence and major depression was greater than the association between abuse and major depression and the association between alcohol abuse and major depression was consistently greater for females and blacks, compared to their male and non-black counterparts. Implications of the results are discussed in terms of professional help seeking, the self-medication hypothesis, and differential social control theory. RP GRANT, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 32 TC 335 Z9 337 U1 3 U2 34 PU ELSEVIER SCI PUBL 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 OCT PY 1995 VL 39 IS 3 BP 197 EP 206 DI 10.1016/0376-8716(95)01160-4 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TA921 UT WOS:A1995TA92100005 PM 8556968 ER PT J AU DERMIME, S BARRETT, J GAMBACORTIPASSERINI, C AF DERMIME, S BARRETT, J GAMBACORTIPASSERINI, C TI THE ROLE OF THE IMMUNE-SYSTEM IN ANTITUMOR RESPONSES - POTENTIAL FOR DRUG-THERAPY SO DRUGS & AGING LA English DT Review ID ACTIVATED KILLER CELLS; ACUTE PROMYELOCYTIC LEUKEMIA; LYMPHOCYTES-T RECOGNIZE; ACUTE MYELOID-LEUKEMIA; DNA-BINDING DOMAIN; RECOMBINANT INTERLEUKIN-2; INFILTRATING LYMPHOCYTES; CANCER-PATIENTS; NECROSIS-FACTOR; HUMAN-MELANOMA AB In the last 5 years significant progress has been made in our understanding of the molecular nature of anti-tumour T cell-mediated responses. This review describes the involvement of the cellular immune system in the recognition and destruction of cancer cells. Four aspects are discussed: (i) the generalised immune activation induced by the systemic administration of cytokines, in particular, interleukin-2; (ii) the specific T cell-mediated reactions against tumour cells through the recognition of tumour-associated molecules, including the MAGE antigens, MART 1 (melanoma antigen recognised by T cells 1) and tyrosinase proteins described in melanomas, and minor histocompatibility antigens in the setting of allogenic bone marrow transplantation for leukaemia; (iii) the potentially significant but still hypothetical immune-mediated recognition of molecules either tumour-associated or transformation-related (including altered oncogenic proteins); and (iv) the role of co-stimulatory molecules in the induction of tumour-specific immunity. The current and future therapeutic applications in cancer treatment and potential limitations to this approach are discussed. C1 IST NAZL TUMORI,DIV EXPTL ONCOL D,I-20133 MILAN,ITALY. NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANTAT UNIT,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 NR 152 TC 5 Z9 5 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD OCT PY 1995 VL 7 IS 4 BP 266 EP 277 PG 12 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA RW982 UT WOS:A1995RW98200002 PM 8535054 ER PT J AU WIRTH, PJ HOANG, TN BENJAMIN, T AF WIRTH, PJ HOANG, TN BENJAMIN, T TI MICROPREPARATIVE IMMOBILIZED PH GRADIENT 2-DIMENSIONAL ELECTROPHORESIS IN COMBINATION WITH PROTEIN MICROSEQUENCING FOR THE ANALYSIS OF HUMAN LIVER PROTEINS SO ELECTROPHORESIS LA English DT Article DE IMMOBILIZED PH GRADIENT 2-DIMENSIONAL ELECTROPHORESIS; MICROSEQUENCING; HUMAN LIVER PROTEINS ID HEPATOMA-CELL LINE; POLYVINYLIDENE DIFLUORIDE MEMBRANES; POLYACRYLAMIDE-GEL ELECTROPHORESIS; RAT-LIVER; 2-DIMENSIONAL ELECTROPHORESIS; CHEMICAL HEPATOCARCINOGENESIS; NOVIKOFF HEPATOMA; EPITHELIAL-CELLS; DEFINED MEDIUM; C-MYC AB Simplified methodology has been developed for the direct N-terminal amino acid microsequencing of human liver and hepatoma derived polypeptides, following micropreparative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Utilization of immobilized pH gradient (IPG) gel strips in the first dimension permitted protein loading of 0.5-2.0 mg with negligible diminution of polypeptide resolution. Following 2-D separation and electrotransfer to polyvinylidene difluoride (PVDF) membranes nearly 100 well resolved Ponceau S stained polypeptides were readily visualized, from which, 32 adult liver S-9 and 72 HepG2 nuclear cytosolic polypeptides were subjected to N-terminal microsequencing. Twenty normal adult liver and 54 HepG2 polypeptides yielded N-terminal sequence information, of which 17 and 19 polypeptides, respectively, exhibited high sequence homology to previously identified proteins. The initial yields of the proteins sequenced ranged from 2-14 pmols and yielded sequences of 14-26 amino acid residues. Many of the adult liver and HepG2 proteins contained inferred leader sequences since the first sequenced residue was several (20-30) residues from the methionine initiation site predicted by the cDNA of the adult liver. Quantitative comparison of 60 well characterized hepatic proteins between normal adult liver and two nontransformed, Chang and WRL-68, and four human hepatoma derived cell lines, HepG2, Huh-7, FOCUS, and SK-Hep, revealed a high homogeneity of protein expression both qualitatively and quantitatively in both whole cell lysate and purified nuclear preparations. Most notable differences include the previously characterized polypeptides: carbamoyl phosphate synthase, MER5 homologous protein, cytidylate kinase, phosphatidylethanolamine-binding protein and mitochondrial enoyl-CoA hydratase as well as three N-terminally blocked polypeptides: 11 (63 kDa/pI 7.00), 56 (26/6.45) and 59 (22/6.00) all of which were expressed at similar levels in normal adult liver tissue and each of the nontransformed, Chang and WRL-68, cell lines but not expressed or expressed at greatly decreased levels in each of tumor derived liver cell lines. Pyruvate carboxylase, superoxide dismutase, serotransferrin, liver fatty acid binding protein, 1-hydroxyprostaglandin dehydrogenase, NADH dehydrogenase (ubiquinone) as well as three N-terminally blocked polypeptides: 9 (57/6.00), 53 (24/4.90) and 63 (16/4.70) were detected only in whole adult liver tissue and not in any of the cultured cell lines. Two additional polypeptides: U35, (27/6.05) and 58 (22/5.70) yielded N-terminal partial amino acid sequences but were not identified in established protein databases. We have shown that micropreparative IPG 2-D PAGE in combination with protein microsequencing provides a convenient one step procedure to rapidly obtain partial amino acid sequence information for nearly 100 individual polypeptides directly from a single 2-D PAGE gel with numerous applications to a wide variety of biological model systems. RP WIRTH, PJ (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BIOPOLYMER CHEM SECT,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 71 TC 37 Z9 39 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD OCT PY 1995 VL 16 IS 10 BP 1946 EP 1960 DI 10.1002/elps.11501601321 PG 15 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TF548 UT WOS:A1995TF54800023 PM 8586070 ER PT J AU RICE, JM AF RICE, JM TI HELICOBACTER HEPATICUS, A RECENTLY RECOGNIZED BACTERIAL PATHOGEN, ASSOCIATED WITH CHRONIC HEPATITIS AND HEPATOCELLULAR NEOPLASIA IN LABORATORY MICE SO EMERGING INFECTIOUS DISEASES LA English DT Note ID PYLORI RP RICE, JM (reprint author), NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701, USA. NR 13 TC 21 Z9 21 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT-DEC PY 1995 VL 1 IS 4 BP 129 EP 131 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TE849 UT WOS:A1995TE84900004 PM 8903182 ER PT J AU AKAMIZU, T KOHN, LD MORI, T AF AKAMIZU, T KOHN, LD MORI, T TI MOLECULAR STUDIES ON THYROTROPIN (TSH) RECEPTOR AND ANTI-TSH RECEPTOR ANTIBODIES SO ENDOCRINE JOURNAL LA English DT Review ID FRTL-5 THYROID-CELLS; GRAVES-DISEASE; EXTRACELLULAR DOMAIN; BLOCKING ANTIBODIES; IDIOPATHIC MYXEDEMA; GONADOTROPIN RECEPTORS; STIMULATING ANTIBODIES; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; CAMP SIGNAL C1 NIDDK,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892. RP AKAMIZU, T (reprint author), KYOTO UNIV,SCH MED,DEPT LAB MED,SAKYO KU,54 SHOGOIN KAWAHARACHO,KYOTO 606,JAPAN. NR 46 TC 24 Z9 25 U1 0 U2 0 PU JAPAN ENDOCRINE SOCIETY PI TOKYO PA C/O DEPT VETERINARY PHYSIOL, VET MED SCI, UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO 113, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD OCT PY 1995 VL 42 IS 5 BP 617 EP 627 DI 10.1507/endocrj.42.617 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB203 UT WOS:A1995TB20300003 PM 8574284 ER PT J AU NEUENSCHWANDER, S ROBERTS, CT LEROITH, D AF NEUENSCHWANDER, S ROBERTS, CT LEROITH, D TI GROWTH-INHIBITION OF MCF-7 BREAST-CANCER CELLS BY STABLE EXPRESSION OF AN INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR ANTISENSE RIBONUCLEIC-ACID SO ENDOCRINOLOGY LA English DT Article ID IGF-I; SOMATOMEDIN RECEPTOR; BINDING-PROTEINS; KINASE-ACTIVITY; ATHYMIC MICE; ANTIBODY; ANALOGS; TRANSFORMATION; PEPTIDE; LIGAND AB Insulin-like growth factors (IGFs) play an important role in cellular proliferation, and IGF action appears to be involved in tumorigenesis. To determine the role of the IGF-I receptor in breast cancer cell growth, we stably transfected MCF-7 breast cancer cells with a construct encoding an antisense RNA complementary to the region surrounding the translation initiation site of the IGF-I receptor messenger RNA (mRNA). Control cells were transfected with vector alone. Clones expressing the antisense RNA exhibited a 30% reduction in endogenous IGF-I receptor mRNA levels and a significant reduction in receptor protein levels, as measured by both ligand binding assays and Western blot analysis. Antisense-expressing clones expressed similar to 30,000 receptors/cell compared with similar to 48,000-58,000 receptors/cell in control (neo) cells (P < 0.05). Although endogenous RNA:RNA hybrids were demonstrable in antisense-expressing cells, our results suggest that the major effect of the antisense may be the reduction in mRNA levels and not via an inhibition of translation. The reduction in receptor expression reduced both IGF-I- and serum-stimulated cellular proliferation. The maximum cell number reached at 96 h in the presence of IGF-I (100 ng/ml) was significantly reduced in antisense-expressing clones (22,000-30,000) compared with that in control(neo) cells (39,000-42,000). Furthermore, IGF-I-induced c-fos gene expression was reduced by 30% in the clones expressing the antisense RNA. These results strongly support a role for the IGF-I receptor in the proliferation of human breast cancer cells and suggest that strategies using this type of technology may prove useful in cancer therapy. C1 NIDDKD, MOLEC & CELLULAR PHYSIOL SECT, DIABET BRANCH, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 36 TC 120 Z9 121 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4298 EP 4303 DI 10.1210/en.136.10.4298 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100022 PM 7664648 ER PT J AU PACAK, K MCCARTY, R PALKOVITS, M CIZZA, G KOPIN, IJ GOLDSTEIN, DS CHROUSOS, GP AF PACAK, K MCCARTY, R PALKOVITS, M CIZZA, G KOPIN, IJ GOLDSTEIN, DS CHROUSOS, GP TI DECREASED CENTRAL AND PERIPHERAL CATECHOLAMINERGIC ACTIVATION IN OBESE ZUCKER RATS SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; BODY-FAT DISTRIBUTION; BROWN ADIPOSE-TISSUE; PARAVENTRICULAR NUCLEUS; IMMOBILIZATION STRESS; GENETIC OBESITY; FA/FA; ADRENOCORTICOTROPIN; CORTICOSTERONE AB The Zucker rat is an animal model of autosomal recessive obesity characterized by excessive hypothalamic-pituitary-adrenal (HPA) axis and parasympathetic activities and deficient sympathetic outflow. Alterations in norepinephrine (NE) release, reuptake, and metabolism in the hypothalamic paraventricular nucleus (PVN) could also contribute to dysregulation of the HPA axis in obese Zucker rats via effects on corticotropin-releasing hormone neurons or could be secondary to some other primary defect. The present study assessed whether the obese phenotype (fa/fa) compared to the lean phenotype (Fa/?) of this strain was also associated with alterations in basal and immobilization (IMMO) stress-induced noradrenergic activation in the PVN, using in vivo microdialysis. To evaluate concurrent activity of the peripheral sympathetic nervous system and the HPA axis, we also measured plasma concentrations of catecholamines, ACTH, and corticosterone. IMMO-induced increases in PVN NE levels were significantly lower in obese Zucker rats, as were elevations in plasma concentrations of dihydroxyphenylglycol and epinephrine. Basal and IMMO-stimulated plasma ACTH concentrations were similar in obese and lean rats. Basal plasma corticosterone concentrations were also similar in obese and lean rats; however, IMMO-stimulated corticosterone levels were significantly greater in obese than in lean animals. Basal plasma free corticosterone levels, measured by ultrafiltration, were significantly higher in obese than in lean rats, confirming the state of chronic hypercorticosteronism in these animals. These findings indicate that obese Zucker rats have diminished central noradrenergic and peripheral sympathetic nervous system responses to IMMO stress along with a chronically hyperactive HPA axis. We suggest that defective regulation of PVN NE reflects and contributes to the development and/or maintenance of obesity in Zucker rats via central hypoactivity of the sympathetic system. The hypercorticosteranism of these animals, apparently sustained by some nonadrenergic stimulatory input, might participate in the suppression of the sympathetic system. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NINCDS, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. NIMH, DEPT CELL BIOL, BETHESDA, MD 20892 USA. UNIV VIRGINIA, DEPT PSYCHOL, CHARLOTTESVILLE, VA 22903 USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 47 TC 44 Z9 44 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4360 EP 4367 DI 10.1210/en.136.10.4360 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100029 PM 7664655 ER PT J AU VARRAULT, A PENA, MSR GOLDSMITH, PK MITHAL, A BROWN, EM SPIEGEL, AM AF VARRAULT, A PENA, MSR GOLDSMITH, PK MITHAL, A BROWN, EM SPIEGEL, AM TI EXPRESSION OF G-PROTEIN ALPHA-SUBUNITS IN BOVINE PARATHYROID SO ENDOCRINOLOGY LA English DT Article ID NUCLEOTIDE-BINDING-PROTEIN; PERTUSSIS TOXIN; SIGNAL TRANSDUCTION; CYTOSOLIC CALCIUM; HUMAN PLATELETS; PTH SECRETION; CDNA SEQUENCE; CELL-FUNCTION; RECEPTOR; ACCUMULATION AB A G protein-coupled Ca2+-sensing receptor was recently cloned from bovine parathyroid and shown to mediate divalent cation regulation of PTH secretion. To define which G proteins might be coupled to the Ca2+-sensing receptor in parathyroid cells, we determined which G protein alpha-subunit messenger RNAs (mRNAs) are expressed in the parathyroid. We also considered the possibility that a novel parathyroid-specific G alpha might be present. We, therefore, used the reverse transcription-polymerase chain reaction to study the expression of G alpha subunits in a bovine parathyroid mRNA preparation. Degenerate primers, corresponding to two regions conserved in every G alpha subunit, the G3 and G4 sequences, were used to amplify G alpha complementary DNA fragments that were subcloned and sequenced. We found that mRNAs corresponding to G alpha s, G alpha i2, G alpha 11, G alpha 12, and G alpha z are the predominant G alpha mRNAs expressed in the bovine parathyroid. No novel G alpha mRNA was identified. Northern blots confirmed the expression of the cloned G alpha subunits and showed lower expression of G alpha o and G alpha i1 mRNAs. Immunoblots confirmed abundant expression of G alpha s, G alpha i2, and G alpha 11 and provided evidence for expression of G alpha i1 and G alpha i3, but not G alpha o. G alpha q mRNA was not identified by the degenerate primer reverse transcription-polymerase chain reaction strategy, but the immunoblot detected G alpha q protein, albeit at considerably lower levels than G alpha 11. The abundance of G alpha 11 relative to G alpha q in bovine parathyroid is consistent with but does not prove a role far G alpha 11 in coupling the Ca2+-sensing receptor to phospholipase C. C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DEPT MED,DIV ENDOCRINE HYPERTENS,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-44588, DK-48330, DK-41415] NR 39 TC 32 Z9 32 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4390 EP 4396 DI 10.1210/en.136.10.4390 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100033 PM 7664659 ER PT J AU DIRAMI, G RAVINDRANATH, N KLEINMAN, HK DYM, M AF DIRAMI, G RAVINDRANATH, N KLEINMAN, HK DYM, M TI EVIDENCE THAT BASEMENT-MEMBRANE PREVENTS APOPTOSIS OF SERTOLI CELLS IN-VITRO IN THE ABSENCE OF KNOWN REGULATORS OF SERTOLI-CELL FUNCTION SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ANDROGEN-BINDING-PROTEIN; EXTRACELLULAR-MATRIX COMPONENTS; DNA-SYNTHESIS; RAT; CULTURE; DIFFERENTIATION; PROLIFERATION; SECRETION; SURVIVAL AB Although the role of basement membrane in the morphological and functional differentiation of Sertoli cells has been well characterized, very little is known about its involvement in Sertoli cell survival and maintenance throughout life. When cultured on laminin or Matrigel, 80-90% of Sertoli cells retained their viability. Sertoli cells prevented from attachment and basement membrane deposition by plating on plastic surfaces coated with polyhydroxyethylmethacrylate (poly-HEMA) exhibited a loss of viability by approximately 50% within 24 h. Addition of soluble laminin did not prevent the loss of viability of Sertoli cells, whereas soluble Matrigel enhanced the survival significantly when added at a concentration of 100 mu g/ml or more. The addition of FSH, epidermal growth factor, testosterone, retinoic acid, or a mixture of insulin, transferrin, and selenium had no significant effect on the viability of Sertoli cells cultured on polyHEMA for up to 72 h. When all of these hormones and factors were added together, a significantly higher percentage of cell survival was observed at 24, 48, and 72 h, but the percent survival was significantly lower than that seen on either laminin or Matrigel. The nature of cell death occurring in the Sertoli cells plated on polyHEMA was determined by agarose gel analysis that revealed a ladder of similar to 200-base pair DNA multiple fragments. Flow cytometric analysis of propidium iodide-stained cells indicated that most of the cells were apoptotic. Freshly isolated Sertoli cells and adherent cells on basement membrane did not show internucleosomal DNA breakdown or an apoptotic peak in the flow cytometric analysis. These results suggest that basement membrane plays a crucial role in Sertoli cell survival in vitro when it is used as a solid substratum for culture, and in the absence of basement membrane, FSH and other regulators of Sertoli cell function cannot prevent Sertoli cell apoptosis. C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. FU NICHD NIH HHS [HD-16260] NR 42 TC 51 Z9 52 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4439 EP 4447 DI 10.1210/en.136.10.4439 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100039 PM 7664664 ER PT J AU FRIEDMAN, TC LOH, YP CAWLEY, NX BIRCH, NP HUANG, SS JACKSON, IMD NILLNI, EA AF FRIEDMAN, TC LOH, YP CAWLEY, NX BIRCH, NP HUANG, SS JACKSON, IMD NILLNI, EA TI PROCESSING OF PROTHYROTROPIN-RELEASING HORMONE (PRO-TRH) BY BOVINE INTERMEDIATE LOBE SECRETORY VESICLE MEMBRANE PC1 AND PC2 ENZYMES SO ENDOCRINOLOGY LA English DT Article ID PROHORMONE CONVERTASES PC1; CELL-LINE; FUNCTIONAL EXPRESSION; PROPROTEIN CONVERTASE; SERINE PROTEASE; RAT PITUITARY; GENE-PRODUCT; ATT20 CELLS; IDENTIFICATION; KEX2 AB TRH is synthesized from a larger 26-kilodalton (kDa) prohormone (pro-TRH). Rat pro-TRH contains five copies of the TRH progenitor sequence (Gln-His-Pro-Gly) and seven other cryptic peptides. Each of the five TRH progenitor sequences is flanked by pairs of basic amino acids. We used a bovine intermediate lobe secretory vesicle membrane preparation, which contains the prohormone convertases (PCs) PC1 and PC2, to study the in vitro processing of pro-TRH. Pro-TRH was radiolabeled using [H-3]Leu in AtT20 cells transfected with prepro-TRH complementary DNA, and the labeled 26-kDa pro-TRH was isolated from the cell extract by preparative sodium dodecyl sulfate-gel electrophoresis. Incubation of [H-3]pro-TRH with the intermediate lobe secretory vesicle membrane preparation was followed by immunoprecipitation with antibodies specific for various regions of the pro-TRH sequence, and the immunoprecipitates were analyzed by sodium dodecyl sulfate-gel electrophoresis. Immunoprecipitation of the reaction mixture with anti-pCC(10) antibody (an antibody that recognizes the intact precursor and amino-terminal intermediate products of processing) showed a time-dependent appearance of a 15-kDa and a 6-kDa peptide and, at times, a 3.8-kDa peptide with diminution of the 26-kDa substrate. Immunoprecipitation of the incubate with the C-terminal-directed antibody, pYE(17) (an antibody that recognizes the intact precursor and C-terminal intermediate products of processing), showed the generation of 16.5-, 10-, and 5.4-kDa products in a time-dependent manner, with disappearance of the substrate. Western blot analysis demonstrated that the secretory vesicle membrane preparation contains PC1 and PC2. Immunodepletion studies with antiserum specific for PC1 or PC2 demonstrated that PC1 and PC2 can process pro-TRH to these intermediate products. An initial site of cleavage appeared to be either at the 152-153 or the 158-159 pair of basic residues to yield a 15-kDa N-terminal fragment that was then processed to the 6-kDa [TRH-(25-74)] and 3.8-kDa [TRH-(83-112)] forms. The 10-kDa C-terminal peptide generated by this cleavage was then processed to a 5.4-kDa peptide [TRH-(208-255)]. Alternatively, an initial cleavage at the 107-108 or the 112-113 bonds was also observed, yielding a 16.5-kDa C-terminal product that was further processed to the 5.4-kDa peptide. The pH profile for the appearance of both C- and N-terminal products showed a bimodal distribution, with optima at both 5.5 and 7.5. The cleavage of pro-TRH was enhanced by Ca2+ and partially inhibited by Zn2+. This study provides evidence for the first time that PC enzymes can process pro-TRH. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. BROWN UNIV,RHODE ISL HOSP,DEPT MED,DIV ENDOCRINOL,PROVIDENCE,RI 02903. UNIV AUCKLAND,SCH BIOL SCI,AUCKLAND,NEW ZEALAND. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 51 TC 41 Z9 41 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4462 EP 4472 DI 10.1210/en.136.10.4462 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100042 PM 7664666 ER PT J AU MAKINO, S SCHULKIN, J SMITH, MA PACAK, K PALKOVITS, M GOLD, PW AF MAKINO, S SCHULKIN, J SMITH, MA PACAK, K PALKOVITS, M GOLD, PW TI REGULATION OF CORTICOTROPIN-RELEASING HORMONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE RAT-BRAIN AND PITUITARY BY GLUCOCORTICOIDS AND STRESS SO ENDOCRINOLOGY LA English DT Article ID REPEATED IMMOBILIZATION STRESS; FACTOR CRF; PARAVENTRICULAR NUCLEUS; DIFFERENTIAL REGULATION; BINDING; ADRENALECTOMY; LOCALIZATION; VASOPRESSIN; EXPRESSION; FEEDBACK AB Glucocorticoids and stress are known to influence the synthesis of corticotropin-releasing hormone (CRH) at a variety of sites in brain, including the hypothalamus and amygdala. The recent cloning of the CRH receptor (CRH-R) enabled us to determine whether glucocorticoids or stress influenced CRH action via regulation of CRH-R. We, therefore, used in situ. hybridization to measure CRH-R messenger RNA (mRNA) levels in the hypothalamic paraventricular nucleus (PVN), anterior pituitary (AP), amygdala, and bed nucleus of the stria terminalis (BNST) under several conditions. Systemic corticosterone (CORT) treatment, both daily injection (5 mg/rat . day) up to 14 days and pellet implant (200 mg) for 14 days, decreased CRH-R mRNA in the PVN and lateral and basolateral nucleus of the amygdala (BLA). Corticosterone injection (10 mg/rat . day, for 7 days) decreased CRH-R mRNA in the AP. Adrenalectomy also decreased CRH-R mRNA in the PVN and AP, but did not alter it in the BLA. In both sham and adrenalectomized rats with CORT pellet replacement (39 mg; ADX + CORT rats), acute (2-h) and repeated (2 h daily for 14 days) immobilization stress (which produced a large increase in plasma CORT in sham rats) increased CRH-R mRNA in the PVN and decreased it in the AP, but did not affect CRH-R mRNA in the BLA. However, ADX + CORT rats consistently had higher levels of CRH-R mRNA in both the PVN and AP than sham rats after stress. Brain stem hemisection, which damaged all ascending catecholaminergic fibers with the exception of the locus ceruleus, attenuated immobilization stress-induced up-regulation of CRH-R mRNA ipsilaterally in the PVN. None of the treatments affected CRH-R mRNA levels in the central and medial nucleus of the amygdala or the BNST. These results suggest that high concentrations of CORT or CRH synergistically decrease CRH-R mRNA levels in the AP, and that at least high CORT has an inhibitory effect on PVN CRH-R mRNA levels. However, stress input can override such inhibitory effects and thus up-regulate CRH-R mRNA in the PVN. The extrahypothalamic regions, such as amygdala and BNST may have different sensitivities to CORT or CRH for the regulation of CRH-R mRNA. C1 NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. NINCDS, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. RP NIMH, CLIN NEUROENDOCRINOL BRANCH, BLDG 10, ROOM 3S-231, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 42 TC 168 Z9 169 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4517 EP 4525 DI 10.1210/en.136.10.4517 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100048 PM 7664672 ER PT J AU EDMONDSON, SR WERTHER, GA RUSSELL, A LEROITH, D ROBERTS, CT BECK, F AF EDMONDSON, SR WERTHER, GA RUSSELL, A LEROITH, D ROBERTS, CT BECK, F TI LOCALIZATION OF GROWTH-HORMONE RECEPTOR-BINDING PROTEIN MESSENGER-RIBONUCLEIC-ACID (MESSENGER-RNA) DURING RAT FETAL DEVELOPMENT - RELATIONSHIP TO INSULIN-LIKE GROWTH-FACTOR-I MESSENGER-RNA SO ENDOCRINOLOGY LA English DT Article ID LONGITUDINAL BONE-GROWTH; START SITE USAGE; INSITU HYBRIDIZATION; TRANSGENIC MICE; SOMATOMEDIN-C; ELEVATED LEVELS; SOMATIC GROWTH; LEADER EXONS; IGF-I; EXPRESSION AB Although GH plays a key role in postnatal growth, prenatal growth is thought to be GH independent. However, recent data has shown GH receptor/binding protein (GHR/BP) to be present in rat fetal tissues as early as fetal stage E12. The aim of the present study was to investigate tissue-specific production of the GHR/BP messenger RNA (mRNA) and its relationship to locally transcribed insulin-like growth factor-I (IGF-I) mRNA in the fetus. We have used in situ hybridization to localize GHR/BP and IGF-I mRNAs in 16.5-, 18.5-, and 20.5-day-old rat fetuses. Furthermore, because the two promoters of the IGF-I gene differentially respond to GH stimulation, we have also investigated the presence and localization of promoter-specific IGF-I mRNAs. We found the distribution of IGF-I and GHR/BP mRNAs to be widespread but distinct during the fetal stages examined. High levels of IGF-I mRNA were found in connective tissues or their precursors, including the dermis, perichondrium, and gut. In contrast, GHR/BP mRNA exhibited three distinct patterns of distribution. First, GHR/BP mRNA was found at epithelial sites adjacent to sites of IGF-I transcription. Second, GHR/BP and IGF-I mRNAs were found to colocalize in some connective tissues, but GHR/BP mRNA levels in these sites were often lower than at other sites (i.e. epithelial) of GHR/BP gene transcription. Third, GHR/BP mRNA was also found in regions remote from IGF-I mRNA, including the nerve ganglia and inner olfactory bulb. Using promoter-specific IGF-I RNA probes, we detected only promoter 1 transcripts in all fetal tissues examined. The only exception occurred in specialized epithelial cells of the cochlea where we detected high levels of both promoter 1- and 2-derived IGF-I transcripts. We have thus demonstrated a distinct distribution of GHR/BP and TGF-I mRNAs in the developing rat fetus with coordinate expression at some sites. These findings suggest a role for GH or a GH-like peptide, acting both directly and indirectly via IGF-I, in fetal growth and development. C1 UNIV MELBOURNE,HOWARD FLOREY INST EXPTL PHYSIOL & MED,PARKVILLE,VIC 3052,AUSTRALIA. OREGON HLTH SCI UNIV,SCH MED,DEPT PEDIAT,PORTLAND,OR 97201. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. RP EDMONDSON, SR (reprint author), ROYAL CHILDRENS HOSP,CTR HORMONE RES,PARKVILLE,VIC 3052,AUSTRALIA. RI Werther, George/B-3784-2012 NR 47 TC 39 Z9 40 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4602 EP 4609 DI 10.1210/en.136.10.4602 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100058 PM 7664680 ER PT J AU MASTORAKOS, G BOUZAS, EA SILVER, PB SARTANI, G FRIEDMAN, TC CHAN, CC CASPI, RR CHROUSOS, GP AF MASTORAKOS, G BOUZAS, EA SILVER, PB SARTANI, G FRIEDMAN, TC CHAN, CC CASPI, RR CHROUSOS, GP TI IMMUNE CORTICOTROPIN-RELEASING HORMONE IS PRESENT IN THE EYES OF AND PROMOTES EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN RODENTS SO ENDOCRINOLOGY LA English DT Article ID RAT LEYDIG-CELLS; IMMUNOREACTIVE CORTICOTROPIN; FACTOR RECEPTORS; HUMAN-PLACENTA; BETA-ENDORPHIN; NERVOUS-SYSTEM; SPINAL-CORD; FACTOR CRF; LOCALIZATION; SECRETION AB We examined the presence and potential role of local corticotropin-releasing hormone (CRH) in experimental uveitis in rodents. This 41-amino acid peptide, originally isolated from the hypothalamus, is also secreted locally in experimentally induced and natural inflammatory sites, where it exerts autocrine or paracrine proinflammatory effects. Female Lewis rats were immunized with the major pathogenic epitope (R16 peptide) of the interphotoreceptor retinoid-binding protein in complete Freund's adjuvant, monitored daily, and killed 8, 9, 10, 12, 14, or 18 days later, after having developed uveoretinitis. Immunoreactive CRH (IrCRH) was detected by immunohistochemistry in the uveitic eyes in the cytoplasm of inflammatory cells (macrophages, lymphocytes, and polymorphonuclear cells) infiltrating the iris, ciliary body, vitreous, retina, and choroid depending on the stage of the disease. The intensity of the IrCRH staining was positively correlated with the severity of the disease based on morphological criteria. The amount of IrCRH measured by RIA varied between 0.18 +/- 0.03 (mean +/- SE) and 0.79 +/- 0.07 pmol/g wet tissue (8th and 14th day of the disease, respectively). Ophthalmic IrCRH in uveitic rat eyes had similar chromatographic mobility as rat/human CRH-(1-41) by HPLC. Furthermore, female B10.A mice were immunized with interphotoreceptor retinoid-binding protein and treated during the induction (0-7 days) or expression (8-16 days) stages of the disease with ip injections of the anti-CRH antibody TS-2 or placebo nonimmune rabbit serum The early anti-CRH treatment significantly decreased the disease intensity compared to that in placebo- or late-treated animals (P < 0.05, by analysis of variance). We conclude that IrCRH is present at the site of inflammation in rodent experimental uveitis and that its expression correlates with the natural history and intensity of the disease. Immune CRH appears to play an early pathogenetic role in the induction of experimental uveitis. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA. NEI, IMMUNOL LAB, BETHESDA, MD 20892 USA. NEI, OCULAR GENET BRANCH, BETHESDA, MD 20892 USA. NR 61 TC 45 Z9 49 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4650 EP 4658 DI 10.1210/en.136.10.4650 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100063 PM 7664685 ER PT J AU LICINIO, J BONGIORNO, PB GOLD, PW WONG, ML AF LICINIO, J BONGIORNO, PB GOLD, PW WONG, ML TI THE GENE ENCODING FOR THE NOVEL TRANSACTING FACTOR PROOPIOMELANOCORTIN CORTICOTROPIN-RELEASING HORMONE-RESPONSIVE ELEMENT-BINDING PROTEIN-1 (PCRH-REB-1) IS CONSTITUTIVELY EXPRESSED IN RAT PITUITARY AND IN DISCRETE BRAIN-REGIONS CONTAINING CRH OR CRH RECEPTORS - PATHOPHYSIOLOGICAL IMPLICATIONS SO ENDOCRINOLOGY LA English DT Note ID BIOCHEMICAL MANIFESTATIONS; STRESS; DEPRESSION; NEUROBIOLOGY; SECRETION; DISEASE; CLONING; SYSTEM AB The nucleotide sequence CTGTGCGCGCAG is a core corticotropin-releasing hormone (CRH) responsive element in the proopiomelanocortin (POMC) promoter that gives 5-7 fold stimulation of POMC transcription by CRH. This region binds a novel transacting factor, proopiomelanocortin corticotropin-releasing hormone responsive element binding protein 1 (PCRH-REB-1), recently cloned from CRH-stimulated pituitary cells. We conducted in situ hybridization histochemistry experiments, using a species-specific, antisense, S-35-labeled PCRH-REB-1 riboprobe, to determine the pattern of PCRH-REB-1 gene expression in the brain, and showed that PCRH-REB-1 mRNA is localized not only in pituitary, but it is also found in discrete brain regions such as septal nuclei, hypothalamus, cortex, hippocampus, amygdala, and cerebellum. Those regions contain CRH or CRH receptors, and respond to CRH. We hypothesize that PCRH-REB-1 may be a marker of cellular responsiveness to CRH in the brain and pituitary, and might therefore be useful in the evaluation of CRH function and in the identification of clinically effective CRH agonists and antagonists. RP LICINIO, J (reprint author), NIMH,INTRAMURAL RES PROGRAM,CLIN NEUROENDOCRINOL BRANCH,CNE,BLDG 10,RM 3S231,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 23 TC 6 Z9 8 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4709 EP 4712 DI 10.1210/en.136.10.4709 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100072 PM 7664694 ER PT J AU MCLACHLAN, JA KORACH, S AF MCLACHLAN, JA KORACH, S TI SYMPOSIUM ON ESTROGENS IN THE ENVIRONMENT .3. SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP MCLACHLAN, JA (reprint author), TULANE UNIV,TULANE XAVIER CTR BIOENVIRONM RES,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. NR 0 TC 82 Z9 86 U1 0 U2 2 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 SU 7 BP 3 EP 4 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TG782 UT WOS:A1995TG78200001 PM 8593871 ER PT J AU KORACH, KS MCLACHLAN, JA AF KORACH, KS MCLACHLAN, JA TI TECHNIQUES FOR DETECTION OF ESTROGENICITY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID PROLIFERATION; CELLS RP KORACH, KS (reprint author), NIEHS, REPROD & DEV TOXICOL LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 9 TC 57 Z9 62 U1 1 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 SU 7 BP 5 EP 8 DI 10.2307/3432499 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TG782 UT WOS:A1995TG78200002 PM 8593874 ER PT J AU TENG, C AF TENG, C TI MOUSE LACTOFERRIN GENE - A MARKER FOR ESTROGEN AND EPIDERMAL GROWTH-FACTOR SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Estrogens in the Environment, III - Global Health Implications CY JAN 09-11, 1994 CL WASHINGTON, DC DE ESTROGEN; EGF; MOUSE UTERUS; LACTOFERRIN ID HUMAN TRANSFERRIN GENE; LACTOTRANSFERRIN GENE; RECEPTOR; PROTEIN; CELLS; DIFFERENTIATION; IDENTIFICATION; TRANSCRIPTION; ORGANIZATION; ACTIVATION AB Lactoferrin mRNA in the 21-day-old mouse uterus can be increased several hundredfold by estrogen. The physiological role of lactoferrin in mouse uterus is unclear; however, it can be a useful marker for the estrogen action in the uterus. The structural organization and the chromosome location of the lactoferrin gene are similar to members of the transferrin gene family. At the 5' flanking region of the lactoferrin gene, we have characterized two modules that respond to estrogen and growth factor stimulation. Each module is composed of either overlapping or multiple transcription factor-binding elements. The well-characterized estrogen and growth factor response modules in the mouse lactoferrin gene could serve as the foundation to understand the intricate molecular mechanisms of estrogen action and its relationship to growth factors. RP TENG, C (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 23 Z9 24 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 SU 7 BP 17 EP 20 DI 10.2307/3432501 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TG782 UT WOS:A1995TG78200004 PM 8593866 ER PT J AU IGNARTROWBRIDGE, DM PIMENTEL, M TENG, CT KORACH, KS MCLACHLAN, JA AF IGNARTROWBRIDGE, DM PIMENTEL, M TENG, CT KORACH, KS MCLACHLAN, JA TI CROSS-TALK BETWEEN PEPTIDE GROWTH-FACTOR AND ESTROGEN-RECEPTOR SIGNALING SYSTEMS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE GROWTH FACTORS; EGF; TGF; IGF; ESTROGEN; ESTROGEN RECEPTOR ID LIGAND-INDEPENDENT ACTIVATION; MESSENGER RIBONUCLEIC-ACID; BREAST-CANCER CELLS; FACTOR-I; MOUSE UTERUS; MEDIATED TRANSCRIPTION; PROGESTERONE-RECEPTOR; GENE-EXPRESSION; STIMULATION; PROTEIN AB Epidermal growth factor reproduces many of the effects of estrogen on the murine female reproductive tract and may partially mediate estrogen-induced growth and differentiation. The mechanism by which the actions of estrogens and epidermal growth factor (EGF) converge is unknown. The studies described herein were performed to investigate the possibility that some of the actions of EGF may be mediated through the estrogen receptor. A specific estrogen receptor (ER) antagonist inhibited estrogenlike effects of EGF in the mouse uterus, specifically induction of DNA synthesis and phosphatidylinositol turnover. in addition, EGF elicited enhanced nuclear localization of uterine ER and formation of a unique nuclear form of ER that is present after estrogen treatment. These in vivo observations indicated that EGF may elicit some of its actions by activation of nuclear ER. Thus, the effect of peptide growth factors on activation of a consensus estrogen response element was assessed in Ishikawa human endometrial adenocarcinoma cells, which contain negligible ER levels, and in BG-1 human ovarian adenocarcinoma cells, which contain abundant ER. EGF and TGF alpha induced transcriptional activation of a consensus estrogen response element (ERE) in an ER-dependent manner in both cell types. In addition, insulinlike growth factor 1 (IGF-I) was as potent as 17 beta-estradiol in BG-1 cells. Synergism between growth factors and estrogen was observed in both cell types, although synergism was not observed between the different classes of growth factors [i.e., transforming growth factor alpha (TGF alpha) and IGF-I] in BG-1 cells. The most potent activator of ERE-dependent transcription was a protein kinase C activator (TPA), which acted synergisticaily with 17 beta-estradiol. A protein kinase C inhibitor abolished the effect of TPA but not that of 17 beta-estradiol, IGF-I, or TGF alpha. A protein kinase A activator elicited ER-dependent activation of transcription and did not synergize with estrogen or growth factors. in conclusion, some physiologic actions of peptide growth factors are dependent on ER. indeed, growth factors are capable of eliciting ER-dependent activation of an ERE. Both the protein kinase A and protein kinase C pathways can elicit ER-dependent transcriptional activation; however, it is unlikely that these pathways mediate the effects of peptide growth factors on the ER in BG-1 cells. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 34 TC 84 Z9 84 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 SU 7 BP 35 EP 38 DI 10.2307/3432505 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TG782 UT WOS:A1995TG78200008 PM 8593872 ER PT J AU CREWS, D BERGERON, JM MCLACHLAN, JA AF CREWS, D BERGERON, JM MCLACHLAN, JA TI THE ROLE OF ESTROGEN IN TURTLE SEX DETERMINATION AND THE EFFECT OF PCBS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Estrogens in the Environment, III - Global Health Implications CY JAN 09-11, 1994 CL WASHINGTON, DC DE PCBS; TSD; BIOMARKER; ENVIRONMENTAL ESTROGENS; SEX DETERMINATION; GONADAL SEX; REPTILES; EGGS AB In the current model of vertebrate sex determination and sexual differentiation, gonadal sex is fixed at fertilization by specific chromosomes, a process known as genotypic sex determination (GSD). Only after the gonad is formed do hormones begin to exert an influence that modifies specific structures that eventually will differ between the sexes. Many egg-laying reptiles do not exhibit GSD but rather depend on the temperature of the incubating egg to determine the gonadal sex of the offspring, a process termed temperature-dependent sex determination (TSD). Research on TSD indicates that sex determination in these species is fundamentally different in at least one way. Gonadal sex is not irrevocably set by the genetic composition inherited at fertilization but depends ultimately on which genes encoding for steroidogenic enzymes and hormone receptors are activated during the midtrimester of embryonic development by temperature. incubation temperature modifies the activity as well as the temporal and spatial sequence of enzymes and hormone receptors such that sex-specific hormone milieus, created in the urogenital system of the developing embryo, determine gonad type. Estrogen is the physiologic equivalent of incubation temperature and the proximate cue that initiates female sex determination. There is increasing evidence that some polychlorinated biphenyl (PCB) compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans. Reproductive disorders resulting from exposure to these xenobiotic compounds may include reductions in fertility, hatch rate in fish and birds, and viability of offspring, as well as alterations in hormone levels or adult sexual behaviors, all of which have further implications, particularly in wildlife population dynamics. Research on the mechanism through which these compounds may be acting to alter reproductive function indicates estrogenic activity, by which the compounds may be altering sexual differentiation. In TSD turtles, the estrogenic effect of some PCBs reverses gonadal sex in individuals incubating at an otherwise male-producing temperature. Furthermore, certain PCBs are synergistic in their effect at very low concentrations. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP CREWS, D (reprint author), UNIV TEXAS,INST REPROD BIOL,DEPT ZOOL,AUSTIN,TX 78712, USA. NR 19 TC 79 Z9 80 U1 6 U2 34 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 SU 7 BP 73 EP 77 DI 10.2307/3432512 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TG782 UT WOS:A1995TG78200015 PM 8593879 ER PT J AU NEWBOLD, R AF NEWBOLD, R TI CELLULAR AND MOLECULAR EFFECTS OF DEVELOPMENTAL EXPOSURE TO DIETHYLSTILBESTROL - IMPLICATIONS FOR OTHER ENVIRONMENTAL ESTROGENS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Estrogens in the Environment, III - Global Health Implications CY JAN 09-11, 1994 CL WASHINGTON, DC DE DIETHYLSTILBESTROL; DES; ESTROGENIC; ESTROGEN; ESTROGEN RECEPTOR; EMBRYOGENESIS; PERINATAL EXPOSURE; REPRODUCTIVE TRACT DEVELOPMENT; GENITAL TRACT; SEX HORMONES SEX DIFFERENTIATION ID MOUSE REPRODUCTIVE TRACTS; PRENATAL EXPOSURE; MICE; IMMUNODETECTION; ADENOCARCINOMA; RECEPTORS; FETAL; DES AB Concerns have been raised regarding the role of environmental and dietary estrogens as possible contributors to an increased incidence of various abnormalities in estrogen-target tissues of both sexes. These abnormalities include breast cancer, endometriosis, fibroids, and uterine adenocarcinoma in females, as well as alterations in sex differentiation, decreased sperm concentrations, benign prostatic hyperplasia, prostatic cancer, testicular cancer, and reproductive problems in males. Whether these concerns are valid remains to be determined; however, studies with the potent synthetic estrogen diethylstilbestrol (DES) suggest that exogenous estrogen exposure during critical stages of development can result in permanent cellular and molecular alterations in the exposed organism. These alterations manifest themselves in the female and male as structural, functional, or long-term pathological changes including neoplasia. Although DES has potent estrogenic activity, it may be used as a model compound to study the effects of weaker environmental estrogens, many of which may fit into the category of endocrine disruptors. RP NEWBOLD, R (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,E4-02,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 167 Z9 173 U1 6 U2 15 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 SU 7 BP 83 EP 87 DI 10.2307/3432514 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TG782 UT WOS:A1995TG78200017 PM 8593881 ER PT J AU MIGLIACCIO, S NEWBOLD, RR MCLACHLAN, JA KORACH, KS AF MIGLIACCIO, S NEWBOLD, RR MCLACHLAN, JA KORACH, KS TI ALTERATIONS IN ESTROGEN-LEVELS DURING DEVELOPMENT AFFECTS THE SKELETON - USE OF AN ANIMAL-MODEL SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Estrogens in the Environment, III - Global Health Implications CY JAN 09-11, 1994 CL WASHINGTON, DC DE BONE TISSUE; ESTROGENS; DEVELOPMENT; MICE ID OSTEOBLAST-LIKE CELLS; OVARIECTOMIZED RATS; BONE; DIETHYLSTILBESTROL; 17-BETA-ESTRADIOL; RECEPTORS; WOMEN; MICE AB Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. The recent finding of the presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of steroid hormones on bone tissue. Furthermore, estrogens have important effects on bone turnover in both humans and experimental animal models. Thus, this tissue is now regarded as a specific estrogen target tissue. To investigate whether a short-term developmental exposure to estrogens can influence bone tissue, we have injected female mice with diethylstilbestrol (DES) from day 1 through day 5 of life. Additionally a group of pregnant female mice were injected with different doses of DES from day 9 through 16 of pregnancy. Mice were then weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (7-12 months of age). These short-term treatments did not affect body weight of exposed mice. However, a dose-dependent increase in bone mass, both in the trabecular and compact compartments, was observed in the DES-exposed female offspring. Furthermore, femurs from DES-exposed females were shorter than femurs from controls. A normal skeletal mineralization accompanied these changes in the bone tissue. in fact, a parallel increase in total calcium content of the skeleton was found in concomitance with the increase in bone mass. Estrogen treatment induced an increase in the amount of mineralized skeleton when compared to untreated controls. In summary, this report shows that alterations of estrogen levels during development can influence the early phases of bone tissue development inducing permanent changes in the skeleton. These changes appear to be related to bone cell programming in early phases of life. C1 UNIV ROMA LA SAPIENZA,DEPT EXPTL MED,I-00185 ROME,ITALY. RP MIGLIACCIO, S (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,RBS,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Migliaccio, Silvia/0000-0002-4563-6630; Korach, Kenneth/0000-0002-7765-418X NR 23 TC 21 Z9 21 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 SU 7 BP 95 EP 97 DI 10.2307/3432516 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TG782 UT WOS:A1995TG78200019 PM 8593884 ER PT J AU TENNANT, RW FRENCH, JE SPALDING, JW AF TENNANT, RW FRENCH, JE SPALDING, JW TI IDENTIFYING CHEMICAL CARCINOGENS AND ASSESSING POTENTIAL RISK IN SHORT-TERM BIOASSAYS USING TRANSGENIC MOUSE MODELS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE BIOASSAYS; CARCINOGENS; RISK; TRANSGENIC MOUSE MODELS ID NATIONAL-TOXICOLOGY-PROGRAM; WILD-TYPE P53; B6C3F1 MICE; RODENT CARCINOGENICITY; P53-DEFICIENT MICE; GENE AMPLIFICATION; ETHYL ACRYLATE; MUTAGENICITY; SALMONELLA; TOXICITY AB Cancer is a worldwide public health concern. Identifying carcinogens and limiting their exposure is one approach to the problem of reducing risk. Currently, epidemiology and rodent bioassays are the means by which putative human carcinogens are identified. Both methods have intrinsic limitations: they are slow and expensive processes with many uncertainties. The development of methods to modify specific genes in the mammalian genome has provided promising new tools for identifying carcinogens and characterizing risk. Transgenic mice may provide advantages in shortening the time required for bioassays and improving the accuracy of carcinogen identification; transgenic mice might now be included in the testing armamentarium without abandoning the two-year bioassay, the current standard. We show that mutagenic carcinogens can be identified with increased sensitivity and specificity using hemizygous p53 mice in which one allele of the p53 gene has been inactivated. Furthermore, the TG.AC transgenic model, carrying a v-Haras construct, has developed papillomas and malignant tumors in response to a number of mutagenic and nonmutagenic carcinogens and tumor promoters, but not to noncarcinogens. We present a decision-tree approach that permits, at modest extra cost, the testing of more chemicals with improved ability to extrapolate from rodents to humans. RP TENNANT, RW (reprint author), NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-15321] NR 68 TC 212 Z9 213 U1 2 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 1995 VL 103 IS 10 BP 942 EP 950 DI 10.2307/3432740 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA RZ257 UT WOS:A1995RZ25700015 PM 8529591 ER PT J AU Morgan, DL Shines, CJ Jeter, SP Wilson, RE Elwell, MP Price, HC Moskowitz, PD AF Morgan, DL Shines, CJ Jeter, SP Wilson, RE Elwell, MP Price, HC Moskowitz, PD TI Acute pulmonary toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride intratracheally instilled into rats SO ENVIRONMENTAL RESEARCH LA English DT Article ID ARSENIDE AB Acute toxicity studies were conducted on copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CT), three novel compounds used in the photovoltaic and semiconductor industries. Female Sprague-Dawley rats (six rats/dose) were administered 0, 12, 25, 50, or 100 mg/kg body wt of CGS, CIS, or CT by intratracheal instillation. At 72 hr after treatment, body weight gain was significantly decreased in the 100 mg/kg CIS group and in all CT dose groups. Lung weights were increased in most chemical-treated rats, with CT causing the greatest increase. Total numbers of cells in bronchoalveolar lavage fluid (BALF) were significantly increased in treated rats and were greatest in the 100 mg/kg CIS group. Differential cell counts of BALF demonstrated a marked decrease in the percentage of alveolar macrophages and an increase in the percentage of polymorphonuclear leukocytes in all dose groups of all three chemicals. Slight to moderate increases in lactate dehydrogenase activity were observed in BALF from CGS- and CIS-treated rats; marked increases were observed in CT-treated rats. BALF protein was significantly increased in rats treated with CIS and CT. Microscopic examination revealed lymphoid hyperplasia in lungs of rats treated with all three chemicals. CT caused necrosis of the terminal bronchiolar epithelium and epithelium of the alveolar duct region with inflammation, prominent fibrin exudates, and type II cell hyperplasia. CGS and CIS also caused intraalveolar inflammation and type II cell hyperplasia, but did not cause the necrosis and fibrin exudate observed in lungs of CT-treated rats. Based on changes in lung weight, BALF indices, and histopathology, CT was the most toxic for the lung; CIS had intermediate toxicity and CGS was the least toxic. The solubilities of CGS and CIS were relatively low and similar at both pH levels and do not readily explain the observed differences in pulmonary toxicity. The solubility of CdTe was considerably greater than that of CGS and CIS and likely contributed to the greater toxicity of this compound. (C) 1995 Academic Press, Inc. C1 MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. BROOKHAVEN NATL LAB,UPTON,NY 12401. RP Morgan, DL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 27 Z9 28 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1995 VL 71 IS 1 BP 16 EP 24 DI 10.1006/enrs.1995.1062 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA VC747 UT WOS:A1995VC74700003 PM 8757234 ER PT J AU Daniel, LN Mao, Y Wang, TCL Markey, CJ Markey, SP Shi, XL Saffiotti, U AF Daniel, LN Mao, Y Wang, TCL Markey, CJ Markey, SP Shi, XL Saffiotti, U TI DNA strand breakage, thymine glycol production, and hydroxyl radical generation induced by different samples of crystalline silica in vitro SO ENVIRONMENTAL RESEARCH LA English DT Article ID POLYVINYLPYRIDINE-N-OXIDE; ALVEOLAR MACROPHAGES; PARTICLE SURFACE; DUST EXPOSURE; QUARTZ; INHALATION; MECHANISMS; HEMOLYSIS; ASBESTOS; DAMAGE AB Five preparations of alpha-quartz [Min-U-Sil 5 (MQZ), MQZ pretreated with hydrofluoric acid (HFMQZ), Chinese standard alpha-quartz (CSQZ), and two German samples, DQ-12 and F600] and two preparations of the crystalline silica polymorphs, cristobalite and tridymite, previously characterized for surface area and surface charge, were evaluated for their relative activities in the following assays: (i) in vitro assays of short duration (less than or equal to 15 min) for oxygen consumption and for generation of hydroxyl radicals (measured by electron spin resonance spin trapping), and (ii) in vitro assays of longer duration for DNA strand breakage (measured using linear DNA as a detector molecule) and for production of the oxidized DNA base, thymine glycol (measured by gas chromatography-mass spectrometry). Marked differences among the samples were found for their levels of oxygen consumption and of hydroxyl radicals' generation. All samples caused increased formation of thymine glycol, with wide variations in activity among samples. When normalized for equal surface area, the samples produced different levels of DNA strand breakage. Addition of hydrogen peroxide strongly accelerated DNA damage-more for cristobalite than for the alpha-quartz samples. DNA damage by quartz was enhanced by ferric chloride and inhibited by iron chelators. The order of relative activity of the samples varied with different types of in vitro assays and was not directly correlated to surface area. Electrophoretic mobility, as measured by zeta potential, was not significantly different among samples. The results suggest that the ability of different crystalline silica samples to generate a rapid burst of oxygen free radicals is distinct from their ability to induce DNA damage and DNA base oxidation over longer time periods. The relative activities of the samples in cellular assays (hemolysis of human erythrocytes; cytotoxicity and neoplastic transformation of BALB/3T3/A31 . 1 . 1 cells) were in turn markedly different from those listed above, suggesting a more critical role for surface area. The mechanisms of carcinogenesis by crystalline silica need to be further investigated in relation 60 the underlying physicochemical characteristics. (C) 1995 Academic Press, Inc. C1 NCI,LAB EXPT PATHOL,NIH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892. RI Shi, Xianglin/B-8588-2012 NR 68 TC 41 Z9 42 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1995 VL 71 IS 1 BP 60 EP 73 DI 10.1006/enrs.1995.1068 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA VC747 UT WOS:A1995VC74700009 PM 8757240 ER PT J AU KUBOTA, S ADACHI, Y COPELAND, TD OROSZLAN, S AF KUBOTA, S ADACHI, Y COPELAND, TD OROSZLAN, S TI BINDING OF HUMAN PROTHYMOSIN-ALPHA TO THE LEUCINE-MOTIF/ACTIVATION DOMAINS OF HTLV-I REX AND HIV-1 REV SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE PROTHYMOSIN ALPHA; INTERACTION WITH REV AND REX; HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1); REX OF HUMAN T-CELL LEUKEMIA VIRUS TYPE I (HTLV-I) ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOLAR-TARGETING SIGNAL; NORMAL HUMAN-LYMPHOCYTES; VIRAL MESSENGER-RNA; TYPE-1 REV; GENE-EXPRESSION; ACTIVATION DOMAIN; THYMOSIN ALPHA-1; TRANS-ACTIVATOR; PROTEIN AB Rex of human T-cell leukemia virus type I (HTLV-I) and Rev of human immunodeficiency virus 1 (HIV-1) are post-transcriptional regulators of viral gene expression. By means of affinity chromatography, we purified an 18-kDa cellular protein that bound to the conserved leucine-motif/activation domain of HTLV-I Rex or HIV-1 Rev. The protein that was purified through a Rev-affinity column was found to bind to Rex immunoprecipitated with anti-Rex IgG from an HTLV-I-producing cell line. We analyzed the purified approximate to 18-kDa protein biochemically and identified it as prothymosin alpha. The binding activity of prothymosin alpha to Rev or Rex was completely abolished when the epsilon-amino groups of its lysine residues were chemically modified by N-succinimidyl-3-(4-hydroxy-3,5-diodo-phenyl)propionate. The functional relationship between the nuclear protein prothymosin alpha and Rex-Rev is discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,SPECIAL PROGRAM PROT CHEM,FREDERICK,MD 21702. NR 49 TC 28 Z9 28 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 OCT 1 PY 1995 VL 233 IS 1 BP 48 EP 54 DI 10.1111/j.1432-1033.1995.048_1.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RZ497 UT WOS:A1995RZ49700007 PM 7588773 ER PT J AU JONES, PS SAVORY, R BARRATT, P BELL, AR GRAY, TJB JENKINS, NA GILBERT, DJ COPELAND, NG BELL, DR AF JONES, PS SAVORY, R BARRATT, P BELL, AR GRAY, TJB JENKINS, NA GILBERT, DJ COPELAND, NG BELL, DR TI CHROMOSOMAL LOCALIZATION, INDUCIBILITY, TISSUE-SPECIFIC EXPRESSION AND STRAIN DIFFERENCES IN 3 MURINE PEROXISOME-PROLIFERATOR-ACTIVATED-RECEPTOR GENES SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE PEROXISOME; CYTOCHROME P-450; BROWN ADIPOSE TISSUE; ADIPOSE; PEROXISOME-PROLIFERATOR-ACTIVATED-RECEPTOR (PPAR) ID ACYL-COA OXIDASE; RAT-LIVER; INDUCTION; MOUSE; CLONING; ACID; CYTOCHROME-P450IVA1; HEPATOCYTE; CLOFIBRATE; PROTEIN AB Three murine peroxisome-proliferator-activated-receptor (PPAR) genes were localised to chromosome 15 (PPAR alpha), chromosome 17 (PPAR beta) and chromosome 6 (PPAR gamma). The expression of the three PPAR RNAs was determined using a specific RNase protection assay. In liver RNA, PPAR alpha: was expressed at the highest level, with 20-fold lower levels of PPAR beta, and very low levels of PPAR gamma. The three PPAR RNAs showed no sex-specific differences in expression, and the levels of these transcripts were unaffected by treatment of mice with testosterone or the potent peroxisome proliferator, methylclofenapate. In agreement with this data, the level of PPAR alpha protein in liver was unchanged after treatment of mice with methylclofenapate, Investigation of the tissue-specific distribution revealed that the PPAR alpha RNA was expressed at highest levels in liver, to moderate levels in kidney and brown adipose tissue, and at low levels elsewhere. PPAR beta was expressed at moderate levels in live;, and lower levels in other tissues, including brown adipose tissue. In contrast, PPAR gamma KNA was expressed at low levels in liver or epididymal white adipose tissue and at very low levels elsewhere, but was expressed at high levels in brown adipose tissue. The tissue distribution of these receptors suggests an important role in lipid metabolism and toxicity for individual members of the PPAR family. The expression of PPAR alpha and PPAR beta RNAs was examined in 13 strains of mice, and the levels of expression varied within a fourfold range. Polymorphism in the size of PPAR alpha RNA from Swiss-Webster mice was detected, and shown to be due to a 2-bp mutation in the 3' non-coding region of PPAR alpha in Swiss Webster mice. C1 UNIV NOTTINGHAM,DEPT LIFE SCI,NOTTINGHAM NG7 2RD,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; Wellcome Trust NR 35 TC 69 Z9 72 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 OCT 1 PY 1995 VL 233 IS 1 BP 219 EP 226 DI 10.1111/j.1432-1033.1995.219_1.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RZ497 UT WOS:A1995RZ49700029 PM 7588749 ER PT J AU SCHAFF, Z SAROSI, I HSIA, CC KISS, A TABOR, E AF SCHAFF, Z SAROSI, I HSIA, CC KISS, A TABOR, E TI P53 IN MALIGNANT AND BENIGN LIVER-LESIONS SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE P53; HEPATOCELLULAR CARCINOMA; HEPATOBLASTOMA; BENIGN LIVER LESIONS; IMMUNOHISTOCHEMISTRY ID HUMAN HEPATOCELLULAR CARCINOMAS; TUMOR-SUPPRESSOR GENE; LUNG-CANCER; HEPATITIS-B; MUTATION; EXPRESSION; MARKER; PROTEIN; OVEREXPRESSION; ACCUMULATION AB p53 expression was studied by immunohistochemical methods in benign and malignant human epithelial liver lesions in 46 patients from Hungary. Positive immunostaining for p53 protein, indicating the overexpression or prolonged half-life of p53 protein, was detected in the nuclei of tumour cells of seven of the 16 hepatocellular carcinomas (HCC) (44%), including three HCC patients with hepatitis B virus infection. Immunostaining of p53 was seen in one of the seven hepatoblastomas, none of the 17 focal nodular hyperplasias, and none of the six hepatocellular adenomas. The detection of p53 in a relatively high percentage of the HCC cases in Hungary, a country in which aflatoxin contamination of the diet is rare, suggests that factors other than aflatoxin led to the accumulation or overexpression of p53 in these patients. C1 NCI,BETHESDA,MD 20892. RP SCHAFF, Z (reprint author), SEMMELWEIS UNIV MED,INST PATHOL & EXPTL CANC RES 1,H-1085 BUDAPEST,HUNGARY. NR 38 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1995 VL 31A IS 11 BP 1847 EP 1850 DI 10.1016/0959-8049(95)00380-2 PG 4 WC Oncology SC Oncology GA TF390 UT WOS:A1995TF39000026 PM 8541111 ER PT J AU JACOBS, MC GOLDSTEIN, DS WILLEMSEN, JJ SMITS, P THIEN, T DIONNE, RA LENDERS, JWM AF JACOBS, MC GOLDSTEIN, DS WILLEMSEN, JJ SMITS, P THIEN, T DIONNE, RA LENDERS, JWM TI NEUROHUMORAL ANTECEDENTS OF VASODEPRESSOR REACTIONS SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ADRENALINE; CATECHOLAMINES; FAINTING; KINETICS; NORADRENALINE ID SYMPATHETIC-NERVE ACTIVITY; VASOVAGAL SYNCOPE; VASOCONSTRICTOR RESPONSES; UNEXPLAINED SYNCOPE; CONTROL MECHANISMS; HUMANS; BARORECEPTORS; VASOPRESSIN; HYPOTENSION; HEMORRHAGE AB Vasodepressor (vasovagal) syncope, the most common cause of acute loss of consciousness, can occur in otherwise vigorously healthy people during exposure to stimuli decreasing cardiac filling. Antecedent physiological or neuroendocrine conditions for this dramatic syndrome are poorly understood. This study compared neurocirculatory responses to non-hypotensive lower body negative pressure (LBNP) in subjects who subsequently developed vasodepressor reactions during hypotensive LBNP with responses in subjects who did not. In 26 healthy subjects, LBNP at -15 and -40 mmHg was applied to inhibit cardiopulmonary and arterial baroreceptors. All the subjects tolerated 30 min of LBNP at -15 mmHg, but during subsequent LBNP at -40 mmHg 11 subjects had vasodepressor reactions, with sudden hypotension, nausea, and dizziness. In these subjects, arterial plasma adrenaline responses to LBNP both at -15 and at -40 mmHg exceeded those in subjects who did not experience these reactions. In 16 of the 26 subjects, forearm noradrenaline spillover was measured; in the eight subjects with a vasodepressor reaction, mean forearm noradrenaline spillover failed to increase during LBNP at -15 mmHg (Delta = -0.06 +/- (SEM) 0.04 pmol min(-1) 100 mL(-1)), whereas in the eight without a vasodepressor reaction, mean noradrenaline spillover increased significantly (Delta = 0.31 +/- 0.13 pmol min(-1) 100 mL(-1)). Plasma levels of beta-endorphin during LBNP at -15 mmHg increased in some subjects who subsequently had a vasodepressor reaction during LBNP at -40 mmHg. The findings suggest that a neuroendocrine pattern including adrenomedullary stimulation, skeletal sympathoinhibition, and release of endogenous opioids can precede vasodepressor syncope. C1 UNIV NIJMEGEN HOSP,DIV GEN INTERNAL MED,6500 HB NIJMEGEN,NETHERLANDS. UNIV NIJMEGEN HOSP,EXPTL & CHEM ENGN LAB,6500 HB NIJMEGEN,NETHERLANDS. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIDR,NEUROBIOL & ANAESTHESIOL BRANCH,BETHESDA,MD 20892. RI Lenders, J.W.M./L-4487-2015 NR 38 TC 18 Z9 19 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD OCT PY 1995 VL 25 IS 10 BP 754 EP 761 DI 10.1111/j.1365-2362.1995.tb01954.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA RZ986 UT WOS:A1995RZ98600007 PM 8557062 ER PT J AU RENNARD, SI WEISS, S WOOLCOCK, AJ LERTZMAN, M PAOLETTI, P BILLO, NE DONNER, C HENNINGFIELD, JE MOXHAM, J RIGOTTI, N SAMET, J SNELL, J SOFFER, A BREELING, JL AF RENNARD, SI WEISS, S WOOLCOCK, AJ LERTZMAN, M PAOLETTI, P BILLO, NE DONNER, C HENNINGFIELD, JE MOXHAM, J RIGOTTI, N SAMET, J SNELL, J SOFFER, A BREELING, JL TI SMOKING AND HEALTH - A PHYSICIANS RESPONSIBILITY - A STATEMENT OF THE JOINT COMMITTEE ON SMOKING AND HEALTH SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID TOBACCO; MORTALITY; CESSATION; NICOTINE C1 BRIGHAM & WOMENS HOSP,CHANNING LAB,BOSTON,MA 02115. UNIV SYDNEY,SYDNEY,NSW 2006,AUSTRALIA. CNR,INST CLIN PHYSIOL,I-56100 PISA,ITALY. IUATLD,PARIS,FRANCE. VERUNO MED CTR,VERUNO,ITALY. NIDA,BALTIMORE,MD. UNIV LONDON KINGS COLL,SCH MED & DENT,LONDON WC2R 2LS,ENGLAND. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. VANDERBILT CLIN,NASHVILLE,TN. ACCP,NORTHBROOK,IL. RP RENNARD, SI (reprint author), UNIV NEBRASKA,MED CTR,OMAHA,NE 68182, USA. NR 15 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 1995 VL 8 IS 10 BP 1808 EP 1811 PG 4 WC Respiratory System SC Respiratory System GA TG619 UT WOS:A1995TG61900033 ER PT J AU CHANAUD, NP VISTICA, BP EUGUI, E NUSSENBLATT, RB ALLISON, AC GERY, I AF CHANAUD, NP VISTICA, BP EUGUI, E NUSSENBLATT, RB ALLISON, AC GERY, I TI INHIBITION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS BY MYCOPHENOLATE MOFETIL, AN INHIBITOR OF PURINE METABOLISM SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE MYCOPHENOLATE MOFETIL (MM); EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU); ADOPTIVE TRANSFER OF EAU; S-ANTIGEN (SAG); CELLULAR AND HUMORAL IMMUNE RESPONSES; IMMUNOSUPPRESSION; PURINE METABOLISM ID RETINOID-BINDING PROTEIN; ADHESION MOLECULES; S-ANTIGEN; LYMPHOCYTES; RS-61443; ACID; INDUCTION; INVITRO; MICE AB Mycophenolate mofetil (MM), an inhibitor of purine metabolism, was found to effectively inhibit the development of experimental autoimmune uveoretinitis (EAU) induced by S-antigen (SAg) in Lewis rats. MM completely inhibited EAU development in the majority of rats when administered daily, on days 0-13, at a dose of 30 mg kg(-1) day(-1). The drug was less effective, however, when given on days 7-20: minimal disease inhibition was achieved with the drug at 30 mg kg(-1) day(-1), although at 60 mg kg(-1) day(-1) the drug inhibited EAU development in most treated rats during the period of its administration. MM also completely inhibited in most treated rats the development of EAU adoptively transferred by SAg-sensitized lymphocytes, thus depicting its capacity to inhibit the efferent limb of the immune response. Treatment with MM also suppressed the cellular and humoral immune responses against SAg, with a good correlation being observed between the inhibition of these responses and suppression of EAU in the different groups of rats. MM is currently being examined for its immunosuppressive effects in humans and the data recorded here thus suggest this compound may be useful in treatment of immune-mediated uveitic conditions. (C) 1995 Academic Press Limited C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. SYNTEX RES,PALO ALTO,CA. NR 29 TC 49 Z9 53 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 1995 VL 61 IS 4 BP 429 EP 434 DI 10.1016/S0014-4835(05)80138-1 PG 6 WC Ophthalmology SC Ophthalmology GA RZ675 UT WOS:A1995RZ67500006 PM 8549684 ER PT J AU FREED, WJ GIORDANO, M TAKASHIMA, H DILLONCARTER, O TRUCKENMILLER, ME KULAGA, H GELLER, HM TONATORE, C AF FREED, WJ GIORDANO, M TAKASHIMA, H DILLONCARTER, O TRUCKENMILLER, ME KULAGA, H GELLER, HM TONATORE, C TI CONDITIONAL IMMORTALIZATION STRATEGIES - CELL-LINES DERIVED USING SV40 LARGE-T TSA58 SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,NPB,PRECLIN NEUROSCI SECT,WASHINGTON,DC 20032. UNIV NACL AUTONOMA MEXICO,MEXICO CITY,DF,MEXICO. KAWATANA NATL HOSP,NAGASAKI,JAPAN. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,NEWARK,NJ 07103. NIH,LMMN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1995 VL 135 IS 2 BP 164 EP 164 PG 1 WC Neurosciences SC Neurosciences & Neurology GA TC202 UT WOS:A1995TC20200030 ER PT J AU MISIEWICZ, B POLTORAK, M GOMEZ, M GLOWA, JR GOLD, PW STERNBERG, EM AF MISIEWICZ, B POLTORAK, M GOMEZ, M GLOWA, JR GOLD, PW STERNBERG, EM TI INTRACEREBROVENTRICULARLY TRANSPLANTED EMBRYONIC F344/N NEURONAL TISSUE DECREASES STARTLE RESPONSES IN LEW/N RATS SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1995 VL 135 IS 2 BP 168 EP 168 PG 1 WC Neurosciences SC Neurosciences & Neurology GA TC202 UT WOS:A1995TC20200054 ER PT J AU MITCHELL, PB GIORDANO, M CANNONSPOOR, HE OKOYE, GS GELLER, HM FREED, WJ AF MITCHELL, PB GIORDANO, M CANNONSPOOR, HE OKOYE, GS GELLER, HM FREED, WJ TI CHARACTERIZATION OF THE HOST RESPONSE TO TRANSPLANTS OF THE IMMORTALIZED A7 GLIAL-CELL LINE IN THE RAT STRIATUM SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 USN HOSP,DEPT NEUROSURG,BETHESDA,MD 20814. UNIV NACL AUTONOMA MEXICO,MEXICO CITY,DF,MEXICO. NIMH,NEUROSCI CTR ST ELIZABETHS,NPB,PRECLIN NEUROSCI SECT,WASHINGTON,DC 20032. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,NEWARK,NJ 07103. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1995 VL 135 IS 2 BP 168 EP 168 PG 1 WC Neurosciences SC Neurosciences & Neurology GA TC202 UT WOS:A1995TC20200053 ER PT J AU POLTORAK, M KHOJA, I HEMPERLY, JJ FREED, WJ AF POLTORAK, M KHOJA, I HEMPERLY, JJ FREED, WJ TI INTRACEREBRAL INJECTION OF L1 ANTIGEN PROMOTES GROWTH OF NEURITES IN LESIONED RAT STRIATUM IN-VIVO SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. BECTON DICKINSON RES CTR,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1995 VL 135 IS 2 BP 168 EP 168 PG 1 WC Neurosciences SC Neurosciences & Neurology GA TC202 UT WOS:A1995TC20200056 ER PT J AU STANLEY, SM MARKMAN, HJ STPETERS, M LEBER, BD AF STANLEY, SM MARKMAN, HJ STPETERS, M LEBER, BD TI STRENGTHENING MARRIAGES AND PREVENTING DIVORCE - NEW DIRECTIONS IN PREVENTION RESEARCH SO FAMILY RELATIONS LA English DT Article DE COMMUNICATION; DIVORCE; MARRIAGE; PREVENTION; PSYCHO-EDUCATION ID MARITAL DISTRESS; POSTPARTUM DEPRESSION; CONFLICT; PROGRAM; QUALITY; PREVALENCE; PREDICTION; FRAMEWORK; CHILD AB We highlight findings from the first 12 years of a longitudinal study of the prediction and prevention of marital distress and divorce and discuss new directions in the dissemination and evaluation of an empirically based prevention program for couples. We summarize the history and state of our program and discuss the key issues and implications of moving an empirically validated intervention out of the laboratory and into settings where it can help a wider base of couples prevent marital breakdown. We then describe our pilot studies that investigate the dissemination and use of our preventive intervention with couples who marry within religious organizations and with expectant couples where the mother is at high risk for maternal depression. C1 UNIV DENVER,DEPT PSYCHOL,CTR MARITAL & FAMILY STUDIES,DENVER,CO 80208. UNIV DENVER,DEPT PSYCHOL,NIMH,FAMILY RES CONSORTIUM,DENVER,CO 80208. NR 70 TC 51 Z9 51 U1 1 U2 3 PU NATL COUNC FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0197-6664 J9 FAM RELAT JI Fam. Relat. PD OCT PY 1995 VL 44 IS 4 BP 392 EP 401 DI 10.2307/584995 PG 10 WC Family Studies; Social Work SC Family Studies; Social Work GA TC678 UT WOS:A1995TC67800009 ER PT J AU MORIOKA, H TACHIBANA, M AF MORIOKA, H TACHIBANA, M TI AGGLUTINATION OF STAPHYLOCOCCUS-SAPROPHYTICUS - A STRUCTURAL AND CYTOCHEMICAL STUDY SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE STAPHYLOCOCCUS SAPROPHYTICUS; AGGLUTINATION; ERYTHROCYTE; LECTIN; WGA; N-ACETYLGLUCOSAMINE ID ULTRASTRUCTURAL-LOCALIZATION; LIPOTEICHOIC ACID; SLIME PRODUCTION; GOLD COMPLEX; ADHERENCE; PROTEIN AB Staphylococcus saprophyticus was shown to be agglutinated by wheat germ agglutinin, wheat germ agglutinin-biotin and bovine serum albumin-p-aminophenyl-N-acetyl-beta-D-glucosaminide (GlcNAc-BSA), and sheep red blood cells. In these agglutinations, filamentous or amorphous structures radiating from the surface of S. saprophyticus were demonstrated by electron microscope observation. Cytochemical analyses of the agglutination revealed the binding sites of wheat germ agglutinin in S. saprophyticus and the binding sites of GlcNAc in the sheep red blood cells and S. saprophyticus. Since GlcNAc-BSA contains N-acetylglucosamine to which wheat germ agglutinin can bind, it is most likely that an interaction between a wheat germ agglutinin-bindable substance in S. saprophyticus and an N-acetylglucosamine-bindable substance in sheep red blood cells is involved in the agglutination. C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS,MOLEC GENET LAB,BETHESDA,MD. RP MORIOKA, H (reprint author), KYOTO PREFECTURAL UNIV MED,ELECTRON MICROSCOPY LAB,KAMIKYO KU,KYOTO 602,JAPAN. NR 20 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD OCT 1 PY 1995 VL 132 IS 1-2 BP 101 EP 105 DI 10.1111/j.1574-6968.1995.tb07818.x PG 5 WC Microbiology SC Microbiology GA RX768 UT WOS:A1995RX76800017 PM 7590154 ER PT J AU ARNO, JN YUAN, Y CLEARY, RE MORRISON, RP AF ARNO, JN YUAN, Y CLEARY, RE MORRISON, RP TI SEROLOGIC RESPONSES OF INFERTILE WOMEN TO THE 60-KD CHLAMYDIAL HEAT-SHOCK PROTEIN (HSP60) SO FERTILITY AND STERILITY LA English DT Article DE TUBAL INFERTILITY; CHLAMYDIA TRACHOMATIS; ANTIBODY RESPONSES; HEAT SHOCK PROTEINS ID DISEASE PATHOGENESIS; TRACHOMATIS; ANTIBODIES; INFECTION; EPITOPES; INFLAMMATION; SALPINGITIS; ASSOCIATION; PREGNANCY AB Objective: To determine whether women with Chlamydia trachomatis-associated tubal infertility are more likely than other infertile women to have antibodies to a particular region of the 60-kd chlamydial heat shock protein, hsp60. Design: Serologic responses to the chlamydial hsp60 were examined in 43 infertile women seropositive for Chlamydia trachomatis, including 21 women with tubal infertility, 13 women with endometriosis, and 9 women with other causes of infertility. Antibody responses were localized to regions of hsp60 using five nonoverlapping recombinant polypeptides. Results: Sixteen women with tubal infertility had anti-hsp60 antibodies compared with seven women with endometriosis and two women with other causes of infertility. Antibodies of 11 women with tubal infertility reacted predominantly with a region of hsp60 containing amino acids (201 to 300) compared with 1 woman without tubal infertility. In contrast, antibodies that localized to the carboxyl terminus, amino acids (401 to 544), were seen equally in all groups. Conclusions: Among seropositive infertile women, antibodies that localized to amino acids (201 to 300) were immunodominant in those with tubal infertility but not in those with infertility due to other causes. C1 RICHARD L ROUDEBUSH VET ADM MED CTR,INDIANAPOLIS,IN 46202. ST VINCENTS HOSP,INDIANAPOLIS,IN. HLTH CARE CTR,INDIANAPOLIS,IN. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RP ARNO, JN (reprint author), INDIANA UNIV,SCH MED,545 BARNHILL DR EM 435,INDIANAPOLIS,IN 46202, USA. FU NIAID NIH HHS [AI31494] NR 24 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 1995 VL 64 IS 4 BP 730 EP 735 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA RW249 UT WOS:A1995RW24900011 PM 7672143 ER PT J AU ROSSOUW, JE FINNEGAN, LP HARLAN, WR AF ROSSOUW, JE FINNEGAN, LP HARLAN, WR TI DONT READ MY LIPS - READ THE EXCLUSIONS SO FERTILITY AND STERILITY LA English DT Letter RP ROSSOUW, JE (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 1995 VL 64 IS 4 BP 872 EP 873 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA RW249 UT WOS:A1995RW24900037 PM 7672167 ER PT J AU NIHEI, N ICHIKAWA, T KAWANA, Y KURAMOCHI, H KUGO, H OSHIMURA, M KILLARY, AM RINKERSCHAEFFER, CW BARRETT, JC ISAACS, JT SHIMAZAKI, J AF NIHEI, N ICHIKAWA, T KAWANA, Y KURAMOCHI, H KUGO, H OSHIMURA, M KILLARY, AM RINKERSCHAEFFER, CW BARRETT, JC ISAACS, JT SHIMAZAKI, J TI LOCALIZATION OF METASTASIS SUPPRESSOR GENE(S) FOR RAT PROSTATIC-CANCER TO THE LONG ARM OF HUMAN-CHROMOSOME-10 SO GENES CHROMOSOMES & CANCER LA English DT Article ID PROGRESSION; HETEROZYGOSITY; CARCINOMA; DELETION; ABILITY; REGIONS AB To examine the role of human chromosome 10 in development of prostatic cancer, we introduced human chromosome 10 into highly metastatic rat prostatic cancer cells by microcell-mediated chromosome transfer. Microcell hybrid cells introduced with human chromosome 10 showed suppression of the metastatic ability to the lung to some extent without any suppression of tumorigenicity, although the tumor growth rate decreased slightly. To minimize the region that contains metastasis suppressive activity, the hybrid cells in metastasis foci of lung were established in culture and reanalyzed for portions of human chromosome 10 retained in the metastasis tissues. Cytogenetic and molecular analyses demonstrated that loss of the region between 10cen and D10S215 on human chromosome arm 10q was related to expression of the metastatic phenotype. These results demonstrate that the region between 10cen and D10S215 on human chromosome arm 10q contains at least one of the metastasis suppressor genes for rat prostatic cancer. (C) 1995 Wiley-Liss, Inc. C1 CHIBA UNIV,SCH MED,DEPT UROL,CHUO KU,CHIBA 260,JAPAN. TOTTORI UNIV,SCH MED,DEPT MOLEC & CELL GENET,YONAGO,TOTTORI 683,JAPAN. UNIV TEXAS,MD ANDERSON CANCER CTR,DIV LAB MED,HEMATOPATHOL PROGRAM,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA 58236] NR 21 TC 54 Z9 54 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 OCT PY 1995 VL 14 IS 2 BP 112 EP 119 DI 10.1002/gcc.2870140205 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA RX766 UT WOS:A1995RX76600004 PM 8527392 ER PT J AU RAMSDEN, DA GELLERT, M AF RAMSDEN, DA GELLERT, M TI FORMATION AND RESOLUTION OF DOUBLE-STRAND BREAK INTERMEDIATES IN V(D)J REARRANGEMENT SO GENES & DEVELOPMENT LA English DT Article DE V(D)J RECOMBINATION; DOUBLE-STRAND BREAK REPAIR; IMMUNOGLOBULIN LIGHT CHAIN; TS-ABL; DNA HAIRPINS ID BROKEN DNA-MOLECULES; GENE REARRANGEMENT; MOUSE THYMOCYTES; RECOMBINATION; POLYMORPHISM; COMPLEXITY; SEQUENCES; FAMILIES; LINKAGE AB A recently described pre-B cell line can be induced at high temperature to actively rearrange its immunoglobulin light-chain loci. We used this cell line to determine the fate of double-strand breaks generated by V(D)J rearrangement. After induction, 30%-40% of kappa loci had broken J kappa 1 signal ends. J kappa 1-coding ends were detectable, but 10- to 100-fold less frequent. Both covalently closed (hairpin) and open, blunt, processed coding ends were observed. Coding junctions involving J kappa 1 accumulated with similar kinetics as J kappa 1 Signal ends, arguing that coding ends can be resolved quickly and efficiently to coding junctions, whereas signal ends remain mostly unjoined. Signal ends are then joined rapidly when cells are returned to the low temperature. These results support the model that broken signal ends and hairpin coding ends are authentic intermediates in V(D)J recombination. It appears that hairpin coding ends are rapidly opened, processed, and resolved to coding junctions, whereas joining of signal ends is clearly uncoupled from the joining of coding ends and can be much slower. Efficient formation of signal junctions may require cell cycle progression, or down-regulation of the recombination machinery. RP RAMSDEN, DA (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 27 TC 129 Z9 131 U1 1 U2 2 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 OCT 1 PY 1995 VL 9 IS 19 BP 2409 EP 2420 DI 10.1101/gad.9.19.2409 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RZ238 UT WOS:A1995RZ23800008 PM 7557392 ER PT J AU Liang, BC AF Liang, BC TI Use of 'long' polymerase chain reaction and magnetic beads for extraction of chromosome-specific cDNAs SO GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING LA English DT Article DE polymerase chain reaction; magnetic beads; alu primer; long polymerase chain reaction ID MICRODISSECTION; AMPLIFICATION; REGION; DNA AB The detection of expressed sequences of genomic DNA is an important aspect of the human genome project. A technique is described where 'long' polymerase chain reaction (LPCR), which allows for extended large fragment production of > 10-20 kb, is used with Alu primers to generate a biotinylated template for cDNA hybridization. Streptavidin-coated magnetic beads are used to extract the long PCR templates and bound cDNAs, which are recovered by standard PCR. This method allows the isolation of cDNAs from virtually any human DNA source and should be valuable in expression mapping, positional cloning and gene isolation. RP Liang, BC (reprint author), NIH,NCI,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BLDG 10-12CL03,BETHESDA,MD 20892, USA. NR 11 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1050-3862 J9 GENET ANAL-BIOMOL E JI Genet. Anal.-Biomol. Eng. PD OCT PY 1995 VL 12 IS 2 BP 105 EP 108 DI 10.1016/1050-3862(95)00115-8 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TY153 UT WOS:A1995TY15300007 PM 8574893 ER PT J AU OAKEY, RJ MATTESON, PG LITWIN, S TILGHMAN, SM NUSSBAUM, RL AF OAKEY, RJ MATTESON, PG LITWIN, S TILGHMAN, SM NUSSBAUM, RL TI NONDISJUNCTION RATES AND ABNORMAL EMBRYONIC-DEVELOPMENT IN A MOUSE CROSS BETWEEN HETEROZYGOTES CARRYING A (7,18)-ROBERTSONIAN TRANSLOCATION CHROMOSOME SO GENETICS LA English DT Article ID NUCLEAR TRANSPLANTATION; MICE; DISJUNCTION; GENOMES AB Mice bearing Robertsonian translocation chromosomes frequently produce aneuploid gametes. They are therefore excellent tools for studying nondisjunction in mammals. Genotypic analysis of embryos from a mouse cross between thio different strains of mice carrying a (7, 18) Robertsonian chromosome enabled us to measure the rate of nondisjunction for chromosomes 7 and 18. Embryos (429) were harvested from 76 litters of mice and the parental origin of each chromosome 7 and 18 determined. Genotyping these embryos has allowed us to conclude the following: (1) there were 96 embryos in which at least one nondisjunction event had taken place; (2) the rate of maternal nondisjunction was greater than paternal nondisjunction for the chromosomes sampled in these mice; (3) a bias against chromosome 7 and 18 nullisomic gametes was observed, reflected in a smaller than expected number of uniparental disomic embryos; (4) nondisjunction events did not seem to occur at random throughout the 76 mouse litters, but were clustered into fewer than would be expected by chance; and (5) a deficiency of paternal chromosome IS uniparental disomic embryos was observed along with a higher than normal rate of developmental retardation at 8.5 days post coitum, raising the possibility that this chromosome has at least one imprinted gene. C1 NIH,NATL CTR RES RESOURCES,GENET DIS RES LAB,BETHESDA,MD 20892. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. PRINCETON UNIV,LEWIS THOMAS LAB,DEPT MOLEC BIOL,PRINCETON,NJ 08544. RI Oakey, Rebecca/A-5958-2011 OI Oakey, Rebecca/0000-0003-2706-8139 NR 29 TC 19 Z9 19 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 1995 VL 141 IS 2 BP 667 EP 674 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA RX019 UT WOS:A1995RX01900020 PM 8647401 ER PT J AU TORIGOE, K SATO, S KUSABA, H KOHNO, K KUWANO, M OKUMURA, K GREEN, ED TSUI, LC SCHERER, SW SCHLESSINGER, D WADA, M AF TORIGOE, K SATO, S KUSABA, H KOHNO, K KUWANO, M OKUMURA, K GREEN, ED TSUI, LC SCHERER, SW SCHLESSINGER, D WADA, M TI A YAC-BASED CONTIG OF 1.5 MB SPANNING THE HUMAN MULTIDRUG-RESISTANCE GENE REGION AND DELINEATING THE AMPLIFICATION UNIT IN 3 HUMAN MULTIDRUG-RESISTANT CELL-LINES SO GENOME RESEARCH LA English DT Article ID KB CARCINOMA-CELLS; P-GLYCOPROTEIN GENE; DNA-SEQUENCES; DRUG-RESISTANCE; MDR1 GENE; DOUBLE MINUTES; HAMSTER-CELLS; HUMAN CANCER; YEAST; EXPRESSION AB A contig of 21 nonchimeric yeast artificial chromosomes (YACs) has been assembled across 1.5 Mb of the multidrug resistance (MDR) gene region located at 7q21, and formatted with Four previously reported probes, six newly isolated probes, and three sequence-tagged sites (STSs) From internal and end Fragments of YACs. A physical map of rare cutter restriction enzyme sites across the region was also constructed by pulsed-field gel electrophoretic (PFGE) analysis of four overlapping YAC clones. The amplification unit of this region in different cell lines was then determined by Southern blot analysis on the basis of the physical map and probes. Amplified DNA was located in extrachromosomal elements in human MDR cell lines studied here, and the size of the amplification unit was determined to be discrete in one MDR amplification but variable in others. C1 KYUSHU UNIV,SCH MED,DEPT BIOCHEM,FUKUOKA 812,JAPAN. MIE UNIV,FAC BIORESOURCES,TSU,MIE 514,JAPAN. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. HOSP SICK CHILDREN,RES INST,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. RI Tsui, Lap-chee/A-1081-2010; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU NHGRI NIH HHS [HG00247] NR 60 TC 11 Z9 11 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 OCT PY 1995 VL 5 IS 3 BP 233 EP 244 DI 10.1101/gr.5.3.233 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TF348 UT WOS:A1995TF34800004 PM 8593611 ER PT J AU KUSABA, H KOHNO, K ASAKUNO, K KUWANO, M OKUMURA, K GREEN, ED SCHLESSINGER, D WADA, M AF KUSABA, H KOHNO, K ASAKUNO, K KUWANO, M OKUMURA, K GREEN, ED SCHLESSINGER, D WADA, M TI FUNCTIONAL EXPRESSION OF YEAST ARTIFICIAL CHROMOSOME HUMAN MULTIDRUG-RESISTANCE GENES IN MOUSE CELLS SO GENOME RESEARCH LA English DT Article ID P-GLYCOPROTEIN GENE; MAMMALIAN REPLICATION ORIGIN; BACTERIAL TRANSPORT PROTEINS; MULTIPLE-DRUG RESISTANCE; DNA-SEQUENCES; MDR1 GENE; MONOCLONAL-ANTIBODIES; COMPLEMENTARY-DNA; CARCINOMA-CELLS; TRANSGENIC MICE AB Multidrug resistance (MDR) genes, which are ATP-binding cassette family genes, encode the cell surface pe glycoprotein, P-glycoprotein, which functions as an energy-dependent drug efflux pump. Two relevant human genes, PGY1 and PGY3, are located on human chromosome 7, and three relevant mouse genes, mdr1a, mdr1b, and mdr2, are located on mouse chromosome 5. An LMD1 cell line was established after the transfer of a 580-kb yeast artificial chromosome (YAC) clone carrying the human MDR locus into mouse L cells; the cell line was shown to have stably integrated YAC DNA in an apparent intact Form. Using LMD1 cells as the pal ental cell line, five vincristine-resistant sublines, designated LMD1-V50, LMD1-V100, LMD1-V200, LMD1-V500, and LMD1-V1000, were isolated by exposure to increasing concentrations of the drug. LMD1-V50, LMD1-V100, LMD1-V200, LMD1-V500, and LMD1-V1000 showed 3-, 7-, 13-, 45-, and 110-fold higher resistance to the cytotoxic effects of vincristine, respectively, than their parental counterpart, LMD1. Immunofluorescence, Western blot, and Northern blot analyses revealed that the human PGY1 gene or its product was overexpressed, accompanied by gene amplification. The human PGY3 gene was also overexpressed in the LMD1-V20, LMD1-V100, and LMD1-V1000 cell lines. Southern blot and fluorescence in situ hybridization (FISH) analyses demonstrated that although essentially the entire YAC DNA was integrated in mouse genome and amplified, the endogenous mouse mdr genes were not amplified in these drug-resistant cell lines. Similar results were obtained by the analyses of vincristine-resistant cell lines isolated from four independent subclones of LMD1 cells. Thus, in contrast to their mouse counterparts, the integrated human MDR genes retained susceptibility to both gene activation and amplification, during the selection of drug-resistant mouse cell lines. The possibility that transferred YACs may retain regulatory propel-ties observed in the cells of origin, and may have a chromatin structure that favors augmented expression, is discussed. C1 KYUSHU UNIV,SCH MED,DEPT BIOCHEM,FUKUOKA 81282,JAPAN. MIE UNIV,FAC BIORESOURCES,TSU,MIE 514,JAPAN. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. FU NHGRI NIH HHS [P50-HG00201] NR 67 TC 14 Z9 14 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 OCT PY 1995 VL 5 IS 3 BP 245 EP 258 DI 10.1101/gr.5.3.245 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TF348 UT WOS:A1995TF34800005 PM 8593612 ER PT J AU FUKUSHIMA, K RAMESH, A SRISAILAPATHY, CRS NI, L WAYNE, S ONEILL, ME VANCAMP, G COUCKE, P JAIN, P WILCOX, ER SMITH, SD KENYON, JB ZBAR, RIS SMITH, RJH AF FUKUSHIMA, K RAMESH, A SRISAILAPATHY, CRS NI, L WAYNE, S ONEILL, ME VANCAMP, G COUCKE, P JAIN, P WILCOX, ER SMITH, SD KENYON, JB ZBAR, RIS SMITH, RJH TI AN AUTOSOMAL RECESSIVE NONSYNDROMIC FORM OF SENSORINEURAL HEARING-LOSS MAPS TO 3P-DFNB6 SO GENOME RESEARCH LA English DT Letter AB Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of congenitally acquired inherited hearing impairment. Although numerous loci ale believed to exist, only five have been identified. Using a pooled genomic DNA screening strategy, we have identified a sixth locus, DFNB6, on 3p in the interval bounded by D3S1619 and D3S1766. C1 UNIV IOWA,DEPT OTOLARYNGOL,MOLEC OTOLARYNGOL RES LABS,IOWA CITY,IA 52242. UNIV MADRAS,DEPT GENET,MADRAS,TAMIL NADU,INDIA. UNIV ANTWERP,DEPT MED GENET,B-2610 ANTWERP,BELGIUM. NIDOCD,ROCKVILLE,MD 20850. BOYS TOWN NATL RES HOSP,OMAHA,NE 68131. RI Van Camp, Guy/F-3386-2013 OI Van Camp, Guy/0000-0001-5105-9000 NR 19 TC 44 Z9 44 U1 0 U2 2 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 OCT PY 1995 VL 5 IS 3 BP 305 EP 308 DI 10.1101/gr.5.3.305 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TF348 UT WOS:A1995TF34800008 PM 8593615 ER PT J AU SMITH, JR CARPTEN, JD BROWNSTEIN, MJ GHOSH, S MAGNUSON, VL GILBERT, DA TRENT, JM COLLINS, FS AF SMITH, JR CARPTEN, JD BROWNSTEIN, MJ GHOSH, S MAGNUSON, VL GILBERT, DA TRENT, JM COLLINS, FS TI APPROACH TO GENOTYPING ERRORS CAUSED BY NONTEMPLATED NUCLEOTIDE ADDITION BY TAQ DNA-POLYMERASE SO GENOME RESEARCH LA English DT Article ID LOCI AB Thermostable DNA polymerases can catalyze nontemplated addition of a nucleotide to the 3' end of amplification products. This presents a potential source of error in genotyping studies employing Taq DNA polymerase to amplify microsatellite loci. Although the activity is marker specific, experimental variation is often seen In the degree of modification. Consequently, for a given microsatellite marker, an allele may be inconsistently identified as either the unmodified or modified amplification product. Full automation of high-throughput genotyping has been hampered by the need for manual editing of data because of this source of allele misidentification. In this study we estimate a 1% to 3% error rate attributable to nontemplated nucleotide addition in the ABI PRISM genotyping system. We present a PCR-based strategy to minimize this source of error. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. NIMH,BETHESDA,MD 20892. PERKIN ELMER CORP,DIV APPL BIOSYST,FOSTER CITY,CA 94404. RP SMITH, JR (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. RI Brownstein, Michael/B-8609-2009; Smith, Jeff/C-3484-2012 NR 6 TC 85 Z9 85 U1 0 U2 4 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 OCT PY 1995 VL 5 IS 3 BP 312 EP 317 DI 10.1101/gr.5.3.312 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TF348 UT WOS:A1995TF34800010 PM 8593617 ER PT J AU BAKER, GT AF BAKER, GT TI PRACTICAL HANDBOOK OF HUMAN BIOLOGIC AGE-DETERMINATION - BALIN,AK SO GERONTOLOGIST LA English DT Book Review C1 CENT INST MENTAL HLTH,DEPT PSYCHOPHARMACOL,D-68159 MANNHEIM,GERMANY. RP BAKER, GT (reprint author), NIA,HOPKINS BAYVIEW MED CTR,GERONTOL RES CTR,NATHAN W SHOCK LABS,BALTIMORE,MD 21224, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 1995 VL 35 IS 5 BP 707 EP 710 PG 4 WC Gerontology SC Geriatrics & Gerontology GA RZ733 UT WOS:A1995RZ73300022 ER PT J AU CISAR, JO SANDBERG, AL ABEYGUNAWARDANA, C REDDY, GP BUSH, CA AF CISAR, JO SANDBERG, AL ABEYGUNAWARDANA, C REDDY, GP BUSH, CA TI LECTIN RECOGNITION OF HOST-LIKE SACCHARIDE MOTIFS IN STREPTOCOCCAL CELL-WALL POLYSACCHARIDES SO GLYCOBIOLOGY LA English DT Article DE BACTERIAL ADHESINS; CELLULAR RECOGNITION; LECTINS; MICROBIAL COLONIZATION; STREPTOCOCCAL POLYSACCHARIDES ID RICINUS-COMMUNIS AGGLUTININ; ACTINOMYCES-VISCOSUS T14V; SURFACE POLYSACCHARIDE; AGARICUS-BISPORUS; COAGGREGATION; BINDING; NAESLUNDII; SPECIFICITY; STREPTOCOCCUS-SANGUIS-34; GLYCOSPHINGOLIPIDS AB Viridans streptococci that participate in the microbial colonization of teeth have cell wall polysaccharides composed of linear phosphodiester-linked hexa- or heptasaccharide repeating units, each containing a host-like disaccharide motif, either Gal beta 1-->3GalNAc or GalNAc beta 1-->3Gal. Whereas strains with GalNAc beta 1-->3Gal-containing polysaccharides co-aggregated with streptococci that possess GalNAc-sensitive lectins, strains with either host-like moth co-aggregated with Actinomyces spp, The latter interactions reflected the specificity of Actinomyces spp, lectins for common features of Gal beta 1-->3GalNAc and GalNAc beta 1--> 3Gal, Thus, alpha-linked glycosides of both disaccharides were much more potent inhibitors of co-aggregation than Gal or GalNAc Six non-bacterial lectins also reacted with the streptococcal polysaccharides, In general, precipitation of each lectin with each polysaccharide involved binding of Gal or GalNAc within the host-like moths, but not saccharides outside these regions, The lectins of Ricinus communis, Abrus precatorius, Codium fragile and Agaricus bisporus were most reactive with the Gal beta 1-->3GalNAc-containing polysaccharides, the Wisteria floribunda lectin with the GalNAc beta 1-->3Gal-containing polysaccharides and the Bauhinia purpurea lectin with polysaccharides containing either disaccharide, Thus, lectin recognition of the streptococcal cell wall polysaccharides involved either the common or specific sides of the Gal beta 1-->3GalNAc and GalNAc beta 1-->3Gal moths present within these molecules. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. RP CISAR, JO (reprint author), NIDR,MICROBIAL ECOL LAB,BLDG 30,ROOM 302,BETHESDA,MD 20892, USA. FU NIDCR NIH HHS [DE-09445] NR 32 TC 57 Z9 57 U1 1 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1995 VL 5 IS 7 BP 655 EP 662 DI 10.1093/glycob/5.7.655 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH399 UT WOS:A1995TH39900002 PM 8608267 ER PT J AU KAWAHITO, Y SANO, H MUKAI, S ASAI, K KIMURA, S YAMAMURA, Y KATO, H CHROUSOS, GP WILDER, RL KONDO, M AF KAWAHITO, Y SANO, H MUKAI, S ASAI, K KIMURA, S YAMAMURA, Y KATO, H CHROUSOS, GP WILDER, RL KONDO, M TI CORTICOTROPIN-RELEASING HORMONE IN COLONIC MUCOSA IN PATIENTS WITH ULCERATIVE-COLITIS SO GUT LA English DT Article DE CORTICOTROPIN RELEASING HORMONE; ULCERATIVE COLITIS; COLONIC MUCOSA IMMUNOHISTOCHEMISTRY; POLYMERASE CHAIN REACTION; IN SITU HYBRIDIZATION ID RAT SPINAL-CORD; MESSENGER-RNA; RHEUMATOID-ARTHRITIS; LEWIS RATS; FACTOR CRF; SECRETION; NEUROHORMONE; TISSUES; STRESS; IMMUNOREACTIVITY AB Corticotropin releasing hormone (CRH) is a key hormone in integrated response to stress, acting as the major regulator of the hypothalamic-pituitary-adrenal axis. Recently, local production of CRH has been detected in normal human colonic enterochromaffin cells. CRH is locally secreted in granulomatous and arthritic tissues in rats and humans, where it seems to act as a local proinflammatory agent. To find out if CRH is present in colonic tissues of patients with ulcerative colitis, this study examined the expression of this peptide in the large bowel of patients with ulcerative colitis. Colonic tissues of patients with ulcerative colitis obtained by endoscopic biopsy were immunostained with anti-CRH antibody. CRH messenger (m) RNA was also examined in biopsy specimens of ulcerative colitis by the reverse transcribed polymerase chain reaction method and by in situ hybridisation. Considerably enhanced expression of immunoreactive CRH was found in mucosal inflammatory cells. Intense staining with anti-CRH antibody was also shown in mucosal macrophages. CRH mRNA was expressed in mucosal epithelial cells. The expression of immunoreactive CRH in colonic mucosal epithelial cells of ulcerative colitis slightly increased, but not significantly, compared with normal colonic mucosal epithelial cells. These results suggest that CRH may play a part in the modulation of intestinal immune and inflammatory system, and as a modulator in the pathogenesis of ulcerative colitis. C1 KYOTO PREFECTURAL UNIV MED,DEPT INTERNAL MED 1,KAMIKYO KU,KYOTO 602,JAPAN. MEIJI COLL ORIENTAL MED,KYOTO,JAPAN. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NIAMS,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. NR 43 TC 106 Z9 107 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD OCT PY 1995 VL 37 IS 4 BP 544 EP 551 DI 10.1136/gut.37.4.544 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RY745 UT WOS:A1995RY74500018 PM 7489943 ER PT J AU LUBIN, JH BOICE, JD EDLING, C HORNUNG, RW HOWE, G KUNZ, W KUSIAK, RA MORRISON, HI RADFORD, EP SAMET, JM TIRMARCHE, M WOODWARD, A YAO, SX AF LUBIN, JH BOICE, JD EDLING, C HORNUNG, RW HOWE, G KUNZ, W KUSIAK, RA MORRISON, HI RADFORD, EP SAMET, JM TIRMARCHE, M WOODWARD, A YAO, SX TI RADON-EXPOSED UNDERGROUND MINERS AND INVERSE DOSE-RATE (PROTRACTION ENHANCEMENT) EFFECTS SO HEALTH PHYSICS LA English DT Article DE RADON; CANCER; LUNGS, HUMAN; EPIDEMIOLOGY ID ONCOGENIC TRANSFORMATION; LUNG-CANCER; CHARGED-PARTICLES; URANIUM MINERS; NEUTRONS; DEPENDENCE AB Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern, That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, rye evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data, There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose, As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose, Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution. C1 NCI, EPIDEMIOL & BIOSTAT PROGRAM, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. UPPSALA UNIV, DEPT OCCUPAT MED, UPPSALA, SWEDEN. NIOSH, CINCINNATI, OH 45226 USA. UNIV TORONTO, FAC MED, NATL CANC INST CANADA, EPIDEMIOL UNIT, TORONTO, ON M5S 1A8, CANADA. NATL PUBL HLTH INST, CTR RADIAT HYG, CR-10042 PRAGUE, CZECH REPUBLIC. MINIST LABOR, RES & REGULAT BRANCH, HLTH & SAFETY UNIT, TORONTO, ON M7A 1T7, CANADA. DEPT NATL HLTH & WELFARE, DIV SURVEILLANCE & RISK ASSESSEMENT, OTTAWA, ON K1A 0L2, CANADA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, BALTIMORE, MD 21205 USA. INST PROTECT & SURETE NUCL, DEPT PROTECT SANTE HOUME & DOSIMETRIE, F-92265 FONTENAY ROSES, FRANCE. UNIV ADELAIDE, DEPT COMMUNITY MED, ADELAIDE, SA, AUSTRALIA. NATL NONFERROUS MET IND CORP, GEJIU, PEOPLES R CHINA. RP LUBIN, JH (reprint author), NCI, EPIDEMIOL & BIOSTAT PROGRAM, BIOSTAT BRANCH, 6130 EXECUT BLVD, EPN-403, BETHESDA, MD 20892 USA. OI Woodward, Alistair/0000-0001-5425-6018 NR 23 TC 98 Z9 105 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD OCT PY 1995 VL 69 IS 4 BP 494 EP 500 DI 10.1097/00004032-199510000-00007 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA RX491 UT WOS:A1995RX49100008 PM 7558839 ER PT J AU FOSS, FM SAUSVILLE, EA AF FOSS, FM SAUSVILLE, EA TI PROGNOSIS AND STAGING OF CUTANEOUS T-CELL LYMPHOMA SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; CLASSIFICATION-SYSTEM; REARRANGEMENTS; DIAGNOSIS AB Staging of cutaneous T-cell lymphoma incorporates both clinical features of the disease, including type of skin involvement and adenopathy, along with histopathologic information from lymph node and bone marrow biopsies. Prognostic significance of bone marrow involvement and gene rearrangement studies on lymph node tissue are discussed, and a simplified staging evaluation is outlined. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP FOSS, FM (reprint author), BOSTON UNIV,MED CTR,MED ONCOL SECT,80 E NEWTON ST,BOSTON,MA 02118, USA. NR 22 TC 22 Z9 24 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 1995 VL 9 IS 5 BP 1011 EP & PG 0 WC Oncology; Hematology SC Oncology; Hematology GA RX256 UT WOS:A1995RX25600005 PM 8522481 ER PT J AU HOOFNAGLE, JH CONJEEVARAM, HS KLEINER, DE LAU, D DIBISCEGLIE, AM AF HOOFNAGLE, JH CONJEEVARAM, HS KLEINER, DE LAU, D DIBISCEGLIE, AM TI 2-YEAR COURSE OF RIBAVIRIN FOR CHRONIC HEPATITIS-C SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 48 EP 48 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000047 ER PT J AU CONJEEVARAM, HS BERGASA, NV KLEINER, DE SALLIE, R WELLS, M HOOFNAGLE, JH AF CONJEEVARAM, HS BERGASA, NV KLEINER, DE SALLIE, R WELLS, M HOOFNAGLE, JH TI METHOTREXATE THERAPY OF PRIMARY BILIARY-CIRRHOSIS - 2-YR STUDY COMPARING 2 DOSES SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 69 EP 69 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000072 ER PT J AU MARRONE, A KLEINER, D CONJEEVARAM, H VERGALLA, J HOOFNAGLE, JH SALLIE, R AF MARRONE, A KLEINER, D CONJEEVARAM, H VERGALLA, J HOOFNAGLE, JH SALLIE, R TI MEDIUM-TERM TREATMENT OF PBC WITH METHOTREXATE (MTX) DOES NOT INCREASE HEPATIC DNA-DAMAGE SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. NCI,EXTRACELLULAR PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 71 EP 71 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000069 ER PT J AU LAKE, JR KROM, R BELLE, S AF LAKE, JR KROM, R BELLE, S TI PREDICTIONS AND OUTCOME OF EARLY ALLOGRAFT DYSFUNCTION (EAD) FOLLOWING ORTHOTOPIC LIVER-TRANSPLANTATION (OLT) SO HEPATOLOGY LA English DT Meeting Abstract C1 MAYO CLIN,PITTSBURGH,PA. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV CALIF SAN FRANCISCO,NIDDK,LIVER TRANSPLANTAT DATABASE,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 130 EP 130 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000130 ER PT J AU EVERHART, JE LOMBARDERO, M AF EVERHART, JE LOMBARDERO, M TI ABO BLOOD-TYPE AND MORTALITY FOLLOWING ACTIVATION - WHAT IS THE EFFECT OF DELAYING ORTHOTOPIC LIVER-TRANSPLANTATION (OLT) SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDKD,LIVER TRANSPLANTAT DATABASE LTD,BETHESDA,MD 20892. UNIV PITTSBURGH,PITTSBURGH,PA 15260. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 134 EP 134 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000134 ER PT J AU BELLE, S ZETTERMAN, RK AF BELLE, S ZETTERMAN, RK TI DONOR ORGAN COLD ISCHEMIA TIME AND OUTCOME FOLLOWING LIVER-TRANSPLANTATION SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV PITTSBURGH,NIDDK LIVER TRANSPLANTAT DATABASE,PITTSBURGH,PA. UNIV NEBRASKA,MED CTR,LINCOLN,NE 68583. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 191 EP 191 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000189 ER PT J AU TEDESCHI, V MAHANEY, K CONJEEVARAM, H MAERTENS, G BEAMES, M VERGALLA, J HOOFNAGLE, JH SALLIE, R AF TEDESCHI, V MAHANEY, K CONJEEVARAM, H MAERTENS, G BEAMES, M VERGALLA, J HOOFNAGLE, JH SALLIE, R TI THE EFFECT OF ANTIVIRAL THERAPY ON HCV GENOTYPE SO HEPATOLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,DIV GASTROENTEROL,WASHINGTON,DC 20057. NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. INNOGENET,ZWIJNAARDE,BELGIUM. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 254 EP 254 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000254 ER PT J AU NAKATSUJI, Y SHIH, JWK TANAKA, E WAGES, J KIYOSAWA, K KIM, JP ALTER, HJ AF NAKATSUJI, Y SHIH, JWK TANAKA, E WAGES, J KIYOSAWA, K KIM, JP ALTER, HJ TI PREVALENCE OF HEPATITIS-G VIRUS (HGV) IN JAPAN SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. SHINSHU UNIV,MATSUMOTO,NAGANO 390,JAPAN. GENELABS TECHNOL INC,REDWOOD CITY,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 303 EP 303 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000301 ER PT J AU HAO, YW TABOR, E AF HAO, YW TABOR, E TI IDENTIFICATION OF PROTEINS FROM A HUMAN LIVER CDNA LIBRARY THAT BIND TO WILD-TYPE HUMAN P53 SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 330 EP 330 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000330 ER PT J AU KAZACHKOV, Y KHAOUSTOV, VI YOFFE, B SOLOMON, H KLINTMALM, GBG TABOR, E AF KAZACHKOV, Y KHAOUSTOV, VI YOFFE, B SOLOMON, H KLINTMALM, GBG TABOR, E TI P53 ABNORMALITIES IN HEPATOCELLULAR CARCINOMAS FROM THE UNITED-STATES SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. BAYLOR COLL MED,VAMC,HOUSTON,TX 77030. BAYLOR UNIV,MED CTR,DALLAS,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 332 EP 332 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000331 ER PT J AU HSIA, CC YUWEN, H TABOR, E AF HSIA, CC YUWEN, H TABOR, E TI GENOMIC VARIATIONS IN THE HEPATITIS-B VIRUS X GENE IN HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 345 EP 345 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000348 ER PT J AU HSIA, CC TABOR, E AF HSIA, CC TABOR, E TI DETECTION OF HEPATITIS-B VIRUS (HBV) X GENE DNA IN HEPATOCELLULAR-CARCINOMA TISSUES WITH NEGATIVE IMMUNOSTAINING FOR HEPATITIS-B SURFACE AND CORE ANTIGENS (HBSAG AND HBCAG) SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 347 EP 347 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000345 ER PT J AU HAYASHI, PH TOKIWA, T AKATSUKA, T MIHALIK, K SHERMAN, G HOOFNAGLE, JH RICE, CM AF HAYASHI, PH TOKIWA, T AKATSUKA, T MIHALIK, K SHERMAN, G HOOFNAGLE, JH RICE, CM TI HCV PROTEINS DO NOT BIND P53 OR RETINOBLASTOMA TUMOR-SUPPRESSOR PROTEINS, IN-VITRO SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 350 EP 350 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000350 ER PT J AU BOJES, HK GERMOLEC, DR BRUCCOLERI, A SCHOONHOVEN, R LUSTER, MI THURMAN, RG AF BOJES, HK GERMOLEC, DR BRUCCOLERI, A SCHOONHOVEN, R LUSTER, MI THURMAN, RG TI ANTIBODIES TO TUMOR-NECROSIS-FACTOR-ALPHA INHIBIT CELL CAUSED BY THE PEROXISOME WY-14,643 SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT ENVIRONM SCI & ENGN,CHAPEL HILL,NC 27599. NIEHS,IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 362 EP 362 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000362 ER PT J AU KUROKOHCHI, K CARRINGTON, M MANN, D SIMONIS, TB FEINSTONE, SM AKATSUKA, T BERZOFSKY, JA AF KUROKOHCHI, K CARRINGTON, M MANN, D SIMONIS, TB FEINSTONE, SM AKATSUKA, T BERZOFSKY, JA TI ANALYSIS OF GENE AND PROTEIN EXPRESSION OF HLA-CLASS-I MOLECULES AND THE TRANSPORTER ASSOCIATED WITH ANTIGEN-PROCESSING (TAP) IN HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,IMMUNOGENT SECT,FREDERICK,MD 21701. US FDA,DIV VIROL,BETHESDA,MD 20014. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1995 VL 22 IS 4 SU S BP 372 EP 372 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000371 ER PT J AU KIM, JP LINNEN, J WAGES, J SHIH, J NAKATSUJI, Y FRY, K ZHANGKECK, ZY YOUNG, L GALLAGHER, P KRAWCZYNSKI, K ISMAY, S HYAMS, C LIFSON, J ALTER, M MARGOLIS, H FOUNG, S BRADLEY, D ALTER, H AF KIM, JP LINNEN, J WAGES, J SHIH, J NAKATSUJI, Y FRY, K ZHANGKECK, ZY YOUNG, L GALLAGHER, P KRAWCZYNSKI, K ISMAY, S HYAMS, C LIFSON, J ALTER, M MARGOLIS, H FOUNG, S BRADLEY, D ALTER, H TI IDENTIFICATION OF A NEW HEPATITIS-VIRUS (HGV) AND ITS IMPLICATION IN POST TRANSFUSION HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 GENELABS TECHNOL INC,REDWOOD CITY,CA. NIH,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NSW BLOOD TRANSFUS SERV,SYDNEY,NSW,AUSTRALIA. USN,MED RES INST,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 447 EP 447 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000445 ER PT J AU SANTONIRUGIU, E PREISEGGER, KH KISS, A SCHMIDT, EV THORGEIRSSON, SS AF SANTONIRUGIU, E PREISEGGER, KH KISS, A SCHMIDT, EV THORGEIRSSON, SS TI INHIBITION OF NEOPLASTIC DEVELOPMENT IN THE LIVER BY HEPATOCYTE GROWTH-FACTOR IN A TRANSGENIC MOUSE MODEL SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 451 EP 451 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000449 ER PT J AU FARCI, P SHIMODA, A WONG, D CABEZON, T DEGIOANNIS, D STRAZZERA, A SHAPIRO, M ALTER, HJ PURCELL, RH AF FARCI, P SHIMODA, A WONG, D CABEZON, T DEGIOANNIS, D STRAZZERA, A SHAPIRO, M ALTER, HJ PURCELL, RH TI PREVENTION OF HCV INFECTION IN CHIMPANZEES BY HYPERIMMUNE SERUM AGAINST THE HYPERVARIABLE REGION-1 (HRV1) - EMERGENCE OF NEUTRALIZATION ESCAPE MUTANTS IN-VIVO SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. SMITHKLINE BEECHAM BIOL,RIXENSART,BELGIUM. UNIV CAGLIARI,DEPT INTERNAL MED,I-09124 CAGLIARI,ITALY. NIH,BETHESDA,MD 20892. BIOQUAL,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 455 EP 455 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000453 ER PT J AU FACTOR, VM JENSEN, MR THORGEIRSSON, SS AF FACTOR, VM JENSEN, MR THORGEIRSSON, SS TI IMPAIRED LIVER-REGENERATION IN TRANSGENIC MICE OVEREXPRESSING C-MYC AND TRANSFORMING GROWTH-FACTOR-ALPHA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Jensen, Michael/E-9677-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 506 EP 506 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000505 ER PT J AU THURMAN, RG IIMURO, Y BRADFORD, BU SPESANOVIC, B BRENNER, DA KADIISKA, M MASON, RP AF THURMAN, RG IIMURO, Y BRADFORD, BU SPESANOVIC, B BRENNER, DA KADIISKA, M MASON, RP TI THE PANCREAS PRODUCES ALPHA-HYDROXYETHYL RADICAL ADDUCTS DURING CHRONIC EXPOSURE TO ALCOHOL SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 549 EP 549 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000548 ER PT J AU HERION, D REYNOLD, J CONJEEVARAM, H VERGALLA, J WELLS, M HOOFNAGLE, JH SALLIE, R AF HERION, D REYNOLD, J CONJEEVARAM, H VERGALLA, J WELLS, M HOOFNAGLE, JH SALLIE, R TI VITAMIN-D-RECEPTOR (VDR) POLYMORPHISMS AND BONE-MINERAL DENSITY (BMD) IN PRIMARY BILIARY-CIRRHOSIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. NCI,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 731 EP 731 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000728 ER PT J AU LIETARD, J LEVAVASSEUR, F BURBELO, P YAMADA, Y CLEMENT, B AF LIETARD, J LEVAVASSEUR, F BURBELO, P YAMADA, Y CLEMENT, B TI A SILENCER ELEMENT IN THE LAMC1 PROMOTER CONTAINS 2 SEQUENCES, INTERACTING WITH THE LARGE SUBUNIT OF REPLICATION FACTOR-C AND FACTOR-SP1, WHICH ARE INVOLVED IN LAMININ-GAMMA-1 EXPRESSION IN FAZA-567 RAT HEPATOMA-CELL LINE SO HEPATOLOGY LA English DT Meeting Abstract C1 CHRU PONTCHAILLOU,UNITE RECH HEPATOL,INSERM,U49,F-35033 RENNES,FRANCE. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RI Burbelo, Peter/B-1027-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 782 EP 782 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000781 ER PT J AU WOITACH, JT CONNER, EA WIRTH, PJ THORGEIRSSON, SS AF WOITACH, JT CONNER, EA WIRTH, PJ THORGEIRSSON, SS TI ANALYSIS OF PROLONGED EXPOSURE TO EGF ON SIGNAL-TRANSDUCTION IN THE C-MYC TRANSGENIC MOUSE SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 795 EP 795 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000792 ER PT J AU LAU, D KLEINER, DE PARK, Y VERGALLA, J HOOFNAGLE, JH AF LAU, D KLEINER, DE PARK, Y VERGALLA, J HOOFNAGLE, JH TI LONG-TERM FOLLOW-UP OF PATIENTS WITH CHRONIC HEPATITIS-B TREATED WITH ALPHA-INTERFERON SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NCI,PATHOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 876 EP 876 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000874 ER PT J AU MORIMITSU, Y KLEINER, DE CONJEEVARAM, HS HSIA, CC DIBISCEGLIE, AM TABOR, E AF MORIMITSU, Y KLEINER, DE CONJEEVARAM, HS HSIA, CC DIBISCEGLIE, AM TABOR, E TI EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA IN THE LIVER BEFORE AND AFTER INTERFERON-ALFA THERAPY FOR CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; HEPATOCELLULAR-CARCINOMA; VIRUS; INFECTION AB The effect of interferon alfa (IFN-alpha) therapy on the expression of transforming growth factor alpha (TGF-alpha) in the liver during chronic hepatitis B was investigated. Serial fiver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-alpha for the treatment of chronic hepatitis B, Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-alpha in an avidin-biotin-peroxidase-complex system, The expression of TGF-alpha in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored, There was no significant difference in TGF-alpha expression before or after therapy between 13 patients receiving daily IFN-alpha, 13 receiving alternate-day IFN-alpha, and 9 receiving no therapy, Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients (''responders''); the 18 other patients were ''nonresponders.'' Expression of TGF-alpha before IFN-alpha therapy was significantly higher in responders than in nonresponders; after IFN-alpha therapy, TGF-alpha expression decreased significantly among responders compared with nonresponders and untreated controls, Thus, the level of expression of TGF-alpha in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-alpha therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond. C1 NCI,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. OI Kleiner, David/0000-0003-3442-4453 NR 13 TC 12 Z9 12 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 OCT PY 1995 VL 22 IS 4 BP 1021 EP 1026 DI 10.1016/0270-9139(95)90604-5 PN 1 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX924 UT WOS:A1995RX92400001 PM 7557846 ER PT J AU LOREAL, O LHELGOUALCH, A TURLIN, B CAMPION, JP UTANI, A RAMEE, MP YAMADA, Y CLEMENT, B AF LOREAL, O LHELGOUALCH, A TURLIN, B CAMPION, JP UTANI, A RAMEE, MP YAMADA, Y CLEMENT, B TI OVEREXPRESSION OF LAMININ AND COLLAGEN ALPHA-1(IV) MESSENGER-RNA IN NONTUMORAL AREAS OF LIVERS FROM PATIENTS WITH METASTASIS OR HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 CHRU PONTCHAILLOU,FAC MED,CHIRURG CLIN B,F-35033 RENNES,FRANCE. CHRU PONTCHAILLOU,FAC MED,ANAT PATHOL LAB B,F-35033 RENNES,FRANCE. CHRU PONTCHAILLOU,FAC MED,INSERM,U49,UNITE RECH HEPATOL,F-35033 RENNES,FRANCE. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RI Loreal, Olivier/G-3366-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 1048 EP 1048 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69001045 ER PT J AU MICAN, JM DIBISCEGLIE, AM FONG, TL TRAVIS, WD KLEINER, DE BAKER, B METCALFE, DD AF MICAN, JM DIBISCEGLIE, AM FONG, TL TRAVIS, WD KLEINER, DE BAKER, B METCALFE, DD TI HEPATIC INVOLVEMENT IN MASTOCYTOSIS - CLINICOPATHOLOGICAL CORRELATIONS IN 41 CASES SO HEPATOLOGY LA English DT Article ID MAST-CELL DISEASE; SYSTEMIC MASTOCYTOSIS; GENERALIZED MASTOCYTOSIS; DIFFERENTIAL-DIAGNOSIS; PORTAL-HYPERTENSION; LIVER; GRADIENT; ASCITES; SPLEEN AB Mastocytosis is a disease of mast cell hyperplasia that may involve several organ systems, including liver. Between 1988 and 1991, we conducted a retrospective-prospective study of 41 patients with mastocytosis and found 61% had evidence of liver disease. Hepatomegaly was detected in 24%, splenomegaly in 41%, and elevated serum alkaline phosphatase, serum aminotransaminases, 5'nucleotidase, or gamma-glutamyltranspeptidase (GGTP) in 54% of the patients, Alkaline phosphatase levels directly correlated with GGTP levels, hepatomegaly, splenomegaly, and liver mast cell infiltration and fibrosis. Elevated alkaline phosphatase levels and splenomegaly were observed more frequently in patients with categories II and III mastocytosis, Five patients in combined disease categories II or III developed ascites or portal hypertension and died of complications of mastocytosis; three had hypoprothrombinemia at the time of death. Thirty-five liver biopsy specimens from 25 patients were examined. Mast cell infiltration was commonly observed in the biopsy specimens, more severe in those patients with either category nor UI disease, and correlated with hepatomegaly, splenomegaly, alkaline phosphatase levels, and GGTP levels. Mast cells were often only detected by using special stains (toluidine blue and chloracetate esterase). Increased portal fibrosis was seen in 68% of the biopsy specimens and correlated with mast cell infiltration and portal inflammation. Cirrhosis was not observed. Nodular regenerative hyperplasia, portal venopathy, and venoocclusive disease was observed in eight biopsy specimens and may have been the cause of the portal hypertension or ascites in four patients, These findings demonstrate that liver disease with mast cell infiltration is a common finding in patients with mastocytosis. Severe liver disease, however, is uncommon except in patients with mastocytosis who are in categories II and III, where it may contribute to both morbidity and mortality. C1 NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RP MICAN, JM (reprint author), NIAID,CLIN INVEST LAB,ALLERG DIS SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 115231,BETHESDA,MD 20892, USA. NR 22 TC 51 Z9 54 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 BP 1163 EP 1170 DI 10.1016/0270-9139(95)90625-8 PN 1 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX924 UT WOS:A1995RX92400022 PM 7557867 ER PT J AU GOLDING, M SARRAF, CE LALANI, EN ANILKUMAR, TV EDWARDS, RJ NAGY, P THORGEIRSSON, SS ALISON, MR AF GOLDING, M SARRAF, CE LALANI, EN ANILKUMAR, TV EDWARDS, RJ NAGY, P THORGEIRSSON, SS ALISON, MR TI OVAL CELL-DIFFERENTIATION INTO HEPATOCYTES IN THE ACETYLAMINOFLUORENE-TREATED REGENERATING RAT-LIVER SO HEPATOLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; BILE-DUCTS; D-GALACTOSAMINE; HEPATITIS-B; STEM-CELLS; EXPRESSION; HEPATOCARCINOGENESIS; PROLIFERATION; TISSUES; FETOPROTEIN AB When hepatocyte regeneration after a two-thirds partial hepatectomy (PH) in rats is blocked by oral gavage of acetylaminofluorene, a proliferation of ductular cells ensues that results in a profusion of neoductules radiating from each portal tract. To examine the possibility that this population of newly emerging cells harbors cells capable of differentiating into hepatocytes, we have looked in these cells for expression of functional markers of hepatocyte commitment at both the RNA and protein levels, Expression of albumin and alpha-fetoprotein (alpha-FP) messenger RNA (mRNA) transcripts were sought in situ using antisense riboprobes, and the expression of a number of cytochrome P450 enzymes was examined immunohistochemically. Before any signs of differentiation the ductular cells strongly expressed cytokeratins 7, 8, 18, and 19 in the same manner as authentic bile ducts, but unlike the latter also expressed vimentin. lit situ hybridization studies showed that small bile ducts close to the limiting plate, as well as the newly formed ducts, expressed albumin and alpha-fetoprotein messenger RNAs, and immunocytochemistry showed that the distribution of the respective proteins was similar. Beginning at 1 week after partial hepatectomy, areas of differentiation could be found in the new ducts, with cells resembling either columnar intestinal-type epithelia or hepatocytes. Intestinal-like cells expressed neither albumin, alpha-FP, nor cytochrome P450 enzymes, whereas ductular cells appearing Like hepatocytes with the typical membranous distribution of cytokeratin 8 strongly expressed a variety of cytochrome P450 enzymes normally associated with functional hepatocytes. These observations further support the belief that reactive ductules, sprouted from small ducts, can represent an adaptive response of the Liver to replenish lost hepatocytes, although some of the newborn cells appear to differentiate along intestinal lines. C1 ROYAL POSTGRAD MED SCH,DEPT HISTOPATHOL,LONDON W12 0NN,ENGLAND. ROYAL POSTGRAD MED SCH,DEPT CLIN PHARMACOL,LONDON W12 0NN,ENGLAND. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 49 TC 130 Z9 135 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 OCT PY 1995 VL 22 IS 4 BP 1243 EP 1253 DI 10.1016/0270-9139(95)90635-5 PN 1 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX924 UT WOS:A1995RX92400032 PM 7557877 ER PT J AU GUARDIOLA, J XIOL, X ESCRIBA, JM NOLLA, JM JAURRIETTA, E SALLIE, R AF GUARDIOLA, J XIOL, X ESCRIBA, JM NOLLA, JM JAURRIETTA, E SALLIE, R TI VITAMIN-D-RECEPTOR GENE POLYMORPHISM AND BONE LOSS AFTER LIVER-TRANSPLANTATION SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. HOSP BELLVITGE & VILAFRANCA,BARCELONA,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 1267 EP 1267 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69001263 ER PT J AU CONJEEVARAM, HS EVERHART, JE HOOFNAGLE, JH AF CONJEEVARAM, HS EVERHART, JE HOOFNAGLE, JH TI PREDICTORS OF A SUSTAINED BENEFICIAL RESPONSE TO INTERFERON-ALFA THERAPY IN CHRONIC HEPATITIS-C SO HEPATOLOGY LA English DT Editorial Material ID HUMAN ALPHA-INTERFERON; NON-B HEPATITIS; TERM FOLLOW-UP; CONTROLLED TRIAL; NON-A; MULTICENTER; VIRUS C1 NIDDKD,DIV DIGEST DIS,EPIDEMIOL & CLIN TRIALS BRANCH,BETHESDA,MD 20892. RP CONJEEVARAM, HS (reprint author), NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BLDG 10,ROOM 4D52,BETHESDA,MD 20892, USA. NR 30 TC 67 Z9 67 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 OCT PY 1995 VL 22 IS 4 BP 1326 EP 1329 DI 10.1016/0270-9139(95)90646-0 PN 1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX924 UT WOS:A1995RX92400043 PM 7557888 ER PT J AU GRIFFIN, RJ BURKA, LT DEMBY, KB AF GRIFFIN, RJ BURKA, LT DEMBY, KB TI OXIDATIVE BIOTRANSFORMATION OF OXAZEPAM TO REACTIVE AND NONREACTIVE PRODUCTS IN RAT, MOUSE AND HUMAN MICROSOMES SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE OXAZEPAM; MICROSOMES; BIOTRANSFORMATION; ADDUCTS; DIHYDRODIOL ID METABOLITES; DRUGS; MICE AB 1 The oxidative metabolism of oxazepam by human, B6C3F1 mouse and F344 rat microsomes was examined. The major metabolite in all three species was 6-chloro-4-phenyl-2(1H)-quinazolinecarboxylic acid (CPQ-carboxylic acid). In addition, rat microsomes produced 4'-hydroxyoxazepam and oxazepam-dihydrodiol in NADPH-containing incubations. 2 Covalent protein adducts were increased by the addition of NADPH to rat and mouse microsomes but not human microsomes. The magnitude of adduct formation was rats > mice > humans. 3 Formation of oxazepam-dihydrodiol was reduced by the addition of cyclohexene oxide and GSH to the incubations. Two additional metabolites were produced under these conditions. One of these was tentatively identified as a GSH conjugate. Covalent adduct formation was unaffected by GSH or cyclohexene oxide. 4 These results suggest that adduct formation occurred via an unknown reactive product rather than via oxazepam-epoxide, and that the relative rates of oxidative metabolism in vitro parallel that in vivo for the three species examined. C1 UNIV N CAROLINA,SCH MED,OFF ACAD & STUDENT PROGRAMS,CHAPEL HILL,NC 27599. RP GRIFFIN, RJ (reprint author), NIEHS,CHEM BRANCH,POB 12233,MD C3-02,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD OCT PY 1995 VL 14 IS 10 BP 779 EP 786 PG 8 WC Toxicology SC Toxicology GA RZ831 UT WOS:A1995RZ83100001 PM 8562117 ER PT J AU MONOS, DS KAMOUN, M UDALOVA, IA CSANKY, E CIZMAN, B TURETSKAYA, RL SMIRNOVA, JB ZHARKOV, VG GASSER, D ZMIJEWSKI, CM SPIELMAN, RS NEDOSPASOV, SA AF MONOS, DS KAMOUN, M UDALOVA, IA CSANKY, E CIZMAN, B TURETSKAYA, RL SMIRNOVA, JB ZHARKOV, VG GASSER, D ZMIJEWSKI, CM SPIELMAN, RS NEDOSPASOV, SA TI GENETIC-POLYMORPHISM OF THE HUMAN TUMOR-NECROSIS-FACTOR REGION IN INSULIN-DEPENDENT DIABETES-MELLITUS - LINKAGE DISEQUILIBRIUM OF TNFAB MICROSATELLITE ALLELES WITH HLA HAPLOTYPES SO HUMAN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; BETA-GENE; FACTOR-ALPHA; CLASS-II; DR4 HAPLOTYPE; NOD MOUSE; LYMPHOTOXIN; ASSOCIATION; EXPRESSION; LOCUS AB The TNF region within the MHC includes a number of immunologically important genes. Microsatellites TNFa and TNFb adjacent to TNF exhibit extensive polymorphism. Employing a PCR-based technique, we identified TNFab haplotypes and defined their distribution in 97 controls and 48 diabetics of Caucasoid origin in a search for other genes within the MHC potentially associated with IDDM. Twenty-five different TNFab haplotypes were identified. A significant difference (p < 0.0005) in frequency between patients and controls was found for TNFa1b5 (relative risk 53). However, no other TNFab microsatellites demonstrated significantly different frequencies. Among diabetics TNFa1b5 was found to be in linkage disequilibrium with HLA-DR3-B18, a haplotype known to be associated with IDDM. Thus the increased frequency of TNFalb5 among diabetics could reflect a linkage disequilibrium with a gene within the TNF region or with other genes, including the HLAs, which characterite this haplotype. In both controls and diabetics TNFa2b3 and TNFa7b4 were in linkage disequilibrium with DR3-B8 and DR7, respectively. Among diabetics, TNFa2b1 and TNFa6b5 were in linkage disequilibrium with DR4-B62 and DR4-B44, respectively. It is intriguing that TNFab haplotypes, represented by a short piece of about 200 nucleotides in the untranslated region upstream of TNF beta gene, maintain strong linkage disequilibria with different HLA haplotypes extending over 1 million base pairs. The identification of TNFab microsatellites exhibiting a high polymorphic index in a region lacking known polymorphic markers may provide potentially important information regarding the association of HLA haplotypes with autoimmune diseases, as they are in close proximity to other genes of immunologic importance. C1 UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. RUSSIAN ACAD SCI,ENGELHARDT INST MOLEC BIOL,MOSCOW,RUSSIA. RUSSIAN ACAD SCI,INST GENE BIOL,MOSCOW,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BCDP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BRMP,LMI,FREDERICK,MD 21702. RP MONOS, DS (reprint author), UNIV PENN,MED CTR,SEVEN FOUNDERS,DEPT PATHOL & LAB MED,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU NIDCR NIH HHS [DE09164]; NIDDK NIH HHS [DK38011, DK35047] NR 53 TC 65 Z9 65 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 1995 VL 44 IS 2 BP 70 EP 79 DI 10.1016/0198-8859(95)00060-H PG 10 WC Immunology SC Immunology GA RY884 UT WOS:A1995RY88400002 PM 8847231 ER PT J AU WALKER, GJ HUSSUSSIAN, CJ FLORE, JF GLENDENING, JM HALUSKA, FG DRACOPOLI, NC HAYWARD, NK FOUNTAIN, JW AF WALKER, GJ HUSSUSSIAN, CJ FLORE, JF GLENDENING, JM HALUSKA, FG DRACOPOLI, NC HAYWARD, NK FOUNTAIN, JW TI MUTATIONS OF THE CDKN2/P16(INK4) GENE IN AUSTRALIAN MELANOMA KINDREDS SO HUMAN MOLECULAR GENETICS LA English DT Article ID FAMILIAL MELANOMA; LINKAGE; MLM; LOCUS; NEVUS AB The cyclin dependent kinase inhibitor 2 (CDKN2) gene on chromosome 9p21 is potentially involved in the genesis of many cancers and is currently under intense investigation as a possible melanoma susceptibility locus. We have analyzed 18 Australian melanoma kindreds for mutations within the coding and neighboring splice junction portions of the CDKN2 gene. In seven kindreds (including our six largest), CDKN2 mutations were found to segregate with the putative melanoma chromosome previously assigned by 9p haplotype analysis. These changes included the duplication of a 24 bp repeat, a deleted C residue resulting in the introduction of a premature stop codon, and four single basepair changes causing amino acid substitutions. Mutations segregated to 46 of 51 affected individuals in these seven kindreds, with three apparent sporadic cases in one family and one in each of another two families. Penetrance was variable (55-100%) among the different mutations. These data provide additional strong support that the CDKN2 gene is the chromosome 9p21 familial melanoma locus. C1 QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. NIH,NCHGR,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. MASSACHUSETTS GEN HOSP,DEPT ONCOL,BOSTON,MA 02114. SEQUANA THERAPEUT INC,LA JOLLA,CA 92037. RP WALKER, GJ (reprint author), UNIV SO CALIF,INST MED GENET,DEPT BIOCHEM & MOLEC BIOL,2011 ZONAL AVE HMR601,LOS ANGELES,CA 90033, USA. RI hayward, nicholas/C-1367-2015 OI hayward, nicholas/0000-0003-4760-1033 NR 33 TC 132 Z9 133 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1995 VL 4 IS 10 BP 1845 EP 1852 DI 10.1093/hmg/4.10.1845 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RZ885 UT WOS:A1995RZ88500004 PM 8595405 ER PT J AU LESPERANCE, MM HALL, JW BESS, FH FUKUSHIMA, K JAIN, PK PLOPLIS, B AGUSTIN, TBS SKARKA, H SMITH, RJH WILLS, M WILCOX, ER AF LESPERANCE, MM HALL, JW BESS, FH FUKUSHIMA, K JAIN, PK PLOPLIS, B AGUSTIN, TBS SKARKA, H SMITH, RJH WILLS, M WILCOX, ER TI A GENE FOR AUTOSOMAL-DOMINANT NONSYNDROMIC HEREDITARY HEARING IMPAIRMENT MAPS TO 4P16.3 SO HUMAN MOLECULAR GENETICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; HUMAN GENOME; LINKAGE ANALYSIS; DEAFNESS; REGION; EXPRESSION; LOCUS AB Mapping genes for nonsyndromic hereditary hearing impairment may lead to identification of genes that are essential for the development and preservation of hearing. We studied a family with autosomal dominant, progressive, low frequency sensorineural hearing loss. Linkage analysis employing microsatellite polymorphic markers revealed a fully linked marker (D4S126) at 4p16.3, a gene-rich region containing IT15, the gene for Huntington's disease (HD). For D4S126, the logarithm-of-odds (led) score was 3.64 at theta = 0, and the overall maximum lod score was 5.05 at theta = 0.05 for D4S412. Analysis of recombinant individuals maps the disease gene to a 1.7 million base pair (Mb) region between D4S412 and D4S432, Genes for two types of mutant mice with abnormal cochleovestibular function, tilted (tit) and Bronx waltzer (by), have been mapped to the syntenic region of human 4p16.3 on mouse chromosome 5. Further studies with the goals of cloning a gene for autosomal nonsyndromic hearing impairment and identifying the murine homologue may explain the role of this gene in the development and function of the cochlea. C1 NIDOCD,MOLEC GENET LAB,ROCKVILLE,MD 20850. VANDERBILT UNIV,SCH MED,DIV HEARING & SPEECH SCI,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT OTOLARYNGOL,NASHVILLE,TN 37212. BILL WILKERSON CTR,NASHVILLE,TN 37212. UNIV IOWA,DEPT OTOLARYNGOL,MOLEC OTOLARYNGOL RES LABS,IOWA CITY,IA 52242. NATL INST DISABIL & REHABIL RES,WASHINGTON,DC 20202. NR 58 TC 70 Z9 73 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1995 VL 4 IS 10 BP 1967 EP 1972 DI 10.1093/hmg/4.10.1967 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RZ885 UT WOS:A1995RZ88500022 PM 8595423 ER PT J AU KWAN, SP HAGEMANN, TL BLAESE, RM KNUTSEN, A ROSEN, FS AF KWAN, SP HAGEMANN, TL BLAESE, RM KNUTSEN, A ROSEN, FS TI SCANNING OF THE WISKOTT-ALDRICH SYNDROME (WAS) GENE - IDENTIFICATION OF 18 NOVEL ALTERATIONS INCLUDING A POSSIBLE MUTATION HOTSPOT AT ARG86 RESULTING IN THROMBOCYTOPENIA, A MILD WAS PHENOTYPE SO HUMAN MOLECULAR GENETICS LA English DT Article ID LOCALIZATION; MARKERS; DEFECT; LOCUS; TIMP C1 NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. ST LOUIS UNIV,HLTH SCI CTR,DEPT PEDIAT,ST LOUIS,MO 63104. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP KWAN, SP (reprint author), RUSH MED SCH,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612, USA. FU NCRR NIH HHS [RR02172]; NIAID NIH HHS [AI31587, AI31541] NR 22 TC 38 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1995 VL 4 IS 10 BP 1995 EP 1998 DI 10.1093/hmg/4.10.1995 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RZ885 UT WOS:A1995RZ88500029 PM 8595430 ER PT J AU YU, SH YU, DW HAINLINE, BE BRENER, JL WILSON, KA WILSON, LC OUDELUTTIKHUIS, ME TREMBATH, RC WEINSTEIN, LS AF YU, SH YU, DW HAINLINE, BE BRENER, JL WILSON, KA WILSON, LC OUDELUTTIKHUIS, ME TREMBATH, RC WEINSTEIN, LS TI A DELETION HOT-SPOT IN EXON-7 OF THE G(S)ALPHA GENE (GNAS1) IN PATIENTS WITH ALBRIGHT HEREDITARY OSTEODYSTROPHY SO HUMAN MOLECULAR GENETICS LA English DT Article ID STIMULATORY G-PROTEIN; GRADIENT GEL-ELECTROPHORESIS; NUCLEOTIDE-BINDING PROTEIN; ALPHA-SUBUNIT GENE; ADENYLYL CYCLASE; PSEUDOHYPOPARATHYROIDISM; MUTATIONS C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. INDIANA UNIV,DEPT PEDIAT,INDIANAPOLIS,IN 46202. NEW YORK MED COLL,METROPOLITAN HOSP,NEW YORK,NY 10029. CARLE CLIN ASSOC,URBANA,IL 61801. UNIV LEICESTER,DEPT MED & THERAPEUT,LEICESTER LE1 7RH,LEICS,ENGLAND. UNIV LEICESTER,DEPT GENET,LEICESTER LE1 7RH,LEICS,ENGLAND. RI Weinstein, Lee/I-5575-2015 NR 17 TC 47 Z9 48 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1995 VL 4 IS 10 BP 2001 EP 2002 DI 10.1093/hmg/4.10.2001 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RZ885 UT WOS:A1995RZ88500031 PM 8595432 ER PT J AU ARBER, DA KAMEL, OW VANDERIJN, M DAVIS, RE MEDEIROS, LJ JAFFE, ES WEISS, LM AF ARBER, DA KAMEL, OW VANDERIJN, M DAVIS, RE MEDEIROS, LJ JAFFE, ES WEISS, LM TI FREQUENT PRESENCE OF THE EPSTEIN-BARR-VIRUS IN INFLAMMATORY PSEUDOTUMOR SO HUMAN PATHOLOGY LA English DT Article DE INFLAMMATORY PSEUDOTUMOR; PLASMA CELL GRANULOMA; LYMPH NODE; SPLEEN; LIVER; EPSTEIN-BARR VIRUS ID PLASMA-CELL GRANULOMA; LYMPH-NODES; SPLEEN; LIVER; LUNG; PNEUMONIA AB Inflammatory pseudotumor is a presumably nonneoplastic, hematopoietic, and spindled fibrous proliferation that may occur at a variety of anatomic sites. The origin of these proliferations is generally unknown. To evaluate the role of the Epstein-Barr virus (EBV) in inflammatory pseudotumor, 18 specimens from 17 patients were studied by in situ hybridization for EBV ribonucleic acid (RNA), and the morphological and immunologic characteristics of the infected cells were evaluated. These specimens included 10 lymph nodes, six splenic masses, and two hepatic masses. Overall, EBV RNA was detected in 41.2% (seven of 18) of the cases. These included two of 10 (20%) lymph nodes, four of six (66.7%) splenic pseudotumors, and one of two (50%) hepatic lesions. The degree of EBV infection was significantly greater within the tumors in comparison with the surrounding, uninvolved tissue. Two morphologically different EBV-positive cell types, spindled and round cells, were evident, and the infected cell type differed significantly when the nodal and extranodal cases were compared. All of the positive extranodal cases shown, numerous EBV-positive spindled cells, whereas no positive spindle cells (only positive round cells, morphologically consistent with lymphocytes) were noted in the two EBV-positive lymph node pseudotumors. Double-labeling immunohistochemical and in situ hybridization studies in some cases identified rare EBV-positive B cells and rare EBV positive T cells in four and three cases, respectively. Most EBV-positive cells in all cases failed to immunoreact with any B- or T-cell markers. Three of five cases studied, however, did show a subpopulation of smooth muscle actin/EBV-positive spindled cells, five of seven cases showed vimentin/EBV-positive spindled cells, and one of four cases had EBV-positive spindled cells that inmunoreacted as follicular dendritic cells. These results suggest that EBV plays a role in a significant number of cases of inflammatory pseudotumor with differences in the incidence of EBV infection and the cell type (spindled vs round cell) infected when extranodal and nodal cases are compared, suggesting a difference in pathogenesis. The cell type infected in extranodal eases seemed to be of mesenchymal origin but could not be clearly defined. Copyright (C) 1995 by W.B. Saunders Company C1 TEXAS A&M UNIV,SCOTT & WHITE MEM HOSP,COLL MED,HLTH SCI CTR,DEPT PATHOL,TEMPLE,TX 76508. STANFORD UNIV,MED CTR,STANFORD,CA 94305. RHODE ISL HOSP,PROVIDENCE,RI 02902. NCI,HEMATOPATHOL SECT,BETHESDA,MD 20892. RP ARBER, DA (reprint author), CITY HOPE NATL MED CTR,1500 E DUARTE RD,DUARTE,CA 91010, USA. FU NCI NIH HHS [CA 50341] NR 26 TC 204 Z9 210 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 1995 VL 26 IS 10 BP 1093 EP 1098 DI 10.1016/0046-8177(95)90271-6 PG 6 WC Pathology SC Pathology GA RZ220 UT WOS:A1995RZ22000007 PM 7557942 ER PT J AU MORIMITSU, Y HSIA, CC KOJIRO, M TABOR, E AF MORIMITSU, Y HSIA, CC KOJIRO, M TABOR, E TI NODULES OF LESS-DIFFERENTIATED TUMOR WITHIN OR ADJACENT TO HEPATOCELLULAR-CARCINOMA - RELATIVE EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND ITS RECEPTOR IN THE DIFFERENT AREAS OF TUMOR SO HUMAN PATHOLOGY LA English DT Article DE CARCINOGENESIS; EPIDERMAL GROWTH FACTOR RECEPTOR; HEPATITIS B SURFACE ANTIGEN; HEPATITIS B VIRUS; TRANSFORMING GROWTH FACTOR ALPHA ID HEPATITIS-B; DEVELOPMENTAL EXPRESSION; HIGH PREVALENCE; MESSENGER-RNA; CELL-LINES; LIVER; EGF; FAMILY; VIRUS AB Expression of transforming growth factor-alpha (TGF-alpha) and its receptor, the epidermal growth factor receptor (EGFR), in hepatocellular carcinomas (HCCs) and adjacent nontumorous livers from 25 Japanese patients were examined using immunoperoxidase staining of paraffin-embedded sections. TGF-alpha was detected in 24 of 25 (96%) HCCs and 23 of 24 (96%) available adjacent nontumorous livers. EGFR was detected in 16 of 25 (64%) HCCs and 17 of 24 (71%) adjacent nontumorous livers, TGF-alpha and EGFR were not detected by immunohistochemical staining in normal livers. Fifteen of 25 HCCs contained an apparent area of a second tumor (two of the 15 also contained a third tumor) that had a less-differentiated histological grade developing within or adjacent to the first tumor. In those cases, staining in the less-differentiated area of tumor was usually less intense than in the more highly differentiated area (80% of cases for TGF-alpha; 91% for EGFR). These data confirm that increased expression of TGF-alpha and EGFR occur frequently in human HCC. Furthermore, the detection of greater staining in more highly differentiated portions of the tumors suggests that increased expression of TGF-alpha and EGFR may be events of the early stages of human hepatocarcinogenesis. C1 NCI,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. KURUME UNIV,SCH MED,DEPT PATHOL 1,KURUME,FUKUOKA 830,JAPAN. NR 28 TC 67 Z9 67 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 1995 VL 26 IS 10 BP 1126 EP 1132 DI 10.1016/0046-8177(95)90275-9 PG 7 WC Pathology SC Pathology GA RZ220 UT WOS:A1995RZ22000011 PM 7557946 ER PT J AU KASHMIRI, SVS SHU, L PADLAN, EA MILENIC, DE SCHLOM, J HAND, PH AF KASHMIRI, SVS SHU, L PADLAN, EA MILENIC, DE SCHLOM, J HAND, PH TI GENERATION, CHARACTERIZATION, AND IN-VIVO STUDIES OF HUMANIZED ANTICARCINOMA ANTIBODY CC49 SO HYBRIDOMA LA English DT Article ID MURINE MONOCLONAL-ANTIBODY; RESHAPING HUMAN-ANTIBODIES; 3-DIMENSIONAL STRUCTURE; IMMUNE-RESPONSE; HYPERVARIABLE REGIONS; BINDING-PROPERTIES; CRYSTAL-STRUCTURE; ANTIGEN COMPLEX; MOUSE; CELLS AB Monoclonal antibody (MAb) CC49 reacts with tumor-associated glycoprotein (TAG)-72, a human pancarcinoma antigen, In clinical trials, radiolabeled CC49 has shown excellent turner localization; however, many of the patients receiving MAb CC49 develop a human antimouse antibody response, In an attempt to prevent this antiimmunoglobulin response, we have developed a humanized CC49 (HuCC49) by grafting the MAb CC49 hypervariable regions onto the variable light (V-L) and variable heavy (V,) frameworks of the human MAbs LEN and 21/28' CL, respectively, while retaining those murine framework residues that may be required for the integrity of the antigen combining-site structure, The HuCC49 MAb was compared with native murine CC49 (nCC49) and chimeric CC49 (cCC49), using a variety of assays, SDS-PAGE analysis under nonreducing conditions showed that the HuCC49 MAb has virtually identical mobility to that of cCC49, Under reducing conditions, the HuCC49 yielded two bands of approximate to 25-28 and approximate to 50-55 kDa, characteristic of heavy and light immunoglobulin chains, In competition radioimmunoassays, HuCC49 completely inhibited the binding of I-125-labeled nCC49 to TAG-72, although 23- to 30-fold more HuCC49 was required to achieve a level of competition similar to those of cCC49 and nCC49, The relative affinity of HuCC49 was 2- to 3-fold less than those of the cCC49 and nCC49 MAbs, respectively, The plasma clearance in mice of HuCC49 was virtually identical to that of cCC49, Biodistribution studies demonstrated equivalent tumor-targeting of HuCC49 and cCC49 to human colon carcinoma xenografts, These studies thus suggest that HuCC49 and genetically modified molecules, such as sFv and domain-deleted immunoglobulins developed by using the HuCC49 variable region as a cassette, may be potentially useful in both diagnostic and therapeutic clinical trials in patients with TAG-72-positive tumors. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 55 TC 65 Z9 66 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD OCT PY 1995 VL 14 IS 5 BP 461 EP 473 DI 10.1089/hyb.1995.14.461 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA TC622 UT WOS:A1995TC62200006 PM 8575795 ER PT J AU SCHLOM, J AF SCHLOM, J TI HUMANIZED (HU) CC49 ANTIGEN IS TUMOR-ASSOCIATED GLYCOPROTEIN (TAG)-72 SO HYBRIDOMA LA English DT Note RP SCHLOM, J (reprint author), NCI,LTIB,10-8B07,10 CTR DR MSC 1750,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD OCT PY 1995 VL 14 IS 5 BP 516 EP 516 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA TC622 UT WOS:A1995TC62200025 ER PT J AU UNSER, M THEVENAZ, P YAROSLAVSKY, L AF UNSER, M THEVENAZ, P YAROSLAVSKY, L TI CONVOLUTION-BASED INTERPOLATION FOR FAST, HIGH-QUALITY ROTATION OF IMAGES SO IEEE TRANSACTIONS ON IMAGE PROCESSING LA English DT Article ID DESIGN AB This paper focuses on the design of fast algorithms for rotating images and preserving high quality, The basis for the approach is a decomposition of a rotation into a sequence of one-dimensional translations, As the accuracy of these operations is critical, we introduce a general theoretical framework that addresses their design and performance. We also investigate the issue of optimality and present an improved least-square formulation of the problem, This approach leads to a separable three-pass implementation of a rotation using one-dimensional convolutions only, We provide explicit filter formulas for several continuous signal models including spline and bandlimited representations. Finally, we present rotation experiments and compare the currently standard techniques with the various versions of our algorithm, Our results indicate that the present algorithm in its higher-order versions outperforms all standard high-accuracy methods of which we are aware, both in terms of speed and quality, Its computational complexity increases linearly with the order of accuracy, The best-quality results are obtained with the sine-based algorithm, which can be implemented using simple one-dimensional FFT's. RP UNSER, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008 NR 25 TC 105 Z9 112 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 1057-7149 J9 IEEE T IMAGE PROCESS JI IEEE Trans. Image Process. PD OCT PY 1995 VL 4 IS 10 BP 1371 EP 1381 DI 10.1109/83.465102 PG 11 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA RY664 UT WOS:A1995RY66400003 PM 18291969 ER PT J AU ROSE, NR POTTER, M AF ROSE, NR POTTER, M TI THE SILICONE CONTROVERSY - TOWARDS A RESOLUTION SO IMMUNOLOGY TODAY LA English DT Editorial Material AB Silicones have achieved widespread rise, particularly in breast implants. Once considered inert, certain silicon products can induce chronic inflammation and enhance immune responses to foreign antigens in experimental animals. A recent workshop* discussed the immunological effects of silicones. C1 NCI,BETHESDA,MD 20892. RP ROSE, NR (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOLEC MICROBIOL & IMMUNOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD OCT PY 1995 VL 16 IS 10 BP 459 EP 460 DI 10.1016/0167-5699(95)80026-3 PG 2 WC Immunology SC Immunology GA RX838 UT WOS:A1995RX83800001 PM 7576046 ER PT J AU FERRONE, S MARINCOLA, FM AF FERRONE, S MARINCOLA, FM TI LOSS OF HLA CLASS-I ANTIGENS BY MELANOMA-CELLS - MOLECULAR MECHANISMS, FUNCTIONAL-SIGNIFICANCE AND CLINICAL RELEVANCE SO IMMUNOLOGY TODAY LA English DT Review ID BETA-2-MICROGLOBULIN MESSENGER-RNA; TUMOR-ASSOCIATED ANTIGENS; HUMAN-MALIGNANT-MELANOMA; MONOCLONAL-ANTIBODIES; C-MYC; LEUKOCYTE ANTIGEN; B2M GENE; EXPRESSION; LYSIS; LYMPHOCYTES AB Malignant transformation of melanocytes may be associated with changes in the expression of major histocompatibility complex (MHC) HLA class I antigens. Interest in the characterization of abnormalities in the expression of MHC class I by melanoma cells has been rekindled by the current emphasis on the application of T-cell-based immunotherapy to melanoma. Here, Soldano Ferrone and Francesco Marincola review defects in class I expression as described in melanoma cells, as well as the molecular mechanisms, functional significance and clinical implications of such defects. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP FERRONE, S (reprint author), NEW YORK MED COLL,DEPT MICROBIOL & IMMUNOL,VALHALLA,NY 10595, USA. FU NCI NIH HHS [CA67108, CA51814, CA37959] NR 57 TC 409 Z9 415 U1 4 U2 8 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 OCT PY 1995 VL 16 IS 10 BP 487 EP 494 DI 10.1016/0167-5699(95)80033-6 PG 8 WC Immunology SC Immunology GA RX838 UT WOS:A1995RX83800008 PM 7576053 ER PT J AU DiPietro, JA Suess, PE Wheeler, JS Smouse, PH Newlin, DB AF DiPietro, JA Suess, PE Wheeler, JS Smouse, PH Newlin, DB TI Reactivity and regulation in cocaine-exposed neonates SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article; Proceedings Paper CT 9th Biennial International Conference on Infant Studies CY JUN 02-09, 1994 CL PARIS, FRANCE DE neonate; cocaine; terotogen; vagal tone; behavioral state ID HEART-RATE; PERINATAL COCAINE; PRENATAL EXPOSURE; PRETERM INFANTS; 1ST MONTH; PREGNANCY; ALCOHOL; BEHAVIOR; VULNERABILITY; PATTERNS AB This study examined behavioral and physiologic regulation in 14 full-term neonates who were exposed to cocaine antenatally. A group of 14 non-cocaine-exposed infants served as controls. Data on behavioral state, cardiac patterning (heart period and vagal tone), and habituation to a standardized stimulus were collected. There were no differences between cocaine-exposed and nonexposed infants in heart period or vagal tone during an undisturbed period. There were significant differences in behavioral state regulation: Cocaine-exposed infants displayed significantly greater state lability and shorter sleep bouts, fussed or cried more often, and spent less time asleep and more time in transitional states. Both groups responded to an auditory stimulus with shorter heart period, but cocaine-exposed neonates demonstrated a larger response. In addition, cocaine-exposed neonates displayed less behavioral response decrement to repeated presentations of the stimulus. Although there are limitations to attribution of these results to cocaine alone, the results are discussed in relation to prevailing clinical impressions of cocaine-exposed neonates. C1 NIDA,BETHESDA,MD. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. RP DiPietro, JA (reprint author), JOHNS HOPKINS UNIV,DEPT MATERNAL & CHILD HLTH,624 N BROADWAY,BALTIMORE,MD 21205, USA. NR 31 TC 41 Z9 41 U1 2 U2 3 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PD OCT-DEC PY 1995 VL 18 IS 4 BP 407 EP 414 DI 10.1016/0163-6383(95)90030-6 PG 8 WC Psychology, Developmental SC Psychology GA TQ370 UT WOS:A1995TQ37000003 ER PT J AU PERLMANN, H KUMAR, S VINETZ, JM KULLBERG, M MILLER, LH PERLMANN, P AF PERLMANN, H KUMAR, S VINETZ, JM KULLBERG, M MILLER, LH PERLMANN, P TI CELLULAR MECHANISMS IN THE IMMUNE-RESPONSE TO MALARIA IN PLASMODIUM VINCKEI-INFECTED MICE SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CD4+ T-CELLS; INTERFERON-GAMMA; MURINE MALARIA; SCHISTOSOMA-MANSONI; CYTOKINE PRODUCTION; MONOCLONAL-ANTIBODY; CHABAUDI-CHABAUDI; CEREBRAL MALARIA; DEFICIENT MICE AB Infection of mice with the malaria parasite Plasmodium vinckei vinckei is 100% lethal. However, after two infections followed by drug cure, BALB/c mice develop a solid immunity which is antibody independent but mediated by CD4(+) T cells. To elucidate the mechanisms of this immunity, spleen cells from immune mice were challenged in vitro with lysates of P. vinckei-infected or uninfected erythrocytes. The parasite antigen induced proliferation of T cells from immune mice but not from nonimmune mice. When gamma interferon production by cells from immune mice was assayed at the single-cell level, 1 to 3 cells per 1,000 cells were found to release this cytokine when exposed to antigen. In contrast, the numbers of interleukin 4 (IL-4)-producing cells from both immune and control mice were less than or equal to 4 per 10(6) cells, regardless of antigen exposure. Investigation in a bioassay showed that P. vinckei antigen induced the release of IL-4 from spleen cells of immune mice but not from those of control mice. Nevertheless, that IL-4 is of minor significance in this system is also suggested by the absence of elevation of immunoglobulin E levels in blood samples from these mice, in contrast to what is seen with P. chabaudi infection, in which IL-4-producing Th2 cells are of major importance for immunity during later phases of infection. Taken together, the present results indicate that immunity to P. vinckei is a Th1 response, with gamma interferon being an important protective factor. Whether or not the Th1 response, through overproduction of tumor necrosis factor alpha, is also responsible for pathology and death in this infection remains to be clarified. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP PERLMANN, H (reprint author), UNIV STOCKHOLM,DEPT IMMUNOL,S-10691 STOCKHOLM,SWEDEN. OI Vinetz, Joseph/0000-0001-8344-2004 NR 55 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1995 VL 63 IS 10 BP 3987 EP 3993 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW006 UT WOS:A1995RW00600034 PM 7558309 ER PT J AU GU, XX TSAI, CM APICELLA, MA LIM, DJ AF GU, XX TSAI, CM APICELLA, MA LIM, DJ TI QUANTITATION AND BIOLOGICAL PROPERTIES OF RELEASED AND CELL-BOUND LIPOOLIGOSACCHARIDES FROM NONTYPABLE HAEMOPHILUS-INFLUENZAE SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL OTITIS-MEDIA; MIDDLE-EAR EFFUSIONS; HEMOPHILUS-INFLUENZAE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; POLYACRYLAMIDE GELS; LIPOPOLYSACCHARIDE; ENDOTOXIN; HETEROGENEITY; INOCULATION AB Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing otitis media in children. NTHi releases lipooligosaccharide (LOS) as outer membrane fragments during its growth. The release of LOS may play an important role in the pathogenicity of otitis media caused by this organism. The amounts of LOS in bacterial cells and growth media for five NTHi strains were determined by quantitative silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These strains were estimated to have 1.6 x 10(6) to 4.8 x 10(6) LOS molecules per bacterium, During a 3-day growth period, these NTHi strains released variable but significant amounts of LOS into the growth medium. Cells started to release detectable amounts of LOS into the medium st 2 to 5 h and continued to do so for up to 48 or 72 h. The concentrations of LOS in the culture supernatants released by these five strains were 10 to 55 mu g/ml at 24 h and 40 to 100 mu g/ml at 72 h, which was 34 to 189% of the cell-bound LOS concentration, The biological properties of released and cell-bound LOSs from two representative strains were compared. Released LOS showed an approximately 10-fold increase in inducing human monocytes to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6, a 13- to 28-fold increase in mouse lethal toxicity, and a 16- to 37-fold increase in the clotting of Limulus amebocyte lysate, These results suggested that released LOS or its inflammatory mediators play a more important role than the LOS in bacteria in the pathogenicity of otitis media caused by this organism. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. UNIV IOWA,DEPT MICROBIOL,IOWA CITY,IA 52242. RP GU, XX (reprint author), NIDCD,CELLULAR BIOL LAB,BLDG 29,ROOM 402,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01 AI24616] NR 57 TC 40 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1995 VL 63 IS 10 BP 4115 EP 4120 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW006 UT WOS:A1995RW00600052 PM 7558327 ER PT J AU KOLOBOW, T GIACOMINI, M REALIFORSTER, C TRAWOGER, R AF KOLOBOW, T GIACOMINI, M REALIFORSTER, C TRAWOGER, R TI THE CURRENT STATUS OF INTRACHEAL-PULMONARY VENTILATION (ITPV) SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article; Proceedings Paper CT 4th European Congress of Extracorporeal Life Support CY MAY 10-12, 1995 CL BERGAMO, ITALY ID MECHANICAL VENTILATION; LUNG INJURY; PRESSURE RP KOLOBOW, T (reprint author), NHLBI,PULM & CARDIAC ASSIST DEVICES SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 5D17,BETHESDA,MD 20892, USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD OCT PY 1995 VL 18 IS 10 BP 670 EP 673 PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA TG728 UT WOS:A1995TG72800019 PM 8647600 ER PT J AU WERNER, H HERNANDEZSANCHEZ, C KARNIELI, E LEROITH, D AF WERNER, H HERNANDEZSANCHEZ, C KARNIELI, E LEROITH, D TI THE REGULATION OF IGF-I RECEPTOR GENE-EXPRESSION SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE INSULIN-LIKE GROWTH FACTOR I (IGF-I) RECEPTOR; GENE EXPRESSION; PROMOTER; TRANSCRIPTION FACTORS; DEVELOPMENT ID GROWTH FACTOR-I; HUMAN-BREAST-CANCER; PROMOTER REGION; WILMS-TUMOR; INSULIN; BINDING; KIDNEY; CLONING; SERUM; CELLS AB The insulin-like growth factor I (IGF-I) receptor mediates most of the biological effects of IGF-I and -II. Despite its structural similarity to the insulin receptor, the IGF-I receptor is mainly involved in the transduction of growth and differentiation types of signals. The IGF-I receptor gene is constitutively expressed by most cells in the organism as well as in culture, consistent with the role of the IGFs as survival factors. In addition, the expression of the IGF-I receptor gene is modulated by a number of physiological and pathological factors, including developmental stage, nutritional status, hormones, growth disorders and malignancy. The regulatory region of the IGF-I receptor gene has been characterized and shown to display a high level of basal promoter activity. Transcription factor Sp1 is a strong activator of IGF-I receptor gene expression, whereas tumor suppressor WT1 represses its activity. The biological implications of these findings in both normal development and disease are described in this review. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20876. RI Hernandez Sanchez, Catalina/N-1737-2014 OI Hernandez Sanchez, Catalina/0000-0002-0846-5019 NR 46 TC 37 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD OCT PY 1995 VL 27 IS 10 BP 987 EP 994 DI 10.1016/1357-2725(95)00074-Y PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TB582 UT WOS:A1995TB58200001 PM 7497000 ER PT J AU Ciatto, S Bonardi, R Mazzotta, A Santoni, R AF Ciatto, S Bonardi, R Mazzotta, A Santoni, R TI Reliability of volume or age-adjusted prostate specific antigen to improve diagnostic accuracy SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE prostate cancer; diagnosis; prostate specific antigen ID SERUM AB Prostate Specific Antigen (PSA), PSA density, PSA excess, and PSA age-specific range have been compared in 331 subjects (35 cancers, 296 benign) with equivocal findings at screening by PSA or palpation + transrectal ultrasonography. The specificity of PSA using a cut-off of 4 ng/ml was only 0.49. A cutoff of 10 ng/ml improved the specificity to 0.88 but the sensitivity decreased from 0.97 to 0.63. The sensitivity and specificity for. PSA density (cutoff 0.15), PSA excess (cutoff -5), and age-specific range were 0.86 and 0.80, 0.80 and 0.82, and 0.91 and 0.67, respectively. Avoided benign biopsies vs missed cancers on the basis of PSA density:, PSA excess and PSA age-specific range would have been 19 and 5, 26 and 7, and 16 and 3, respectively. Methods adjusting for prostate volume allow a better interpretation of PSA values and may reduce the benign biopsy rate, bur the consequent cost of delayed cancer diagnoses when the choice of biopsy is based only on these methods seems unacceptable. C1 NATL CANC INST,GENOA,ITALY. SS ANNUNZIATA HOSP,CENT LAB,FLORENCE,ITALY. RP Ciatto, S (reprint author), CTR STUDIO & PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. NR 6 TC 4 Z9 4 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD OCT-DEC PY 1995 VL 10 IS 4 BP 226 EP 228 PG 3 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA TQ115 UT WOS:A1995TQ11500007 PM 8750650 ER PT J AU ZAWIA, NH HARRY, GJ AF ZAWIA, NH HARRY, GJ TI EXPOSURE TO LEAD-ACETATE MODULATES THE DEVELOPMENTAL EXPRESSION OF MYELIN GENES IN THE RAT FRONTAL-LOBE SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE PB; MYELIN; MESSENGER-RNA; FRONTAL LOBE; DEVELOPMENT ID MESSENGER-RNAS; PROTEOLIPID PROTEIN; BRAIN; HYPOMYELINATION; NEUROTOXICITY; HYBRIDIZATION; MECHANISMS AB Postnatal exposure to high levels (4%) of lead (Pb) have been shown to disrupt myelin formation and result in abnormal conduction of nerve impulses, components necessary for information processing in the CNS. To investigate whether the pathological changes in myelin, due to Pb exposure, might be partially mediated by modulations of the expression of genes involved in CNS myelin, we have examined the developmental profiles of the proteolipid protein (PLP) and myelin basic protein (MBP), two major structural constituents of CNS myelin and 2',3'-cyclic nucleotide 3' phosphodiesterase (CNP), a non-structural enzyme associated with myelin formation. Rat pups were postnatally exposed, from birth to weaning, to moderate amounts of Pb (0.2%), in the drinking water of the dam, and their frontal cortices were assayed for changes in the expression profile of the above genes by Northern Analysis. On PND 20, Pb resulted in a dramatic stimulation of the mRNA levels of PLP and a small increase in MBP mRNA levels, but had no effect on the CNP message. These data suggest that moderate levels of Pb selectively interfere with the gene expression of structural proteins of CNS myelin and may thus influence the composition of myelin in this way. C1 NIEHS,BIOCHEM RISK ASSESSMENT LAB,RES TRIANGLE PK,NC 27709. NR 34 TC 20 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD OCT PY 1995 VL 13 IS 6 BP 639 EP 644 DI 10.1016/0736-5748(95)00032-C PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA RW957 UT WOS:A1995RW95700016 PM 8553899 ER PT J AU BAHRO, M SILBER, E BOX, P SUNDERLAND, T AF BAHRO, M SILBER, E BOX, P SUNDERLAND, T TI GIVING UP DRIVING IN ALZHEIMERS-DISEASE - AN INTEGRATIVE THERAPEUTIC APPROACH SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Note DE ALZHEIMERS DISEASE; DRIVING; PSYCHOTHERAPY; SELF-ESTEEM; INDEPENDENCE; AUTONOMY; LOSS; MOURNING ID DEMENTIA; DRIVER AB For patients with Alzheimer's disease (AD), a recommendation to stop operating a motor vehicle can be a serious event complicated by a loss of self-esteem and personal dignity. Patients are often reluctant to give up an activity so essential, both practically and symbolically, to independent living. We describe here a patient with moderately progressed AD who lacked insight of his need to cease driving. Through an integrative treatment approach, combining behavioral and psychodynamic modalities, we helped him to formulate effective ways of coping with his loss of access to independent transportation. We favor a psychotherapeutic strategy that combines behavioral and managerial measures with dynamic patient interaction, thereby developing the patient's insight of the need to give up driving while fostering his sense of autonomy. C1 WASHINGTON PSYCHOANALYT INST,WASHINGTON,DC. RP BAHRO, M (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,GERIATR PSYCHIAT SERV,BLDG 10,ROOM 3D41,10 CTR DR MSC 1264,BETHESDA,MD 20892, USA. NR 25 TC 14 Z9 14 U1 2 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 1995 VL 10 IS 10 BP 871 EP 874 DI 10.1002/gps.930101010 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA TA816 UT WOS:A1995TA81600011 ER PT J AU GALANIS, DJ MCGARVEY, ST SOBAL, J BAUSSERMAN, L LEVINSON, PD AF GALANIS, DJ MCGARVEY, ST SOBAL, J BAUSSERMAN, L LEVINSON, PD TI RELATIONS OF BODY-FAT AND FAT DISTRIBUTION TO THE SERUM-LIPID, APOLIPOPROTEIN AND INSULIN CONCENTRATIONS OF SAMOAN MEN AND WOMEN SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE ABDOMINAL ADIPOSITY; SERUM LIPIDS; RISK FACTORS; SAMOANS ID DENSITY LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR RISK-FACTORS; 38-YEAR-OLD EUROPEAN MEN; PLASMA-INSULIN; PHYSICAL-ACTIVITY; BLOOD-PRESSURE; DIETARY-INTAKE; UNITED-STATES; OBESITY; ASSOCIATION AB OBJECTIVE: To examine relations between obesity and serum concentrations of lipoprotein cholesterol, apolipoproteins, triglycerides and insulin in American and Western Samoans. Associations are also described between these CHD risk factors and abdominal adiposity, and the potential mediating role of insulin in these relationships is examined. DESIGN: Cross-sectional, using a sub-sample from an observational epidemiological study of cardiovascular disease risk factors among Samoans. MEASUREMENT: Obesity is estimated by the body mass index (BMI), and fat distribution by the abdomen-hip circumference ratio (AHR). All biochemical parameters were measured in the fasted stated. SUBJECTS: The sub-sample is 178 men and 147 women who were free from hypertension, diabetes and heart disease. RESULTS: In multivariate linear regression analyses in men the BMI was positively associated with levels of total cholesterol, the total-HDL cholesterol ratio, apolipoprotein B, and the log of triglyceride and insulin concentrations, and negatively associated with HDL and HDL2 cholesterol. The quadratic term for BMI was also found to be significantly predictive of all metabolic parameters in men, except for the log of serum insulin concentrations. Among the women, in contrast, BMI levels were significantly associated only with concentrations of HDL2 cholesterol, triglyceride and insulin. In men, the associations between the AHR and the metabolic parameters were similar to those described for the BMI, but showed no indication of non-linearity. Addition of the log of insulin to these models had little effect on the relations between the AHR and the lipid parameters, with the exceptions of total cholesterol and triglycerides. As with BMI, the AHR was much res predictive of metabolic parameters in women than in men, with a significant relation existing only with the log of insulin concentrations. CONCLUSIONS: These cross sectional data indicate that overall and abdominal adiposity are important correlates of serum lipid parameters among Samoan men, though the associations with BMI are attenuated at higher levels. Neither anthropometric indicator has much relation with these CHD risk factors among the women, perhaps due to extremely high levels of obesity in this group. C1 BROWN UNIV,DEPT MED,PROVIDENCE,RI 02912. BROWN UNIV,INST INT HLTH,PROVIDENCE,RI 02912. CORNELL UNIV,DIV NUTR SCI,ITHACA,NY 14853. BROWN UNIV,MEM HOSP RHODE ISL,DEPT MED,DIV ENDOCRINOL,PAWTUCKET,RI 02860. RP GALANIS, DJ (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,SUITE 3C-309,BETHESDA,MD 20892, USA. RI McGarvey, Stephen/I-1788-2014 FU NCRR NIH HHS [S07-RR05818]; NIA NIH HHS [R01-AG09375] NR 51 TC 22 Z9 22 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD OCT PY 1995 VL 19 IS 10 BP 731 EP 738 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA RX644 UT WOS:A1995RX64400006 PM 8589767 ER PT J AU TATARANNI, PA RAVUSSIN, E AF TATARANNI, PA RAVUSSIN, E TI VARIABILITY IN METABOLIC-RATE - BIOLOGICAL SITES OF REGULATION SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT Satellite Symposium of the 7th ICO on Exercise and Obesity - Morphological, Metabolic and Clinical Implications CY AUG 17-19, 1994 CL QUEBEC CITY, CANADA SP Med Res Council Canada, Nat Sci & Engn Res Council Canada, Hlth & Welfare Canada, Canadian Diabet Assoc, Fonds Rech Sante Quebec, Merck Frosst, Bristol Myers Squibb Canada, Servier Canada, M&M Mars, Pepsi Cola ID RESTING ENERGY-EXPENDITURE; BODY-WEIGHT GAIN; FAT-FREE MASS; RESPIRATORY CHAMBER; CONSUMPTION; INVIVO; TISSUE RP TATARANNI, PA (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,RM 541,PHOENIX,AZ 85016, USA. NR 27 TC 41 Z9 42 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD OCT PY 1995 VL 19 SU 4 BP S102 EP S106 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA TB483 UT WOS:A1995TB48300020 PM 8581083 ER PT J AU UEDA, H OHKOSHI, S HARRIS, CC JAY, G AF UEDA, H OHKOSHI, S HARRIS, CC JAY, G TI SYNERGISM BETWEEN THE HBX GENE AND AFLATOXIN B-1 IN THE DEVELOPMENT OF MURINE LIVER-CANCER SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE LIVER CANCER; HEPATITIS B VIRUS; AFLATOXIN B-1; TRANSGENIC MICE ID HEPATITIS-B VIRUS; TUMOR-SUPPRESSOR GENE; PRIMARY HEPATOCELLULAR CARCINOMAS; POLYMERASE CHAIN-REACTION; P53 GENE; CLINICAL IMPLICATIONS; TRANSGENIC MICE; MOUSE-LIVER; SKIN TUMORS; CELL-LINES AB Infection by hepatitis B virus (HBV) and exposure to dietary aflatoxin B-1 (AFB(1)) have both been implicated by epidemiological studies to be important risk factors in the development of hepatocellular carcinoma (HCC). Our ability to derive transgenic mice which develop liver cancer as a consequence of the expression of a single gene from HBV, the HBx gene, provides an opportunity to use this animal model to test whether AFB(1) can induce p53 mutations, particularly at codon 249, which are frequently detected in HCC and, as a result, act synergistically with HBV to accelerate the manifestation of disease. While AFB(1) significantly shortened the latency of tumor development in the HBx transgenic mice, the tumors did not have p53 mutations. As in tumors from the untreated transgenic mice, the p53 tumor suppressor protein is found bound to the HBx protein and sequestered in the cytoplasmic compartment of the tumor cell. Despite the frequent involvement of ras mutations in mouse tumors, we also have not detected activation of the ms p21 protein in the tumors from the AFB(1)-treated mice. We conclude that although AFB(1) can act as a co-factor with HBx to induce HCC in mice, its mode of action in vivo remains obscure. C1 AMER RED CROSS,JEROME H HOLLAND LAB,DEPT VIROL,ROCKVILLE,MD 20855. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Jay, Gregory/C-6346-2013 NR 51 TC 4 Z9 4 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1995 VL 7 IS 4 BP 735 EP 740 PG 6 WC Oncology SC Oncology GA RW001 UT WOS:A1995RW00100005 PM 21552896 ER PT J AU SUPKO, JG MALSPEIS, L AF SUPKO, JG MALSPEIS, L TI PLASMA PHARMACOKINETICS OF GENISTEIN IN MICE SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ANTINEOPLASTIC AGENTS; ENTEROHEPATIC CYCLING; GENISTEIN; PHARMACOKINETICS; PRECLINICAL PHARMACOLOGY ID TYROSINE KINASE-ACTIVITY; CELL-CYCLE PROGRESSION; DNA STRAND BREAKAGE; ENTEROHEPATIC CIRCULATION; DRUGS SUBJECT; CANCER CELLS; PHOSPHATIDYLINOSITOL TURNOVER; LEUKEMIA-CELLS; NIH-3T3 CELLS; JAPANESE MEN AB Genistein (GEN) has recently generated considerable interest as a potential agent for the prevention and treatment of cancer. The present investigation was undertaken to determine if the concentrations of drug shown to inhibit the growth of human tumor cell lines by 50% in vitro (IC50=2-27 mu g/ml) can be achieved and sustained systemically in mice. We found that GEN plasma levels decreased biexponetially from 64 mu g/ml to 0.55 mu g/ml during the initial 40 min after i.v. injection of a 52 mg/kg dose. Mean half-lives of the two initial disposition phases were 2.5+/-0.4 min and 7.1+/-1.1 min in mice treated with doses of 9-52 mg/kg. Plasma profiles of i.v. GEN exhibited a prominent secondary peak near 78 min followed by a terminal decay phase with a 39.5+/-16.8 min half-life. Although these features are suggestive of enterohepatic cycling, the mean apparent total plasma clearance of GEN (66.5+/-7.3 ml/min/kg) was nevertheless similar to hepatic blood flow. The systemic availability of GEN from a 180 mg/kg p.o. dose, which afforded 1.1 mu g/ml peak plasma concentration, was only 12%. Thus, bolus i.v. and p.o. administration of GEN failed to either achieve or adequately sustain plasma levels of the drug within the target range established by in vitro antitumor studies. Plasma levels resulting from i.p. injection of a 185 mg/kg dose were 5-times greater on average than achieved by the p.o. route. While the plasma concentration exceeded the IC50 values for the majority of human cancer cell lines responsive to GEN for only a short period of time, drug levels remained above 2 mu g/ml, the IC50 of the most sensitive cell lines, for 4 h. Extrapolation from the single dose study suggests that repetitive i.p. injection of at least 200 mg/kg GEN every 8 h will afford continuous systemic exposure to potentially cytostatic concentrations of the drug against these cell lines. This information should facilitate efforts to assess the effectiveness of GEN in appropriate in vivo tumor models. RP SUPKO, JG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,PHARMACEUT CHEM LAB,SUITE 206,1003 W 7TH ST,FREDERICK,MD 21701, USA. NR 60 TC 33 Z9 33 U1 1 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1995 VL 7 IS 4 BP 847 EP 854 PG 8 WC Oncology SC Oncology GA RW001 UT WOS:A1995RW00100022 PM 21552913 ER PT J AU SMITH, SB BORA, N MCCOOL, D KUTTY, G WONG, P KUTTY, RK WIGGERT, B AF SMITH, SB BORA, N MCCOOL, D KUTTY, G WONG, P KUTTY, RK WIGGERT, B TI PHOTORECEPTOR CELLS IN THE VITILIGO MOUSE DIE BY APOPTOSIS - TRPM-2 CLUSTERIN EXPRESSION IS INCREASED IN THE NEURAL RETINA AND IN THE RETINAL-PIGMENT EPITHELIUM SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE APOPTOSIS; CLUSTERIN; MICROPHTHALMIA; PHOTORECEPTOR CELLS; RETINAL DEGENERATION; TRPM-2; VITILIGO ID GENE; LOCUS; DEATH; RHODOPSIN; TRANSCRIPTION; ORGANIZATION; MODEL AB Purpose. To determine the mechanism of photoreceptor cell death in the vitiligo mouse, a model of retinal degeneration in which the genetic defect is not retina specific but is instead caused by single point mutation in the microphthalmia (mi) gene that codes for a basic helix-loop-helix DNA transcription factor. Methods. Detection of apoptotic cells was performed in fixed retinal tissue using the TUNEL assay in animals 1, 2, 4, 6, 8, 16, 32, 40, and 52 weeks. Electron microscopic analysis was used to confirm the morphologic hallmarks of apoptosis, and Southern blot analysis was used to detect internucleosomal DNA fragmentation. Additionally, the expression of a gene associated with apoptosis, TRPM-2/clusterin, was examined. Results. At ages beyond the time of normal retinal programmed cell death, vitiligo retinas had significantly more TUNEL-positive photoreceptor cells and more photoreceptor cells with condensed chromatin than controls. DNA internucleosomal fragmentation ladders were present in vitiligo retinas even as late as 15 weeks, a time well beyond developmental apoptosis in controls. TRPM-2/clusterin mRNA levels in vitiligo neural retinas were similar to controls initially but were two times greater than controls by 12 weeks. Surprisingly, TRPM9/clusterin mRNA levels were elevated in the retinal pigment epithelium in the mutant; the expression at one week was two times greater than normals and remained elevated for many months, even though retinal pigment epithelial cells showed no morphologic evidence of apoptosis. Conclusions. The morphologic and biochemical data suggest that photoreceptor cells die by apoptosis in vitiligo mice. The increased retinal TRPM-2/clusterin mRNA levels may be a direct response to these events. The increased expression of this gene in the retinal pigment epithelium, however, may reflect its role in tissue regression and membrane remodeling. Mechanisms by which the mi gene defect might result in the vitiligo retinopathy are proposed. C1 MED COLL GEORGIA, DEPT OPHTHALMOL, AUGUSTA, GA 30912 USA. NEI, RETINAL CELL & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP SMITH, SB (reprint author), MED COLL GEORGIA, DEPT CELLULAR BIOL & ANAT, CB1619, AUGUSTA, GA 30912 USA. FU NEI NIH HHS [EY09682, EY6859] NR 39 TC 37 Z9 37 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 1995 VL 36 IS 11 BP 2193 EP 2201 PG 9 WC Ophthalmology SC Ophthalmology GA RY891 UT WOS:A1995RY89100009 PM 7558712 ER PT J AU OHMURA, H TAHARA, H SUZUKI, M IDE, T SHIMIZU, M YOSHIDA, MA TAHARA, E SHAY, JW BARRETT, JC OSHIMURA, M AF OHMURA, H TAHARA, H SUZUKI, M IDE, T SHIMIZU, M YOSHIDA, MA TAHARA, E SHAY, JW BARRETT, JC OSHIMURA, M TI RESTORATION OF THE CELLULAR SENESCENCE PROGRAM AND REPRESSION OF TELOMERASE BY HUMAN-CHROMOSOME-3 SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Note DE CELLULAR SENESCENCE; TELOMERE; TELOMERASE; CHROMOSOME 3 ID INDEFINITE DIVISION; GENETIC-ANALYSIS; HUMAN FIBROBLAST; HUMAN-CELLS AB Telomeres, at the end of chromosomes, shorten with each cell division, resulting in cellular senescence. Tumor cells, unlike normal somatic cells, express a telomerase that maintains the telomere length. Deletion of a gene(s) on chromosome 3 is common in human renal cell carcinoma (RCC) and reintroduction of a normal chromosome 3 into an RCC immortal cell line restored the program of cellular senescence. The loss of indefinite growth potential was associated with the loss of telomerase activity and shortening of telomeres in the RCC cells with a normal chromosome 3. However, microcell hybrids that escaped from senescence and microcell hybrids with an introduced chromosome 7 or 11 maintained telomere lengths and telomerase activity similar to those of the parental RCC23. Thus, restoration of the cellular senescence program by chromosome 3 is associated with repression of telomerase function in RCC cells. C1 HIROSHIMA UNIV,SCH MED,DEPT CELLULAR & MOLEC BIOL,MINAMI KU,HIROSHIMA 734,JAPAN. TOKYO MED & DENT UNIV,DEPT CYTOGENET,BUNKYO KU,TOKYO 113,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT PATHOL 1,MINAMI KU,HIROSHIMA 734,JAPAN. UNIV TEXAS,SW MED CTR,DEPT CELL BIOL & NEUROSCI,DALLAS,TX 75235. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP OHMURA, H (reprint author), TOTTORI UNIV,FAC MED,SCH LIFE SCI,DEPT MOLEC & CELL GENET,NISHIMACHI 86,YONAGO,TOTTORI 683,JAPAN. RI Shay, Jerry/F-7878-2011 NR 23 TC 116 Z9 117 U1 0 U2 1 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD OCT PY 1995 VL 86 IS 10 BP 899 EP 904 PG 6 WC Oncology SC Oncology GA TA251 UT WOS:A1995TA25100002 PM 7493906 ER PT J AU VADENKIERNAN, N IALONGO, NS PEARSON, J KELLAM, S AF VADENKIERNAN, N IALONGO, NS PEARSON, J KELLAM, S TI HOUSEHOLD FAMILY-STRUCTURE AND CHILDRENS AGGRESSIVE-BEHAVIOR - A LONGITUDINAL-STUDY OF URBAN ELEMENTARY-SCHOOL-CHILDREN SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID MARITAL DISRUPTION; ECONOMIC HARDSHIP; MENTAL-HEALTH; ADJUSTMENT; PATTERNS; DIVORCE; PARENT; ADOLESCENCE; IMPACT AB The relationship between contemporary household family structures at fourth-grade and sixth-grade parent- and teacher-rated aggression was examined in an epidemiologically defined population of urban school children. The relationship between family structure and aggression varied by child gender and by parent and teacher ratings in the home and school, respectively. After taking into account family income, urban area, and fourth-grade aggressive behavior, boys in both mother-father and mother-male partner families were significantly less likely than boys in mother-alone families to be raced as aggressive by teachers. No significant relations between family structure and teacher- or parent-rated aggression were found for girls. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD 21205. NIMH,ROCKVILLE,MD 20857. FU NIMH NIH HHS [2T32MH18834-06A1, P50 MH38725, R01 MH42968] NR 54 TC 35 Z9 35 U1 2 U2 7 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD OCT PY 1995 VL 23 IS 5 BP 553 EP 568 DI 10.1007/BF01447661 PG 16 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA TD016 UT WOS:A1995TD01600002 PM 8568079 ER PT J AU NEWBOUND, GC ANDREWS, JM OROURKE, J BRADY, J LAIRMORE, MD AF NEWBOUND, GC ANDREWS, JM OROURKE, J BRADY, J LAIRMORE, MD TI THE LTR OF HTLV-I IS A DETERMINANT OF CELL TROPISM SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 OHIO STATE UNIV, CTR RETROVIRUS RES, COLUMBUS, OH 43210 USA. OHIO STATE UNIV, DEPT VET BIOSCI, COLUMBUS, OH 43210 USA. NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. OHIO STATE UNIV, CTR RETROVIRUS RES, COLUMBUS, OH 43210 USA. OHIO STATE UNIV, DEPT VET BIOSCI, COLUMBUS, OH 43210 USA. NCI, MOLEC VIROL LAB, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD OCT 1 PY 1995 VL 10 IS 2 BP 44 EP 44 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000061 ER PT J AU MULLOY, J CERESETO, A KLOTMAN, M MIGONE, TS AF MULLOY, J CERESETO, A KLOTMAN, M MIGONE, TS TI HTLV-I AND THE IL-2R PATHWAY SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI klotman, mary/A-1921-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 2 EP 2 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000019 ER PT J AU CIMINALE, V DAGOSTINO, DM ZOTTI, L CALABRO, ML DEARAUJO, AC FELBER, BK FRANCHINI, G CHIECOBIANCHI, L AF CIMINALE, V DAGOSTINO, DM ZOTTI, L CALABRO, ML DEARAUJO, AC FELBER, BK FRANCHINI, G CHIECOBIANCHI, L TI ANALYSIS OF THE CODING POTENTIAL OF THE X-REGION OF THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-II (HTLV-II) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV PADUA,INST ONCOL,PADUA,ITALY. INST ALDOFO LUTZ,SAO PAULO,BRAZIL. NCI,FREDERICK CANC RES & DEV CTR,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21701. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 3 EP 3 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000020 ER PT J AU DERSE, D MIKOVITS, J RUSCETTI, F AF DERSE, D MIKOVITS, J RUSCETTI, F TI MUTATIONS OF STRUCTURAL AND REGULATORY GENES IN AN INFECTIOUS MOLECULAR CLONE OF HTLV-I - DETERMINANTS OF INFECTIVITY AND T-CELL TRANSFORMATION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,FCRDC,BRMP,LEUKOCYTE BIOL LAB,FREDERICK,MD 21701. NCI,FCRDC,SAIC,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 4 EP 4 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000021 ER PT J AU ROSIN, O KOCH, C RADANT, I SEMMES, O JEANG, KT GRASSMANN, R AF ROSIN, O KOCH, C RADANT, I SEMMES, O JEANG, KT GRASSMANN, R TI THE CAPACITY OF HTLV-1 TAX TO INDUCE NFKB ACTIVITY IS NOT REQUIRED FOR T-CELL IMMORTALIZATION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV ERLANGEN NURNBERG,INST KLIN & MOLEK VIROL,W-8520 ERLANGEN,GERMANY. NIAID,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 7 EP 7 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000024 ER PT J AU FELBER, BK BEAR, J ZOLOTUKHIN, AS TABERNERO, C VALENTIN, A PAVLAKIS, GN AF FELBER, BK BEAR, J ZOLOTUKHIN, AS TABERNERO, C VALENTIN, A PAVLAKIS, GN TI EXPRESSION OF REX-INDEPENDENT MOLECULAR CLONES OF HTLV-I MEDIATED VIA A CIS-ACTING TRANSACTIVATION ELEMENT OF THE SIMIAN RETROVIRUS TYPE-1 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,FCRDC,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21701. NCI,FCRDC,HUMAN RETROVIRUS SECT,FREDERICK,MD 21701. NCI,FCRDC,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 16 EP 16 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000033 ER PT J AU CERESETO, A DIELLA, F CARA, A MULLOY, J GALLO, R GRASSMANN, R FRANCHINI, G KLOTMAN, M AF CERESETO, A DIELLA, F CARA, A MULLOY, J GALLO, R GRASSMANN, R FRANCHINI, G KLOTMAN, M TI CONSTITUTIVE HIGH EXPRESSION OF P(21WAFL/CIP1) IN HTLVI-INFECTED T-CELLS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI klotman, mary/A-1921-2016; Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 19 EP 19 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000036 ER PT J AU XU, X KANG, SH HEIDENREICH, O OSHEA, JJ NERENBERG, MI AF XU, X KANG, SH HEIDENREICH, O OSHEA, JJ NERENBERG, MI TI CONSTITUTIVE ACTIVATION OF DIFFERENT JAK TYROSINE KINASES IN HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 (HTLV-1) TAX PROTEIN CELLS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 SCRIPPS RES INST, LA JOLLA, CA USA. NCI, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 20 EP 20 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000037 ER PT J AU COWAN, EP ALEXANDER, RK DANIEL, S KASHANCHI, F BRADY, JN AF COWAN, EP ALEXANDER, RK DANIEL, S KASHANCHI, F BRADY, JN TI A POSTMITOTIC HUMAN NEURONAL CELL-LINE PRODUCES TNF-ALPHA AND UNDERGOES CELL-DEATH IN RESPONSE TO TREATMENT WITH SOLUBLE HTLV-I TAX SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 26 EP 26 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000043 ER PT J AU TABERNERO, C ZOLOTUKHIN, AS VALENTIN, A PAVLAKIS, GN FELBER, BK AF TABERNERO, C ZOLOTUKHIN, AS VALENTIN, A PAVLAKIS, GN FELBER, BK TI THE POSTTRANSCRIPTIONAL CONTROL ELEMENT OF THE SIMIAN RETROVIRUS TYPE-1 (SRV-I) FORMS AN EXTENSIVE RNA SECONDARY STRUCTURE NECESSARY FOR ITS FUNCTION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,FCRDC,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NCI,FCRDC,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. NCI,FCRDC,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 35 EP 35 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000052 ER PT J AU WATERS, D BRINING, S BLATTNER, W ARTHUR, L DERSE, D AF WATERS, D BRINING, S BLATTNER, W ARTHUR, L DERSE, D TI COMPARISON AND CHARACTERISTICS OF CELL-FREE INFECTION OF DBS-FRHL RHESUS LUNG-CELL CLONE (B5) WITH A HTLV-I MOLECULAR CLONE(PCS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,FCRDC,SAIC,FREDERICK,MD 21701. NCI,FCRDC,BRMP,FREDERICK,MD 21701. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 40 EP 40 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000057 ER PT J AU LEVIN, MC LEHKY, T FLERLAGE, T KATZ, N JACOBSON, S AF LEVIN, MC LEHKY, T FLERLAGE, T KATZ, N JACOBSON, S TI PCR/IN SITU HYBRIDIZATION (PCR/ISH)AND IN-SITU HYBRIDIZATION (ISH) ANALYSIS OF HTLV-I-TAX IN THE CENTRAL-NERVOUS-SYSTEM (CNS) OF PATIENTS WITH HAM/TSP SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 54 EP 54 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000071 ER PT J AU FOX, RJ LEVIN, MC JACOBSON, S AF FOX, RJ LEVIN, MC JACOBSON, S TI TUMOR-NECROSIS-FACTOR-ALPHA EXPRESSION IN THE SPINAL-CORD OF HAM/TSP PATIENTS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NINCDS,NEUROIMMUNOL BRANCH,VIRAL IMMUNOL SECT,BETHESDA,MD 20892. NIH,HHMI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 56 EP 56 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000073 ER PT J AU LEHKY, TJ FLERLAGE, N HOUFF, S DJIBJALBUT, S MCFARLAND, H JACOBSON, S AF LEHKY, TJ FLERLAGE, N HOUFF, S DJIBJALBUT, S MCFARLAND, H JACOBSON, S TI HTLV-II-ASSOCIATED MYELOPATHY - CLINICAL AND IMMUNOLOGICAL PROFILES OF HTLV-II INFECTED PATIENTS WITH CENTRAL-NERVOUS-SYSTEM DISEASE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 58 EP 58 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000075 ER PT J AU LEVIN, M BERK, J DALMAU, J ROSENFELD, M POSNER, JB JACOBSON, S AF LEVIN, M BERK, J DALMAU, J ROSENFELD, M POSNER, JB JACOBSON, S TI IGG FROM PATIENTS WITH HAM/TSP REACT WITH NEURONS OF THE CENTRAL-NERVOUS-SYSTEM (CNS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 63 EP 63 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000080 ER PT J AU LEVIN, MC FOX, R LEHKY, T CLERGHORN, F FLERLAGE, N YOUNG, N WHITE, J JACOBSON, S AF LEVIN, MC FOX, R LEHKY, T CLERGHORN, F FLERLAGE, N YOUNG, N WHITE, J JACOBSON, S TI PCR IN-SITU HYBRIDIZATION (PCR/ISH) OF HTLV-I-TAX SEQUENCES IN IMMUNE ORGANS OF PATIENTS WITH HTLV-I-ASSOCIATED MYELOPATHY TROPICAL SPASTIC PARAPARESIS (HAM/TSP) REVEAL EXTENSIVE VIRAL SIGNAL IN BONE-MARROW SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 64 EP 64 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000081 ER PT J AU LAGRENADE, L RICHARDS, S GIBBS, WN HANCHARD, B WILLIAMS, E WILLIAMS, NP BLATTNER, WA MANNS, A AF LAGRENADE, L RICHARDS, S GIBBS, WN HANCHARD, B WILLIAMS, E WILLIAMS, NP BLATTNER, WA MANNS, A TI CUTANEOUS MANIFESTATIONS OF ADULT T-CELL LYMPHOMA LEUKEMIA IN JAMAICA - A 12 YEAR REVIEW SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV W INDIES,KINGSTON,JAMAICA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 89 EP 89 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000106 ER PT J AU KAWANISHI, T HAGIWARA, E LEHKY, T BIDDISON, W KLINMAN, D JACOBSON, S AF KAWANISHI, T HAGIWARA, E LEHKY, T BIDDISON, W KLINMAN, D JACOBSON, S TI IL-2, IFN-GAMMA, AND IL-4-SECRETING CELL-POPULATIONS ARE INCREASED IN PBMC FROM HAM/TSP PATIENTS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 129 EP 129 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000146 ER PT J AU RICHARDSON, JH ZANI, C SODROSKI, JG WALDMANN, TA MARASCO, WA AF RICHARDSON, JH ZANI, C SODROSKI, JG WALDMANN, TA MARASCO, WA TI PHENOTYPIC KNOCKOUT OF THE INTERLEUKIN-2 RECEPTOR IN HTLV-I TRANSFORMED-CELL LINES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. NCI,METAB BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 131 EP 131 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000148 ER PT J AU VENKATESHAN, CN DE, SK GAJDUSEK, DC MARSH, JW GIBBS, CJ AF VENKATESHAN, CN DE, SK GAJDUSEK, DC MARSH, JW GIBBS, CJ TI FC-GAMMA RECEPTORS EXPRESSION MODULATION BY HTLV-I INFECTION IN HUMAN MONOCYTES MACROPHAGES AND THEIR ROLE IN HTLV-I DISEASES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 138 EP 138 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000155 ER PT J AU KAWANISHI, T CLEMENS, K SIOMI, H BRADY, J JACOBSON, S AF KAWANISHI, T CLEMENS, K SIOMI, H BRADY, J JACOBSON, S TI IMMUNOLOGICAL EFFECT OF ASTROCYTE-SPECIFIC EXPRESSION OF HTLV-I TAX SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIB,BETHESDA,MD. NCI,BETHESDA,MD 20892. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. RI Siomi, Haruhiko/A-7020-2015 OI Siomi, Haruhiko/0000-0001-8690-3822 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 144 EP 144 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000161 ER PT J AU VARNIER, OE LILLO, F BONO, M MARTINI, I MCDERMOTT, J GIRI, A FRANCHINI, G AF VARNIER, OE LILLO, F BONO, M MARTINI, I MCDERMOTT, J GIRI, A FRANCHINI, G TI HTLV INDETERMINATE SEROREACTIVITY IN GUINEA-BISSAU IS NOT DUE TO HTLV-II INFECTION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,LTCB,BETHESDA,MD 20892. ABC,MOLEC VIROL UNIT,GENOA,ITALY. AIDS CTR,VIROL LAB,MILAN,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 157 EP 157 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000173 ER PT J AU WILKS, R HANCHARD, B MORGAN, O CRANSTON, B SMITH, L RODGERSJOHNSON, P MANNS, A AF WILKS, R HANCHARD, B MORGAN, O CRANSTON, B SMITH, L RODGERSJOHNSON, P MANNS, A TI PATTERNS OF HTLV-I INFECTION AMONG FAMILY MEMBERS OF PATIENTS WITH ADULT T-CELL LEUKEMIA-LYMPHOMA AND HTLV-I-ASSOCIATED MYELOPATHY TROPICAL SPASTIC PARAPARESIS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV W INDIES,TROP METAB RES UNIT,KINGSTON 7,JAMAICA. UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 180 EP 180 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000196 ER PT J AU MALONEY, EM WIKTOR, SZ PATE, EJ GRAY, R TURK, K WATERS, D MANNS, A BLATTNER, WA AF MALONEY, EM WIKTOR, SZ PATE, EJ GRAY, R TURK, K WATERS, D MANNS, A BLATTNER, WA TI HTLV-I TITERS IN CHILDREN ARE ASSOCIATED WITH MATERNAL TITERS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 183 EP 183 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000199 ER PT J AU BIGGAR, RJ BLACK, FL LAL, R AF BIGGAR, RJ BLACK, FL LAL, R TI 25 YEARS OF HIGH HTLV-II ENDEMICITY IN THE KAPAYO-INDIANS OF BRAZIL SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD. YALE UNIV,NEW HAVEN,CT. CTR DIS CONTROL,ATLANTA,GA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 185 EP 185 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000201 ER PT J AU GRACIA, F CASTILLO, LC LARREATEGUI, M ROBERTS, B CEDENO, V HENEINE, W BLATTNER, W KAPLAN, JE LEVINE, PH AF GRACIA, F CASTILLO, LC LARREATEGUI, M ROBERTS, B CEDENO, V HENEINE, W BLATTNER, W KAPLAN, JE LEVINE, PH TI RELATION BETWEEN HUMAN T-LYMPHOTROPIC VIRUS TYPE-I AND NEUROLOGIC DISEASES IN PANAMA - 1985-1990 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HUMAN T-CELL LYMPHOTROPIC VIRUS (HTLV) I II; TROPICAL SPASTIC PARAPARESIS; HTLV-I-ASSOCIATED MYELOPATHY ID TROPICAL SPASTIC PARAPARESIS; LEUKEMIA-LYMPHOMA VIRUS; HTLV-I; MULTIPLE-SCLEROSIS; CELL LEUKEMIA; SEROPOSITIVE INDIVIDUALS; CHRONIC MYELOPATHY; GUAYMI INDIANS; INFECTION; ANTIBODIES AB Human T-cell lymphotropic virus type I (HTLV-I) is endemic in the Caribbean basin and in Japan. HTLV-II, a closely related virus, is endemic in several groups of native Americans, including Panamanian Guaymi. In Panama, a nationwide HTLV-I/II seroprevalence of 1-2% has been reported. We evaluated the frequency of HTLV-I/II infection in patients with neurologic diseases admitted to state tertiary hospitals in Panama City between 1985 and 1990. Nineteen of 322 patients with eligible diagnoses had antibodies to HTLV-I/II, 17 with HTLV-I and 2 with HTLV-II. HTLV-I was associated with spastic paraparesis (13 of 23, 56.5% versus 4 of 299, 1.3%, p < 0.001) and with cerebellar syndrome (2 of 13, 15.4%) and multiple sclerosis (2 of 54, 3.7%) (p < 0.05 for both diseases compared with subject with none of these diagnoses). The two HTLV-I infected patients with cerebellar syndrome later developed spastic paraparesis. HTLV-II infection was noted in one patient with cerebellar syndrome and one with amyotrophic lateral sclerosis. All patients with other diagnoses were seronegative. Among patients with spastic paraparesis, HTLV-I-infected patients were clinically indistinguishable from seronegative subjects. There is apparently an overlapping clinical spectrum of neurologic diseases associated with HTLV-I and HTLV-II infection. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. LAB COMMEMORAT GORGAS,PANAMA CITY,PANAMA. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30341. NR 42 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 192 EP 197 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000013 PM 7552485 ER PT J AU JACK, N CLEGHORN, F EDWARDS, J MURPHY, J MAHABIR, B BARTHOLOMEW, C BLATTNER, W AF JACK, N CLEGHORN, F EDWARDS, J MURPHY, J MAHABIR, B BARTHOLOMEW, C BLATTNER, W TI THE EFFECT OF HTLV-I STATUS ON HIV-1 SEROCONVERSIONS AMONG STD CLINIC ATTENDERS IN TRINIDAD SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV W INDIES,CAREC,ST AUGUSTINE,TRINID & TOBAGO. MINIST HLTH,ST JOSEPH,TRINID & TOBAGO. NCI,DCE,BETHESDA,MD. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 192 EP 192 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000208 ER PT J AU MANNS, A MALONEY, E PATE, E WIKTOR, S ZIEGLER, R GRAY, R BLATTNER, W AF MANNS, A MALONEY, E PATE, E WIKTOR, S ZIEGLER, R GRAY, R BLATTNER, W TI SERUM RETINOL AND BETA-CAROTENE LEVELS AMONG PREGNANT-WOMEN WITH HTLV-I INFECTION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD. UNIV W INDIES,KINGSTON 7,JAMAICA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 208 EP 208 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000224 ER PT J AU MURPHY, EL WATANABE, KK SCHREIBER, GB SACHER, RA AF MURPHY, EL WATANABE, KK SCHREIBER, GB SACHER, RA TI DIFFERENCES IN CLINICAL LABORATORY PARAMETERS ASSOCIATED WITH HTLV-I AND HTLV-II INFECTION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NHLBI,RETROVIRUS EPIDEMIOL DONOR STUDY,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. WESTAT CORP,ROCKVILLE,MD. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20057. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 209 EP 209 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000225 ER PT J AU DOSIK, H LEVINE, PH DUSSEK, N ORAV, EJ LANDESMAN, S MANNS, A WELLES, SL AF DOSIK, H LEVINE, PH DUSSEK, N ORAV, EJ LANDESMAN, S MANNS, A WELLES, SL TI THE BROOKLYN HTLV-I STUDY - DESIGN CONSIDERATIONS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NEW YORK METHODIST HOSP,BROOKLYN,NY. GEORGE WASHINGTON UNIV,WASHINGTON,DC. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA. SUNY HLTH SCI CTR,BROOKLYN,NY. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 213 EP 213 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000229 ER PT J AU DEKABAN, GA WARD, R WATERS, D OGER, J AF DEKABAN, GA WARD, R WATERS, D OGER, J TI LOW-LEVEL ENDEMIC INFECTION OF HTLV-I AND HTLV-II IN AN AMERINDIAN TRIBE ON VANCOUVER-ISLAND, BRITISH-COLUMBIA, CANADA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 JOHN P ROBARTS RES INST,LONDON,ON,CANADA. UNIV UTAH,SALT LAKE CITY,UT. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. UNIV VANCOUVER HOSP,DEPT MED,VANCOUVER,BC,CANADA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 216 EP 216 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000232 ER PT J AU GALLO, RC AF GALLO, RC TI COMPARATIVE MOLECULAR PATHOGENESIS OF HUMAN RETROVIRUSES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 223 EP 223 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000239 ER PT J AU SAGGIORO, D ROSATO, A ESPOSITO, G ROSENBERG, MP HARRISON, J FELBER, B PAVLAKIS, GN CHIECOBIANCHI, L AF SAGGIORO, D ROSATO, A ESPOSITO, G ROSENBERG, MP HARRISON, J FELBER, B PAVLAKIS, GN CHIECOBIANCHI, L TI INFLAMMATORY POLYARTHRITIS AND BONE REABSORPTION IN TAX-TRANSGENIC MICE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 UNIV PADUA,INST ONCOL,CIRC,IST BIOTECHNOL SECT,PADUA,ITALY. GLAXO INC,RES INST,DEPT PHARMACOL,RES TRIANGLE PK,NC 27709. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Rosato, Antonio/E-8626-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 227 EP 227 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000243 ER PT J AU MIKOVITS, JA HOFFMAN, PM RETHWILM, A RUSCETTI, FW AF MIKOVITS, JA HOFFMAN, PM RETHWILM, A RUSCETTI, FW TI IN-VITRO INFECTION BY HUMAN FOAMY VIRUS - IMPLICATIONS FOR PATHOGENESIS IN HTLV-I AND HIV-I INFECTED OR UNINFECTED TARGET-CELLS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. VET ADM MED CTR,BALTIMORE,MD. UNIV MARYLAND,BALTIMORE,MD. UNIV WURZBURG,INST VIROL & IMMUNOBIOL,W-8700 WURZBURG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 247 EP 247 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000263 ER PT J AU DIGILIO, L GIRI, A FULLEN, J GALLO, RC FRANCHINI, G AF DIGILIO, L GIRI, A FULLEN, J GALLO, RC FRANCHINI, G TI MOLECULAR AND BIOLOGICAL CHARACTERIZATION OF STLV PAN-P, A NOVEL INFECTIOUS RETROVIRUS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 262 EP 262 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000278 ER PT J AU RICHARDS, AL PAMUNGKAS, J ANTHONY, RL SIE, A ROSEN, L ISKANDRIATI, D FRANCHINI, G AF RICHARDS, AL PAMUNGKAS, J ANTHONY, RL SIE, A ROSEN, L ISKANDRIATI, D FRANCHINI, G TI AMPLIFICATION BY POLYMERASE CHAIN-REACTION (PCR) OF STLV NUCLEIC-ACID IN MACACA-NEMESTRIMA FROM SUMATRA, INDONESIA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 USN,MED RES UNIT 2,JAKARTA,INDONESIA. PRIMATE RES CTR,BOGOR,INDONESIA. INST PASTEUR,PARIS,FRANCE. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 283 EP 283 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000298 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI THE PROMISCUOUS IL-2 RECEPTOR - A TARGET FOR IMMUNOTHERAPY OF HTLV-I-ASSOCIATED DISEASES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 284 EP 284 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000299 ER PT J AU LEHKY, TJ LEVIN, M FLERLAGE, N WHITE, J FLEISHER, T MCFARLAND, H WALDMANN, T JACOBSON, S AF LEHKY, TJ LEVIN, M FLERLAGE, N WHITE, J FLEISHER, T MCFARLAND, H WALDMANN, T JACOBSON, S TI THE TREATMENT OF HAM/TSP PATIENTS WITH HUMANIZED ANTI-TAC ANTIBODY - PRELIMINARY IMMUNOLOGICAL STUDIES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 289 EP 289 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000304 ER PT J AU JENKINS, AJ OYLER, JM CONE, EJ AF JENKINS, AJ OYLER, JM CONE, EJ TI COMPARISON OF HEROIN AND COCAINE CONCENTRATIONS IN SALIVA WITH CONCENTRATIONS IN BLOOD AND PLASMA SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID HEPATOTOXICITY; DRUGS; URINE; BASE C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 23 TC 107 Z9 108 U1 2 U2 13 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol PD OCT PY 1995 VL 19 IS 6 BP 359 EP 374 PG 16 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA RX548 UT WOS:A1995RX54800004 PM 8926729 ER PT J AU CONE, EJ YOUSEFNEJAD, D HILLSGROVE, MJ HOLICKY, B DARWIN, WD AF CONE, EJ YOUSEFNEJAD, D HILLSGROVE, MJ HOLICKY, B DARWIN, WD TI PASSIVE INHALATION OF COCAINE SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID EXPOSURE; INFANTS; CRACK; CHILDREN RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 17 TC 15 Z9 15 U1 0 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol PD OCT PY 1995 VL 19 IS 6 BP 399 EP 411 PG 13 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA RX548 UT WOS:A1995RX54800009 PM 8926734 ER PT J AU HUESTIS, MA MITCHELL, JM CONE, EJ AF HUESTIS, MA MITCHELL, JM CONE, EJ TI DETECTION TIMES OF MARIJUANA METABOLITES IN URINE BY IMMUNOASSAY AND GC-MS SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; FLUORESCENCE POLARIZATION IMMUNOASSAY; GAS-CHROMATOGRAPHY; ENZYME-IMMUNOASSAY; HALF-LIFE; CANNABINOIDS; USERS; TETRAHYDROCANNABINOL; EXCRETION; ACID C1 USN,DRUG SCREENING LAB,NAVAL AIR STN,JACKSONVILLE,FL 32212. RP HUESTIS, MA (reprint author), NIDA,ADDICT RES CTR,CHEM & DRUG METAB SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 28 TC 71 Z9 75 U1 1 U2 15 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol PD OCT PY 1995 VL 19 IS 6 BP 443 EP 449 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA RX548 UT WOS:A1995RX54800014 PM 8926739 ER PT J AU CONE, EJ AF CONE, EJ TI PHARMACOKINETICS AND PHARMACODYNAMICS OF COCAINE SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID INTRAVENOUS COCAINE; ORAL COCAINE; HUMANS; KINETICS; PLASMA; SMOKING; BENZOYLECGONINE; METABOLITES; DISPOSITION; INTRANASAL RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 34 TC 121 Z9 123 U1 6 U2 27 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol PD OCT PY 1995 VL 19 IS 6 BP 459 EP 478 PG 20 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA RX548 UT WOS:A1995RX54800016 PM 8926741 ER PT J AU WILKINS, D HAUGHEY, H CONE, E HUESTIS, M FOLTZ, R ROLLINS, D AF WILKINS, D HAUGHEY, H CONE, E HUESTIS, M FOLTZ, R ROLLINS, D TI QUANTITATIVE-ANALYSIS OF THC, 11-OH-THC, AND THCCOOH IN HUMAN HAIR BY NEGATIVE-ION CHEMICAL-IONIZATION MASS-SPECTROMETRY SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID TESTING HUMAN-HAIR; GAS-CHROMATOGRAPHY; ABUSE; METHAMPHETAMINE; COCAINE; MORPHINE; DRUGS; IDENTIFICATION; RADIOIMMUNOASSAY; AMPHETAMINE C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP WILKINS, D (reprint author), UNIV UTAH,CTR HUMAN TOXICOL,DEPT PHARMACOL & TOXICOL,490 BIOMED POLYMERS RES BLDG,SALT LAKE CITY,UT 84112, USA. FU NIDA NIH HHS [DA09096, DA07820] NR 32 TC 59 Z9 63 U1 0 U2 1 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol PD OCT PY 1995 VL 19 IS 6 BP 483 EP 491 PG 9 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA RX548 UT WOS:A1995RX54800018 PM 8926743 ER PT J AU Nsamenang, AB Lamb, ME AF Nsamenang, AB Lamb, ME TI The force of beliefs: How the parental values of the Nso of Northwest Cameroon shape children's progress toward adult models SO JOURNAL OF APPLIED DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID INFANT; IDEAS AB Socialization values vary across cultures and social ecologies. In this study, intracultural variations in parental values associated with gender, generation (grandparents vs. parents), habitat (rural vs. urban), religion (Africa theodicy, Christianity and Islam), and educational history were investigated among the Nso of Northwest Cameroon. Overall, the results revealed greater agreement than disagreement in the responses of the various parental cohorts, although religion, generation, habitat, gender, and education were all significantly associated with variations in parental values. The findings ore discussed in the context of ethnographic information regarding the diversity of parental beliefs, even within a single ethnic group. Among the Nso, enculturation proceeds via anticipatory socialization, guided participation, and integration into the peer culture. C1 NICHHD, SECT SOCIAL & EMOT DEV, BETHESDA, MD 20814 USA. ECOLE NORMALE SUPER, BAMENDA, CAMEROON. NR 51 TC 22 Z9 22 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0193-3973 J9 J APPL DEV PSYCHOL JI J. Appl. Dev. Psychol. PD OCT-DEC PY 1995 VL 16 IS 4 BP 613 EP 627 DI 10.1016/0193-3973(95)90007-1 PG 15 WC Psychology, Developmental SC Psychology GA TN862 UT WOS:A1995TN86200007 ER PT J AU REUVEN, NB KOONIN, EV RUDD, KE DEUTSCHER, MP AF REUVEN, NB KOONIN, EV RUDD, KE DEUTSCHER, MP TI THE GENE FOR THE LONGEST KNOWN ESCHERICHIA-COLI PROTEIN IS A MEMBER OF HELICASE SUPERFAMILY-II SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ENCODING RNASE-T; CLONED GENES; SEQUENCES; EXPRESSION; POLYMERASE; MULTIPLE; REPLICATION; TERMINUS; DNA AB The Escherichia coli rnt gene, which encodes the RNA-processing enzyme RNase T, is cotranscribed with a downstream gene. Complete sequencing of this gene indicates that its coding region encompasses 1,538 amino acids, making it the longest known protein in E. coli, The gene (tentatively termed lhr for long helicase related) contains the seven conserved motifs of the DNA and RNA helicase superfamily II, An similar to 170-kDa protein is observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of S-35-labeled extracts prepared from cells in which lhr is under the control of an induced T7 promoter, This protein is absent when lhr is interrupted or when no plasmid is present, Downstream of lhr is the C-terminal region of a convergent gene with homology to glutaredoxin, Interruptions of chromosomal lhr at two different positions within the gene do not affect the growth of E. coli at various temperatures in rich or minimal medium, indicating that lhr is not essential for usual laboratory growth. lhr interruption also has no effect on anaerobic growth, In addition, cells lacking Lhr recover normally from starvation, plate phage normally, and display normal sensitivities to UV irradiation and H2O2. Southern analysis showed that no other gene closely related to lhr is present on the E. coli chromosome, These data expand the known size range of E. coli proteins and suggest that very large helicases are present in this organism. C1 UNIV CONNECTICUT,CTR HLTH,DEPT BIOCHEM,FARMINGTON,CT 06032. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. FU NIGMS NIH HHS [GM16317] NR 33 TC 22 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1995 VL 177 IS 19 BP 5393 EP 5400 PG 8 WC Microbiology SC Microbiology GA RX423 UT WOS:A1995RX42300001 PM 7559321 ER PT J AU FIJALKOWSKA, IJ SCHAAPER, RM AF FIJALKOWSKA, IJ SCHAAPER, RM TI EFFECTS OF ESCHERICHIA-COLI DNAE ANTIMUTATOR ALLELES IN A PROOFREADING-DEFICIENT MUTD5 STRAIN SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POLYMERASE-III HOLOENZYME; MISMATCH REPAIR; EPSILON-SUBUNIT; MUTATOR MUTD5; SALMONELLA-TYPHIMURIUM; REPLICATION ERRORS; ALPHA-SUBUNIT; HIGH FIDELITY; GENE; EXONUCLEASE AB We have previously isolated seven mutants of Escherichia coli which replicate their DNA with increased fidelity. These mutants were isolated as suppressors of the elevated mutability of a mismatch-repair-defective mutL strain. Each mutant was shown to contain a single amino acid substitution in the dnaE gene product, the alpha (i.e., polymerase) subunit of DNA polymerase III holoenzyme responsible for replicating the E. coli chromosome, The mechanism(s) by which these antimutators exert their effect is of interest. Here, we have examined the effects of the antimutator alleles in a mutD5 mutator strain. This strain carries a mutation in the dnaQ gene, which results in defective exonucleolytic proofreading. Our results show that dnaE mutations also confer a strong antimutator phenotype in this background, the effects being generally much greater than those observed previously in the mutL background. The results suggest that the dnaE antimutator alleles can exert their effect independently of exonucleolytic proofreading activity. The large magnitude of the antimutator effects in the mutD5 background can be ascribed, at least in part, to the (additional) restoration of DNA mismatch repair, which is generally impaired in mutD5 strains because of error saturation. The high mutability of mutD5 strains was exploited to isolate a strong new dnaE antimutator allele on the basis of its ability to suppress the high reversion rate of an A . T-->T . A transversion in this background. A model suggesting how the dnaE antimutator alleles might exert their effects in proofreading-proficient and -deficient backgrounds is presented. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. RI Fijalkowska, Iwona/I-7796-2016 NR 43 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1995 VL 177 IS 20 BP 5979 EP 5986 PG 8 WC Microbiology SC Microbiology GA RZ770 UT WOS:A1995RZ77000038 PM 7592352 ER PT J AU LEVINSON, SF SHINAGAWA, M SATO, T AF LEVINSON, SF SHINAGAWA, M SATO, T TI SONOELASTIC DETERMINATION OF HUMAN SKELETAL-MUSCLE ELASTICITY SO JOURNAL OF BIOMECHANICS LA English DT Article DE ELASTICITY; ULTRASOUND; DOPPLER EFFECT; VIBRATION; SKELETAL MUSCLE ID BLOOD-FLOW; ULTRASOUND; TISSUE; ELASTOGRAPHY; VELOCITY; BREAST; IMAGES AB It is not currently practical to directly measure viscoelastic parameters in human muscles in situ. Methods used in vitro cannot readily be applied, and motion analysis provides only a gross estimate. We report on the application of a hybrid approach, sonoelastography, which uses ultrasound to measure the propagation of shear waves induced by externally applied vibrations. Because shear waves predominate in incompressible viscoelastic media at low frequencies, sonoelastic data should be comparable to those obtained using conventional means. We recorded vibration propagation speeds as a function of applied load in the quadriceps muscles of ten volunteers as they underwent a series of static contractions. Data collection during dynamic contractions, not possible with the current equipment, will be the subject of future experimentation. Although statistically significant correlations were not uniformly obtained above 60 Hz nor for propagation perpendicular to the muscle fibers, this is felt to have resulted from deviations from the applied plane wave model. Calculated values of Young's modulus for 30 Hz propagation parallel to the muscle fibers were 7 +/- 3, 29 +/- 12 and 57 +/- 37 x 10(3) N m(-2) for applied loads of 0, 7.5 and 15 kg, respectively. The corresponding values at 60 Hz were 25 +/- 6, 75 +/- 61 and 127 +/- 65. These values were statistically significant and linearly correlated with the applied load, as expected. Our data represent the first in situ human measurements of their kind. It is anticipated that sonoelastography will provide a useful adjunct to the study of human biomechanics. C1 NIH,DEPT REHABIL MED,BETHESDA,MD 20892. TOKYO INST TECHNOL,TOKYO 152,JAPAN. RI CHASSAGNE, Fanette/B-7212-2012 NR 29 TC 124 Z9 129 U1 4 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD OCT PY 1995 VL 28 IS 10 BP 1145 EP 1154 DI 10.1016/0021-9290(94)00173-2 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA RT922 UT WOS:A1995RT92200001 PM 8550633 ER PT J AU SIDOROVA, NY GAZONI, P RAU, DC AF SIDOROVA, NY GAZONI, P RAU, DC TI COMPETITION BETWEEN NETROPSIN AND RESTRICTION NUCLEASE ECORI FOR DNA-BINDING SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID MINOR-GROOVE; CRYSTAL-STRUCTURE; TRIPLE HELIX; SPECIFICITY; PROTEIN; DRUG; DISTAMYCIN; REPRESSOR; COMPLEXES; SITES AB We find that netropsin and netropsin analogue protect DNA from EcoRI restriction nuclease cleavage by inhibiting the binding of EcoRI to its recognition site. The drug - EcoRI competitive binding constants measured by a electrophoretic gel mobility shift assay are in excellent agreement with the nuclease protection results for the netropsin analogue and in reasonable agreement for netropsin itself. Crystal structures of complexes show that netropsin and EcoRI recognize different regions of the DNA helix and would not be expected to compete for binding to the restriction nuclease site. The large distortions in DNA structure caused by EcoRI binding are most likely responsible for an indirect structural competition with netropsin binding. The structural change in the netropsin binding region induced by EcoRI binding to its region essentially prevents drug association. Given the reciprocal nature of competition, binding of netropsin to a minimally perturbed structure then also makes the association of EcoRI energetically more costly. Since many sequence specific DNA binding proteins significantly bend or distort the DNA helix drugs that compete indirectly can be as effective as drugs that act through a direct steric inhibition. C1 NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NIDDKD,BETHESDA,MD 20892. NR 40 TC 10 Z9 10 U1 0 U2 2 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD OCT PY 1995 VL 13 IS 2 BP 367 EP 385 PG 19 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TB324 UT WOS:A1995TB32400014 PM 8579794 ER PT J AU MARKS, MS ROCHE, PA VANDONSELAAR, E WOODRUFF, L PETERS, PJ BONIFACINO, JS AF MARKS, MS ROCHE, PA VANDONSELAAR, E WOODRUFF, L PETERS, PJ BONIFACINO, JS TI A LYSOSOMAL TARGETING SIGNAL IN THE CYTOPLASMIC TAIL OF THE BETA-CHAIN DIRECTS HLA-DM TO MHC CLASS-II COMPARTMENTS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANS-GOLGI NETWORK; HISTOCOMPATIBILITY COMPLEX-MOLECULES; INVARIANT CHAIN; ENDOPLASMIC-RETICULUM; MEMBRANE-GLYCOPROTEINS; INTRACELLULAR-TRANSPORT; MICE LACKING; CELL-SURFACE; T-CELLS; ANTIGENS AB In human B cells, class II molecules of the major histocompatibility complex (MHC-II) accumulate in an endosomal/lysosomal compartment, the MIIC, in which they may encounter and bind peptides. An additional molecule required for MHC-II peptide binding, HLA-DM (DM), has also been localized to the MIIC. Neither the relationship of the MIIC to the endosomal system nor the mechanisms by which DM localizes to the MIIC are understood. To address these issues, DM localization was analyzed in cells that do or do not express MHC-II. DM alpha beta heterodimers were localized in transfected MHC-II-negative HeLa and NRK cells, in the absence of the MHC-II-associated invariant chain, to a prelysosomal/lysosomal compartment by immunofluorescence microscopy. To identify a potential targeting determinant, we analyzed the localization of a chimeric protein, T-T-Mb, in which the cytoplasmic tail of murine DM beta (Mb) was appended to the lumenal and transmembrane domains of a cell surface protein, Tac, Like intact DM, T-T-Mb was localized to a lysosomal compartment in HeLa and NRK cells, as judged by immunofluorescence and immunoelectron microscopy. T-T-Mb was rapidly degraded in this compartment by a process that was blocked by inhibitors of lysosomal proteolysis. The DM beta cytoplasmic tail also mediated internalization of anti-Tac antibody from the cell surface and delivery to lysosomes. Deletion from the DM beta cytoplasmic tail of the tyrosine-based motif, YTPL, resulted in cell surface expression of T-T-Mb and a loss of both degradation and internalization; alanine scanning mutagenesis showed that the Y and L residues were critical for these functions. Similarly, mutation of the same Y residue within full-length DM beta resulted in cell surface expression of DM alpha beta heterodimers. Lastly, T-T-Mb was localized by immunoelectron microscopy to the MIIC in a human B lymphoblastoid cell line. Our results suggest that a motif, YTPL, in the cytoplasmic tail of the beta chain of DM is sufficient for targeting either to lysosomes or to the MIIC. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV UTRECHT,FAC MED,DEPT CELL BIOL,UTRECHT,NETHERLANDS. UNIV UTRECHT,FAC MED,INST BIOMEMBRANES,UTRECHT,NETHERLANDS. OI Marks, Michael/0000-0001-7435-7262 NR 92 TC 166 Z9 166 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1995 VL 131 IS 2 BP 351 EP 369 DI 10.1083/jcb.131.2.351 PG 19 WC Cell Biology SC Cell Biology GA RZ595 UT WOS:A1995RZ59500007 PM 7593164 ER PT J AU BENAYAHU, D FRIED, A EFRATY, M ROBEY, PG WIENTROUB, S AF BENAYAHU, D FRIED, A EFRATY, M ROBEY, PG WIENTROUB, S TI BONE-MARROW INTERFACE - PREFERENTIAL ATTACHMENT OF AN OSTEOBLASTIC MARROW STROMAL CELL LINE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE STROMAL CELLS; OSTEOBLASTS; ATTACHMENT; BONE MATRIX; BONE FORMATION ID OSTEO-SARCOMA CELLS; GROWTH-FACTOR-BETA; CHEMOTACTIC RESPONSE; EXTRACELLULAR-MATRIX; GLA PROTEIN; SIALOPROTEIN; LINES; ADHESION; COLLAGEN; INVITRO AB In this study, we report on the cell adhesion properties of marrow stromal cells to extracellular matrix components such as collagen and noncollagenous proteins. The osteoblastic cells and their non-osteoblastic counterparts (MBA series) from the marrow stroma differentially recognized a spectrum of extracellular matrix proteins. The osteoblastic cells, MBA-15, preferentially attached to bone matrix proteins, whereas fibroendothelial MBA-2.1 and adipocytic 14F1.1 cells did not. The MBA-15 cells demonstrated a preference in their attachment to fibronectin > mixture of collagens > bone matrix extracts > collagen type I > noncollagenous proteins. Clonal subpopulations derived from the MBA-15 cell line representing various stages along the osteogenic lineage expressed differential attachment preference. MBA-15.4, a less differentiated clonal line, was compared to MBA-15.6, a mature cell line. (C) 1995 Wiley-Liss, Inc. C1 TEL AVIV UNIV,SACKLER SCH MED,DIV ORTHOPAED,IL-69978 TEL AVIV,ISRAEL. TEL AVIV MED CTR & SCH MED,DANA CHILDRENS HOSP,DEPT PEDIAT ORTHOPAED,IL-64239 TEL AVIV,ISRAEL. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP BENAYAHU, D (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 48 TC 8 Z9 8 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT PY 1995 VL 59 IS 2 BP 151 EP 160 DI 10.1002/jcb.240590204 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TB905 UT WOS:A1995TB90500003 PM 8904309 ER PT J AU BOULANGER, J FAULDS, D EDDY, EM LINGWOOD, CA AF BOULANGER, J FAULDS, D EDDY, EM LINGWOOD, CA TI MEMBERS OF THE 70 KDA HEAT-SHOCK PROTEIN FAMILY SPECIFICALLY RECOGNIZE SULFOGLYCOLIPIDS - ROLE IN GAMETE RECOGNITION AND MYCOPLASMA-RELATED INFERTILITY SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MOUSE SPERMATOGENIC CELLS; SULFATED GLYCOLIPIDS; COGNATE PROTEIN; PLASMODIUM-FALCIPARUM; IMMOBILIZING PROTEIN; SEQUENCE HOMOLOGY; STRESS PROTEINS; BINDING-PROTEIN; COMMON ANTIGEN; RECEPTOR AB We have previously shown that several mycoplasma species associated with infertility bind specifically to sulfated glycolipids isolated from the mammalian reproductive tract. We now show that a germ cell-specific sulfoglycolipid binding protein (SLIP 1), which is a potent inhibitor of sperm/egg binding in vitro, is immunologically related to the heat shock protein(Hsp) 70 family of stress proteins and that Hsps are surface antigens in male germ cells. Our present data demonstrate that several mycoplasma and mammalian Hsps share this glycolipid binding specificity in vitro, and suggest that surface Hsps can function as adhesins which mediate sulfoglycolipid recognition in infectious disease and normal reproductive physiology. (C) 1995 Wiley-Liss, Inc. C1 HOSP SICK CHILDREN,RES INST,DEPT MICROBIOL,TORONTO,ON M5G 1X8,CANADA. UNIV TORONTO,DEPT MICROBIOL,TORONTO,ON M58 1A8,CANADA. UNIV TORONTO,DEPT CLIN BIOCHEM,TORONTO,ON M58 1A8,CANADA. UNIV TORONTO,DEPT BIOCHEM,TORONTO,ON M58 1A8,CANADA. BURLEX CORP,RICHMOND,CA 94804. NIEHS,RES TRIANGLE PK,NC 27709. NR 73 TC 63 Z9 67 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 1995 VL 165 IS 1 BP 7 EP 17 DI 10.1002/jcp.1041650103 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RW531 UT WOS:A1995RW53100002 PM 7559808 ER PT J AU SCHNAPER, HW BARNATHAN, ES MAZAR, A MAHESHWARI, S ELLIS, S CORTEZ, SL BARICOS, WH KLEINMAN, HK AF SCHNAPER, HW BARNATHAN, ES MAZAR, A MAHESHWARI, S ELLIS, S CORTEZ, SL BARICOS, WH KLEINMAN, HK TI PLASMINOGEN ACTIVATORS AUGMENT ENDOTHELIAL-CELL ORGANIZATION IN-VITRO BY 2 DISTINCT PATHWAYS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX COMPONENTS; PROTEOLYTIC ACTIVITY; UROKINASE RECEPTOR; TISSUE INHIBITOR; IV COLLAGENASE; MESSENGER-RNA; INVITRO; ANGIOGENESIS; MEMBRANE; EXPRESSION AB Endothelial cell differentiation into capillary structures is a complex process that requires the concerted effects of several extracellular matrix proteases, including plasminogen activators. Here, the role of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) was evaluated in an in vitro model of endothelial morphogenesis involving organization of human umbilical vein endothelial cells into tubular structures when they are cultured on the basement membrane preparation, Matrigel. Both uPA and tPA were detected in HUVEC cultures on Matrigel, and inhibitors of plasminogen activators or of serine proteases decreased the extent of the tube network formed by the cells. The decrease resulting from serine protease inhibitors was additive to that from matrix metalloproteinase inhibitors which have previously been shown to decrease tube formation in this model, suggesting that the two classes of proteases modulate tube formation by distinct mechanisms. Plasminogen activator inhibitor (PAI)-1 decreased tube formation by 50% when added up to 4.5 h after the initiation of an 18 h assay and caused 25% inhibition when added 9.5 h after culture initiation, indicating that the effects of plasminogen activators are not limited to an early event in the differentiation process. Steady-state expression of mRNA for uPA increased during the first several hours of culture on Matrigel, further supporting a role for PA activity throughout the process of tube formation. These findings suggested that PAs may affect multiple events during tube-forming activity. A fucosylated peptide comprising the amino-terminal domain of uPA that binds to the uPA receptor (uPAR) but lacking proteolytic activity enhanced tube formation. In contrast, a defucosylated form of the same peptide had no effect. Since fucosylation of this fragment has been shown to be essential in other models of cell stimulation by uPA-uPAR interaction, these data support the hypothesis that uPA enhances endothelial morphogenesis both through proteolytic activity and via uPAR occupancy. Plasminogen activators could facilitate angiogenesis in vivo. (C) 1995 Wiley-Liss, Inc. C1 NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. UNIV PENN, DEPT MED, DIV CARDIOL, PHILADELPHIA, PA 19104 USA. TULANE UNIV, SCH MED, DEPT BIOCHEM, NEW ORLEANS, LA 70112 USA. ABBOTT LABS, ABBOTT PK, IL 60064 USA. RP SCHNAPER, HW (reprint author), NORTHWESTERN UNIV, SCH MED,DEPT PEDIAT,DIV NEPHROL,PEDIAT W-140, 303 E CHICAGO AVE, CHICAGO, IL 60611 USA. FU NHLBI NIH HHS [HL-44508]; NIDDK NIH HHS [DK-08712, DK-45449, R01 DK049362] NR 47 TC 69 Z9 69 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 1995 VL 165 IS 1 BP 107 EP 118 DI 10.1002/jcp.1041650114 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RW531 UT WOS:A1995RW53100013 PM 7559792 ER PT J AU MARTIN, A WIGGS, CL ALTEMUS, M RUBENSTEIN, C MURPHY, DL AF MARTIN, A WIGGS, CL ALTEMUS, M RUBENSTEIN, C MURPHY, DL TI WORKING-MEMORY AS ASSESSED BY SUBJECT-ORDERED TASKS IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID FRONTAL-LOBE; DYSFUNCTION; PICTURES; DEFICITS; LESIONS AB We tested patients with obsessive-compulsive disorder (OCD) and normal subjects (n = 18 per group) on a self-paced, working memory task that, based on studies of patients with focal brain lesions and functional brain imaging studies of normals, is largely mediated by prefrontal cortex. The OCD patients had normal working memory spans and normal recognition memory for all types of material tested (abstract words, common objects, and novel nonsense objects). The patients, however, were slow (p < .005), and the time they took to complete the tasks was significantly correlated with ratings of OCD symptoms (r = .539, p < .05) and depression (r = .643, p < .01), but not anxiety. Slowed performance on this self-paced task was discussed in relation to normal response times by OCD patients under typical laboratory conditions. It was suggested that this discrepancy may be related to a broader dissociation between real-world and laboratory performance as seen in some patients with prefrontal lobe dysfunction. RP MARTIN, A (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-41,BETHESDA,MD 20892, USA. RI martin, alex/B-6176-2009 NR 26 TC 49 Z9 50 U1 11 U2 16 PU SWETS ZEITLINGER BV PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 1995 VL 17 IS 5 BP 786 EP 792 DI 10.1080/01688639508405167 PG 7 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA TD240 UT WOS:A1995TD24000013 PM 8557818 ER PT J AU GORDEN, P SKARULIS, MC ROACH, P COMI, RJ FRAKER, DL NORTON, JA ALEXANDER, HR DOPPMAN, JL AF GORDEN, P SKARULIS, MC ROACH, P COMI, RJ FRAKER, DL NORTON, JA ALEXANDER, HR DOPPMAN, JL TI PLASMA PROINSULIN-LIKE COMPONENT IN INSULINOMA - A 25-YEAR EXPERIENCE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ISLET CELL TUMORS C1 NCI, SURG BRANCH, BETHESDA, MD 20892 USA. NATL INST HLTH, WARREN GRANT MAGNUSON CLIN CTR, HENRY M JACKSON FDN, DEPT RADIOL, BETHESDA, MD 20892 USA. DARTMOUTH COLL, HITCHCOCK MED CTR, DEPT MED, HANOVER, NH 03756 USA. WASHINGTON UNIV, SCH MED, DEPT SURG, ST LOUIS, MO 63110 USA. RP GORDEN, P (reprint author), NIDDK, DIABET BRANCH, BETHESDA, MD 20892 USA. NR 22 TC 45 Z9 46 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1995 VL 80 IS 10 BP 2884 EP 2887 DI 10.1210/jc.80.10.2884 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RZ377 UT WOS:A1995RZ37700010 PM 7559869 ER PT J AU ALTEMUS, M DEUSTER, PA GALLIVEN, E CARTER, CS GOLD, PW AF ALTEMUS, M DEUSTER, PA GALLIVEN, E CARTER, CS GOLD, PW TI SUPPRESSION OF HYPOTHALMIC-PITUITARY-ADRENAL AXIS RESPONSES TO STRESS IN LACTATING WOMEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; HORMONE-SECRETION; LUTEINIZING-HORMONE; TREADMILL EXERCISE; GLUCOSE-METABOLISM; MESSENGER-RNA; FEMALE RAT; OXYTOCIN; VASOPRESSIN; PREGNANCY AB In the rat, lactation suppresses a variety of physiological responses to stress. We investigated whether stress-responsive neurohormonal systems are also restrained during breast feeding in humans. We chose treadmill exercise as a stressor because this stimulus produces an exercise intensity-dependent activation of the hypothalamic-pituitary-adrenal axis and the sympathomedullary system that is independent of differences in physical, conditioning among subjects. Ten lactating and ten nonlactating women who were between 7 and 18 weeks postpartum performed 20 min of graded treadmill exercise. The final 5 min of exercise was set to elicit 90% of the maximal oxygen uptake of each subject. Plasma ACTH, cortisol, and glucose responses to exercise were significantly attenuated in lactating women (P < 0.001, P < 0.05, and P < 0.001, respectively). Basal norepinephrine levels were also reduced in lactating women (P < 0.05). These results indicate that stress-responsive neurohormonal systems are restrained in lactating women. C1 NIMH, DIV INTRAMURAL RES PROGRAMS, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT MIL & EMERGENCY MED, BETHESDA, MD 20814 USA. UNIV MARYLAND, DEPT ZOOL, COLLEGE PK, MD 20742 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 65 TC 229 Z9 231 U1 3 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1995 VL 80 IS 10 BP 2954 EP 2959 DI 10.1210/jc.80.10.2954 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RZ377 UT WOS:A1995RZ37700021 PM 7559880 ER PT J AU CASSORLA, F MERICQ, V GARCIA, H CRISTIANO, A AVILA, A BORIC, A INIGUEZ, G MERRIAM, GR AF CASSORLA, F MERICQ, V GARCIA, H CRISTIANO, A AVILA, A BORIC, A INIGUEZ, G MERRIAM, GR TI THE EFFECTS OF BETA(1)-ADRENERGIC BLOCKADE ON THE GROWTH-RESPONSE TO GROWTH-HORMONE (GH)-RELEASING HORMONE-THERAPY IN GH-DEFICIENT CHILDREN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATION TEST; RELEASE; PROPRANOLOL; ACCELERATION; SECRETION; BOYS AB Acute suppression of SRIH secretion with a beta-adrenergic antagonist can increase the GH response to GHRH. To determine whether chronic beta-blockade could enhance the growth-promoting effects of GHRH therapy, we conducted a double blind, placebo-controlled, randomized, cross-over trial of coadministration of the selective beta(1)-antagonist atenolol together with GHRH in 11 GH-deficient children. In randomly chosen order, each patient received two 12-month treatment periods with a single daily injection of GHRH (20 mu g/kg, sc, at bedtime), plus daily oral administration of either atenolol (1 mg/kg) or placebo. The growth velocity increased, rising from a mean +/- SD of 2.6 +/- 0.4 cm/yr before treatment to 5.4 +/- 1.0 cm/yr during the first year of treatment with GHRH plus placebo and to 6.8 +/- 1.2 cm/yr during the first year of treatment with GHRH plus atenolol. The mean growth velocity during treatment with GHRH plus atenolol was significantly greater than that observed during GHRH plus placebo (P < 0.05). After cross-over, however, during the second year of therapy, we did not observe any significant differences in growth velocity between the two groups (4.2 +/- 1.4 us. 3.9 +/- 0.8 cm/yr during treatment with GHRH plus placebo and GHRH plus atenolol, respectively). The mean 24-h serum GH levels were 1.4 +/- 0.9 mu g/L during the baseline period, 1.3 +/- 0.2 and 2.0 +/- 1.4 mu g/L during the first year of GHRH plus placebo and GHRH plus atenolol, respectively (P = NS), and 2.7 +/- 1.4 and 1.4 +/- 0.4 mu g/L during the second year of GHRH plus placebo and GHRH plus atenolol, respectively (P < 0.05). This is the first demonstration that alteration of neurotransmitter action can enhance the therapeutic response to a hypothalamic releasing factor. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. AMER LAKE VET ADM MED CTR, SEATTLE, WA 98195 USA. UNIV WASHINGTON, DIV METAB ENDOCRINOL & NUTR, SEATTLE, WA 98195 USA. RP CASSORLA, F (reprint author), UNIV CHILE, SCH MED, INST INVEST MATERNO INFANTIL, CASILLA 226-3, SANTIAGO, CHILE. RI Mericq, Veronica/F-3927-2010 NR 34 TC 7 Z9 7 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1995 VL 80 IS 10 BP 2997 EP 3001 DI 10.1210/jc.80.10.2997 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RZ377 UT WOS:A1995RZ37700028 PM 7559887 ER PT J AU EISENHOFER, G RUNDQUIST, B ANEMAN, A FRIBERG, P DAKAK, N KOPIN, IJ JACOBS, MC LENDERS, JWM AF EISENHOFER, G RUNDQUIST, B ANEMAN, A FRIBERG, P DAKAK, N KOPIN, IJ JACOBS, MC LENDERS, JWM TI REGIONAL RELEASE AND REMOVAL OF CATECHOLAMINES AND EXTRANEURONAL METABOLISM TO METANEPHRINES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BLOOD-FLOW; PLASMA; NOREPINEPHRINE; PHEOCHROMOCYTOMA; DIHYDROXYPHENYLGLYCOL; EPINEPHRINE; DIAGNOSIS; HEART AB Norepinephrine (NE) and epinephrine (E) are metabolized extra-neuronally by catechol-O-methyl-transferase to the metanephrines (MNs), normetanephrine (NMN) and metanephrine (MN). Subjects in this study received infusions of tritium-labeled NE and E. Concentrations of MNs and catecholamines were measured in plasma flowing into and out of the heart, forearm, lungs, kidneys, mesenteric organs (gastrointestinal tract, spleen, and pancreas), liver, and adrenals to examine the regional production of MNs from circulating and locally released catecholamines. NE spillover from mesenteric organs and a kidneys accounted for 64% of the spillover from all tissues. There was detectable spillover off from most extraadrenal tissues, but 91% was from the adrenals. The production of MNs from locally released and circulating catecholamines varied widely among tissues. The liver made the largest contribution to removal of circulating NE (57%) and E (32%) and the largest contribution to the production of NMN (54%) and MN (37%) from metabolism of circulating catecholamines. In all other tissues mere NMN was produced from locally released than from circulating NE. Thus, the metabolism of circulating NE was responsible for only 19% of the total production of NMN. An even smaller portion (6%) of plasma MN was derived from metabolism of circulating E. Most plasma MN (91%) was produced within the adrenals, which also provided the largest single source (23%) of NMN. The regional variation in extraneuronal production of MNs indicates considerable heterogeneity in how circulating and locally released catecholamines are handled by different tissues. The substantial contribution of the adrenals to the production of MNs explains the extraordinary sensitivity of these metabolites for the diagnosis of pheochromocytoma. C1 NHLBI, CARDIOL BRANCH, BETHESDA, MD 20892 USA. UNIV NIJMEGEN ST RADBOUD HOSP, DEPT INTERNAL MED, 6500 HB NIJMEGEN, NETHERLANDS. GOTHENBURG UNIV, DEPT CARDIOL, GOTHENBURG, SWEDEN. GOTHENBURG UNIV, DEPT PHYSIOL, GOTHENBURG, SWEDEN. GOTHENBURG UNIV, DEPT CLIN PHYSIOL, GOTHENBURG, SWEDEN. RP EISENHOFER, G (reprint author), NINCDS, CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N214,10 CTR DR, MSC 1424, BETHESDA, MD 20892 USA. RI Lenders, J.W.M./L-4487-2015 NR 30 TC 109 Z9 112 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1995 VL 80 IS 10 BP 3009 EP 3017 DI 10.1210/jc.80.10.3009 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RZ377 UT WOS:A1995RZ37700030 PM 7559889 ER PT J AU NIELSEN, S MARPLES, D BIRN, H MOHTASHAMI, M DALBY, NO TRIMBLE, W KNEPPER, M AF NIELSEN, S MARPLES, D BIRN, H MOHTASHAMI, M DALBY, NO TRIMBLE, W KNEPPER, M TI EXPRESSION OF VAMP2-LIKE PROTEIN IN KIDNEY COLLECTING DUCT INTRACELLULAR VESICLES - COLOCALIZATION WITH AQUAPORIN-2 WATER CHANNELS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE VASOPRESSIN; VESICULAR TRAFFICKING; TETANUS TOXIN; IMMUNOELECTRON MICROSCOPY ID INTEGRAL MEMBRANE-PROTEIN; NEUROTRANSMITTER RELEASE; SYNAPTIC VESICLES; TETANUS-TOXIN; VAMP FAMILY; RAT-KIDNEY; SYNAPTOBREVIN; INHIBITION; RECEPTORS; SYNTAXIN AB Body water balance is controlled by vasopressin, which regulates Aquaporin-2 (AQP2) water channels in kidney collecting duct cells by vesicular trafficking between intracellular vesicles and the plasma membrane, To examine the molecular apparatus involved in vesicle trafficking and vasopressin regulation of AQP2 in collecting duct cells, we tested if targeting proteins expressed in the synaptic vesicles, namely vesicle-associated membrane proteins 1 and 2 (VAMP1 and 2), are expressed in kidney collecting duct, Immunoblotting revealed specific labeling of VAMP2 (18-kD band) but not VAMP1 in membrane fractions prepared from kidney inner medulla, Controls using preadsorbed antibody or preimmune serum were negative, Bands of identical molecular size were detected in immunoblots of brain membrane vesicles and purified synaptic vesicles, VAMP2 in kidney membranes was cleaved by tetanus toxin, revealing a tetanus toxin-sensitive VAMP homologue, Similarly, tetanus toxin cleaved VAMP2 in synaptic vesicles, In kidney inner medulla, VAMP2 was predominantly expressed in the membrane fraction enriched for intracellular vesicles, with little or no VAMP2 in the plasma membrane enriched fraction, This was confirmed by immunocytochemistry using semithin cryosections, which showed mainly vesicular labeling in collecting duct principal cells, with no labeling of intercalated cells, VAMP2 immunolabeling colocalized with AQP2 labeling in intracellular vesicles, as determined by immunoelectron microscopy after double immunolabeling of isolated vesicles. Quantitative analysis of 1,310 vesicles revealed a highly significant association of both AQP2 and VAMP2 in the same vesicles (P < 0.0001), Furthermore, the presence of AQP2 in vesicles immunoisolated with anti-VAMP2 antibodies was confirmed by im munoblotting, In conclusion, VAMP2, a component of the neuronal SNARE; complex, is expressed in vesicles carrying AQP2, suggesting a role in vasopressin-regulated vesicle trafficking of AQP2 water channels. C1 UNIV TORONTO,DEPT PHYSIOL,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,NEURODEGENERAT DIS RES CTR,TORONTO,ON M5S 1A8,CANADA. AARHUS UNIV,DEPT BIOL MOLEC,DK-8000 AARHUS,DENMARK. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. RP NIELSEN, S (reprint author), AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS,DENMARK. RI Birn, Henrik/C-3931-2009; OI Birn, Henrik/0000-0003-3715-7266 NR 38 TC 128 Z9 130 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1995 VL 96 IS 4 BP 1834 EP 1844 DI 10.1172/JCI118229 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RY954 UT WOS:A1995RY95400018 PM 7560075 ER PT J AU BILATO, C PAULY, RR MELILLO, G MONTICONE, R GORELICKFELDMAN, D GLUZBAND, YA SOLLOTT, SJ ZIMAN, B LAKATTA, EG CROW, MT AF BILATO, C PAULY, RR MELILLO, G MONTICONE, R GORELICKFELDMAN, D GLUZBAND, YA SOLLOTT, SJ ZIMAN, B LAKATTA, EG CROW, MT TI INTRACELLULAR SIGNALING PATHWAYS REQUIRED FOR RAT VASCULAR SMOOTH-MUSCLE CELL-MIGRATION - INTERACTIONS BETWEEN BASIC FIBROBLAST GROWTH-FACTOR AND PLATELET-DERIVED GROWTH-FACTOR SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CALCIUM/CALMODULIN-DEPENDENT KINASE II; CELL MIGRATION; SMOOTH MUSCLE CELLS; BASIC FIBROBLAST GROWTH FACTOR; PLATELET-DERIVED GROWTH FACTOR ID PROTEIN KINASE-II; AORTIC ENDOTHELIAL-CELLS; MESSENGER-RNA; PC12 CELLS; PROLIFERATION; INVITRO; INJURY; ACCUMULATION; ANGIOGENESIS; ANGIOPLASTY AB Intracellular signaling pathways activated by both PDGF and basic fibroblast growth factor (bFGF) have been implicated in the migration of vascular smooth muscle cells (VSMC), a key step in the pathogenesis of many vascular diseases, We demonstrate here that, while bFGF is a weak chemoattractant for VSMCs, it is required for the PDGF-directed migration of VSMCs and the activation of calcium/calmodulin-dependent protein kinase II (CamKinase II), an intracellular event that we have previously shown to be important in the regulation of VSMC migration, Neutralizing antibodies to bFGF caused a dramatic reduction in the size; of the intracellular calcium transient normally seen after PDGF stimulation and inhibited both PDGF-directed VSMC migration and CamKinase II activation, Partially restoring the calcium transient with ionomycin restored migration and CamKinase II activation as did the forced expression of a mutant CamKinase II that had been ''locked'' in the active state by site-directed mutagenesis. These results suggest that bFGF links PDGF receptor stimulation to changes in intracellular calcium and CamKinase II activation, reinforcing the central role played by CamKinase II in regulating VSMC migration. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,VASC BIOL GRP,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21287. RI Melillo, Guido/K-6341-2016 OI Melillo, Guido/0000-0002-2379-9471 NR 61 TC 81 Z9 83 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1995 VL 96 IS 4 BP 1905 EP 1915 DI 10.1172/JCI118236 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RY954 UT WOS:A1995RY95400025 PM 7560082 ER PT J AU UBAGAI, T LEI, KJ HUANG, S MUDD, SH LEVY, HL CHOU, JY AF UBAGAI, T LEI, KJ HUANG, S MUDD, SH LEVY, HL CHOU, JY TI MOLECULAR MECHANISMS OF AN INBORN ERROR OF METHIONINE PATHWAY - METHIONINE ADENOSYLTRANSFERASE DEFICIENCY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE METHIONINE ADENOSYLTRANSFERASE DEFICIENCY; GENETIC MUTATIONS; HUMAN METHIONINE ADENOSYLTRANSFERASE GENE; SINGLE-STRANDED CONFORMATION POLYMORPHISM ID S-ADENOSYLMETHIONINE SYNTHETASE; RAT-LIVER; PURIFICATION; EXPRESSION; CLONING; HYPERMETHIONINEMIA AB Methionine adenosyltransferase (MAT) is a key enzyme in transmethylation, transsulfuration, and the biosynthesis of polyamines. Genetic deficiency of alpha/beta-MAT causes isolated persistent hypermethioninemia and, in some cases, unusual breath odor or neural demyelination. However, the molecular mechanism(s) underlying this deficiency has not been clearly defined. In this study, we characterized the human alpha/beta-MAT transcription unit and identified several mutations in the gene of patients with enzymatically confirmed diagnosis of MAT deficiency. Site-directed mutagenesis and transient expression assays demonstrated that these mutations partially inactivate MAT activity. These results establish the molecular basis of this disorder and allow for the development of DNA-based methodologies to investigate and diagnose hypermethioninemic individuals suspected of having abnormalities at this locus. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. NR 25 TC 47 Z9 48 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1995 VL 96 IS 4 BP 1943 EP 1947 DI 10.1172/JCI118240 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RY954 UT WOS:A1995RY95400029 PM 7560086 ER PT J AU PANOS, RJ BAK, PM SIMONET, WS RUBIN, JS SMITH, LJ AF PANOS, RJ BAK, PM SIMONET, WS RUBIN, JS SMITH, LJ TI INTRATRACHEAL INSTILLATION OF KERATINOCYTE GROWTH-FACTOR DECREASES HYPEROXIA-INDUCED MORTALITY IN RATS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ALVEOLAR TYPE II CELL; KERATINOCYTE GROWTH FACTOR; PROLIFERATION OXYGEN ID PULMONARY SUPEROXIDE-DISMUTASE; INDUCED LUNG INJURY; II CELLS; OXYGEN-TOXICITY; PROTECTS RATS; DNA-SYNTHESIS; EXPRESSION; MICE; EPITHELIUM; PROLIFERATION AB Alveolar type II cell proliferation occurs after many forms of lung injury and is thought to play a critical role in alveolar epithelial repair. Keratinocyte growth factor/fibroblast growth factor 7 (KGF) has been shown to promote alveolar type II cell growth in primary culture and alveolar epithelial hyperplasia in vivo. In this study, we used immunohistochemical analysis to determine the intrapulmonary distribution and cellular localization of recombinant human KGF (rhKGF) instilled into the trachea of rats. 6 h after administration, immunoreactive KGF was observed within the lung parenchyma and along alveolar epithelial cell membranes. By 18-24 h, KGF was detected intracellularly in alveolar epithelial cells and intraalveolar macrophages. Immunoreactive KGF was not demonstrable 48 h after delivery or in lung sections from PBS-treated animals. Intratracheal instillation of 5 mg/kg rhRGF stimulated a marked, time-dependent increase in the alveolar type II cell specific labeling index to a maximum level of 33+/-3% 48 h after rhKGF administration compared with 1.3+/-0.3% after PBS instillation. In addition, this increase in type II cell proliferation in vivo was documented by flow cytometric analysis of isolated type II cells which revealed a nearly fivefold increase in the proportion of cells traversing through the S and G2/M phases of the cell cycle. To test the hypothesis that KGFs effects on type II cells in vivo might affect the response to lung injury, rats were treated with rhKGF and exposed to hyperoxia. Animals that received 1 or 5 mg/kg rhKGF exhibited dramatically reduced mortality (P < 0.001, for both doses). Survival for animals treated with 0.1 mg/kg rhKGF was not significantly different from either untreated rats or animals treated with heat-denatured rhKGF. The lungs of rhKGE-treated animals that survived hyperoxia exposure had minimal hemorrhage and no exudate within the intraalveolar space. These experiments established that intratracheal administration of rhKGF stimulated alveolar type II cell proliferation in vivo and reduced hyperoxia-induced lung injury in rats. Directed delivery of KGF to the lungs may provide a therapeutic strategy to preserve or restore the alveolar epithelium during exposure to hyperoxia or other injurious agents. C1 LAKESIDE VET ADM MED CTR,CHICAGO,IL 60611. AMGEN INC,THOUSAND OAKS,CA 91320. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP PANOS, RJ (reprint author), NORTHWESTERN UNIV,SCH MED,DIV PULM,ROOM 777,PASSAVANT PAVIL,303 E SUPERIOR ST,CHICAGO,IL 60611, USA. OI Smith, Lewis J/0000-0002-4728-1562 NR 59 TC 188 Z9 192 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1995 VL 96 IS 4 BP 2026 EP 2033 DI 10.1172/JCI118250 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RY954 UT WOS:A1995RY95400039 PM 7560096 ER PT J AU GREVER, M KOPECKY, K APPELBAUM, F FOUCAR, MK AF GREVER, M KOPECKY, K APPELBAUM, F FOUCAR, MK TI OPTIMAL TREATMENT FOR UNTREATED PATIENTS WITH HAIRY-CELL LEUKEMIA - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. UNIV NEW MEXICO HOSP,ALBUQUERQUE,NM. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY. MAYO CLIN,ROCHESTER,MN. LONG ISL JEWISH MED CTR,NEW HYDE PK,NY 11042. QUEENS UNIV,KINGSTON,ON,CANADA. NCI,BETHESDA,MD 20892. RP GREVER, M (reprint author), JOHNS HOPKINS UNIV,BALTIMORE,MD 21218, USA. NR 5 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1995 VL 13 IS 10 BP 2678 EP 2679 PG 2 WC Oncology SC Oncology GA RZ744 UT WOS:A1995RZ74400030 ER PT J AU KETTER, TA POST, RM PAREKH, PI WORTHINGTON, K AF KETTER, TA POST, RM PAREKH, PI WORTHINGTON, K TI ADDITION OF MONOAMINE-OXIDASE INHIBITORS TO CARBAMAZEPINE - PRELIMINARY EVIDENCE OF SAFETY AND ANTIDEPRESSANT EFFICACY IN TREATMENT-RESISTANT DEPRESSION SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID IMPORTANT DRUG-INTERACTIONS; ANERGIC BIPOLAR DEPRESSION; DOUBLE-BLIND CROSSOVER; REFRACTORY DEPRESSION; PHARMACOKINETIC INTERACTION; RECURRENT DEPRESSION; TRANYLCYPROMINE; IMIPRAMINE; PHENELZINE; PRINCIPLES AB Background: Depression is often resistant to treatment with mood stabilizers. The antidepressant effects of carbamazepine can be potentiated by lithium supplementation, but some patients fail to respond-to the combination. Although monoamine oxidase inhibitors (MAOIs) appear useful in atypical and bipolar depressions, concerns have been raised regarding safety and pharmacokinetic interactions when they are combined with carbamazepine. Method: Ten inpatients (7 bipolar, 3 unipolar) with refractory DSM-III-R major depression, also resistant to double-blind treatment with carbamazepine, plus lithium augmentation in 8, received double-blind MAOI augmentation (phenelzine in 4, tranylcypromine in 6). Results: All 10 patients tolerated the addition of an MAOI well, and mean self-rated side effect scores did not change significantly. Four of 10 patients improved substantially and became euthymic, allowing discharge from hospital on the carbamazepine +/- lithium plus MAOI combination. These 4 patients improved in spite of pries inadequate responses to the same MAOI without carbamazepine and carbamazepine without an MAOI. Conclusion: This preliminary evidence suggests that the addition of MAOIs to carbamazepine +/- lithium may be well tolerated, may not affect carbamazepine and lithium pharmacokinetics, and may provide relief of refractory depressive symptoms in some patients. Further studies are needed to establish the safety and efficacy of combining carbamazepine with MAOIs. RP KETTER, TA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 33 Z9 33 U1 1 U2 2 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 OCT PY 1995 VL 56 IS 10 BP 471 EP 475 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA TA463 UT WOS:A1995TA46300006 PM 7559374 ER PT J AU KETTER, TA JENKINS, JB SCHROEDER, DH PAZZAGLIA, PJ MARANGELL, LB GEORGE, MS CALLAHAN, AM HINTON, ML CHAO, J POST, RM AF KETTER, TA JENKINS, JB SCHROEDER, DH PAZZAGLIA, PJ MARANGELL, LB GEORGE, MS CALLAHAN, AM HINTON, ML CHAO, J POST, RM TI CARBAMAZEPINE BUT NOT VALPROATE INDUCES BUPROPION METABOLISM SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID IMPORTANT DRUG-INTERACTIONS; MAJOR BASIC METABOLITES; BIPOLAR DISORDER; 3 METABOLITES; PLASMA; PHARMACOKINETICS; ANTIDEPRESSANTS; DISPOSITION; DEPRESSION; VOLUNTEERS AB Bupropion (BUP) may be less likely than other antidepressants to cause switches into mania and rapid cycling, suggesting utility in bipolar disorder. The combination of BW with the mood-stabilizing anticonvulsants carbamazepine (CBZ) or valproate (VPA) is a strategy that might further lessen the risk of mania. CBZ induces, and to a lesser extent WA inhibits the hepatic metabolism of various medications, but their effects on BUP have not been previously studied. Inpatients with mood disorders had pharmacokinetic profiles of BUP and metabolites assessed after single, oral, 150-mg doses of BUP while receiving placebo (N = 17) or during chronic blind CBZ (N = 12) or VPA (N = 5) monotherapy. CBZ but not VPA therapy decreased BUP peak concentrations (C-max) by 87% (p < 0.0001) and 24-h area under the curve (AUG) by 90% (p < 0.0001), threohydrobupropion C-max by 81% (p < 0.0009) and AUC by 86% (p < 0.002), and erythropydrobupropion C-max by 86% (p < 0.05) and AUC by 96% (p < 0.05). CBZ increased hydroxybupropion (H-BUP) C-max by 71% (p < 0.007) and AUC by 50% (p < 0.05). VPA increased H-BW C-max by 56% (p < 0.09) and H-BUP AUC by 94% (p < 0.02). Thus, CBZ markedly decreased BUP and increased H-BUP concentrations, whereas VPA did not affect BUP but increased H-BUP concentrations. Further studies are required to determine how these differential effects of CBZ and VPA on BUP pharmacokinetics influence the tolerability and efficacy of combination therapies with these agents. C1 NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. RP KETTER, TA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,ROCKVILLE,MD 20857, USA. NR 58 TC 69 Z9 69 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 1995 VL 15 IS 5 BP 327 EP 333 DI 10.1097/00004714-199510000-00004 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA RY196 UT WOS:A1995RY19600004 PM 8830063 ER PT J AU HOAGWOOD, K HIBBS, E BRENT, D JENSEN, P AF HOAGWOOD, K HIBBS, E BRENT, D JENSEN, P TI INTRODUCTION TO THE SPECIAL SECTION - EFFICACY AND EFFECTIVENESS IN STUDIES OF CHILD AND ADOLESCENT PSYCHOTHERAPY SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article AB This article introduces a special series on ''transporting'' studies of the efficacy of psychotherapy into studies of their effectiveness. Models of the relationship between efficacy and effectiveness are described. Traditional linear models of the phases of scientific expansion suggest that findings from efficacy studies can be transported into broader population samples only after a prescribed series of steps have been followed, with the ultimate goal of implementing treatments that have broad public health implications. An alternative 3-dimensional model is described. This new model posits as its organizing principle flexible movement between dimensions of efficacy and effectiveness across multiple axes. C1 WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA. RP HOAGWOOD, K (reprint author), NIMH,SERV RES BRANCH,5600 FISHERS LANE,ROCKVILLE,MD 20852, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 22 TC 175 Z9 176 U1 0 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 1995 VL 63 IS 5 BP 683 EP 687 DI 10.1037/0022-006X.63.5.683 PG 5 WC Psychology, Clinical SC Psychology GA RY275 UT WOS:A1995RY27500001 PM 7593860 ER PT J AU Nelson, R Pettitt, DJ Knowler, WC Bennett, PH AF Nelson, R Pettitt, DJ Knowler, WC Bennett, PH TI Prediabetic blood pressure and familial predisposition to renal disease in Pima Indians with non-insulin-dependent diabetes mellitus SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article; Proceedings Paper CT 4th International Symposium on Hypertension Associated With Diabetes Mellitus, a Satellite Symposium of the 15th International-Diabetes-Federation Congress CY NOV 04-05, 1994 CL OTSU, JAPAN SP Int Diabet Federat ID URINARY ALBUMIN EXCRETION; MICROALBUMINURIA; SUSCEPTIBILITY; NEPHROPATHY AB Renal disease is a frequent complication of non-insulin-dependent diabetes in the Pima Indians from the Gila River Indian Community in Arizona, This review describes the relationship between prediabetic blood pressure and the subsequent development of renal disease, and characterizes the familial aggregation of diabetic renal disease in this population. RP Nelson, R (reprint author), NIDDK,NIH,PHOENIX EPIDEMIOL & CLIN RES BRANCH,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. NR 12 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 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD OCT-DEC PY 1995 VL 9 IS 4 BP 212 EP 214 DI 10.1016/1056-8727(95)80004-X PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UA696 UT WOS:A1995UA69600004 PM 8573729 ER PT J AU MURABITO, JM LARSON, MG LIN, ST EVANS, JC LEVY, D AF MURABITO, JM LARSON, MG LIN, ST EVANS, JC LEVY, D TI UNEXPLAINED GRADUAL-ONSET Q-WAVE PATTERNS - A CASE SERIES FROM THE FRAMINGHAM-STUDY SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Q WAVE; MYOCARDIAL INFARCTION; PROGNOSIS AB Original cohort members of the Framingham Study were studied to determine prognosis associated with unexplained (gradual-onset) Q wave pat terns detected on routine electrocardiograms (ECGs). Biennial ECGs were obtained on Subjects beginning in 1948. The index ECG was read independently and then serially in relation to all previous tracings for evidence of myocardial infarction. Proportional hazards modeling was used to assess the risk for outcomes in those with unexplained (gradual-onset) Q wave patterns compared with subjects with unrecognized myocardial infarcts (abrupt-onset Q waves) and compared with referent subjects. Unexplained Q wave patterns developed in 53 men and 39 women. Subjects with unexplained Q wave patterns had less than 40% of the risk for myocardial infarction or coronary death as compared with those with unrecognized myocardial infarction after adjusting for risk factors (hazard ratio, 0.38; 95% confidence interval, 0.19, 0.78; P = .008) and a trend toward a lower risk for overall mortality (adjusted hazard ratio, 0.73; 95% confidence interval, 0.46, 1.16; P = .18). Risks for myocardial infarction or coronary death and overall mortality were similar in subjects with unexplained Q wave patterns and referent subjects in the fully adjusted models. Detection of prominent Q waves on an ECG requires comparison with prior tracings to differentiate the unexplained Q wave pattern from the unrecognized infarct, conditions that have significantly different prognostic implications. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. BOSTON UNIV,SCH MED,PREVENT MED SECT,BOSTON,MA 02118. NHLBI,BETHESDA,MD 20892. METROWEST MED CTR,FRAMINGHAM,MA. BETH ISRAEL HOSP,DIV CARDIOL & CLIN EPIDEMIOL,BOSTON,MA 02215. BOSTON UNIV,SCH MED,GEN INTERNAL MED SECT,BOSTON,MA 02118. FU NHLBI NIH HHS [N01-HC-3803] NR 26 TC 3 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD OCT PY 1995 VL 28 IS 4 BP 267 EP 275 DI 10.1016/S0022-0736(05)80044-5 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TB529 UT WOS:A1995TB52900001 PM 8551169 ER PT J AU Friedman, TC Yanovski, JA AF Friedman, TC Yanovski, JA TI Morning plasma free cortisol: Inability to distinguish patients with mild Cushing syndrome from patients with pseudo-Cushing states SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE hypercortisolism; Cushing syndrome; cortisol; depression; obesity; pseudo-Cushing states ID CORTICOSTEROID-BINDING GLOBULIN; CORTICOTROPIN-RELEASING HORMONE; RADIOIMMUNOASSAY; GLUCOCORTICOIDS AB Patients with Cushing syndrome have elevated 24 h urinary free cortisol excretion and loss of diurnal rhythm of plasma cortisol, however, morning total plasma cortisol concentrations are often similar to those of normal individuals, To test the hypothesis that an elevated morning plasma free cortisol could distinguish patients with Cushing syndrome from those without the disorder, we measured plasma free cortisol levels at 08:00 in 20 patients with surgically-confirmed mild Cushing syndrome, 19 patients with pseudo-Cushing states, and 9 normal volunteers, We then determined the sensitivity, specificity and diagnostic accuracy of plasma free cortisol for the diagnosis of hypercortisolism and for the diagnosis of Cushing syndrome, Plasma free cortisol was compared to 08:00 total plasma cortisol and to basal 24 hour urinary free cortisol, Morning plasma free cortisol was significantly elevated in patients with mild Cushing syndrome (58+/-6 nmol/L; mean+/-SE) compared to plasma free cortisol in patients with pseudo-Cushing states (36+/-6 nmol/L) (p<0.005) and normal volunteers (22+/-4 nmol/L) (p<0.0005). Total morning cortisol was significantly greater in patients with mild Cushing syndrome (470+/-28 nmol/L) than in normal volunteers (310+/-33 nmol/L, p<0.05) but was not different from patients with pseudo-Cushing states (410+/-47 nmol/L, p=NS), Urinary free cortisol was also significantly greater in mild Cushing syndrome (540+/-50 nmol/d) than in patients with pseudo-Cushing states (430+/-41 nmol/d, p<0.05) or normal volunteers (160+/-28 nmol/d, p<0.0001). However, there was considerable overlap of plasma free cortisol, plasma total cortisol and urinary free cortisol between the three groups precluding these tests alone from being useful to distinguish patients with mild Cushing syndrome from patients with pseudo-Cushing states, To achieve 100% sensitivity for the diagnosis of Cushing syndrome, the specificity for plasma free cortisol, plasma total cortisol and urinary free cortisol was 0.11, 0.32 and 0.32, respectively, We conclude that plasma free cortisol is of limited value in the differential diagnosis of hypercortisolism. C1 NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD USA. NR 27 TC 8 Z9 8 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD OCT PY 1995 VL 18 IS 9 BP 696 EP 701 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TN191 UT WOS:A1995TN19100004 PM 8719300 ER PT J AU MUROI, M MUROI, Y ITO, N RICE, NR SUZUKI, T AF MUROI, M MUROI, Y ITO, N RICE, NR SUZUKI, T TI EFFECTS OF PROTEASE INHIBITORS ON LPS-MEDIATED ACTIVATION OF A MOUSE MACROPHAGE CELL-LINE (J774) SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; BINDING PROTEIN; KINASE-C; ALPHA; LIPOPOLYSACCHARIDE; PHOSPHORYLATION; TRANSCRIPTION; EXPRESSION; MECHANISM AB Pretreatment (1 h) of a mouse macrophage-like cell line, J774, with the protease inhibitor, phenylalanine-chloromethyl ketone (PCK) or its structural analogue, tosylphenylalanine chloromethyl ketone (TPCK) was found to cause substantial inhibition of LPS-triggered activation of NF-kappa B. Pretreatment of cells with other types of protease inhibitors or their various structural analogues had no effect, PCK or TPCK appeared to exert its inhibitory effect by: (i) partially preventing LPS-triggered degradation of I kappa B alpha protein; (ii) preventing LPS-triggered nuclear translocation of NF-kappa B proteins (p50, RelA and Rel); and (iii) inhibiting the DNA-binding activities of NF-kappa B proteins, Pretreatment of cells with PCK or TPCK also resulted in the total or partial inhibition of LPS activatable (AP-1 or CREB) or constitutivety-existing (Oct-1) transcription factors, but not of another constitutively-expressed transcription factor (SP-1), Pretreatment of J774 cells with PCK was found to substantially suppress LPS-induced expression of mRNAs specific for cytokine genes (TNF alpha, IL-1 alpha and beta, and IL-6), inducible nitric oxide synthase (iNOS) gene and I kappa B alpha gene, but not NF-kappa B1 p105 gene or beta-actin gene, Furthermore, PCK pretreatment inhibited, in a dose-dependent manner, LPS-triggered production of nitric oxide production and tumoricidal activity. C1 UNIV KANSAS,MED CTR,DEPT MICROBIOL MOLEC GENET & IMMUNOL,KANSAS CITY,KS 66160. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 37 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PD OCT PY 1995 VL 2 IS 5 BP 337 EP 347 PG 11 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA TD921 UT WOS:A1995TD92100004 ER PT J AU EPSTEIN, MM DIROSA, F JANKOVIC, D SHER, A MATZINGER, P AF EPSTEIN, MM DIROSA, F JANKOVIC, D SHER, A MATZINGER, P TI SUCCESSFUL T-CELL PRIMING IN B-CELL-DEFICIENT MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN-PRESENTING CELLS; MIXED LEUKOCYTE REACTION; MONOCLONAL-ANTIBODY; SCHISTOSOMA-MANSONI; LYMPHOCYTES-B; GRANULOMA-FORMATION; DIFFERENTIATION ANTIGENS; DENDRITIC CELLS; LYMPH-NODES; INDUCTION AB B cells are an abundant population of lymphocytes that can efficiently capture, process, and present antigen for recognition by activated or memory T cells. Controversial experiments and arguments exist, however, as to whether B cells are or should be involved in the priming of virgin T cells in vivo. Using B cell-deficient mice, we have studied the role of B cells as antigen-presenting cells in a wide variety of tests, including assays of T cell proliferation and cytokine production in responses to protein antigens, T cell killing to minor and major histocompatibility antigens, skin graft rejection, and the in vitro and in vivo responses to shistosome eggs. We found that B cells are not critical for either CD4 or CD8 T cell, priming in any of these systems. This finding lends support to the notion that the priming of T cells is reserved for specialized cells such as dendritic cells and that antigen presentation by B cells serves distinct immunological functions. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP EPSTEIN, MM (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BLDG 4,ROOM 111,BETHESDA,MD 20892, USA. RI Di Rosa, Francesca/J-8116-2014 NR 73 TC 254 Z9 257 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1995 VL 182 IS 4 BP 915 EP 922 DI 10.1084/jem.182.4.915 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RW879 UT WOS:A1995RW87900003 PM 7561694 ER PT J AU SEDER, RA GRABSTEIN, KH BERZOFSKY, JA MCDYER, JF AF SEDER, RA GRABSTEIN, KH BERZOFSKY, JA MCDYER, JF TI CYTOKINE INTERACTIONS IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS - ROLES OF INTERLEUKIN (IL)-2, IL-12, AND IL-15 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACQUIRED IMMUNE-DEFICIENCY; CD4+ T-CELLS; SEROPOSITIVE INDIVIDUALS; MONOCLONAL-ANTIBODIES; SYNDROME AIDS; LYMPHOCYTES; RESPONSES; HELPER AB Cytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4(+) T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toroid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the beta chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endoge- nous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-gamma induction from PBMC's or CD4(+) T cells in response to mitogen or tetanus toroid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL-2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4(+) T cells had little effect on IL-2, IL-4, or IFN-gamma production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN-gamma production from these cultures. The role that endogenous cytokines have on IFN-gamma induction was also studied. Addition of a neutralizing antibody to the cr chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-gamma production. Neutralization of endogenous IL-15 also resulted in diminished IFN-gamma production from cultures stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs and CD4(+) T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts of IL-4 were detected from CD4(+) T cells but not PBMCs from most individuals tested. IFN-gamma and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism of cytokine regulation in HIV- infected individuals, and they provide evidence that IL-15 may be a useful immune modulator. C1 IMMUNEX CORP,SEATTLE,WA 98101. NCI,METAB BRANCH,BETHESDA,MD 20892. RP SEDER, RA (reprint author), NIAID,9000 ROCKVILLE PIKE,BLDG 10,ROOM 11C215,BETHESDA,MD 20892, USA. NR 32 TC 100 Z9 102 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1995 VL 182 IS 4 BP 1067 EP 1077 DI 10.1084/jem.182.4.1067 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RW879 UT WOS:A1995RW87900018 PM 7561680 ER PT J AU NIE, JY KIRK, KL AF NIE, JY KIRK, KL TI SYNTHESIS OF FLUORO-VERATRALDEHYDES AND POLYFLUORO-VERATRALDEHYDES BY ELECTROPHILIC FLUORINATION SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE FLUOROVERATRALDEHYDES; POLYFLUOROVERATRALDEHYDES; ELECTROPHILIC FLUORINATION; NMR SPECTROSCOPY; MASS SPECTROMETRY AB Lithiation of oxazolines derived from fluorinated veratric acid, followed by electrophilic fluorination and subsequent reductive oxazoline cleavage, provides a convenient route to di- and tri-fluoroveratraldehydes. Similarly, 4-fluoroveratrol was converted by lithiation and fluorination to 3,4-difluoroveratrol, which can be used to prepare 5,6-difluoroveratraldehyde. C1 NIDDKD, BETHESDA, MD 20892 USA. NR 6 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD OCT PY 1995 VL 74 IS 2 BP 297 EP 301 DI 10.1016/0022-1139(95)90108-T PG 5 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA TA727 UT WOS:A1995TA72700028 ER PT J AU NIE, JY KIRK, KL AF NIE, JY KIRK, KL TI SYNTHESIS OF 2,6-DIFLUORODOPAMINE AND 3-(2,6-DIFLUORO-3,4-DIHYDROXYPHENYL)ALANINE SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE SYNTHESIS; DIFLUORODOPAMINE; DIFLUORODIHYDROXYPHENYLALANINE; NMR SPECTROSCOPY; MASS SPECTROMETRY ID FLUORINE AB 2,6-Difluorodopamine and 3-(2,6-difluoro-3,4-dihydroxyphenyl)alanine were prepared by side-chain elaboration of 2,6-difluoroveratraldehyde, followed by removal of protecting groups. C1 NIDDKD, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD OCT PY 1995 VL 74 IS 2 BP 303 EP 306 DI 10.1016/0022-1139(95)90109-U PG 4 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA TA727 UT WOS:A1995TA72700029 ER PT J AU HELDER, MN OZKAYNAK, E SAMPATH, KT LUYTEN, FP LATIN, V OPPERMANN, H VUKICEVIC, S AF HELDER, MN OZKAYNAK, E SAMPATH, KT LUYTEN, FP LATIN, V OPPERMANN, H VUKICEVIC, S TI EXPRESSION PATTERN OF OSTEOGENIC PROTEIN-1 (BONE MORPHOGENETIC PROTEIN-7) IN HUMAN AND MOUSE DEVELOPMENT SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE OSTEOGENIC PROTEIN-1 (BONE MORPHOGENETIC PROTEIN-7); TRANSFORMING GROWTH FACTOR-BETA SUPERFAMILY; HUMAN DEVELOPMENT; KIDNEY DEVELOPMENT; LIMB DEVELOPMENT; BONE; CARTILAGE; IN SITU HYBRIDIZATION; NORTHERN HYBRIDIZATION ID GROWTH-FACTOR-BETA; TGF-BETA; INSITU HYBRIDIZATION; FOLLICULAR-FLUID; AXIAL MESODERM; MESSENGER-RNA; DIFFERENTIATION; SUPERFAMILY; XENOPUS; EMBRYOGENESIS AB Osteogenic protein-1 (OP-1; BMP-7) is a member of the bone morphogenetic protein subfamily. Because members of the TGF-beta superfamily have a role in tissue development, the distribution of OP-1 expression in developing human embryos (5-8 gestational weeks) and fetuses (8-14 gestational weeks) and mouse (9.5-17.5 gestational days) fetuses was examined. Northern hybridization with specific OP-1 probes revealed two mRNA species of 4 and 2.2 KB. Highest levels of OP-1 mRNA were found in human fetal kidney and heart between 12-14 weeks of gestation. By in situ hybridization, the OP-1 transcripts were found in various tissues, i.e., the ectodermal epithelium of the mouse fore- and hindlimbs, heart, teeth, intestinal epithelium, perichondrium, hypertrophic chondrocytes, and periosteum/osteoblast layer of developing human bones, in kidneys, transcripts were first detected in the epithelium of the branching uretheric buds, whereas at later stages glomeruli were the major site of OP-1 mRNA accumulation. These data suggest that, although OP-1 has been isolated from bone matrix, it may have additional regulatory roles in the morphogenesis and/or function of the kidney, limb bud, tooth, heart, and intestine. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. UNIV ZAGREB,SCH MED,DEPT ANAT,ZAGREB 41001,CROATIA. UNIV ZAGREB,SCH MED,DEPT GYNECOL,ZAGREB 41001,CROATIA. CREAT BIOMOLECULES INC,HOPKINTON,MA 01748. NR 42 TC 145 Z9 154 U1 0 U2 4 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD OCT PY 1995 VL 43 IS 10 BP 1035 EP 1044 PG 10 WC Cell Biology SC Cell Biology GA RW326 UT WOS:A1995RW32600008 PM 7560881 ER PT J AU MONGINI, PKA HIGHET, PF INMAN, JK AF MONGINI, PKA HIGHET, PF INMAN, JK TI HUMAN B-CELL ACTIVATION - EFFECT OF T-CELL CYTOKINES ON THE PHYSICOCHEMICAL BINDING REQUIREMENTS FOR ACHIEVING CELL-CYCLE PROGRESSION VIA THE MEMBRANE IGM SIGNALING PATHWAY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN LYMPHOCYTES-B; STIMULATORY FACTOR-I; INTERFERON-GAMMA; GROWTH-FACTOR; ANTI-IGM; MOLECULAR-WEIGHT; PROLIFERATIVE RESPONSE; INDEPENDENT ANTIGENS; GERMINAL-CENTERS; CLONAL EXPANSION AB Given the range of mIg-binding affinities expressed by Ag-specific B cells, the ligand:receptor affinity threshold for achieving full B cell activation via the mIgM-mediated signaling pathway is quite high. Several recombinant, or semi-purified, cytokines were found to reduce the very high mIgM:ligand affinity threshold for induction of human B cell S phase entry by bivalent, affinity-diverse anti-IgM mAbs without notably affecting the lower affinity threshold for G(1)-related RNA synthesis. Two-stage culture experiments suggested that one major means by which IL-4 , IL-2, and low m.w. B cell growth factor lower the affinity threshold for S phase entry is an indirect one, i.e., rescue of B cells whose mIg engagements with Ag are of sufficient affinity for achieving G(1) entry, but of insufficient affinity for initiating the late-phase mIgM-mediated signals needed for the G(1)-->S phase transition, IL-4 had additional effects in early G(1). In contrast to the above cytokines, IFN-gamma, did not function as an independent cell cycle progression factor, but rather required the concomitant presence of mIgM-cross-linking ligand for enhancement. A greater potential of multivalent anti-IgM-dextran conjugates to trigger S phase entry in the absence of cytokines was found to reflect a greater potential for initiating mIgM signals during the late phase in B cell activation, The results indicate that progression of mIgM receptor-activated B cells past a G(1)-->S phase restriction point is dependent upon continued signal transduction via either the mIgM receptor and/or a cytokine receptor signaling pathway. When mIgM-engaging ligands are ineffective at initiating late-phase signals, due to limited size and binding site valency and/or affinity, ancillary signal transduction through cytokine receptors becomes most relevant. C1 NYU,SCH MED,KAPLAN COMPREHENS CANC CTR,DEPT PATHOL,NEW YORK,NY 10016. NIH,IMMUNOL LAB,BETHESDA,MD 20892. RP MONGINI, PKA (reprint author), HOSP JOINT DIS & MED CTR,DEPT RHEUMATOL & MOLEC MED,301 E 17TH ST,NEW YORK,NY 10003, USA. FU NIGMS NIH HHS [R01 GM35174] NR 80 TC 16 Z9 17 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1995 VL 155 IS 7 BP 3385 EP 3400 PG 16 WC Immunology SC Immunology GA RV939 UT WOS:A1995RV93900016 PM 7561033 ER PT J AU RIBAUDO, RK MARGULIES, DH AF RIBAUDO, RK MARGULIES, DH TI POLYMORPHISM AT POSITION-9 OF THE MHC CLASS-I HEAVY-CHAIN AFFECTS THE STABILITY OF ASSOCIATION WITH BETA(2)-MICROGLOBULIN AND PRESENTATION OF A VIRAL PEPTIDE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR-HISTOCOMPATIBILITY-COMPLEX; SURFACE EXPRESSION; MONOCLONAL-ANTIBODIES; MOLECULAR CHAPERONE; RESTRICTED PEPTIDES; ANTIGENIC PEPTIDE; LYMPHOCYTES-T; CELL-SURFACE; BINDING; BETA-2-MICROGLOBULIN AB To identify residues that control the interactions between MHC-heavy chains and (beta(2)m) sequence comparisons were made between murine class I MHC molecules with high (H-2D(d), H-2K(b)) and low (H-2L(d), H-2D(b)) affinities for beta(2)m. A single residue at position 9 was evaluated for its contribution to the stability of the complex, Mutagenesis of the glutamic acid at position 9 of H-2L(d) to valine, as is found in H-2D(d) and H-2K(b), resulted in both qualitative and quantitative effects on inter-chain interactions, intracellular transport, peptide binding, and peptide presentation, In in vitro translation and assembly studies, the E9V mutation resulted in a more stable association of beta(2)m with the heavy chain after immunoprecipitation with the alpha 2 domain-specific Ab 30-5-7 in the presence of an H-2L(d)-restricted peptide. E9V variant expressed in transfected L cells had similar surface expression compared with H-2L(d) despite exhibiting a slower rate of maturation, However, cells expressing E9V were unable to present peptide Ag to a specific T cell hybridoma, H-2L(d)E9V in E-3 cells, which are defective in TAP-dependent peptide transport, was expressed at higher levels than H-2L(d) and was stabilized more efficiently by the addition of exogenous human beta(2)m. Thus, amino acid position 9 not only plays an important role in the interaction of the MHC-I molecule with the beta(2)m, it also qualitatively and quantitatively influences peptide binding and Ag presentation. C1 NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013 NR 61 TC 25 Z9 26 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 OCT 1 PY 1995 VL 155 IS 7 BP 3481 EP 3493 PG 13 WC Immunology SC Immunology GA RV939 UT WOS:A1995RV93900026 PM 7561043 ER PT J AU Wang, M Chen, PW Bronte, V Rosenberg, SA Restifo, NP AF Wang, M Chen, PW Bronte, V Rosenberg, SA Restifo, NP TI Anti-tumor activity of cytotoxic T lymphocytes elicited with recombinant and synthetic forms of a model tumor-associated antigen SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE recombinant vaccinia virus; peptide; adoptive immunotherapy; T lymphocyte; MHC class I ID ACTIVATED KILLER CELLS; INFILTRATING LYMPHOCYTES; ADOPTIVE IMMUNOTHERAPY; MELANOMA-CELLS; B2M GENE; INTERLEUKIN-2; CANCER; IDENTIFICATION; REGRESSION; EXPRESSION AB The recent cloning of tumor-associated antigens (TAAs) recognized by CD8(+) T lymphocytes (T-CD8+) has made it possible to use recombinant and synthetic forms of TAAs to generate T-CD8+ with anti-tumor activity. To explore new therapeutic strategies in a mouse model, we retrovirally transduced the experimental murine tumor CT26 (H-2(d)), with the lacZ gene encoding our model TAA, beta-galactosidase (beta-gal). The transduced cell line, CT26.CL25, grew as rapidly and as lethally as the parental cell line in normal, immunocompetent animals. In an attempt to elicit T-CD8+ directed against our model TAA by using purely recombinant and synthetic forms of our model TAA, we synthesized a nine-amino-acid long immunodominant peptide of beta-gal (TPH-PARIGL), corresponding to amino acid residues 876-884, which was known to be presented by the L(d) major histocompatibility complex (MHC) class I molecule, and a recombinant vaccinia virus encoding the full-length beta-gal protein (VJS6). Splenocytes obtained from naive mice and co-cultured with beta-gal peptide could not be expanded in primary ex vivo cultures. However, mice immunized with VJS6, but not with a control recombinant vaccinia virus, yielded splenocytes that were capable of specifically lysing CT26.CL25 in vitro after co-culture with beta-gal peptide. Most significantly, adoptive transfer of these cells could effectively treat mice bearing 3-day-old established pulmonary metastases. These observations show that therapeutic T-CD8+ directed against a model TAA could be generated by using purely recombinant and synthetic forms of this antigen. These findings point the way to a potentially useful immunotherapeutic strategy, which has been made possible by the recent cloning of immunogenic TAAs that are expressed by human malignancies. C1 NCI, SURG BRANCH, BETHESDA, MD 20892 USA. NATL INST HLTH, HOWARD HUGHES MED INST, RES SCHOLARS PROGRAM, BETHESDA, MD USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 53 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 EI 1537-4513 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1995 VL 18 IS 3 BP 139 EP 146 DI 10.1097/00002371-199510000-00001 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA TN419 UT WOS:A1995TN41900001 PM 8770769 ER PT J AU ROILIDES, E SEIN, T HOLMES, A CHANOCK, S BLAKE, C PIZZO, PA WALSH, TJ AF ROILIDES, E SEIN, T HOLMES, A CHANOCK, S BLAKE, C PIZZO, PA WALSH, TJ TI EFFECTS OF MACROPHAGE-COLONY-STIMULATING FACTOR ON ANTIFUNGAL ACTIVITY OF MONONUCLEAR PHAGOCYTES AGAINST ASPERGILLUS-FUMIGATUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PHASE-I TRIAL; HUMAN-MONOCYTES; MURINE MACROPHAGES; RHIZOPUS-ORYZAE; INVITRO; HYPHAE; DEFENSE; INVIVO; DAMAGE; NEUTROPHILS AB The effects of recombinant human macrophage colony-stimulating factor (M-CSF) on antifungal activity of human monocytes (MNC), MNC-derived macrophages (MDM), and rabbit pulmonary alveolar macrophages (PAM) against Aspergillus fumigatus were studied, MNC-induced hyphal damage was augmented by incubation with M-CSF (P = .027); PAM-induced hyphal damage was moderately enhanced by M-CSF (P = .046), Phagocytosis of Aspergillus conidia by MDM and PAM was strongly enhanced by M-CSF (P < .01), MNC pretreated with M-CSF exhibited enhanced superoxide anion production in response to PMA (P = .026), This effect was not associated with increased levels of mRNA transcripts of the components of NADPH oxidase, the enzyme responsible for superoxide anion production, M-CSF augments antifungal activity of mononuclear phagocytes against both conidia and hyphae of Aspergillus fumigatus partly by enhancement of oxidation-dependent mechanisms and may have an important immunomodulatory role in prevention and treatment of invasive aspergillosis in leukopenic patients. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 31 TC 62 Z9 63 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 OCT PY 1995 VL 172 IS 4 BP 1028 EP 1034 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RW062 UT WOS:A1995RW06200017 PM 7561176 ER PT J AU PADIAN, NS ABRAMS, J SKURNICK, JH VANDEVANTER, NL OBRIEN, TR AF PADIAN, NS ABRAMS, J SKURNICK, JH VANDEVANTER, NL OBRIEN, TR TI RISK-FACTORS FOR POSTCOITAL BLEEDING AMONG WOMEN WITH OR AT RISK FOR INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID MALE TRANSMISSION; HAITIAN WOMEN; SMOKING; FEMALE; HIV-1 AB Risk factors for postcoital bleeding were examined in 475 women who were enrolled in a study of heterosexual transmission of human immunodeficiency virus (HIV). In bivariate analyses, history of sexually transmitted diseases (STDs; P = .03), HIV infection (P = .008), and dyspareunia or pain during intercourse (P = .0001) were significant risk factors, In multivariate analysis, the two latter factors remained significant (for HIV, odds ratio [OR] = 2.1, P = .02, 95% confidence interval [CI] = 1.1-4.0; for dyspareunia, OR = 3.5, P < .001, 95% CI = 1.8-6.6), as did the interaction term of STD history and heavy smoking (OR = 2.4, P = .02, 95% CI = 1.2-5.0). Pain during intercourse was the strongest predictor of postcoital bleeding but may be part of the same phenomenon. Similarly, because this study relied on cross-sectional data, the direction of the causal pathway linking HIV to postcoital bleeding cannot be established. However, these data suggest that smoking, a modifiable risk factor, may increase risk of postcoital bleeding and contribute to susceptibility for HIV and other STDs. C1 UNIV CALIF SAN FRANCISCO,DEPT OBSTET GYNECOL & REPROD SCI,SAN FRANCISCO,CA 94143. HENRY FORD HLTH SCI CTR,DIV BIOSTAT & RES EPIDEMIOL & MED INFORMAT,DETROIT,MI. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PREVENT MED & COMMUNITY HLTH,NEWARK,NJ 07103. COLUMBIA UNIV,SCH PUBL HLTH,DIV SOCIOMED SCI,NEW YORK,NY. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. FU PHS HHS [R64/CCR903266] NR 13 TC 7 Z9 7 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1995 VL 172 IS 4 BP 1084 EP 1087 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RW062 UT WOS:A1995RW06200025 PM 7561184 ER PT J AU KIRTSCHIG, G MARINKOVICH, MP BURGESON, RE YANCEY, KB AF KIRTSCHIG, G MARINKOVICH, MP BURGESON, RE YANCEY, KB TI ANTIBASEMENT MEMBRANE AUTOANTIBODIES IN PATIENTS WITH ANTI-EPILIGRIN CICATRICIAL PEMPHIGOID BIND THE ALPHA-SUBUNIT OF LAMININ-5 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SKIN-DISEASE; COMPONENT; KALININ; LIGAND; ALPHA-3-BETA-1; KERATINOCYTES; PROTEINS; CELLS AB Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the alpha subunit of laminin 5 but show no reactivity to its beta or gamma subunits. In addition, circulating IgG from a representative patient was affinity-purified against the alpha subunit of laminin 5 and shown to bind the dermal side of 1 M NaCl split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the alpha subunit of laminin 5 (i.e., laminin subunit alpha 3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit alpha 3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,SHRINERS HOSP CRIPPLED CHILDREN,DEPT DERMATOL,PORTLAND,OR 97201. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. FU NIAMS NIH HHS [AR 35689] NR 22 TC 143 Z9 146 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1995 VL 105 IS 4 BP 543 EP 548 DI 10.1111/1523-1747.ep12323431 PG 6 WC Dermatology SC Dermatology GA RY598 UT WOS:A1995RY59800004 PM 7561156 ER PT J AU YOUNG, HA HARDY, KJ AF YOUNG, HA HARDY, KJ TI ROLE OF INTERFERON-GAMMA IN IMMUNE CELL REGULATION SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE INTERFERON; T CELL; MACROPHAGE; B CELL; TRANSGENIC MICE; KNOCKOUT MICE ID TUMOR NECROSIS FACTOR; COLONY-STIMULATING FACTOR; LARGE GRANULAR LYMPHOCYTES; MURINE B-CELLS; HUMAN T-CELLS; CLASS-II MHC; IFN-GAMMA; MESSENGER-RNA; TRANSGENIC MICE; HUMAN-MONOCYTES AB In 1965 Wheelock reported that phytohemagglutinin could induce from human leukocytes an interferon-like virus inhibitor [1]. This substance, which turned out to be interferon-gamma (IFN-gamma), has been the subject, directly or indirectly, of thousands of scientific publications since that initial report. Past research has led to the general conclusion that IFN-gamma is much more than an interferon in that it has broader effects on the various arms of the immune system than most any other lymphokine or cytokine. In this review we discuss the effects of IFN-gamma on the various cell lineages of the immune system, focusing on the biology of its actions. In addition, we summarize research focused on the consequences of introducing IFN-gamma cDNA into tumor cells, aberrant IFN-gamma production in transgenic animals, and inhibition of IFN-gamma effects by knocking out either the IFN-gamma gene itself or the IFN-gamma receptor gene. C1 JACKSON VET ADM HOSP,JACKSON,MS. UNIV MISSISSIPPI,SCH MED,DEPT INTERNAL MED,DIV RHEUMATOL MOLEC IMMUNOL,JACKSON,MS 39216. RP YOUNG, HA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. NR 165 TC 304 Z9 312 U1 1 U2 16 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 OCT PY 1995 VL 58 IS 4 BP 373 EP 381 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA RY386 UT WOS:A1995RY38600001 PM 7561512 ER PT J AU ZHENG, ZM HE, PJ CAUEFFIELD, D NEUMANN, M SPECTER, S BAKER, CC BANKOWSKI, MJ AF ZHENG, ZM HE, PJ CAUEFFIELD, D NEUMANN, M SPECTER, S BAKER, CC BANKOWSKI, MJ TI ENTEROVIRUS-71 ISOLATED FROM CHINA IS SEROLOGICALLY SIMILAR TO THE PROTOTYPE E71 BRCR STRAIN BUT DIFFERS IN THE 5'-NONCODING REGION SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE PICORNAVIRUS; POLYMERASE CHAIN REACTION; HAND-FOOD-AND-MOUTH DISEASE ID COMPLETE NUCLEOTIDE-SEQUENCE; POLYMERASE CHAIN-REACTION; 5' NONCODING REGION; RNA SECONDARY STRUCTURE; CENTRAL NERVOUS-SYSTEM; POLIOVIRUS RNA; TYPE-71 INFECTIONS; PICORNAVIRUS RNA; ATTENUATION; VACCINE AB Enterovirus 71 H (E71 H), an isolate from an adult patient with hand-foot-mouth disease (HFMD) in China, was serologically similar to the prototype strain E71 BrCr, which was isolated from a patient with aseptic meningitis. The study further analyzed the similarity of E71 H to E71 BrCr at the 5'-noncoding region (NCR), a location in genomic RNA that recently was found to be related to neurovirulence in poliovirus and Venezuelan equine encephalitis virus. Using a reverse transcription-polymerase chain reaction (RT-PCR) technique and a unique primer pair I, a 397 bp product was detected from E71 BrCr, Cox A9 (Griggs), Cox A 16 (NIH), Cox 61 (HA antigen 201-468), Cox B5 (wild type), and ECHO 11 (Gregory), but not from E71 H, Cox A24 (Joseph), and ECHO 5 (Noyce). However, all of the viruses generated a 154 bp product using a universal enterovirus primer pair II. Further comparative analysis using primer-directed sequencing of both the E71 H and E71 BrCr 154 bp products revealed that they differed by 12 bases. The variations between the two viruses were clustered in two loci, one in the region of nucleotides 43-61 with eight variations, and the other in the region of nucleotides 120-133 with three variations. The differences within the 5'-NCR between the E71 H (HFMD) and the E71 BrCr (aseptic meningitis) viruses might provide a clue to explain why E71 was associated with two different clinical patterns: polio-like disease in the United States, Australia, and Eastern Europe, HFMD in China, Japan, and Singapore. (C) 1995 Wiley-Liss, Inc. C1 HUBEI MED UNIV,INST VIRUS RES,WUHAN,PEOPLES R CHINA. UNIV S FLORIDA,COLL MED,DEPT MED MICROBIOL & IMMUNOL,TAMPA,FL 33620. DIAGNOST SERV INC,CLIN VIROL LAB,NAPLES,FL. DIAGNOST SERV INC,MOLEC MED LAB,NAPLES,FL. NAPLES COMMUNITY HOSP,NAPLES,FL. RP ZHENG, ZM (reprint author), NCI,TUMOR VIRUS BIOL LAB,BLDG 41,RM C-111,BETHESDA,MD 20892, USA. NR 51 TC 40 Z9 52 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD OCT PY 1995 VL 47 IS 2 BP 161 EP 167 DI 10.1002/jmv.1890470209 PG 7 WC Virology SC Virology GA RX424 UT WOS:A1995RX42400008 PM 8830120 ER PT J AU LIANG, BC ROSS, DA REED, E AF LIANG, BC ROSS, DA REED, E TI GENOMIC COPY NUMBER CHANGES OF DNA-REPAIR GENES ERCC1 AND ERCC2 IN HUMAN GLIOMAS SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE ERCC1; ERCC2; DNA REPAIR; GLIOMA ID HAMSTER OVARY CELLS; XERODERMA-PIGMENTOSUM; ASTROCYTOMAS; SENSITIVITY; CHROMOSOME; CLONING; CANCER AB Abnormalities of the genomic region of chromosome 19q13.2-13.4 are a common occurrence in brain malignancies and contain a possible tumor suppressor gene involved in gliomas. Since abnormalities of DNA repair are associated with malignancy, we assessed DNA status of the nucleotide excision repair genes located in this area, viz. ERCC1 and ERCC2. Radiodensitometry was used to assess gene copy number in samples obtained from brain tumor specimens from 24 patients. Nine tumors were of lower grade histology (3 pilocytic astrocytomas, 2 gangliogliomas, 4 astrocytomas); 15 tumors were pathologiclly higher grade (4 anaplastic astrocytomas, 11 glioblastomas). Tumor samples were obtained prior to radiation or chemotherapy. Abnormalities of gene copy number of ERCC1 and ERCC2 were observed in 11/24 specimens (46%). Whereas increased and decreased copy numbers were observed for ERCC1, only decreases in copy number of ERCC2 were seen. Three tumors (all lower grade) showed concurrent allelic loss of ERCC1 and ERCC2. Abnormalities of copy number for these genes were not associated with response to subsequent therapy nor survival. However, allelic loss of ERCC2 was associated with younger age at diagnosis when compared to those specimens which did not show loss. There were no significant differences between lower grade and higher grade tumors with respect to these investigations. Abnormalities in copy number of ERCC1 and ERCC2 are common in glial tumors. Further study of this genomic region is necessary to define the importance of these observations in tumor pathophysiology and treatment. C1 NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT SURG,NEUROSURG SECT,ANN ARBOR,MI 48109. NR 26 TC 23 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 1995 VL 26 IS 1 BP 17 EP 23 DI 10.1007/BF01054765 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA TD920 UT WOS:A1995TD92000003 PM 8583241 ER PT J AU HIRATA, Y WHALIN, M GINTY, DD XING, J GREENBERG, ME MILBRANDT, J GUROFF, G AF HIRATA, Y WHALIN, M GINTY, DD XING, J GREENBERG, ME MILBRANDT, J GUROFF, G TI INDUCTION OF A NERVE GROWTH FACTOR-SENSITIVE KINASE THAT PHOSPHORYLATES THE DNA-BINDING DOMAIN OF THE ORPHAN NUCLEAR RECEPTOR NGFI-B SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE NERVE GROWTH FACTOR; PC12 CELLS; NGFI-B; KINASE ID PROTEIN-KINASE; PC12 CELLS; MEMBRANE DEPOLARIZATION; SIGNAL-TRANSDUCTION; MAP KINASES; GENE; TRANSCRIPTION; ACTIVATION; NUR77; IDENTIFICATION AB Nerve growth factor (NGF) induces the synthesis and the phosphorylation of the orphan nuclear receptor NGFI-B in PC12 cells. Previous work has shown that phosphorylation, by protein kinase A, of a specific serine in the DNA-binding domain inhibits its binding to the NGFI-B response element. Also, cytoplasmic extracts from PC12 cells phosphorylate this serine, and phosphorylation is greater in extracts from cells treated with NGF. The present work describes the induction, identification, and partial purification of a kinase (termed NGFI-B kinase I) from PC12 cell extracts that catalyzes this phosphorylation. Phosphorylation of the DNA-binding domain with this purified preparation inhibits its binding to the NGFI-B response element, The kinase is rapidly activated by treatment of the cells with NGF, and the activation lasts for at least several hours. It also is activated by fibroblast growth factor and epidermal growth factor (EGF), but the activation by EGF is quite transient. The kinase requires Mg2+ but will use Mn2+. The molecular mass of the kinase is 95-100 kDa, and it is different from protein kinase A, Fos kinase, or pp90(rsk). Comparison with a partially purified preparation of cyclic AMP response element-binding protein kinase, however, indicates that the two are either Very similar or identical. C1 NICHHD, GROWTH FACTORS SECT, BETHESDA, MD 20892 USA. HARVARD UNIV, SCH MED, DEPT MICROBIOL & MOLEC GENET, BOSTON, MA 02115 USA. WASHINGTON UNIV, SCH MED, DEPT PATHOL, DIV LAB MED, ST LOUIS, MO 63110 USA. WASHINGTON UNIV, SCH MED, DEPT INTERNAL MED, DIV LAB MED, ST LOUIS, MO 63110 USA. NR 39 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1995 VL 65 IS 4 BP 1780 EP 1788 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RW335 UT WOS:A1995RW33500041 PM 7561876 ER PT J AU RAPOPORT, SI AF RAPOPORT, SI TI DOCOSAHEXAENOATE TURNOVER IN BRAIN PHOSPHOLIPIDS SO JOURNAL OF NEUROCHEMISTRY LA English DT Letter ID ACID RP RAPOPORT, SI (reprint author), NIA,NEUROSCI LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 9 TC 5 Z9 5 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 OCT PY 1995 VL 65 IS 4 BP 1903 EP 1904 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RW335 UT WOS:A1995RW33500057 PM 7561892 ER PT J AU STOJILKOVIC, SS CATT, KJ AF STOJILKOVIC, SS CATT, KJ TI NOVEL ASPECTS OF GNRH-INDUCED INTRACELLULAR SIGNALING AND SECRETION IN PITUITARY GONADOTROPHS SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE PHOSPHOLIPASE C; PHOSPHOLIPASE D; DIACYLGLYCEROL; CALCIUM; LH; C-FOS ID PROTEIN-KINASE-C; TRIPHOSPHATE-BINDING PROTEIN; INDUCED CALCIUM OSCILLATIONS; HORMONE-RELEASING HORMONE; CYTOSOLIC FREE CALCIUM; PHOSPHOLIPASE-D; PHOSPHATIDIC-ACID; GUANOSINE TRIPHOSPHATE; RAT GONADOTROPES; CELL-LINE RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,ROOM 6A-36,BETHESDA,MD 20892, USA. NR 110 TC 68 Z9 68 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD OCT PY 1995 VL 7 IS 10 BP 739 EP 757 DI 10.1111/j.1365-2826.1995.tb00711.x PG 19 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TE309 UT WOS:A1995TE30900001 PM 8563717 ER PT J AU AGUILERA, G KISS, A LUO, X AF AGUILERA, G KISS, A LUO, X TI INCREASED EXPRESSION OF TYPE-1 ANGIOTENSIN-II RECEPTORS IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS FOLLOWING STRESS AND GLUCOCORTICOID ADMINISTRATION SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; AT; RECEPTOR MESSENGER-RNA; ALL BINDING; STRESS; GLUCOCORTICOIDS ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; MALE-RAT BRAIN; MESSENGER-RNA; SUBFORNICAL ORGAN; ACTH-SECRETION; VASOPRESSIN; HYBRIDIZATION; RESPONSES; SYSTEM AB Double staining in situ hybridization studies have shown that angiotensin II (AII) type 1 receptors (AT1) in the hypothalamic paraventricular nucleus (PVN) are located primarily in corticotropin releasing hormone (CRH) neurons of the parvicellular subdivision, The purpose of these studies was to investigate the role of AII regulating the hypothalamic-pituitary adrenal (HPA) axis, by correlating AT(1) receptor expression levels in the PVN with the known changes in activity of the HPA axis under different stress paradigms, and manipulation of circulating glucocorticoids. AT(1) receptor mRNA was measured by in situ hybridization using S-35-labelled cRNA probes and AII binding by autoradiography using I-125[Sar(1),Ile(8)]AII in slide mounted hypothalamic sections. AT(1) receptor mRNA levels and AII binding in the PVN were reduced by about 20% 18 h after adrenalectomy remaining at these levels up to 6 days after. This effect was prevented by corticosterone administration in the drinking water, or dexamethasone injection (100 mg, s.c., daily). Conversely, dexamethasone injection in intact rats caused a 20% increase in AT(1) receptor mRNA in the PVN. AT(1) receptor mRNA and binding in the PVN increased 4 h after exposure to stress paradigms associated with activation of the HPA axis (immobilization for 1 h, or i.p. injection of 1.5 M NaCl), and remained elevated after repeated daily stress for 14 days. Unexpectedly, two osmotic stress models associated with inhibition of the HPA axis (60 h water deprivation or 12 days of 2% saline intake) also resulted in increased AT(1) receptor mRNA levels and AII binding in the parvicellular PVN. In intact rats, the stimulatory effect of acute stress on AT(1) receptor mRNA in the PVN was significantly enhanced by dexamethasone administration (100 mu g, s.c., 14 h and 1 h prior to stress), while in adrenalectomized rats, with or without glucocorticoid replacement, stress reduced rather than increased, AT(1) receptor mRNA. Dexamethasone, 100 mu g, injected sc within 1 min the beginning of immobilization in adrenalectomized rats, increased AT(1) receptor mRNA in the PVN to levels significantly higher than those after dexamethasone alone, indicating that the stress induced glucocorticoid surge is required for the stimulatory effect of stress on AT(1) receptor mRNA. The data suggest that AT(1) receptor expression in the PVN is under dual control during stress: stress-activated inhibitory pathways and the stimulatory effect of glucocorticoids. The lack of specificity of the changes in AT(1) receptor expression in the PVN following stressors with opposite effects on ACTH secretion (osmotic and physical-psychological stress) does not support a role for AII as a major determinant of the response of the HPA axis during stress. RP AGUILERA, G (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINOL PHYSIOL SECT,BLDG 10,RM 10N262,10 CTR DR,MSC 1862,BETHESDA,MD 20892, USA. NR 44 TC 63 Z9 65 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD OCT PY 1995 VL 7 IS 10 BP 775 EP 783 DI 10.1111/j.1365-2826.1995.tb00714.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TE309 UT WOS:A1995TE30900004 PM 8563720 ER PT J AU DAS, KP MCMILLIAN, MK BING, GY HONG, JS AF DAS, KP MCMILLIAN, MK BING, GY HONG, JS TI MODULATORY EFFECTS OF [MET(5)]-ENKEPHALIN ON INTERLEUKIN-1-BETA SECRETION FROM MICROGLIA IN MIXED BRAIN-CELL CULTURES SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE INTERLEUKIN-1-BETA; LIPOPOLYSACCHARIDE; MICROGLIA; MIXED BRAIN CELL CULTURE; MOUSE; OPIOID ID CENTRAL NERVOUS-SYSTEM; DELTA-OPIOID RECEPTOR; MESSENGER-RNA; IMMUNE-SYSTEM; ENDOGENOUS OPIOIDS; AMEBOID MICROGLIA; OPIATE RECEPTORS; GROWTH-FACTOR; MOUSE-BRAIN; MACROPHAGES AB In the present study, functional interactions between [Met(5)]-enkephalin (ME), naloxone and lipopolysaccharide (LPS) on interleukin-1 beta (IL-1 beta) immunostaining and secretion have been assessed in mixed brain cell cultures from embryonic day 17 mice. Adding ME alone or together with LPS to the culture increased the release of IL-1 beta after 48 h in a concentration-dependent fashion. In situ hybridization studies showed that LPS, but not ME, increased the abundance of IL-1 beta mRNA. The enhanced release of IL-1 beta caused by ME or LPS was partially blocked by naloxone. LPS induced concentration-dependent morphological changes in microglia in mixed brain cell cultures, identified by a monoclonal antibody F4/80 which is specific for macrophages/microglia. Despite increasing IL-1 beta release into the media, ME (10(-8) M) did not induce morphological changes in microglia. Naloxone alone also had no effect on glial morphology; however, the LPS-induced morphological changes were blocked by naloxone. Our data indicate that both exogenous and endogenous opioids regulate IL-1 beta production by microglial cells in the mixed brain cell cultures. C1 NIEHS,ENVIRONM NEUROSCI LAB,NEUROPHARMACOL SECT,RES TRIANGLE PK,NC 27709. NR 61 TC 37 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT PY 1995 VL 62 IS 1 BP 9 EP 17 DI 10.1016/0165-5728(95)00083-E PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA TF123 UT WOS:A1995TF12300002 PM 7499497 ER PT J AU FULHAM, MJ BRUNETTI, A ALOJ, L RAMAN, R DWYER, AJ DICHIRO, G AF FULHAM, MJ BRUNETTI, A ALOJ, L RAMAN, R DWYER, AJ DICHIRO, G TI DECREASED CEREBRAL GLUCOSE-METABOLISM IN PATIENTS WITH BRAIN-TUMORS - AN EFFECT OF CORTICOSTEROIDS SO JOURNAL OF NEUROSURGERY LA English DT Article DE BRAIN NEOPLASM; [F-18] FLUORO-2-DEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY; GLUCOSE METABOLISM; CORTICOSTEROIDS ID CENTRAL-NERVOUS-SYSTEM; CUSHINGS-SYNDROME; BLOOD-FLOW; TRANSHEMISPHERIC DIASCHISIS; CEREBELLAR DIASCHISIS; OXYGEN UTILIZATION; RAT-BRAIN; ATROPHY; INFARCTION; DEOXYGLUCOSE AB The authors measured cerebral glucose metabolism (CMR(glc)) using [F-18]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in patients with brain tumors to evaluate the effect of exogenous corticosteroids (in this instance, dexamethasone) on glucose metabolism. Fifty-six FDG-PET studies obtained in 45 patients with unilateral supratentorial brain tumors were analyzed. Patients with brain tumors were divided into three groups: 1) patients with cushingoid symptoms, who had been treated with combinations of radiotherapy and chemotherapy taking oral dexamethasone; 2) patients not taking dexamethasone but treated with radiotherapy; and 3) patients not taking dexamethasone who had not been treated with radiotherapy. Serial FDG-PET scans were obtained in eight of the cushingoid patients. Glucose metabolism was measured in the contralateral cerebral and ipsilateral cerebellar hemispheres in patients and compared to measurements taken from 19 normal volunteers. The authors found that in the cushingoid brain tumor patients there was a marked reduction in CMR(glc) compared to normal volunteers and other brain tumor patients (Kruskal-Wallis test; p 0.001). In the majority of patients who had serial FDG-PET scans, there was a decline in glucose metabolism over time and in one patient, in whom dexamethasone was reduced in dosage, there was a subsequent increase in CMR The authors conclude that there is a generalized reduction in CMR in brain tumor patients taking dexamethasone compared to other brain tumor patients and normal volunteers, and that this effect is independent of radiotherapy, concurrent anticonvulsant medication: acid transhemispheric functional disconnection (transhemispheric diaschisis). C1 NINCDS, NEUROIMAGING BRANCH, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NR 51 TC 37 Z9 40 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1995 VL 83 IS 4 BP 657 EP 664 DI 10.3171/jns.1995.83.4.0657 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RW703 UT WOS:A1995RW70300014 PM 7674016 ER PT J AU STOCKHAMMER, G MANLEY, GT JOHNSON, R ROSENBLUM, MK SAMID, D LIEBERMAN, FS AF STOCKHAMMER, G MANLEY, GT JOHNSON, R ROSENBLUM, MK SAMID, D LIEBERMAN, FS TI INHIBITION OF PROLIFERATION AND INDUCTION OF DIFFERENTIATION IN MEDULLOBLASTOMA-DERIVED AND ASTROCYTOMA-DERIVED CELL-LINES WITH PHENYLACETATE SO JOURNAL OF NEUROSURGERY LA English DT Article DE MEDULLOBLASTOMA; GLIOMA; PHENYLACETATE; DIFFERENTIATION THERAPY; TRANSFORMING GROWTH FACTOR-BETA ID CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-BETA; NEUROFILAMENT PROTEINS; RETINOIC ACID; SENSORY NEURONOPATHY; MALIGNANT GLIOMAS; FETAL HEMOGLOBIN; NEURO-BLASTOMA; LUNG-CANCER; EXPRESSION AB The authors investigated the effects of a nontoxic differentiation inducer, phenylacetate (PA), on neuroectodermal tumor-derived cell lines. Treatment of medulloblastoma (Daoy and D283 MED) and glioma (U-251MG, C6, and RG2) cell lines resulted in a dose-dependent decline in DNA synthesis and cell proliferation, associated with accumulation in the G(0)/G(1) phase of the cell cycle. Phenylacetate decreased transforming growth factor (TGF)-beta(2) production by medulloblastoma Daoy cells. Neutralizing antibodies against either TGF beta(2) or TGF beta(1) failed to block the growth arrest observed. This suggests that, unlike other differentiation agents, such as retinoic acid, the effect of PA on medulloblastoma proliferation is not mediated by a TGF beta pathway. In addition to cytostasis, PA induced marked morphological changes in U-251MG and C6 glioma cells associated with increased abundance of glial fibrillary acidic protein-positive processes. Although the morphology of PA-treated medulloblastoma cells was not significantly altered, the D283 MED cells exhibited increased expression of neurofilament proteins and Hu antigen, indicative of differentiation along a neuronal pathway. The effects of PA on the medulloblastoma cell lines were compared to its effects on the human neuroblastoma cell line BE(2)C, which is capable of a bidirectional differentiation toward a neuronal or a glial/schwann cell pathway. In BE(2)C cells, PA induced differentiation toward a schwann/glial cell-like phenotype, suggesting that the choice of differentiation pathway is cell type and agent specific. These in vitro antiproliferative and differentiation inducing effects of PA suggest that this agent warrants further evaluation as a potential therapeutic modality for the treatment of medulloblastoma and malignant glioma in humans. C1 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,COTZIAS LAB NEUROONCOL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,NEW YORK,NY 10021. NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD. NR 48 TC 52 Z9 52 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1995 VL 83 IS 4 BP 672 EP 681 DI 10.3171/jns.1995.83.4.0672 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RW703 UT WOS:A1995RW70300016 PM 7674018 ER PT J AU CLEVIDENCE, BA TAYLOR, PR CAMPBELL, WS JUDD, JT AF CLEVIDENCE, BA TAYLOR, PR CAMPBELL, WS JUDD, JT TI LEAN AND HEAVY WOMEN MAY NOT USE ENERGY FROM ALCOHOL WITH EQUAL EFFICIENCY SO JOURNAL OF NUTRITION LA English DT Article DE ALCOHOL; ENERGY BODY MASS INDEX; HUMANS ID UNITED-STATES ADULTS; NUTRIENT INTAKE; BODY-WEIGHT; CONSUMPTION; METABOLISM; CALORIES; ETHANOL; PLASMA; DIET AB To assess whether energy from alcohol is efficiently utilized to maintain body mass, we examined changes in energy intake of young women when they drank alcohol. The women ate controlled diets typical of the American diet with regard to macronutrients. Body weights were controlled to within 1 kg of entry level weights. The subjects were given alcohol (30 g/d) and no alcohol treatments for 3 mo each in a crossover design. The treatments were isoenergetic; for the no alcohol treatment alcohol energy was replaced with energy from carbohydrate. The average change in energy intake associated with the alcohol treatment was negligible when all subjects were considered collectively. There was, however, a divergence in response between lean and heavy subjects. Fifteen women required, on average, an additional 886 +/- 147 (mean +/- SEM) kJ/d to maintain body weight during the alcohol treatment, and these women were leaner (body mass index 22.6 +/- 0.8 kg/m(2) vs. 25.2 +/- 1.0, P < 0.05) than the 22 women who required, on average, 559 +/- 139 fewer kJ/d when on the alcohol treatment. This study suggests that all subjects do not use energy from alcohol with equal efficiency. C1 USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,DIET & HUMAN PERFORMANCE LAB,BELTSVILLE,MD 20705. NCI,DEPT HLTH & HUMAN SERV,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [Y01-CN-40620] NR 20 TC 19 Z9 19 U1 1 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 1995 VL 125 IS 10 BP 2536 EP 2540 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RZ088 UT WOS:A1995RZ08800011 PM 7562088 ER PT J AU HEIDBREDER, CA BABOVICVUKSANOVIC, D SHOAIB, M SHIPPENBERG, TS AF HEIDBREDER, CA BABOVICVUKSANOVIC, D SHOAIB, M SHIPPENBERG, TS TI DEVELOPMENT OF BEHAVIORAL SENSITIZATION TO COCAINE - INFLUENCE OF KAPPA-OPIOID RECEPTOR AGONISTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PRODYNORPHIN MESSENGER-RNA; RAT SPINAL-CORD; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; EXTRACELLULAR DOPAMINE; AUTOMATED MEASUREMENT; ADENYLATE-CYCLASE; OPIATE AGONISTS; C-FOS; DIFFERENTIALLY ALTERS AB The effects of acute or repeated administrations of the selective kappa opioid receptor agonists U-69593 and U-50488H on cocaine-induced locomotor stimulation were examined in the rat, Acute administration of cocaine (10-30 mg/kg i.p.) produced a dose-dependent increase in locomotor activity. A single injection of U-69593 (0.04-0.32 mg/kg s.c.) or U-50488H (2.5-7.5 mg/kg s.c.) administered 15 min before cocaine did not modify the effects of an acute cocaine challenge. In contrast, repeated administration of U-69593 or U-50488H in combination with saline for 3-days prevented the acute locomotor-activating effects of cocaine. Repeated administration of cocaine (10-30 mg/kg i.p.) for 3 days resulted in an enhancement of its locomotor-activating effects, i.e., sensitization. No such sensitized responses were observed in animals that had received U-69593 or U-50488H in combination with the cocaine treatment regimen. Repeated administration of U-69593 (0.16 mg/kg s.c.) for 3 days failed to block the acute locomotor-activating effects of nicotine (0.6 mg/kg s.c.). Furthermore, when U-69593 was given in combination with nicotine, sensitized motor responses to a subsequent nicotine challenge were still observed. These data demonstrate that the repeated activation of kappa opioid receptors prevents the locomotor activation that occurs in response to an acute cocaine challenge as well as the sensitized motor responses that develop after the repeated administration of cocaine. RP HEIDBREDER, CA (reprint author), NIDA, PRECLIN PHARMACOL LAB, INTRAMURAL RES PROGRAM, BEHAV PHARMACOL & GENET SECT, POB 5180, BALTIMORE, MD 21224 USA. NR 90 TC 72 Z9 72 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1995 VL 275 IS 1 BP 150 EP 163 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA467 UT WOS:A1995TA46700020 PM 7562544 ER PT J AU IMAMURA, Y BENNETT, GJ AF IMAMURA, Y BENNETT, GJ TI FELBAMATE RELIEVES SEVERAL ABNORMAL PAIN SENSATIONS IN RATS WITH AN EXPERIMENTAL PERIPHERAL NEUROPATHY SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SPONTANEOUS DISCHARGE; SPINAL-CORD; ANTICONVULSANT; MONONEUROPATHY; HYPERALGESIA; STRYCHNINE; RECEPTORS; NEURONS; HYPOXIA; MODEL AB The antiepileptic drug, felbamate, was tested in a rat model of painful peripheral neuropathy (the chronic constriction injury model). Intraperitoneal doses of 150, 300 and 600 mg/kg were given to animals with established heat-hyperalgesia, mechanohyperalgesia, mechano-allodynia and signs of spontaneous pain (hindpaw guarding). Postinjection tests were conducted 2, 6, 12, 24 and 48 h later, The 150 mg/kg dose had little or no effect on any measure. Significant reductions in all measures of abnormal pain were seen after the 300 and 600 mg/kg doses; relief lasted 2 to 12 h. Side effects were trivial or absent by 2 h postinjection. Felbamate's actions were generally antihyperalgesic and antiallodynic, rather than analgesic, in that the responsiveness of the control (sham-operated) hindpaw was unaffected, We conclude that felbamate suppresses neuropathic pain sensations and that its effectiveness may be due to multiple mechanisms of action. The recently discovered severe side-effect liability of felbamate is likely to preclude its clinical application. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 36 TC 16 Z9 16 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 OCT PY 1995 VL 275 IS 1 BP 177 EP 182 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA467 UT WOS:A1995TA46700023 PM 7562547 ER PT J AU SANNERUD, CA ATOR, NA AF SANNERUD, CA ATOR, NA TI DRUG DISCRIMINATION ANALYSIS OF MIDAZOLAM UNDER A 3-LEVER PROCEDURE .2. DIFFERENTIAL-EFFECTS OF BENZODIAZEPINE RECEPTOR AGONISTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID STIMULUS PROPERTIES; DIAZEPAM; MORPHINE; SALINE; RATS; CHLORDIAZEPOXIDE; ZOLPIDEM; PIGEONS; RO-15-1788; LORAZEPAM AB Twelve rats were trained to discriminate 0.32 and 3.2 mg/kg s.c. midazolam from no drug under a three-lever, multiple trials drug discrimination procedure. In cumulative dose-response tests, midazolam s.c. (0.032-10 mg/kg) and i.p. (0.1-10 mg/kg) occasioned dose-dependent increases first in 0.32 mg/kg (low-dose) lever responding and then in 3.2 mg/kg (high-dose) lever responding. The benzodiazepines diazepam (0.032-18 mg/kg) and triazolam (0.0032-3.2 mg/kg) produced patterns of generalization similar to that of midazolam; however, chlordiazepoxide (0.1-32 mg/kg), lorazepam (0.032-10 mg/kg), flurazepam (0.01-10 mg/kg), bretazenil (0.01-32 mg/kg) and the imidazo-pyridazine zolpidem (0.032-3.2 mg/kg) dose-dependently occasioned >80% responding on the low- but not the high-dose midazolam lever. Clonazepam (0.1-10 mg/kg) occasioned 0% responding on the high-dose lever, but also failed to occasion full generalization to the low-dose midazolam lever in 40% of the rats. Bretazenil has been well-characterized as a partial benzodiazepine agonist and zolpidem as benzodiazepine-receptor-subtype selective; the present results are consistent with their partial or selective agonist effects in those other paradigms. The differential effects of the classic 1,4 benzodiazepine agonists tested suggest that the discriminative stimulus effects of these other compounds may be more differentiable than previous drug discrimination studies have suggested. This three-choice drug discrimination procedure appears to be a useful model for studying relative intrinsic efficacies of this class of compounds. C1 JOHNS HOPKINS UNIV,SCH MED,BEHAV BIOL RES CTR,BALTIMORE,MD 21205. NIDA,INTRAMURAL RES PROGRAM,BEHAV PHARMACOL & GENET SECT,PRECLIN PHARMACOL LAB,BALTIMORE,MD. FU NIDA NIH HHS [DA-04133] NR 43 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 OCT PY 1995 VL 275 IS 1 BP 183 EP 193 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA467 UT WOS:A1995TA46700024 PM 7562548 ER PT J AU LIN, JT COY, DH MANTEY, SA JENSEN, RT AF LIN, JT COY, DH MANTEY, SA JENSEN, RT TI PEPTIDE STRUCTURAL REQUIREMENTS FOR ANTAGONISM DIFFER BETWEEN THE 2 MAMMALIAN BOMBESIN RECEPTOR SUBTYPES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GASTRIN-RELEASING PEPTIDE; CELL LUNG-CANCER; SWISS 3T3 CELLS; PANCREATIC ACINAR-CELLS; VASOACTIVE INTESTINAL PEPTIDE; COOH-TERMINAL FRAGMENTS; NEUROMEDIN-B-RECEPTOR; GUINEA-PIG PANCREAS; P ANALOGS FUNCTION; SUBSTANCE-P AB Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals. Five different classes of peptides that function as GRP receptor antagonists have been identified;; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor. In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified. [DPhe(12)]Bn analogs; des Met(14) amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist. All of these antagonists had low affinity for the NMB receptor. Application of similar strategies to NMB by formation of [DPhes(8)]NMB, [psi 9-10]NMB pseudopeptides, des-Met(10) NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists. D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists. No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist. These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs. These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different. These results indicate that the development of receptor subtype-specific peptide agonists or peptide antagonists for newly discovered receptor subtypes of gastrointestinal hormones/neurotransmitters may be difficult because the strategies developed for one well-studied subtype may not apply to the other even though it is structurally closely related. C1 NIDDK, DIGEST DIS BRANCH, BETHESDA, MD 20892 USA. TULANE UNIV, MED CTR, NEW ORLEANS, LA USA. FU NCI NIH HHS [CA-45153] NR 78 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1995 VL 275 IS 1 BP 285 EP 295 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA467 UT WOS:A1995TA46700036 PM 7562561 ER PT J AU SEBRING, NG GUCKES, AD LI, SH MCCARTHY, GR AF SEBRING, NG GUCKES, AD LI, SH MCCARTHY, GR TI NUTRITIONAL ADEQUACY OF REPORTED INTAKE OF EDENTULOUS SUBJECTS TREATED WITH NEW CONVENTIONAL OR IMPLANT-SUPPORTED MANDIBULAR DENTURES SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; STANDARD; ABILITY AB The nutrient content of the diet of edentulous patients who have various oral prostheses is of concern. This study compared baseline food records to those records kept semiannually for 3 years after treatment to ascertain whether nutrient intake of edentulous patients changed after they received new implant-supported mandibular dentures (n = 41) or new conventional dentures (n = 30). No significant differences in intake of calories or of 27 nutrients were noted between the two groups (p > 0.01). A decline in the percent of calories hom fat with a corresponding increase in carbohydrate calories within both groups (p < 0.01) reflected a national trend; a slight decrease in calories was similarly observed (p < 0.02). More than 40% of patients in both groups were found to have inadequate intakes of dietary fiber, calcium, or both, and 25% to 50% had low intakes of vitamins A, E, D, B-6 and/or magnesium. Intakes were similar to those reported for two age-matched populations. RP SEBRING, NG (reprint author), NIH,CTR CLIN,DEPT NUTR,BLDG 10,ROOM B1S-234,10 CTR DR,MSC 1078,BETHESDA,MD 20892, USA. NR 21 TC 50 Z9 51 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD OCT PY 1995 VL 74 IS 4 BP 358 EP 363 DI 10.1016/S0022-3913(05)80374-9 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TB895 UT WOS:A1995TB89500006 PM 8531152 ER PT J AU Weissman, G Melchior, L Huba, G Smereck, G Needle, R McCarthy, S Jones, A Genser, S Cottler, L Booth, R Altice, F AF Weissman, G Melchior, L Huba, G Smereck, G Needle, R McCarthy, S Jones, A Genser, S Cottler, L Booth, R Altice, F TI Women living with drug abuse and HIV disease: Drug abuse treatment access and secondary prevention issues SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE drug abuse; HIV disease; secondary prevention; treatment access; women ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HETEROSEXUAL TRANSMISSION; TREATMENT SERVICES; DEPENDENT WOMEN; AIDS; USERS; CRACK; CARE; ZIDOVUDINE; RISK AB In collaboration with the National Institute on Drug Abuse, the Health Resources and Services Administration is conducting a multisite, longitudinal study oil issues of service needs, service utilization, and access to care for drug abusers with HIV. This article discusses access to drug abuse treatment and HIV secondary prevention for 116 women interviewed during the study's first year in five U.S. cities. Using interview data from 115 service providers in those same cities, it also discusses drug abuse treatment availability and barriers to service expansion for drug users with HIV. Study findings indicate that there are highly significant gaps between the drug abuse treatment services these women feel they need and those they have been able to receive; these were particularly pronounced for drug detoxification and residential and outpatient drug-free treatment. Women who used crack cocaine or injection drugs had particularly high levels of need for residential and outpatient drug abuse treatment, while women who use crack were found to have significantly less experience with the drug abuse treatment system than IDUs. HIV secondary prevention was also found to be a critical need for these women, many of whom were engaging in behaviors that place them at risk for reinfection, infection with other diseases, and transmission to others. Providers indicated that lack of funding was the major barrier to expanding services for this population; other barriers, such as lack of ancillary services and transportation, were also noted. Two positive findings were that many drug abuse treatment agencies in these cities provide a wide range of ancillary services and that many different kinds of agencies offer drug abuse treatment services. C1 MEASUREMENT GRP, CULVER CITY, CA USA. PERSONALIZED NURSING CORP, ANN ARBOR, MI USA. NIDA, DIV EPIDEMIOL & PREVENT, COMMUNITY RES BRANCH, BALTIMORE, MD 21224 USA. RP Weissman, G (reprint author), HLTH RESOURCES & SERV ADM, ROCKVILLE, MD USA. OI Melchior, Lisa/0000-0002-0569-836X NR 48 TC 16 Z9 16 U1 4 U2 4 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD OCT-DEC PY 1995 VL 27 IS 4 BP 401 EP 411 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA TP337 UT WOS:A1995TP33700009 PM 8788695 ER PT J AU STEINBERG, AD GOURLEY, M AF STEINBERG, AD GOURLEY, M TI CYCLOPHOSPHAMIDE IN LUPUS NEPHRITIS SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID CONTROLLED TRIAL; ERYTHEMATOSUS; INFECTION C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BALTIMORE,MD. RP STEINBERG, AD (reprint author), MITRE CORP,7525 COLSHIRE DR,MCLEAN,VA 22102, USA. NR 12 TC 12 Z9 13 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 1995 VL 22 IS 10 BP 1812 EP 1815 PG 4 WC Rheumatology SC Rheumatology GA RX863 UT WOS:A1995RX86300002 PM 8991974 ER PT J AU ALAGHBANDRAD, J MCKENNA, K GORDON, CT ALBUS, KE HAMBURGER, SD RUMSEY, JM FRAZIER, JA LENANE, MC RAPOPORT, JL AF ALAGHBANDRAD, J MCKENNA, K GORDON, CT ALBUS, KE HAMBURGER, SD RUMSEY, JM FRAZIER, JA LENANE, MC RAPOPORT, JL TI CHILDHOOD-ONSET SCHIZOPHRENIA - THE SEVERITY OF PREMORBID COURSE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE CHILDHOOD-ONSET SCHIZOPHRENIA; PREMORBID; PRODROME; PREPSYCHOTIC ID 1ST-EPISODE SCHIZOPHRENIA; ADULT SCHIZOPHRENICS; AUTISTIC-CHILDREN; BLOOD-FLOW; PHENOMENOLOGY; CLASSIFICATION; PSYCHOSES AB Objective: To review the premorbid histories of 23 children meeting DSM-III-R criteria for schizophrenia with onset before age 12 years and to compare these with childhood data of later-onset schizophrenics. Method: Premorbid features up to 1 year before onset of first psychotic symptoms were rated from hospital and clinic records, clinical interviews, rating scales, and tests. Results: In keeping with previous studies, specific developmental disabilities and transient early symptoms of autism, particularly motor stereotypies, were common. Comparison with the childhood of later-onset schizophrenics showed greater delay in language development, and more premorbid speech and language disorders, learning disorders, and disruptive behavior disorders. (Sixty percent had received or were estimated to meet criteria for one or more clinical diagnoses.) Conclusions: Childhood-onset schizophrenia may represent a more malignant form of the disorder, although selection and ascertainment bias cannot be ruled out. The presence of prepsychotic language difficulties focuses attention on the importance of early temporal and frontal lobe development; early transient motor stereotypies suggest developmental basal ganglia abnormalities and extend previous findings seen in the childhood of later-onset patients. RP ALAGHBANDRAD, J (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. NR 64 TC 138 Z9 140 U1 3 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 1995 VL 34 IS 10 BP 1273 EP 1283 DI 10.1097/00004583-199510000-00012 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RX165 UT WOS:A1995RX16500012 PM 7592264 ER PT J AU NOVAKOVIC, B CLARK, WH FEARS, TR FRASER, MC TUCKER, MA AF NOVAKOVIC, B CLARK, WH FEARS, TR FRASER, MC TUCKER, MA TI MELANOCYTIC NEVI, DYSPLASTIC NEVI, AND MALIGNANT-MELANOMA IN CHILDREN FROM MELANOMA-PRONE FAMILIES SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID NAEVI; RISK; POPULATION AB Background: Melanocytic nevi, particularly dysplastic nevi (DN), are important markers of increased risk of malignant melanoma in adults, but little is known about their prevalence and relation to melanoma in children. Objective: Our purpose was to define the prevalence of DN, number of nevi, and their relation to the risk of melanoma in children younger than 20 years of age from melanoma-prone families. Methods: One hundred twenty-five persons younger than 20 years of age, from 23 melanoma-prone families, underwent clinical evaluation with nevus counts, photography, and biopsy of suspected melanocytic lesions and were observed for development of DN and melanoma. Results: In melanoma-prone families, 37% of children had DN. The patients were divided into four categories: those with melanoma, DN (without melanoma), indeterminant (largely because of age at examination), and unaffected. The risk of melanoma was assessed by news number and presence of DN. High nevus number was strongly correlated with the presence of DN. The risk of the development of melanoma in children from melanoma-prone families appeared most related to the presence of DN (relative risk, 45; 95% confidence intervals, 2.6-786.4) and started at an early age. Of note, all children in whom melanoma developed had DN. Conclusion: Family history of melanoma and the presence of DN defines children with a high risk for melanoma developing at an early age. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. RP NOVAKOVIC, B (reprint author), NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 18 TC 26 Z9 26 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 OCT PY 1995 VL 33 IS 4 BP 631 EP 636 DI 10.1016/0190-9622(95)91284-3 PG 6 WC Dermatology SC Dermatology GA RX311 UT WOS:A1995RX31100012 PM 7673498 ER PT J AU NORMAN, JE LEVY, D AF NORMAN, JE LEVY, D TI IMPROVED ELECTROCARDIOGRAPHIC DETECTION OF ECHOCARDIOGRAPHIC LEFT-VENTRICULAR HYPERTROPHY - RESULTS OF A CORRELATED DATA-BASE APPROACH SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RV6-RV5 VOLTAGE RATIO; CRITERIA; VALIDATION; SENSITIVITY; SPECIFICITY; MASS AB Objectives. We used electrocardiographic (ECG) and echocardiographic measurements from 3,351 adults from the Framingham Heart Study to evaluate the performance of 10 ECG criteria in detecting left ventricular hypertrophy before and after adjust ment for gender, age and obesity. Background. Significant improvement in the sensitivity and specificity of ECG voltage based criteria for detection of echocardiographic left ventricular hypertrophy using gender-specific criteria adjusted for age and obesity has been demonstrated. Methods. Gender-specific correlation and regression analyses were used to identify the five most sensitive ECG criteria and to adjust them for age and obesity, Standard and truncated receiver operating characteristic curves were used to compare the selected criteria. Results. Linear regression of left ventricular mass on ECG voltages, body mass index and age yielded considerably stronger relations for women than for men because of the greater correlation between ventricular mass and body mass index in women. Obesity and age adjustment of the five voltage criteria produced considerable improvement in their performance. The voltage sum of the R wave in lead aVL and the S wave in lead V-3, alone and in combination with QRS duration, had a sensitivity at 95% specificity of 32% and 39%, respectively, in men and 46% and 51%, respectively, in women after adjustment. Tables of critical voltages for the adjusted criteria and representative performance values are presented. Conclusions. Incorporation of obesity and age in ECG algorithms consistently improves their performance in the detection of hypertrophy. The development of such criteria will enhance the utility of this inexpensive screening test. Such ECG approaches should be used in clinical trials to assess the efficacy of antihypertensive treatment to effect regression of left ventricular hypertrophy. A search for further improvements in the efficacy of ECG criteria for this purpose is warranted. Independent validation of this approach is needed. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. RP NORMAN, JE (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,2 ROCKLEDGE CTR,ROOM 8148,6701 ROCKLEDGE DR,MSC 7,BETHESDA,MD 20892, USA. NR 31 TC 68 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO 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 OCT PY 1995 VL 26 IS 4 BP 1022 EP 1029 DI 10.1016/0735-1097(95)00269-5 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RX427 UT WOS:A1995RX42700029 PM 7560595 ER PT J AU LAUER, MS LARSON, MG LEVY, D AF LAUER, MS LARSON, MG LEVY, D TI GENDER-SPECIFIC REFERENCE M-MODE VALUES IN ADULTS - POPULATION-DERIVED VALUES WITH CONSIDERATION OF THE IMPACT OF HEIGHT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR MASS; ISOLATED SYSTOLIC HYPERTENSION; CORONARY-ARTERY DISEASE; ECHOCARDIOGRAPHIC MEASUREMENTS; PROGNOSTIC IMPLICATIONS; CARDIOVASCULAR-DISEASE; HYPERTROPHY; AGE AB Objectives. The purpose of this investigation was to derive population-based reference values for M-mode echocardiographic dimensions that can be applied in epidemiologic studies, clinical trials and clinical practice and to determine optimal methods for adjusting these dimensions for body size. Background. M-mode echocardiography remains an important modality for studying cardiovascular disease; this is especially true with regard to detecting target organ damage in systemic hypertension, Most previously published reference values were derived from hospital-based series or relatively small samples and mere not gender specific. Methods. Using a sample of 288 men and 524 women who were between 20 and 45 years of age and who were free of cardiovascular disease, reference values were derived for end-diastolic and end-systolic left ventricular internal dimensions, left ventricular wall thickness and left atrial dimension. The relations between these dimensions and height, a measure of body size relatively independent of obesity, were investigated using various regression models. Results. Nomograms for mean and 95th percentile values in men and women were constructed on the basis of linear regression models relating echocardiographic dimensions to height. Adjustment for body surface area greatly attenuated associations between obesity and cardiac dimensions in a separate healthy but less restricted sample of 411 men and 503 women. Conclusions. Gender-specific M-mode reference values and nomograms, with mean and 95th percentile values for echocardiographic dimensions as a function of height, are reported. The use of body surface area as means of body size adjustment is called into question. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. BOSTON UNIV,SCH MED,DEPT PREVENT MED & EPIDEMIOL,BOSTON,MA. NHLBI,BETHESDA,MD. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 39 TC 57 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO 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 OCT PY 1995 VL 26 IS 4 BP 1039 EP 1046 DI 10.1016/0735-1097(95)00275-0 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RX427 UT WOS:A1995RX42700031 PM 7560597 ER PT J AU ROSENSTEIN, DL RYSCHON, TW NIEMELA, JE ELIN, RJ BALABAN, RS RUBINOW, DR AF ROSENSTEIN, DL RYSCHON, TW NIEMELA, JE ELIN, RJ BALABAN, RS RUBINOW, DR TI SKELETAL-MUSCLE INTRACELLULAR IONIZED MAGNESIUM MEASURED BY P-31-NMR SPECTROSCOPY ACROSS THE MENSTRUAL-CYCLE SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE MAGNESIUM; MAGNETIC RESONANCE SPECTROSCOPY; (31)PHOSPHORUS; MENSTRUAL CYCLE; HUMAN ID RED-BLOOD-CELL; PREMENSTRUAL-SYNDROME; SERUM MAGNESIUM; NMR; METABOLISM; RAT AB Objective: The hormonal regulation of magnesium (Mg) metabolism is poorly understood. Preliminary evidence suggests that reproductive hormones may influence Mg concentrations in various tissues. The purpose of this study was to determine if Mg concentrations in blood and muscle are affected by the phase of the menstrual cycle. Methods: Magnesium measures were obtained from 16 women over the course of one complete menstrual cycle. The principal outcome measure was intracellular ionized Mg ([Mg++]i) in skeletal muscle as measured by P-31 nuclear magnetic resonance spectroscopy. Three blood measures (serum, red blood cell, and mononuclear blood cell) of total Mg ([Mg]) were also obtained. Results: Mean Mg concentrations were stable across the menstrual cycle with no evidence of a menstrual cycle phase effect for any of the measures. Furthermore, skeletal muscle [Mg++]i was not correlated with any blood measure of [Mg]. Conclusion: These results suggest that physiologic fluctuations in reproductive hormones do not influence either blood [Mg] or skeletal muscle [Mg++]i in healthy, regularly cycling women. C1 NHLBI,CTR CLIN,DEPT CLIN PATHOL,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RP ROSENSTEIN, DL (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BLDG 10 ROOM 3N238,10 CTR DR,MSC 1276,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 34 TC 6 Z9 6 U1 1 U2 2 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD OCT PY 1995 VL 14 IS 5 BP 486 EP 490 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RX307 UT WOS:A1995RX30700013 PM 8522728 ER PT J AU HODES, RJ ORY, MG PRUZAN, MR AF HODES, RJ ORY, MG PRUZAN, MR TI COMMUNICATING WITH OLDER PATIENTS - A CHALLENGE FOR RESEARCHERS AND CLINICIAN SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material RP HODES, RJ (reprint author), NIA,BLDG 31,RM 5C35,31 CTR DR,MSC 2292,BETHESDA,MD 20892, USA. NR 4 TC 8 Z9 8 U1 0 U2 0 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 OCT PY 1995 VL 43 IS 10 BP 1167 EP 1168 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY285 UT WOS:A1995RY28500018 PM 7560712 ER PT J AU LECCHI, P PANNELL, LK AF LECCHI, P PANNELL, LK TI THE DETECTION OF INTACT DOUBLE-STRANDED DNA BY MALDI SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Note ID LASER-DESORPTION IONIZATION; FLIGHT MASS-SPECTROMETRY; OLIGONUCLEOTIDE DUPLEX; MATRIX; ULTRAVIOLET; ACIDS AB DNA fragments have been analyzed by matrix-assisted laser desorption ionization (MALDI) and electrospray mass spectrometry. In many cases, only the single-stranded oligonucleotides have been detected. Recently, spectra of intact double-stranded DNA have been obtained in both electrospray and massive duster impact ionization. We show here the first MALDI spectra of intact double-stranded DNA (EcoR1 adaptor 12/16) that is clearly not due to nonspecific dimer formation. 6-Aza-2-thiothymine was used as the matrix in the presence of ammonium citrate. Via the same procedure but with other matrices commonly employed for oligonucleotide analysis, the intact DNA duplex was not detected. No sign of the homodimer of either of the single strands is observed. Although the spectrum also shows peaks attributable to each of the single strands, these are demonstrated to arise from the DNA solution and not the sample preparation or desorption process. RP LECCHI, P (reprint author), NIDDK,ANALYT CHEM LAB,BLDG 8,ROOM B2A23,BETHESDA,MD 20892, USA. NR 26 TC 64 Z9 65 U1 1 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD OCT PY 1995 VL 6 IS 10 BP 972 EP 975 DI 10.1016/1044-0305(95)00524-H PG 4 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA RX572 UT WOS:A1995RX57200011 PM 24214041 ER PT J AU SHI, XL MAO, Y SAFFIOTTI, U WANG, LY ROJANASAKUL, Y LEONARD, SS VALLYATHAN, V AF SHI, XL MAO, Y SAFFIOTTI, U WANG, LY ROJANASAKUL, Y LEONARD, SS VALLYATHAN, V TI ANTIOXIDANT ACTIVITY OF TETRANDRINE AND ITS INHIBITION OF QUARTZ-INDUCED LIPID-PEROXIDATION SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID FREE-RADICALS; NITRIC-OXIDE; SILICA; SUPEROXIDE; HYDROXYL; DESFERRIOXAMINE; CYTOTOXICITY; HEMOLYSIS; MECHANISM; SURFACE AB Tetrandrine is a benzylisoquinoline alkaloid that has been used in China as an antifibrotic drug to treat the lesions of silicosis. Its mechanism in the treatment of silicosis is unclear. Electron spin resonance (ESR) spin trapping was employed to investigate the antioxidant properties of tetrandrine. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Tetrandrine efficiently reacted with hydroxyl ((OH)-O-.) radicals with a reaction rate of approximately 1.4 x 10(10) M(-1) s(-1). The (OH)-O-. radicals were generated by the Fenton reaction [Fe(II) + H2O2) as well as by reaction of chromium(V) with H2O2. Similar results were obtained using (OH)-O-. radicals generated by reaction of freshly fractured quartz particles with aqueous medium. Tetrandrine also scavenged superoxide (O-2(-)) radicals produced from xanthine/xanthine oxidase. The effect or tetrandrine on lipid peroxidation induced by freshly fractured quartz particles was evaluated using linoleic acid as a model lipid. The results showed that tetrandrine caused a significant inhibition on freshly fractured quartz-induced lipid peroxidation. C1 W VIRGINIA UNIV,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV. NIOSH,PATHOL SECT,MORGANTOWN,WV. RP SHI, XL (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012; OI Rojanasakul, Yon/0000-0002-8839-6462 NR 39 TC 28 Z9 33 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD OCT PY 1995 VL 46 IS 2 BP 233 EP 248 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA RZ405 UT WOS:A1995RZ40500008 PM 7563220 ER PT J AU SUBBARAO, EK PARK, EJ LAWSON, CM CHEN, AY MURPHY, BR AF SUBBARAO, EK PARK, EJ LAWSON, CM CHEN, AY MURPHY, BR TI SEQUENTIAL ADDITION OF TEMPERATURE-SENSITIVE MISSENSE MUTATIONS INTO THE PB2 GENE OF INFLUENZA-A TRANSFECTANT VIRUSES CAN EFFECT AN INCREASE IN TEMPERATURE SENSITIVITY AND ATTENUATION AND PERMITS THE RATIONAL DESIGN OF A GENETICALLY-ENGINEERED LIVE INFLUENZA-A VIRUS-VACCINE SO JOURNAL OF VIROLOGY LA English DT Article ID A VIRUS; REASSORTANT VIRUS; SQUIRREL-MONKEYS; RNA-POLYMERASE; PHENOTYPE; CHILDREN; MUTANTS; H3N2; VOLUNTEERS AB We have previously described a strategy for the recovery of a synthetic influenza A virus wild-type (wt) PB2 gene (derived from influenza A/Ann Arbor/6/60 [AA] virus) into an infectious virus. It was possible to introduce an attenuating temperature-sensitive (ts) mutation at amino acid residue 265 of the AA wt PB2 gene and to rescue this mutant gene into infectious virus, Application of this new technology to influenza A virus vaccine development requires that multiple attenuating mutations be introduced to achieve a satisfactorily attenuated virus that retains the attenuation (att) phenotype following replication in vivo. In this report, we demonstrate that putative ts mutations at amino acids 112, 556, and 658 each indeed specify the ts and att phenotypes. Each of these mutations was introduced into a cDNA copy of the AA mutant mt265 PB2 gene to produce three double-mutant PB2 genes, each of which was rescued into an infectious virus. In general, the double-mutant PB2 transfectant viruses were more ts and attenuated in the lower respiratory tracts of hamsters than the single-mutant transfectant viruses, and the ts phenotype of two of three double-mutant PB2 transfectant viruses was stable even after prolonged replication in the upper respiratory tracts of immunocompromised mice. Two triple-mutant PB2 transfectant viruses with three predicted amino acid substitutions resulting from five nucleotide substitutions in the cDNA were then generated. The triple-mutant PB2 transfectant viruses were more ts and more attenuated than the double-mutant PB2 transfectant viruses. These results indicate that sequential introduction of additional fs mutations into the PB2 gene can yield mutants that exhibit a stepwise increase in temperature sensitivity and attenuation compared with the preceding mutant(s) in the series. Furthermore, the level of temperature sensitivity of the transfectant viruses correlated significantly with the level of attenuation of these viruses in hamsters, Although the triple-mutant PB2 transfectant viruses were attenuated in hamsters, intranasal administration of these viruses elicited a vigorous serum hemagglutination-inhibiting antibody response, and this was associated with resistance of the lower respiratory tract to subsequent wt virus challenge. These observations suggest the feasibility of using PB2 reverse genetics to generate a live influenza A virus vaccine donor strain that contains three attenuating mutations in one gene. It is predicted that reassortant viruses derived from such a donor virus would have the properties of attenuation, genetic stability, immunogenicity, and protective efficacy against challenge with wt virus. RP SUBBARAO, EK (reprint author), NIAID,RESP VIRUSES SECT,INFECT DIS LAB,BLDG 7,ROOM 106,7 CTR DR,MSC 0720,BETHESDA,MD 20892, USA. NR 31 TC 40 Z9 42 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 OCT PY 1995 VL 69 IS 10 BP 5969 EP 5977 PG 9 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400006 PM 7666501 ER PT J AU WU, SC SPOUGE, JL CONLEY, SR TSAI, WP MERGES, MJ NARA, PL AF WU, SC SPOUGE, JL CONLEY, SR TSAI, WP MERGES, MJ NARA, PL TI HUMAN PLASMA ENHANCES THE INFECTIVITY OF PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND MONOCYTE-DERIVED MACROPHAGES SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELLS; CD4+ CELLS; HIV; ENTRY; RECEPTOR; REPLICATION; MOLECULES; ANTIGEN; NEUTRALIZATION; PATHOGENESIS AB Physiological microenvironments such as blood, seminal plasma, mucosal secretions, or lymphatic fluids may influence the biology of the virus-host cell and immune interactions for human immunodeficiency virus type 1 (HIV-1). Relative to media, physiological levels of human plasma were found to enhance the infectivity of HIV-1 primary isolates in both phytohemagglutinin-stimulated peripheral blood mononuclear cells and monocyte-derived macrophages. Enhancement was observed only when plasma was present during the virus cell incubation and resulted in a 3- to 30-fold increase in virus titers in all of the four primary isolates tested, Both infectivity and virion binding experiments demonstrated a slow, time-dependent process generally requiring between 1 and 10 h. Human plasma collected in anticoagulants CPDA-1 and heparin, but not EDTA, exhibited this effect at concentrations from 90 to 40%. Furthermore, heat-inactivated plasma resulted in a loss of enhancement in peripheral blood mononuclear cells but not in monocyte-derived macrophages. Physiological concentrations of human plasma appear to recruit additional infectivity, thus increasing the infectious potential of the virus inoculum. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP WU, SC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRUS BIOL SECT,TUMOR CELL BIOL LAB,BLDG 560,R 12-92,FREDERICK,MD 21702, USA. NR 57 TC 28 Z9 28 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 OCT PY 1995 VL 69 IS 10 BP 6054 EP 6062 PG 9 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400016 PM 7666510 ER PT J AU GOLDING, H DIMITROV, DS MANISCHEWITZ, J BRODER, CC ROBINSON, J FABIAN, S LITTMAN, DR LAPHAM, CK AF GOLDING, H DIMITROV, DS MANISCHEWITZ, J BRODER, CC ROBINSON, J FABIAN, S LITTMAN, DR LAPHAM, CK TI PHORBOL ESTER-INDUCED DOWN-MODULATION OF TAILLESS CD4 RECEPTORS REQUIRES PRIOR BINDING OF GP120 AND SUGGESTS A ROLE FOR ACCESSORY MOLECULES SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; RECOMBINANT VACCINIA VIRUSES; MEMBRANE-FUSION; CONFORMATIONAL-CHANGES; CD4-MEDIATED FUSION; CYTOPLASMIC DOMAIN; HIV-1 INFECTION; CELL-FUSION; T-CELLS AB The entry of human immunodeficiency virus type 1 into cells proceeds via a fusion mechanism that is initiated by binding of the viral glycoprotein gp120-gp41 to its cellular receptor CD4. Species- and tissue-specific restrictions to viral entry suggested the participation of additional membrane components in the postbinding fusion events. In a previous study (H. Golding, J. Manischewitz, L. Vujcic, R. Blumenthal, and D. Dimitrov, J. Virol. 68:1962-1968, 1994), it was found that phorbol myristate acetate (PMA) inhibits human immunodeficiency virus type 1 envelope-mediated cell fusion by inducing down modulation of an accessory component(s) in the CD4 expressing cells. The fusion inhibition was seen in a variety of cells, including T-cell transfectants expressing engineered CD4 receptors (CD4.401 and CD4.CD8) which are not susceptible to down modulation by PMA treatment. In the current study, it was found that preincubation of A2.01.CD4.401 cells with soluble monomeric gp120 for 1 h at 37 degrees C primed them for PMA-induced down modulation (up to 70%) of the tailless CD4 receptors. The gp120-priming effect was temperature dependent, and the down modulation may have occurred via clathrin-coated pits. Importantly, nonhuman cell lines expressing tailless CD4 molecules did not down modulate their CD4 receptors under the same conditions. The gp120-dependent PMA-induced down modulation of tailless CD4 receptors could be efficiently blocked by the human monoclonal antibodies 48D and 17B, which bind with increased avidity to gp120 that was previously bound to CD4 (M. Thali, J. P. Moore, C. Furman, M. Charles, D. D. Ho, J. Robinson, and J. Sodroski, J. Virol. 67:3978-3988, 1993). These findings suggest that gp120 binding to cellular CD4 receptors induces conformational changes leading to association of the gp120-CD4 complexes with accessory transmembrane molecules that are susceptible to PMA-induced down modulation and can target the virions to clathrin-coated pits. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. UNIV CONNECTICUT,HLTH SCI CTR,FARMINGTON,CT. UNIV CALIF SAN FRANCISCO,SCH MED,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. RP GOLDING, H (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-24030] NR 39 TC 38 Z9 39 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 OCT PY 1995 VL 69 IS 10 BP 6140 EP 6148 PG 9 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400025 PM 7545243 ER PT J AU WHITCOMB, JM ORTIZCONDE, BA HUGHES, SH AF WHITCOMB, JM ORTIZCONDE, BA HUGHES, SH TI REPLICATION OF AVIAN-LEUKOSIS VIRUSES WITH MUTATIONS AT THE PRIMER BINDING-SITE - USE OF ALTERNATIVE TRANSFER-RNAS AS PRIMERS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; TRYPTOPHAN TRANSFER-RNA; MOLECULAR-WEIGHT RNAS; REVERSE TRANSCRIPTION; NUCLEOTIDE-SEQUENCE; DNA-POLYMERASE; GENOMIC RNA; AIDS VIRUS; TYPE-1; INITIATION AB We have tested whether avian leukosis viruses (ALVs) can use tRNAs other than tRNA(Trp) to initiate reverse transcription, The primer binding site (PBS) of a wild-type ALV provirus, which is complementary to the 3' end of tRNA(Trp), was replaced with sequences homologous to the 3' ends of six different chicken tRNAs (tRNA(Pro) tRNA(Lys), tRNA(Met), tRNA(Ile), tRNA(Phe), and tRNA(Ser)). Transfection of these proviruses into chicken embryo fibroblasts resulted in the production of infectious viruses, all of which apparently used the tRNA specified by the mutated PBS to replicate. However, growth of these viruses resulted in reversion to the wild-type (tRNA(Trp)) PBS. Some of the viruses revert quite quickly, while others are more stable. The relative stability of, a given PBS correlated with the concentration of the corresponding tRNA in the virion. We determined the percentage of viral RNA that had a tRNA bound to the PBS and found that the occupancy rate is lower in the mutants than in the wild-type virus. We conclude that;many different tRNAs can be used as primers to initiate reverse transcription in ALV. However, ALVs that use tRNA(Trp) have a growth advantage over ALVs that use other tRNAs. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 50 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1995 VL 69 IS 10 BP 6228 EP 6238 PG 11 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400034 PM 7545245 ER PT J AU GIRARD, M MEIGNIER, B BARRESINOUSSI, F KIENY, MP MATTHEWS, T MUCHMORE, E NARA, PL WEI, Q RIMSKY, L WEINHOLD, K FULTZ, PN AF GIRARD, M MEIGNIER, B BARRESINOUSSI, F KIENY, MP MATTHEWS, T MUCHMORE, E NARA, PL WEI, Q RIMSKY, L WEINHOLD, K FULTZ, PN TI VACCINE-INDUCED PROTECTION OF CHIMPANZEES AGAINST INFECTION BY A HETEROLOGOUS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODY; GP160 SUBUNIT VACCINE; ENVELOPE GLYCOPROTEIN; RECOMBINANT VACCINIA; T-CELLS; SYNTHETIC PEPTIDES; MONONUCLEAR-CELLS; HIV INFECTION; ENV PROTEIN; GP120 AB The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1) is a major problem to overcome in the development of an effective vaccine, In the most reliable animal model of HIV-1 infection, chimpanzees were immunized with various combinations of HIV-1 antigens, which were derived primarily from the surface glycoprotein, gp160, of HIV-1 strains LAT and MN, The immunogens also included a live recombinant canarypox virus expressing a gp160-MN protein. In one experiment, two chimpanzees were immunized multiple times; one animal received antigens derived only from HIV-I-LAI and the second animal received antigens from both HIV-1(LAI) and HIV-1(MN). In another experiment, four chimpanzees were immunized in parallel a total of five times over 18 months; two animals received purified gp160 and V3-MN peptides, whereas the other two animals received the recombinant canarypox virus and gp160. At 3 months after the final booster, all immunized and naive control chimpanzees were challenged by intravenous inoculation of HIV-1(SF2); therefore, the study represented an intrasubtype B heterologous virus challenge. Virologic and serologic follow-up showed that the controls and the two chimpanzees immunized with the live recombinant canarypox virus became infected, whereas the other animals that were immunized with gp160 and V3-MN peptides were protected from infection. Evaluation of both cellular and humoral HIV-specific immune responses at the time of infectious HIV-1 challenge identified the following as possible correlates of protection: antibody titers to the V3 loop of MN and neutralizing antibody titers to HIV-1(MN) or HIV-1(LAI) but not to HIV-1(SF2). The results of this study indicate that vaccine-mediated protection against intravenous infection with heterologous HIV-1 strains of the same subtype is possible with some immunogens. C1 UNIV ALABAMA,SCH MED,DEPT MICROBIOL,BIRMINGHAM,AL 35294. PASTEUR MERIEUX SERUMS & VACCINS,F-69280 MARCY LETOILE,FRANCE. INST PASTEUR,F-75015 PARIS,FRANCE. TRANSGENE SA,F-67000 STRASBOURG,FRANCE. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. NYU,MED CTR,EXPTL MED & SURG PRIMATES LAB,NEW YORK,NY 10016. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RI Barre-Sinoussi, Francoise/G-8355-2011 NR 69 TC 89 Z9 90 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 OCT PY 1995 VL 69 IS 10 BP 6239 EP 6248 PG 10 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400035 PM 7666524 ER PT J AU HOGERVORST, E DEJONG, J VANWIJK, A BAKKER, M VALK, M NARA, P GOUDSMIT, J AF HOGERVORST, E DEJONG, J VANWIJK, A BAKKER, M VALK, M NARA, P GOUDSMIT, J TI INSERTION OF PRIMARY SYNCYTIUM-INDUCING (SI) AND NON-SI ENVELOPE V3 LOOPS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) LAI REDUCES NEUTRALIZATION SENSITIVITY TO AUTOLOGOUS, BUT NOT HETEROLOGOUS, HIV-1 ANTIBODIES SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-ACID SUBSTITUTION; 3RD VARIABLE DOMAIN; SOLUBLE CD4; BIOLOGICAL PHENOTYPE; ANTIGENIC VARIATION; GLYCOPROTEIN GP120; PRIMARY INFECTION; VIRAL ENVELOPE; HTLV-III; SEQUENCE AB The aim of the study was to investigate the influence of V3 loops from naturally occurring viruses on the neutralization sensitivity of a molecularly cloned virus, A selection of well-defined syncytium-inducing (SI) and non-SI V3 loops of a single human immunodeficiency virus type 1-infected individual (H594) and the V3 regions of two SI laboratory strains were inserted in an infectious molecular clone of human immunodeficiency type 1 LAI. Neutralization was performed with a heterologous serum pool and autologous patient serum, using the virus reduction neutralization assay and peripheral blood lymphocytes as target cells. High sensitivity of the chimeric viruses containing the laboratory strain V3 regions to neutralization by H594 sequential sera as well as the heterologous serum pool was found. A statistically significant correlation between the sensitivities of these viruses was seen. In contrast, insertion of the primary isolate NSI and SI envelope V3 loops significantly reduced the neutralization by autologous serum but not by the heterologous serum pool. No correlation was found between the neutralization of the viruses with laboratory strain-derived V3 regions and the viruses with primary isolate V3 domains. We conclude that heterologous antibodies are able to neutralize infectious molecular clones with V3 loops of both SI and NSI viruses, regardless of whether they originated from laboratory strains or primary isolates. However, serum of patient H594 discriminated between the two types of viruses and showed reduced neutralization of the viruses with the autologous NSI and SI primary isolate V3 loops. These results indicated that the neutralization sensitivity of the viruses depended on the capacity of the V3 region to influence the conformation of the virus envelope. These V3-dependent conformational changes partially explain the neutralization sensitivity of laboratory strains and the relative neutralization resistance of primary isolates. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRUS BIOL SECT,FREDERICK,MD 21701. RP HOGERVORST, E (reprint author), UNIV AMSTERDAM,ACAD MED CTR,HUMAN RETROVIRUS LAB,MEIBERGDREEF 15,1105 AZ AMSTERDAM,NETHERLANDS. NR 83 TC 16 Z9 17 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 OCT PY 1995 VL 69 IS 10 BP 6342 EP 6351 PG 10 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400047 PM 7666535 ER PT J AU MALDARELLI, F SATO, H BERTHOLD, E ORENSTEIN, J MARTIN, MA AF MALDARELLI, F SATO, H BERTHOLD, E ORENSTEIN, J MARTIN, MA TI RAPID INDUCTION OF APOPTOSIS BY CELL-TO-CELL TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTED CHIMPANZEES; THYMOCYTE APOPTOSIS; DEATH; HIV-1; DNA; ACTIVATION; MECHANISM; ABSENCE; CD4; FRAGMENTATION AB The kinetics of human immunodeficiency virus type 1 (HIV-1)-induced cell death were investigated in cell-to-cell and cell-free models of virus transmission. Cocultivation of HIV-1 chronically infected H9 donor cells with uninfected H9 recipient cells resulted in rapid induction of programmed cell death, Within 8 h, apoptotic chromatin condensation was identified by histologic staining. In addition, many single cells with apoptotic nuclei were observed, indicating that stable cell fusion was not a requirement for apoptosis to occur. By 12 to 18 h of coculture, a DNA fragmentation ladder characteristic of apoptosis was detected by agarose gel electrophoresis. Quantitation of apoptosis hy measurement of nuclear DNA content revealed that at least 20 to 30% of the nuclei were undergoing apoptosis by 24 h after cocultivation. The appearance of condensed nuclei and fragmented DNA occurred as HIV reverse transcription was completed, and it was not inhibited by zidovudine, suggesting that induction of apoptosis did not require new HIV replication. Soluble CD4 inhibited apoptosis, demonstrating that Env-CD4 interactions were required for apoptosis. In contrast to that in cell-to-cell transmission, apoptosis in cell-free HIV infections was markedly inefficient and was not observed until 70 to 90 h after infections were initiated. These findings indicate that HIV-1 induction of programmed destruction of the nucleus is initiated at the time of cell-cell cocultivation by a mechanism which requires CD4-Env interactions but not new HIV replication. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20036. RP MALDARELLI, F (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 328,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 59 TC 61 Z9 61 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 OCT PY 1995 VL 69 IS 10 BP 6457 EP 6465 PG 9 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400060 PM 7666547 ER PT J AU STAEBLER, A PIERCE, JH BRAZINSKI, S HEIDARAN, MA LI, WQ SCHLEGEL, R GOLDSTEIN, DJ AF STAEBLER, A PIERCE, JH BRAZINSKI, S HEIDARAN, MA LI, WQ SCHLEGEL, R GOLDSTEIN, DJ TI MUTATIONAL ANALYSIS OF THE BETA-TYPE PLATELET-DERIVED GROWTH-FACTOR RECEPTOR DEFINES THE SITE OF INTERACTION WITH THE BOVINE PAPILLOMAVIRUS TYPE-1 E5 TRANSFORMING PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID OPEN READING FRAME; SIGNAL TRANSDUCTION; CELLS; EGF; ONCOPROTEIN; PATHWAYS; BINDING; ENCODES; DOMAIN; GENE AB The E5 polypeptide of bovine papillomavirus type 1 is a small membrane-bound protein which induces the transformation of immortalized fibroblasts, apparently via the formation of a ternary complex with the platelet-derived growth factor receptor (PDGFR) and the 16-kDa V-ATPase protein. This interaction seems to be mediated, at least in part, by their respective transmembrane domains. E5 also cooperates with transfected beta PDGFR to induce interleukin-3 (IL-3)-independent growth of a mouse myeloid precursor cell line (32D) which normally lacks expression of most known tyrosine kinase growth factor receptors. Cell proliferation induced by beta PDGFR and E5 is also highly specific, since the highly conserved alpha PDGFR and other related receptors did not physically or functionally interact with E5 in these cells. In the current study, analysis of chimeric alpha and beta PDGFRs confirmed that a short region encompassing the beta PDGFR transmembrane domain was sufficient for complex formation with E5, receptor autophosphorylation, and sustained proliferation of 32D cells in the absence of IL-3. Furthermore, a deletion mutant lacking the entire extracellular domain efficiently bound E5 and induced IL-3-independent growth. These data provide direct evidence that the interaction between E5 and the beta PDGFR involves amino acids 531 to 556 of the receptor transmembrane region and that this specific interaction is critical for activation of the PDGFR signalling complex. C1 GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT GYNECOL ONCOL,WASHINGTON,DC 20007. FU NCI NIH HHS [R01 CA-53371, R29 CA-63044] NR 31 TC 32 Z9 34 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 OCT PY 1995 VL 69 IS 10 BP 6507 EP 6517 PG 11 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400066 PM 7666552 ER PT J AU BARKSDALE, SK BAKER, CC AF BARKSDALE, SK BAKER, CC TI DIFFERENTIATION-SPECIFIC ALTERNATIVE SPLICING OF BOVINE PAPILLOMAVIRUS LATE MESSENGER-RNAS SO JOURNAL OF VIROLOGY LA English DT Note ID MONOCLONAL-ANTIBODIES; TYPE-1; IDENTIFICATION; CELLS AB Activation of the late promoter (P-L) of bovine papillomavirus type 1 (BPV-1) is dependent on the differentiation state of keratinocytes and occurs in the upper layers of the bovine fibropapilloma. In this study, we show by in situ hybridization that a differentiation-specific pattern of BPV-1 late RNA splicing is also seen in the fibropapilloma. RNAs containing the 7385/3605 and 3764/5609 splice junctions were confined to the granular cell layer. In contrast, RNAs containing the 7385/3225 splice junction were present in both the granular and spinous layers. The switch in splice site usage in the granular cell layer limits the expression of the mRNA encoding the major capsid protein to these most terminally differentiated cells. Thus, BPV-1 late mRNA expression is regulated at both transcriptional and posttranscriptional levels. C1 NCI, TUMOR VIRUS BIOL LAB, BETHESDA, MD 20892 USA. NR 14 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 1995 VL 69 IS 10 BP 6553 EP 6556 PG 4 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400072 PM 7666558 ER PT J AU KAWASE, M MOMOEDA, M YOUNG, NS KAJIGAYA, S AF KAWASE, M MOMOEDA, M YOUNG, NS KAJIGAYA, S TI MODEST TRUNCATION OF THE MAJOR CAPSID PROTEIN ABROGATES B19 PARVOVIRUS CAPSID FORMATION SO JOURNAL OF VIROLOGY LA English DT Note ID SEQUENCE; INFECTION; UNIQUE; VIRUS AB In vitro studies have suggested an important role for the minor capsid protein (VP1) unique region and the junction between VP1 and the major capsid protein (VP2) in the neutralizing immune response to B19 parvovirus. We investigated the role of the NH2-terminal region of the major structural protein in capsid structure by expressing progressively more truncated versions of the VP2 gene followed by analysis using immunoblotting and electron microscopy of density gradient-purified particles. Deletion of the first 25 amino acids (aa) of VP2 did not affect capsid assembly. Altered VP2 with truncations to aa 26 to 30, including a single amino acid deletion at position 25, failed to self-assemble but did participate,vith normal VP2 in the capsid structure. The altered region corresponds to the beginning of the beta A antiparallel strand. Truncations beyond aa 30 were incompatible with either self-assembly or coassembly, probably because of deletion of the beta B strand, which helps to form the core structure of the virus. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 27 TC 9 Z9 13 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 OCT PY 1995 VL 69 IS 10 BP 6567 EP 6571 PG 5 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400075 PM 7666560 ER PT J AU SHAFFER, DR EMERSON, SU MURPHY, PC GOVINDARAJAN, S LEMON, SM AF SHAFFER, DR EMERSON, SU MURPHY, PC GOVINDARAJAN, S LEMON, SM TI A HEPATITIS-A VIRUS DELETION MUTANT WHICH LACKS THE FIRST PYRIMIDINE-RICH TRACT OF THE 5'-NONTRANSLATED RNA REMAINS VIRULENT IN PRIMATES AFTER DIRECT INTRAHEPATIC NUCLEIC-ACID TRANSFECTION SO JOURNAL OF VIROLOGY LA English DT Note ID A VIRUS; CELL-CULTURE; VIRAL-HEPATITIS; MUTATIONS; ADAPTATION; REGION; ATTENUATION; INVITRO; DISEASE; GROWTH AB Cell culture-adapted variants of hepatitis A virus (HAV) in which the first pyrimidine-rich tract (pY1;nucleotides 99 to 138) of the 5' nontranslated region has been deleted (Delta 96-137 or Delta 96-139) replicate as well as parental virus in cultured cells (D. R. Shaffer, E. A. Bro,vn, and S. M. Lemon, J. Virol. 68:5568-5578, 1994). To determine whether viruses with such large deletion mutations are able to replicate and to produce acute hepatitis in primates, we reconstructed the Delta 96-137 deletion in the genetic background of a virulent virus which differs from the wild type by only one mutation in the 2B-coding region (HM175/8Y). Full-length synthetic Delta 96-137/8Y RNA was injected into the livers of two HAV-seronegative marmosets (Saguinus mystax). Both animals developed serum liver enzyme elevations and inflammatory changes in serial liver biopsies within 3 to 4 weeks of inoculation which were comparable in magnitude to those observed previously following intrahepatic inoculation of marmosets with HM175/8Y RNA. Sequencing of RNA from virus shed in feces demonstrated the presence of the Delta 96-137 deletion. These results indicate that the pY1 sequence of HAV is not required for efficient viral replication in hepatocytes in situ or for production of acute hepatic injury following intrahepatic RNA transfection in primates. C1 UNIV N CAROLINA,DEPT MICROBIOL & IMMUNOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. NIAID,INFECT DIS LAB,BETHESDA,MD 20205. UNIV SO CALIF,RANCHO LOS AMIGOS MED CTR,DOWNEY,CA 90242. FU NIAID NIH HHS [R01-AI32599, N01-AI-05069, T32-AI07151] NR 23 TC 16 Z9 17 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 OCT PY 1995 VL 69 IS 10 BP 6600 EP 6604 PG 5 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400081 PM 7666566 ER PT J AU NIELSEN, S AGRE, P AF NIELSEN, S AGRE, P TI THE AQUAPORIN FAMILY OF WATER CHANNELS IN KIDNEY SO KIDNEY INTERNATIONAL LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; INTEGRAL MEMBRANE-PROTEIN; MAJOR INTRINSIC PROTEIN; CELL CHIP28 PROTEIN; RAT-KIDNEY; COLLECTING DUCT; MESSENGER-RNA; VASOPRESSIN; EXPRESSION; PERMEABILITY AB The longstanding puzzle of membrane water permeability was advanced by the discovery of channel-forming integral protein (CHIP). This protein was shown to function as a water channel when expressed in Xenopus oocytes or when reconstituted into synthetic membranes. Site-directed mutagenesis and electron crystallography reveal tetrameric organization of CHIP, and the two halves of CHIP are tandem repeats folded into an obversely symmetric structure which resembles an hourglass. Each tetramer is comprised of functionally independent subunits. CHIP is the archetypal member of a newly-recognized family of membrane water transporters known as the ''Aquaporins'' (AQPs). AQP1 (CHIP) is abundant in the apical and basolateral membranes of renal proximal tubules and descending thin limbs, and is also present in a number of extra renal tissues. In the collecting duct, AQP2 is the predominant vasopressin-sensitive water channel. AQP2 is loclized in the apical membrane and in intracellular vesicles which are targeted to the apical plasma membranes when stimulated by antidiuretic hormone. Humans are identified with mutations in AQP1 and AQP2 and exhibit contrasting clinical phenotypes. AQP3 resides in the basolateral membranes of collecting duct principal cells providing an exit pathway for water, and AQP4 is abundant in brain, where it apparently functions as the hypothalamic osmoreceptor responsible for secretion of antidiuretic hormone. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiological problems of water balance and water balance disorders. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME. RP NIELSEN, S (reprint author), AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. NR 83 TC 159 Z9 164 U1 2 U2 9 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1995 VL 48 IS 4 BP 1057 EP 1068 DI 10.1038/ki.1995.389 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA RV926 UT WOS:A1995RV92600019 PM 8569067 ER PT J AU PIMENTEL, JL SUNDELL, CL WANG, SS KOPP, JB MONTERO, A MARTINEZMALDONADO, M AF PIMENTEL, JL SUNDELL, CL WANG, SS KOPP, JB MONTERO, A MARTINEZMALDONADO, M TI ROLE OF ANGIOTENSIN-II IN THE EXPRESSION AND REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA IN OBSTRUCTIVE NEPHROPATHY SO KIDNEY INTERNATIONAL LA English DT Article ID URETERAL OBSTRUCTION; EXTRACELLULAR-MATRIX; MESSENGER-RNA; KIDNEY; CELLS; FACTOR-BETA-1; INHIBITOR; FIBROBLASTS; TGF-BETA-1; FIBROSIS AB Unilateral ureteral obstruction (UUO) leads to fibrosis of the obstructed kidney. We tested the hypothesis that interstitial fibrosis in UUO results, at least in part, from enhanced expression of transforming growth factor-beta (TGF-beta) which in turn is regulated by local angiotensin II (Ang II) generation. (The generic name TGF-beta is used to discuss properties shared by all isoforms, but special reference to other isoforms is made when specifically needed.) Using Northern blot and immunohistochemical analysis, we examined the expression of TGF-beta in rat kidneys after 24 hours (aUUO) and one week (cUUO) of obstruction. Obstructed kidneys from both periods had increased interstitial and perivascular TGF-beta immunoreactivity compared to contralateral and sham kidneys, in which immunostaining was confined to the inner medulla. Relative abundance of all TGF-beta mRNA isoforms were higher in the obstructed than in contralateral and sham kidneys in both aUUO and cUUO. Expression of TGF-beta isoforms varied according to site (cortex vs. medulla), segment of the nephron, type of cells and duration of the obstruction. The increase in TGF-beta immunoreactivity and mRNA levels in aUUO and cUUO was almost totally abolished by pretreatment with losartan. We conclude that in UUO: (a) TGF-beta gene expression is increased and differentially regulated; (b) Ang II, at least partially, mediates the overexpression of TGF-beta gene; and (c) Ang II may play a central role in fibrogenesis in this and other models of tubulointerstitial disease. C1 VET ADM MED CTR,MED SERV 111,DECATUR,GA 30033. EMORY UNIV,SCH MED,DEPT MED,DIV RENAL,ATLANTA,GA. EMORY UNIV,SCH MED,DEPT MED,DIV GERIATR,ATLANTA,GA. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [R01-DK 30201] NR 39 TC 112 Z9 115 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1995 VL 48 IS 4 BP 1233 EP 1246 DI 10.1038/ki.1995.407 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA RV926 UT WOS:A1995RV92600037 PM 8569085 ER PT J AU LOCKLEAR, J MAHLER, J THIGPEN, JE GOELZ, MF FORSYTHE, D AF LOCKLEAR, J MAHLER, J THIGPEN, JE GOELZ, MF FORSYTHE, D TI SPONTANEOUS VULVAR CARCINOMAS IN 129/J MICE SO LABORATORY ANIMAL SCIENCE LA English DT Note ID SQUAMOUS-CELL CARCINOMA C1 NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. RP LOCKLEAR, J (reprint author), NIEHS,COMPARAT MED BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1995 VL 45 IS 5 BP 604 EP 606 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA TB765 UT WOS:A1995TB76500027 PM 8569168 ER PT J AU GUHA, A DIBRINO, M SHIELDS, MJ COLIGAN, JE AF GUHA, A DIBRINO, M SHIELDS, MJ COLIGAN, JE TI LEUKEMIA-CELL DERIVED FACTOR (LDF) INDUCES HEMATOPOIESIS SO LEUKEMIA LA English DT Article; Proceedings Paper CT Symposium on Gene Therapy - New Frontiers CY SEP 18-21, 1995 CL TRINITY COLL, DUBLIN, IRELAND SP Int Assoc Comparat Res Leukemia & Related Dis, Leukemia Soc Amer, US NCI, Irish Assoc Canc Res, Stohlman Fdn HO TRINITY COLL ID BURST-PROMOTING ACTIVITY; EXPRESSION AB A leukemic cell line, A(1), derived from a child with acute lymphoblastic leukemia was observed to have early B-cell irradiated A(1) cells were cultured with marrow cells in presence of recombinant erythropoietin (rhEPO), it stimulated burst forming unit erythroid (BFU-E). In order to determine if other leukemia cells or cell lines also induce similar stimulation, we used different leukemic cell lines and fresh B-cells from patients with chronic lymphocytic leukemia in bone marrow bioassay. Our results suggest that not all leukemic cells induce BFU-Es. To further identify the leukemia cell derived factor (LDF), A(1) cells were lysed and differentially centrifuged to separate plasma membrane protein from cytosolic and nuclear proteins. Only membrane associated protein were shown to induce BFU-E. However, when spent medium was collected and used In the bioassay, it also stimulated BFU-E, suggesting LDFs may be shed from plasma membrane. To further identify LDF, A(1) plasma membrane associated proteins were separated by ion-exchange FPLC. Protein fractions were collected and were used in the bioassay to identify the fraction that induced BFU-Es. C1 NIH,MOLEC STRUCT LAB,BETHESDA,MD 20892. RP GUHA, A (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT MED,263 FARMINGTON AVE,ROOM L3092,FARMINGTON,CT 06030, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1995 VL 9 SU 1 BP S102 EP S105 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA TE568 UT WOS:A1995TE56800024 PM 7475299 ER PT J AU RAMSEY, WJ MULLEN, CA BLAESE, RM AF RAMSEY, WJ MULLEN, CA BLAESE, RM TI RETROVIRUS-MEDIATED GENE-TRANSFER AS THERAPY FOR ADENOSINE-DEAMINASE (ADA) DEFICIENCY SO LEUKEMIA LA English DT Article; Proceedings Paper CT Symposium on Gene Therapy - New Frontiers CY SEP 18-21, 1995 CL TRINITY COLL, DUBLIN, IRELAND SP Int Assoc Comparat Res Leukemia & Related Dis, Leukemia Soc Amer, US NCI, Irish Assoc Canc Res, Stohlman Fdn HO TRINITY COLL AB ADA deficiency manifests as a severe combined immunodeficiency with profound T-lymphocytopenia. Affected individuals have variable defects of both T- and B-lymphocyte function and greatly increased morbidity and mortality caused by frequent viral and bacterial infection. In 1990 a clinical protocol for the treatment of this disease using retrovirus mediated transfer of the ADA gene into peripheral lymphocytes was begun and in 1993 an amendment permitting gene transfer to CD34+ stem cells isolated from peripheral blood or from umbilical cord blood was approved. Five patients have been treated on this protocol and have been analyzed for the persistence of cells containing the transferred gene and for immunologic reconstitution. RP RAMSEY, WJ (reprint author), NCHGR,CLIN GENE THERAPY BRANCH,BETHESDA,MD, USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1995 VL 9 SU 1 BP S70 EP S70 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA TE568 UT WOS:A1995TE56800016 PM 7475319 ER PT J AU SPENCE, SE KELLER, JR RUSCETTI, FW CZARRA, KT GOOYA, JM FUNAKOSHI, S LONGO, DL MURPHY, WJ AF SPENCE, SE KELLER, JR RUSCETTI, FW CZARRA, KT GOOYA, JM FUNAKOSHI, S LONGO, DL MURPHY, WJ TI ENGRAFTMENT OF SCID MICE BY HUMAN BONE-MARROW HEMATOPOIETIC-CELLS CULTURED IN-VITRO - AN IN-VIVO MODEL FUR HUMAN GENE-TRANSFER SO LEUKEMIA LA English DT Article; Proceedings Paper CT Symposium on Gene Therapy - New Frontiers CY SEP 18-21, 1995 CL TRINITY COLL, DUBLIN, IRELAND SP Int Assoc Comparat Res Leukemia & Related Dis, Leukemia Soc Amer, US NCI, Irish Assoc Canc Res, Stohlman Fdn HO TRINITY COLL ID SEVERE COMBINED IMMUNODEFICIENCY; IMMUNE-DEFICIENT MICE; MOUSE; TRANSPLANTATION; DNA AB Demonstration of the ability of fresh human hematopoietic cells to engraft severe combined immuno-deficient (scid) mice (1) has provided an in vivo assay for expansion and maturation of early human progenitor cells (2,3). However, engraftment of cultured hematopoietic cells has been difficult to achieve. We wished to further develop this model as an in vivo assay for efficiency of retroviral gene transfer and expression in the differentiated progeny of adult human bone marrow progenitor cells. Human bone marrow cells were cultured in vitro for six days under conditions suitable for infection by retroviral vectors prior to transfer to irradiated acid mice. Cultured human bone marrow cells introduced by both intravenous (i.v.) and intraperitoneal (i.p.) injection persisted in the bone marrow, spleen and peritoneum of recipient animals up to four weeks after transfer. Following irradiation scid mice receiving cultured human bone marrow cells by either i.v. or i.p. routes demonstrated engraftment of the bone marrow and spleen as determined by the growth of human hematopoietic progenitors in soft agar. By flow cytometric analysis human cells were also detected in the peritoneum ct mice receiving cultured human bone marrow cells i.p. These results suggest that the transfer of cultured human bone marrow cells to scid mice with the subsequent engraftment of these cells in the bone marrow, spleen and peritoneum of recipients can routinely occur. This provides an in vivo model for retroviral gene transfer to human cells. RP SPENCE, SE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1995 VL 9 SU 1 BP S43 EP S47 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA TE568 UT WOS:A1995TE56800010 PM 7475312 ER PT J AU YANG, SS FLIAKASBOLTZ, V BADER, JP BUCKHEIT, RW AF YANG, SS FLIAKASBOLTZ, V BADER, JP BUCKHEIT, RW TI CHARACTERISTICS OF A GROUP OF NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITORS WITH STRUCTURAL DIVERSITY AND POTENT ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY SO LEUKEMIA LA English DT Article; Proceedings Paper CT Symposium on Gene Therapy - New Frontiers CY SEP 18-21, 1995 CL TRINITY COLL, DUBLIN, IRELAND SP Int Assoc Comparat Res Leukemia & Related Dis, Leukemia Soc Amer, US NCI, Irish Assoc Canc Res, Stohlman Fdn HO TRINITY COLL ID ANTIVIRAL ACTIVITY; SOLUBLE-FORMAZAN; NATURAL-PRODUCTS; ZIDOVUDINE AZT; TYPE-1; HIV-1; DERIVATIVES; RESISTANCE; 2',3'-DIDEOXYINOSINE; INFECTIVITY AB Current thrust in controlling the Acquired immune Deficiency Syndrome (AIDS) focuses on antiviral drug development targeting the infection and replication of the human immunodeficiency virus (HIV), the causative agent of AIDS. To date, treatment of AIDS has relied on nucleoside reverse transcriptase inhibitors such as AZT, ddl, and ddC, which eventually become ineffective upon the emergence of resistant mutants bearing specific nucleotide substitutions. The Anti-AIDS Drug Screening program of the NCI conducts and coordinates a high-capacity semi-robotic in vitro screening of synthetic or natural compounds submitted by academic, research and pharmaceutical institutions world-wide. About 10000 synthetic compounds are screened annually for anti-HIV activity. Confirmed active agents are subjected to in-depth studies on range and mechanism of action. Emerging from this intense screening activity were a number of potentially promising categories of nonnucleoside reverse transcriptase inhibitors (NNRTI) with structural diversity but strong and reproducible anti-HIV activity. Over 2500 active compounds were evaluated for their Inhibitory activity against a panel or both laboratory and clinical virus isolates in the appropriate established cell line or fresh human peripheral blood leukocyte and macrophage preparations. Out of these, 40 agents could be placed structurally in nine categories with an additional 16 unique compounds that share the characteristics of NNRTI, These NNRTIs were shown to inhibit reverse transcriptase enzymatically using homopolymeric or ribosomal RNA as templates. NNRTIs demonstrated similarity in their inhibitory pattern against the HIV-1 laboratory strains III, and RF, and an AZT-resistant strain; all were inactive against HIV-2. These compounds were further tested against NNRTI-resistant HIV-1 isolates. NNRTI-resistant HIV-1 isolates were selected and characterized with respect to the change(s) in the viral reverse transcriptase nucleotide sequence. Also, differential cross-resistance or sensitivity patterns to NNRTIs were studied in detail among NNRTI-resistant mutants. When tested in combination with AZT, all of the NNRTI's uniformly exhibited synergistic inhibition of HIV-1, suggesting that combination antiviral therapy of NNRTIs with AZT may be therapeutically promising for AIDS treatment. C1 FREDERICK RES CTR,SO RES INST,DIV VIROL RES,FREDERICK,MD 21701. RP YANG, SS (reprint author), NCI,DEV THERAPEUT PROGRAM,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CM-37818] NR 34 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1995 VL 9 SU 1 BP S75 EP S85 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA TE568 UT WOS:A1995TE56800018 PM 7475321 ER PT J AU YANG, SS AF YANG, SS TI THE NCIS AIDS ANTIVIRAL DRUG SCREENING-PROGRAM SO LEUKEMIA LA English DT Article; Proceedings Paper CT Symposium on Gene Therapy - New Frontiers CY SEP 18-21, 1995 CL TRINITY COLL, DUBLIN, IRELAND SP Int Assoc Comparat Res Leukemia & Related Dis, Leukemia Soc Amer, US NCI, Irish Assoc Canc Res, Stohlman Fdn HO TRINITY COLL ID HIV-1; INHIBITORS AB The Developmental Therapeutics Program (DTP) in the National Cancer Institute has an unique mission by serving as a resource for all academic and private research institutions, the National Institutes of Health in the USA, and the global scientific community In the quest for effective therepeutic agents for treating patients with Acquired Immune Deficiency Syndrome (AIDS) as well as for cancer patients. This communication wilt concentrate on the developmental therapeutic program on anti-AIDS drug discovery. RP YANG, SS (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1995 VL 9 SU 1 BP S9 EP S11 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA TE568 UT WOS:A1995TE56800003 PM 7475324 ER PT J AU SHAVLIK, J HUNTER, L SEARLS, D AF SHAVLIK, J HUNTER, L SEARLS, D TI SPECIAL ISSUE ON APPLICATIONS IN MOLECULAR-BIOLOGY - INTRODUCTION SO MACHINE LEARNING LA English DT Editorial Material ID PROTEIN C1 NATL LIB MED,BETHESDA,MD 20894. UNIV PENN,SCH MED,DEPT HUMAN GENET,PHILADELPHIA,PA 19104. RP SHAVLIK, J (reprint author), UNIV WISCONSIN,DEPT COMP SCI,MADISON,WI 53706, USA. NR 7 TC 3 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0885-6125 J9 MACH LEARN JI Mach. Learn. PD OCT-NOV PY 1995 VL 21 IS 1-2 BP 5 EP 9 DI 10.1007/BF00993376 PG 5 WC Computer Science, Artificial Intelligence SC Computer Science GA TG739 UT WOS:A1995TG73900001 ER PT J AU IBARAKI, K KOZAK, CA WEWER, UM ALBRECHTSEN, R YOUNG, MF AF IBARAKI, K KOZAK, CA WEWER, UM ALBRECHTSEN, R YOUNG, MF TI MOUSE TETRANECTIN - CDNA SEQUENCE, TISSUE-SPECIFIC EXPRESSION, AND CHROMOSOMAL MAPPING SO MAMMALIAN GENOME LA English DT Article ID PLASMA-TETRANECTIN; GENE; IMMUNOREACTIVITY; BINDING; PROTEIN; MATRIX; CANCER; LEVEL AB Tetranectin is a plasminogen-binding tetrameric protein originally isolated from plasma. Expression of tetranectin appears ubiquitous, although particularly high expression is noted in the stroma of malignant tumors and during mineralization. To dissect the molecular basis of tetranectin gene regulation, mouse tetranectin cDNA was cloned from a 16-day-old mouse embryo library. Sequence analysis revealed a 992-bp cDNA with an open reading frame of 606 bp, which is identical in length to the human tetranectin cDNA. The deduced amino acid sequence showed high homology to the human cDNA with 76% identity and 87% similarity at the amino acid level. Sequence comparisons between mouse and human tetranectin and some C-type lectins confirmed a complete conservation in the position of six cysteines as well as numerous other amino acid residues, indicating an essential structure for potential function(s) of tetranectin. The sequence analysis revealed a difference in both sequence and size of the noncoding regions between mouse and human cDNAs. Northern analysis of the various tissues from mouse, rat, and cow showed the major transcript(s) to be approximately 1 kb, which is similar in size to that observed in human. Although additional minor bands of 1.5 and 3.3 kb were found in Northern blots, RT-PCR (reverse transcription polymerase chain reaction) analysis failed to provide evidence that these minor bands are products of the tetranectin gene. Finally, the genetic map location for this gene, Tna, was determined to be on distal mouse Chromosome (Chr) 9 by analysis of two sets of multilocus crosses. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. UNIV COPENHAGEN,INST PATHOL ANAT,MOLEC PATHOL LAB,COPENHAGEN,DENMARK. RP IBARAKI, K (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 13 Z9 14 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 OCT PY 1995 VL 6 IS 10 BP 693 EP 696 DI 10.1007/BF00354289 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RZ882 UT WOS:A1995RZ88200001 PM 8563165 ER PT J AU DUNCAN, MK LIEMAN, J CHADA, KK AF DUNCAN, MK LIEMAN, J CHADA, KK TI THE GERM-CELL DEFICIENT LOCUS MAPS TO MOUSE CHROMOSOME 11A2-3 SO MAMMALIAN GENOME LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; CONGENITAL TESTICULAR TERATOMAS; SI-LOCUS; W-LOCUS; MICE; RECEPTOR; LINKAGE; LIGAND; GENE; GCD AB The autosomal recessive mouse mutation, germ cell deficient, gcd, manifests as infertility in both sexes owing to improper migration and/or proliferation of primordial germ cells during embryonic development. Mice harboring this mutation have been hypothesized to be animal models of the human syndromes, premature ovarian failure and Sertoli cell only syndrome. Since the gcd mutation arose from the insertion of over 100 kb of foreign DNA into the chromosome during a transgenic mouse experiment, fluorescent in situ hybridization with the transgene as a probe was used to determine the chromosomal position of the gcd locus. DAPI chromosomal banding in conjunction with double labeling with the alpha 1(I) collagen gene revealed that the gcd locus is situated on mouse Chromosome (Chr) 11A2-3. Two candidate genes, Lif and Oncostatin M, map near the gcd locus; however, Southern blot hybridization analysis revealed no gross rearrangements in these genes in gcd mice. The chromosomal position of the gcd locus will prove valuable in the search for other candidate genes as well as a landmark for positional cloning experiments. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT BIOCHEM,PISCATAWAY,NJ 08854. NR 22 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1995 VL 6 IS 10 BP 697 EP 699 DI 10.1007/BF00354290 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RZ882 UT WOS:A1995RZ88200002 PM 8563166 ER PT J AU GODDARD, AD YUAN, JQ FAIRBAIRN, L DEXTER, M BORROW, J KOZAK, C SOLOMON, E AF GODDARD, AD YUAN, JQ FAIRBAIRN, L DEXTER, M BORROW, J KOZAK, C SOLOMON, E TI CLONING OF THE MURINE HOMOLOG OF THE LEUKEMIA-ASSOCIATED PML GENE SO MAMMALIAN GENOME LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; POLYMERASE CHAIN-REACTION; RAR-ALPHA; PROTEIN SEQUENCES; LOCALIZATION; EXPRESSION; RECEPTOR; T(15-17); CDNA; TRANSLOCATION AB PML, a Ring-finger protein, participates in the disruption of normal myeloid differentiation when fused to the retinoic acid receptor alpha (RAR alpha) by the translocation between Chromosomes (Chrs) 15 and 17 in acute promyelocytic leukemia (APL). As an initial step in the characterization of PML in species other than human, a murine cDNA clone of the PML gene was isolated and sequenced, and the intron/exon organization of the murine locus determined. The predicted amino acid sequence of the mouse PML protein shows 80% similarity to that of its human homolog. However, the mouse and human proteins show greater than 90% similarity in the proposed functional domains of the proteins. Despite its role in the etiology of APL, PML expression is not detectably altered during granulocytic differentiation in a murine in vitro system. Chromosomal localization of the Pml locus by somatic cell hybrids and by linkage analysis indicates that the gene maps to a region of mouse Chr 9 with known linkage homology to the region on human Chr 15q to which PML has been localized. C1 PATERSON INST CANC RES,CHRISTIE CRC RES CTR,MANCHESTER M20 9BX,LANCS,ENGLAND. NIAID,MOLEC MICROBIOL LAB,VIRAL BIOL SECT,BETHESDA,MD 20892. RP GODDARD, AD (reprint author), IMPERIAL CANC RES FUND,SOMAT CELL GENET LAB,44 LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. NR 30 TC 20 Z9 21 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 1995 VL 6 IS 10 BP 732 EP 737 DI 10.1007/BF00354296 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RZ882 UT WOS:A1995RZ88200008 PM 8563172 ER PT J AU BIJWAARD, K HEARING, VJ SONTHEIMER, R LIEU, TS VIEIRA, WD GERSTEN, DM AF BIJWAARD, K HEARING, VJ SONTHEIMER, R LIEU, TS VIEIRA, WD GERSTEN, DM TI STUDIES ON THE EXPRESSION AND IMMUNOGENICITY OF THE B50 MELANOMA ANTIGEN AND ITS RELATIONSHIP WITH CALRETICULIN SO MELANOMA RESEARCH LA English DT Article DE ANTIGEN; B50; MELANOMA; RO/SS-A COMPLEX AB B50 is a 50 kDa protein antigen originally identified and isolated from cultured B16 murine melanoma cells; it is found in close association with a melanoma-specific antigen termed B700, Using a specific rabbit antiserum, B50 (or B50 cross-reactive molecules) has been shown to be expressed by 35 out of 35 cell lines, including melanomas, sarcomas, fibrosarcomas, carcinomas, gliomas, immortalized and primary fibroblasts, melanocyte and keratinocyte cell lines obtained from murine, human, hamster, swine, and canine donors, B50 expression is localized on the cellular membrane and in the cytoplasm in varying amounts in seven of the nine cell lines tested, Mice immunized to B50 demonstrated a significant tumour rejection response when subsequently challenged with B16 F10 melanoma cells. Previous studies had indicated that B50 has significant N-terminal amino acid sequence homology with calreticulin, Calreticulin, a calcium-binding protein, is part of the Ro/SS-A complex. This complex is the primary autoantigenic determinant of the autoimmune diseases systemic lupus erythematosus and primary Sjogren's syndrome, We now show that sera from patients with those diseases contain antibodies which bind B50, although B50 itself does not bind calcium, Thus, B50 and calreticulin are closely related but distinct antigens. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD OCT PY 1995 VL 5 IS 5 BP 327 EP 336 DI 10.1097/00008390-199510000-00005 PG 10 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA RX383 UT WOS:A1995RX38300005 PM 8541723 ER PT J AU FLYVBJERG, A LANDAU, D DOMENE, H HERNANDEZ, L GRONBAEK, H LEROITH, D AF FLYVBJERG, A LANDAU, D DOMENE, H HERNANDEZ, L GRONBAEK, H LEROITH, D TI THE ROLE OF GROWTH-HORMONE, INSULIN-LIKE GROWTH-FACTORS (IGFS), AND IGF-BINDING PROTEINS IN EXPERIMENTAL DIABETIC KIDNEY-DISEASE SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT International Symposium on Glucose Metabolism and Growth Factors CY JAN 20-22, 1995 CL MAINZ, GERMANY ID RECEPTOR GENE-EXPRESSION; INITIAL RENAL HYPERTROPHY; I MESSENGER-RNA; RAT-KIDNEY; COMPENSATORY HYPERTROPHY; ALBUMIN EXCRETION; PROXIMAL TUBULES; SOMATOMEDIN-C; FACTOR SYSTEM; ADULT-RAT AB Early renal changes in type I diabetes are characterized by an increase in renal size, glomerular volume, and kidney function, and later by development of mesangial proliferation, accumulation of glomerular extracellular matrix, and increased urinary albumin excretion (UAE). Growth hormone (GH) and insulin like growth factors (IGFs) have a long and distinguished history in diabetes mellitus, with possible participation in the development of long-term complications. In experimental diabetes in dwarf rats with isolated GH and IGF-I deficiency, a slower and lesser renal and glomerular hypertrophy is observed as compared with diabetic control animals with intact pituitary. Furthermore, diabetic dwarf rats with a diabetes duration of 6 months display a smaller increase in UAE, indicating that GH and IGF-I may be involved in the development of diabetic kidney changes. In line with this, administration Of octreotide to streptozotocin (STZ)-diabetic animals with normal pituitary inhibits initial renal growth without affecting blood glucose levels, and 6 months' administration of octreotide to diabetic rats reduces long-term renal/glomerular hypertrophy and UAE. In addition, the initial increase in renal size and function in experimental diabetes is preceded by an increase in renal IGF-I, IGF-binding proteins (IGFBPs), and IGF-II/mannose-6-phosphate receptor (IGF-II/Man-6-P receptor) concentration. Finally, specific changes occur in renal GH-binding protein (GHBP) mRNA, IGF-I receptor mRNA, and IGFBP mRNA expression in long term diabetes. In conclusion, the knowledge we have today indicates that GH and IGFs, through a complex system consisting of GHBP, IGFs, IGF receptors, and IGFBPs, may be responsible for both early and late renal changes in experimental diabetes. Copyright (C) 1995 by W.B. Saunders Company. C1 DEPT PEDIAT & NEPHROL,BEER SHEVA,ISRAEL. NIDDK,DIABET BRANCH,BETHESDA,MD. RP FLYVBJERG, A (reprint author), AARHUS KOMMUNE HOSP,INST EXPTL CLIN RES,DK-8000 AARHUS C,DENMARK. OI Gronbaek, Henning/0000-0001-8998-7910 NR 62 TC 34 Z9 36 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1995 VL 44 IS 10 SU 4 BP 67 EP 71 DI 10.1016/0026-0495(95)90223-6 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD187 UT WOS:A1995TD18700011 PM 7476314 ER PT J AU HENSON, DE AF HENSON, DE TI SAXON GENITIVE OF EPONYMS SO MODERN PATHOLOGY LA English DT Letter RP HENSON, DE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 1995 VL 8 IS 8 BP 888 EP 888 PG 1 WC Pathology SC Pathology GA TA395 UT WOS:A1995TA39500016 PM 8552581 ER PT J AU WHITESIDE, ST ERNST, MK LEBAIL, O LAURENTWINTER, C RICE, N ISRAEL, A AF WHITESIDE, ST ERNST, MK LEBAIL, O LAURENTWINTER, C RICE, N ISRAEL, A TI N-TERMINAL AND C-TERMINAL SEQUENCES CONTROL DEGRADATION OF MAD3/I-KAPPA-B-ALPHA IN RESPONSE TO INDUCERS OF NF-KAPPA-B ACTIVITY SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ALPHA; ACTIVATION; PHOSPHORYLATION; PROTEINS; PROTEOLYSIS; INHIBITOR; PRECURSOR; PATHWAY; MAD3 AB The proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide, In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-nor-leucinal inhibits this ligand-induced degradation and, in agreement nith previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation, Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein, We propose that treatment of 70Z/3 cells with either phorbol myristate acetate or lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and 36 and that these phosphorylations target the protein for rapid proteolytic degradation, possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to translocate to the nucleus and to activate gene expression. C1 INST PASTEUR,CNRS,URA 1149,UNITE BIOL MOLEC EXPRESS GENET,F-75724 PARIS 15,FRANCE. INST PASTEUR,ELECTROPHORES BIDIMENSION LAB,F-75724 PARIS 15,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000] NR 38 TC 207 Z9 209 U1 0 U2 2 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 OCT PY 1995 VL 15 IS 10 BP 5339 EP 5345 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200015 PM 7565683 ER PT J AU YOKOMORI, N KOBAYASHI, R MOORE, R SUEYOSHI, T NEGISHI, M AF YOKOMORI, N KOBAYASHI, R MOORE, R SUEYOSHI, T NEGISHI, M TI A DNA METHYLATION SITE IN THE MALE-SPECIFIC P450 (CYP 2D-9) PROMOTER AND BINDING OF THE HETEROMERIC TRANSCRIPTION FACTOR GABP SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SEXUAL-DIFFERENTIATION; STEROID-METABOLISM; CPG METHYLATION; GENE-EXPRESSION; ETS; ENHANCER; SUBUNITS; IDENTIFICATION; ACTIVATION; PROTEINS AB The Cyp 2d-9 gene encodes the male-specific steroid 16 alpha-hydroxylase in mouse liver and shares a conserved regulatory element ((-100)TTCCGGGC(-93)) with another male-specific Sip promoter, As shown with the Sip promoter (N. Yokomori, R. Moore, and M. Negishi, Proc. Natl. Acad. Sci. USA 92:1302-1306, 1995), the male-preferential demethylation also occurs at CpG/-97 in the Cyp 2d-9 promoter, The transcription factor which specifically binds to the demethylated element has been purified, The peptide sequences reveal that the factor consists of GABP alpha and GABP beta 1 with Ets and Notch motifs, respectively, Both DNase I footprinting and gel shift assays indicate that the bacterially expressed glutathione S-transferase-GABP fusion proteins hind to the regulatory element only when CpG/-97 is demethylated. Moreover, Cyp 2d-9 promoter is trans-activated hy coexpression of GABP proteins in HepG2 cells, Given the additional results that CpG/-50 of the female-specific steroid 15 alpha-hydroxylase (Cyp 2a-4) promoter is preferentially demethylated in the females, the sex-specific expressions of the P450 genes correlate very well with DNA demethylation, We also conclude that GABP is a methylation-sensitive transcription factor and is a potential transcription activator of the male-specific Cyp 2d-9 promoter. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. NR 38 TC 73 Z9 73 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 OCT PY 1995 VL 15 IS 10 BP 5355 EP 5362 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200017 PM 7565685 ER PT J AU QUON, MJ CHEN, H ING, BL LIU, ML ZARNOWSKI, MJ YONEZAWA, K KASUGA, M CUSHMAN, SW TAYLOR, SI AF QUON, MJ CHEN, H ING, BL LIU, ML ZARNOWSKI, MJ YONEZAWA, K KASUGA, M CUSHMAN, SW TAYLOR, SI TI ROLES OF 1-PHOSPHATIDYLINOSITOL 3-KINASE AND RAS IN REGULATING TRANSLOCATION OF GLUT4 IN TRANSFECTED RAT ADIPOSE-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; GLUCOSE-TRANSPORT ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; GENE-EXPRESSION; PLASMA-MEMBRANE; SH2 DOMAINS; IDENTIFICATION; ASSOCIATION; STIMULATION; REQUIRES AB Insulin stimulates glucose transport in insulin target tissues by recruiting glucose transporters (primarily GLUT4) from an intracellular compartment to the cell surface. Previous studies have demonstrated that insulin receptor tyrosine kinase activity and subsequent phosphorylation of insulin receptor substrate 1 (IRS-1) contribute to mediating the effect of insulin on glucose transport. We have now investigated the roles of 1-phosphatidylinositol 3-kinase (PI 3-kinase) and ras, two signaling proteins located downstream from tyrosine phosphorylation, Rat adipose cells were cotransfected with expression vectors that allowed transient expression of epitope-tagged GLUT4 and the other genes of interest. Overexpression of a mutant p85 regulatory subunit of PI 3-kinase lacking the ability to bind and activate the p110 catalytic subunit exerted a dominant negative effect to inhibit insulin-stimulated translocation of epitope-tagged GLUT4 to the cell surface. In addition, treatment of control cells with wortmannin (an inhibitor of PI 3-kinase) abolished the ability of insulin to recruit epitope-tagged GLUT4 to the cell surface. Thus, our data suggest that PI 3-kinase plays an essential role in insulin-stimulated GLUT4 recruitment in insulin target tissues. In contrast, overexpression of a constitutively active mutant of ras (L61-ras) resulted in high levels of cell surface GLUT4 in the absence of insulin that were comparable to levels seen in control cells treated with a maximally stimulating dose of insulin. However, wortmannin treatment of cells overexpressing LG1-ras resulted in only a small decrease in the amount of cell surface GLUT4 compared with that of the same cells in the absence of wortmannin. Therefore, while activated ras is sufficient to recruit GLUT4 to the cell surface, it does so by a different mechanism that is probably not involved in the mechanism by which insulin stimulates GLUT4 translocation in physiological target tissues. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. KOBE UNIV,SCH MED,DEPT INTERNAL MED 2,CHUO KU,KOBE 650,JAPAN. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 51 TC 136 Z9 136 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 OCT PY 1995 VL 15 IS 10 BP 5403 EP 5411 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200023 PM 7565691 ER PT J AU MOSKOW, JJ BULLRICH, F HUEBNER, K DAAR, IO BUCHBERG, AM AF MOSKOW, JJ BULLRICH, F HUEBNER, K DAAR, IO BUCHBERG, AM TI MEIS1, A PBX1-RELATED HOMEOBOX GENE INVOLVED IN MYELOID-LEUKEMIA IN BXH-2 MICE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN PROTOONCOGENE PBX1; MESSENGER-RNA; MOUSE HOMOLOG; WOBBLER WR; VIRUS DNA; MAP; EXPRESSION; LINKAGE; CHROMOSOME-11; ACTIVATION AB Leukemia results from the accumulation of multiple genetic alterations that disrupt the control mechanisms of normal growth and differentiation, The use of inbred mouse strains that develop leukemia has greatly facilitated the identification of genes that contribute to the neoplastic transformation of hematopoietic cells, BXH-2 mice develop myeloid leukemia as a result of the expression of an ecotropic murine leukemia virus that acts as an insertional mutagen to alter the expression of cellular proto-oncogenes. We report the isolation of a new locus, Meis1, that serves as a site of viral integration in 15% of the tumors arising in BXH-2 mice, Meis1 was mapped to a distinct location on proximal mouse chromosome 11, suggesting that it represents a novel locus, Analysis of somatic cell hybrids segregating human chromosomes allowed localization of MEIS1 to human chromosome 2p23-p12, in a region known to contain translocations found in human leukemias, Northern (RNA) blot analysis demonstrated that a Meis1 probe detected a 3,8-kb mRNA present in all BXH-2 tumors, whereas tumors containing integrations at the Meis1 locus expressed an additional truncated transcript, A Meis1 cDNA clone that encoded a novel member of the homeobox gene family was identified, The homeodomain of Meis1 is most closely related to those of the PBX/exd family of homeobox protein-encoding genes, suggesting that Meis1 functions in a similar fashion by cooperative binding to a distinct subset of HOX proteins, Collectively, these results indicate that altered expression of the homeobox gene Meis1 may be one of the events that lead to tumor formation in BXH-2 mice. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON CANC CTR,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. OI Daar, Ira/0000-0003-2657-526X; Buchberg, Arthur/0000-0002-0543-5631 FU NCI NIH HHS [CA51083, CA58586]; NHLBI NIH HHS [1 T32 HL07780-01] NR 59 TC 226 Z9 230 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1995 VL 15 IS 10 BP 5434 EP 5443 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200026 PM 7565694 ER PT J AU TRAN, HT DEGTYAREVA, NP KOLOTEVA, NN SUGINO, A MASUMOTO, H GORDENIN, DA RESNICK, MA AF TRAN, HT DEGTYAREVA, NP KOLOTEVA, NN SUGINO, A MASUMOTO, H GORDENIN, DA RESNICK, MA TI REPLICATION SLIPPAGE BETWEEN DISTANT SHORT REPEATS IN SACCHAROMYCES-CEREVISIAE DEPENDS ON THE DIRECTION OF REPLICATION AND THE RAD50 AND RAD52 GENES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BACTERIAL TRANSPOSON TN5; ESCHERICHIA-COLI; INVERTED REPEATS; MISMATCH REPAIR; COLORECTAL-CANCER; PRECISE EXCISION; DNA-REPLICATION; LAGGING-STRAND; MUTATIONS; YEAST AB Small direct repeats, which are frequent in all genomes, are a potential source of genome instability, To study the occurrence and genetic control of repeat-associated deletions, we developed a system in the yeast Saccharomyces cerevisiae that was based on small direct repeats separated by either random sequences or inverted repeats. Deletions were examined in the LYS2 gene, using a set of 31- to 156-bp inserts that included inserts with no apparent potential for secondary structure as well as two quasipalindromes. All inserts were flanked by 6- to 9-bp direct repeats of LYS2 sequence, providing an opportunity for Lys(+) reversion via precise excision. Reversions could arise by extended deletions involving either direct repeats or random sequences and by -1- or +2-bp frameshift mutations, The deletion breakpoints were always associated with short (3- to 9-bp) perfect or imperfect direct repeats, Compared with the POL(+) strain, deletions between small direct repeats were increased as much as 100-fold, and the spectrum was changed in a temperature-sensitive DNA polymerase delta pol3-t mutant, suggesting a role for replication. The type of deletion depended on orientation relative to the origin of replication, On the basis of these results, we propose (i) that extended deletions between small repeats arise by replication slippage and (ii) that the deletions occur primarily in either the leading or lagging strand. The RAD50 and RAD52 genes, which are required for the recombinational repair of many kinds of DNA double-strand breaks, appeared to be required also for the production of up to 90% of the deletions arising between separated repeats in the pol3-t mutant, suggesting a newly identified role for these genes in genome stability and possibly replication. C1 NIEHS,GENET MOLEC LAB,RES TRIANGLE PK,NC 27709. ST PETERSBURG STATE UNIV,DEPT GENET,ST PETERSBURG 199034,RUSSIA. OSAKA UNIV,MICROBIAL DIS RES INST,DEPT MOLEC IMMUNOL,SUITA,OSAKA 565,JAPAN. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 59 TC 100 Z9 101 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 OCT PY 1995 VL 15 IS 10 BP 5607 EP 5617 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200044 PM 7565712 ER PT J AU RIVEROLEZCANO, OM MARCILLA, A SAMESHIMA, JH ROBBINS, KC AF RIVEROLEZCANO, OM MARCILLA, A SAMESHIMA, JH ROBBINS, KC TI WISKOTT-ALDRICH SYNDROME PROTEIN PHYSICALLY ASSOCIATES WITH NCK THROUGH SRC HOMOLOGY-3 DOMAINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR; SIGNAL TRANSDUCTION; SH2 DOMAINS; KINASE; CELLS; GENE; TYROSINE; PHOSPHORYLATION; RECEPTORS; SUBSTRATE AB In the second of a series of experiments designed to identify p47(nck)-Src homology 3 (SH3)-binding molecules, we report the cloning of SAKAP II (Src A box Nck-associated protein II) from an HL60 cDNA expression library. This molecule has been identified as a cDNA encoding the protein product of WASP, which is mutated in Wiskott-Aldrich syndrome patients. Studies in vivo and in vitro demonstrated a highly specific interaction between the SH3 domains of p47(nck) and Wiskott-Aldrich syndrome protein. Furthermore, anti-Wiskott-Aldrich syndrome protein antibodies recognized a protein of 66 kDa by Western blot (immunoblot) analysis. In vitro translation studies identified the 66-kDa protein as the protein product of WASP, and subcellular fractionation experiments showed that p66(WASP) i, mainly present in the cytosol fraction, although significant amounts are also present in membrane and nuclear fractions. The main p47(nck) region implicated in the association with p66(WASP) was found to be the carboxy-terminal SH3 domain. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI marcilla, antonio/F-9996-2010; Rivero-Lezcano, Octavio/J-9089-2015 OI marcilla, antonio/0000-0003-0004-0531; Rivero-Lezcano, Octavio/0000-0002-8793-0731 NR 50 TC 267 Z9 268 U1 1 U2 7 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 OCT PY 1995 VL 15 IS 10 BP 5725 EP 5731 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200056 PM 7565724 ER PT J AU RUTHERFURD, KJ CHOU, JY MANSFIELD, BC AF RUTHERFURD, KJ CHOU, JY MANSFIELD, BC TI A MOTIF IN PSG11S MEDIATES BINDING TO A RECEPTOR ON THE SURFACE OF THE PROMONOCYTE CELL-LINE THP-1 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN; HUMAN PLACENTAL-LACTOGEN; ARG-GLY-ASP; IMMUNE-SYSTEM; MACROPHAGES; ADHESION; INVITRO; SERUM; GENE; CD23 AB The pregnancy-specific glycoproteins (PSG) form a large family of essential pregnancy proteins, but their biological function is unknown. We have investigated whether one function of the PSG is to interact with cells of the maternal immune system. Normal human peripheral blood mononuclear cells, activated with phorbol ester, are shown to bind to purified placental PSG. This binding activity can be mimicked using a chemically synthesized peptide ligand containing the Arg-Gly-Asp (RGD) motif present in the N-terminal domain of PSG11s. The PSG11s receptors are present on cells of the myeloid cell lineage but not of the T cell or B cell lineages. The binding is mediated in part by the RGD motif and can be competed against by appropriate RGD-containing, but not Arg-Ala-Asp (RAD)containing, ligands, Ligand binding requires a functional cytoskeleton. By examining the U937 and THP-1 promonocyte cell lines, the presence of receptors with two different binding characteristics are demonstrated, The THP-1 receptor is identified by chemical cross-linking as a protein of 46 kilodaltons (kDa), and affinity chromatography demonstrates the presence of three protein species of 32 kDa, 16.8 kDa, and 15.9 kDa, suggesting the receptor has multiple subunits. C1 GEORGETOWN UNIV, CHILDRENS MED CTR, DEPT PEDIAT, WASHINGTON, DC 20007 USA. MASSEY UNIV, DEPT MICROBIOL & GENET, PALMERSTON NORTH, NEW ZEALAND. NICHHD, HUMAN GENET BRANCH, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-31553-01A1] NR 55 TC 27 Z9 27 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1995 VL 9 IS 10 BP 1297 EP 1305 DI 10.1210/me.9.10.1297 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RY961 UT WOS:A1995RY96100004 PM 8544838 ER PT J AU YANG, H ADAMO, ML KOVAL, AP MCGUINNESS, MC BENHUR, H YANG, YZ LEROITH, D ROBERTS, CT AF YANG, H ADAMO, ML KOVAL, AP MCGUINNESS, MC BENHUR, H YANG, YZ LEROITH, D ROBERTS, CT TI ALTERNATIVE LEADER SEQUENCES IN INSULIN-LIKE GROWTH-FACTOR-I MESSENGER-RNAS MODULATE TRANSLATIONAL EFFICIENCY AND ENCODE MULTIPLE SIGNAL PEPTIDES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; 5' UNTRANSLATED REGION; START SITE USAGE; NON-AUG CODONS; IGF-I; EUKARYOTIC RIBOSOMES; GENE PROMOTER; TRANSCRIPTION INITIATION; DIFFERENTIAL REGULATION; SECONDARY STRUCTURE AB Rat insulin-like growth factor I (IGF-I) mRNAs contain multiple 5'-untranslated regions due to the use of leader exons transcribed from several transcription initiation sites and to alternative splicing within leader exon 1. Synthetic RNAs with 5'-ends corresponding to the use of exon 1 transcription initiation sites were translated in vitro into prepro-IGF-I peptides initiated at a Met-48 codon in exon 1 or a Met-22 codon in exon 3, and RNAs with a 5'-end corresponding to the major exon 2 transcription start site were translated into a prepro-IGF-l peptide initiated at a Met-32 codon in, exon 2. All forms of prepro-IGF-I were processed by canine pancreatic microsomes, suggesting that all these prepeptides function as signal peptides. The translational efficiency of IGF-I RNAs was inversely proportional to the length of the 5'-untranslated region. Mutation of the first of three upstream AUG codons in exon 1, which potentially initiates a 14-amino acid open reading frame, did not affect prepro-IGF-l translation. The other two AUG codons are immediately followed by stop codons. The absence of both upstream AUG codons in a completely spliced exon 1-derived RNA enhanced the in vitro and in vivo translatability of this RNA as compared with the full-length RNA. Mutation of the downstream initiation codon in particular increased translational efficiency in vitro and in intact cells, suggesting that an inefficient reinitiation event at the Met-48 codon contributes to the poorer translation of IGF-I mRNAs in which these upstream AUGUGA motifs occur. We conclude that IGF-I mRNAs potentially encode multiple forms of preprolGF and that specific differences in their 5'-untranslated regions provide a molecular basis for translational control of IGF-I biosynthesis. C1 NIDDKD, DIABET BRANCH, MOLEC & CELLULAR PHYSIOL SECT, BETHESDA, MD 20892 USA. UNIV TEXAS, HLTH SCI CTR, DEPT BIOCHEM, SAN ANTONIO, TX 78284 USA. FU NIDDK NIH HHS [DK-47357] NR 63 TC 48 Z9 48 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 OCT PY 1995 VL 9 IS 10 BP 1380 EP 1395 DI 10.1210/me.9.10.1380 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RY961 UT WOS:A1995RY96100012 PM 8544846 ER PT J AU Nye, SH Pelfrey, CM Burkwit, JJ Voskuhl, RR Lenardo, MJ Mueller, JP AF Nye, SH Pelfrey, CM Burkwit, JJ Voskuhl, RR Lenardo, MJ Mueller, JP TI Purification of immunologically active recombinant 21.5 kDa isoform of human myelin basic protein SO MOLECULAR IMMUNOLOGY LA English DT Article DE recombinant myelin basic protein; multiple sclerosis; purification; antigen processing; peripheral T cell tolerance ID T-CELL RECOGNITION; GLUTAMIC-ACID DECARBOXYLASE; POLYMERASE CHAIN-REACTION; CLASS-II RESTRICTION; MULTIPLE-SCLEROSIS; CODON USAGE; HEALTHY-INDIVIDUALS; FINE SPECIFICITY; EXPRESSION; GENES AB We have designed and expressed in bacteria a recombinant fetal form of human myelin basic protein (21.5 kDa isoform; rhMBP21.5), a candidate autoantigen in multiple sclerosis. An exon 2 insertion, carboxy-terminal histidine tag and preferred bacterial codons differentiate the MBP21.5 gene from that encoding the adult, brain-derived form of human MBP (18.5 kDa isoform; hMBP18.5). MBPs were expressed at high levels in E. coli and extracted from whole cells by simultaneous acid solubilization and mechanical disruption. A nearly two-fold increase in recombinant protein was detected in strains harboring MBP genes with bacterial preferred codons compared to genes containing human codons. The recombinant molecules were purified in two steps, first by reversed-phase chromatographic separation and then by metal affinity chromatography. Dimeric forms of recombinant MBP21.5 were detected under physiological conditions, however, substitution of a serine for the single cysteine at amino acid residue 81 resulted in only monomer formation. All forms of recombinant MBPs induced proliferative responses of human T lymphocytes specific for epitopes in MBP18.5 kDa. In contrast, human T cell lines that recognize an exon 2-encoded epitope of MBP responded to the 21.5 kDa isoform of MBP, but not the 18.5 kDa isoform. C1 ALEXION PHARMACEUT INC,NEW HAVEN,CT 06511. NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIH,IMMUNOL LAB,BETHESDA,MD 20892. OI Pelfrey, Clara/0000-0002-6108-7555 NR 42 TC 20 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 1995 VL 32 IS 14-15 BP 1131 EP 1141 DI 10.1016/0161-5890(95)00066-6 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA TL653 UT WOS:A1995TL65300013 PM 8544862 ER PT J AU FRIEDMAN, DI COURT, DL AF FRIEDMAN, DI COURT, DL TI TRANSCRIPTION ANTITERMINATION - THE LAMBDA-PARADIGM UPDATED SO MOLECULAR MICROBIOLOGY LA English DT Review ID N-GENE-PRODUCT; RIBOSOMAL-PROTEIN S10; HK022 NUN PROTEIN; ANTI-SIGMA FACTOR; ESCHERICHIA-COLI; PHAGE-LAMBDA; BACTERIOPHAGE-LAMBDA; RNA-POLYMERASE; TERMINATION FACTOR; HOST FACTOR AB Coliphage lambda employs systems of transcription termination and antitermination to regulate gene expression. Early gene expression is regulated by the phage-encoded N protein working with a series of Escherichia coli proteins, Nus, at RNA sites, NUT, to modify RNA polymerase to a termination-resistant form. Expression of lambda late genes is regulated by the phage-encoded Q antitermination protein. Q, which appears to use only one host factor, acts at a DNA site, out, to modify RNA polymerase to a termination-resistant form. This review focuses on recent studies which show that: (i) N can mediate antitermination in vitro, independent of Nus proteins. (ii) Early genes in another lambdoid phage HK022 are also regulated by antitermination, where only an RNA signal appears necessary and sufficient to create a termination-resistant RNA polymerase. (iii) A part of the out signal appears to be read from the non-template DNA strand. (iv) A host-encoded inhibitor of N antitermination appears to act through the NUT site as well as with the alpha subunit of RNA polymerase, and is antagonized by NusB protein. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, CHROMOSOME BIOL LAB, FREDERICK, MD 21702 USA. RP UNIV MICHIGAN, SCH MED, DEPT MICROBIOL & IMMUNOL, ANN ARBOR, MI 48109 USA. RI Friedman, David/G-3198-2015 OI Friedman, David/0000-0002-2741-4671 FU NIAID NIH HHS [AI1459-10] NR 80 TC 106 Z9 107 U1 2 U2 4 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1995 VL 18 IS 2 BP 191 EP 200 DI 10.1111/j.1365-2958.1995.mmi_18020191.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA TG433 UT WOS:A1995TG43300002 PM 8709839 ER PT J AU GUPTA, M ABDELMEGEED, M HOKI, Y KOHLHAGEN, G PAULL, K POMMIER, Y AF GUPTA, M ABDELMEGEED, M HOKI, Y KOHLHAGEN, G PAULL, K POMMIER, Y TI EUKARYOTIC DNA TOPOISOMERASES MEDIATED DNA CLEAVAGE INDUCED BY A NEW INHIBITOR - NSC-665517 SO MOLECULAR PHARMACOLOGY LA English DT Article ID CELL-LINES; STRAND CLEAVAGE; INDUCTION; INTERCALATORS; REQUIREMENTS; COMPLEX; DRUGS AB A compound with a novel structure, NSC 665517, was tested in the National Cancer Institute Preclinical Drug Discovery Screen. With the COMPARE algorithm, the pattern of differential cytotoxicity for NSC 665517 most closely resembled those of known topoisomerase II (top2) inhibitors. In vitro data showed that NSC 665517 induced DNA cleavage in the presence of top2 and topoisomerase I (top1) (at a higher concentration). The minimum concentration required to induce top2 cleavage was 0.5 mu M. A substantial decrease in top2-induced cleavage by NSC 665517 was seen when the reaction mixtures were shifted to elevated temperature (55 degrees), suggesting that top2-induced cleavage occurs through the mechanism of stabilizing the reversible enzyme/DNA complex and inhibiting religation. The DNA cleavage pattern induced by NSC 665517 with top2 was different than that of other known top:! inhibitors, including etoposide, mitoxantrone, anthracyclines, amsacrine, and ellipticine. top2 cleavage sites induced by NSC 665517 showed strong preference for G located 3' to the top2-mediated DNA cleavage (position +1). NSC 665517 produced limited DNA unwinding at high drug concentration. DNA damage analyzed in KB cells by alkaline elution showed that NSC 665517 induced strand break. Data from the cytotoxicity in KB-V1 over-expressing P-glycoprotein and COMPARE analysis with rhodamine efflux assay indicated that NSC 665517 is a substrate of P-glycoprotein. These results strongly suggest that NSC 665517 is a novel topoisomerase-targeted drug. Preclinical evaluation of NSC 665517 as an antitumor agent is under way. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. TANTA UNIV,FAC SCI,DEPT CHEM,TANTA,EGYPT. NR 43 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1995 VL 48 IS 4 BP 658 EP 665 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA567 UT WOS:A1995TA56700012 PM 7476891 ER PT J AU CHAVANY, C CONNELL, Y NECKERS, L AF CHAVANY, C CONNELL, Y NECKERS, L TI CONTRIBUTION OF SEQUENCE AND PHOSPHOROTHIOATE CONTENT TO INHIBITION OF CELL-GROWTH AND ADHESION CAUSED BY C-MYC ANTISENSE OLIGOMERS SO MOLECULAR PHARMACOLOGY LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; OLIGODEOXYNUCLEOTIDE; OLIGONUCLEOTIDES; PROLIFERATION; ONCOGENES; DIFFERENTIATION; PROTEIN; CD4 AB c-myc is overexpressed in glioblastoma multiforme, the most common form of brain tumor. To find a suitable target for in vivo antisense therapy of gliomas, we investigated the biological effects on the human glioma cell line, U87MG, of antisense oligonucleotides targeted against the translation start site of c-myc mRNA. Parameters examined included c-myc protein level, cell proliferation, and cell adhesion to substratum. Oligonucleotides were administered by electroporation as capped phosphorothioates. Antisense oligomers caused a reduction in c-myc protein expression, loss of cell adhesion to plastic, and complete growth inhibition. Various control sequences, including sense, scrambled, and three-base mismatched oligomers, were also tested. Some of the controls retained a dG quartet found in the antisense sequence. Reduction in c-myc protein and cell growth and loss of cell adhesion were specific to the antisense sequence. Surprisingly, fully thioated antisense and scrambled sequences, either containing or lacking a dG quartet, were equally inhibitory to both cell growth and adhesion. Loss of cell adhesion was observed with only phosphorothioate-containing oligomers, not with either their phosphodiester or nuclease-resistant PA congeners, and was completely reversed when cells were plated onto fibronectin. These results demonstrate that a commonly used c-myc antisense oligomer also displays dramatic, sequence- but not antisense-specific effects on cell proliferation and cellular adhesion, depending on the backbone. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 34 TC 52 Z9 58 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1995 VL 48 IS 4 BP 738 EP 746 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA567 UT WOS:A1995TA56700023 PM 7476902 ER PT J AU BOHR, VA ANSON, RM AF BOHR, VA ANSON, RM TI DNA-DAMAGE, MUTATION AND FINE-STRUCTURE DNA-REPAIR IN AGING SO MUTATION RESEARCH-DNAGING GENETIC INSTABILITY AND AGING LA English DT Article ID ALZHEIMERS-DISEASE FIBROBLASTS; HUMAN-DIPLOID FIBROBLASTS; HAMSTER OVARY CELLS; MITOCHONDRIAL-DNA; OXIDATIVE DAMAGE; XERODERMA-PIGMENTOSUM; ATAXIA TELANGIECTASIA; RINR-38 CELLS; LIFE-SPAN; DHFR GENE AB The primary focus of this review is on correlations found between DNA damage, repair, and aging. New techniques for the measurement of DNA damage and repair at the level of individual genes, in individual DNA strands and in individual nucleotides will allow us to gain information regarding the nature of these correlations. Fine structure studies of DNA damage and repair in specific regions, including active genes, telomeres, and mitochondria have begun. Considerable intragenomic DNA repair heterogeneity has been found, and there have been indications of relationships between aging and repair in specific regions. More studies are necessary, however, particularly studies of the repair of endogenous damage. It is emphasized that the information obtained must be viewed from a perspective that takes into account the total responses of the cell to damaging events and the inter-relationships that exist between DNA repair and transcription. RP BOHR, VA (reprint author), NIA,GENET MOLEC LAB,BALTIMORE,MD 21224, USA. NR 95 TC 124 Z9 124 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8734 J9 MUTAT RES-DNAGING G JI Mutat. Res. DNAging Genet. Instabil. Aging PD OCT PY 1995 VL 338 IS 1-6 BP 25 EP 34 DI 10.1016/0921-8734(95)00008-T PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RX779 UT WOS:A1995RX77900005 PM 7565878 ER PT J AU LOWE, X COLLINS, B ALLEN, J TITENKOHOLLAND, N BRENEMAN, J VANBEEK, M BISHOP, J WYROBEK, AJ AF LOWE, X COLLINS, B ALLEN, J TITENKOHOLLAND, N BRENEMAN, J VANBEEK, M BISHOP, J WYROBEK, AJ TI ANEUPLOIDIES AND MICRONUCLEI IN THE GERM-CELLS OF MALE-MICE OF ADVANCED AGE SO MUTATION RESEARCH-DNAGING GENETIC INSTABILITY AND AGING LA English DT Article DE AGED MOUSE; SPERM; FISH; ANEUPLOIDY; MICRONUCLEUS; KINETOCHORE ID IN-SITU HYBRIDIZATION; MATERNAL AGE; FEMALE MICE; CHROMOSOME; FREQUENCY; MOUSE; DNA; MEN; LYMPHOCYTES; SPERMATOZOA AB The objective of this research was to determine whether the frequencies of chromosomally defective germ cells increased with age in male laboratory mice. Two types of chromosomal abnormalities were characterized: (1) testicular spermatid aneuploidy (TSA) as measured by a new method of multi-color fluorescence in situ hybridization (FISH) with DNA probes specific for mouse chromosomes X, Y and 8, and (2) spermatid micronucleus (SMN) analyses using anti-kinetochore antibodies. B6C3F1 mice (aged 22.5 to 30.5 months, heavier than controls but otherwise in good health) showed significant similar to 2.0 fold increases in the aneuploidy phenotypes X-X-8, Y-Y-8, 8-8-X and 8-8-Y with the greatest effects appearing in animals aged greater than 28 months. No age effect was observed, however, in X-Y-8 hyperhaploidy. Major age-related increases were seen in Y-Y-8 and X-X-8 hyperhaploidies suggesting that advanced paternal age is associated primarily with meiosis II rather than meiosis I disjunction errors. A similar to 5 fold increase was also found in the frequency of micronucleated spermatids in aged mice when compared with young controls. All micronuclei detected in the aged animals lacked kinetochore labeling, suggesting that they either did not contain intact chromosomes or the chromosomes lacked detectable kinetochores. The findings of the TSA and SMN assays are consistent with meiotic or premeiotic effects of advanced age on germ cell chromosomes, but there were differences in the age dependencies of aneuploidy and micronuclei. In summary, advanced paternal age may be a risk factor for chromosomal abnormalities (both aneuploidy and structural abnormalities) in male germ cells. C1 LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94550. US EPA,RES TRIANGLE PK,NC 27711. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA. NIEHS,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [YO1-ES-10203-00] NR 60 TC 55 Z9 55 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8734 J9 MUTAT RES-DNAGING G JI Mutat. Res. DNAging Genet. Instabil. Aging PD OCT PY 1995 VL 338 IS 1-6 BP 59 EP 76 DI 10.1016/0921-8734(95)00012-U PG 18 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RX779 UT WOS:A1995RX77900009 PM 7565883 ER PT J AU JONES, IM THOMAS, CB TUCKER, B THOMPSON, CL PLESHANOV, P VOROBTSOVA, I MOORE, DH AF JONES, IM THOMAS, CB TUCKER, B THOMPSON, CL PLESHANOV, P VOROBTSOVA, I MOORE, DH TI IMPACT OF AGE AND ENVIRONMENT ON SOMATIC MUTATION AT THE HPRT GENE OF T-LYMPHOCYTES IN HUMANS SO MUTATION RESEARCH-DNAGING GENETIC INSTABILITY AND AGING LA English DT Article DE SOMATIC MUTATION; AGE; HPRT; HUMAN T-LYMPHOCYTE ID POLYMERASE CHAIN-REACTION; MUTANT FREQUENCY; MOLECULAR ANALYSES; CLONING ASSAY; HUMAN-CELLS; INVIVO; POPULATIONS; DELETIONS; QUANTIFY; SUBSETS AB Analysis of two human populations for dependence of somatic mutation on age has revealed both similarities and differences. The studies performed employed peripheral blood lymphocytes and measured the efficiency with which these cells form clones in vitro (cloning efficiency, CE) and the frequency of cells with inactivating mutations of the hypoxanthine phosphoribosyltransferase gene (mutant frequency, MF). The people studied were between 19 and 64 years of age. In one population, composed of 78 never smokers and 140 current smokers from the United States (US), both CE and MF were dependent on age: CE declined with age(p = 0.005); MF increased 0.15 per 10(6) cells per year of age for nonsmokers (p < 0.001) and at 1.3 times that rate for smokers (p = 0.01). In the second population, 80 people of unknown smoking status from Russia, the increase in MF per year was even greater, 2.5 times that of the US nonsmokers (p = 0.001) but the dependence of CE on age was the same as for the US population (p = 0.043). Because the increase of MF of the Russians with age is 2-fold greater than that of the US smokers, the intensity of smoking and/or other environmental exposures, or the susceptibility to these exposures, must account for the difference in age dependent MF increase, not the proportion of Russians that are smokers. Differences in the lymphocyte subpopulations that survived the longer transit from Russia may have contributed to the observed differences in MF. However, overall, the mutant frequency results suggest that the Russians were chronically exposed to higher levels of agents that induce somatic mutation and that, on an age adjusted basis, the Russia population studied is at increased risk for health consequences from accumulated genetic damage. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. MOSCOW BIOL ACT SUBST INST,MOSCOW,RUSSIA. CENT INST ROENTGENOL & RADIOBIOL,ST PETERSBURG,RUSSIA. CALIF PACIFIC MED CTR,SAN FRANCISCO,CA 94110. RP JONES, IM (reprint author), LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,L-452,POB 808,LIVERMORE,CA 94551, USA. FU NCI NIH HHS [CA 59431]; NIEHS NIH HHS [Y01-ES-80171] NR 43 TC 66 Z9 67 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8734 J9 MUTAT RES-DNAGING G JI Mutat. Res. DNAging Genet. Instabil. Aging PD OCT PY 1995 VL 338 IS 1-6 BP 129 EP 139 DI 10.1016/0921-8734(95)00018-2 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RX779 UT WOS:A1995RX77900015 PM 7565868 ER PT J AU SANGO, K YAMANAKA, S HOFFMANN, A OKUDA, Y GRINBERG, A WESTPHAL, H MCDONALD, MP CRAWLEY, JN SANDHOFF, K SUZUKI, K PROIA, RL AF SANGO, K YAMANAKA, S HOFFMANN, A OKUDA, Y GRINBERG, A WESTPHAL, H MCDONALD, MP CRAWLEY, JN SANDHOFF, K SUZUKI, K PROIA, RL TI MOUSE MODELS OF TAY-SACHS AND SANDHOFF DISEASES DIFFER IN NEUROLOGIC PHENOTYPE AND GANGLIOSIDE METABOLISM SO NATURE GENETICS LA English DT Article ID HEXOSAMINIDASE-A; DEGRADATION; STORAGE; PROTEIN; GM2 AB Tay-Sachs and Sandhoff diseases are clinically similar neurodegenerative disorders. These two sphingolipidoses are characterized by a heritable absence of beta-hexosaminidase A resulting in defective G(M2) ganglioside degradation. Through disruption of the Hexa and Herb genes in embryonic stem cells, we have established mouse models corresponding to each disease, Unlike the two human disorders, the two mouse models show very different neurologic phenotypes. Although exhibiting biochemical and pathologic features of the disease, the Tay-Sachs model showed no neurological abnormalities. In contrast, the Sandhoff model was severely affected. The phenotypic difference between the two mouse models is the result of differences in the ganglioside degradation pathway between mice and humans. C1 NIDDKD,GENET & BIOCHEM BRANCH,BIOCHEM GENET SECT,BETHESDA,MD 20892. UNIV BONN,INST ORGAN CHEM & BIOCHEM,D-53121 BONN,GERMANY. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,BRAIN & DEV RES CTR,CHAPEL HILL,NC 27599. RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [HD03110]; NINDS NIH HHS [NS24453] NR 21 TC 274 Z9 280 U1 1 U2 14 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1995 VL 11 IS 2 BP 170 EP 176 DI 10.1038/ng1095-170 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA RX806 UT WOS:A1995RX80600019 PM 7550345 ER PT J AU STRUEWING, JP ABELIOVICH, D PERETZ, T AVISHAI, N KABACK, MM COLLINS, FS BRODY, LC AF STRUEWING, JP ABELIOVICH, D PERETZ, T AVISHAI, N KABACK, MM COLLINS, FS BRODY, LC TI THE CARRIER FREQUENCY OF THE BRCA1 185DELAG MUTATION IS APPROXIMATELY 1 PERCENT IN ASHKENAZI-JEWISH INDIVIDUALS SO NATURE GENETICS LA English DT Letter ID BREAST-CANCER; FAMILIAL BREAST; OVARIAN-CANCER; RISK C1 NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH UNIV HOSP,HADASSAH MED SCH,SHARETT INST,DEPT HUMAN GENET,JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,HADASSAH UNIV HOSP,HADASSAH MED SCH,SHARETT INST,DEPT ONCOL,JERUSALEM,ISRAEL. UNIV CALIF SAN DIEGO,DEPT PEDIAT,SAN DIEGO,CA 92123. UNIV CALIF SAN DIEGO,DEPT REPROD MED,SAN DIEGO,CA 92123. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 34 TC 487 Z9 494 U1 0 U2 12 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1995 VL 11 IS 2 BP 198 EP 200 DI 10.1038/ng1095-198 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA RX806 UT WOS:A1995RX80600023 PM 7550349 ER PT J AU KOHN, DB WEINBERG, KI NOLTA, JA HEISS, LN LENARSKY, C CROOKS, GM HANLEY, ME ANNETT, G BROOKS, JS ELKHOUREIY, A LAWRENCE, K WELLS, S MOEN, RC BASTIAN, J WILLIAMSHERMAN, DE ELDER, M WARA, D BOWEN, T HERSHFIELD, MS MULLEN, CA BLAESE, RM PARKMAN, R AF KOHN, DB WEINBERG, KI NOLTA, JA HEISS, LN LENARSKY, C CROOKS, GM HANLEY, ME ANNETT, G BROOKS, JS ELKHOUREIY, A LAWRENCE, K WELLS, S MOEN, RC BASTIAN, J WILLIAMSHERMAN, DE ELDER, M WARA, D BOWEN, T HERSHFIELD, MS MULLEN, CA BLAESE, RM PARKMAN, R TI ENGRAFTMENT OF GENE-MODIFIED UMBILICAL-CORD BLOOD-CELLS IN NEONATES WITH ADENOSINE-DEAMINASE DEFICIENCY SO NATURE MEDICINE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; LONG-TERM HEMATOPOIESIS; PROGENITOR CELLS; EXPRESSION; MARROW; MOUSE; LINES; VIRUS; STEM AB Haematopoietic stem cells in umbilical cord blood are an attractive target for gene therapy of inborn errors of metabolism. Three neonates with severe combined immunodeficiency were treated by retroviral-mediated transduction of the CD34+ cells from their umbilical cord blood with a normal human adenosine deaminase complementary DNA followed by autologous transplantation. The continued presence and expression of the introduced gene in leukocytes from bone marrow and peripheral blood for 18 months demonstrates that umbilical cord blood cells may be genetically modified with retroviral vectors and engrafted in neonates for gene therapy. C1 GENET THERAPY INC,GAITHERSBURG,MD 20878. CHILDRENS HOSP & HLTH CTR,SAN DIEGO,CA 92123. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP KOHN, DB (reprint author), UNIV SO CALIF,CHILDRENS HOSP,SCH MED,DIV RES IMMUNOL BONE MARROW TRANSPLANTAT,4650 SUNSET BLVD,LOS ANGELES,CA 90027, USA. RI Kohn, Donald/N-5085-2016; OI Kohn, Donald/0000-0003-1840-6087; Nolta, Jan/0000-0003-4576-8542 FU NIDDK NIH HHS [R55 DK053041, R55 DK053041-01] NR 31 TC 432 Z9 436 U1 0 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 OCT PY 1995 VL 1 IS 10 BP 1017 EP 1023 DI 10.1038/nm1095-1017 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RX951 UT WOS:A1995RX95100040 PM 7489356 ER PT J AU LIN, SL NUSSINOV, R AF LIN, SL NUSSINOV, R TI A DISULFIDE-REINFORCED STRUCTURAL SCAFFOLD SHARED BY SMALL PROTEINS WITH DIVERSE FUNCTIONS SO NATURE STRUCTURAL BIOLOGY LA English DT Letter ID BOVINE BETA-TRYPSIN; CRYSTAL-STRUCTURE; INHIBITOR; COMPLEX; CARBOXYPEPTIDASE; RESOLUTION; ALPHA AB We describe the T-knot scaffold, a structural feature shared by the EGF-like toxins and proteinase inhibitors from plants. C1 TEL AVIV UNIV,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RP LIN, SL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. NR 17 TC 38 Z9 38 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 OCT PY 1995 VL 2 IS 10 BP 835 EP 837 DI 10.1038/nsb1095-835 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TD293 UT WOS:A1995TD29300007 PM 7552703 ER PT J AU MAKHATADZE, GI CLORE, GM GRONENBORN, AM AF MAKHATADZE, GI CLORE, GM GRONENBORN, AM TI SOLVENT ISOTOPE EFFECT AND PROTEIN STABILITY SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID HYDROPHOBIC INTERACTION; THERMODYNAMICS; DEPENDENCE; WATER; H2O; D2O; PARAMETERS; HYDRATION; ENTHALPY; BINDING AB Here we present a comparative study of the stability of several proteins in H2O and D2O as a function of pH/pH*. We show that the substitution of D2O for H2O leads to an increase in the transition temperature and a decrease in the enthalpy of unfolding. The stability of the proteins, however, appears to be largely unchanged as a result of entropic compensation for the decrease in enthalpy. This enthalpy-entropy compensation is attributed to changes in hydration of proteins in D2O compared to-H2O. Analysis of thermodynamic data for the transfer of model compounds from H2O to D2O shows that almost all the changes in the enthalpy of unfolding and in the protein-ligand interactions due to water isotopic substitution can be rationalized by changes in hydration of the buried non-polar groups. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP MAKHATADZE, GI (reprint author), JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 31 TC 150 Z9 150 U1 2 U2 8 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 OCT PY 1995 VL 2 IS 10 BP 852 EP 855 DI 10.1038/nsb1095-852 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TD293 UT WOS:A1995TD29300012 PM 7552708 ER PT J AU SMITH, CB SUN, Y SOKOLOFF, L AF SMITH, CB SUN, Y SOKOLOFF, L TI EFFECTS OF AGING ON REGIONAL RATES OF CEREBRAL PROTEIN-SYNTHESIS IN THE SPRAGUE-DAWLEY RAT - EXAMINATION OF THE INFLUENCE OF RECYCLING OF AMINO-ACIDS DERIVED FROM PROTEIN-DEGRADATION INTO THE PRECURSOR POOL SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID SYNTHESIS INVIVO; BRAIN; AGE; NUCLEUS; YOUNG AB The quantitative autoradiographic L-[1-C-14]leucine method for determination of regional rates of cerebral protein synthesis (lCPS(leu)) requires knowledge of the degree of recycling of leucine derived from protein degradation into the precursor pool for protein synthesis. The influence of recycling can be evaluated by measuring lambda, the steady state ratio of the leucine specific activity in the precursor amino acid pool (tRNA-bound leucine) to that in the arterial plasma. To define the changes in lCPS(leu) during the process of normal aging in the rat we have evaluated lambda in middle-aged (14 months) and aged (24 months) rats and compared its values with those obtained previously in young adult rats (two months of age). The results show that the value of lambda, is the same in all three age groups, and that there is no change with aging in the fraction of leucine in the precursor pool derived from protein degradation. Our previously reported regional rates of protein synthesis in young adult and aged rats were based on the assumption that there was no recycling of leucine derived from protein degradation into the precursor pool for protein synthesis [Ingvar M. C., Maeder P., Sokoloff L. and Smith C. B. (1985) Brain 108, 155-170]. These values have been recalculated in the present study in order to take into account the appropriate correction for recycling. The recalculated rates are higher than those reported previously, but the effects of aging in the brain as a whole and in some specific brain regions are confirmed. Decreased lCPS(leu) was observed by middle-age, and in this cross-sectional study did not appear to decrease further. Of the 39 brain regions examined decreases were found throughout the brain with some proclivity for the brain stem. In comparison with young adults the weighted average rate of protein synthesis in the brain as a whole was found to be decreased by 16 and 11% in the middle-aged and aged groups, respectively. RP SMITH, CB (reprint author), NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD OCT-NOV PY 1995 VL 27 IS 4-5 BP 407 EP 416 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RX057 UT WOS:A1995RX05700014 PM 8845741 ER PT J AU STONE, LA ALBERT, PS SMITH, ME DECARLI, C ARMSTRONG, MR MCFARLIN, DE FRANK, JA MCFARLAND, HF AF STONE, LA ALBERT, PS SMITH, ME DECARLI, C ARMSTRONG, MR MCFARLIN, DE FRANK, JA MCFARLAND, HF TI CHANGES IN THE AMOUNT OF DISEASED WHITE-MATTER OVER TIME IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE-SCLEROSIS SO NEUROLOGY LA English DT Article ID RESONANCE-IMAGING LESIONS; MRI AB MRI is a sensitive technique for assessing disease activity in MS. Diseased white matter (WM) can be identified on T-2-weighted images, and active disease is reflected by abnormalities in the blood-brain barrier (BBB) shown on T-1-weighted images after administration of paramagnetic contrast agents. Active disease may be demonstrated by contrast-enhanced NIRI in patients with early, mild relapsing-remitting (RR) MS even during periods of clinical stability, which indicates that MS is an active process even during the early phase of the illness. To examine the amount of abnormal WM at frequent intervals over time, we studied seven mildly affected RRMS patients, all of whom had frequent contrast-enhancing lesions. These RRMS patients were imaged monthly for 26 to 36 months at 1.5 tesla; the area of abnormal increased WM signal was calculated by image-processing software that utilizes both the T-2-and T-1-weighted images. All patients showed fluctuations over time in amount of abnormal WM signal, which reflected factors such as the amount of BBB breakdown (measured by number or area of enhancing lesions) and measurement error. All seven RRMS patients, however, showed an overall increase in abnormal WM. Because of the fluctuations between individual measurements, the increase was most accurately reflected when the mean of the first 6 months' measurements was compared with the mean of the final 6 months' measurements, or when a linear regression model was applied. Although the accumulation of abnormal WM provides an additional tool for assessing disease activity in MS, its usefulness may be increased by the measurements obtained with additional techniques that are currently available or as yet undeveloped. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD 20892. NIH,DIAGNOST RADIOL RES PROGRAM LAB,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,DEPT RADIOL,NEW YORK,NY. RP STONE, LA (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BLDG 10,ROOM 5B16,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009 NR 26 TC 63 Z9 63 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1995 VL 45 IS 10 BP 1808 EP 1814 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TA765 UT WOS:A1995TA76500003 PM 7477973 ER PT J AU CUENOD, CA BOOKHEIMER, SY HERTZPANNIER, L ZEFFIRO, TA THEODORE, WH LEBIHAN, D AF CUENOD, CA BOOKHEIMER, SY HERTZPANNIER, L ZEFFIRO, TA THEODORE, WH LEBIHAN, D TI FUNCTIONAL MRI DURING WORD GENERATION, USING CONVENTIONAL EQUIPMENT - A POTENTIAL TOOL FOR LANGUAGE LOCALIZATION IN THE CLINICAL ENVIRONMENT SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SENSORY STIMULATION; HUMAN BRAIN; CORTEX; AREA; ANATOMY; TIME; PET AB Objective. To test the accuracy of bilateral language mapping using a standard clinical magnetic resonance (MR) imaging device during word generation. Design. A study of normal volunteers. Setting. Volunteers from the Washington, DC, area. Participants. Nine normal, right-handed, native English speakers (four women, five men, mean age 31 years). Interventions. During four MR acquisition periods, subjects would alternately rest and silently generate words. Sagittal MR images covered the middle and inferior frontal gyri, insulae, and part of the temporal and parietal lobes bilaterally. Main. outcome measures. (1) Anatomic maps of task-related signal changes obtained by comparing, in each voxel, the signal during word generation and;rest periods, and (2) analysis of the time course of the signal. Results. Maximum responses were in the left hemisphere, mainly in the frontal lobe (Broca's area, premotor cortex, and dorsolateral prefrontal cortex) but also in posterior regions such as Wernicke's area. In agreement with previous studies, some degree of task-related changes was present in a subset of the corresponding regions in the right hemisphere. Conclusion. Despite certain limitations, it is possible, using widely available MR equipment, to obtain results consistent with previous studies. The technique may have important implications for assessment of cognitive functions in patients with neurologic disorders in a clinical environment. C1 NINCDS, DIAGNOST RADIOL RES LAB, BETHESDA, MD 20892 USA. NINCDS, EPILEPSY RES BRANCH, BETHESDA, MD 20892 USA. NIH, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NINCDS, BETHESDA, MD 20892 USA. NR 42 TC 167 Z9 169 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD OCT PY 1995 VL 45 IS 10 BP 1821 EP 1827 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TA765 UT WOS:A1995TA76500005 PM 7477975 ER PT J AU GAILLARD, WD FAZILAT, S WHITE, S MALOW, B SATO, S REEVES, P HERSCOVITCH, P THEODORE, WH AF GAILLARD, WD FAZILAT, S WHITE, S MALOW, B SATO, S REEVES, P HERSCOVITCH, P THEODORE, WH TI INTERICTAL METABOLISM AND BLOOD-FLOW ARE UNCOUPLED TEMPORAL-LOBE CORTEX OF PATIENTS WITH COMPLEX PARTIAL EPILEPSY SO NEUROLOGY LA English DT Article ID CEREBRAL GLUCOSE-METABOLISM; POSITRON EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; PRESURGICAL EVALUATION; OXYGEN-CONSUMPTION; PARTIAL SEIZURES; HIPDM-SPECT; ICTAL EEG; BRAIN; PET AB We used positron emission tomography (PET) with F-18-2-deoxyglucose (FDG) and O-15 water in 20 patients with complex partial seizures to compare glucose metabolism and blood flow in temporal lobe epileptic foci identified by ictal scalp-sphenoidal video-EEG telemetry. Glucose metabolism was measured 20 minutes after blood flow without moving the patient from the scanner. We also studied 11 patients with Tc-99m-HMPAO single-photon emission computed tomography (SPECT). Both local cerebral metabolic rate of glucose (LCMRGlc) and regional cerebral blood flow (rCBF) were significantly decreased in temporal cortex ipsilateral to the EEG focus. However, LCMRGlc was reduced by 11.2% in inferior lateral and 11.1% in inferior mesial temporal cortex and rCBF by only 3.2% and 6.1%. The ratio of LCMRGlc to rCBF was significantly reduced in inferior lateral temporal cortex ipsilateral to the ictal focus (p < 0.009). Moreover, using standardized criteria, blinded raters found that 16 of 20 patients had focal FDG-PET hypometabolism, all in the epileptogenic region; 10 of 20 had focal 150 water PET hypoperfusion, but it was falsely lateralized in two of these 10; and five of 11 had focal Tc-99m-HMPAO SPECT hypoperfusion, but it was falsely lateralized in two of these five. Our data suggest that interictal glucose metabolism and blood flow may be uncoupled in epileptogenic cortex. C1 NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD. NIH,CTR CLIN,DEPT PET,PET IMAGING SECT,BETHESDA,MD 20892. RP GAILLARD, WD (reprint author), GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT NEUROL,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 38 TC 78 Z9 78 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1995 VL 45 IS 10 BP 1841 EP 1847 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TA765 UT WOS:A1995TA76500009 PM 7477979 ER PT J AU BAMFORD, KA CAINE, ED KIDO, DK COX, C SHOULSON, I AF BAMFORD, KA CAINE, ED KIDO, DK COX, C SHOULSON, I TI A PROSPECTIVE EVALUATION OF COGNITIVE DECLINE IN EARLY HUNTINGTONS-DISEASE - FUNCTIONAL AND RADIOGRAPHIC CORRELATES SO NEUROLOGY LA English DT Article ID NEUROPSYCHOLOGICAL DEFICITS; BASAL GANGLIA; DEMENTIA; MEMORY; NEURONS AB We examined prospectively the relationship between progressive disability in Huntington's disease (HD) and concomitant alterations in neuropsychological functioning and brain imaging indices in a cohort of 60 patients who were enrolled and followed for 30 to 42 months in a controlled clinical trial. Standardized measures of functional capacity and neuropsychological performance were collected, and CT was performed, at regular intervals every 6 to 12 months. Psychomotor skills showed the most significant and consistent decline among the cognitive functions assessed. Memory disturbances were already present at the time of enrollment, but memory did not deteriorate until patients reached advanced stages. Other cognitive operations, such as visual construction and semantic knowledge, manifested small and variable changes over time. CT indices of striatal atrophy correlated only with changes in psychomotor function, while the CT index of frontal atrophy weakly predicted memory and semantic knowledge scores at 42 months. These results confirmed earlier cross-sectional findings and extended our knowledge of the evolution of cognitive dysfunction in HD. C1 UNIV ROCHESTER,SCH MED,DEPT PSYCHIAT,ROCHESTER,NY. UNIV ROCHESTER,SCH MED,DEPT BIOSTAT,ROCHESTER,NY. UNIV ROCHESTER,SCH MED,DEPT NEUROL,ROCHESTER,NY. UNIV WASHINGTON,SCH MED,DEPT RADIOL,ST LOUIS,MO. UNIV ROCHESTER,SCH MED,NIMH,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,ROCHESTER,NY. FU NCRR NIH HHS [RR 00044]; NIMH NIH HHS [MH40381]; NINDS NIH HHS [NS17978] NR 35 TC 77 Z9 77 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1995 VL 45 IS 10 BP 1867 EP 1873 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TA765 UT WOS:A1995TA76500014 PM 7477984 ER PT J AU SIMON, ES AF SIMON, ES TI INVOLVEMENT OF GLYCINE AND GABA(A) RECEPTORS IN THE PATHOGENESIS OF SPINAL MYOCLONUS - IN-VITRO STUDIES IN THE ISOLATED NEONATAL RODENT SPINAL-CORD SO NEUROLOGY LA English DT Article ID SPASTIC MUTANT MOUSE; IN-VITRO; INTERSEGMENTAL COORDINATION; RECURRENT INHIBITION; CELLULAR MECHANISMS; MOTO-NEURONS; MOTONEURONS; STRYCHNINE; POTENTIALS; INVITRO AB Studies of pathogenetic mechanisms of myoclonus and spinal spasticity have established a strong association between deficient inhibitory glycinergic transmission and pathologic rigidity and tremor. Consistent with known cases in the clinical literature, electrophysiologic data from animal models of myoclonus implicate dysfunction of segmental spinal cord circuitry. The present study sought to further explore pathogenetic mechanisms at the circuit level. In vitro preparations of isolated spinal cord from neonatal rodents allowed for stable recordings of individual cells as well as populations of motoneurons. Blockade of glycine receptors enhanced 5- to 15-Hz sinusoidal oscillations that were synchronous in entire populations of motoneurons as well as along multiple segments of the spinal cord. Oscillations at motoneurons were mediated largely by non-NMDA excitatory synaptic inputs. Blockade of GABA(A) receptors, and not GABA(B) receptors, abolished sinusoidal oscillations, suggesting a critical role for GABA, receptors in the premotoneuronal circuitry responsible for generation or transmission of the sinusoidal oscillations. These data offer new insights into possible pathogenetic mechanisms of spinal myoclonus and may help guide future research leading to specific therapies for hyperkinetic movement disorders of spinal origin. C1 NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. RP SIMON, ES (reprint author), NINCDS,NEURAL CONTROL LAB,BLDG 49,ROOM 3A50,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 65 TC 18 Z9 18 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1995 VL 45 IS 10 BP 1883 EP 1892 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA TA765 UT WOS:A1995TA76500017 PM 7477987 ER PT J AU SCHWARTZ, PJ WEHR, TA ROSENTHAL, NE BARTKO, JJ OREN, DA LUETKE, C MURPHY, DL AF SCHWARTZ, PJ WEHR, TA ROSENTHAL, NE BARTKO, JJ OREN, DA LUETKE, C MURPHY, DL TI SEROTONIN AND THERMOREGULATION - PHYSIOLOGICAL AND PHARMACOLOGICAL ASPECTS OF CONTROL REVEALED BY INTRAVENOUS M-CPP IN NORMAL HUMAN-SUBJECTS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE TEMPERATURE; META-CHLOROPHENYLPIPERAZINE; SEROTONIN; NOREPINEPHRINE ID SEASONAL AFFECTIVE-DISORDER; BROWN ADIPOSE-TISSUE; OBSESSIVE-COMPULSIVE DISORDER; M-CHLOROPHENYLPIPERAZINE; BODY-TEMPERATURE; META-CHLOROPHENYLPIPERAZINE; BEHAVIORAL-RESPONSES; NEURO-ENDOCRINE; CONSCIOUS RATS; RECEPTORS AB Meta-chlorophenylpiperazine (m-CPP), a probe of central serotonergic function, elevates core temperature in rodents, nonhuman primates, and humans via serotonin receptor-mediated mechanisms. To further characterize the thermoregulatory aspects of this response, we studied 16 healthy volunteers using multiple core and skin temperature recording sites. Compared to placebo, intravenous m-CPP (0.08 mg/kg) produced statistically significant biphasic changes in rectal temperature, characterized by initial hypothermia (-0.04 degrees C at 12 minutes) followed by progressive hyperthermia (+0.17 degrees C at 90 minutes). m-CPP also produced significant increases in plasma norepinephrine concentrations. Analysis of the skin temperature recordings suggests that the effector mechanism primarily responsible for m-CPP-induced care hyperthermia is increased metabolic thermogenesis. Individual differences in the magnitude of the hyperthermia were independent of m-CPP plasma concentrations but were found to be linearly correlated with the level of the previous night's core rectal temperature minimum and mean. If appears that m-CPP activates a mode of metabolic thermogenesis governed by a nocturnally sensitive proportional control mechanism. The operation of suck a proportional controller is characterized by a set point and a gain, and has been implicated in the general economy of mammalian energy balance. C1 NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP SCHWARTZ, PJ (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. NR 95 TC 38 Z9 38 U1 1 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 1995 VL 13 IS 2 BP 105 EP 115 DI 10.1016/0893-133X(95)00026-A PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TB941 UT WOS:A1995TB94100002 PM 8597522 ER PT J AU BRAUN, AR RANDOLPH, C STOETTER, B MOHR, E COX, C VLADAR, K SEXTON, R CARSON, RE HERSOVITCH, P CHASE, TN AF BRAUN, AR RANDOLPH, C STOETTER, B MOHR, E COX, C VLADAR, K SEXTON, R CARSON, RE HERSOVITCH, P CHASE, TN TI THE FUNCTIONAL NEUROANATOMY OF TOURETTES-SYNDROME - AN FDG-PET STUDY .2. RELATIONSHIPS BETWEEN REGIONAL CEREBRAL METABOLISM AND ASSOCIATED BEHAVIORAL AND COGNITIVE FEATURES OF THE ILLNESS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE TOURETTES (TOURETTE) SYNDROME; POSITRON EMISSION TOMOGRAPHY; FDG; OBSESSIVE-COMPULSIVE DISORDER; IMPULSIVITY; SELF-INJURIOUS BEHAVIOR; DEPRESSION; COPROLALIA; ECHOPHENOMENA; ATTENTION; VISUOSPATIAL; ORBITOFRONTAL CORTEX; INSULA; BASAL GANGLIA ID OBSESSIVE-COMPULSIVE DISORDER; OLD-WORLD MONKEY; GLUCOSE-METABOLISM; FRONTAL LOBES; HUMAN AUTONOMY; LESIONS; CORTEX; INSULA; CIRCUITS; RATES AB We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioral features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and if is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofronfal cortex. C1 NINCDS, ETB, BETHESDA, MD 20892 USA. NIH, PET DEPT, BETHESDA, MD 20892 USA. NORTHWESTERN UNIV, SCH MED, DEPT NEUROL, CHICAGO, IL 60611 USA. NORTHWESTERN UNIV, SCH MED, DEPT PSYCHIAT, CHICAGO, IL 60611 USA. UNIV OTTAWA, MENTAL HLTH RES INST, OTTAWA, ON, CANADA. KENNEDY KRIEGER INST, BALTIMORE, MD USA. NIMH, NEUROSCI CTR ST ELIZABETHS, CBDB, WASHINGTON, DC 20032 USA. RP BRAUN, AR (reprint author), NIDCD, VSLB, VSS, BLDG 10, ROOM 5D-38, BETHESDA, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 87 TC 64 Z9 69 U1 1 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 1995 VL 13 IS 2 BP 151 EP 168 DI 10.1016/0893-133X(95)00052-F PG 18 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TB941 UT WOS:A1995TB94100006 PM 8597526 ER PT J AU LUO, L JI, RR ZHANG, Q IADAROLA, MJ HOKFELT, T WIESENFELDHALLIN, Z AF LUO, L JI, RR ZHANG, Q IADAROLA, MJ HOKFELT, T WIESENFELDHALLIN, Z TI EFFECT OF ADMINISTRATION OF HIGH-DOSE INTRATHECAL CLONIDINE OR MORPHINE PRIOR TO SCIATIC-NERVE SECTION ON C-FOS EXPRESSION IN RAT LUMBAR SPINAL-CORD SO NEUROSCIENCE LA English DT Article ID IMMEDIATE-EARLY GENES; SUBSTANCE-P; INJURY DISCHARGE; PERIPHERAL-NERVE; DORSAL HORN; IMMUNOHISTOCHEMICAL ANALYSIS; PERSISTENT EXPRESSION; ANTIBODY MICROPROBES; NOXIOUS-STIMULATION; TRIGEMINAL NUCLEUS AB The effect of moderate and high intrathecal doses of clonidine, an alpha(2) adrenoceptor agonist, or a high dose of morphine on sciatic nerve section-induced expression of c-Fos-like immunoreactivity was studied in laminae I and II of the dorsal horn and laminae VIII and IX of the ventral horn of rat lumbar spinal cord. c-Fos-like immunoreactivity was examined by immunohistochemistry in normal rats (group 1), rats implanted with an intrathecal catheter with its tip on the lumbar spinal cord (group 2), injected with 10 mu g (group 3) or 50 mu g (group 4) clonidine intrathecally 3 h before being killed. In other groups, saline, 10 or 50 mu g clonidine or 30 mu g morphine was injected 1 h before unilateral nerve section, and the expression of c-Fos-like immunoreactivity was examined 2 h after axotomy. Few labeled neurons were found in normal controls. The intrathecal catheter itself caused a significant increase in bilateral c-Fos-like immunoreactivity in spinal dorsal and ventral horn compared to normals. The level of c-Fos-like immunoreactivity after 10 or 50 mu g intrathecal clonidine was similar as in the intrathecal catheter group. Sciatic nerve section caused a significant ipsilateral increase in c-Fos-like immunoreactivity in the dorsal horn compared to the intact side in rats injected with saline. Pretreatment with 10 or 50 mu g clonidine did not reduce sciatic nerve section-induced expression of c-Fos-like immunoreactivity, but instead caused a significant bilateral increase in c-Fos-like immunoreactivity. The lower dose of clonidine increased c-Fos-like immunoreactivity bilaterally in laminae I and II, the higher dose in both dorsal and ventral horn, compared to animals injected with saline prior to nerve section or rats with intact nerves injected with clonidine. However, the level of c-Fos-like immunoreactivity after clonidine was in general higher on the axotomized than on the intact side. In contrast, pretreatment with 30 mu g intrathecal morphine prevented the expression of c-Fos-like immunoreactivity following axotomy in dorsal and ventral horn bilaterally, resulting in a similar level of labeling as in normal controls. Thus, the present results indicate that nerve injury induced the expression of c-Fos-like immunoreactivity in spinal cord, and that this can be prevented by a high intrathecal dose of morphine. In contrast, intrathecal clonidine potentiated nerve section-induced c-Fos-like immunoreactivity expression bilaterally, which might be due to a synergistic effect between clonidine and nerve section. The possible role of the expression of c-Fos-like immunoreactivity in experimental neuropathic pain is discussed. C1 HUDDINGE UNIV HOSP, DEPT MED LAB SCI & TECHNOL, CLIN NEUROPHYSIOL SECT, S-14186 HUDDINGE, SWEDEN. KAROLINSKA INST, DEPT NEUROSCI, STOCKHOLM, SWEDEN. NIDR, BETHESDA, MD USA. OI Ji, Ru-Rong/0000-0002-9355-3688 NR 61 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1995 VL 68 IS 4 BP 1219 EP 1227 DI 10.1016/0306-4522(95)00197-Q PG 9 WC Neurosciences SC Neurosciences & Neurology GA RW400 UT WOS:A1995RW40000023 PM 8544995 ER PT J AU GODSCHALK, M MITZ, AR VANDUIN, B VANDERBURG, H AF GODSCHALK, M MITZ, AR VANDUIN, B VANDERBURG, H TI SOMATOTOPY OF MONKEY PREMOTOR CORTEX EXAMINED WITH MICROSTIMULATION SO NEUROSCIENCE RESEARCH LA English DT Article DE MONKEY; PREMOTOR CORTEX; SOMATOTOPY; MICROSTIMULATION ID PRIMARY MOTOR CORTEX; ADJACENT CINGULATE CORTEX; MOVEMENT-RELATED ACTIVITY; SUPPLEMENTARY EYE FIELD; MACAQUE MONKEY; FRONTAL-LOBE; INTRACORTICAL MICROSTIMULATION; RHESUS-MONKEYS; TOPOGRAPHIC ORGANIZATION; FUNCTIONAL-ORGANIZATION AB We reinvestigated the organization of the premotor cortex (PM) using intracortical microstimulation. Movements of forelimb, hindlimb, and orofacial structures were evoked from broad regions of PM that appeared to be contiguous with other motor areas. There were two principal findings: (1) the somatotopy of PM lies roughly parallel to that of the primary motor cortex (MI). Forelimb movements were evoked from sites deep in the caudal bank of the arcuate sulcus and throughout the adjacent cortex bounded by a face representation (laterally) and a hindlimb representation (medially and caudally); (2) unlike the MI, the PM forelimb representation overlaps significantly with its own face representation. PM hindlimb movement sites overlap only slightly with PM forelimb sites, in a manner similar to the MI. There was no obvious boundary between PM, MI, or supplementary motor area hindlimb representations. The present findings are discussed in relation to recently identified subdivisions of the PM. C1 NIMH,SYST NEUROSCI LAB,CTR ANIM,POOLESVILLE,MD 20837. RP GODSCHALK, M (reprint author), ERASMUS UNIV ROTTERDAM,FAC MED & HLTH SCI,DEPT ANAT,POB 1738,3000 DR ROTTERDAM,NETHERLANDS. NR 67 TC 111 Z9 111 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD OCT PY 1995 VL 23 IS 3 BP 269 EP 279 DI 10.1016/0168-0102(95)00950-7 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TC706 UT WOS:A1995TC70600005 PM 8545075 ER PT J AU CLARKSON, JG CHUANG, E GASS, D PEDROSO, M CUBILLAS, T DURIA, ES HESS, DJ RAMS, I BALL, M GUTIERREZ, A MUNIZ, N THOMPSON, J PALL, M PAPPAS, CJ FINKELSTEIN, D PATZ, A RYTEL, D BELT, J CAIN, D CAIN, T EMMERT, D GEORGE, T HERRING, M SOTIRAKOS, P ORTH, H FLOOD, TP PACKO, KH LARSEN, T PEREZ, N BRYANT, D DOHERTY, D FITZGERALD, J GORDON, M HOLOD, C KWIATKOWSKI, K MACLEOD, C MORISON, C WESTCOTT, C KLEIN, ML WILSON, D WELEBER, RG NOLTE, S HURLBURT, N EVANS, M WALLACE, P STEINKAMP, P FUNKNER, D GORDON, C JALKH, A WEITER, J ANDERSON, S DONOVAN, D ODAY, T FRIEDMAN, G IMMERMAN, R SOUBRANE, G HARAN, RM DEBIBIE, C GIZELSKY, J WALLOW, HL DEVENECIA, G BRESNICK, G LARSON, S FULLER, S HARRISON, B KNUTSON, G NEIDER, M WEBER, G BAHR, R GROSNICK, B LAZORIK, R LYNGAAS, H QUACKENBOSS, D SOMERS, G GUTMAN, FA MYERS, S KISS, T ROSS, D VARGO, P EDGARTON, J HANSON, S NADER, J TOMSAK, N SINGERMAN, LJ ZEGARRA, H LICHTERMAN, S KRAMER, AF SMITHBREWER, S ROWE, PB DALY, G PINTER, A CORENO, K COOPER, L DELISIO, M CROSS, D LORD, W HILLIS, A RIGGS, MW KASBERGPREECE, C RAJAB, MH GINIEWICZ, KC GILMORE, K ZIMMERMAN, C LEWIS, ML WELLS, MC FORBES, JL FETZER, KC MCNISH, H MCNULTY, L BALIKER, J ALANEN, L GENTRY, L MOWERY, RL EVERETT, DF COSCAS, G EVERETT, F ORTH, DH TREMPE, C HARDY, RJ ABRAMS, G FRANK, RN MAGUIRE, MG MCCALL, AV AF CLARKSON, JG CHUANG, E GASS, D PEDROSO, M CUBILLAS, T DURIA, ES HESS, DJ RAMS, I BALL, M GUTIERREZ, A MUNIZ, N THOMPSON, J PALL, M PAPPAS, CJ FINKELSTEIN, D PATZ, A RYTEL, D BELT, J CAIN, D CAIN, T EMMERT, D GEORGE, T HERRING, M SOTIRAKOS, P ORTH, H FLOOD, TP PACKO, KH LARSEN, T PEREZ, N BRYANT, D DOHERTY, D FITZGERALD, J GORDON, M HOLOD, C KWIATKOWSKI, K MACLEOD, C MORISON, C WESTCOTT, C KLEIN, ML WILSON, D WELEBER, RG NOLTE, S HURLBURT, N EVANS, M WALLACE, P STEINKAMP, P FUNKNER, D GORDON, C JALKH, A WEITER, J ANDERSON, S DONOVAN, D ODAY, T FRIEDMAN, G IMMERMAN, R SOUBRANE, G HARAN, RM DEBIBIE, C GIZELSKY, J WALLOW, HL DEVENECIA, G BRESNICK, G LARSON, S FULLER, S HARRISON, B KNUTSON, G NEIDER, M WEBER, G BAHR, R GROSNICK, B LAZORIK, R LYNGAAS, H QUACKENBOSS, D SOMERS, G GUTMAN, FA MYERS, S KISS, T ROSS, D VARGO, P EDGARTON, J HANSON, S NADER, J TOMSAK, N SINGERMAN, LJ ZEGARRA, H LICHTERMAN, S KRAMER, AF SMITHBREWER, S ROWE, PB DALY, G PINTER, A CORENO, K COOPER, L DELISIO, M CROSS, D LORD, W HILLIS, A RIGGS, MW KASBERGPREECE, C RAJAB, MH GINIEWICZ, KC GILMORE, K ZIMMERMAN, C LEWIS, ML WELLS, MC FORBES, JL FETZER, KC MCNISH, H MCNULTY, L BALIKER, J ALANEN, L GENTRY, L MOWERY, RL EVERETT, DF COSCAS, G EVERETT, F ORTH, DH TREMPE, C HARDY, RJ ABRAMS, G FRANK, RN MAGUIRE, MG MCCALL, AV TI EVALUATION OF GRID PATTERN PHOTOCOAGULATION FOR MACULAR EDEMA IN CENTRAL VEIN OCCLUSION - THE CENTRAL VEIN OCCLUSION STUDY-GROUP-M REPORT SO OPHTHALMOLOGY LA English DT Article AB Purpose: To evaluate the efficacy of macular grid photocoagulation in preserving or improving central visual acuity in eyes with macular edema due to central vein occlusion (CVO) and best-corrected visual acuity of 20/50 or poorer. Methods: Patients with angiographically documented macular edema due to CVO were entered into a multicenter randomized controlled clinical trial supported by the National Eye Institute. Eligibility was determined based on both clinical examination findings and photographic documentation evaluated at a photograph reading center. Eyes were assigned randomly to macular grid photocoagulation (77 eyes) or no treatment (78 eyes). Patients were followed every 4 months for 3 years or until the end of the study. The outcome measure was visual acuity. Results: The study population consisted of 155 eyes in 155 patients. There was no difference between treated and untreated eyes in visual acuity at any point during the follow-up period. Initial median visual acuity was 20/160 in treated eyes and 20/125 in control eyes. Final median visual acuity was 20/200 in treated eyes and 20/160 in control eyes. However, treatment clearly reduced angiographic evidence of macular edema. Conclusion: The results of this study do not support a recommendation for macular grid photocoagulation for the population meeting the Central Vein Occlusion Study macular edema group eligibility criteria. C1 JOHNS HOPKINS UNIV,WILMER OPHTHALMOL INST,BALTIMORE,MD 21218. ILLINOIS RETINA ASSOCIATES,HARVEY,IL. ILLINOIS RETINA ASSOCIATES,CHICAGO,IL. OREGON HLTH SCI UNIV,CASEY EYE INST,PORTLAND,OR 97201. RETINA ASSOCIATES,BOSTON,MA. CLIN OPHTALMOL,CRETEIL,FRANCE. UNIV WISCONSIN,MADISON,WI. CLEVELAND CLIN,CLEVELAND,OH 44106. RETINA ASSOCIATES,CLEVELAND,OH. TEXAS A&M UNIV,SCOTT & WHITE MEM HOSP,HLTH SCI CTR,CTR COORDINATING,TEMPLE,TX 76508. UNIV MIAMI,MCKNIGHT VIS RES CTR,CTR READING,CORAL GABLES,FL 33124. UNIV WISCONSIN,CTR ERG READING,MADISON,WI. NEI,BETHESDA,MD 20892. RP CLARKSON, JG (reprint author), UNIV MIAMI,BASCOM PALMER EYE INST,900 NW 17TH ST,MIAMI,FL 33136, USA. NR 10 TC 248 Z9 256 U1 0 U2 7 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1995 VL 102 IS 10 BP 1425 EP 1433 PG 9 WC Ophthalmology SC Ophthalmology GA RZ487 UT WOS:A1995RZ48700012 ER PT J AU CLARKSON, JG CHUANG, E GASS, D PEDROSO, M CUBILLAS, T DURIA, ES HESS, DJ RAMS, I BALL, M GUTIERREZ, A MUNIZ, N THOMPSON, J PALL, M PAPPAS, CJ FINKELSTEIN, D PATZ, A RYTEL, D BELT, J CAIN, D CAIN, T EMMERT, D GEORGE, T HERRING, M SOTIRAKOS, P ORTH, DH FLOOD, TP PACKO, KH LARSEN, T PEREZ, N BRYANT, D DOHERTY, D FITZGERALD, J GORDON, M HOLOD, C KWIATKOWSKI, K MACLEOD, C MORISON, C WESTCOTT, C KLEIN, L WILSON, D WELEBER, RG NOLTE, S HURLBURT, N EVANS, M WALLACE, P STEINKAMP, P FUNKNER, D GORDON, C WEITER, J JALKH, A ANDERSON, S DONOVAN, D ODAY, T FRIEDMAN, G IMMERMAN, R COSCAS, G SOUBRANE, G HARAN, RM DEBIBIE, C GIZELSKY, J WALLOW, L DEVENECIA, G BRESNICK, G LARSON, S FULLER, S HARRISON, B KNUTSON, G NEIDER, M WEBER, G BAHR, R GROSNICK, B LAZORIK, R LYNGAAS, H QUACKENBOSS, D SOMERS, G GUTMAN, GA MYERS, S KISS, T ROSS, D VARGO, P EDGARTON, J HANSON, S NADER, J TOMSAK, N SINGERMAN, LJ ZEGARRA, H LICHTERMAN, S KRAMER, AF SMITHBREWER, S ROWE, PB DALY, G PINTER, A CORENO, K COOPER, L DELISIO, M CROSS, D LORD, W HILLIS, A RIGGS, MW KASBERGPREECE, C RAJAB, MH GINIEWICZ, KC GILMORE, K ZIMMERMAN, C LEWIS, ML WELLS, MC FORBES, JL FETZER, KC MCNISH, H MCNULTY, L BALIKER, J ALANEN, L GENTRY, L MOWERY, RL GUTMAN, FA KLEIN, ML TREMPE, C HARDY, RJ ABRAMS, G FRANK, RN MAGUIRE, MG MCCALL, AV AF CLARKSON, JG CHUANG, E GASS, D PEDROSO, M CUBILLAS, T DURIA, ES HESS, DJ RAMS, I BALL, M GUTIERREZ, A MUNIZ, N THOMPSON, J PALL, M PAPPAS, CJ FINKELSTEIN, D PATZ, A RYTEL, D BELT, J CAIN, D CAIN, T EMMERT, D GEORGE, T HERRING, M SOTIRAKOS, P ORTH, DH FLOOD, TP PACKO, KH LARSEN, T PEREZ, N BRYANT, D DOHERTY, D FITZGERALD, J GORDON, M HOLOD, C KWIATKOWSKI, K MACLEOD, C MORISON, C WESTCOTT, C KLEIN, L WILSON, D WELEBER, RG NOLTE, S HURLBURT, N EVANS, M WALLACE, P STEINKAMP, P FUNKNER, D GORDON, C WEITER, J JALKH, A ANDERSON, S DONOVAN, D ODAY, T FRIEDMAN, G IMMERMAN, R COSCAS, G SOUBRANE, G HARAN, RM DEBIBIE, C GIZELSKY, J WALLOW, L DEVENECIA, G BRESNICK, G LARSON, S FULLER, S HARRISON, B KNUTSON, G NEIDER, M WEBER, G BAHR, R GROSNICK, B LAZORIK, R LYNGAAS, H QUACKENBOSS, D SOMERS, G GUTMAN, GA MYERS, S KISS, T ROSS, D VARGO, P EDGARTON, J HANSON, S NADER, J TOMSAK, N SINGERMAN, LJ ZEGARRA, H LICHTERMAN, S KRAMER, AF SMITHBREWER, S ROWE, PB DALY, G PINTER, A CORENO, K COOPER, L DELISIO, M CROSS, D LORD, W HILLIS, A RIGGS, MW KASBERGPREECE, C RAJAB, MH GINIEWICZ, KC GILMORE, K ZIMMERMAN, C LEWIS, ML WELLS, MC FORBES, JL FETZER, KC MCNISH, H MCNULTY, L BALIKER, J ALANEN, L GENTRY, L MOWERY, RL GUTMAN, FA KLEIN, ML TREMPE, C HARDY, RJ ABRAMS, G FRANK, RN MAGUIRE, MG MCCALL, AV TI A RANDOMIZED CLINICAL-TRIAL OF EARLY PANRETINAL PHOTOCOAGULATION FOR ISCHEMIC CENTRAL VEIN OCCLUSION - THE CENTRAL VEIN OCCLUSION STUDY-GROUP-N REPORT SO OPHTHALMOLOGY LA English DT Article AB Purpose: To answer whether prophylactic panretinal photocoagulation (PRP) in ischemic central vein occlusion (CVO) prevents development of 2 clock hours of iris neovascularization or any angle neovascularization (TC-INV/ANV) or whether it is more appropriate to apply PRP only when TC-INV/ANV occurs. Methods: Multicenter randomized controlled clinical trial in eyes with ischemic CVO. Eyes were assigned to immediate prophylactic PRP (90 eyes) or to frequent close observation (91 eyes), If TC-INV/ANV developed, untreated eyes received PRP and previously treated eyes received supplemental PRP. Results: In both groups, TC-INV/ANV developed less often in prophylactically treated than untreated eyes, but the difference was not statistically significant when adjusted for baseline imbalance. Treatment of TC-INV/ANV was followed by prompt regression (within 1 month) in 18 (56%) of 32 previously untreated eyes and in 4 (22%) of 18 eyes that had had prophylactic treatment, All eyes except eight eventually stabilized without neovascularization. TC-INV/ANV was correlated with the amount of nonperfused retina (P = 0.0001) and extent of retinal hemorrhage (P = 0.03). Males were at higher risk than females for TC-INV/ANV (P = 0.01), as were patients with occlusions of less than one month duration (P = 0.01), Conclusions: Prophylactic PRP does not totally prevent TC-INV/ANV, and prompt regression of TC-INV/ANV in response to PRP is more likely to occur in eyes that have not been treated previously. The authors recommend careful observation with frequent follow-up examinations in the early months (including undilated slit-lamp examination of the iris and gonioscopy) and prompt PRP of eyes in which TC-INV/ANV develops. C1 JOHNS HOPKINS UNIV,WILMER OPHTHALMOL INST,BALTIMORE,MD 21218. ILLINOIS RETINA ASSOCIATES,HARVEY,IL. ILLINOIS RETINA ASSOCIATES,CHICAGO,IL. OREGON HLTH SCI UNIV,CASEY EYE INST,PORTLAND,OR 97201. RETINA ASSOCIATES,BOSTON,MA. CLIN OPHTALMOL,CRETEIL,FRANCE. UNIV WISCONSIN,MADISON,WI. CLEVELAND CLIN,CLEVELAND,OH 44106. RETINA ASSOCIATES,CLEVELAND,OH. TEXAS A&M UNIV,SCOTT & WHITE MEM HOSP,HLTH SCI CTR,CTR COORDINATING,TEMPLE,TX 76508. UNIV MIAMI,MCKNIGHT VIS RES CTR,CTR READING,CORAL GABLES,FL 33124. UNIV WISCONSIN,CTR ERG READING,MADISON,WI. NEI,BETHESDA,MD 20892. RP CLARKSON, JG (reprint author), UNIV MIAMI,BASCOM PALMER EYE INST,900 NW 17TH ST,MIAMI,FL 33136, USA. NR 5 TC 167 Z9 167 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1995 VL 102 IS 10 BP 1434 EP 1444 PG 11 WC Ophthalmology SC Ophthalmology GA RZ487 UT WOS:A1995RZ48700013 ER PT J AU IADAROLA, MJ MAX, MB BERMAN, KF BYASSMITH, MG COGHILL, RC GRACELY, RH BENNETT, GJ AF IADAROLA, MJ MAX, MB BERMAN, KF BYASSMITH, MG COGHILL, RC GRACELY, RH BENNETT, GJ TI UNILATERAL DECREASE IN THALAMIC ACTIVITY OBSERVED WITH POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH CHRONIC NEUROPATHIC PAIN SO PAIN LA English DT Article DE REGIONAL CEREBRAL BLOOD FLOW; REFLEX SYMPATHETIC DYSTROPHY; FUNCTIONAL BRAIN IMAGING; VENTROPOSTEROLATERAL THALAMUS; SOMATOSENSORY PROCESSING; NEUROPATHIC PAIN ID PARTIAL EPILEPSY; PERIPHERAL MONONEUROPATHY; VPM NUCLEUS; COMPARTMENTS; NECROSIS; MONKEYS; CORTEX; RATS AB The oxygen-15 water bolus positron emission tomography (PET) method was used to image regional brain activity in 4 patients with chronic post-traumatic neuropathic pain confined to one lower limb and in 1 patient with post-herpetic neuralgia. In comparison to 13 normal subjects, scans of the patients disclosed a statistically significant decrease in thalamic activity contralateral to the symptomatic side. Examination of the right/left ratio for all the subjects showed that the values for the patients fell at the extremes of the normal range, according to the side of the affected body part. These initial observations suggest that functional alterations in thalamic pain processing circuits may be an important component of chronic neuropathic pain. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. NR 34 TC 200 Z9 202 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 1995 VL 63 IS 1 BP 55 EP 64 DI 10.1016/0304-3959(95)00015-K PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA TA642 UT WOS:A1995TA64200008 PM 8577491 ER PT J AU MERICQ, V CASSORLA, F GARCIA, H AVILA, A BORIC, MA MERRIAM, G AF MERICQ, V CASSORLA, F GARCIA, H AVILA, A BORIC, MA MERRIAM, G TI EFFECT OF CHRONIC SOMATOSTATIN SUPPRESSION DURING TREATMENT WITH GH RELEASING-FACTOR (GHRH) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV CHILE,IDIMI,SANTIAGO,CHILE. NICHHD,DEB,BETHESDA,MD. RI Mericq, Veronica/F-3927-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 1995 VL 38 IS 4 BP 7 EP 7 PG 1 WC Pediatrics SC Pediatrics GA RV971 UT WOS:A1995RV97100031 ER PT J AU DOMENE, HM LEROITH, D ROBERTS, CT CASSORLA, F AF DOMENE, HM LEROITH, D ROBERTS, CT CASSORLA, F TI RAT GH RECEPTOR GH-BINDING PROTEIN MRNAA WITH DIVERGENT 5'-UNTRANSLATED REGIONS ARE EXPRESSED IN A TISSUE-SPECIFIC AND TRANSCRIPT-SPECIFIC MANNER SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NIDDK,DIABET BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 1995 VL 38 IS 4 BP 32 EP 32 PG 1 WC Pediatrics SC Pediatrics GA RV971 UT WOS:A1995RV97100056 ER PT J AU GAHL, WA INGELFINGER, J MOHAN, P BERNARDINI, I HYMAN, PE TANGERMAN, A AF GAHL, WA INGELFINGER, J MOHAN, P BERNARDINI, I HYMAN, PE TANGERMAN, A TI INTRAVENOUS CYSTEAMINE THERAPY FOR NEPHROPATHIC CYSTINOSIS SO PEDIATRIC RESEARCH LA English DT Article ID VOLATILE SULFUR-COMPOUNDS; GAS-CHROMATOGRAPHY; CHILDREN; INSUFFICIENCY; METHIONINE; TRANSPORT; FRACTIONS; PATIENT; PROTEIN; ADULT AB A 4-y-old boy with nephropathic cystinosis and gastrointestinal dysmotility of unknown etiology was treated with i.v. cysteamine over a period of 10 mo. Thirty minutes after a dose of 10 mg/kg cysteamine free base, the leukocyte cystine value had fallen from 11.9 to 4.9 nmol of half-cystine/mg of protein. When cysteamine was given every 6 h, the leukocyte cystine concentration, measured 5-7 h after a dose, decreased with increasing cysteamine doses up to 17 mg/kg; at this dose the cystine value was 1.1 nmol of half-cystine/mg of protein, or 9% of the untreated value. Oral administration of approximately 16 mg/kg per dose every 6 h to this patient over the previous 3 y achieved similar leukocyte cystine depletion, to 1.2 nmol of half-cystine/mg of protein. The plasma cysteamine concentration 30 min after a dose of 10 mg/kg was 71 mu M; 5-7 after a dose of up to 20 mg/kg, the concentration was below 5 mu M. Dimethylsulfide was elevated in the breath and urine of this boy after, but not before, the initiation of i.v. cysteamine therapy. Ten months after the start of therapy, the patient tolerated 250 mg (14 mg/kg) every 8 h. Adverse effects of this treatment included lethargy and increased nausea and vomiting when a schedule of therapy every 6 h was attempted. This investigation demonstrates that cysteamine given through a central venous catheter is effective in reducing leukocyte cystine levels. C1 CHILDRENS NATL MED CTR,DIV GASTROENTEROL & NUTR,WASHINGTON,DC 20010. CHILDRENS HOSP ORANGE CTY,DEPT PEDIAT GASTROENTEROL,ORANGE,CA 92668. UNIV NIJMEGEN HOSP,DIV GASTROINTESTINAL & LIVER DIS,6500 HB NIJMEGEN,NETHERLANDS. MASSACHUSETTS GEN HOSP,DEPT NEPHROL,BOSTON,MA 02115. RP GAHL, WA (reprint author), NICHHD,HUMAN BIOCHEM GENET SECT,BLDG 10,ROOM 9S-242,BETHESDA,MD 20892, USA. NR 41 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 1995 VL 38 IS 4 BP 579 EP 584 DI 10.1203/00006450-199510000-00018 PG 6 WC Pediatrics SC Pediatrics GA RV971 UT WOS:A1995RV97100018 PM 8559613 ER PT J AU ROSENTHAL, DI DOPPELT, SH MANKIN, HJ DAMBROSIA, JM XAVIER, RJ MCKUSICK, KA ROSEN, BR BAKER, J NIKLASON, LT HILL, SC MILLER, SPF BRADY, RO BARTON, NW AF ROSENTHAL, DI DOPPELT, SH MANKIN, HJ DAMBROSIA, JM XAVIER, RJ MCKUSICK, KA ROSEN, BR BAKER, J NIKLASON, LT HILL, SC MILLER, SPF BRADY, RO BARTON, NW TI ENZYME REPLACEMENT THERAPY FOR GAUCHER DISEASE - SKELETAL RESPONSES TO MACROPHAGE-TARGETED GLUCOCEREBROSIDASE SO PEDIATRICS LA English DT Article DE GAUCHER DISEASE; ENZYME REPLACEMENT THERAPY; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; BONE MARROW; COMBINED CORTICAL THICKNESS; TRABECULAR BONE DENSITY ID BONE-MARROW; CELLS; OSTEOPOROSIS; DEFICIENCY; PATIENT; WOMEN; CT AB Objectives. Reversal of the hematologic and Visceral abnormalities characteristic of Gaucher disease, the most common lipid storage disorder, with biweekly infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well documented. The extent to which the skeleton responds to enzyme replacement therapy has not been systematically investigated. Methods. To assess the skeletal response to enzyme replacement therapy, we treated 12 patients with type 1 Gaucher disease, who had intact spleens, with macrophage-targeted glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2 weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body weight every 2 weeks, each for 9 months. Results. The lipid composition of bone marrow, determined by direct chemical analysis, began to improve after 6 months of treatment at a time when noninvasive imaging studies showed no significant changes. By 42 months, improvement in marrow composition was demonstrable on all noninvasive, quantitative imaging modalities (magnetic resonance score, quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in this study. Quantitative chemical shift imaging, the most sensitive technique, demonstrated a dramatic normalization of the marrow fat content in all patients. Net increases in either cortical or trabecular bone mass, as assessed by combined cortical thickness measurements and dual-energy quantitative computed tomography, respectively, occurred in 10 patients. Conclusions. Prolonged treatment over 31/2 years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked mass in both children and adults. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP ROSENTHAL, DI (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,WHITE 289,BOSTON,MA 02114, USA. NR 48 TC 154 Z9 158 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 OCT PY 1995 VL 96 IS 4 BP 629 EP 637 PN 1 PG 9 WC Pediatrics SC Pediatrics GA RY677 UT WOS:A1995RY67700005 PM 7567322 ER PT J AU CATZ, C HANSON, JW SIMPSON, L YAFFE, SJ AF CATZ, C HANSON, JW SIMPSON, L YAFFE, SJ TI SUMMARY OF WORKSHOP - EARLY DISCHARGE AND NEONATAL HYPERBILIRUBINEMIA SO PEDIATRICS LA English DT Article C1 NICHHD,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892. US DEPT HHS,AGCY HLTH CARE POLICY & RES,ROCKVILLE,MD 20852. NR 15 TC 48 Z9 50 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 OCT PY 1995 VL 96 IS 4 BP 743 EP 745 PN 1 PG 3 WC Pediatrics SC Pediatrics GA RY677 UT WOS:A1995RY67700025 PM 7567342 ER PT J AU OH, W BLACKMON, LR ESCOBEDO, M FANAROFF, AA FERNBACH, SA KIRKPATRICK, BV LIGHT, IJ SHOEMAKER, CT CONNER, GK MARTIN, JN MCMILLAN, DD ROWLEY, D WRIGHT, LL LANGER, JC BAILEY, EN GARTNER, LM MOLTENI, RA AF OH, W BLACKMON, LR ESCOBEDO, M FANAROFF, AA FERNBACH, SA KIRKPATRICK, BV LIGHT, IJ SHOEMAKER, CT CONNER, GK MARTIN, JN MCMILLAN, DD ROWLEY, D WRIGHT, LL LANGER, JC BAILEY, EN GARTNER, LM MOLTENI, RA TI HOSPITAL STAY FOR HEALTHY TERM NEWBORNS - COMMITTEE ON FETUS AND NEWBORN SO PEDIATRICS LA English DT Editorial Material ID DISCHARGE; POPULATION; HOME C1 AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NICHHD,BETHESDA,MD 20892. NR 28 TC 88 Z9 93 U1 2 U2 2 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 OCT PY 1995 VL 96 IS 4 BP 788 EP 790 PN 1 PG 3 WC Pediatrics SC Pediatrics GA RY677 UT WOS:A1995RY67700034 ER PT J AU VOGEL, SS BEUSHAUSEN, S LESTER, DS AF VOGEL, SS BEUSHAUSEN, S LESTER, DS TI APPLICATION OF A MEMBRANE-FUSION ASSAY FOR RAPID DRUG SCREENING SO PHARMACEUTICAL RESEARCH LA English DT Article DE DRUG SCREENING; SECRETION; TAMOXIFEN; TAXOL; SEA URCHIN ID SEA-URCHIN EGGS; CALCIUM-TRIGGERED FUSION; PLASMA-MEMBRANE; CORTICAL GRANULES; EXOCYTOSIS; TAXOL; INVITRO; VESICLES; PROTEINS; FERTILIZATION AB Purpose. The purpose of this study is to develop an in vitro assay for screening drug and their effects on membrane fusion and lysis of intracellular organelles. Methods. A 96-well microtiter-dish turbidimetric assay using membrane components of the eggs of sea urchins, a marine invertebrate, was applied to monitor granule fusion and/or lysis: Results. Of 18 drugs screened, 16 had no effect. One antineoplastic drug, tamoxifen, disrupted intracellular membranes in a calcium independent manner. Taxol, another antineoplastic drug, specifically inhibited calcium triggered exocytosis. Conclusions. This assay is inexpensive, simple, rapid, and does not require the sacrifice of animal life. It has the potential to identify drugs that are membrane active, as well as those which specifically perturb events involved in the secretion process. C1 NINCDS,NEUROBIOL LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,LAUREL,MD 20708. RP VOGEL, SS (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 10D-09,BETHESDA,MD 20892, USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 25 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD OCT PY 1995 VL 12 IS 10 BP 1417 EP 1422 DI 10.1023/A:1016258615076 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA RZ474 UT WOS:A1995RZ47400004 PM 8584473 ER PT J AU BROSEN, K DEMORAIS, SMF MEYER, UA GOLDSTEIN, JA AF BROSEN, K DEMORAIS, SMF MEYER, UA GOLDSTEIN, JA TI A MULTIFAMILY STUDY ON THE RELATIONSHIP BETWEEN CYP2C19 GENOTYPE AND S-MEPHENYTOIN OXIDATION PHENOTYPE SO PHARMACOGENETICS LA English DT Article DE S-MEPHENYTOIN; CYP2C19; GENETIC POLYMORPHISM; DRUG OXIDATION; FAMILY STUDY; GENOTYPE ID HYDROXYLATION DEFICIENCY; GENETIC POLYMORPHISMS; SPARTEINE; DEBRISOQUIN; METABOLISM; POPULATIONS; CAUCASIANS; JAPANESE AB It has recently been shown that the most common mutation (named m1) in both Caucasian and Japanese poor metabolizers (PM) of S-mephenytoin is a single base pair mutation (G-->A) in exon 5 of the CYP2C19 gene. In Japanese, a second defective allele of CYP2C19 named m2 consists of a G-->A mutation in exon 4. In the present study, we have investigated the inheritance of the CYP2C19 wild type allele (wt) and the two defective alleles (mi and m2) in families of 11 Danish PM probands, The study was carried out for two principal reasons, First, we wanted to confirm the autosomal recessive inheritance of the defective alleles, and second, we wanted to examine the specificity and sensitivity of the CYP2C19 genotyping test, Individuals were phenotyped by measuring the ratio of S/R mephenytoin excreted in the urine after administration of mephenytoin, and genotyping was carried out by a PCR-based DNA amplification procedure. The genotypes of nine of the 11 probands were consistent with their phenotypes. Eight were homozygous m1/m1, and one was heterozygous m1/m2. The genotypes of two putative PM probands (wt/m1) were not consistent with their phenotypes. On the basis of extended phenotyping (additional late urine collections (24-36 h) and acidification of urine), one of these could probably be reclassified as an extensive metabolizer (EM) while the other was considered to be a true PM. This suggests the presence of an additional unknown mutant allele in the latter, Seven of the 41 phenotyped relatives in the 11 families were phenotyped as PMs, and with the exception of the father of family 10, their genotypes (m1/m1) were consistent with their phenotypes, Extended phenotyping (acidification of urine) suggested that the father of family 10 in fact is an EM and hence that his genotype (wt/m1) is concordant with his phenotype. Thus, the specificity of genotyping tests for PM was 100%, while the sensitivity was 15/16 or 94%. Our study provides unequivocal evidence for autosomal recessive inheritance of the PM trait. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV BASEL,BIOZENTRUM,DEPT PHARMACOL,CH-4056 BASEL,SWITZERLAND. RP BROSEN, K (reprint author), ODENSE UNIV,INST MED BIOL,DEPT CLIN PHARMACOL,WINSLOWPARKEN 19,DK-5000 ODENSE C,DENMARK. RI Goldstein, Joyce/A-6681-2012; Brosen, Kim/F-6023-2011 OI Brosen, Kim/0000-0001-8444-7835 NR 28 TC 66 Z9 67 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1995 VL 5 IS 5 BP 312 EP 317 DI 10.1097/00008571-199510000-00007 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA TB999 UT WOS:A1995TB99900007 PM 8563772 ER PT J AU MCCUTCHEN, CW AF MCCUTCHEN, CW TI PHOTON TUNNELING GOES BACK IN TIME SO PHYSICS TODAY LA English DT Letter ID MICROSCOPY; SURFACES RP MCCUTCHEN, CW (reprint author), NATL INST HLTH,BETHESDA,MD, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0031-9228 J9 PHYS TODAY JI Phys. Today PD OCT PY 1995 VL 48 IS 10 BP 104 EP 104 DI 10.1063/1.2808232 PG 1 WC Physics, Multidisciplinary SC Physics GA RY678 UT WOS:A1995RY67800031 ER PT J AU Gahl, WA Potterf, B DurhamPierre, D Brilliant, MH Hearing, VJ AF Gahl, WA Potterf, B DurhamPierre, D Brilliant, MH Hearing, VJ TI Melanosomal tyrosine transport in normal and pink-eyed dilution murine melanocytes SO PIGMENT CELL RESEARCH LA English DT Article DE pink-eyed dilution; melanogenesis; tyrosine transport; melanosome; melanocyte ID OCULOCUTANEOUS ALBINISM; MOUSE; LOCUS; GENE; ACID AB Tyrosine is the endogenous substrate for melanin production within melanosomes, but the method of tyrosine transport into the melanosome has not been investigated. In the mouse, melanogenesis is disrupted by mutations in the p gene resulting in the pink-eyed dilution phenotype; it has been suggested that the p gene codes for a tyrosine transport protein. We determined that normal (melan-a) melanosome-rich granular fractions take up 10 mu m [H-3]tyrosine at 21.1 +/- 6.1 (SEM, standard error of the mean) pmol/min/ mg protein (N=7) compared with 21.3 +/- 5.8 SEM pmol/min/mg protein (N=5) for pink-eyed dilution, whose plasma membrane tyrosine transport was also normal (K-m 89 mu M; V-max 302 pmol/min/mg cell protein). We also demonstrated that pink-eyed dilution melanosomes are immature by virtue of their low density, high hexosaminidase activity, and lack of pigment. These data indicate that a tyrosine transport system exists in the melanosomal membrane and that the p gene does not encode a tyrosine transporter of critical importance. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. RP Gahl, WA (reprint author), NICHHD,HUMAN GENET BRANCH,SECT HUMAN BIOCHEM GENET,BLDG 10,ROOM 9S-241,10 CTR DR MSC 1830,BETHESDA,MD 20892, USA. NR 24 TC 41 Z9 42 U1 0 U2 3 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 OCT PY 1995 VL 8 IS 5 BP 229 EP 233 DI 10.1111/j.1600-0749.1995.tb00668.x PG 5 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA TN310 UT WOS:A1995TN31000001 PM 8789196 ER PT J AU CHEN, PS AF CHEN, PS TI INTRODUCTORY-REMARKS SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Editorial Material RP CHEN, PS (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD OCT PY 1995 VL 210 IS 1 BP 83 EP 84 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RV747 UT WOS:A1995RV74700014 ER PT J AU Fischer, D Tsai, CJ Nussinov, R Wolfson, H AF Fischer, D Tsai, CJ Nussinov, R Wolfson, H TI A 3D sequence-independent representation of the protein data bank SO PROTEIN ENGINEERING LA English DT Article DE geometric hashing; non-redundant dataset of protein structures; protein structural classification; protein structure comparison; sequence-order dependence; sequence-structure relationship ID 3-DIMENSIONAL STRUCTURAL MOTIFS; GRAPH-THEORETICAL TECHNIQUES; VISION-BASED TECHNIQUE; BETA-BARREL; CRYSTAL-STRUCTURE; COMMON; FOLD; RESEMBLANCE; ALIGNMENT; BINDING AB Here we address the following questions, How many structurally different entries are there in the Protein Data Bank (PDB)? How do the proteins populate the structural universe? To investigate these questions a structurally nonredundant set of representative entries was selected from the PDB, Construction of such a dataset is not trivial: (i) the considerable size of the PDB requires a large number of comparisons (there were more than 3250 structures of protein chains available in May 1994); (ii) the PDB is highly redundant, containing many structurally similar entries, not necessarily with significant sequence homology, and (iii) there is no clear-cut definition of structural similarity, The latter depend on the criteria and methods used, Here, we analyze structural similarity ignoring protein topology. To date, representative sets have been selected either by hand, by sequence comparison techniques which ignore the three-dimensional (3D) structures of the proteins or by using sequence comparisons followed by linear structural comparison (i.e., the topology, or the sequential order of the chains, is enforced in the structural comparison), Here we describe a 3D sequence-independent automated and efficient method to obtain a representative set of protein molecules from the PDB which contains all unique structures and which is structurally non-redundant. The method has two novel features, The first is the use of strictly structural criteria in the selection process without taking into account the sequence information, To this end we employ a fast structural comparison algorithm which requires on average similar to 2 s per pairwise comparison on a workstation, The second novel feature is the iterative application of a heuristic clustering algorithm that greatly reduces the number of comparisons required, We obtain a representative set of 220 chains with resolution better than 3.0 Angstrom, or 268 chains including lower resolution entries, NMR entries and models, The resulting set can serve as a basis for extensive structural classification and studies of 3D recurring motifs and of sequence-structure relationships, The clustering algorithm succeeds in classifying into the same structural family chains with no significant sequence homology, e.g. all the globins in one single group, all the trypsin-like serine proteases in another or all the immunoglobulin-like folds into a third, In addition, unexpected structural similarities of interest have been automatically detected between pairs of chains, A cluster analysis of the representative structures demonstrates the way the 'structural universe' is populated. C1 TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,PRI DYNCORP,FREDERICK,MD 21702. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 66 TC 48 Z9 48 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD OCT PY 1995 VL 8 IS 10 BP 981 EP 997 DI 10.1093/protein/8.10.981 PG 17 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA TN009 UT WOS:A1995TN00900002 PM 8771179 ER PT J AU SMITH, MBK ROUZER, CA TANEYHILL, LA SMITH, NA HUGHES, SH BOYER, PL JANSSEN, PAJ MOEREELS, H KOYMANS, L ARNOLD, E DING, JP DAS, K ZHANG, WY MICHEJDA, CJ SMITH, RH AF SMITH, MBK ROUZER, CA TANEYHILL, LA SMITH, NA HUGHES, SH BOYER, PL JANSSEN, PAJ MOEREELS, H KOYMANS, L ARNOLD, E DING, JP DAS, K ZHANG, WY MICHEJDA, CJ SMITH, RH TI MOLECULAR MODELING STUDIES OF HIV-1 REVERSE-TRANSCRIPTASE NONNUCLEOSIDE INHIBITORS - TOTAL-ENERGY OF COMPLEXATION AS A PREDICTOR OF DRUG PLACEMENT AND ACTIVITY SO PROTEIN SCIENCE LA English DT Article DE AIDS; BINDING ENERGY; BINDING POCKET; DRUG-PROTEIN INTERACTION; HIV-1 REVERSE TRANSCRIPTASE; MOLECULAR MODELING; NONNUCLEOSIDE INHIBITORS ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID SUBSTITUTIONS; PI-PI-INTERACTIONS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; TYPE-1; RESISTANCE; DERIVATIVES; PROTEINS; REPLICATION AB Computer modeling studies have been carried out on three nonnucleoside inhibitors complexed with human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), using crystal coordinate data from a subset of the protein surrounding the binding pocket region. Results from the minimizations of solvated complexes of 2-cyclopropyl-4-methyl-5,11-dihydro-5H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (nevirapine), alpha-anilino-2, 6-dibromophenylacetamide (alpha-APA), and 8-chloro-tetrahydro-imidazo (4,5,1-jk)(1,4)-benzodiazepin-2(1H)-thione (TIBO) show that all three inhibitors maintain a very similar conformational shape, roughly overlay each other in the binding pocket, and appear to function as pi-electron donors to aromatic side-chain residues surrounding the pocket. However, side-chain residues adapt to each bound inhibitor in a highly specific manner, closing down around the surface of the drug to make tight van der Waals contacts. Consequently, the results from the calculated minimizations reveal that only when the inhibitors are modeled in a site constructed from coordinate data obtained from their particular RT complex can the calculated binding energies be relied upon to predict the correct orientation of the drug in the pocket. In the correct site, these binding energies correlate with EC(50) values determined for all three inhibitors in our laboratory. Analysis of the components of the binding energy reveals that, for all three inhibitors, solvation of the drug is endothermic, but solvation of the protein is exothermic, and the sum favors complex formation. In general, the protein is energetically more stable and the drug less stable in their complexes as compared to the reactant conformations. For all three inhibitors, interaction with the protein in the complex is highly favorable. Interactions of the inhibitors with individual residues correlate with crystallographic and site-specific mutational data. pi-Stacking interactions are important in binding and correlate with drug HOMO RHF/6-31G* energies. Modeling results are discussed with respect to the mechanism of complex formation and the design of nonnucleoside inhibitors that will be more effective against mutants of HIV-1 RT that are resistant to the currently available drugs. C1 WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. RP SMITH, MBK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. RI Taneyhill, Lisa/K-1815-2013 NR 54 TC 33 Z9 34 U1 0 U2 0 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 OCT PY 1995 VL 4 IS 10 BP 2203 EP 2222 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RZ766 UT WOS:A1995RZ76600026 ER PT J AU MARSHALL, RD KLEIN, DF AF MARSHALL, RD KLEIN, DF TI PHARMACOTHERAPY IN THE TREATMENT OF POSTTRAUMATIC-STRESS-DISORDER SO PSYCHIATRIC ANNALS LA English DT Article ID POST-TRAUMATIC STRESS; ANXIETY DISORDERS; PANIC DISORDER; PHYSICAL ABUSE; LIFE EVENTS; DEPRESSION; HISTORIES; SYMPTOMS; PTSD; DISSOCIATION C1 COLUMBIA UNIV,NEW YORK STATE PSYCHIAT ASSOC,NIMH,PROGRAM AFFECT & ANXIETY DISORDERS,NEW YORK,NY 10027. AMER SOC CLIN PSYCHOPHARMACOL,NEW YORK,NY. RP MARSHALL, RD (reprint author), NEW YORK STATE PSYCHIAT INST & HOSP,ANXIETY DISORDERS CLIN,UNIT 13,722 W 168TH ST,NEW YORK,NY 10032, USA. NR 65 TC 6 Z9 6 U1 3 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 1995 VL 25 IS 10 BP 588 EP & PG 0 WC Psychiatry SC Psychiatry GA RZ921 UT WOS:A1995RZ92100001 ER PT J AU MAZZOLAPOMIETTO, P AULAKH, CS MURPHY, DL AF MAZZOLAPOMIETTO, P AULAKH, CS MURPHY, DL TI TEMPERATURE, FOOD-INTAKE, AND LOCOMOTOR-ACTIVITY EFFECTS OF A 5-HT3 RECEPTOR AGONIST AND 2 5-HT3 RECEPTOR ANTAGONISTS IN RATS SO PSYCHOPHARMACOLOGY LA English DT Article DE 1-M-CHLOROPHENYLBIGUANIDE; MDL-72222; ONDANSETRON; TEMPERATURE; FOOD INTAKE; LOCOMOTOR ACTIVITY ID SEROTONIN RECEPTOR; RADIOLIGAND BINDING; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; ACTIVATION; SUBTYPE; EXPRESSION; RESPONSES; CLONING; SYSTEM AB This study investigated three physiologic functions known to be modulated by serotonin - temper ature, food intake and locomotor activity - using the 5-HT3 receptor agonist, m-chlorophenylbiguanide (m-CPBG), and two 5-HT3 antagonists, MDL-72222 and ondansetron. m-CPBG produced dose-dependent elevations in rectal temperature. MDL-72222, which had no effects on temperature when given alone, significantly attenuated m-CPBG-induced hyperthermia. Food intake in food-deprived rats was reduced during the first hour by the highest dose of m-CPBG. Food intake was also dose-dependently reduced by MDL-72222; m-CPBG plus MDL-72222 led to greater reductions in food intake. Food intake in freely fed rats was unaffected by m-CPBG or MDL-72222. Locomotor activity was unaffected by m-CPBG, but was dose-dependently reduced by MDL-72222, an effect which may have contributed to its hypophagic effects. Ondansetron, used in ten-fold lower doses than MDL-72222, was inactive in all of these paradigms. These data: (1) provide some evidence for 5-HT3 receptor-mediated changes in temperature; (2) are in agreement with two prior studies which reported locomotor activity reductions following 5-HT3 antagonists; but (3) do nor support an important role for 5-HT, receptors in the regulation of food intake in rats. RP MAZZOLAPOMIETTO, P (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D41,BETHESDA,MD 20892, USA. NR 48 TC 27 Z9 28 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1995 VL 121 IS 4 BP 488 EP 493 DI 10.1007/BF02246499 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TG132 UT WOS:A1995TG13200011 PM 8619014 ER PT J AU BLAIR, A BURG, J FORAN, J GIBB, H GREENLAND, S MORRIS, R RAABE, G SAVITZ, D TETA, J WARTENBERG, D WONG, O ZIMMERMAN, R AF BLAIR, A BURG, J FORAN, J GIBB, H GREENLAND, S MORRIS, R RAABE, G SAVITZ, D TETA, J WARTENBERG, D WONG, O ZIMMERMAN, R TI GUIDELINES FOR APPLICATION OF METAANALYSIS IN ENVIRONMENTAL EPIDEMIOLOGY SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID FORMALDEHYDE EXPOSURE; CANCER; METAANALYSIS; FARMERS; BIAS; RISK AB The use of meta-analysis in environmental epidemiology can enhance the value of epidemiologic data in debates about environmental health risks. Meta-analysis may be particularly useful to formally examine sources of heterogeneity, to clarify the relationship between environmental exposures and health effects, and to generate information beyond that provided by individual studies or a narrative review. However, meta-analysis may not be useful when the relationship between exposure and disease is obvious, when there are only a few studies of the key health outcomes, or when there is substantial confounding or other biases which cannot be adjusted for in the analysis. Recent increases in the use of meta-analysis in environmental epidemiology have highlighted the need for guidelines for the application of the technique, Guidelines, in the form of desirable and undesirable attributes, are presented in this paper for various components of a metaanalysis including study identification and selection; data extraction and analysis; and interpretation, presentation, and communication of results, Also discussed are the appropriateness of the use of meta-analysis in environmental health studies and when metaanalysis should or should not be used. (C) 1995 Academic Press, Inc C1 ILSI,RSI,WASHINGTON,DC 20037. AGCY TOX SUBST DIS REGISTRY,ATLANTA,GA. NCI,BETHESDA,MD 20892. US EPA,WASHINGTON,DC 20460. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. MED COLL WISCONSIN,MILWAUKEE,WI 53226. MOBIL OIL CORP,PRINCETON,NJ 08540. UNIV N CAROLINA,CHAPEL HILL,NC 27515. UNION CARBIDE CORP,DANBURY,CT. ENVIRONM & OCCUPAT HLTH SCI INST,PISCATAWAY,NJ. APPL HLTH SCI,SAN MATEO,CA. NYU,NEW YORK,NY 10012. NR 32 TC 68 Z9 68 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 1995 VL 22 IS 2 BP 189 EP 197 DI 10.1006/rtph.1995.1084 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA TC391 UT WOS:A1995TC39100010 PM 8577954 ER PT J AU SINAI, AP HAYES, SF SMALL, PLC BAVOIL, PM AF SINAI, AP HAYES, SF SMALL, PLC BAVOIL, PM TI LOW-EFFICIENCY (MACRO-)PINOCYTIC INTERNALIZATION OF NONPATHOGENIC ESCHERICHIA-COLI INTO HEP-2 CELLS SO RESEARCH IN MICROBIOLOGY LA English DT Article DE ENDOCYTOSIS, MACROPINOCYTOSIS, MICROTUBULE, ESCHERICHIA COLI; ENDOSOMES, CYTOSKELETON ID EPIDERMAL GROWTH-FACTOR; RECEPTOR-MEDIATED ENDOCYTOSIS; TYROSINE KINASE-ACTIVITY; CULTURED ANIMAL-CELLS; CHLAMYDIA-TRACHOMATIS; SIGNAL TRANSDUCTION; PROTEIN-KINASE; BREFELDIN-A; ORGANELLE STRUCTURE; ADENYLATE-CYCLASE AB HEp-2 cells internalize non-pathogenic Escherichia coli bacteria by a low-efficiency internalization mechanism which is upregulated in Pho-derepressed strains (as shown by Sinai and Bavoil in 1993), and is independent of microfilament integrity but requires functional microtubules. Here, we further characterize the microtubule requirement of this pathway using various effecters of microtubule integrity and function. Furthermore, we show that internalization is enhanced upon treatment with monodansylcadaverine, a specific inhibitor of receptor mediated endocytosis, and is insensitive to brefeldin A,which promotes the microtubule-dependent reorganization of the endosome. An assay system is also described to directly evaluate the contribution of pinocytosis to this pathway based on the ability of the bacteria to cointernalize and consequently colocalize with the fluid-phase marker, Texas-red-conjugated dextran (TRD). Using this assay, Hoescht-stained bacteria were observed in TRD-containing vesicles in numbers that are consistent with their observed internalization rate. Overall, these data are strongly supportive of the existence of a low-efficiency macropinocytic mechanism of entry for these non-pathogenic bacteria. Moreover, the observed requirements for host tyrosine kinase and protein kinase C activities suggest that it is inducible. C1 UNIV ROCHESTER,MED CTR,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642. NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. FU NIAID NIH HHS [AI01057, AI26216, AI26280] NR 70 TC 1 Z9 1 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD OCT PY 1995 VL 146 IS 8 BP 617 EP 631 DI 10.1016/0923-2508(96)81060-6 PG 15 WC Microbiology SC Microbiology GA TF567 UT WOS:A1995TF56700002 PM 8584786 ER PT J AU WATKINS, BA DAVIS, AE FIORENTINI, S REITZ, MS AF WATKINS, BA DAVIS, AE FIORENTINI, S REITZ, MS TI V-REGION AND CLASS-SPECIFIC RT-PCR AMPLIFICATION OF HUMAN-IMMUNOGLOBULIN HEAVY AND LIGHT-CHAIN GENES FROM B-CELL LINES SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID OLIGONUCLEOTIDE PROBES; VARIABLE REGION; PHAGE SURFACES; REPERTOIRE; SEQUENCES; SEGMENTS; LAMBDA; GENERATION; LIBRARIES; CLONING AB We have designed and tested primers that amplify complete human kappa and lambda light chain genes, and human Fd fragments from gamma, mu and alpha heavy chain genes. These primers were tested for efficiency and specificity on monoclonal sources of human immunoglobulin RNA, obtained from human B-cell lines of known immunoglobulin gene expression, Analysis of the sequences derived from these B-cells confirms the specificity of the PCR primers and the extent of somatic mutation seen in different B-cell malignancies supports existing concepts for differing aetiologies in the tumours concerned. RP WATKINS, BA (reprint author), NCI,TUMOR CELL BIOL LAB,ROOM 6A11,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 29 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD OCT PY 1995 VL 42 IS 4 BP 442 EP 448 DI 10.1111/j.1365-3083.1995.tb03678.x PG 7 WC Immunology SC Immunology GA RY704 UT WOS:A1995RY70400006 PM 7569777 ER PT J AU GOLDBERG, TE WEINBERGER, DR AF GOLDBERG, TE WEINBERGER, DR TI A CASE AGAINST SUBTYPING IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE SUBTYPING; COGNITION; SYMPTOM; (SCHIZOPHRENIA) ID MONOZYGOTIC TWINS DISCORDANT; VENTRICULAR SIZE; ABNORMALITIES; PERFORMANCE; PET AB In this paper we consider the generally accepted view that schizophrenia is 'heterogeneous'. We point out that the view derives from prima facie evidence from clinical presentation, studies of course, and factor analysis. However, upon closer examination internal contradictions are apparent, e.g., subtypes change, different groupings of symptoms cooccur in the same individual. Another type of paradigm, depending on careful study of case controls (e.g., monozygotic twins discordant for schizophrenia) and distributions, indicates that abnormalities in neurocognition, regional cerebral blood flow, and regional neuroanatomy may be present in nearly every patient, irrespective of absolute level or diagnostic subtype. These results suggest that a simple model in which patients vary along a severity dimension might parsimoniously explain much of the variance. Thus, while it is possible and even probable that schizophrenia may have many etiologies, phenocopies may represent the expression of a unitary pathogenesis of greater or lesser impact. C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 39 TC 33 Z9 33 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 1995 VL 17 IS 2 BP 147 EP 152 DI 10.1016/0920-9964(95)00060-Y PG 6 WC Psychiatry SC Psychiatry GA TE002 UT WOS:A1995TE00200003 PM 8562489 ER PT J AU FITZGERALD, D AF FITZGERALD, D TI THERAPY TARGETED TO SURFACE-ANTIGENS AND RECEPTORS .1. INTRODUCTION SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material RP FITZGERALD, D (reprint author), NCI,MOLEC BIOL LAB,BLDG 37,4B-03,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD OCT PY 1995 VL 6 IS 5 BP 257 EP 257 DI 10.1006/scbi.1995.0033 PG 1 WC Oncology SC Oncology GA TE297 UT WOS:A1995TE29700001 ER PT J AU KREITMAN, RJ PASTAN, I AF KREITMAN, RJ PASTAN, I TI TARGETING PSEUDOMONAS EXOTOXIN TO HEMATOLOGIC MALIGNANCIES SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE IMMUNOTOXIN; INTERLEUKIN; FV; LEUKEMIA; LYMPHOMA ID T-CELL LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; BETA-CHAIN P70-75; INTERLEUKIN-2 RECEPTOR; RECOMBINANT IMMUNOTOXIN; MONOCLONAL-ANTIBODY; GROWTH-FACTOR; DIPHTHERIA-TOXIN; VARIABLE DOMAINS; TAC ANTIGEN AB Malignant cells of hematopoietic origin often express a variety of different growth factor receptors and antigens on their surface, at levels much higher than normal cells. These malignant cells can be selectively Pseudomonas exotoxin (PE) derivatives interleukins 2, 4 and 6, and by FV fragments of monoclonal antibodies to interleukin 2 receptor (IL2R) subunits, CD22 and other antigens present on these cells. Anti-Tac(Fv)-PE38, a single-chain recombinant immunotoxin which targets cells bearing the IL2R alpha, is furthest along in preclinical development and is being prepared for clinical testing in patients with IL2R alpha-positive leukemia, lymphoma and Hodgkin's disease. (C) Academic Press Ltd RP KREITMAN, RJ (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,37-4E16,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 54 TC 51 Z9 52 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD OCT PY 1995 VL 6 IS 5 BP 297 EP 306 DI 10.1006/scbi.1995.0038 PG 10 WC Oncology SC Oncology GA TE297 UT WOS:A1995TE29700006 PM 8562907 ER PT J AU JOHNSTON, PG ALLEGRA, CJ AF JOHNSTON, PG ALLEGRA, CJ TI COLORECTAL-CANCER BIOLOGY - CLINICAL IMPLICATIONS SO SEMINARS IN ONCOLOGY LA English DT Review ID LARGE-BOWEL CARCINOMA; CARCINOEMBRYONIC ANTIGEN CEA; RAS GENE-MUTATIONS; HUMAN-COLON CANCER; PROGNOSTIC-SIGNIFICANCE; THYMIDYLATE SYNTHASE; PROLIFERATIVE ACTIVITY; ADJUVANT THERAPY; DNA ANEUPLOIDY; SIALOSYL-TN RP JOHNSTON, PG (reprint author), NCI,NATL NAVAL MED CTR,MED ONCOL BRANCH,8901 WISCONSIN AVE,BLDG 8,RM 5101,BETHESDA,MD 20889, USA. NR 112 TC 27 Z9 27 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 OCT PY 1995 VL 22 IS 5 BP 418 EP 432 PG 15 WC Oncology SC Oncology GA RZ178 UT WOS:A1995RZ17800003 PM 7570055 ER PT J AU BROWN, KE OSULLIVAN, MG YOUNG, NS AF BROWN, KE OSULLIVAN, MG YOUNG, NS TI SIMIAN PARVOVIRUS SO SEMINARS IN VIROLOGY LA English DT Review DE PARVOVIRUS INFECTIONS; ERYTHROVIRUS; PRIMATE INFECTIONS; PARVOVIRIDAE; HAPLORINAE; BONE MARROW ID B19 PARVOVIRUS; INFECTION; GENOME; ANEMIA AB Parvovirus B19 is currently the only member of the Erythrovirus genus. Recently a second parvovirus, simian parvovirus, was identified in cynomolgus monkeys which also appeared to be highly tropic for erythroid progenitor cells. This review describes the identification of this new arrival parvovirus and summarizes current knowledge of its clinical, molecular and epidemiological features. The virus has many biological similarities to the parvovirus B19 and close homology to the B19 genome at the molecular level, both of which justify the inclusion of this novel virus as a new member of the Erythrovirus genus. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27103. RP BROWN, KE (reprint author), NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD OCT PY 1995 VL 6 IS 5 BP 339 EP 346 DI 10.1006/smvy.1995.0040 PG 8 WC Virology SC Virology GA TF654 UT WOS:A1995TF65400009 ER PT J AU NETTO, EJ PETERSON, JI MCSHANE, M HAMPSHIRE, V AF NETTO, EJ PETERSON, JI MCSHANE, M HAMPSHIRE, V TI A FIBEROPTIC BROAD-RANGE PH SENSOR SYSTEM FOR GASTRIC MEASUREMENTS SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article; Proceedings Paper CT 2nd European Conference on Optical Chemical Sensors and Biosensors (EUROPT(R)ODE II) CY APR 19-21, 1994 CL FLORENCE, ITALY DE FIBER OPTICS; PH SENSORS; GASTRIC MEASUREMENTS ID HIGH ACIDITIES AB The construction and performance of a fiber-optic broad-range pH sensor system are described. The general construction of the sensor is similar to the original fiber-optic pH sensor, but two dyes with three pH values have been immobilized to provide resonse over the pH range of 0.5-7 with a precision better than 0.1 pH unit. The range extends to pH 9 with less precision. The primary objective of the design is for gastric measurements. The system is based on absorbance dyes bound to polyacrylamide gel containing light-scattering particles. The sensor is constructed on a single 0.25-mm diameter plastic optical fiber. The optical system consists of a tungsten lamp, fiber-optic splitter and CCD/grating detector connected to a computer for spectral analysis, using two wavelength regions. The computer displays the pH graphically over 24 h. The system shows stability within 0.2 pH unit over 24 h, and has been tested with gastric samples in a dog. C1 NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,NCRR,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP NETTO, EJ (reprint author), FED CTR TECHNOL EDUC PARANA,AV SETE SETEMBRO 3165,BR-8023090 CURITIBA,PARANA,BRAZIL. RI McShane, Mike/D-3489-2009 OI McShane, Mike/0000-0001-6838-3982 NR 13 TC 21 Z9 21 U1 0 U2 5 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD OCT PY 1995 VL 29 IS 1-3 BP 157 EP 163 DI 10.1016/0925-4005(95)01677-5 PG 7 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA TD753 UT WOS:A1995TD75300023 ER PT J AU ZHANG, P XIE, M ZAGORSKI, J SPITZER, JA AF ZHANG, P XIE, M ZAGORSKI, J SPITZER, JA TI ATTENUATION OF HEPATIC NEUTROPHIL SEQUESTRATION BY ANTI-CINC ANTIBODY IN ENDOTOXIC RATS SO SHOCK LA English DT Article ID ESCHERICHIA-COLI ENDOTOXIN; TUMOR NECROSIS FACTOR; CHEMOTACTIC FACTOR; INTERLEUKIN-8 FAMILY; CELL-LINE; HEPATOCYTES; LIPOPOLYSACCHARIDE; LEUKOCYTES; ADHERENCE; INFUSION AB Cytokine-induced neutrophil chemoattractant (CINC) is a member of the chemokine alpha subfamily. it is induced in rats by tumor necrosis factor-alpha (TNF-alpha), interleukin-1, and lipopolysaccharide and is implicated in neutrophil infiltration in response to inflammatory stimuli. We tested the hypothesis that pretreatment with anti-CINC antibody or by cobra venom factor attenuates hepatic neutrophil accumulation induced by a 90 min infusion of Escherichia coli endotoxin. Changes in the expression of CD11b/c and CD18 and in plasma TNF-alpha levels were also investigated. Cultured hepatocytes and Kupffer cells of endotoxic rats produced significantly more CINC than those of saline-infused controls. CINC generation by Kupffer cells was much lower than generation by hepatocytes. Pretreatment with anti-CINC antibody or cobra venom factor significantly reduced hepatic neutrophil sequestration, but did not affect the upregulation of CD11b/c and CD18 expression on liver-sequestered neutrophils or plasma TNF-alpha levels. We conclude that CINC-mediated hepatic neutrophil accumulation may not be necessarily associated with up-regulation of neutrophil adhesion molecules or elevated circulating TNF-alpha levels. Attenuation of hepatic neutrophil sequestration by anti-CINC antibody is likely based on blocking of the chemotactic activity of CINC and thus diminishing the chemotactic gradient established in the liver. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,NEW ORLEANS,LA 70112. UNIV CHICAGO,MED CTR,DEPT PATHOL,CHICAGO,IL 60637. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM32654] NR 37 TC 62 Z9 62 U1 0 U2 0 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9, AUGUSTA, GA 30901 SN 1073-2322 J9 SHOCK JI Shock PD OCT PY 1995 VL 4 IS 4 BP 262 EP 268 DI 10.1097/00024382-199510000-00006 PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA RZ173 UT WOS:A1995RZ17300006 PM 8564554 ER PT J AU BOOTH, V ERNEUX, T AF BOOTH, V ERNEUX, T TI UNDERSTANDING PROPAGATION FAILURE AS A SLOW CAPTURE NEAR A LIMIT-POINT SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE PROPAGATION FAILURE; DISCRETE REACTION-DIFFUSION SYSTEMS; FITZHUGH-NAGUMO EQUATION; SINGULAR PERTURBATIONS ID MULTIPLE STEADY-STATES; EXCITABLE CELLS; SYSTEMS; JUMP; REFLECTION; TRANSITION; REACTORS AB This paper investigates the phenomenon of propagation failure in spatially discrete reaction-diffusion systems with excitable kinetics. Excitable kinetics are modeled by the FitzHugh-Nagumo equations. In the limit of weak coupling strength, a traveling pulse propagating in a chain of cells is constructed. The asymptotic solution for the first three cells is studied in detail. A single Riccati equation describes propagation through each cell. From this equation, a first approximation for the critical coupling strength below which the pulse is blocked is obtained. Near this critical coupling strength, propagation or failure results from a slow passage near a limit point leading either to a successful jump (propagation) or to capture by a slowly varying steady state (failure). The analysis of the behavior of the first three cells suggests an algorithmic method to analyze propagation through an arbitrary number of coupled cells. Failure may appear at any cell in the chain but is described by the same Riccati equation. The solution of this equation satisfies a matching condition which depends on the cell position. The results of the algorithm are compared with numerical solutions and excellent agreement is obtained. C1 NORTHWESTERN UNIV, DEPT ENGN SCI & APPL MATH, EVANSTON, IL 60208 USA. FREE UNIV BRUSSELS, B-1050 BRUSSELS, BELGIUM. RP BOOTH, V (reprint author), NIDDKD, MATH RES BRANCH, 9190 WISCONSIN AVE, SUITE 350, BETHESDA, MD 20814 USA. NR 27 TC 17 Z9 17 U1 0 U2 3 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 EI 1095-712X J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD OCT PY 1995 VL 55 IS 5 BP 1372 EP 1389 DI 10.1137/S0036139994264944 PG 18 WC Mathematics, Applied SC Mathematics GA RV223 UT WOS:A1995RV22300011 ER PT J AU LAYTON, HE PITMAN, EB KNEPPER, MA AF LAYTON, HE PITMAN, EB KNEPPER, MA TI A DYNAMIC NUMERICAL-METHOD FOR MODELS OF THE URINE CONCENTRATING MECHANISM SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE NUMERICAL METHODS; HYPERBOLIC PARTIAL DIFFERENTIAL EQUATIONS; MATHEMATICAL MODELS; KIDNEY; RENAL DYNAMICS; URINE CONCENTRATING MECHANISM ID CENTRAL CORE MODEL; MEDULLARY COLLECTING DUCT; RENAL COUNTERFLOW SYSTEMS; UREA TRANSPORT; NONOSCILLATORY SCHEMES; COUNTERCURRENT SYSTEM; 3-DIMENSIONAL ANATOMY; QUANTITATIVE-ANALYSIS; MATHEMATICAL-MODEL; WATER PERMEABILITY AB Dynamic models of the urine concentrating mechanism consist of large systems of hyperbolic partial differential equations, with stiff source terms, coupled with fluid conservation relations. Efforts to solve these equations numerically with explicit methods have been frustrated by numerical instability and by long computation times. As a consequence, most models have been reformulated as steady-state boundary value problems, which have usually been solved by an adaptation of Newton's method. Nonetheless, difficulties arise in finding conditions that lead to stable convergence, especially when the very large membrane permeabilities measured in experiments are used. In this report, an explicit method, previously introduced to solve the model equations of a single renal tubule, is extended to solve a large-scale model of the urine concentrating mechanism, This explicit method tracks concentration profiles in the upwind direction and thereby avoids instability arising from flow reversal. To attain second-order convergence in space and time: the recently developed ENO (essentially non-oscillatory) methodology is implemented, The method described here, which has been rendered practical for renal models by the emergence of desktop workstations, is adaptable to various medullary geometries and permits the inclusion of experimentally measured permeabilities. This report describes an implementation of the method, makes comparisons with results obtained previously by a different method, and presents an example calculation using some recently measured membrane properties. C1 SUNY BUFFALO, DEPT MATH, BUFFALO, NY 14214 USA. NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. RP LAYTON, HE (reprint author), DUKE UNIV, DEPT MATH, DURHAM, NC 27708 USA. NR 53 TC 19 Z9 19 U1 0 U2 2 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 EI 1095-712X J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD OCT PY 1995 VL 55 IS 5 BP 1390 EP 1418 DI 10.1137/S0036139993252864 PG 29 WC Mathematics, Applied SC Mathematics GA RV223 UT WOS:A1995RV22300012 ER PT J AU COHENMANSFIELD, J WERNER, P FREEDMAN, L AF COHENMANSFIELD, J WERNER, P FREEDMAN, L TI SLEEP AND AGITATION IN AGITATED NURSING-HOME RESIDENTS - AN OBSERVATIONAL STUDY SO SLEEP LA English DT Article DE SLEEP; AGITATION; NURSING HOME RESIDENTS; DEMENTIA ID SENILE DEMENTIA; DISTURBANCES; WAKEFULNESS; PATTERNS; APNEA; CARE; EEG; AGE AB An observational study was conducted to describe the physical and social environment of sleep of 16 highly agitated and cognitively impaired nursing home residents, and the relationships between manifestations of agitation and sleep. Results showed that nursing home residents were more likely to be observed asleep when alone, in their own rooms, and between 9 p.m. and 5 a.m. Considerable amounts of sleep were also observed during the day. Great individual variation was observed in the presence of sleep-related disorders, although a tendency was observed for more fragmented sleep during the day hours. Almost all the agitated behaviors observed decreased immediately after sleep. Similar to findings of objective studies, much individual variation was found in sleep patterns and sleep pathology of cognitively impaired and highly agitated nursing home residents. Findings suggest that agitation may be exacerbated by fatigue. C1 HEBREW HOME GREATER WASHINGTON,RES INST,ROCKVILLE,MD 20852. GEORGETOWN UNIV,DEPT PSYCHIAT,WASHINGTON,DC. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD. FU NIA NIH HHS [R01 AG08675] NR 30 TC 27 Z9 28 U1 5 U2 8 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD OCT PY 1995 VL 18 IS 8 BP 674 EP 680 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TD542 UT WOS:A1995TD54200008 PM 8560134 ER PT J AU Prewitt, TW Alexander, HR Sindelar, WF AF Prewitt, TW Alexander, HR Sindelar, WF TI Hemipelvectomy for soft tissue sarcoma: Clinical results in fifty-three patients SO SURGICAL ONCOLOGY-OXFORD LA English DT Article DE amputation; hemipelvectomy; lower extremity; sarcoma ID ADJUVANT CHEMOTHERAPY; CONSERVATIVE SURGERY; LOWER-EXTREMITY; ADULT PATIENTS; SURVIVAL; RECURRENCE; RADIOTHERAPY; AMPUTATION; PATTERNS AB The management of high-grade extremity sarcomas typically combines local surgical excision with some form of adjuvant therapy. However, some patients with large proximal lesions present with no local resection options, and high radical amputation is often the only way to accomplish complete tumour excision. A retrospective review was made of the clinical courses of 53 patients with high-grade sarcomas of the lower extremity who underwent hemipelvectomy with curative intent at the National Institutes of Health between 1975 and 1989. Hemipelvectomy provided excellent local control, with no local recurrences. Although 60% of the patients experienced post-operative complications, the operative mortality was zero. Ten years after hemipelvectomy, the actuarial disease-free rate was 25% and the survival rate was 35%. There were no statistically significant survival differences when patients were stratified according to tumour size, perioperative blood transfusion requirements or the use of adjuvant chemotherapy. We conclude that hemipelvectomy provides excellent local control and a reasonable cure rate for patients with locally unresectable soft tissue sarcomas of the lower extremity. C1 NCI,NIH,SURG BRANCH,BETHESDA,MD 20892. NR 40 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7404 J9 SURG ONCOL JI Surg. Oncol.-Oxf. PD OCT PY 1995 VL 4 IS 5 BP 261 EP 269 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA TU115 UT WOS:A1995TU11500005 PM 8850028 ER PT J AU CADET, JL LADENHEIM, B HIRATA, H ROTHMAN, RB ALI, S CARLSON, E EPSTEIN, C MORAN, TH AF CADET, JL LADENHEIM, B HIRATA, H ROTHMAN, RB ALI, S CARLSON, E EPSTEIN, C MORAN, TH TI SUPEROXIDE RADICALS MEDIATE THE BIOCHEMICAL EFFECTS OF METHYLENEDIOXYMETHAMPHETAMINE (MDMA) - EVIDENCE FROM USING CUZN-SUPEROXIDE DISMUTASE TRANSGENIC MICE SO SYNAPSE LA English DT Article DE TRANSGENIC MICE; SUPEROXIDE DISMUTASE; MDMA; NEUROTOXICITY; FREE RADICALS; DOPAMINE; STRIATUM; ECSTASY ID RAT-BRAIN; SEROTONIN TERMINALS; HYDROGEN-PEROXIDE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; NEUROTOXICITY; 3,4-METHYLENEDIOXYAMPHETAMINE; DOPAMINE; 6-HYDROXYDOPAMINE; NEURODEGENERATION; GENERATION AB The subacute and long-term biochemical effects of methylenedioxymethamphetamine (MDMA) were assessed in homozygous and heterozygous transgenic (Tg) mice that carry the complete sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD) gene. Non-transgenic (Non-Tg) mice showed significant decreased in striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels both at 24 h and at 2 weeks after a single injection of MDMA (50 mg/kg). Heterozygous SOD-Tg mice showed DA depletion only at the 24 h time point. In contrast, homozygous SOD-Tg mice show no DA or DOPAC depletion at either the 24 h or at the 2 week time points. Moreover, three injections of MDMA. (50 mg/kg) given 24 h apart also caused marked reduction of striatal DA and DOPAC in Non-Tg mice when these substances were measured 2 weeks after the last MDMA injection. That injection schedule also caused small decreases in DA levels in the heterozygous animals but no changes in the homozygous mice; DOPAC levels were not affected in the heterozygous nor in the homozygous SOD-Tg mice. Furthermore, the multiple injection schedule caused significant decreases in DA and DOPAC in female Non-Tg mice but not in the two strains of transgenic mice. Neither the single dose nor the multiple dose schedule of MDMA injections affected striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in any of the three strains of mice. These results support previous observations that MDMA-induced biochemical effects are observed in the DA systems of mice, whereas these effects are seen in the 5-HT systems of rats. The present observations also document for the first time a role for the production of superoxide radicals in these effects of MDMA. These mice are an important tool for dissecting pathways involved in drug-induced neurotoxicity. (C) 1995 Wiley-Liss, Inc. C1 NATL CTR TOXICOL RES,NEUROCHEM LAB,JEFFERSON,AR 72079. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NIDA,INTRAMURAL RES PROGRAM,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. RP CADET, JL (reprint author), NIDA,INTRAMURAL RES PROGRAM,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [AG-08938]; NICHD NIH HHS [HD 24605] NR 41 TC 68 Z9 69 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 OCT PY 1995 VL 21 IS 2 BP 169 EP 176 DI 10.1002/syn.890210210 PG 8 WC Neurosciences SC Neurosciences & Neurology GA RX413 UT WOS:A1995RX41300009 PM 8584978 ER PT J AU SCALISE, AC AF SCALISE, AC TI EVALUATION OF A RECOMBINANT IMMUNOBLOT ASSAY FOR CONFIRMATION OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP 113 EP 113 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800112 ER PT J AU BUTZ, RE BOWMAN, C WANNEBO, C PROCTER, JL READ, EJ AF BUTZ, RE BOWMAN, C WANNEBO, C PROCTER, JL READ, EJ TI ADSORPTION OF RBC AUTOANTIBODIES USING PHOSPHOLIPID AND PHOSPHODIESTER LIGANDS ON AN ACTIVATED MATRIX SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. ARC,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S81 EP S81 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800080 ER PT J AU CONRYCANTILENA, C MELPOLDER, JC VANRADEN, M ALTER, HI AF CONRYCANTILENA, C MELPOLDER, JC VANRADEN, M ALTER, HI TI CHARACTERISTICS AND MOTIVATION OF ANTI-HCV POSITIVE BLOOD-DONORS ADMITTING INTRAVENOUS DRUG-USE (IVDU) SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S229 EP S229 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800227 ER PT J AU DAVEY, RJ STEC, NM LEE, JL LEITMAN, SF AF DAVEY, RJ STEC, NM LEE, JL LEITMAN, SF TI THE EFFECT OF PRESTORAGE LEUKOCYTE REDUCTION ON THE IRRADIATION-INDUCED RED-CELL STORAGE LESION SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S219 EP S219 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800217 ER PT J AU KIM, JP AF KIM, JP TI CHARACTERIZATION OF NEW HUMAN HEPATITIS-VIRUS (HGV) AND ITS IMPLICATION IN PTH SO TRANSFUSION LA English DT Meeting Abstract C1 GENELABS TECHNOL INC,REDWOOD CITY,CA. NIH,CDC,NMRI,NSWBTS,HGV STUDY GRP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S158 EP S158 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800156 ER PT J AU LEE, JH STEC, NM SHELDON, SL AF LEE, JH STEC, NM SHELDON, SL TI EFFECT OF IRRADIATION ON THERMAL THRESHOLD FOR RED-CELL INJURY SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S35 EP S35 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800034 ER PT J AU LEIBY, DA LENES, BA NYSTROM, SR TALLENT, PP READ, EJ PAN, AA STUMPF, RJ DODD, RY AF LEIBY, DA LENES, BA NYSTROM, SR TALLENT, PP READ, EJ PAN, AA STUMPF, RJ DODD, RY TI SEROPREVALENCE OF TRYPANOSOMA-CRUZI ANTIBODIES IN BLOOD-DONORS FROM METROPOLITAN MIAMI SO TRANSFUSION LA English DT Meeting Abstract C1 ARC,ROCKVILLE,MD. ARC,MIAMI,FL. NIH,ROCKVILLE,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S254 EP S254 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800252 ER PT J AU LEITMAN, SF SEKHSARIA, S GLADDEN, D VOWELLS, S FLEISHER, TA MALECH, HL AF LEITMAN, SF SEKHSARIA, S GLADDEN, D VOWELLS, S FLEISHER, TA MALECH, HL TI SAFETY AND EFFICACY OF RECOMBINANT GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) IN MOBILIZING BLOOD STEM-CELLS IN HEALTHY DONORS SO TRANSFUSION LA English DT Meeting Abstract C1 NIAID,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S262 EP S262 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800260 ER PT J AU LEITMAN, SF YU, M LEKSTROM, J AF LEITMAN, SF YU, M LEKSTROM, J TI PAIR-CONTROLLED STUDY OF GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) PLUS DEXAMETHASONE (DEXA) FOR GRANULOCYTAPHERESIS DONORS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S210 EP S210 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800208 ER PT J AU LUBAN, NLC FEARON, T LEITMAN, SF MOROFF, G AF LUBAN, NLC FEARON, T LEITMAN, SF MOROFF, G TI ABSORPTION OF GAMMA-RADIATION IN SIMULATED BLOOD COMPONENTS USING CESIUM (CS) IRRADIATORS SO TRANSFUSION LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,CHILDRENS HOSP,WASHINGTON,DC 20010. NIH,BETHESDA,MD 20892. AMER RED CROSS,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S250 EP S250 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800248 ER PT J AU MECHLING, ML PROCTER, JL DAVEY, RJ AF MECHLING, ML PROCTER, JL DAVEY, RJ TI COMPARISON OF 4 ANTIBODY DETECTION METHODOLOGIES SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S240 EP S240 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800238 ER PT J AU VIGUE, F ALEGRE, E HE, R REID, D PROCTER, JL AF VIGUE, F ALEGRE, E HE, R REID, D PROCTER, JL TI BATCH SCREENING OF PLATELET DONORS FOR PL(A1) ALLOANTIGEN USING A SOLID-PHASE MICROPLATE ASSAY SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S74 EP S74 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800073 ER PT J AU WANNEBO, C MUUL, L CARTER, C CHANG, L MAY, F READ, EJ BLAESE, RM KLEIN, HG AF WANNEBO, C MUUL, L CARTER, C CHANG, L MAY, F READ, EJ BLAESE, RM KLEIN, HG TI MAGNETIC BEAD DEPLETION OF CD8(+) T-LYMPHOCYTES FROM PERIPHERAL MONONUCLEAR-CELLS FOR USE IN HUMAN GENE-THERAPY SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S165 EP S165 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800163 ER PT J AU DILISA, F SILVERMAN, HS HANSFORD, RG AF DILISA, F SILVERMAN, HS HANSFORD, RG TI MITOCHONDRIAL-FUNCTION AND CELL INJURY IN SINGLE CARDIAC MYOCYTES EXPOSED TO ANOXIA AND REOXYGENATION SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st International Symposium on the Ischemia-Reperfusion Syndrome CY MAR 09-11, 1995 CL LIEGE, BELGIUM SP Univ Liege, Dept Cardiovasc & Transplant Surg, Univ Liege, Interdisciplinary Ctr Oxygen Biochem ID PORE C1 JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD. NIA,CARDIOVASC SCI LAB,BALTIMORE,MD. RP DILISA, F (reprint author), UNIV CATANIA,IST CHIM BIOL,DIPARTIMENTO CHIM BIOL,VIALE A DORIA 6,I-95125 CATANIA,ITALY. NR 8 TC 3 Z9 3 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD OCT PY 1995 VL 27 IS 5 BP 2829 EP 2830 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TB654 UT WOS:A1995TB65400110 PM 7482933 ER PT J AU WICKNER, RB AF WICKNER, RB TI PRIONS OF YEAST AND HEAT-SHOCK-PROTEIN-104 - COPRION AND CURE SO TRENDS IN MICROBIOLOGY LA English DT Note ID SACCHAROMYCES-CEREVISIAE; SCRAPIE PRION; GENE; PRP; IDENTIFICATION; PSI C1 NIDDKD,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. NR 21 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD OCT PY 1995 VL 3 IS 10 BP 367 EP 369 DI 10.1016/S0966-842X(00)88978-7 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA RZ156 UT WOS:A1995RZ15600001 PM 8564353 ER PT J AU GONZALEZ, FJ FERNANDEZSALGUERO, P AF GONZALEZ, FJ FERNANDEZSALGUERO, P TI DIAGNOSTIC-ANALYSIS, CLINICAL IMPORTANCE AND MOLECULAR-BASIS OF DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID SEVERE 5-FLUOROURACIL TOXICITY; PURIFICATION; DEGRADATION; LIVER RP GONZALEZ, FJ (reprint author), NIH,MOLEC CARCINOGENESIS LAB,BLDG 10,ROOM 3E-24,BETHESDA,MD 20892, USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 22 TC 65 Z9 67 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD OCT PY 1995 VL 16 IS 10 BP 325 EP 327 DI 10.1016/S0165-6147(00)89065-3 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RZ598 UT WOS:A1995RZ59800001 PM 7491709 ER PT J AU BUNDY, LM RU, M ZHENG, BF CHENG, L PATTENGALE, PK PORTIS, JL FAN, H AF BUNDY, LM RU, M ZHENG, BF CHENG, L PATTENGALE, PK PORTIS, JL FAN, H TI BIOLOGICAL CHARACTERIZATION AND MOLECULAR-CLONING OF MURINE C-TYPE RETROVIRUSES DERIVED FROM THE TSZ COMPLEX FROM MAINLAND CHINA SO VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; LEUKEMIA-VIRUS; MONOCLONAL-ANTIBODIES; ERYTHROLEUKEMIA-CELLS; INTEGRATION SITE; HOST-REACTION; WILD MICE; IDENTIFICATION; COMMON; SEQUENCES AB Characterization of the SRS murine retrovirus complex, derived from the TSZ system of murine leukemia developed in China, was carried out. The initial stock contained XC(+), NB-tropic virus (and possibly other viruses), and induced several neoplastic diseases in neonatally inoculated NIH Swiss mice: erythroid leukemia, myeloid leukemia (acute myeloblastic leukemia), and lymphoblastic lymphoma (both B- and T-lymphoid). In addition, approximately 30% of inoculated animals developed central nervous system disease - hindlimb paralysis or semilateral paralysis. Rescue of virus from the spleen of an animal with combined erythroid/myeloid leukemia, followed by endpoint dilution gave two stocks: 19-6 (XC(+), NB-tropic) and 19-7 (XC(-), NB-tropic). Both stocks induced erythroid and myeloid leukemia, and 19-6 induced CNS symptoms as well. Southern blot analysis indicated that the predominant viruses from the 19-6 and the 19-7 cultures were related, but different in the env region. An infectious molecular clone of provirus from 19-6 cells was obtained. The resulting cloned virus [SRS 19-6 murine leukemia virus (MuLV)] induced four kinds of leukemia: erythroid, myeloid, B-lymphoma, and T-lymphoma; in many cases, more than one tumor type was identified in the same animal. Such a broad spectrum of leukemias induced by a cloned MuLV is unusual. Flaccid hindlimb paralysis induced by SRS 19-6 MuLV could be attributed to meningeal B-lymphoma. Immunofluorescent staining with a panel of env-specific monoclonal antibodies confirmed that the 19-6 and 19-7 viral stocks contained different viruses, which differed from previously characterized MuLVs. The viruses of the SRS complex may provide interesting reagents for investigations of MuLV-induced disease. (C) 1995 Academic Press, Inc. C1 UNIV CALIF IRVINE,DEPT MOLEC BIOL & BIOCHEM,IRVINE,CA 92717. UNIV CALIF IRVINE,INST CANC RES,IRVINE,CA 92717. SHANGHAI MED UNIV,DEPT BIOPHYS,SHANGHAI 200032,PEOPLES R CHINA. SHANGHAI MED UNIV,DEPT PATHOPHYSIOL,SHANGHAI 200032,PEOPLES R CHINA. UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90054. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. FU NCI NIH HHS [CA32455] NR 34 TC 13 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 1 PY 1995 VL 212 IS 2 BP 367 EP 382 DI 10.1006/viro.1995.1494 PG 16 WC Virology SC Virology GA RY725 UT WOS:A1995RY72500009 PM 7571406 ER PT J AU TAMM, E LUTJENDRECOLL, E AF TAMM, E LUTJENDRECOLL, E TI INNERVATION OF MYOFIBROBLAST-LIKE SCLERAL SPUR CELLS IN HUMAN EYES SO VISION RESEARCH LA English DT Meeting Abstract C1 UNIV ERLANGEN NURNBERG,DEPT ANAT,ERLANGEN,GERMANY. NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD OCT PY 1995 VL 35 SU S BP 2132 EP 2132 PG 1 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA RZ562 UT WOS:A1995RZ56200131 ER PT J AU JACOT, JL LOIS, N GLOVER, JP ROBISON, WG AF JACOT, JL LOIS, N GLOVER, JP ROBISON, WG TI DECREASED CENTRAL CORNEAL SENSITIVITY IN THE 50-PERCENT GALACTOSE-FED RAT MODEL OF DIABETIC OCULAR COMPLICATIONS SO VISION RESEARCH LA English DT Meeting Abstract C1 NEI,PATHOPHYSIOL SECT,BETHESDA,MD 20892. HOSP GEN GALICIA,SANTIAGO,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD OCT PY 1995 VL 35 SU S BP P155 EP P155 PG 1 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA RZ562 UT WOS:A1995RZ56200460 ER PT J AU PUTILINA, T KADIRI, M KOZHICH, A CHADER, G AF PUTILINA, T KADIRI, M KOZHICH, A CHADER, G TI RPE CELL-DEATH IN CULTURE AS FOLLOWED BY FLUORESCENT-PROBES SO VISION RESEARCH LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD OCT PY 1995 VL 35 SU S BP P381 EP P381 PG 1 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA RZ562 UT WOS:A1995RZ56200629 ER PT J AU PEEHL, DM RUBIN, JS AF PEEHL, DM RUBIN, JS TI KERATINOCYTE GROWTH-FACTOR - AN ANDROGEN-REGULATED MEDIATOR OF STROMAL EPITHELIAL INTERACTIONS IN THE PROSTATE SO WORLD JOURNAL OF UROLOGY LA English DT Article ID FACTOR RECEPTORS; CELL-GROWTH; FIBROBLAST; EXPRESSION; DIFFERENTIATION; PROLIFERATION; KGF; ACTIVATION; FAMILY AB Members of the fibroblast growth factor (FGF) family are important growth-regulatory elements. Of the FGFs, keratinocyte growth factor (KGF) appears to have unique properties that implicate it as a paracrine factor in the prostate. Two KGF transcripts (approximate to 2.4 and 5.0 kb) encode a protein of approximate to 22 kDa. In contrast to several other members of the FGF family, KGF has a signal peptide and is actively secreted. Cellular response to KGF is mediated by a specific receptor that is transcribed from an alternately spliced variant of the FGF type 2 receptor (FGFR-2). KGF transcripts have been detected in prostatic tissues and in stromal cells cultured from rat and human prostates as well as in a variety of stromal cells derived from other organs. Prostatic epithelial cells and numerous other types of epithelial cells are targets of KGF's mitogenic activity. Several factors involved in wound healing regulate the expression of KGF, but androgen regulation of KGF is of greatest relevance to the role of KGF in the prostate. Current efforts to localize and manipulate KGF activity in vivo should reveal the significance of KGF expression and function in the prostate and in other organs. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP PEEHL, DM (reprint author), STANFORD UNIV,SCH MED,DEPT UROL,STANFORD,CA 94305, USA. NR 43 TC 51 Z9 52 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD OCT PY 1995 VL 13 IS 5 BP 312 EP 317 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA TC933 UT WOS:A1995TC93300008 PM 8581003 ER PT J AU NAM, JM AF NAM, JM TI SAMPLE-SIZE DETERMINATION IN STRATIFIED TRIALS TO ESTABLISH THE EQUIVALENCE OF 2 TREATMENTS SO STATISTICS IN MEDICINE LA English DT Article ID NULL HYPOTHESIS; DIFFERENCE; TABLES AB When designing a trial to establish that a new treatment is as effective as a standard one, the conventional test procedure and sample size based on a null hypothesis of no difference between two treatments is inappropriate. Several authors have investigated test statistics and corresponding sample sizes based on the null hypothesis that the standard treatment is more effective than the new by at least some specific value for a single 2x2 table. This paper considers a trial that involves several 2x2 tables and presents an approximate formula for the sample size required to obtain a given power of a one-tailed score test for a null hypothesis of a specific common non-zero difference between two treatments across strata. I show that the sample size for a trial based on an unstratified test is always larger than that based on a stratified test when the design is balanced. RP NAM, JM (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 16 TC 29 Z9 31 U1 0 U2 0 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 SEP 30 PY 1995 VL 14 IS 18 BP 2037 EP 2049 DI 10.1002/sim.4780141809 PG 13 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 RW623 UT WOS:A1995RW62300008 PM 8677403 ER PT J AU DINMAN, JD AF DINMAN, JD TI RIBOSOMAL FRAMESHIFTING IN YEAST VIRUSES SO YEAST LA English DT Article DE SACCHAROMYCES CEREVISIAE; RIBOSOMES; RIBOSOMAL FRAMESHIFTING; L-A DSRNA VIRUS; TY; RETROTRANSPOSON; RETROVIRUS; HUNGRY CODONS; POLYAMINES ID STRANDED-RNA VIRUS; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; TY ELEMENT; TRANSLATIONAL SUPPRESSION; REVERSE-TRANSCRIPTASE; MUTATIONAL ANALYSIS; MESSENGER-RNA; COAT PROTEIN; PSEUDOKNOT AB Proper maintenance of translational reading frame by ribosomes is essential for cell growth and viability. In the last 10 years it has been shown that a number of viruses induce ribosomes to shift reading frame in order to regulate the expression of gene products having enzymatic functions. Studies on ribosomal frameshifting in viruses of yeast have been particularly enlightening. The roles of viral mRNA sequences and secondary structures have been elucidated and a picture of how these interact with host chromosomal gene products is beginning to emerge. The efficiency of ribosomal frameshifting is important for viral particle assembly, and has identified ribosomal frameshifting as a potential target for antiviral agents. The availability of mutants of host chromosomal gene products involved in maintaining the efficiency of ribosomal frameshifting bodes well for the use of yeast in future studies of ribosomal frameshifting. C1 NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. OI Dinman, Jonathan/0000-0002-2402-9698 NR 60 TC 59 Z9 62 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD SEP 30 PY 1995 VL 11 IS 12 BP 1115 EP 1127 DI 10.1002/yea.320111202 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA RX005 UT WOS:A1995RX00500001 PM 8619310 ER PT J AU NIGHTINGALE, KP WOLFFE, AP AF NIGHTINGALE, KP WOLFFE, AP TI THE INTERACTION OF TFIIIA WITH SPECIFIC RNA-DNA HETERODUPLEXES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID TRANSCRIPTION FACTOR-IIIA; INTERNAL CONTROL REGION; 5S RNA; ZINC FINGERS; 5S-RNA GENE; BINDING-SITE; B-FORM; PROTEIN; COMPLEX; POLYMERASE AB We examine the association of transcription factor TFIIIA with RNA-DNA heteroduplexes containing sequences from the Xenopus borealis 5 S rRNA gene. Under conditions where TFIIIA selectively binds to 5 S rRNA or the internal control region of the 5 S rRNA gene, no specific association of TFIIIA with DNA-RNA heteroduplexes containing either strand of 5 S DNA could be detected. We discuss our results with respect to specific models of TFIIIA recognition of the internal control region and of DNA-RNA hybrids by zinc finger proteins. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 43 TC 5 Z9 5 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 SEP 29 PY 1995 VL 270 IS 39 BP 22665 EP 22668 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400004 PM 7559384 ER PT J AU SRIVASTAVA, M AF SRIVASTAVA, M TI GENOMIC STRUCTURE AND EXPRESSION OF THE HUMAN GENE ENCODING CYTOCHROME B(561), AN INTEGRAL PROTEIN OF THE CHROMAFFIN GRANULE MEMBRANE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE ELECTRON-TRANSFER; CHROMOMEMBRIN-B; COMMON ANTIGENS; PROMOTER; VESICLES; BINDING; ELEMENTS; INVITRO AB Cytochrome b(561) is an electron transfer protein unique to neuroendocrine secretory vesicles, The Southern blot hybridization shows that it is a single copy gene highly conserved throughout phylogeny, The transcription unit spans approximately 11 kilobases, and heterologous transcription sites are located 404 bases 5' to the translation initiation codon, The sequence of the 5'-flanking region is GC-rich and lacks a typical TATA box at the usual position, However, it has a CAAT sequence at -132 and potential recognition sequences for several transcription factors including SP1, GR-PR-MMTV, AP4, gERE, JCV repeat, AP2, and NF-kappa B, Each of the five transmembrane segments are encoded by five consecutive exons, This corroborates the five-transmembrane model proposed for human, mouse, and Xenopus rather than six proposed for bovine, The cytochrome was found to be highly expressed in colon cancer cell lines, T cell lymphomas, and K-562 cell lines. However, in B-cell lymphomas such as Burkitt's and Daudi, the cytochrome b(561) expression was completely shut down. The results in this report are the first to demonstrate the structural organization and regulatory sequences of the cytochrome b(561) gene encoding an integral membrane protein of neuroendocrine storage vesicles of neurotransmitters and peptide hormones, Unexpected results on cytochrome b(561) expression in cells of lymphocytic origin and its complex regulation in tumor cells provide new insights into cytochrome b(561) gene regulation. RP SRIVASTAVA, M (reprint author), NIDDK,CELL BIOL & GENET LAB,BLDG 8,RM 405,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 15 Z9 16 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 SEP 29 PY 1995 VL 270 IS 39 BP 22714 EP 22720 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400016 PM 7559396 ER PT J AU NORRIS, J FAN, DJ ALEMAN, C MARKS, JR FUTREAL, PA WISEMAN, RW IGLEHART, JD DEININGER, PL MCDONNELL, DP AF NORRIS, J FAN, DJ ALEMAN, C MARKS, JR FUTREAL, PA WISEMAN, RW IGLEHART, JD DEININGER, PL MCDONNELL, DP TI IDENTIFICATION OF A NEW SUBCLASS OF ALU DNA REPEATS WHICH CAN FUNCTION AS ESTROGEN RECEPTOR-DEPENDENT TRANSCRIPTIONAL ENHANCERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESPONSIVE ELEMENT; THYROID-HORMONE; SACCHAROMYCES-CEREVISIAE; BREAST-CANCER; BINDING-SITE; GENE; TAMOXIFEN; DELETION; YEAST AB We have utilized a genetic selection system in yeast to identify novel estrogen-responsive genes within the hu man genome and to define the sequences in the BRCA-1 gene responsible for its estrogen responsiveness, This approach led to the identification of a new subclass within the Alu family of DNA repeats which have diverged from known Alu sequences and have acquired the ability to function as estrogen receptor-dependent enhancers, Importantly, these new elements confer receptor-dependent estrogen responsiveness to a heterologous promoter when assayed in mammalian cells, This transcriptional activity can be attenuated by the addition of either of three different classes of estrogen receptor antagonists, indicating that these elements function as classical estrogen receptor-dependent enhancers, Furthermore, this enhancer activity is restricted to a specific subset of DNA repeats because consensus Alu elements of four major subfamilies do not respond to the estrogen receptor. Previously, most Alu sequences have been considered to be functionally inert, However, this work provides strong evidence that a significant subset can confer estrogen responsiveness upon a promoter within which they are located, Clearly, Alu sequences must now be considered as important contributors to the regulation of gene transcription in estrogen receptor-containing cells. C1 DUKE UNIV,MED CTR,SCH MED,DEPT PHARMACOL,DURHAM,NC 27710. DUKE UNIV,SCH MED,DEPT SURG,DURHAM,NC 27710. NIEHS,MOLEC CARCINOGENESIS LAB,DURHAM,NC 27709. LOUISIANA STATE UNIV,MED CTR,DEPT BIOCHEM,NEW ORLEANS,LA 70112. LOUISIANA STATE UNIV,MED CTR,DEPT BIOL MOLEC,NEW ORLEANS,LA 70112. LOUISIANA STATE UNIV,MED CTR,STANLEY S SCOTT CANC CTR,NEW ORLEANS,LA 70112. OI Deininger, Prescott/0000-0002-1067-3028 FU NIDDK NIH HHS [DK48807] NR 33 TC 179 Z9 180 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 SEP 29 PY 1995 VL 270 IS 39 BP 22777 EP 22782 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400025 PM 7559405 ER PT J AU HOULE, MG KAHN, RA NACCACHE, PH BOURGOIN, S AF HOULE, MG KAHN, RA NACCACHE, PH BOURGOIN, S TI ADP-RIBOSYLATION FACTOR TRANSLOCATION CORRELATES WITH POTENTIATION OF GTP-GAMMA-S-STIMULATED PHOSPHOLIPASE-D ACTIVITY IN MEMBRANE-FRACTIONS OF HL-60 CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET-ACTIVATING-FACTOR; HUMAN NEUTROPHILS; BINDING-PROTEIN; PHORBOL ESTERS; MECHANISMS; CALCIUM; ARF; PHOSPHATIDYLCHOLINE; DIACYLGLYCEROL; GRANULOCYTES AB Phospholipase D (PLD) activation by guanine nucleotides requires protein cofactors from both the membrane and the cytosol. The small GTP-binding protein ADP-ribosylation factor (ARF) has been established as one important component of PLD activation. By stimulating HL-60 cells with various agonists and then isolating the membrane fraction and assaying PLD activity in the presence and absence of GTP gamma S, we observed that fMet-Leu-Phe (fMLP) and phorbol esters induced a potentiation of GTP gamma S-stimulated PLD activity in the membrane fractions of these cells. Inactive phorbol esters induced no such potentiation. Both fMLP and active phorbol esters induced a 2-3-fold increase in GTP gamma S-stimulated PLD in HL-60 membranes, Membranes derived from stimulated HL-60 cells contained 60-70% more ARF as compared with membranes derived from control cells. Membrane contents of ARF were assessed by Western blotting with the anti-ARF monoclonal antibody 1D9 followed by densitometric evaluation. Therefore, ARF translocation correlates with the potentiation of the GTP gamma S-stimulated PLD activity. The effect on PLD activity and ARF membrane content achieved through fMLP stimulation was greatly enhanced by prior treatment of the cells with cytochalasin B. Membranes derived from control and fMLP-stimulated cells were assayed for PLD activity in the presence of exogenous ARF and a 50-kDa fraction known to contain elements implicated in PLD activation. The ability of ARF and the 50-kDa fraction to enhance GTP gamma S-sensitive PLD activity was significantly reduced when the membranes were derived from fMLP-stimulated cells. The data indicate that, in addition to ARF, elements of the 50-kDa PLD-inducing factors were likely already translocated to the membranes upon stimulation. We propose that ARF, upon stimulation with agonists such as fMLP or phorbol esters, is translocated to the membrane and in concert with other protein components of the 50-kDa fraction enhances PLD activity. C1 CHU LAVAL,CTR RECH,CTR RECH RHUMATOL & IMMUNOL,ST FOY,PQ G1V 4G2,CANADA. UNIV LAVAL,FAC MED,DEPT MED,ST FOY,PQ G1V 4G2,CANADA. UNIV LAVAL,FAC MED,DEPT PHYSIOL,ST FOY,PQ G1V 4G2,CANADA. NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 46 TC 84 Z9 85 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 SEP 29 PY 1995 VL 270 IS 39 BP 22795 EP 22800 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400028 PM 7559408 ER PT J AU ARORA, KK SAKAI, A CATT, KJ AF ARORA, KK SAKAI, A CATT, KJ TI EFFECTS OF 2ND INTRACELLULAR LOOP MUTATIONS ON SIGNAL-TRANSDUCTION AND INTERNALIZATION OF THE GONADOTROPIN-RELEASING-HORMONE RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; HUMAN BETA-2-ADRENERGIC RECEPTOR; BETA-ADRENERGIC-RECEPTOR; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; LIGAND-BINDING; RAT PITUITARY; GNRH RECEPTOR; AMINO-ACID AB The gonadotropin-releasing hormone (GnRH) receptor belongs to the superfamily of heptahelical G protein coupled receptors, most of which have a highly conserved DRYXXV/IXXPL sequence in the second intracellular (2i) loop that has been implicated in G protein coupling. The predicted 2i loop of the GnRH receptor contains serine rather than tyrosine in the DRY sequence but retains the conserved hydrophobic Leu residue, which is required for G protein coupling and internalization of muscarinic receptors. The present study examined the effects of mutating the unique Ser(140) to the conserved Tyr, and the conserved Leu(147) to Ala or Asp, on agonist binding, internalization, and signal transduction. The S140Y mutant showed a 100% increase in agonist binding affinity, and its internalization was increased by 60% above that of the wild-type receptor. The binding characteristics of the Leu(147) mutants were indistinguishable from those of the wild-type receptor, but their internalization was reduced by about 50%. The L147A and L147D mutants also showed significant impairment of GnRH-stimulated inositol phosphate production, These findings demonstrate that substitution of Ser(140) by Tyr does not affect G protein coupling but significantly increases receptor affinity and internalization rate. In contrast, replacement of a conserved aliphatic residue (Leu(147)) impairs both G protein coupling and agonist-induced receptor internalization. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 66 TC 108 Z9 109 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 SEP 29 PY 1995 VL 270 IS 39 BP 22820 EP 22826 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400033 PM 7559413 ER PT J AU DUHE, RJ FARRAR, WL AF DUHE, RJ FARRAR, WL TI CHARACTERIZATION OF ACTIVE AND INACTIVE FORMS OF THE JAK2 PROTEIN-TYROSINE KINASE PRODUCED VIA THE BACULOVIRUS EXPRESSION VECTOR SYSTEM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN GROWTH-HORMONE; GAMMA SIGNAL-TRANSDUCTION; RECOMBINANT BACULOVIRUS; EXTRACELLULAR DOMAIN; CRYSTAL-STRUCTURE; LYMPHOMA-CELLS; RECEPTOR; STIMULATION; ACTIVATION; PROLACTIN AB Three forms of rat JAK2 (type 2 Janus tyrosine kinase) mere produced via the baculovirus expression vector system, Recombinant baculoviruses encoded either the full-length rat jak2 cloned from the Nb2-SP cell line (rJAK2), a carboxyl-terminal deletion mutant lacking the putative catalytic domain (rJAK2(C Delta 795)), or an amino-terminal deletion mutant containing the putative catalytic domain ((N Delta 661)rJAK2). The proteins produced in infected Sf21 cells were assayed for phosphotyrosine content and autophosphorylating activity. Tyrosine phosphorylation of rJAK2 was not observed 1 day postinfection when rJAK2 was initially produced but was apparent 2 or more days postinfection when the rJAK2 level had significantly increased. Tyrosine phosphorylation of rJAK2(C Delta 795) was not observed; further, coproduction of rJAK2(C Delta 795) with rJAK2 blocked tyrosine phosphorylation of rJAK2, consistent with previously published results (Zhuang, H., Patel, S. V., He, T-C., Sonsteby, S. K., Niu, Z., and Wojchowski, D. M. (1994) J. Biol. Chem. 269, 21411-21414). Mutant (N Gamma 661)rJAK2 exhibited a robust tyrosine phosphorylation signal. A second 62-kDa tyrosine phosphoprotein co-immunoprecipitated with (N Delta 661)rJAK2 but not with rJAK2 or rJAK2(C Delta 795). Both rJAK2 and (N Delta 661)rJAK2 incorporated phosphate under in vitro kinase assay conditions, but rJAK2(C Delta 795) did not. A JAK2 oligomer with interacting catalytic sites and/or inhibitory sites would provide a simple model to describe these results. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP DUHE, RJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 34 TC 40 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 SEP 29 PY 1995 VL 270 IS 39 BP 23084 EP 23089 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400070 PM 7559450 ER PT J AU GLOVER, CJ FELSTED, RL AF GLOVER, CJ FELSTED, RL TI IDENTIFICATION AND CHARACTERIZATION OF MULTIPLE FORMS OF BOVINE BRAIN N-MYRISTOYLTRANSFERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREVISIAE MYRISTOYL-COA; HUMAN IMMUNODEFICIENCY VIRUS-1; SACCHAROMYCES-CEREVISIAE; SUBSTRATE-SPECIFICITY; ESCHERICHIA-COLI; ACYL-COA; BINDING PROTEIN; ACID ANALOGS; CELL LINE; REPLICATION AB N-Myristoyltransferase (NMT) catalyzes the co-translational addition of myristic acid to the N-terminal glycine of many cellular, viral, and fungal proteins which are essential to normal cell functioning and/or are potential therapeutic targets. We have found that bovine brain NMT exists as a heterogeneous mixture of interconvertible high molecular mass multimers involving approximate to 60-kDa NMT subunit(s). Gel filtration chromatography of partially purified NMT at low to moderate ionic strength yields NMT activity eluting as 391 +/- 52 and 126 +/- 17 kDa peaks as well as activity which profiles the protein fractions and Likely results from NMT nonspecifically associating with background proteins and/or column matrix. Chromatography in 1 M NaCl causes 100% of this activity to elute as a single peak of approximate to 391 kDa. Subsequent treatment of the approximate to 391 kDa activity peak with an NMT peptide reaction product (i.e. N-myristoyl-peptide) results in approximate to 75% of the activity re-eluting as a approximate to 126-kDa peak in 1 M NaCl. Rechromatography also yields small amounts of a approximate to 50-kDa NMT monomer which increases with prior storage at 4 degrees C. Up to 5 NMT subunits were identified by SDS-polyacrylamide gel electrophoresis and specific immunoblotting with a human NMT peptide antibody and by cofactor-dependent chemical cross-linking with an I-125-peptide substrate of NMT. The prominent 60 kDa and minor 57-, 53-, 49-, and 47-kDa NMT immunoblotted subunits co-migrate with five of nine silver-stained proteins in an enzyme preparation purified >7,000-fold with approximate to 50% yield by selective elution from octyl-agarose with the myristoyl-CoA analog, S-(2-ketopentadecyl)-CoA. Storage at 4 degrees C also leads to conversion of the larger NMT subunit(s) into 49 and 47 kDa forms with no loss of NMT activity. These results identify two interconvertible forms of NR;IT in bovine brain that result from NMT subunit multimerization and/or complex formation with other cellular proteins. The data also identify a fully active NMT monomer which arises from subunit proteolysis. This study thus reveals a previously unappreciated level of NMT complexity which may have important mechanistic and/or regulatory significance for N-myristoylation in mammalian cells. RP GLOVER, CJ (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892, USA. NR 52 TC 41 Z9 42 U1 1 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 SEP 29 PY 1995 VL 270 IS 39 BP 23226 EP 23233 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400091 PM 7559471 ER PT J AU NEWMAN, AH KLINE, RH ALLEN, AC IZENWASSER, S GEORGE, C KATZ, JL AF NEWMAN, AH KLINE, RH ALLEN, AC IZENWASSER, S GEORGE, C KATZ, JL TI NOVEL 4'-SUBSTITUTED AND 4',4''-DISUBSTITUTED 3-ALPHA-(DIPHENYLMETHOXY)TROPANE ANALOGS AS POTENT AND SELECTIVE DOPAMINE UPTAKE INHIBITORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COCAINE RECEPTOR; RAT STRIATUM; UPTAKE SITES; BINDING; AFFINITY; ANTAGONIST; BRAIN AB A series of 4'-substituted and 4',4 ''-disubstituted 3 alpha-(diphenylmethoxy)tropane analogs were prepared as novel probes for the dopamine transporter. These compounds were evaluated in radiolabeled binding assays for the dopamine, norepinephrine, and serotonin transporters. All of these compounds monophasically displaced [H-3]WIN 35,428 binding in rat caudate putamen with Ki values ranging from 11.8 to 2000 nM. The most potent compound in this series was 4',4 ''-difluoro 3 alpha-(diphenylmethoxy)tropane 7c with a K-i = 11.8 nM. All of the compounds inhibited dopamine uptake in rat caudate putamen (IC50 = 24-4456 nM) which correlated significantly (r = 0.907;p > 0.0001) with binding affinities at the dopamine transporter. None of the compounds demonstrated high-affinity binding at the norepinephrine (K-i > 4800 nM) or serotonin (K-i > 690 nM) transporters. Therefore, the most potent dopamine uptake inhibitors in this series were highly selective for the dopamine transporter. Preliminary behavioral studies of several of these analogs (7a-e) suggested that the compounds did not display a cocaine-like behavioral profile, despite their ability to inhibit dopamine uptake. The present data coupled with the observed differences from cocaine in structure-activity relationships suggested that the 3 alpha-(diphenylmethoxy)tropane analogs may be interacting at a different active site than cocaine on the dopamine transporter and that an additional binding domain might be exploited for the identification of potential therapeutics for the treatment of cocaine abuse. C1 USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. RP NEWMAN, AH (reprint author), NIDA,DIV INTRAMURAL RES,PSYCHOBIOL SECT,BOX 5180,BALTIMORE,MD 21224, USA. RI Izenwasser, Sari/G-9193-2012 NR 36 TC 95 Z9 97 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 29 PY 1995 VL 38 IS 20 BP 3933 EP 3940 DI 10.1021/jm00020a006 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RY255 UT WOS:A1995RY25500006 PM 7562926 ER PT J AU PU, YM TOROK, DS ZIFFER, H PAN, XQ MESHNICK, SR AF PU, YM TOROK, DS ZIFFER, H PAN, XQ MESHNICK, SR TI SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF SEVERAL FLUORINATED ARTEMISININ DERIVATIVES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID QINGHAOSU ARTEMISININ; DRUG; CHEMISTRY; ARTEETHER AB The carbonyl groups in several artemisinin derivatives were converted into geminal difluorinated compounds on treatment with diethylaminosulfur trifluoride. A number of other mono- and polyfluorinated artemisinin derivatives were prepared. Their in vitro antimalarial activities were all equal to or greater than the nonfluorinated analogs or precursors. C1 NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. UNIV MICHIGAN,SCH PUBL HLTH,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. NR 19 TC 48 Z9 50 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 29 PY 1995 VL 38 IS 20 BP 4120 EP 4124 DI 10.1021/jm00020a028 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RY255 UT WOS:A1995RY25500028 PM 7562948 ER PT J AU POSTNIKOV, YV TRIESCHMANN, L RICKERS, A BUSTIN, M AF POSTNIKOV, YV TRIESCHMANN, L RICKERS, A BUSTIN, M TI HOMODIMERS OF CHROMOSOMAL-PROTEINS HMG-14 AND HMG-17 IN NUCLEOSOME CORES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CHROMATIN; HMG PROTEINS; NUCLEOSOMES ID MOBILITY GROUP PROTEIN-14; HUMAN CDNA SEQUENCE; MULTIGENE FAMILY; BINDING-SITES; CHROMATIN; DNA; PARTICLE; COMPLEX; DOMAIN AB In this work, we report that nucleosome core particles interact with an equimolar mixture of the chromosomal proteins HMG-14 and HMG-17 to form, exclusively, complexes containing two molecules of either HMG-14 or HMG-17 (homodimers). Analysis of the binding of various mixtures of wild-type proteins and their deletion mutants indicates that homodimer formation is not dependent on contacts between the nucleosome-bound HMG-14/-17 proteins themselves. We suggest that HMG-14/-17 proteins in nucleosomes cross-talk by inducing specific allosteric transitions in the chromatin subunit. (C) 1995 Academic Press Limited RP POSTNIKOV, YV (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,BETHESDA,MD 20892, USA. RI Bustin, Michael/G-6155-2015 NR 36 TC 44 Z9 44 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 29 PY 1995 VL 252 IS 4 BP 423 EP 432 DI 10.1006/jmbi.1995.0508 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX458 UT WOS:A1995RX45800005 PM 7563062 ER PT J AU TORTELLA, FC KLETTE, KL DECOSTER, MA DAVIS, BJ NEWMAN, AH AF TORTELLA, FC KLETTE, KL DECOSTER, MA DAVIS, BJ NEWMAN, AH TI DEXTROMETHORPHAN ANALOGS ARE NEUROPROTECTIVE IN-VITRO AND BLOCK GLUTAMATE-INDUCED EXCITOTOXIC CALCIUM SIGNALS IN NEURONS SO NEUROSCIENCE LETTERS LA English DT Article DE DEXTROMETHORPHAN; DEXTROMETHORPHAN ANALOGS; GLUTAMATE; NEURONAL INJURY; CALCIUM; CELL CULTURE ID NEUROTOXICITY; DEXTRORPHAN; LIGANDS AB Consistent with the neuroprotective effects of the non-opioid antitussive dextromethorphan (DM) described in several models of CNS injury, micromolar concentrations of three novel analogs of DM markedly attenuated the injury produced by glutamate in cultured rat cortical neurons. Furthermore, the neuroprotective actions of the DM analogs correlated with their effects to block glutamate-induced excitotoxic calcium signals and were unrelated to metabolism to the phencyclidine (PCP)-like drug dextrorphan (DX). These observations establish a new class of compounds related to DM which, by virtue of their efficacy to protect neurons against a severe glutamate insult, may possess therapeutic potential as treatment modalities for a number of neurodegenerative diseases. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD 21224. RP TORTELLA, FC (reprint author), WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT NEUROPHARMACOL & MOLEC BIOL,WASHINGTON,DC 20307, USA. NR 13 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI PUBL 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 SEP 29 PY 1995 VL 198 IS 2 BP 79 EP 82 DI 10.1016/0304-3940(95)11966-Z PG 4 WC Neurosciences SC Neurosciences & Neurology GA TA406 UT WOS:A1995TA40600003 PM 8592646 ER PT J AU OHNO, H STEWART, J FOURNIER, MC BOSSHART, H RHEE, I MIYATAKE, S SAITO, T GALLUSSER, A KIRCHHAUSEN, T BONIFACINO, JS AF OHNO, H STEWART, J FOURNIER, MC BOSSHART, H RHEE, I MIYATAKE, S SAITO, T GALLUSSER, A KIRCHHAUSEN, T BONIFACINO, JS TI INTERACTION OF TYROSINE-BASED SORTING SIGNALS WITH CLATHRIN-ASSOCIATED PROTEINS SO SCIENCE LA English DT Article ID TRANS-GOLGI NETWORK; PLASMA-MEMBRANE; COATED VESICLES; CYTOPLASMIC DOMAIN; INVITRO BINDING; RECEPTOR; SEQUENCE; CLONING; TGN38; MOTIF AB Tyrosine-based signals within the cytoplasmic domain of integral membrane proteins mediate clathrin-dependent protein sorting in the endocytic and secretory pathways. A yeast two-hybrid system was used to identify proteins that bind to tyrosine-based signals. The medium chains (mu(1) and mu(2)) of two clathrin-associated protein complexes (AP-1 and AP-2, respectively) specifically interacted with tyrosine-based signals of several integral membrane proteins. The interaction was confirmed by in vitro binding assays. Thus, it is likely that the medium chains serve as signal-binding components of the clathrin-dependent sorting machinery. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. CHIBA UNIV,SCH MED,CTR BIOMED SCI,DIV MOLEC GENET,CHIBA 260,JAPAN. RI Yang, Chen/G-1379-2010; Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014; OI Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 NR 35 TC 733 Z9 740 U1 5 U2 20 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 29 PY 1995 VL 269 IS 5232 BP 1872 EP 1875 DI 10.1126/science.7569928 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX194 UT WOS:A1995RX19400038 PM 7569928 ER PT J AU ROSSOUW, JE AF ROSSOUW, JE TI LIPID-LOWERING INTERVENTIONS IN ANGIOGRAPHIC TRIALS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cholesterol-Lowering Trials - New Results and Emerging Issues CY MAR 03-04, 1995 CL PALM BEACH, FL SP Bristol Myers Squibb ID CORONARY-ARTERY DISEASE; ATHEROSCLEROSIS-REGRESSION; HEART-DISEASE; THERAPY; PROGRESSION; HYPERCHOLESTEROLEMIA; CHOLESTYRAMINE; PATHOGENESIS; MECHANISMS; DIET AB This analysis examines the pooled data from all 14 published randomized angiographic trials (with 16 treatment arms) by type of cholesterol-lowering intervention evaluated, and for all the trials combined. All interventions reduced low density lipoprotein (LDL) cholesterol levels (average reduction, 26%), whereas the effects on high density lipoprotein (HDL) cholesterol and triglycerides varied by type of intervention. Meta-analyses of the angiographic outcomes indicated that treatment reduced the odds for disease progression by 49%, increased the odds for no change by 33%, and increased the odds for regression by 219%. Cardiovascular events were reduced by 47%. Thus, lipid reduction is effective for modifying the angiographic outcome and for reducing the incidence of coronary artery disease events. All types of intervention (lifestyle, drugs, or surgery) had overall favorable effects on angiographic and clinical outcomes. There was no class effect for the statin group of drugs. Surgery (partial ileal bypass) had the most favorable angiographic outcome, possibly because of a longer duration of therapy. Trials with higher baseline LDL levels tended to have more favorable angiographic outcomes. Analyses of in-trial levels of LDL were confounded by baseline levels, and analyses of change in LDL levels in the treatment groups were confounded by not including zero change (i.e., no treatment). It is hypothesized that lowering LDL levels by 30 mg/dl (0.8 mmol/liter) is sufficient on average to modify the angiographic outcome, with modest gains from further reductions in LDL levels. RP ROSSOUW, JE (reprint author), NIH,OFF DIS PREVENT,OFF DIRECTOR,FED BLDG,ROOM 6A09,BETHESDA,MD 20982, USA. NR 20 TC 80 Z9 82 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 28 PY 1995 VL 76 IS 9 SI SI BP C86 EP C92 DI 10.1016/S0002-9149(99)80476-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RW474 UT WOS:A1995RW47400014 PM 7572693 ER PT J AU FERNANDEZSALGUERO, P GONZALEZ, FJ ETIENNE, MC MILANO, G KIMURA, S AF FERNANDEZSALGUERO, P GONZALEZ, FJ ETIENNE, MC MILANO, G KIMURA, S TI CORRELATION BETWEEN CATALYTIC ACTIVITY AND PROTEIN-CONTENT FOR THE POLYMORPHICALLY EXPRESSED DIHYDROPYRIMIDINE DEHYDROGENASE IN HUMAN-LYMPHOCYTES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE TLC, DIHYDROPYRIMIDINE DEHYDROGENASE ASSAY; 5-FLUOROURACIL TOXICITY ID MONONUCLEAR-CELLS; PIG-LIVER; DEFICIENCY; ENZYMES; PURIFICATION; CATABOLISM; THYMINE; URACIL; BLOOD AB A TLC procedure was developed to determine dihydropyrimidine dehydrogenase (DPD) activity in human peripheral lymphocytes. The assay, which used radiolabeled uracil as a substrate, was validated using recombinant pig DPD in which it was demonstrated to yield kinetic constants similar to those found by methods that rely on either spectroscopic determination of NADPH oxidation or HPLC. DPD activity was measured in a group of human lymphocyte extracts, including an extract from a subject that actually presented toxicity to 5-fluorouracil treatment. Measurements of DPD protein content using western immunoblots revealed a significant correlation with activity levels in human lymphocytes. Thus, this correlation could be used to determine not only the levels of expression of this enzyme, which is the cause of an inherited genetic deficiency in pyrimidine catabolism, but also to estimate the degree of sensitivity to pyrimidine-based cancer drugs such as 5-fluorouracil. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. CTR ANTOINE LACASSAGNE,ONCOPHARMACOL LAB,F-06050 NICE,FRANCE. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 19 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 28 PY 1995 VL 50 IS 7 BP 1015 EP 1020 DI 10.1016/0006-2952(95)00231-N PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA192 UT WOS:A1995TA19200017 PM 7575656 ER PT J AU ZHENG, LX FISHER, G MILLER, RE PESCHON, J LYNCH, DH LENARDO, MJ AF ZHENG, LX FISHER, G MILLER, RE PESCHON, J LYNCH, DH LENARDO, MJ TI INDUCTION OF APOPTOSIS IN MATURE T-CELLS BY TUMOR-NECROSIS-FACTOR SO NATURE LA English DT Article ID FACTOR-ALPHA; MICE AB T-CELL receptor-induced apoptosis regulates immune responses and can result from interactions between Fas (Apo1/CD95) and Fas ligand (FasL)(1-12). Mutations in the genes for Fas and FasL cause disorders resembling human autoimmune diseases in lpr and gld mice, respectively(13,14). However, peripheral T-cell deletion takes place in lpr mice, acid autoimmune syndromes occur in mouse strains without Fas or FasL defects(15,16). Here we show that tumour necrosis factor (TNF) can mediate mature T-cell receptor-induced apoptosis through the p75 TNF receptor. Blockage of both TNF and Fast is required to abrogate T-cell death and TNF mediates the death of most CD8(+) T cells, whereas FasL mediates the death of most CD4(+) T cells. Our results suggest that autoregulatory apoptosis of the mature T cells can occur by two distinct molecular mechanisms. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. IMMUNEX RES & DEV CORP,DEPT IMMUNOBIOL,SEATTLE,WA 98101. NR 29 TC 951 Z9 961 U1 2 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 28 PY 1995 VL 377 IS 6547 BP 348 EP 351 DI 10.1038/377348a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX111 UT WOS:A1995RX11100059 PM 7566090 ER PT J AU HIRSCHTICK, RE GLASSROTH, J JORDAN, MC WILCOSKY, TC WALLACE, JM KVALE, PA MARKOWITZ, N ROSEN, MJ MANGURA, BT HOPEWELL, PC STANSELL, J TURNER, J OSMOND, D MERRIFIELD, C MOSSAR, M HIRSCHTICK, R MEISELMAN, L MANGHISI, KJ SCHNEIDER, RF REICHMAN, LB MANGURA, B BARNES, S RICHER, B AU, J COULSON, A CLEMENTE, V SARAVOLATZ, LD JOHNSON, C HUITSING, J KRYSTOFORSKI, A POOLE, WK RAO, AV CLAYTON, K HANSON, N JORDAN, M THOMPSON, J MYERS, D LAVANGE, L KATZIN, J FULKERSON, W WILCOSKY, T LOU, Y KALICA, AR WITTES, J FOLLMANN, D AF HIRSCHTICK, RE GLASSROTH, J JORDAN, MC WILCOSKY, TC WALLACE, JM KVALE, PA MARKOWITZ, N ROSEN, MJ MANGURA, BT HOPEWELL, PC STANSELL, J TURNER, J OSMOND, D MERRIFIELD, C MOSSAR, M HIRSCHTICK, R MEISELMAN, L MANGHISI, KJ SCHNEIDER, RF REICHMAN, LB MANGURA, B BARNES, S RICHER, B AU, J COULSON, A CLEMENTE, V SARAVOLATZ, LD JOHNSON, C HUITSING, J KRYSTOFORSKI, A POOLE, WK RAO, AV CLAYTON, K HANSON, N JORDAN, M THOMPSON, J MYERS, D LAVANGE, L KATZIN, J FULKERSON, W WILCOSKY, T LOU, Y KALICA, AR WITTES, J FOLLMANN, D TI BACTERIAL PNEUMONIA IN PERSONS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; COMMUNITY-ACQUIRED PNEUMONIA; INTRAVENOUS-DRUG-USERS; TRIMETHOPRIM-SULFAMETHOXAZOLE; PULMONARY COMPLICATIONS; AEROSOLIZED PENTAMIDINE; HOSPITALIZED-PATIENTS; CONTROLLED TRIAL; AIDS AB Background. Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined. Methods. In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men, Results. There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P<0.001). The rate of bacterial pneumonia increased with decreasing CD4 lymphocyte counts (2.3, 6.8, and 10.8 episodes per 100 person-years in the strata with more than 500, 200 to 500, and fewer than 200 cells per cubic millimeter, respectively; P less than or equal to 0.022 for each comparison). injection-drug users had a higher rate of bacterial pneumonia than did homosexual or bisexual men or female partners, In the stratum with the fewest CD4 lymphocytes, cigarette smoking was associated with an increased rate of pneumonia. Mortality was almost four times higher among participants with an episode of pneumonia than among the others, Prophylaxis with trimethoprim-sulfamethoxazole was associated with a 67 percent reduction in confirmed episodes of bacterial pneumonia (P=0.007). Conclusions. Bacterial pneumonia is more frequent in HIV-positive persons than in seronegative controls, and the risk is highest among those with CD4 lymphocyte counts below 200 per cubic millimeter and among injection-drug users. C1 NORTHWESTERN UNIV,PULM MED SECT,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. HENRY FORD HOSP,DETROIT,MI 48202. BETH ISRAEL MED CTR,NEW YORK,NY 10003. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. UNIV MED & DENT NEW JERSEY HOSP,NEW JERSEY MED SCH,NEWARK,NJ. RES TRIANGLE INST,CTR COORDINATING,RES TRIANGLE PK,NC 27709. NHLBI,BETHESDA,MD 20892. RP HIRSCHTICK, RE (reprint author), NORTHWESTERN UNIV,INFECT DIS SECT,303 E SUPERIOR,PASSAVANT 828,CHICAGO,IL 60611, USA. FU NHLBI NIH HHS [N01-HR7-6029, N01-HR7-6030, N01-HR7-6031] NR 42 TC 439 Z9 444 U1 1 U2 3 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 SEP 28 PY 1995 VL 333 IS 13 BP 845 EP 851 DI 10.1056/NEJM199509283331305 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RW883 UT WOS:A1995RW88300005 PM 7651475 ER PT J AU SHACK, S CHEN, LC MILLER, AC DANESI, R SAMID, D AF SHACK, S CHEN, LC MILLER, AC DANESI, R SAMID, D TI INCREASED SUSCEPTIBILITY OF RAS-TRANSFORMED CELLS TO PHENYLACETATE IS ASSOCIATED WITH INHIBITION OF P21(RAS) ISOPRENYLATION AND PHENOTYPIC REVERSION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID FATTY-ACIDS; LOVASTATIN; EXPRESSION; GROWTH; ACTIVATION; SYNTHETASE; PHENYL AB Alterations in the expression of res oncogenes are characteristic of a wide variety of human neoplasms. Accumulating evidence has linked elevated res expression with disease progression and with failure of tumors to respond to conventional therapies, including radiotherapy and certain chemotherapies. These observations led us to investigate the response of ras-transformed cells to the differentiation-inducer phenylacetate (PA), Using gene transfer models, we show that PA caused cytostasis in res-transformed mesenchymal cells, associated with increased expression of 2',5'-oligoadenylate synthetase, an enzyme implicated in negative growth control. PA also induced phenotypic reversion characterized by loss of anchorage-independent growth, reduced invasiveness and increased expression of collagen alpha type 1, a marker of cell differentiation. The anti-tumor activity of PA was observed in cases involving either Ha- or Ki-rat and was independent of the mode of oncogene activation. Interestingly, in contrast to their relative resistance to radiation and doxorubicin, res-transformed cells were significantly more sensitive to PA than their parental cells. The profound changes in tumor cell and molecular biology were associated with reduced isoprenylation of the res-encoded p21. Our results indicate that PA can suppress the growth of res-transformed cells, resistant otherwise to free-radical based therapies, through interference with p21(ras) isoprenylation, critical to signal transduction and maintenance of the malignant phenotype. (C) 1995 Wiley-Liss, Inc. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. ARMED FORCES RADIAT RES INST,DEPT RADIAT BIOCHEM,BETHESDA,MD 20814. NR 28 TC 26 Z9 28 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 SEP 27 PY 1995 VL 63 IS 1 BP 124 EP 129 DI 10.1002/ijc.2910630122 PG 6 WC Oncology SC Oncology GA RX634 UT WOS:A1995RX63400021 PM 7558439 ER PT J AU WILLINGER, M AF WILLINGER, M TI SUDDEN-INFANT-DEATH-SYNDROME AND CIRCADIAN-RHYTHM - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP WILLINGER, M (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 27 PY 1995 VL 274 IS 12 BP 944 EP 944 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RV734 UT WOS:A1995RV73400026 ER PT J AU PICKAR, D HSIAO, JK AF PICKAR, D HSIAO, JK TI CLOZAPINE TREATMENT OF SCHIZOPHRENIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; DOPAMINE; CHLORPROMAZINE; ABNORMALITIES; NEUROLEPTICS; DRUGS RP PICKAR, D (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 4N-212,BETHESDA,MD 20892, USA. NR 25 TC 7 Z9 7 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 SEP 27 PY 1995 VL 274 IS 12 BP 981 EP 983 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA RV734 UT WOS:A1995RV73400034 PM 7674530 ER PT J AU EHRENSTEIN, D FILIACI, M SCHARF, B ENGELHARD, M STEINBACH, PJ NIENHAUS, GU AF EHRENSTEIN, D FILIACI, M SCHARF, B ENGELHARD, M STEINBACH, PJ NIENHAUS, GU TI LIGAND-BINDING AND PROTEIN DYNAMICS IN CUPREDOXINS SO BIOCHEMISTRY LA English DT Article ID PSEUDOMONAS-AERUGINOSA AZURIN; BARRIER HEIGHT DISTRIBUTIONS; TYPE-2 COPPER SITES; HEME-PROTEINS; NITRIC-OXIDE; EXOGENOUS LIGANDS; CRYSTAL-STRUCTURE; HIS117GLY MUTANT; CARBON-MONOXIDE; BLUE AB Type 1 copper sites bind nitric oxide (NO) in a photolabile complex. We have studied the NO binding properties of the type 1 copper sites in two cupredoxins, azurin and halocyanin, by measuring the temperature dependence of the ligand binding equilibria and the kinetics of the association reaction after photodissociation over a wide range of temperature (80-280 K) and time (10(-6)-10(-7) s). In both proteins, we find nonexponential kinetics below 200 K that do not depend on the NO concentration, Consequently, this process is interpreted as geminate recombination. In azurin, the rebinding can be modeled with the Arrhenius law using a single pre-exponential factor of 10(8.3) s(-1) and a Gaussian distribution of enthalpy barriers centered at 22 kJ/mol with a width [full width at half-maximum (FWHM)] of 11 kJ/mol. In halocyanin, a more complex behavior is observed. About 97% of the rebinding population can also be characterized by a Gaussian distribution of enthalpy barriers at 12 kJ/mol with a width of 6.0 kJ/mol (FWHM). The pre-exponential of this population is 1.6 x 10(12) s(-1) at 100 K. After the majority population has rebound, a power-law phase that can be modeled with a gamma-distribution of enthalpy barriers is observed. Between 120 and 180 K, an additional feature that can be interpreted as a relaxation of the barrier distribution toward higher barriers shows up in the kinetics. Above 200 K, a slower, exponential rebinding appears in both cupredoxins. Since the kinetics depend on the NO concentration, this process is identified as bimolecular rebinding, Structural aspects of the copper-NO complex are discussed. NO binding to cupredoxins shows interesting analogies to the ligand binding reaction in heme proteins. Thus, we conclude that the concepts regarding conformational heterogeneity and dynamics, which have been developed from heme protein experiments, are also applicable to proteins with different active sites and secondary structures. C1 UNIV ILLINOIS,DEPT PHYS,URBANA,IL 61801. MAX PLANCK INST MOLEK PHYSIOL,D-44139 DORTMUND,GERMANY. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RI Nienhaus, Gerd Ulrich/G-8698-2012 OI Nienhaus, Gerd Ulrich/0000-0002-5027-3192 FU NIGMS NIH HHS [GM 18051] NR 54 TC 14 Z9 14 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 26 PY 1995 VL 34 IS 38 BP 12170 EP 12177 DI 10.1021/bi00038a010 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX235 UT WOS:A1995RX23500010 PM 7547957 ER PT J AU ROBERTS, MS FRAGOSO, G HAGER, GL AF ROBERTS, MS FRAGOSO, G HAGER, GL TI NUCLEOSOMES RECONSTITUTED IN-VITRO ON MOUSE MAMMARY-TUMOR VIRUS-B REGION DNA OCCUPY MULTIPLE TRANSLATIONAL AND ROTATIONAL FRAMES SO BIOCHEMISTRY LA English DT Article ID GLUCOCORTICOID RECEPTOR; MMTV PROMOTER; 5S RNA; POSITIONED NUCLEOSOMES; RETROVIRAL INTEGRATION; REGULATORY NUCLEOSOME; STRUCTURAL FEATURES; SATELLITE DNA; CORE PARTICLE; HISTONE CORE AB The mouse mammary tumor virus acquires a highly reproducible chromatin structure when integrated into cellular DNA. Previous studies have suggested that the LTR is arranged as a series of six phased nucleosomes, that occupy specific positions on the LTR. On the basis of nucleosome reconstitution studies using DNA from the B region of the LTR, it has been argued that this sequence directs a uniquely positioned nucleosome. Here we demonstrate in vitro that reconstituted B region nucleosomes adopt at least five distinct translational positions in two rotational frames on a 206 bp fragment of DNA. We have resolved an initial reconstitute into its component species using nondenaturing gel electrophoresis, and precisely mapped the positions of each species using a hydroxyl radical footprinting assay. To confirm the nucleosome positions determined with the hydroxyl radical assay, nucleosome boundaries were mapped using exonuclease III. Comparison of the results from the hydroxyl radical footprinting and exonuclease III assays revealed a symmetrical pattern of overdigestion by exonuclease III which made unequivocal determination of nucleosome boundaries dubious. We conclude that the general use of exonuclease III to map the positions of nucleosomes may lead to incorrect assignment of position, and that assignment of position through the determination of the nucleosome pseudo-dyad from hydroxyl radical footprinting data represents a superior method of analysis. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 63 TC 44 Z9 44 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 26 PY 1995 VL 34 IS 38 BP 12470 EP 12480 DI 10.1021/bi00038a046 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX235 UT WOS:A1995RX23500046 PM 7547993 ER PT J AU SZKUDLINSKI, MW THOTAKURA, NR WEINTRAUB, BD AF SZKUDLINSKI, MW THOTAKURA, NR WEINTRAUB, BD TI SUBUNIT-SPECIFIC FUNCTIONS OF N-LINKED OLIGOSACCHARIDES IN HUMAN THYROTROPIN - ROLE OF TERMINAL RESIDUES OF ALPHA-SUBUNIT AND BETA-SUBUNIT OLIGOSACCHARIDES IN METABOLIC-CLEARANCE AND BIOACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; THYROID-STIMULATING HORMONE; HAMSTER OVARY CELLS; GLYCOPROTEIN HORMONES; SIGNAL TRANSDUCTION; BIOLOGICAL-ACTIVITY; SIALIC-ACID; CARBOHYDRATE; SULFATION; BOVINE AB The recombinant human thyroid stimulating hormone (rhTSH) containing oligosaccharides terminated with NeuAc(alpha 2-3)Gal(beta 1-4)GlcNAc beta 1 showed higher in vivo activity and lower metabolic clearance rate (MCR) than pituitary human TSH (phTSH), which contains oligosaccharides terminating predominantly in SO(4)GalNAc(beta 1-4)GlcNAc beta 1. To elucidate the relative contribution of the sulfated and sialylated carbohydrate chains of each subunit in the MCR and bioactivity of the hormone, the alpha and beta subunits of phTSH, rhTSH, and enzymatically desialylated rhTSH (asialo-rhTSH; asrhTSH) were isolated, their oligosaccharides were analyzed, and the respective subunits were dimerized in various combinations, The hybrids containing alpha subunit from phTSH or asrhTSH showed higher in vitro activity than those with alpha subunit from rhTSH, indicating that sialylation of alpha but not beta subunit attenuates the intrinsic activity of TSH. In contrast, hybrids with beta subunit from rhTSH displayed lower MCR compared to those with beta subunit from phTSH. The phTSH alpha-rhTSH beta hybrid had the highest in vivo bioactivity followed by rhTSH alpha-rhTSH beta, rhTSH alpha-phTSH beta, phTSH alpha-phTSR beta, and asrhTSH dimers, These differences indicated that hybrids with beta subunit from rhTSH displayed the highest in vivo activity and relatively low MCR, probably due to higher sialylation, more multiantennary structure, and/or the unique location of the beta-subunit oligosacharide chain in the molecule, Thus, the N-linked oligosaccharides of the beta subunit of glycoprotein hormones have a more pronounced role than those from the alpha subunit in the metabolic clearance and thereby in the in vivo bioactivity, In contrast, the terminal residues of alpha-subunit oligosaccharides have a major impact on TSH intrinsic potency. C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 33 TC 31 Z9 31 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 SEP 26 PY 1995 VL 92 IS 20 BP 9062 EP 9066 DI 10.1073/pnas.92.20.9062 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000012 PM 7568073 ER PT J AU HALEEMSMITH, H CHANG, EY SZALLASI, Z BLUMBERG, PM RIVERA, J AF HALEEMSMITH, H CHANG, EY SZALLASI, Z BLUMBERG, PM RIVERA, J TI TYROSINE PHOSPHORYLATION OF PROTEIN-KINASE C-DELTA IN RESPONSE TO THE ACTIVATION OF THE HIGH-AFFINITY RECEPTOR FOR IMMUNOGLOBULIN-E MODIFIES ITS SUBSTRATE RECOGNITION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MAST CELL; SIGNALING; FC-EPSILON-RI ID BASOPHILIC RBL-2H3 CELLS; FC-EPSILON-RI; IGE RECEPTORS; MAST-CELLS; EXOCYTOSIS; EXPRESSION; MEMBRANE; ISOZYMES AB The delta isoform of protein kinase C is phosphorylated on tyrosine in response to antigen activation of the high-affinity receptor for immunoglobulin E, While protein kinase C-delta associates with and phosphorylates this receptor, immunoprecipitation of the receptor revealed that little, if any, tyrosine-phosphorylated protein kinase C-delta is receptor associated, rn vitro kinase assays with immunoprecipitated tyrosine-phosphorylated protein kinase C-delta showed that the modified enzyme had diminished activity toward the receptor gamma-chain peptide as a substrate but not toward histones or myelin basic protein peptide. We propose a model in which the tyrosine phosphorylation of protein kinase C-delta regulates the kinase specificity toward a given substrate, This may represent a general mechanism by which in vivo protein kinase activities are regulated in response to external stimuli. C1 NIAMSD,CHEM IMMUNOL SECT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 22 TC 62 Z9 62 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 SEP 26 PY 1995 VL 92 IS 20 BP 9112 EP 9116 DI 10.1073/pnas.92.20.9112 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000022 PM 7568083 ER PT J AU JI, H ZHENG, W ZHANG, Y CATT, KJ SANDBERG, K AF JI, H ZHENG, W ZHANG, Y CATT, KJ SANDBERG, K TI GENETIC TRANSFER OF A NONPEPTIDE ANTAGONIST BINDING-SITE TO A PREVIOUSLY UNRESPONSIVE ANGIOTENSIN RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID II RECEPTORS; SUBSTANCE-P; EXPRESSION; DISTINCT; CLONING AB Mutational analysis based on the pharmacological differences between mammalian and amphibian angiotensin II receptors (AT receptors) previously identified 7 aa residues located in transmembrane domains (TMs) III (Val-108), IV (Ala-163), V (Pro-192, Thr-198), VI (Ser-252), and VII (Leu-300, Phe-301) of the rat AT receptor type 1b (rAT(1b) receptor) that significantly influenced binding of the nonpeptide antagonist Losartan. Further studies have shown that an additional 6 residues in the rAT(1b) receptor TMs II (Ala-73), III (Ser-109, Ala-114, Ser-115), VI (Phe-248), and VII (Asn-295) are important in Losartan binding. The 13 residues required for Losartan binding in the mammalian receptor were exchanged for the corresponding amino acids in the Xenopus AT receptor type a (xAT(a) receptor) to generate a mutant amphibian receptor that bound Losartan with the same affinity as the rAT(1b) receptor (Losartan IC50 values: rAT(1b), 2.2 +/- 0.2 nM: xATa, > 50 mu M; mutant, 2.0 +/- 0.1 nM), To our knowledge, this is the first report of a gain-of-function mutant in which the residues crucial to formation of a ligand binding site in a mammalian peptide hormone receptor were transferred to a previously unresponsive receptor by site-directed mutagenesis. Ala substitutions and comparison of mammalian and amphibian combinatorial mutants indicated that TM III in the rAT(1b) receptor plays a key role in Losartan binding, Identification of residues involved in nonpeptide ligand binding will facilitate studies aimed at elucidating the chemical basis for ligand recognition in the AT receptor and peptide hormone receptors in general. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,DIV NEPHROL & HYPERTENS,WASHINGTON,DC 20007. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 30 TC 52 Z9 52 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 SEP 26 PY 1995 VL 92 IS 20 BP 9240 EP 9244 DI 10.1073/pnas.92.20.9240 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000048 PM 7568109 ER PT J AU DONEVAN, SD ROGAWSKI, MA AF DONEVAN, SD ROGAWSKI, MA TI INTRACELLULAR POLYAMINES MEDIATE INWARD RECTIFICATION OF CA2+-PERMEABLE ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID RECEPTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SPERMINE; SPERMIDINE; EXCITATORY AMINO ACID RECEPTOR ID RAT HIPPOCAMPAL-NEURONS; STRUCTURAL DETERMINANTS; AMPHOTERICIN-B; SINGLE-CHANNEL; WHOLE-CELL; ION FLOW; PERMEABILITY; RESPONSES; PERMEATION; SUBUNIT AB alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that lack the glutamate receptor GluR2 subunit are Ca2+-permeable and exhibit inwardly rectifying current responses to kainate and AMPA. A proportion of cultured rat hippocampal neurons show similar Ca2+-permeable inwardly rectifying AMPA receptor currents. Inward rectification in these neurons was lost with intracellular dialysis and was not present in excised outside-out patches but was maintained in perforated-patch whole-cell recordings, suggesting that a diffusible cytoplasmic factor may be responsible for rectification. Inclusion of the naturally occurring polyamines spermine and spermidine in the recording pipette prevented loss of rectification in both whole-cell and excised-patch recordings; Mg2+ and putrescine were without effect. Inward rectification of Ca2+-permeable AMPA receptors may reflect voltage-dependent channel block by intracellular polyamines. C1 NINDS,EPILEPSY RES BRANCH,NEURONAL EXCITABIL SECT,BETHESDA,MD. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 40 TC 162 Z9 162 U1 0 U2 4 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 SEP 26 PY 1995 VL 92 IS 20 BP 9298 EP 9302 DI 10.1073/pnas.92.20.9298 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000060 PM 7568121 ER PT J AU LI, M DYDA, F BENHAR, I PASTAN, I DAVIES, DR AF LI, M DYDA, F BENHAR, I PASTAN, I DAVIES, DR TI THE CRYSTAL-STRUCTURE OF PSEUDOMONAS-AERUGINOSA EXOTOXIN DOMAIN-III WITH NICOTINAMIDE AND AMP - CONFORMATIONAL DIFFERENCES WITH THE INTACT EXOTOXIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVE-SITE; DIPHTHERIA-TOXIN; GLUTAMIC ACID-553; ESCHERICHIA-COLI; NAD; EXPRESSION; MECHANISM; DELETION; SEQUENCE; HOMOLOGY AB Domain III of Pseudomonas aeruginosa exotoxin A catalyses the transfer of ADP-ribose from NAD to a modified histidine residue of elongation factor 2 in eukaryotic cells, thus inactivating elongation factor 2. This domain III is inactive in the intact toxin but is active in the isolated form. We report here the 2.5-Angstrom crystal structure of this isolated domain crystallized in the presence of NAD and compare it with the corresponding structure in the intact Pseudomonas aeruginosa exotoxin A. We observe a significant conformational difference in the active site region from Arg-458 to Asp-463. Contacts with part of domain II in the intact toxin prevent the adoption of the isolated domain conformation and provide a structural explanation for the observed inactivity. Additional electron density in the active site region corresponds to separate AMP and nicotinamide and indicates that the NAD has been hydrolyzed. The structure has been compared with the catalytic domain of the diphtheria toxin, which was crystallized with ApUp. C1 NIDDK, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NIH, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 35 TC 52 Z9 53 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 26 PY 1995 VL 92 IS 20 BP 9308 EP 9312 DI 10.1073/pnas.92.20.9308 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000062 PM 7568123 ER PT J AU MORIUCHI, H MORIUCHI, M PICHYANGKURA, R TRIEZENBERG, SJ STRAUS, SE COHEN, JI AF MORIUCHI, H MORIUCHI, M PICHYANGKURA, R TRIEZENBERG, SJ STRAUS, SE COHEN, JI TI HYDROPHOBIC CLUSTER-ANALYSIS PREDICTS AN AMINO-TERMINAL DOMAIN OF VARICELLA-ZOSTER VIRUS OPEN-READING-FRAME-10 REQUIRED FOR TRANSCRIPTIONAL ACTIVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HERPESVIRUS; VP16; TRANSCRIPTION ID IMMEDIATE-EARLY PROTEIN; DNA-SEQUENCE; REGULATORY PROTEIN; ACID-SEQUENCES; BINDING; VP16; GENE; PROMOTERS; POLYMERASE; NUCLEOTIDE AB Varicella-zoster virus open reading frame 10 (ORF10) protein, the homolog of the herpes simplex virus protein VP16, fan transactivate immediate-early promoters from both viruses. A protein sequence comparison procedure termed hydrophobic cluster analysis was used to identify a motif centered at Phe-28, near the amino terminus of ORF10, that strongly resembles the sequence of the activating domain surrounding Phe-442 of VP16. With a series of GAL4-ORF10 fusion proteins, we mapped the ORF10 transcriptional-activation domain to the amino-terminal region (aa 5-79). Extensive mutagenesis of Phe-28 in GAL4-ORF10 fusion proteins demonstrated the importance of an aromatic or bulky hydrophobic amino acid at this position, as shown previously for Phe-442 of VP16. Transactivation by the native ORF10 protein was abolished when Phe-28 was replaced by Ala. Similar amino-terminal domains were identified in the VP16 homologs of other alphaherpesviruses. Hydrophobic cluster analysis correctly predicted activation domains of ORF10 and VP16 that share critical characteristics of a distinctive subclass of acidic activation domains. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. FU NIAID NIH HHS [K04-AI01284, R05-AI27323] NR 34 TC 20 Z9 20 U1 1 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 SEP 26 PY 1995 VL 92 IS 20 BP 9333 EP 9337 DI 10.1073/pnas.92.20.9333 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000067 PM 7568128 ER PT J AU PASSINI, N LARIGAN, JD GENOVESE, S APPELLA, E SINIGAGLIA, F ROGGE, L AF PASSINI, N LARIGAN, JD GENOVESE, S APPELLA, E SINIGAGLIA, F ROGGE, L TI THE 37/40-KILODALTON AUTOANTIGEN IN INSULIN-DEPENDENT DIABETES-MELLITUS IS THE PUTATIVE TYROSINE PHOSPHATASE IA-2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ISLET CELL ANTIBODIES; AUTOANTIBODIES; EXPRESSION CLONING; PREDICTION OF TYPE I DIABETES; ANTIGENS ID ISLET-CELL ANTIBODIES; GLUTAMATE-DECARBOXYLASE; DISTINCT; ANTIGEN; IDDM AB Major targets for autoantibodies associated with the development of insulin-dependent diabetes mellitus (IDDM) include tryptic fragments with a molecular mass of 37 kDa and/or 40 kDa of a pancreatic islet cell antigen of unknown identity, The assay identifying autoantibodies against the 37/40-kDa antigen in human sera is based on the immunoprecipitation of S-35-labeled rat insulinoma cell proteins with sera from IDDM patients, followed by limited trypsin digestion of the immunoprecipitated material, To identify cDNA clones coding for the 37/40-kDa antigen, we have screened a cDNA expression library from rat insulinoma cells with a serum from an IDDM patient that precipitated the 37/40-kDa antigen in our assay, Among the cDNA products that reacted with the IDDM serum, we identified one cDNA clone whose open reading frame encodes a protein with a predicted mass of 105 kDa that we termed ''ICA105'' for 105-kDa islet cell antibody, The deduced amino acid sequence has high homology to a recently cloned putative tyrosine phosphatase IA-2 from human and mouse cDNA libraries, Translation of the cDNA in vitro results in a polypeptide with the expected molecular mass of 105 kDa, The evidence that ICA105 is indeed the precursor of the 37/40-kDa tryptic fragments is based on the following three results: (i) Sera from IDDM patients containing autoantibodies to the 37/40-kDa antigen precipitate the in vitro translated polypeptide, whereas sera from healthy subjects as well as sera from IDDM patients not reactive with the 37/40-kDa antigen do not precipitate the cDNA product, (ii) Immunoprecipitation of the in vitro translated protein with sera containing autoantibodies to the 37/40-kDa antigen followed by limited trypsin digestion of the precipitated proteins results in a 40-kDa polypeptide. (iii) The protein derived from our cDNA but not from an unrelated control cDNA clone fan block immunoprecipitation of the 37/40-kDa antigen from a labeled rat insulinoma cell extract, The availability of the cloned 37/40-kDa antigen should facilitate the identification of individuals at risk of IDDM with increased accuracy, Furthermore, the identification of the 37/40-kDa antigen as the putative tyrosine phosphatase IA-2 is of relevance in elucidating the role of this antigen in the development of IDDM. C1 ROCHE MILANO RIC,I-20132 MILAN,ITALY. HOFFMANN LA ROCHE INC,DEPT BIOTECHNOL,NUTLEY,NJ 07110. IST SCI SAN RAFFAELE,DEPT MED,I-20132 MILAN,ITALY. NCI,DEPT HLTH,BETHESDA,MD 20892. NCI,HUMAN SERV,BETHESDA,MD 20892. NR 21 TC 75 Z9 76 U1 0 U2 6 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 SEP 26 PY 1995 VL 92 IS 20 BP 9412 EP 9416 DI 10.1073/pnas.92.20.9412 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000083 PM 7568143 ER PT J AU BIESECKER, LG ROSENBERG, M DZIADZIO, L LEDBETTER, DH NING, Y SARNESO, C ROSENBAUM, K AF BIESECKER, LG ROSENBERG, M DZIADZIO, L LEDBETTER, DH NING, Y SARNESO, C ROSENBAUM, K TI DETECTION OF A SUBTLE REARRANGEMENT OF CHROMOSOME-22 USING MOLECULAR TECHNIQUES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CHROMOSOME 22; PERICENTRIC INVERSION; DINUCLEOTIDE REPEAT POLYMORPHISMS; MULTIPLE ABNORMALITIES ID SEGMENT AB Conventional cytogenetics is a useful clinical tool that has a lower limit of sensitivity of 2-5 Mb for detection of duplications or deletions. Because the threshold of clinically significant aneusomy is below this range, there is a need for approaches to improve the sensitivity of the detection of aneusomy. We have implemented a system of screening for subtle unbalanced translocations in children with multiple congenital anomalies of unknown cause. Our approach uses subtelomeric microsatellite markers to detect small areas of segmental aneusomy due to unbalanced translocations. Herein we report a patient with severe multiple congenital anomalies and a normal karyotype who was diagnosed by this approach. Microsatellite markers from 41 telomeres were analyzed and were normal with the exception of those on distal chromosome 22. Further analysis with additional microsatellites and fluorescent in situ hybridization confirmed duplication of 22q13.2-qter. We conclude that microsatellite screening can detect subtle unbalanced translocations in children with severe anomalies. (C) 1995 Wiley-Liss, Inc. C1 CHILDRENS NATL MED CTR,DEPT MED GENET,WASHINGTON,DC. RP BIESECKER, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,DIAGNOST DEV BRANCH,49 CONVENT DR,ROOM 4A80,BETHESDA,MD 20892, USA. NR 14 TC 24 Z9 24 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 SEP 25 PY 1995 VL 58 IS 4 BP 389 EP 394 DI 10.1002/ajmg.1320580426 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA RV001 UT WOS:A1995RV00100024 PM 8533859 ER PT J AU GLYNN, RJ BROCH, DB HARRIS, T HAVLIK, RJ CHRISCHILLES, EA OSTFELD, AM TAYLOR, JO HENNEKENS, CH AF GLYNN, RJ BROCH, DB HARRIS, T HAVLIK, RJ CHRISCHILLES, EA OSTFELD, AM TAYLOR, JO HENNEKENS, CH TI USE OF ANTIHYPERTENSIVE DRUGS AND TRENDS IN BLOOD-PRESSURE IN THE ELDERLY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; MODERATE HYPERTENSION; THERAPY; MORTALITY; TRIAL; MILD; MEN; MORBIDITY; STROKE; MODELS AB Background: During the 1980s data became available from randomized trials concerning the clear benefits of heating hypertension in the elderly. In three large communities, we examined the impact of these findings on rates of treatment, use of specific antihypertensive drugs, and rates of elevated blood pressure as well as distributions of levels. Methods: In 1981 the National Institute on Aging initiated population-based cohort studies in the residents of three communities who were 65 years and older: East Boston, Mass; Washington and Iowa counties, Iowa; and New Haven, Conn. Participation rates ranged from 80% to 85% across sites with 10 294 community-dwelling participants in the combined cohorts. Baseline evaluation included in-home blood pressure assessment and medication inventory. Repeated in-home evaluations occurred 3 and 6 years after baseline and follow-up rates ranged from 71% to 88%. Results: Use of antihypertensive drugs increased over time in all three communities: the age- and sex-adjusted rates of use were between 14% and 32% higher in 1988 and 1989 relative to 1982 and 1983. Parallel declines in the use of thiazide diuretics occurred in all three populations along with large increases in the use of angiotensin-converting enzyme inhibitors and calcium channel blockers. In East Boston and New Haven mean systolic blood pressure decreased substantially over time and the prevalence of elevated systolic pressure (greater than or equal to 160 mm Hg) decreased overall as well as by age and sex. In Iowa the mean levels of systolic blood pressure were lowest at baseline and increased slightly. Conclusions: The reported evidence about the benefits of treatment for hypertension in the elderly was followed by substantial increases in treatment rates. The use of drugs with proven efficacy declined while the use of newer agents with theoretical advantages, not yet tested in clinical trials of mortality, increased. In the United States, the ongoing therapeutic efforts to lower elevated blood pressure in elderly populations may be contributing to the continuing decline in cardiovascular and stroke mortality. C1 BRIGHAM & WOMENS HOSP,DEPT MED,E BOSTON NEIGHBORHOOD HLTH CTR,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT AMBULATORY CARE & PREVENT,E BOSTON NEIGHBORHOOD HLTH CTR,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT AMBULATORY CARE & PREVENT,DIV PREVENT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. RP GLYNN, RJ (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV PREVENT MED,900 COMMONWEALTH AVE E,BOSTON,MA 02215, USA. FU NIA NIH HHS [AG02105, AG02106, AG02107] NR 45 TC 34 Z9 35 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD SEP 25 PY 1995 VL 155 IS 17 BP 1855 EP 1860 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RV804 UT WOS:A1995RV80400004 PM 7677551 ER PT J AU BOYER, GS TEMPLIN, DW GORING, WP CORNONIHUNTLEY, JC EVERETT, DF LAWRENCE, RC HEYSE, SP BOWLER, A AF BOYER, GS TEMPLIN, DW GORING, WP CORNONIHUNTLEY, JC EVERETT, DF LAWRENCE, RC HEYSE, SP BOWLER, A TI DISCREPANCIES BETWEEN PATIENT RECALL AND THE MEDICAL RECORD - POTENTIAL IMPACT ON DIAGNOSIS AND CLINICAL-ASSESSMENT OF CHRONIC DISEASE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SPONDYLOARTHROPATHIES; CRITERIA; CLASSIFICATION; ACCURACY; BIAS AB Background: During a case-control study, data necessary for fulfilling diagnostic and classification criteria for spondyloarthropathy were collected from 121 patients. Objective: To study the potential impact of differences between patient recall and the medical record on diagnosis and clinical characterization of spondyloarthropathy as a model of chronic disease. Methods: The study was conducted among four Alaskan Eskimo populations served by the Alaska Native Health Service. Two sets of historical data were compiled for each subject, one acquired during the interview and the other derived from the medical record. Paired items from the interview and the medical record were analyzed to determine discrepancies and consequent effects on diagnosis, classification, and disease characterization. Results: Significant differences were observed in the reporting of genitourinary or diarrheal illnesses preceding or associated with arthritis, the occurrence of eye inflammation in association with joint pain, the occurrence of joint pain and back pain together, and the age at onset of back pain, all of which are important to the diagnosis and classification of spondyloarthropathy. In contrast, for information needed to establish the probable inflammatory nature of back pain, patient interview was more helpful than the medical records, which did not provide adequate details to differentiate inflammatory from mechanical back pain. Conclusions: Patient recall bias can substantially affect diagnosis and clinical assessment of chronic disease, as exemplified by spondyloarthropathy. Reliance on records alone, however, may lead to underestimation of features that require subjective appraisal by the patient. C1 ALASKA AREA NATIVE HLTH SERV,ANCHORAGE,AK. UNIV ARIZONA,OFF VICE PRESIDENT RES,TUCSON,AZ. DUKE UNIV,SCH PUBL HLTH,DURHAM,NC. NEI,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. PROSPECT ASSOCIATES,ROCKVILLE,MD. FU NIAMS NIH HHS [Y02-AR-00005] NR 22 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD SEP 25 PY 1995 VL 155 IS 17 BP 1868 EP 1872 DI 10.1001/archinte.155.17.1868 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RV804 UT WOS:A1995RV80400006 PM 7677553 ER PT J AU SZALLASI, Z DENNING, MF CHANG, EY RIVERA, J YUSPA, SH LEHEL, C OLAH, Z ANDERSON, WB BLUMBERG, PM AF SZALLASI, Z DENNING, MF CHANG, EY RIVERA, J YUSPA, SH LEHEL, C OLAH, Z ANDERSON, WB BLUMBERG, PM TI DEVELOPMENT OF A RAPID APPROACH TO IDENTIFICATION OF TYROSINE PHOSPHORYLATION SITES - APPLICATION TO PKC-DELTA PHOSPHORYLATED UPON ACTIVATION OF THE HIGH-AFFINITY RECEPTOR FOR IGE IN RAT BASOPHILIC LEUKEMIA-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID KINASE-C-DELTA; PROTEIN; EXPRESSION AB In rat basophilic leukemia cells (RBL-2H3) activation of the high affinity receptor for IgE induces tyrosine phosphorylation of PKC delta. We carried out solid phase synthesis of 15 amino acid long oligopeptides corresponding to the sequences around each of the 19 tyrosine residues in PKC delta. Only three oligopeptides, corresponding to tyrosine 52, 155, and 565, were phosphorylated when exposed to lyn kinase. Single mutants in each of these three tyrosine residues of PKC delta were prepared. Upon expression in the RBL-2H3 cells, only the mutant in tyrosine 52 showed abolition of the IgE-antigen induced tyrosine phosphorylation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NIAMSD,CHEM IMMUNOL SECT,BETHESDA,MD 20892. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 17 TC 64 Z9 67 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 25 PY 1995 VL 214 IS 3 BP 888 EP 894 DI 10.1006/bbrc.1995.2370 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RW556 UT WOS:A1995RW55600021 PM 7575560 ER PT J AU KIESER, A GOODNIGHT, J KOLCH, W MISCHAK, H MUSHINSKI, JF AF KIESER, A GOODNIGHT, J KOLCH, W MISCHAK, H MUSHINSKI, JF TI IDENTIFICATION OF THE PRIMARY GROWTH-RESPONSE GENE, ST2/T1, AS A GENE WHOSE EXPRESSION IS DIFFERENTIALLY REGULATED BY DIFFERENT PROTEIN-KINASE-C ISOZYMES SO FEBS LETTERS LA English DT Article DE PROTEIN KINASE C (MOUSE); ISOZYME; DIFFERENTIAL DISPLAY; ST2; T1; EXPRESSION ID PHORBOL ESTER RECEPTOR; INTERLEUKIN-1 RECEPTOR; HEMATOPOIETIC-CELLS; MESSENGER-RNA; RAT-BRAIN; BETA-II; FAMILY; ACTIVATION; NPKC; ISOFORM AB Individual protein kinase C isozymes have been shown to play different roles in mediating proliferation, differentiation and transformation, but it is not known to what extent these effects involve induction of expression of particular genes. To explore the differential gene expression that might be induced by activation of different PKC isozymes, we stably transfected NIH 3T3 cells with expression vectors that encode the isozymes PKC-alpha, -beta II, -gamma -delta, -epsilon, -zeta and -eta. Using differential display-reverse transcription-polymerase chain reaction we isolated a small cDNA that encodes a portion of the primary response gene, ST2 (also referred to as T1 or DER4), and we confirmed by RNA blot studies that ST2/T1 expression is differentially regulated by PKC isozymes. ST2/T1 mRNA is undetectable in the unstimulated parental NIH 3T3 cells that express only the alpha isozyme of PKC, but it can be induced by phorbol ester treatment. Clones that overexpress PKC-alpha, -delta or -epsilon similarly do not express ST2/T1 until they are stimulated with phorbol esters, which induces expression of ST2/T1 with kinetics similar to wild-type NM 3T3 but to different extents. In contrast, ST2/T1 mRNA is already present in unstimulated cells that overexpress PKC-beta II, -gamma, -zeta and -eta, but phorbol ester greatly enhances ST2/T1 expression in these cells. These results suggest a differential role for PKC isozymes in mediating the ST2/T1 expression that is induced by growth stimuli. C1 NCI,GENET LAB,MOLEC GENET SECT,BETHESDA,MD 20892. GSF MUNICH,INST KLIN MOLEK BIOL & TUMORGENET,D-81377 MUNICH,GERMANY. RI Mischak, Harald/E-8685-2011; Kieser, Arnd/M-4616-2014; OI Kieser, Arnd/0000-0003-0783-1950; Kolch, Walter/0000-0001-5777-5016 NR 39 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 25 PY 1995 VL 372 IS 2-3 BP 189 EP 193 DI 10.1016/0014-5793(95)00975-F PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RX921 UT WOS:A1995RX92100014 PM 7556667 ER PT J AU CHMIELOWSKA, J PONS, TP AF CHMIELOWSKA, J PONS, TP TI PATTERNS OF THALAMOCORTICAL DEGENERATION AFTER ABLATION OF SOMATOSENSORY CORTEX IN MONKEYS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE GABA; VENTROPOSTERIOR NUCLEUS; DEGENERATION; CYTOCHROME OXIDASE ID GABA-IMMUNOREACTIVE NEURONS; SOMATIC SENSORY CORTEX; THALAMIC VPM NUCLEUS; SAIMIRI-SCIUREUS; SQUIRREL-MONKEY; HORSERADISH-PEROXIDASE; DIFFERENT LAYERS; MACAQUE MONKEYS; LATERAL SULCUS; CONNECTIONS AB We examined the pattern of cytochrome oxidase (GO), Nissl staining, and gamma-amino butyric acid (GABA) immunoreactivity in the ventroposterior lateral nucleus (VPL) of the thalamus in monkeys that received no, total, or subtotal, ablation of the hand representations in postcentral somatosensory cortex. In unoperated animals, the region of VPL representing the hand was characterized by relatively dense and homogeneous CO staining throughout the rostral-caudal extent of VPL. Counts of neurons in the VPL hand representation from adjacent thalamic sections processed for Nissl and GABA immunostaining indicated that there were approximately 261.4 neurons/mm(2) of which 78.4/mm(2) stained positive for GABA. GABA(+) puncta-like terminals were readily apparent throughout the VPL. By contrast, animals that received total removals of the postcentral hand representations showed a dramatic reduction in CO staining in the VPL, which was confined to the expected location of the thalamic hand representation. Counts of neurons in the affected region from adjacent sections that underwent Nissl staining and GABA immunostaining also revealed a dramatic reduction of Nissl-stained neurons, with a smaller reduction in the number of neurons staining positive for GABA. Specifically, large to medium-sized (> 180 mu m(2)) GABA(-) neurons were virtually eliminated in the affected portion of the VPL, and the numbers of GABA(+) neurons were significantly reduced. The remaining population of GABA(+) neurons was typically shrunken, and no GABA(+) puncta-like terminals were observed in the affected region. The results obtained after subtotal ablation of the postcentral hand representations (only one postcentral area spared, 3b or 3a) differed from those obtained when total removals were made. Instead of virtually complete degeneration of medium-sized to large neurons throughout the hand representation in VPL, as was the case with total removals, after partial removals, we found alternating regions in the VPL hand representation that appeared qualitatively normal, or dramatically degenerated. Thalamic sections stained with CO revealed light, moderate, and darkly stained patches of label within the hand representation in VP, depending on the type of cortical ablation. The most dramatic reduction of Nissl-stained neurons coincided precisely with the lightest staining CO patches. Interestingly, the only statistically significant reduction in the number of GABA(+) neurons occurred in the light CO patches. In the thalamic regions coincident with the dark and moderately stained CO patches, the number of medium-sized and large neurons decreased, but the number of GABA(+) neurons was comparable to normal. Optical density measurements of the dark patches also indicated a statistically significant difference from normal CO staining in this region. These findings indicate that following cortical damage, complex changes occur in thalamic circuitry. Interestingly, these changes are not confined to regions of the thalamus that have their major projection to the damaged region of cortex, but include thalamic regions in which the major projection is to undamaged regions of cortex. Thus, relatively restricted cortical damage has the potential to affect regions of cortex not directly damaged, through post-injury changes in thalamic circuitry. Such changes in neuronal circuitry, especially at the thalamocortical level, may serve as the neural substrate for the limited recovery of behavioral function often seen after strokes or head injury. (C) 1995 Wiley-Liss, Inc. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROSURG,WINSTON SALEM,NC 27103. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [MH53369-01] NR 29 TC 10 Z9 11 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 25 PY 1995 VL 360 IS 3 BP 377 EP 392 DI 10.1002/cne.903600302 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RW086 UT WOS:A1995RW08600001 PM 8543646 ER PT J AU BENBARUCH, A XU, LL YOUNG, PR BENGALI, K OPPENHEIM, JJ WANG, JM AF BENBARUCH, A XU, LL YOUNG, PR BENGALI, K OPPENHEIM, JJ WANG, JM TI MONOCYTE CHEMOTACTIC PROTEIN-3 (MCP3) INTERACTS WITH MULTIPLE LEUKOCYTE RECEPTORS - C-C-CKR1, A RECEPTOR FOR MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA, RANTES, IS ALSO A FUNCTIONAL RECEPTOR FOR MCP3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; MOLECULAR-CLONING; CYTOKINE FAMILY; EXPRESSION; IDENTIFICATION; CHEMOKINES; BIOLOGY; BINDING; CELLS; CDNA AB Monocyte chemotactic protein-3 (MCP3) is a recently identified and molecularly cloned C-C chemokine that is chemotactic for and activates a great variety of inflammatory cell types. MCP3 has been reported to interact with several C-C chemokine receptors, which can be simultaneously or selectively expressed on leukocyte subpopulations. In order to isolate receptor(s) for MCP3, a cDNA library was constructed using mRNA from a human Mt-like cell line, YT. These cells showed high affinity binding sites for I-125-MCP3 and migrated in response to MCP3. A chemokine receptor cDNA clone, designated YT4, was sequenced and found to be identical to the known C-C CKR1 or macrophage inflammatory protein-1 alpha (MIP1 alpha)/Rantes receptor. YT4 cDNA was subcloned into a mammalian expression vector, and stable transfectants were prepared using the embryonic kidney cell line 293. The transfectants (YT4/293) showed high affinity binding for I-125-MCP3 in addition to specifically binding I-125-MIP1 alpha and I-125-Rantes. All three C-C chemokines were able to cross compete for binding sites on YT4/293 cells and induced directional migration of YT4/293 cells in vitro, with MCP3 being the most potent chemoattractant. MCP3, MTP1 alpha, and Rantes were equally able to cross-attenuate the migratory response of YT4/293 cells to one another. In contrast, MCP1 and MIP1 beta had very limited capacity to compete for MCP3 binding on YT4/293 cells and had only a minor attenuating effect on MCP3-induced migration. Since MCP3 has been reported to use MCP1 receptor(s), our results with transfected 293 cells expressing only C-C CKR1 clearly establish that C-C CKR1 is also a functional receptor for MCP3. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. SMITHKLINE BEECHAM PHARMACEUT INC,DEPT MOLEC IMMUNOL,KING OF PRUSSIA,PA 19406. NR 32 TC 109 Z9 110 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 SEP 22 PY 1995 VL 270 IS 38 BP 22123 EP 22128 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW314 UT WOS:A1995RW31400013 PM 7545673 ER PT J AU JOE, YA WOLFF, EC PARK, MH AF JOE, YA WOLFF, EC PARK, MH TI CLONING AND EXPRESSION OF HUMAN DEOXYHYPUSINE SYNTHASE CDNA - STRUCTURE-FUNCTION STUDIES WITH THE RECOMBINANT ENZYME AND MUTANT PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID; HYPUSINE; IDENTIFICATION; SPERMIDINE; PURIFICATION; FIBROBLAST; PRECURSOR AB Deoxyhypusine synthase catalyzes the first step in the post-translational formation of hypusine (N-epsilon-(4-amino-2-hydroxybutyl)lysine). cDNA clones encoding deoxyhypusine synthase were isolated from a human HeLa cell library. Full-length cDNA clones encoding a 369-amino acid protein (calculated molecular mass of 40,970 Da) and a shorter cDNA clone that would potentially encode a protein with an internal deletion of 56 amino acids (Asp(262)-Ser(317)) were isolated. The deduced amino acid sequence of the human enzyme shows a high degree of identity to that of yeast deoxyhypusine synthase and to the known sequences of tryptic peptides from the rat and Neurospora crassa enzymes. The recombinant enzyme formed upon expression in Escherichia coli effectively catalyzed deoxyhypusine synthesis. Variant human recombinant proteins with (i) a truncation of 48 or 97 NH2-terminal amino acids, (ii) a truncation of 39 COOH-terminal amino acids, or (iii) an internal deletion (Asp(262)-Ser(317)) were inactive. A chimeric protein consisting of the complete human sequence and 16 amino acids of the yeast sequence (Gln(197)-Asn(212), not present in the human enzyme) inserted between Glu(193) and Gln(194) exhibited moderate activity. C1 NIDR,CELLULAR DEV & ONCOL LAB,ENZYME CHEM SECT,BETHESDA,MD 20892. NR 32 TC 66 Z9 68 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 SEP 22 PY 1995 VL 270 IS 38 BP 22386 EP 22392 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW314 UT WOS:A1995RW31400051 PM 7673224 ER PT J AU FREEDMAN, BD FLEISCHMANN, BK PUNT, JA GAULTON, G HASHIMOTO, Y KOTLIKOFF, MI AF FREEDMAN, BD FLEISCHMANN, BK PUNT, JA GAULTON, G HASHIMOTO, Y KOTLIKOFF, MI TI IDENTIFICATION OF KV1.1 EXPRESSION BY MURINE CD4(-)CD8(-) THYMOCYTES - A ROLE FOR VOLTAGE-DEPENDENT K+ CHANNELS IN MURINE THYMOCYTE DEVELOPMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; CELL-VOLUME REGULATION; POTASSIUM CHANNELS; T-CELLS; CALCIUM INFLUX; CHARYBDOTOXIN; RECEPTOR; INTERLEUKIN-2; CA-2+; OSCILLATIONS AB The patch-clamp recording technique and RNA-polymerase chain reaction were used to identify the voltage-dependent K+ channels expressed by murine fetal and adult CD4(-)CD8(-) thymocytes. Two distinct currents, encoded by the genes Kv1.1 and Kv1.3 were identified based upon their biophysical and pharmacologic characteristics and confirmed with RNA-polymerase chain reaction. Peptide blockers of Kv1.1 and Kv1.3 gene products were also applied to a murine fetal thymic organ culture system to investigate the developmental role of these K+ channels. Dendrotoxin (DTX) and charybdotoxin (CTX), antagonists of Kv1.1 and Kv1.3 channels, respectively, decreased thymocyte yields in organ culture without affecting thymocyte viability. DTX-treated thymi contained 56 +/- 8% (n = 8 experiments), and CTX-treated thymi contained 74 +/- 4% (n = 7 experiments) as many thymocytes as untreated lobes. DTX and CTX also altered the developmental progression of thymocytes in fetal organ culture. These data provide the first evidence of Kv1.1 expression in a lymphoid cell and indicate that thymocyte voltage-dependent K+ channels are critical to thymocyte preclonal expansion and/or maturation. C1 UNIV PENN,SCH VET MED,DEPT ANIM BIOL,PHILADELPHIA,PA 19104. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. SYNTEX INST IMMUNOL,NIIHARI,IBARAKI 30041,JAPAN. RP FREEDMAN, BD (reprint author), UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104, USA. FU NIAID NIH HHS [R01 AI060921]; NIAMS NIH HHS [AR-39910]; NICHD NIH HHS [HD-01056]; PHS HHS [A132748] NR 36 TC 34 Z9 35 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 SEP 22 PY 1995 VL 270 IS 38 BP 22406 EP 22411 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW314 UT WOS:A1995RW31400054 PM 7673227 ER PT J AU KING, C EISENBERG, E GREENE, L AF KING, C EISENBERG, E GREENE, L TI POLYMERIZATION OF 70-KDA HEAT-SHOCK PROTEIN BY YEAST DNAJ IN ATP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; PEPTIDE BINDING; COATED VESICLES; TRANSLOCATION; HSP70; HOMOLOG; TEMPERATURES; POLYPEPTIDES AB DnaK, the Escherichia coli hsp(70) protein, interacts with DnaJ, a protein cofactor that appears to be involved in presenting protein substrates to DnaK. The yeast DnaJ homolog, YDJ1, has also been shown to interact with yeast hsp70, although the function of this interaction is unknown. In the present study, we investigated the interaction of YDJ1 with both yeast and bovine brain hsp70. We found that, in the presence of ATP, where hsp70 is normally monomeric, YDJ1 induced almost all of the yeast and bovine brain hsp70 to form large polymers, which are readily sedimentable. These polymers were much larger than the dimers and trimers of hsp70, which normally form in the presence of ADP. YDJ1 appeared to be acting catalytically since very little YDJ1 copolymerized with the hsp70, and maximum polymerization occurred at low ratios of YDJ1 to hsp70. The polymerization required ATP and was completely reversed when ATP was replaced by ADP. These data suggest that, in the presence of ATP, YDJ1 may present one hsp70 to another just as under other conditions DnaJ is able to present protein substrates to DnaK. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 43 TC 49 Z9 50 U1 1 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 SEP 22 PY 1995 VL 270 IS 38 BP 22535 EP 22540 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW314 UT WOS:A1995RW31400074 PM 7673245 ER PT J AU SELKIRK, JK HE, C MERRICK, BA AF SELKIRK, JK HE, C MERRICK, BA TI GEL-ELECTROPHORETIC ANALYSIS OF CELLULAR AND SECRETED PROTEINS FROM RESTING AND ACTIVATED RAT ALVEOLAR MACROPHAGES TREATED WITH PENTAMIDINE ISETHIONATE SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; RANDOMIZED TRIAL; AIDS; THERAPY AB Pneumocystic carinii pneumonia, which is a major cause of death among patients suffering from acquired immunodeficiency syndrome, has often been treated successfully with pentamidine isethionate. This study examines pentamidine effects on cellular and secreted proteins from rat alveolar macrophages by two-dimensional gel electrophoresis and computerized image analysis. Over 100 secreted proteins were detected by fluorography. Fluorography showed pentamidine diminished tumor necrosis factor and interleukin-1 release along with other proteins. Effects of combined bacterial lipopolysaccharide and pentamidine were more pronounced on secreted versus cellular proteins in protein amount and pattern difference. Thus pentamidine exhibited a general repressive effect on cellular and secreted protein expression in resting and activated macrophages. RP SELKIRK, JK (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 0 Z9 0 U1 0 U2 0 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 SEP 22 PY 1995 VL 711 IS 2 BP 331 EP 337 DI 10.1016/0021-9673(95)00607-O PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RY346 UT WOS:A1995RY34600011 PM 7581850 ER PT J AU BAMBERGER, AM PU, LP COOL, DR LOH, YP AF BAMBERGER, AM PU, LP COOL, DR LOH, YP TI THE NEURO-2A NEUROBLASTOMA CELL-LINE EXPRESSES [MET]-ENKEPHALIN AND VASOPRESSIN MESSENGER-RNA AND PEPTIDE SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE NEURO-2A CELL; ENKEPHALIN; PROHORMONE CONVERTASE 2; VASOPRESSIN ID ANGIOTENSIN-II; BLASTOMA CELLS; MESSENGER-RNA; INCREASES; ENZYME; FURIN; BRAIN AB Mouse neuroblastoma Neuro-2a cells were examined for the expression of pro-enkephalin mRNA, protein, and Met-enkephalin ([Met]-Enk) peptide. Reverse transcriptase/polymerase chain reaction (RT/PCR) and in situ hybridization demonstrated the presence of pro-enkephalin mRNA in these cells. Immunocytochemistry using an antibody which recognizes pro-enkephalin and high pressure liquid chromatography (HPLC) followed by radioimmunoassay indicated that pro-enkephalin was synthesized in these cells and processed to yield the bioactive pentapeptide, [Met]-Enk. Furthermore, release studies showed that the [Met]-Enk was secreted from these cells with high K+ stimulation. Using double labeling, in situ hybridization combined with immunocytochemistry, we demonstrated that prohormone convertase 2 (PC2) mRNA is colocalized with pro-enkephalin in the same Neuro-2a cells, suggesting that this enzyme may be responsible for processing this precursor. We also showed the presence of vasopressin mRNA and arginine-vasopressin peptide in these cells using in situ hybridization and immunocytochemistry, respectively. Thus, the Neuro-2a cells are a multiple neuropeptide-producing cell line and an excellent model for studying the mechanisms involved in the synthesis, intracellular targeting and processing of endogenous pro-enkephalin and pro-vasopressin, as well as other transfected neuropeptide precursors. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. NR 20 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD SEP 22 PY 1995 VL 113 IS 2 BP 155 EP 163 DI 10.1016/0303-7207(95)03625-H PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA RX361 UT WOS:A1995RX36100005 PM 8674823 ER PT J AU CRAWLEY, JN AF CRAWLEY, JN TI BIOLOGICAL ACTIONS OF GALANIN SO REGULATORY PEPTIDES LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; INHIBITS INSULIN-SECRETION; RAT ANTERIOR-PITUITARY; GASTRIC-ACID SECRETION; MEDIAL SEPTAL AREA; INSITU HYBRIDIZATION; GENE-EXPRESSION; MESSENGER-RNA; VENTRAL HIPPOCAMPUS; INTRATHECAL GALANIN RP CRAWLEY, JN (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BLDG 10,ROOM 4N212,BETHESDA,MD 20892, USA. NR 199 TC 121 Z9 121 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 22 PY 1995 VL 59 IS 1 BP 1 EP 16 DI 10.1016/0167-0115(95)00083-N PG 16 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RX286 UT WOS:A1995RX28600001 PM 12506409 ER PT J AU LARRALDE, H WEISS, GH AF LARRALDE, H WEISS, GH TI A GENERATING FUNCTION FOR THE 2ND MOMENT OF THE DISTINCT NUMBER OF SITES VISITED BY AN N-STEP LATTICE RANDOM-WALK SO JOURNAL OF PHYSICS A-MATHEMATICAL AND GENERAL LA English DT Article ID RANGE AB We derive a generating function for the second moment of the distinct number of sites visited by an n-step lattice random walk. The formalism allows us to find asymptotic forms for the second moment as previously given in the mathematical literature using much more complicated techniques. The general technique can, in principle, be utilized in a derivation of higher moments. C1 NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. RP UNIV CAMBRIDGE, CAVENDISH LAB, CAMBRIDGE CB3 0HE, ENGLAND. NR 17 TC 7 Z9 7 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0305-4470 J9 J PHYS A-MATH GEN JI J. Phys. A-Math. Gen. PD SEP 21 PY 1995 VL 28 IS 18 BP 5217 EP 5225 DI 10.1088/0305-4470/28/18/012 PG 9 WC Physics, Multidisciplinary; Physics, Mathematical SC Physics GA RX443 UT WOS:A1995RX44300012 ER PT J AU VARMUS, H AF VARMUS, H TI SHATTUCK-LECTURE - BIOMEDICAL-RESEARCH ENTERS THE STEADY-STATE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article RP VARMUS, H (reprint author), NIH,BLDG 1,RM 126,1 CTR DR,MSC 0148,BETHESDA,MD 20892, USA. NR 7 TC 27 Z9 28 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 SEP 21 PY 1995 VL 333 IS 12 BP 811 EP 815 DI 10.1056/NEJM199509213331224 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RU809 UT WOS:A1995RU80900030 PM 7643903 ER PT J AU KATZAV, S PACKHAM, G SUTHERLAND, M AROCA, P SANTOS, E CLEVELAND, JL AF KATZAV, S PACKHAM, G SUTHERLAND, M AROCA, P SANTOS, E CLEVELAND, JL TI VAV AND RAS INDUCE FIBROBLAST TRANSFORMATION BY OVERLAPPING SIGNALING PATHWAYS, WHICH REQUIRE C-MYC FUNCTION SO ONCOGENE LA English DT Article DE VAV; VAS; C-MYC; SH2 ID TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; ORNITHINE DECARBOXYLASE; HEMATOPOIETIC-CELLS; TRANSCRIPTIONAL ACTIVATION; NEOPLASTIC TRANSFORMATION; SH2 DOMAIN; PROTEIN; EXPRESSION; KINASE AB Recent evidence has suggested that the Vav oncoprotein may function as a hematopoietic-specific GTP exchange factor for the Ras superfamily of proteins, However, transformation of NIH3T3 fibroblast cells by Vav is morphologically distinct from that induced by activated Ras oncogenes, suggesting that the two oncoproteins induce separate signal transduction pathways which promote transformation, To address this issue, the effects of dominant negative mutants of H-ras and proto-Vav (proto-VavR695L, a mutation in the VavSH2 domain) were tested on Vav- and Ras-induced transformation, These mutants partially inhibited both Vav- and Ras-induced transformation, suggesting that they may induce a common downstream signaling pathway which potentiates transformation, As an independent measure of Vav function we also tested the ability of the purified protein encoded by VavSH2 to influence Germinal Vesicle Breakdown (GVBD) during Xenopus oocyte maturation, Microinjection of the VavSH2 protein alone, but not mutant VavR695L SH2 protein, was sufficient to induce GVBD and accelerated maturation induced by normal Ras, suggesting that in this system as well Vav and Ras signals overlap through a common effector, A key target of multiple signalling pathways is c-Myc. Dominant negative versions of c-Myc totally abolished morphologic transformation of NIH3T3 cells by both Vav and Ras oncogenes, These results suggest that distinct, but overlapping, signalling pathways are induced by Vav and Ras and that fibroblast cell transformation by either oncogene requires c-Myc functions. C1 MCGILL UNIV, DEPT ONCOL, MONTREAL, PQ H3G 1Y6, CANADA. MCGILL UNIV, DEPT MED, MONTREAL, PQ H3G 1Y6, CANADA. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. UNIV TENNESSEE, CTR HLTH SCI, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. RP KATZAV, S (reprint author), MCGILL UNIV, JEWISH GEN HOSP, LADY DAVIS INST MED RES, TERRY FOX MOLEC ONCOL GRP, MONTREAL, PQ H3T 1E2, CANADA. FU NCI NIH HHS [P0 CA21765]; NIDDK NIH HHS [DK44158] NR 84 TC 33 Z9 33 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 1995 VL 11 IS 6 BP 1079 EP 1088 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RX180 UT WOS:A1995RX18000010 PM 7566967 ER PT J AU SASTRY, L LIN, WH WONG, WT DIFIORE, PP SCOPPA, CA KING, CR AF SASTRY, L LIN, WH WONG, WT DIFIORE, PP SCOPPA, CA KING, CR TI QUANTITATIVE-ANALYSIS OF GRB2-SOS1 INTERACTION - THE N-TERMINAL SH3 DOMAIN OF GRB2 MEDIATES AFFINITY SO ONCOGENE LA English DT Article DE GRB2; SOS1; BIACORE; SPR; KINETICS ID RECEPTOR TYROSINE KINASES; BIOSPECIFIC INTERACTION ANALYSIS; NUCLEOTIDE EXCHANGE FACTOR; SURFACE-PLASMON RESONANCE; PHOSPHORYLATED PEPTIDES; SIGNAL TRANSDUCTION; RAS; PROTEIN; BINDS; ASSOCIATION AB Grb2 is an adaptor protein that links receptor and cytoplasmic tyrosine kinases to the Ras signalling pathway by binding the Ras-specific guanine nucleotide exchange factor, Sos1, through its SH3 domains, The Grb2-SH3 domain binding has been localized to the carboxy-terminal two hundred amino acids of Sos1 (Sos1-c). By using real time biospecific interaction analysis (BIAcore), we studied the kinetic parameters and binding affinity of the Grb2-Sos1-c interaction, The binding of Grb2 to Sos1-c is a high affinity interaction with a moderate association rate (9.45 x 10(4) per M per s), a slow dissociation rate (13.8 x 10(-5) s), and an affinity constant of 1.48 nM. BIAcore measurements on isolated N-terminal and C-terminal SH3 domains (NSH3 and CSH3) further indicate that the high affinity Grb2-Sos1-c interaction is primarily mediated through the NSH3 domain (K-d=1.68 nM). The CSH3 domain shows substantially reduced binding to Sos1-c in these measurements, Inhibition studies with BIAcore using proline rich peptides derived from the C-terminus of Sos1 show that there is a single major binding site for Grb2 in Sos1, This binding site is contained within the peptide N20, which corresponds to amino acids 1143-1162 of Sos1, This peptide completely blocks the Grb2-Sos1-c and NSH3-Sos1-c interactions with IC50 values of 8 mu M and 4 mu M respectively, The discrete interaction between the NSH3 domain and the N20 peptide may be amenable for drug discovery through screening or peptidomimetic approaches. C1 ONCOL INC,GAITHERSBURG,MD 20878. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,LOMBARDI CANC CTR,WASHINGTON,DC 20007. FAC MED & CHIRURG,IST MICROBIOL,BARI,ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 31 TC 50 Z9 50 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 1995 VL 11 IS 6 BP 1107 EP 1112 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RX180 UT WOS:A1995RX18000013 PM 7566970 ER PT J AU AVANTAGGIATO, V TORINO, A WONG, WT DIFIORE, PP SIMEONE, A AF AVANTAGGIATO, V TORINO, A WONG, WT DIFIORE, PP SIMEONE, A TI EXPRESSION OF THE RECEPTOR TYROSINE KINASE SUBSTRATE GENES EPS8 AND EPS15 DURING MOUSE DEVELOPMENT SO ONCOGENE LA English DT Article DE EPS8; EPS15; DEVELOPMENT; EXPRESSION ID GROWTH-FACTOR RECEPTOR; DROSOPHILA-TRITHORAX; INT-1 PROTOONCOGENE; SIGNAL TRANSDUCTION; ACUTE LEUKEMIAS; ONCOGENE INT-1; EGF RECEPTOR; CELLS; DOMAINS; WNT-1 AB Receptor tyrosine kinases (RTKs) control proliferation and differentiation through their ability to bind and/or phosphorylate intracellular substrates, The repertoire of substrates recruited by different RTK is largely overlapping, It is not clear, therefore, how a cell distinguishes among signals originating from different RTKs. One possibility is that selective availability of substrates participates in the regulation of this process, To gain insight into this issue, we studied the expression pattern, embryogenesis, of the eps8 and eps15 encode two recently identified RTK substrates, Both genes are expressed from E 10 in a restricted fashion, eps8 is first expressed in frontonasal neural crest-derived cells, in the mesenchyme of branchial arches and in the liver primordium. At E 12.5-E 14, eps8 is additionally expressed in the central nervous system (CNS) in a regional restricted pattern at the met-mesencephalic transition area and in the developing submandibular salivary glands, eps15 is expressed at E 10 in the liver primordium, in the spinal ganglia and in the encephalic ganglia derived from the hindbrain neural crest, In addition, at E 12.5-E 14, eps15 is expressed, along all the CNS, in the ventricular zone where undifferentiated neuroblasts are located. The regional pattern of developmental expression of these two substrates sharply contrasts with their ubiquitous expression in adults, raising the possibility that their expression during embryogenesis is linked to selective proliferative and/or differentiative responses of specific neuroectodermal regions and body organs. C1 CNR,INT INST GENET & BIOPHYS,I-80125 NAPLES,ITALY. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. EUROPEAN INST ONCOL,IEO,I-20132 MILAN,ITALY. UNIV BARI,IST MICROBIOL,I-70100 BARI,ITALY. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 31 TC 10 Z9 11 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 1995 VL 11 IS 6 BP 1191 EP 1198 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RX180 UT WOS:A1995RX18000023 PM 7566980 ER PT J AU OTTERSON, GA KHLEIF, SN CHEN, WD COXON, AB KAYE, FJ AF OTTERSON, GA KHLEIF, SN CHEN, WD COXON, AB KAYE, FJ TI CDKN2 GENE SILENCING IN LUNG-CANCER BY DNA HYPERMETHYLATION AND KINETICS OF P16(INK4) PROTEIN INDUCTION BY 5-AZA 2'DEOXYCYTIDINE SO ONCOGENE LA English DT Article DE P16(INK4); CDKN2; METHYLATION; 5-AZA 2'DEOXYCYTIDINE; LUNG CANCER ID RETINOBLASTOMA GENE; MUTATION AB Absent expression of the cyclin dependent kinase-inhibitor, p16(INK4), is observed in a wide range of primary human cancers. Although homozygous deletions and point mutations have been reported in a subset of these tumors, the molecular basis for absent p16(INK4) in other samples is unknown. We have examined 33 tumor cell lines and have shown that hypermethylation of a G:C-rich region within exon 1 of the CDKN2 gene was present in 100% of samples with wildtype RE expression and no detectable CDKN2 mutations. Treatment for at least 4 hours with the demethylating agent 5-aza 2'deoxycytidine, but not 5-azacytidine or 6-azacytidine, induces the prolonged expression of p16(INK4) protein each of these samples following a discrete 24-48 hour lag period, Consistent with the hypothesis that hypermethylation of the CDKN2 gene is a tumor-specific mechanism for gene inactivation, we observed hypomethylation at the exon 1 site exclusively in tumor lines that expressed p16(INK4) or that had sustained inactivating point mutations within the CDKN2 open reading frame, These findings demonstrate a link between DNA methylation and the p16(INK4):RB tumor suppressor pathway. C1 NCI,USN HOSP,ONCOL BRANCH,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. RI kaye, frederic/E-2437-2011; CHEN, WEI-DONG/F-4521-2014 OI CHEN, WEI-DONG/0000-0003-2264-5515 NR 28 TC 208 Z9 216 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 1995 VL 11 IS 6 BP 1211 EP 1216 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RX180 UT WOS:A1995RX18000026 PM 7566983 ER PT J AU MARCHESE, A HEIBER, M NGUYEN, T HENG, HHQ SALDIVIA, VR CHENG, R MURPHY, PM TSUI, LC SHI, XM GREGOR, P GEORGE, SR ODOWD, BF DOCHERTY, JM AF MARCHESE, A HEIBER, M NGUYEN, T HENG, HHQ SALDIVIA, VR CHENG, R MURPHY, PM TSUI, LC SHI, XM GREGOR, P GEORGE, SR ODOWD, BF DOCHERTY, JM TI CLONING AND CHROMOSOMAL MAPPING OF 3 NOVEL GENES, GPR9, GPR10, AND GPR14 ENCODING RECEPTORS RELATED TO INTERLEUKIN-8, NEUROPEPTIDE-Y, AND SOMATOSTATIN RECEPTORS SO GENOMICS LA English DT Article ID PROTEIN-COUPLED RECEPTOR; DELTA-OPIOID RECEPTOR; FUNCTIONAL EXPRESSION; INSITU HYBRIDIZATION; MOLECULAR-CLONING; IDENTIFICATION; CELLS AB We employed the polymerase chain reaction and genomic DNA library screening to clone novel human genes, GPR9 and GPR10, and a rat gene, GPR14. GPR9, GPR10, and GPR14 each encode G protein-coupled receptors. GPR10 and GPR14 are intronless within their coding regions, while GPR9 contains at least one intron. The receptor encoded by GPR9 shares the highest identity with human IL-8 receptor type B (38% overall and 53% in the transmembrane regions), followed by IL-8 receptor type A (36% overall and 51% in the transmembrane domains). GPR10 encodes a receptor that shares highest identity with the neuropeptide Y receptor (31% overall and 46% in the transmembrane domains). The receptor encoded by GPR14 shares highest identity with the somatostatin receptor SSTR 4 (27% overall and 41% in the transmembrane domains). Fluorescence in situ hybridization analysis localized GPR9 to chromosome 8p11.2-p12 and GPR10 to chromosome 10q25.3-q26. (C) 1995 Academic Press, Inc. C1 UNIV TORONTO,DEPT PHARMACOL,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,DEPT MED,TORONTO,ON M5S 1A8,CANADA. ADDICT RES FDN,TORONTO,ON M5S 2S1,CANADA. NIAID,DEPT HLTH & HUMAN SERV,HOST DEF LAB,BETHESDA,MD 20892. HOSP SICK CHILDREN,RES INST,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. BAYER,W HAVEN,CT 06516. RI Tsui, Lap-chee/A-1081-2010 FU NIDA NIH HHS [R01-DA07223-01] NR 22 TC 162 Z9 171 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 20 PY 1995 VL 29 IS 2 BP 335 EP 344 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RY055 UT WOS:A1995RY05500004 PM 8666380 ER PT J AU GRZESIEK, S WINGFIELD, P STAHL, S KAUFMAN, JD BAX, A AF GRZESIEK, S WINGFIELD, P STAHL, S KAUFMAN, JD BAX, A TI 4-DIMENSIONAL N-15-SEPARATED NOESY OF SLOWLY TUMBLING PERDEUTERATED N-15-ENRICHED PROTEINS - APPLICATION TO HIV-1 NEF SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID SEQUENTIAL ASSIGNMENT; DEUTERIATION; SPECTRA C1 NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 18 TC 102 Z9 102 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 20 PY 1995 VL 117 IS 37 BP 9594 EP 9595 DI 10.1021/ja00142a040 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA RW496 UT WOS:A1995RW49600040 ER PT J AU SCHIFFMAN, MH AF SCHIFFMAN, MH TI NEW EPIDEMIOLOGY OF HUMAN PAPILLOMAVIRUS INFECTION AND CERVICAL NEOPLASIA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID INTRAEPITHELIAL NEOPLASIA; RISK RP SCHIFFMAN, MH (reprint author), NIH,NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. NR 20 TC 68 Z9 69 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 SEP 20 PY 1995 VL 87 IS 18 BP 1345 EP 1347 DI 10.1093/jnci/87.18.1345 PG 3 WC Oncology SC Oncology GA RU758 UT WOS:A1995RU75800002 PM 7658490 ER PT J AU GANZ, PA DAY, R WARE, JE REDMOND, C FISHER, B AF GANZ, PA DAY, R WARE, JE REDMOND, C FISHER, B TI BASE-LINE QUALITY-OF-LIFE ASSESSMENT IN THE NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT BREAST-CANCER PREVENTION TRIAL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HEALTH SURVEY SF-36; ANTIHYPERTENSIVE THERAPY; POSTMENOPAUSAL WOMEN; TAMOXIFEN TREATMENT; SERUM-LIPOPROTEINS; MEDICAL OUTCOMES; COMMUNITY SAMPLE; PLASMA-LIPIDS; DEPRESSION; VALIDITY AB Background: The Breast Cancer Prevention Trial (BCPT) is a large, multicenter chemoprevention trial testing the efficacy of the antiestrogen drug tamoxifen for prevention of breast cancer and coronary heart disease in healthy women at high risk of breast cancer. The BCPT evolved from a series of prior studies in early stage breast cancer demonstrating the efficacy of tamoxifen in the prevention of systemic breast cancer recurrence and in the reduction of contralateral breast cancers. Purpose: The purpose of this article is to describe the methodologic considerations in the collection of health-related quality-of-life (HRQL) data in the BCPT and to present base-line HRQL data on the first 9749 participants. Methods: An HRQL questionnaire that included the Center for Epidemiologic Studies-Depression Scale, a symptom checklist, the Medical Outcomes Study 36-item short form (MOS-SF-36), and the MOS sexual problems questions was completed by participants in the BCPT at base line (prior to random assignment). Medical and demographic information, as well as projected risk of breast cancer, were collected as part of study eligibility. Descriptive and correlational data were examined for these study participants. Results: BCPT participants report high levels of functioning compared with U.S. general population norms but still report an average of 8.9 distinct symptoms during the past 4 weeks. Depression is less prevalent among the participants than in community samples, which reflects the exclusion of clinically depressed individuals. Sixty-five percent reported being sexually active in the past 6 months, with an age-related decline in sexual activity. Younger women reported fewer sexual problems than older women. There is a strong correlation between the two mental health measures, moderate to weak correlations between HRQL scales and levels of self-reported symptoms, and only weak correlations between measures of breast cancer risk and HRQL scales. The MOS-SF-36 scores were examined for three consecutive recruitment samples (0-6 months, 7-12 months, and 13-20 months), and the base-line scores were slightly better for the earliest group of participants. Conclusions: This article demonstrates the feasibility of collecting HRQL data in a large, multicenter, chemoprevention trial for women at high risk of breast cancer. The successful integration of HRQL data collection into this clinical trial attests to its value as a safety-monitoring end point and as an explicit and measurable outcome for the entire trial. Implications: HRQL data are important for studies in which healthy populations are involved and in which the potential for decrements in quality of life are real or perceived. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. GRAD SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. NSABP BIOSTAT CTR,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. UNIV PITTSBURGH,CTR OPERAT,PITTSBURGH,PA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA. RP GANZ, PA (reprint author), UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,DIV CANC PREVENT & CONTROL RES,LOS ANGELES,CA 90024, USA. RI Page, Andrew/G-5438-2012 OI Page, Andrew/0000-0003-3133-2844 FU NCI NIH HHS [UT10CA37377] NR 45 TC 156 Z9 158 U1 0 U2 6 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 SEP 20 PY 1995 VL 87 IS 18 BP 1372 EP 1382 DI 10.1093/jnci/87.18.1372 PG 11 WC Oncology SC Oncology GA RU758 UT WOS:A1995RU75800011 PM 7658498 ER PT J AU TRIVERS, GE CAWLEY, HL DEBENEDETTI, VMG HOLLSTEIN, M MARION, MJ BENNETT, WP HOOVER, ML PRIVES, CC TAMBURRO, CC HARRIS, CC AF TRIVERS, GE CAWLEY, HL DEBENEDETTI, VMG HOLLSTEIN, M MARION, MJ BENNETT, WP HOOVER, ML PRIVES, CC TAMBURRO, CC HARRIS, CC TI ANTI-P53 ANTIBODIES IN SERA OF WORKERS OCCUPATIONALLY EXPOSED TO VINYL-CHLORIDE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CELLULAR PROTEIN P53; TUMOR-SUPPRESSOR GENE; IMMUNE-RESPONSE; CANCER-PATIENTS; POLYVINYL CHLORIDE; BREAST-CANCER; LUNG-CANCER; ANGIOSARCOMA; LIVER; REPLICATION AB Background: The p53 tumor suppressor gene (also known as TP53) is often mutated in a wide variety of cancers, including angiosarcoma of the liver (ASL). Anti-p53 antibodies have been detected in the sera of patients with leukemia, childhood lymphoma, or cancers such as those of the breast, lung, colon, esophagus, and liver (hepatocellular carcinoma). Purpose: The objective of this study was to determine the prevalence and time of appearance of serum anti-p53 antibodies during the pathogenesis of ASL associated with occupational exposure to vinyl chloride. Methods: Enzyme-linked immunoassay (EIA) was used to detect anti-p53 antibodies in 148 serum samples from 92 individuals occupationally exposed (in France or in Kentucky) to vinyl chloride; 15 of these individuals (six from France and nine from Kentucky) had ASL. A subset of coded EIA-positive and EIA-negative sera was further analyzed for anti-p53 antibodies by immunoblotting and immunoprecipitation. Nucleotide sequence analysis of exons 5-8 of the p53 gene was conducted on ASL DNA from six patients. We tested sera from 31 men who had no occupational exposure to vinyl chloride; they made up the control group. Statistical analyses were done using the Kruskal-Wallis chi-squared approximation and the Wilcoxon two-sample test for normal approximation. All P values result from tyro-sided tests. Results: Fourteen serum samples (from nine individuals) mere positive in the EIA. Five of the 15 individuals with ASL were positive for anti-p53 antibodies by EIA, immunoblotting, and immunoprecipitation: one individual at 11.3 and 10.8 years before diagnosis, another at 4 months before and shortly after diagnosis, and three when diagnosed or shortly thereafter. Four of the 77 vinyl chloride-exposed workers without diagnosed ASL were positive for anti-p53 antibodies; two of the four had symptoms related to vinyl chloride toxicity. Tumors from three of the six vinyl chloride-exposed workers from which sufficient DNA for analysis was obtained had A:T to T:A missense mutations of the p53 gene. Anti-p53 antibodies were detected in two of these individuals. Among the control group, two of 15 serum samples from 15 lung cancer patients and zero of 15 serum samples from control subjects without cancer had anti-p53 antibodies at substantially lower levels than the nine (10%) of 92 vinyl chloride-exposed workers who were positive for anti-p53 antibodies. Conclusions and Implications: Serum anti-p53 antibodies can predate clinical diagnosis of certain tumors, such as ASL, and may be useful in identifying individuals at high cancer risk, such as workers with occupational exposure to vinyl chloride. C1 GERMAN CANC RES CTR,W-6900 HEIDELBERG,GERMANY. INSERM,U271,LYON,FRANCE. COLUMBIA UNIV,DEPT BIOL SCI,NEW YORK,NY 10027. CORIELL INST,CAMDEN,NJ. UNIV LOUISVILLE,DIV OCCUPAT TOXICOL 1198,LOUISVILLE,KY 40292. RP TRIVERS, GE (reprint author), NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BLDG 37,RM 2C04,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [P20ES06832-01] NR 48 TC 113 Z9 116 U1 0 U2 4 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 SEP 20 PY 1995 VL 87 IS 18 BP 1400 EP 1407 DI 10.1093/jnci/87.18.1400 PG 8 WC Oncology SC Oncology GA RU758 UT WOS:A1995RU75800014 PM 7658501 ER PT J AU SANZORTEGA, J CHUAQUI, R ZHUANG, ZP SOBEL, ME SANZESPONERA, J LIOTTA, LA EMMERTBUCK, MR MERINO, MJ AF SANZORTEGA, J CHUAQUI, R ZHUANG, ZP SOBEL, ME SANZESPONERA, J LIOTTA, LA EMMERTBUCK, MR MERINO, MJ TI LOSS OF HETEROZYGOSITY ON CHROMOSOME 11Q13 IN MICRODISSECTED HUMAN MALE BREAST CARCINOMAS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID ENDOCRINE NEOPLASIA TYPE-1; CANCER; GENE; INT-2 C1 NCI,DIV CANC BIOL DIAG & CTR,DEPT SURG PATHOL,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,BETHESDA,MD 20892. HOSP UNIV SAN CARLOS,MADRID,SPAIN. RI Sanz, Julian/G-5276-2013 NR 22 TC 13 Z9 13 U1 0 U2 2 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 SEP 20 PY 1995 VL 87 IS 18 BP 1408 EP 1410 DI 10.1093/jnci/87.18.1408 PG 3 WC Oncology SC Oncology GA RU758 UT WOS:A1995RU75800015 PM 7658502 ER PT J AU MCLAUGHLIN, JK OLSEN, JH FRIIS, S MELLEMKJAER, L FRAUMENI, JF AF MCLAUGHLIN, JK OLSEN, JH FRIIS, S MELLEMKJAER, L FRAUMENI, JF TI BREAST IMPLANTS, CANCER, AND SYSTEMIC-SCLEROSIS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 DANISH CANC REGISTRY,COPENHAGEN,DENMARK. NCI,BETHESDA,MD 20892. RP MCLAUGHLIN, JK (reprint author), INT EPIDEMIOL INST,1550 RES BLVD,ROCKVILLE,MD 20850, USA. NR 2 TC 17 Z9 17 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 SEP 20 PY 1995 VL 87 IS 18 BP 1415 EP 1416 DI 10.1093/jnci/87.18.1415-a PG 2 WC Oncology SC Oncology GA RU758 UT WOS:A1995RU75800020 PM 7658505 ER PT J AU GAO, BC EISENBERG, E GREENE, L AF GAO, BC EISENBERG, E GREENE, L TI INTERACTION OF NUCLEOTIDE-FREE HSC70 WITH CLATHRIN AND PEPTIDE AND EFFECT OF ATP ANALOGS SO BIOCHEMISTRY LA English DT Article ID SHOCK COGNATE PROTEIN; UNCOATING ATPASE; COATED VESICLES; BINDING-PROTEIN; TRANSLOCATION; MEMBRANES; BIP AB The functions of the 70 kDa heat-shock proteins (hsp70s) are regulated by their bound nucleotide. We previously observed major differences in the effect of bound ATP and ADP on the interaction of hsc70 (constitutive hsp70) with its protein substrates. In the present study, we investigated the interaction of protein substrates with nucleotide-free hsc70 and with hsc70 with bound ATP analogues. We found, first, that nucleotide-free hsc70 appeared to interact differently with different substrates. Specifically, nucleotide-free hsc70 behaved much more like hsc70-ATP than hsc70-ADP in that clathrin very rapidly bound to and dissociated from nucleotide-free hsc70 in contrast to its very slow binding to and dissociation from hsc70-ADP. On the other hand, nucleotide-free hsc70 behaved more like hsc70-ADP than hsc70-ATP in that cytochrome c peptide dissociated very slowly from nucleotide-free hsc70 compared to its rapid dissociation from hsc70-ATP. Second, binding of the ATP analogues AMP-PNP, dATP, and ATP gamma S to nucleotide-free hsc70 had very Little further effect on the properties of the nucleotide-free hsc70. Therefore, previously observed effects of ATP analogues may have been due to removal of the bound ADP rather than to the presence of analogues. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 30 TC 12 Z9 12 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 19 PY 1995 VL 34 IS 37 BP 11882 EP 11888 DI 10.1021/bi00037a028 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX003 UT WOS:A1995RX00300028 PM 7547923 ER PT J AU WERNER, MH BIANCHI, ME GRONENBORN, AM CLORE, GM AF WERNER, MH BIANCHI, ME GRONENBORN, AM CLORE, GM TI NMR SPECTROSCOPIC ANALYSIS OF THE DNA CONFORMATION INDUCED BY THE HUMAN TESTIS-DETERMINING FACTOR SRY SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; MINOR-GROOVE; 2D NMR; PROTEINS; SPECTRA; COMPLEX AB The conformation of an eight base pair DNA oligonucleotide duplex bound to the human testis determining factor SRY and the orientation of the protein domain within the complex have been analyzed by a variety of NMR methods which permit the selective observation of protons attached to C-12 nuclei in the presence of uniformly enriched C-13/N-15 protein. Qualitative analysis of nuclear and rotating frame Overhauser enhancement spectra at multiple mixing times indicates that the conformation of the SRY-bound DNA is distinct from that of A- and B-DNA, in agreement with the recent three-dimensional structure determination of the complex [Werner, M. W., Huth, J. R., Gronenborn, A. M., & Clore, G. M. (1995) Cell 81, 705-714]. Selective observation of intermolecular NOEs between protein and DNA indicates that partial intercalation of a protein side chain occurs between two adenine bases in the DNA. octamer. The analysis of structural features by NMR for this unusual DNA conformer and the orientation of the protein domain on the DNA is discussed. The structural features of the DNA complexed to SRY are remarkably similar, but not identical, to those of DNA complexed to the TATA-binding protein (TBP). C1 NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. IST SCI SAN RAFFAELE,DIBIT,I-20132 MILAN,ITALY. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 25 TC 49 Z9 49 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 19 PY 1995 VL 34 IS 37 BP 11998 EP 12004 DI 10.1021/bi00037a042 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX003 UT WOS:A1995RX00300042 PM 7547937 ER PT J AU BENAV, P CROFFORD, LJ WILDER, RL HLA, T AF BENAV, P CROFFORD, LJ WILDER, RL HLA, T TI INDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION IN SYNOVIAL FIBROBLASTS BY PROSTAGLANDIN-E AND INTERLEUKIN-1 - A POTENTIAL MECHANISM FOR INFLAMMATORY ANGIOGENESIS SO FEBS LETTERS LA English DT Article DE ANGIOGENESIS; INTERLEUKIN-1-ALPHA; PROSTAGLANDIN E(2); RHEUMATOID ARTHRITIS; VASCULAR ENDOTHELIAL GROWTH FACTOR ID RHEUMATOID-ARTHRITIS; PERMEABILITY FACTOR; STIMULATION; IDENTIFICATION; COLLAGENASE; PRODUCTS; DISEASE; MITOGEN; LESION; CELLS AB Inflammatory mediators such as prostaglandin E(2) (PGE(2)) and interleukin-l (IL-1) induce angiogenesis by yet undefined mechanisms, We demonstrate that PGE(2) and IL-1 induces the expression of vascular endothelial growth factor (VEGF), a selective angiogenic factor by rheumatoid synovial fibroblast cells, Transcripts for the EP(1) and EP(2) subtypes of PGE receptors are expressed in synovial fibroblasts, Activators of protein kinase A pathway stimulated the expression of VEGF whereas down-regulation of protein kinase C did not influence the PGE effect, suggesting that signalling from the EP(2) receptor via the protein kinase A pathway is important, The induction of VEGF expression by PGE(2) and interleukin-1 alpha may be an important mechanism in inflammatory angiogenesis. C1 AMER RED CROSS,JEROME H HOLLAND LAB,DEPT BIOL MOLEC,ROCKVILLE,MD 20855. UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,DIV RHEUMATOL,ANN ARBOR,MI. NIAMS,BETHESDA,MD. RI Hla, Timothy/G-5873-2012; Crofford, Leslie/J-8010-2013 OI Hla, Timothy/0000-0001-8355-4065; FU NHLBI NIH HHS [HL49094]; NIDDK NIH HHS [DK45659] NR 45 TC 398 Z9 405 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 18 PY 1995 VL 372 IS 1 BP 83 EP 87 DI 10.1016/0014-5793(95)00956-A PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RW245 UT WOS:A1995RW24500017 PM 7556649 ER PT J AU GREEN, SB CORLE, DK GAIL, MH MARK, SD PEE, D FREEDMAN, LS GRAUBARD, BI LYNN, WR AF GREEN, SB CORLE, DK GAIL, MH MARK, SD PEE, D FREEDMAN, LS GRAUBARD, BI LYNN, WR TI INTERPLAY BETWEEN DESIGN AND ANALYSIS FOR BEHAVIORAL INTERVENTION TRIALS WITH COMMUNITY AS THE UNIT OF RANDOMIZATION SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE INTERVENTION STUDIES; MATCHED-PAIR ANALYSIS; RANDOM ALLOCATION; RANDOMIZED CONTROLLED TRIALS; SMOKING CESSATION; STATISTICS ID CLUSTER RANDOMIZATION; POWER AB This paper outlines an approach for the design and analysis of randomized controlled trials investigating community-based interventions for behavioral change aimed at health promotion, The approach is illustrated using the Community Intervention Trial for Smoking Cessation (COMMIT), conducted from 1988 to 1993, involving 11 pairs of communities in North America, matched on geographic location, size, and sociodemographic factors. The situation discussed is when assignment to intervention is done at the community level; for COMMIT, the very nature of the intervention required this. The number of communities is a key determinant of the statistical power of the trial. The use of matched pairs of communities can achieve a gain in statistical efficiency. Randomization is used to obtain an unbiased assessment of the intervention effect; randomization also provides the basis for the statistical analysis. Permutation tests (and corresponding test-based confidence intervals), using community as the unit of analysis, follow directly from the randomization distribution. Within this framework, individual-level covariates can be used for imputation of missing values and for adjusting analyses of intervention effect. C1 INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. RP GREEN, SB (reprint author), NCI,EXECUT PLAZA N,SUITE 344,BETHESDA,MD 20892, USA. NR 21 TC 45 Z9 45 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1995 VL 142 IS 6 BP 587 EP 593 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RT897 UT WOS:A1995RT89700004 PM 7653466 ER PT J AU BRAUN, MM HELZLSOUER, KJ HOLLIS, BW COMSTOCK, GW AF BRAUN, MM HELZLSOUER, KJ HOLLIS, BW COMSTOCK, GW TI COLON-CANCER AND SERUM VITAMIN-D METABOLITE LEVELS 10-17 YEARS PRIOR TO DIAGNOSIS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE COLON; NEOPLASMS; VITAMIN-D ID COLORECTAL-CANCER; 1,25-DIHYDROXYVITAMIN-D; PSORIASIS; CALCIUM; ASSAY AB This study examines the hypothesis that low serum levels of vitamin D metabolites are associated with an increased risk for colon cancer. From August through November 1974, 20,305 residents of Washington County, Maryland, donated blood for storage at -70 degrees C in a serum bank. Colon cancer was subsequently diagnosed among 57 of these residents during the period 1984-1991. Controls had donated blood in 1974 and remained free of colon cancer through the date of diagnosis of the case. Two controls were matched to each case on age (+/-1 year), race, sex, and date of blood draw (+/-1 month). Mean 25-hydroxyvitamin D levels were 23.6 ng/ml and 23.2 ng/ml, and mean 1,25-dihydroxyvitamin D levels were 34.7 pg/ml and 34.6 pg/ml, in cases and controls, respectively. Analysis by quintile of serum level similarly found that none of the 95% confidence intervals of the odds ratios excluded unity, and a dose-response effect was not observed. Our data provide no strong support for the hypothesis that vitamin D metabolite levels affect the subsequent risk for colon cancer. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. NR 19 TC 83 Z9 84 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1995 VL 142 IS 6 BP 608 EP 611 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RT897 UT WOS:A1995RT89700007 PM 7653469 ER PT J AU OBRIEN, TR HOOVER, DR ROSENBERG, PS CHEN, BB DETELS, R KINGSLEY, LA PHAIR, J SAAH, AJ AF OBRIEN, TR HOOVER, DR ROSENBERG, PS CHEN, BB DETELS, R KINGSLEY, LA PHAIR, J SAAH, AJ TI EVALUATION OF SECULAR TRENDS IN CD4+ LYMPHOCYTE LOSS AMONG HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-INFECTED MEN WITH KNOWN DATES OF SEROCONVERSION SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; HIV SEROPOSITIVITY; HIV-1; T4 LYMPHOCYTES ID MULTICENTER AIDS COHORT; HOMOSEXUAL MEN; HIV-INFECTION; DISEASE; PROGRESSION; COUNTS; TIME AB The rate at which immunodeficiency develops in untreated human immunodeficiency virus type 1 (HIV-1)-infected persons might be increasing or decreasing over time because of viral evolution or other factors. Beginning in 1984, Multicenter AIDS Cohort Study investigators recruited HIV-1-seronegative homosexual/bisexual men from four US metropolitan areas and examined them semiannually for HIV-1 seroconversion. To assess possible secular changes in the natural history of HIV-1 infection, the authors examined CD4+ lymphocyte data from 354 men who seroconverted between 1984 and 1991. To control for measurement differences among centers and over time, the authors adjusted CD4+ lymphocyte values to those of persistently seronegative participants. CD4+ lymphocyte percentage measurements at the first seropositive visit formed a U-shaped pattern, with the lowest values observed in 1988 and 1989. The authors observed no consistent secular pattern of CD4+ percentages at later visit dates, except that mean CD4+ percentages were consistently lowest in men who seroconverted in 1988. In a proportional hazards model, the time to the adjusted CD4+ lymphocyte count of <500 cells/mm(3) was not associated with the secular time of seroconversion (relative hazard = 1.05, 95% confidence interval 0.97-1.13). The authors' data do not suggest a major change in the natural history of HIV-1 infection in this population. C1 JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP OBRIEN, TR (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,VIRAL EPIDEMIOL BRANCH,EXECUT PLAZA N BLDG,ROMM 434,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [AI-32520, AI-32513, AI-32511] NR 23 TC 26 Z9 26 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1995 VL 142 IS 6 BP 636 EP 642 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RT897 UT WOS:A1995RT89700012 PM 7653474 ER PT J AU MINAMOTO, S TREISMAN, J HANKINS, WD SUGAMURA, K ROSENBERG, SA AF MINAMOTO, S TREISMAN, J HANKINS, WD SUGAMURA, K ROSENBERG, SA TI ACQUIRED ERYTHROPOIETIN RESPONSIVENESS OF INTERLEUKIN-2-DEPENDENT T-LYMPHOCYTES RETROVIRALLY TRANSDUCED WITH GENES ENCODING CHIMERIC ERYTHROPOIETIN INTERLEUKIN-2 RECEPTORS SO BLOOD LA English DT Article ID RECOMBINANT HUMAN ERYTHROPOIETIN; TUMOR-INFILTRATING LYMPHOCYTES; HUMAN IL-2 RECEPTOR; ELONGATION FACTOR-1-ALPHA; ACTIVATION; CANCER; CHAIN; EXPRESSION; THERAPY; ANEMIA AB Adoptive immunotherapy with tumor-infilitrating lymphocytes (TILs) causes regression of some human tumors, However, the sustained proliferation and antitumor activity of TILs requires the coadministration of potentially toxic amounts of interleukin-a (IL-2). In an effort to overcome the requirement by T cells for IL-2, we have introduced alternative growth factor receptors that use the relatively nontoxic cytokine erythropoietin (Epo) as a ligand. In our model system, the coexpression of chimeric receptors consisting of the extracellular portion of the Epo receptor (EpoR) and the intracellular portions of the IL-2 receptor subunits, beta and gamma, conferred Epo responsiveness on a T-cell line. By contrast, cells expressing the wild-type EpoR did not proliferate in response to Epo, This suggested that Epo binding caused the activation of an IL-2 signal pathway mediated by the chimeric receptors, This approach can be used to minimize toxicity and potentially improve cancer immunotherapy with TILs. (C) 1995 by The American Society of Hematology. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. TOHOKU UNIV,SCH MED,DEPT MICROBIOL,SENDAI,MIYAGI 980,JAPAN. NR 40 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1995 VL 86 IS 6 BP 2281 EP 2287 PG 7 WC Hematology SC Hematology GA RU052 UT WOS:A1995RU05200028 PM 7662975 ER PT J AU WELLMANN, A OTSUKI, T VOGELBRUCH, M CLARK, HM JAFFE, ES RAFFELD, M AF WELLMANN, A OTSUKI, T VOGELBRUCH, M CLARK, HM JAFFE, ES RAFFELD, M TI ANALYSIS OF THE T(2-5)(P23-Q35) TRANSLOCATION BY REVERSE TRANSCRIPTION-POLYMERASE CHAIN-REACTION IN CD30(+) ANAPLASTIC LARGE-CELL LYMPHOMAS, IN OTHER NON-HODGKINS-LYMPHOMAS OF T-CELL PHENOTYPE, AND IN HODGKINS-DISEASE SO BLOOD LA English DT Article ID CHROMOSOMAL ABNORMALITY; KI-1 LYMPHOMA; MALIGNANT HISTIOCYTOSIS; EXPRESSION; CHILDHOOD AB The t(2;5)(p23;q35) translocation is associated with a high percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell phenotype, This translocation was recently cloned and results in the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to a novel tyrosine kinase-encoding gene designated anaplastic lymphoma kinase (ALK) on chromosome 2q23. Using a sensitive and specific reverse transcription-polymerase chain reaction (RT-PCR) assay to detect the NPM/ALK fusion transcript, we assessed the involvement of NPM/ALK in a series of histologically and immunohistochemically confirmed ALCL, in non-ALCL aggressive non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease (HD) to better define the morphologic spectrum of disease associated with this translocation. Twenty-four cases of ALCL were selected on the basis of CD30 positivity and histologic features. Seventeen cases presented as classical nodal and extranodal disease, four cases presented as primary cutaneous disease, and three were associated with human immunodeficiency virus (HIV) infection. As ALCL may show overlapping histology with both HD and other aggressive non-Hodgkin's lymphomas, particularly of T-cell phenotype (T-NHL), we also studied 34 cases of HD and 19 of T-NHL. NPM/ALK chimeric transcripts of identical size were detected in 11 of the 24 (46%) cases of ALCL. NPM/ALK fusion transcripts were found in 11 of 17 (65%) classical ALCL cases but were not detected in the four primary cutaneous cases of ALCL or in the three HIV-related ALCL cases. In addition, NPM/ALK transcripts were not detected in any of the 34 cases of HD or in the 19 cases of T-NHL. These data indicate that NPM/ALK fusion transcripts occur in a high percentage of classical nodal ALCL (65%). In addition, these data strongly suggest that ALCL, as defined in this study, is not pathogenetically related to either HD disease or the majority of other types of aggressive T-NHL. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. NR 28 TC 118 Z9 118 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 SEP 15 PY 1995 VL 86 IS 6 BP 2321 EP 2328 PG 8 WC Hematology SC Hematology GA RU052 UT WOS:A1995RU05200032 PM 7662979 ER PT J AU FABRY, ME SENGUPTA, A SUZUKA, SM COSTANTINI, F RUBIN, EM HOFRICHTER, J CHRISTOPH, G MANCI, E CULBERSON, D FACTOR, SM NAGEL, RL AF FABRY, ME SENGUPTA, A SUZUKA, SM COSTANTINI, F RUBIN, EM HOFRICHTER, J CHRISTOPH, G MANCI, E CULBERSON, D FACTOR, SM NAGEL, RL TI A 2ND-GENERATION TRANSGENIC MOUSE MODEL EXPRESSING BOTH HEMOGLOBIN-S (HBS) AND HBS-ANTILLES RESULTS IN INCREASED PHENOTYPIC SEVERITY SO BLOOD LA English DT Article ID SICKLE-CELL DISEASE; HUMAN BETA-S; ALPHA-GLOBINS; RED-CELLS; POLYMERIZATION; MICE; TRANSPORT; HYPOXIA; INVIVO; CHAINS AB We report on a second generation of transgenic mice produced by crossing a transgenic mouse line expressing high levels of human alpha and beta(S) chains (alpha(H) beta(S)[beta(MDD)]) with a line expressing human alpha and beta(S-Antilles) (beta(SAnt)). We hypothesized that mice expressing both hemoglobins (Hbs) would have a more severe phenotype because the reduced oxygen affinity and solubility of the beta(S-Antilles) might enhance the rate and extent of polymer formation. We obtained mice that expressed both beta(S) and beta(S-Antilles). Th, doubly transgenic mice that are heterozygous for deletion of mouse beta(Major) (beta(MD)) occurred with reduced frequency and those that are homozygous for deletion of mouse beta(Major) (beta(MDD)) occurred at a much reduced frequency and suffered early mortality. Human alpha was 58% of all alpha globin for all animals, whereas beta(S) and beta(S-Antilles) were 34% and 28% of all beta globins for beta(MD) mice and 42% and 36% for beta(MDD) mice. Hematocrit, Hb, and mean corpuscular Hb were normal for all transgenic mice, but reticulocyte levels were higher for the doubly transgenic mice versus (alpha(H) beta(S)[beta(MDD)] mice older than 30 days (10.0% +/- 1.0% v 4.3% +/- 0.4%; P < .001, mean +/- SE, n = 20 and n = 10, respectively) and control mice (3.9% +/- 0.4%). Reticulocytosis was more severe in mice less than 30 days old (>20% for alpha(H) beta(S) beta(S-Ant)[beta(MDD)] mice). The median mean corpuscular hemoglobin concentration of doubly transgenic mice was higher than that of alpha(H) beta(S)[beta(MDD)] mice with a variable number of very dense cells. Delay times for polymerization of Hb in red blood cells from alpha(H) beta(S) beta(S-Ant)[beta(MDD)] mice were shorter than those of alpha(H) beta(S)[beta(MDD)] mice, and there were fewer cells with delay times greater than 100 seconds. Urine-concentrating ability in control mice under ambient conditions is 2,846 +/- 294 mOsm and was reduced 30% to 1,958 +/- 240 mOsm, P < 4 x 10(-8) in all mice expressing both transgenes. We conclude that doubly transgenic mice have a more severe phenotype than either of the two parental lines. These mice may be suitable for validating therapeutic intervention in sickle cell disease. (C) 1995 by The American Society of Hematology. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10461. COLUMBIA UNIV,DEPT GENET & DEV,NEW YORK,NY. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DIV CELL & MOLEC BIOL,BERKELEY,CA 94720. NIH,PHYS CHEM LAB,BETHESDA,MD. UNIV SO ALABAMA,CENTRALIZED PATHOL UNIT SICKLE CELL DIS,MOBILE,AL. RP FABRY, ME (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,ULLMANN 921,1300 MORRIS PK AVE,BRONX,NY 10461, USA. FU NHLBI NIH HHS [HL-38655] NR 30 TC 68 Z9 68 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1995 VL 86 IS 6 BP 2419 EP 2428 PG 10 WC Hematology SC Hematology GA RU052 UT WOS:A1995RU05200044 PM 7662990 ER PT J AU NEWTON, WA GEHAN, EA WEBBER, BL MARSDEN, HB VANUNNIK, AJM HAMOUDI, AB TSOKOS, MG SHIMADA, H HARMS, D SCHMIDT, D NINFO, V CAVAZZANA, AO GONZALEZCRUSSI, F PARHAM, DM REIMAN, HM ASMAR, L BELTANGADY, MS SACHS, NE TRICHE, TJ MAURER, HM AF NEWTON, WA GEHAN, EA WEBBER, BL MARSDEN, HB VANUNNIK, AJM HAMOUDI, AB TSOKOS, MG SHIMADA, H HARMS, D SCHMIDT, D NINFO, V CAVAZZANA, AO GONZALEZCRUSSI, F PARHAM, DM REIMAN, HM ASMAR, L BELTANGADY, MS SACHS, NE TRICHE, TJ MAURER, HM TI CLASSIFICATION OF RHABDOMYOSARCOMAS AND RELATED SARCOMAS - PATHOLOGICAL ASPECTS AND PROPOSAL FOR A NEW CLASSIFICATION - INTERGROUP RHABDOMYOSARCOMA STUDY SO CANCER LA English DT Article DE RHABDOMYOSARCOMA; SOFT TISSUE SARCOMA; CHILDREN; ADOLESCENTS; TUMOR CLASSIFICATION ID CHILDHOOD RHABDOMYOSARCOMA; ALVEOLAR RHABDOMYOSARCOMA; CHILDREN; PROGNOSIS; DIAGNOSIS; TUMORS; FUSION; PAX3; GENE AB Background. There is a need to develop a single prognostically significant classification of rhabdomyosarcomas (RMS) and other related tumors of children, adolescents, and young adults which would be a current guide for their diagnosis, allow valid comparison of outcomes between protocols carried out anywhere in the world, and should enhance recognition of prognostic subsets. Method. Sixteen pathologists from eight pathology groups, representing six countries and several cooperative groups, classified by four histopathologic classification schemes 800 representative tumors of the 999 eligible cases treated on Intergroup Rhabdomyosarcoma Study II. Each tumor was classified according to each of the four systems by each of the pathologists. In addition, two independent subsamples of 200 of the 800 patients were reviewed according to the new system, so that 343 distinct patients were reviewed once, and 57 of these twice. Results. A study of the survival rates of all subtypes in the sample of 800 patients led to the formation of a new system. This was tested on two independent subsets of 200 of the original cases and found to be reproducible and predictive of outcome by univariate analysis. A multivarlate analysis of the 343 patients classified according to the new system indicated that a survival model including pathologic classification and known prognostic factors of primary site, clinical group, and tumor size was significantly better at predicting survival than a model with only the known prognostic factors. Conclusion. This new classification, termed International Classification of Rhabdomyosarcoma (ICR) by the authors, was reproducible and predictive of outcome among patients with differing histologies treated uniformly on the Intergroup Rhabdomyosarcoma II protocols. We believe it should be utilized by all pathologists and cooperative groups to classify rhabdomyosarcomas in order to provide comparability among and within multi-institutional studies. C1 PEDIAT ONCOL GRP, CHICAGO, IL USA. PEDIAT INTERGRP STAT CTR, WASHINGTON, DC USA. CHILDRENS CANC GRP, ARCADIA, CA USA. NCI, BETHESDA, MD 20892 USA. GERMAN ITALIAN COOPERAT SOFT TISSUE SARCOMAS STUD, COLUMBUS, OH USA. INTERGRP RHABDOMYOSARCOMA PATHOL CTR, COLUMBUS, OH USA. FU NCI NIH HHS [CA-13539, CA-24507, CA-29139] NR 42 TC 271 Z9 280 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 15 PY 1995 VL 76 IS 6 BP 1073 EP 1085 DI 10.1002/1097-0142(19950915)76:6<1073::AID-CNCR2820760624>3.0.CO;2-L PG 13 WC Oncology SC Oncology GA RT102 UT WOS:A1995RT10200023 PM 8625211 ER PT J AU HURSTING, SD PERKINS, SN HAINES, DC WARD, JM PHANG, JM AF HURSTING, SD PERKINS, SN HAINES, DC WARD, JM PHANG, JM TI CHEMOPREVENTION OF SPONTANEOUS TUMORIGENESIS IN P53-KNOCKOUT MICE SO CANCER RESEARCH LA English DT Note ID INDUCED REGRESSION; GROWTH; DEHYDROEPIANDROSTERONE; DIFFERENTIATION; LYMPHOPOIESIS; INHIBITION; RETINOIDS; TUMORS; AGENTS; P53 AB Spontaneous tumorigenesis was evaluated in male p53-knockout (p53(-/-)) mice treated with dehydroepiandrosterone (DHEA), quercetin, d-limonene, or all-trans retinoic acid to determine whether tumor development in these mice can be modulated by cancer-chemopreventive agents, DHEA-treated mice experienced a delay in tumorigenesis (particularly lymphomas) and subsequent mortality (P < 0.01) relative to untreated control mice. Quercetin, d-limonene, and all-trans retinoic acid each had no effect on spontaneous tumor development in p53(-/-) mice. These data demonstrate that tumor development in p53(-/-) mice can be delayed by DHEA and suggest that p53(-/-) mice provide a useful model for evaluating strategies to offset the increased risk of tumorigenesis resulting from loss of p53 tumor suppressor function. C1 NCI,FREDERICK CANC RES & DEV CTR,NUTR & MOLEC RECOGNIT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,VET & TUMOR PATHOL LAB ANIM SCI,FREDERICK,MD 21702. NR 25 TC 68 Z9 70 U1 1 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 SEP 15 PY 1995 VL 55 IS 18 BP 3949 EP 3953 PG 5 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900002 PM 7664260 ER PT J AU WILTSHIRE, RN DURAY, P BITTNER, ML VISAKORPI, T MELTZER, PS TUTHILL, RJ LIOTTA, LA TRENT, JM AF WILTSHIRE, RN DURAY, P BITTNER, ML VISAKORPI, T MELTZER, PS TUTHILL, RJ LIOTTA, LA TRENT, JM TI DIRECT VISUALIZATION OF THE CLONAL PROGRESSION OF PRIMARY CUTANEOUS MELANOMA - APPLICATION OF TISSUE MICRODISSECTION AND COMPARATIVE GENOMIC HYBRIDIZATION SO CANCER RESEARCH LA English DT Note ID MALIGNANT-MELANOMA AB Human cutaneous malignant melanoma progresses through a series of well defined clinical and histopathological stages. It has been assumed that the neoplastic progression of this disease advances from a common acquired nevus or dysplastic nevus through the primary radial growth phase (RGP), primary vertical growth phase (VGP), and finally to distant metastasis. However, it has never been directly shown that VGP is clonally derived from RGP. Furthermore, it has not been possible previously to conduct a detailed genetic analysis on pure tumor cells from archival material because the lesions are a heterogenous mixture of normal and neoplastic cells, and the entire specimen must be excised and fixed for clinical diagnosis. This report describes a new approach designed to identify DNA copy number changes in tumor cells from a series of progressive primary stages of cutaneous melanoma archival biopsies. Under direct high-power visualization, cells are procured with a sterile needle from highly specific areas of the tissue section. DNA is extracted from microdissected cells (normal, RGP, and VGP), PCR amplified, fluorescently labeled, and examined by comparative genomic hybridization to determine DNA copy number changes. Data obtained from three representative cases suggest a clonal derivation of VGP cells from RGP. This approach could be useful in identifying the sequence of genetic changes in progressive cutaneous melanoma stages. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NCI,PATHOL LAB,BETHESDA,MD 20892. CLEVELAND CLIN FDN,DEPT PATHOL,CLEVELAND,OH 44195. NR 23 TC 76 Z9 78 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 SEP 15 PY 1995 VL 55 IS 18 BP 3954 EP 3957 PG 4 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900003 PM 7664261 ER PT J AU YANG, CHJ HORTON, JK COWAN, KH SCHNEIDER, E AF YANG, CHJ HORTON, JK COWAN, KH SCHNEIDER, E TI CROSS-RESISTANCE TO CAMPTOTHECIN ANALOGS IN A MITOXANTRONE-RESISTANT HUMAN BREAST-CARCINOMA CELL-LINE IS NOT DUE TO DNA TOPOISOMERASE-I ALTERATIONS SO CANCER RESEARCH LA English DT Note ID DRUG ACCUMULATION; CANCER-CELLS; OVEREXPRESSION; MECHANISM AB We have previously described a mitoxantrone-resistant human breast carcinoma cell line, MCF7/MX, in which resistance was associated with a defect in the energy-dependent accumulation of mitoxantrone in the absence of P-glycoprotein overexpression (M. Nakagawa et al., Cancer Res. 52: 6175-6181, 1992). We now report that this cell line is highly cross-resistant to the camptothecin analogues topotecan (180-fold), 9-aminocamptothecin (120-fold), CPT-11 (56-fold), and SN38 (101-fold), but is only mildly cross-resistant to the parent compound camptothecin (3.2-fold) and 10,11-methylenedioxy-camptothecin (2.9-fold). Topotecan accumulation was decreased in MCF7/MX cells compared to parental MCF7/WT cells, and there was a corresponding reduction in topotecan-mediated stimulation of the enzyme/DNA complex formation in MCF7/MX cells compared to MCF7/WT cells. No overexpression of the multidrug resistance-associated protein was detected compared to parental MCF7/WT cells. Furthermore, both sensitive MCF7/WT and mitoxantrone-resistant MCF7/MX cells contain equal amounts of DNA topoisomerase I protein, and DNA relaxation activities were equal in both cell lines and inhibited to the same extent by topotecan and camptothecin. Thus, these results suggest a novel mechanism of resistance to topoisomerase I inhibitors in cancer cells. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 19 TC 89 Z9 89 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1995 VL 55 IS 18 BP 4004 EP 4009 PG 6 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900014 PM 7664272 ER PT J AU ADAMSON, PC BALLS, FM BELASCO, JE LANGE, B BERG, SL BLANEY, SM CRAIG, C POPLACK, DG AF ADAMSON, PC BALLS, FM BELASCO, JE LANGE, B BERG, SL BLANEY, SM CRAIG, C POPLACK, DG TI A PHASE-I TRIAL OF AMIFOSTINE (WR-2721) AND MELPHALAN IN CHILDREN WITH REFRACTORY CANCER SO CANCER RESEARCH LA English DT Article ID HIGH-DOSE CISPLATIN; CIS-PLATINUM; TOXICITY; CYCLOPHOSPHAMIDE; PROTECTION; MELANOMA AB Melphalan has a steep dose-response curve, but the use of high doses results in unacceptable myelosuppression. Strategies to circumvent this dose-limiting myelosuppression would allow for the administration of higher, more effective doses of melphalan. Amifostine (WR-2721) has been shown in preclinical studies to protect the bone marrow from the myelotoxicity of melphalan, and in clinical trials, to protect from the myelotoxicity of other alkylating agents. A Phase I trial of the combination of amifostine and melphalan was performed in children with refractory cancers to: (a) define the acute toxicities of amifostine and its maximum tolerated dose (MTD); and (b) to determine whether the dose of melphalan could be safely escalated when administered in combination with amifostine. Amifostine was administered i.v, as a 15-min infusion 30 min before melphalan, The starting dose of amifostine was 750 mg/m(2), with planned dose escalations in 30% increments. Melphalan was administered as a 5-min infusion using the previously defined MTD in heavily pretreated patients, 35 mg/m(2), as the starting dose. The dose of melphalan was escalated by 30% increments. Nineteen patients, ranging in age from 3 to 24 years (median, 15 years), were entered on trial. The dose of amifostine was escalated to 2700 mg/m(2), which is approximately 3-fold higher than the adult recommended dose, without reaching a MTD. Fifteen patients experienced nondose-limiting (<25%), transient decreases in blood pressure after the amifostine infusion. Other nondose-limiting toxicities of amifostine included mild nausea and vomiting, flushing, anxiety, diarrhea, and urinary retention. Six patients, three each at the 2100 and 2700 mg/m(2) amifostine dose levels were treated with an escalated dose of melphalan (45 mg/m(2)). All of these patients experienced grade 4 neutropenia (<500/mm(3)), and five of six patients had grade 4 thrombocytopenia. The duration of this dose-limiting myelosuppression exceeded 7 days in four of six patients. Although no dose-limiting (grade 3 or 4) toxicity was attributed to amifostine, significant anxiety and reversible urinary retention occurred at the two highest amifostine dose levels. A dose of 1650 mg/m(2) for pediatric Phase II trials is recommended. High doses of amifostine, however, do not appear to allow for escalation of melphalan beyond its single agent MTD of 35 mg/m(2). C1 CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 37 Z9 37 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 SEP 15 PY 1995 VL 55 IS 18 BP 4069 EP 4072 PG 4 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900025 PM 7664282 ER PT J AU CIOCCO, GM MOSCHEL, RC CHAE, MY MCLAUGHLIN, PJ ZAGON, IS PEGG, AE AF CIOCCO, GM MOSCHEL, RC CHAE, MY MCLAUGHLIN, PJ ZAGON, IS PEGG, AE TI SPECIFIC LABELING OF O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE BY REACTION WITH O-6-(P-HYDROXY[H-3]METHYLBENZYL)GUANINE SO CANCER RESEARCH LA English DT Article ID HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ALKYLATING-AGENTS; O6-BENZYLGUANINE; CELLS; METHYLTRANSFERASE; INACTIVATION; PURIFICATION; SENSITIVITY; EXPRESSION; PREVENTION AB O-6-Alkylguanine-DNA alkyltransferase (AGT) is an important DNA repair protein that removes adducts from the O-6 position of guanine by transferring them to a cysteine residue within its amino acid sequence. Mammalian AGTs are readily inactivated by incubation with O-6-benzylguanine (BG), which is an alternative substrate for the protein. To examine this inactivation in more detail and to develop a procedure for the specific labeling of human AGT, we synthesized a BG derivative, O-6-(p-hydroxy[H-3]methylbenzyl)guanine ([H-3]HMBG) and examined its interaction with AGT in HT29 cell extracts and in HT29 cells, Incubation of human AGT with [3H]HMBG led to the incorporation of radioactivity in the protein in a time- and temperature-dependent manner. This reaction was specific, since neither AGT that was first inactivated by reaction with BG nor proteins other than AGT were labeled. Digestion of the labeled AGT with trypsin showed that a single peptide contained the label. Sequencing of this peptide indicated that the label was bound to cysteine-145. These results demonstrate that AGT accepts HMBG as a substrate and becomes inactivated by transfer of a p-hydroxymethylbenzyl residue to the cysteine-145 acceptor site. When [H-3]HMBG was added to cultures of HT29 cells which are Mer(+) and express active AGT, radioactivity was incorporated in a macromolecule and could be detected by autoradiography. No such labeling occurred with BE or CHO cells, which are Mer(-) and lack AGT. Examination of the interaction of [3H]HMBG with mutant AGT proteins that differ greatly in their abilities to react with BG showed that there was a strong correlation between the reaction with BG and the labeling with [H-3]HMBG. These results indicate that [H-3]HMBG is a potentially useful reagent for the detection and localization of AGT activity and for the investigation of its mechanism of action. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT ANAT & NEUROSCI,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [CA-18137, CA-57725] NR 34 TC 16 Z9 16 U1 0 U2 4 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 SEP 15 PY 1995 VL 55 IS 18 BP 4085 EP 4091 PG 7 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900028 PM 7664284 ER PT J AU GNARRA, JR DRESSLER, GR AF GNARRA, JR DRESSLER, GR TI EXPRESSION OF PAX-2 IN HUMAN RENAL-CELL CARCINOMA AND GROWTH-INHIBITION BY ANTISENSE OLIGONUCLEOTIDES SO CANCER RESEARCH LA English DT Article ID TUMOR ALVEOLAR RHABDOMYOSARCOMA; WILMS-TUMOR; GENE; KIDNEY; MESENCHYME; PROTEIN; SYSTEM; MICE AB Renal cell carcinoma (RCC) is the most common malignancy in the adult kidney. Because RCC is generally thought to arise from the epithelium of the proximal tubules, the expression of Pax-2, a gene required for renal epithelium development, was examined in primary tumors and tumor-derived cell lines. Immunostaining of frozen sections from the primary tumors indicated Pax-2 expression in the malignant cells but not in the surrounding stroma. In a panel of human RCC-derived cell lines, 73% expressed Pax-2 protein and mRNA. Treatment of RCC cell lines with antisense oligodeoxynucleotides resulted in down-regulation of Pax-2 protein expression and growth inhibition after 3 days in culture. These data indicate that Pax-2 gene function is required for proliferation, as well as differentiation during embryonic development, and suggest a novel therapy for RCC. C1 UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. NR 33 TC 106 Z9 107 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 SEP 15 PY 1995 VL 55 IS 18 BP 4092 EP 4098 PG 7 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900029 PM 7664285 ER PT J AU JINDRICH, J JOSEF, P LINDBERG, B AF JINDRICH, J JOSEF, P LINDBERG, B TI SEPARATION OF CYCLODEXTRINS AND THEIR DERIVATIVES BY THIN-LAYER AND PREPARATIVE COLUMN CHROMATOGRAPHY SO CARBOHYDRATE RESEARCH LA English DT Article DE CYCLODEXTRINS; THIN-LAYER CHROMATOGRAPHY; PREPARATIVE COLUMN CHROMATOGRAPHY ID CYCLOMALTOHEPTAOSE AB Cyclodextrins, their derivatives and products of their partial hydrolysis are clearly separated by chromatography on silica gel by mobile phases containing aqueous ammonia and organic solvent (acetonitrile or 1-propanol). This system allows separation of compounds with different numbers of substituents on cyclodextrin, but does not allow the separation of isomers; the system can be used both for thin-layer chromatography and for preparative column chromatography. The isomers in the fraction thus obtained can be in some cases separated, after peracetylation, by chromatography on silica gel using a mobile phase consisting of methanol and dichloromethane. This chromatographic sequence potentially yields derivatives of cyclodextrins in quantities which enable evaluation of their solubilization and biological properties. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. CHARLES UNIV,DEPT ORGAN CHEM,CR-12840 PRAGUE 2,CZECH REPUBLIC. UNIV STOCKHOLM,ARRHENIUS LAB,DEPT ORGAN CHEM,S-10691 STOCKHOLM,SWEDEN. RI Jindrich, Jindrich/A-3527-2008 OI Jindrich, Jindrich/0000-0003-3770-0214 NR 9 TC 23 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 15 PY 1995 VL 275 IS 1 BP 1 EP 7 DI 10.1016/0008-6215(95)00071-Z PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA RX882 UT WOS:A1995RX88200001 PM 7585717 ER PT J AU LEI, PS OGAWA, Y FLIPPENANDERSON, JL KOVAC, P AF LEI, PS OGAWA, Y FLIPPENANDERSON, JL KOVAC, P TI SYNTHESIS AND CRYSTAL-STRUCTURE OF METHYL 4,6-DIDEOXY-4-(3-DEOXY-L-GLYCERO-TETRONAMIDO)-2-O-METHYL-ALPHA-D-MANNOPY RANOSIDE, THE METHYL ALPHA-GLYCOSIDE OF THE TERMINAL UNIT, AND PRESUMED ANTIGENIC DETERMINANT, OF THE O-SPECIFIC POLYSACCHARIDE OF VIBRIO-CHOLERAE O/1, SEROTYPE OGAWA SO CARBOHYDRATE RESEARCH LA English DT Article DE O-POLYSACCHARIDE; VIBRIO CHOLERAE O-1; SEROTYPE OGAWA; ALPHA-D-MANNOPYRANOSIDE; METHYL 4,6-DIDEOXY-4-(3-DEOXY-L-GLYCERO-TETRONAMIDO)-2-O-METHYL; SYNTHESIS; ANTIGENIC DETERMINANT ID LIPOPOLYSACCHARIDE AB Methyl 4-azido-4,6-dideoxy-3-O-benzyl-alpha-D-mannopyranoside and its analogous 3-O-(4-methoxybenzyl) derivative were methylated and the 2-O-methyl derivatives formed were converted into methyl 4-amino-4,6-dideoxy-2-O-methyl-alpha-D-mannopyranoside. Reaction of the latter with 3-deoxy-L-glycero-tetronolactone gave the methyl glycoside of 4,6-dideoxy-4-(3-deoxy-L-glycero-tetronamido)-2-O-methyl-alpha-D-mannopyranose, the monosaccharide that is reported to be the terminal moiety of the O-specific polysaccharide of Vibrio cholerae 0:1, serotype Ogawa. The unit cell packing of the compound, which crystallized as a monohydrate, differs from that of the previously described crystalline compound lacking the 2-O-methyl group. The unmethylated sugar is the terminal moiety of the O-specific polysaccharide of Vibrio cholerae 0:1, serotype Inaba. The crystal structure of methyl 4,6-dideoxy-2-0-methyl-4-trifluoroacetamido-alpha-D-mannopyranoside is also described. C1 NIDDK,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. NR 18 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 15 PY 1995 VL 275 IS 1 BP 117 EP 129 DI 10.1016/0008-6215(95)00147-L PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA RX882 UT WOS:A1995RX88200012 PM 7585718 ER PT J AU LEE, H DARDEN, T PEDERSEN, L AF LEE, H DARDEN, T PEDERSEN, L TI ACCURATE CRYSTAL MOLECULAR-DYNAMICS SIMULATIONS USING PARTICLE-MESH-EWALD - RNA DINUCLEOTIDES - APU AND GPC SO CHEMICAL PHYSICS LETTERS LA English DT Article AB Long molecular dynamics (MD) simulations for two crystal RNA dinucleotides ApU (2.0 ns) and GpC (1.5 ns) were performed, starting from the crystallographic positions of all heavy atoms in the crystals. By employing the particle-mesh-Ewald algorithm [Darden et al., J. Chem. Phys. 98 (1993) 10089] to accommodate the long-range Coulomb interactions, highly accurate MD structures were obtained for both crystals. The instantaneous root-mean-square positional deviations of the heavy atoms equilibrate at approximately 0.4 Angstrom for both systems, while the experimental and calculated temperature factors are comparable in size. These results describe the first successful crystal MD simulation of RNA molecules. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. RP LEE, H (reprint author), NIEHS,QUANTITAT & COMPUTAT BIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 18 TC 45 Z9 46 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD SEP 15 PY 1995 VL 243 IS 3-4 BP 229 EP 235 DI 10.1016/0009-2614(95)00845-U PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA RV057 UT WOS:A1995RV05700007 ER PT J AU BURCHFIEL, CM LAWS, A BENFANTE, R GOLDBERG, RJ HWANG, LJ CHIU, D RODRIGUEZ, BL CURB, JD SHARP, DS AF BURCHFIEL, CM LAWS, A BENFANTE, R GOLDBERG, RJ HWANG, LJ CHIU, D RODRIGUEZ, BL CURB, JD SHARP, DS TI COMBINED EFFECTS OF HDL CHOLESTEROL, TRIGLYCERIDE, AND TOTAL CHOLESTEROL CONCENTRATIONS ON 18-YEAR RISK OF ATHEROSCLEROTIC DISEASE SO CIRCULATION LA English DT Article; Proceedings Paper CT 66th Scientific Session of the American-Heart-Association CY NOV 08-11, 1993 CL ATLANTA, GA SP Amer Heart Assoc DE ASIAN AMERICANS; CARDIOVASCULAR DISEASES INCIDENCE; LIPOPROTEINS; LONGITUDINAL STUDIES ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; HAWAII JAPANESE MEN; PLASMA TRIGLYCERIDE; CARDIOVASCULAR-DISEASE; ARTERY DISEASE; MYOCARDIAL-INFARCTION; SERUM TRIGLYCERIDE AB Background Whether the combination of a low level of HDL cholesterol (HDL-C) and high level of triglyceride (TG) confers increased risk of cardiovascular disease and whether risk varies across levels of total cholesterol (TC) are not well established. Combined effects of HDL-C, TG, and TC on the incidence of atherosclerotic disease were examined prospectively in Japanese-American men from the Honolulu Heart Program. Methods and Results Among 1646 men aged 51 to 72 years who were free of coronary heart disease (CHD), stroke, and cancer and were not taking lipid-lowering medication, 318 developed atherosclerotic events (angina, coronary insufficiency, aortic aneurysm, definite CHD, or thromboembolic stroke) and 170 developed definite CHD between 1970 and 1988. Subjects were stratified by TC level (desirable, <200 mg/dL; borderline high, 200 to 239 mg/dL; high, greater than or equal to 240 mg/dL), HDL-C level (<35 and greater than or equal to 35 mg/dL), and TG level (<200 and greater than or equal to 200 mg/dL). With Cox regression with high HDL-C and low TG as reference, age-adjusted relative risks (RR) of atherosclerotic events were significantly elevated in men with low HDL-C and high TG at borderline-high (RR, 2.46; 95% CI, 1.48 to 4.09) and high (RR, 2.21; 95% CI, 1.34 to 3.66) TC levels but not in men with desirable TC levels (RR, 0.89; 95% CI, 0.38 to 2.09). Elevated risks were independent of blood pressure, obesity, fat distribution, diabetes, smoking, and alcohol. Results were not materially altered by exclusion of subjects with angina alone and were similar but somewhat weaker for CHD. Conclusions Risk of atherosclerotic disease appears elevated in subjects with low HDL-C and high TG levels when TC is borderline high or high, independent of other cardiovascular risk factors. These findings support recent cholesterol screening recommendations and suggest that joint effects of HDL-C and TG may be important to consider. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,HONOLULU EPIDEMIOL RES UNIT,HONOLULU,HI. STANFORD UNIV,SCH MED,DEPT MED,DIV ENDOCRINOL GERONTOL & METAB,PALO ALTO,CA 94304. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA. RP BURCHFIEL, CM (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 48 TC 62 Z9 65 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 15 PY 1995 VL 92 IS 6 BP 1430 EP 1436 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RU672 UT WOS:A1995RU67200012 PM 7664423 ER PT J AU ALTSCHULD, RA STARLING, RC HAMLIN, RL BILLMAN, GE HENSLEY, J CASTILLO, L FERTEL, RH HOHL, CM ROBITAILLE, PML JONES, LR XIAO, RP LAKATTA, EG AF ALTSCHULD, RA STARLING, RC HAMLIN, RL BILLMAN, GE HENSLEY, J CASTILLO, L FERTEL, RH HOHL, CM ROBITAILLE, PML JONES, LR XIAO, RP LAKATTA, EG TI RESPONSE OF FAILING CANINE AND HUMAN HEART-CELLS TO BETA(2)-ADRENERGIC STIMULATION SO CIRCULATION LA English DT Article DE CALCIUM CHANNELS; CELLS; HEART FAILURE; MYOCARDIAL CONTRACTION; RECEPTORS, ADRENERGIC, BETA; SARCOPLASMIC RETICULUM ID CARDIAC SARCOPLASMIC-RETICULUM; HUMAN VENTRICULAR MYOCARDIUM; G-PROTEIN; RECEPTOR SUBTYPES; ADENYLYL CYCLASE; DOWN-REGULATION; RIGHT ATRIUM; BETA-2-ADRENOCEPTORS; PHOSPHORYLATION; MYOCYTES AB Background Failing human hearts lose beta(1)- but not beta(2)-adrenergic receptors. In canine hearts with tachypacing failure, the ratio of beta(2)- to beta(1)-adrenergic receptors is increased. The present study was designed to determine whether heart failure increases sensitivity to beta(2)-adrenergic stimulation in isolated canine ventricular cardiomyocytes and to verify that myocytes from failing human ventricles contain functional beta(2)-adrenergic receptors. Methods and Results Myocytes from healthy dogs, dogs with tachypacing failure, and human transplant recipients were loaded with fura 2-AM and subjected to electric field stimulation in the presence of zinterol, a highly selective beta(2)-adrenergic agonist. Zinterol significantly increased [Ca2+](i) transient amplitudes in all three groups. The failing canine myocytes were significantly more responsive than normal to beta(2)-adrenergic stimulation. We also measured isotonic twitches, indo-1 fluorescence transients, and L-type Ca2+ currents in healthy canine myocytes. Zinterol (10(-5) mol/L) elicited large increases in the amplitudes of simultaneously recorded twitches and [Ca2+](i) transients. Zinterol also increased L-type Ca2+ currents in the normal canine myocytes; this augmentation was abolished by 10(-7) mol/L ICI 118,551. cAMP production by suspensions of healthy and failing canine myocytes was not increased by zinterol (10(-9) to 10(-5) mol/L), nor did 10(-5) mol/L zinterol elicit phospholamban phosphorylation. Conclusions Failing human ventricular cardiomyocytes contain functional beta(2)-adrenergic receptors. Canine myocytes also contain functional beta(2)-adrenergic receptors. The canine ventricular response to beta(2)-agonists is increased in tachypacing failure. Positive inotropic responses to beta(2)-stimulation are not mediated by increases in cAMP or cAMP-dependent phosphorylation of phospholamban. C1 OHIO STATE UNIV,DEPT PHYSIOL,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT PHARMACOL,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT RADIOL,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT INTERNAL MED,DIV CARDIOL,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT VET PHYSIOL & PHARMACOL,COLUMBUS,OH 43210. INDIANA UNIV,KRANNERT INST CARDIOL,INDIANAPOLIS,IN 46202. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP ALTSCHULD, RA (reprint author), OHIO STATE UNIV,DEPT MED BIOCHEM,333 HAMILTON HALL,1645 NEIL AVE,COLUMBUS,OH 43210, USA. RI Billman, George/E-2758-2011 FU NHLBI NIH HHS [HL-36240, HL-48835, P01-HL-06308] NR 27 TC 107 Z9 112 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 15 PY 1995 VL 92 IS 6 BP 1612 EP 1618 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RU672 UT WOS:A1995RU67200037 PM 7664448 ER PT J AU FANANAPAZIR, L PANZA, JA MCAREAVEY, D AF FANANAPAZIR, L PANZA, JA MCAREAVEY, D TI DDD-PACING IN OBSTRUCTIVE HCM - REPLY SO CIRCULATION LA English DT Letter ID LEFT-VENTRICULAR OUTFLOW; HYPERTROPHIC CARDIOMYOPATHY RP FANANAPAZIR, L (reprint author), NHLBI,CARDIOL BRANCH,INHERITED CARDIAC DIS SECT,BETHESDA,MD 20892, USA. NR 17 TC 2 Z9 2 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 SEP 15 PY 1995 VL 92 IS 6 BP 1671 EP 1673 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RU672 UT WOS:A1995RU67200052 ER PT J AU CONNELLY, MC KNIGHT, M GIORGI, JV KAGAN, J LANDAY, AL PARKER, JW PAGE, E SPINO, C WILKENING, C MERCOLINO, TJ AF CONNELLY, MC KNIGHT, M GIORGI, JV KAGAN, J LANDAY, AL PARKER, JW PAGE, E SPINO, C WILKENING, C MERCOLINO, TJ TI STANDARDIZATION OF ABSOLUTE CD4(+) LYMPHOCYTE COUNTS ACROSS LABORATORIES - AN EVALUATION OF THE ORTHO CYTORONABSOLUTE FLOW-CYTOMETRY SYSTEM ON NORMAL DONORS SO CYTOMETRY LA English DT Article DE CD4(+); LYMPHOCYTE COUNTS; FLOW CYTOMETRY ID HUMAN IMMUNODEFICIENCY VIRUS; QUALITY ASSURANCE PROGRAM; HIV-INFECTION; HOMOSEXUAL MEN; T SUBSETS; AIDS; PROGRESSION; MARKERS; SEROCONVERSION; COHORT AB The Ortho CytoronAbsolute is a flow cytometer designed to provide direct absolute counts of lymphocytes and their subsets from a single instrument, This study was designed to determine the performance of four geographically separated CytoronAbsolute instruments using 24-h-old, shipped, whole blood samples and to compare the results obtained on the OytoronAbsolute to those obtained using combinations of hematology instruments and other flow cytometers, The absolute count feature of the CytoronAbsolutes located at the four sites were cross calibrated and gave across-site coefficients of variation (CVs) of <4.0% for absolute count and 8.2% for absolute lymphocyte count, The calibration was stable for at least 2 months, Absolute lymphocyte counts and lymphocyte percentage immunophenotypes were determined on blood from 50 healthy human immunodeficiency virus (HIV)-seronegative donors, There were no significant site-to-site differences (each P >.05) in CD3(+)/CD4(+) absolute lymphocyte counts determined on the CytoronAbsolute. In contrast, there was a significant site-to-site difference (P <.001) between sites 2 and 3 and sites 3 and 4 in the absolute CD3(+)/CD4(+) lymphocyte counts determined via the conventional method of combining a flow cytometry-derived percentage with a hematology instrument-derived lymphocyte count, There was no significant difference (P =.388) in CD3(+)/CD4(+) lymphocyte percent determinations between the CytoronAbsolute and the FACScan or Profile II flow cytometers used in this study, These results demonstrate that different operators can cross calibrate CytoronAbsolutes for absolute CD3(+)/CD4(+) lymphocyte subset determinations, even over large geographic distances. (C) 1995 Wiley-Liss, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. NIAID,DIV AIDS,ROCKVILLE,MD. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV SO CALIF,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90033. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP CONNELLY, MC (reprint author), ORTHO DIAGNOST SYST INC,IMMUNOCYTOMETRY RES & DEV,1001 ROUTE 202,RARITAN,NJ 08869, USA. NR 24 TC 48 Z9 48 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD SEP 15 PY 1995 VL 22 IS 3 BP 200 EP 210 DI 10.1002/cyto.990220307 PG 11 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RX487 UT WOS:A1995RX48700006 PM 8556951 ER PT J AU CHOY, HE PARK, SW AKI, T PARRACK, P FUJITA, N ISHIHAMA, A ADHYA, S AF CHOY, HE PARK, SW AKI, T PARRACK, P FUJITA, N ISHIHAMA, A ADHYA, S TI REPRESSION AND ACTIVATION OF TRANSCRIPTION BY GAL AND LAC REPRESSORS - INVOLVEMENT OF ALPHA-SUBUNIT OF RNA-POLYMERASE SO EMBO JOURNAL LA English DT Article DE ESCHERICHIA COLI; GAL OPERON; GENE REGULATION ID COLI GALACTOSE OPERON; CAMP RECEPTOR PROTEIN; ESCHERICHIA-COLI; LAMBDA-REPRESSOR; P1 PROMOTER; CYCLIC-AMP; DNA; BINDING; OPERATOR; GENE AB Gal or Lac repressor binding to an upstream DNA segment, in the absence of DNA looping, represses the P1 promoter located on the same face and activates the P2 promoter situated on the opposite face of the DNA helix in the gal operon. Both inhibition and stimulation of transcription requires the physical presence of the C-terminal domain of the alpha subunit of RNA polymerase although the latter is not required for transcription itself. We propose that Gal and Lac repressors inhibit or stimulate transcription initiation by disabling or stimulating RNA polymerase activity at a post-binding step by directly or indirectly altering the C-terminal alpha domain to an unfavorable state at P1 or a more favorable state at P2, respectively. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NATL INST GENET,DEPT MOLEC GENET,MISHIMA,SHIZUOKA 411,JAPAN. RI Aki, Tsunehiro/B-6719-2012 OI Aki, Tsunehiro/0000-0001-9753-2043 NR 48 TC 90 Z9 91 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 15 PY 1995 VL 14 IS 18 BP 4523 EP 4529 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RX441 UT WOS:A1995RX44100015 PM 7556095 ER PT J AU LIU, JH WU, TC LICHTEN, M AF LIU, JH WU, TC LICHTEN, M TI THE LOCATION AND STRUCTURE OF DOUBLE-STRAND DNA BREAKS INDUCED DURING YEAST MEIOSIS - EVIDENCE FOR A COVALENTLY-LINKED DNA-PROTEIN INTERMEDIATE SO EMBO JOURNAL LA English DT Article DE DOUBLE-STRAND BREAKS; MEIOSIS; RECOMBINATION; SACCHAROMYCES CEREVISIAE; YEAST ID EARLY MEIOTIC RECOMBINATION; SYNAPTONEMAL COMPLEX-FORMATION; SITE-SPECIFIC ENDONUCLEASE; SACCHAROMYCES-CEREVISIAE; HETERODUPLEX DNA; INITIATION SITE; GENE CONVERSION; CHROMOSOME SYNAPSIS; MISMATCH REPAIR; HIS4 LOCUS AB We have determined the precise location and structure of the double-strand DNA breaks (DSBs) formed during Saccharomyces cerevisiae meiosis. Breaks were examined at two recombination hot spots in both wildtype and rad50S mutant cells. At both loci, breaks occurred at multiple, irregularly spaced sites in a similar to 150 nucleotide interval contained within an area of nuclease-hypersensitive chromatin. No consensus sequence could be discerned at or around break sites. Patterns of cleavage observed on individual strands indicated that breaks initially form with a two nucleotide 5' overhang. Broken strands from rad50S mutant cells contained tightly bound protein at their 5' ends. We suggest that, in S.cerevisiae, meiotic recombination is initiated by a DSB-forming activity that creates a covalently linked protein-DNA intermediate. C1 NCI,DIV CANC BIOL DIAG & CTR,BIOCHEM LAB,BETHESDA,MD 20892. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 52 TC 124 Z9 126 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 15 PY 1995 VL 14 IS 18 BP 4599 EP 4608 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RX441 UT WOS:A1995RX44100023 PM 7556103 ER PT J AU VINEIS, P CANTOR, K GONZALES, C LYNGE, E VALLYATHAN, V AF VINEIS, P CANTOR, K GONZALES, C LYNGE, E VALLYATHAN, V TI OCCUPATIONAL-CANCER IN DEVELOPED AND DEVELOPING-COUNTRIES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID UNITED-STATES; CARCINOGENESIS; PROPORTION; MALES; LUNG C1 UNIV TURIN,I-10126 TURIN,ITALY. NCI,ENVIRONM EPIDEMIOL BRANCH,ENVIRONM STUDIES SECT,BETHESDA,MD 20892. INST CLIN & EPIDEMIOL RES,MATARO,SPAIN. DANISH CANC SOC,COPENHAGEN,DENMARK. W VIRGINIA UNIV,DEPT PATHOL,MORGANTOWN,WV. RP VINEIS, P (reprint author), MAIN HOSP,CANC EPIDEMIOL UNIT,VIA SANTENA 7,I-10126 TURIN,ITALY. NR 31 TC 10 Z9 10 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 SEP 15 PY 1995 VL 62 IS 6 BP 655 EP 660 DI 10.1002/ijc.2910620602 PG 6 WC Oncology SC Oncology GA RW730 UT WOS:A1995RW73000001 PM 7558410 ER PT J AU NORMANNO, N SELVAM, MP BIANCO, C DAMIANO, V DEANGELIS, E GRASSI, M MAGLIULO, G TORTORA, G SALOMON, DS CIARDIELLO, F AF NORMANNO, N SELVAM, MP BIANCO, C DAMIANO, V DEANGELIS, E GRASSI, M MAGLIULO, G TORTORA, G SALOMON, DS CIARDIELLO, F TI AMPHIREGULIN ANTISENSE OLIGODEOXYNUCLEOTIDES INHIBIT GROWTH AND TRANSFORMATION OF A HUMAN COLON-CARCINOMA CELL-LINE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID FACTOR-ALPHA; ANTISENSE OLIGONUCLEOTIDES; PROLIFERATION; EXPRESSION AB Amphiregulin (AR) is a secreted heparin-binding growth factor that is structurally and functionally related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha). GEO cells are from a human colon cancer cell line that expresses high levels of AR protein and mRNA. To assess the role of AR in colon-cancer cell proliferation and transformation, 2 different anti-sense 20-mer phosphorothioate oligodeoxynucleotides (AR AS-1 and AR AS-2 S-oligos) complementary to the 5' sequence of AR mRNA were synthesized. Both AR AS S-oligos were able to inhibit the anchorage-dependent growth (ADG) of GEO cells. The 2 AR AS S-oligos were equipotent when used in equimolar concentrations. In particular, a 40% growth inhibition was observed at a concentration of 10 mu M, while a mis-sense S-oligo used as control had no effect on GEO cell growth. The AR AS-1 S-oligo used at the same concentration also inhibited by 40% the H-3-thymidine incorporation by DNA of GEO cells. The anchorage-independent growth (AIG) of GEO cells was even more significantly affected by AR AS S-oligo treatment. In fact, up to 80% inhibition of the AIG of GEO cells was observed when cells were treated with 10 mu M of both AR AS S-oligos. Finally, the AR AS S-oligos were able to specifically inhibit AR protein expression in GEO cells, as assessed by immunocytochemistry. These data suggest that AR is involved in colon-cancer cell transformation, and that AR may represent a suitable target for gene therapy in human colon carcinomas. (C) 1995 Wiley-Liss, Inc. C1 US FDA,CBER,DTS,BETHESDA,MD 20892. UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,DIPARTIMENTO ENDOCRINOL & ONCOL MOLEC & CLIN,I-80131 NAPLES,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTORS SECT,BETHESDA,MD 20892. RP NORMANNO, N (reprint author), IST TUMORI NAPOLI FDN PASCALE,VIA MARINO SEMMOLA,I-80131 NAPLES,ITALY. OI Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 22 TC 28 Z9 28 U1 1 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 SEP 15 PY 1995 VL 62 IS 6 BP 762 EP 766 DI 10.1002/ijc.2910620619 PG 5 WC Oncology SC Oncology GA RW730 UT WOS:A1995RW73000018 PM 7558427 ER PT J AU ROSENBERG, HF DYER, KD AF ROSENBERG, HF DYER, KD TI EOSINOPHIL CATIONIC PROTEIN AND EOSINOPHIL-DERIVED NEUROTOXIN - EVOLUTION OF NOVEL FUNCTION IN A PRIMATE RIBONUCLEASE GENE FAMILY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN PLACENTAL RIBONUCLEASE; MOLECULAR-CLONING; INHIBITOR; ANGIOGENIN; IDENTITY; MELITTIN; CDNA AB Human eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are members of a unique subfamily of rapidly evolving primate ribonuclease genes that emerged via a gene duplication event occurring after the divergence of Old World from New World monkeys (Rosenberg, H. F., Dyer, K. D., Tiffany, H. L., and Gonzalez, M. (1995) Nature Genet, 10, 219-223). In this work, we studied the activity of the protein encoded by the EDN/ECP homolog of the New World monkey, Saguinus oedipus (marmoset), a representative of the ''ancestral'' single sequences, Although the nucleotide sequence of the single marmoset gene (mEDN) was equally homologous (82%) to both human genes, the en coded amino acid sequence, calculated isoelectric point, and immunoreactivity all suggested a closer relation ship with EDN. Furthermore, mEDN (at 0.3-1.0 mu M concentrations) had no measurable anti-staphylococcal activity, suggesting functional as well as structural similarity to EDN. However, with yeast tRNA as substrate, mEDN had significantly less ribonuclease activity than EDN; Michaelis constants were nearly identical (K-m (mEDN) = 0.67 mu M; K-m (EDN) = 0.70 mu M), while turnover numbers differed by a factor of 100 (k(cat) (mEDN) = 0.91 s(-1); k(cat) (EDN) = 0.64 x 10(-2) s(-1)), Thus, evolutionary constraints appear to have promoted two novel functions: increased cationicity/toxicity (ECP) and enhanced ribonuclease activity (EDN), The latter result is particularly intriguing, as it suggests a crucial role for ribonuclease activity in the (as yet to be determined) physiologic function of EDN. RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N104,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 69 Z9 70 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 SEP 15 PY 1995 VL 270 IS 37 BP 21539 EP 21544 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700021 PM 7665566 ER PT J AU DANEN, EHJ AOTA, SI VANKRAATS, AA YAMADA, KM RUITER, DJ VANMUIJEN, GNP AF DANEN, EHJ AOTA, SI VANKRAATS, AA YAMADA, KM RUITER, DJ VANMUIJEN, GNP TI REQUIREMENT FOR THE SYNERGY SITE FOR CELL-ADHESION TO FIBRONECTIN DEPENDS ON THE ACTIVATION STATE OF INTEGRIN ALPHA-5-BETA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET GPIIB-IIIA; BINDING DOMAIN; MONOCLONAL-ANTIBODY; PLASMA FIBRONECTIN; SURFACE GLYCOPROTEIN; DIRECTED MUTAGENESIS; AFFINITY MODULATION; ENDOTHELIAL-CELLS; RECEPTOR; SUBUNIT AB We investigated the influence of the activation state of integrin alpha 5 beta 1 on its dependence on the PHSRN synergy site for binding to RGD in fibronectin. K562 and MV3 cells lacked alpha v beta 3 expression and adhered to fibronectin through alpha 5 beta 1. Mel57 cells adhered through alpha v beta 3 and alpha 5 beta 1. A recombinant fibronectin polypeptide, containing five type III repeats from the central cell binding domain 3Fn6-10, and a mutated polypeptide lacking the synergy site were equally effective in promoting Mel57 adhesion. For K562 and MV3, the mutated polypeptide was not or poorly active compared to the control polypeptide. Expression of alpha v beta 3 in MV3 induced strong adhesion to the mutated polypeptide. TS2/16 stimulatory beta 1-integrin antibodies or Mn2+ induced alpha 5 beta 1-mediated adhesion of K562 and MV3 to GRGDSP. In the presence of TS2/16 or Mn2+, alpha 5 beta 1-mediated MV3 adhesion to the mutated polypeptide was equally strong as adhesion to the control polypeptide. Mn2+ or TS2/16 induced weak K562 binding to the mutated polypeptide, and in the presence of a combination of phorbol 12-myristate 13-acetate. Mn2+, and TS2/16, alpha 5 beta 1-mediated K562 adhesion to the mutated and control polypeptide was equally strong. Our findings demonstrate that requirement for the PHSRN synergy site for alpha 5 beta 1-mediated adhesion to RGD in fibronectin depends on the activation state of the integrin. C1 UNIV NIJMEGEN HOSP,DEPT PATHOL,6500 HB NIJMEGEN,NETHERLANDS. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 64 TC 126 Z9 127 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 SEP 15 PY 1995 VL 270 IS 37 BP 21612 EP 21618 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700031 PM 7545166 ER PT J AU ZHANG, R CAI, HQ FATIMA, N BUCZKO, E DUFAU, ML AF ZHANG, R CAI, HQ FATIMA, N BUCZKO, E DUFAU, ML TI FUNCTIONAL GLYCOSYLATION SITES OF THE RAT LUTEINIZING-HORMONE RECEPTOR REQUIRED FOR LIGAND-BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LUTROPIN-CHORIOGONADOTROPIN RECEPTOR; PURIFICATION; MUTAGENESIS AB The contribution of N-linked glycosylation to the ligand binding activity of the rat luteinizing hormone receptor (LHR) was studied in wild-type and mutant LHR expressed in mammalian (COS1) cells and overexpressed in insect (Sf9) cells. The binding affinities of the holoreceptor and its truncated splice variant (form B) lacking the transmembrane domain were equivalent in both cell lines. Tunicamycin-treated transfected Sf9 cells expressed a carbohydrate-free LH receptor that lacked hormone binding activity. Functional carbohydrate chains essential for binding activity were localized to glycosylation sites at Asn-173 and Asn-152. Glycosidase treatment of the double mutant N173Q/N152Q revealed the presence of at least one additional carbohydrate chain at Asn-269, Asn-277, or Asn-291 that does not contribute to hormone binding. Asn-77 was not glycosylated, but its mutation to Gln reduced hormone binding. LHR expressed in insect cells contained only high mannose carbohydrate chains, and those located at Asn-173 and Asn-152 were sufficient for high-affinity hormone binding. Enzymatic cleavage of glycosyl chains indicated that only the proximal N-acetylglucosamine residue, which is common to high mannose and complex carbohydrate forms, is necessary for acquisition of the high affinity conformation of the receptor. The carbohydrate chains of the LHR appear to be involved in intramolecular folding of the nascent receptor rather than in its interaction with the hormone. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892. NR 21 TC 70 Z9 70 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 SEP 15 PY 1995 VL 270 IS 37 BP 21722 EP 21728 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700049 PM 7665591 ER PT J AU WAGNER, PD VU, ND AF WAGNER, PD VU, ND TI PHOSPHORYLATION OF ATP-CITRATE LYASE BY NUCLEOSIDE DIPHOSPHATE KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER; TUMOR-METASTASIS; SEQUENCE-ANALYSIS; BINDING PROTEINS; MELANOMA-CELLS; BREAST-CANCER; NM23; EXPRESSION; GENE; AUTOPHOSPHORYLATION AB Rat liver nucleoside diphosphate kinase (NDPK) and PC12 cell cytosol were used to determine whether NDPK could function as a protein kinase. NDPK was phosphorylated on its catalytic histidine using [gamma-P-32]ATP, and the phosphorylated NDPK separated from [gamma-P-32]ATP, The addition of phosphorylated NDPK to dialyzed PC12 cell cytosol resulted in the phosphorylation of a protein with a subunit molecular mass of about 120 kDa, This phosphorylation appeared to occur by a direct transfer of a phosphoryl group from the catalytic histidine of NDPK to a histidine on the 120-kDa protein. The 120-kDa protein was partially purified and shown by peptide sequencing to be ATP-citrate lyase, ATP-citrate lyase is the primary source of cytosolic acetyl-CoA. NDPK phosphorylated the histidine at the catalytic site of ATP-citrate lyase, This histidine can also be phosphorylated by ATP, and its phosphorylation is the first step in the conversion of citrate and CoA to oxaloacetate and acetyl-CoA by ATP-citrate lyase. The level of phosphorylation of PC12 cell ATP-citrate lyase by phosphorylated NDPK was comparable with that by ATP. Thus, in addition to its nucleoside diphosphate kinase activity, NDPK can function as a protein kinase. RP NCI, BIOCHEM LAB, BLDG 37, RM 4C24, 37 CONVENT DR MSC 4255, BETHESDA, MD 20892 USA. NR 56 TC 133 Z9 134 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1995 VL 270 IS 37 BP 21758 EP 21764 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700054 PM 7665595 ER PT J AU KAZANIETZ, MG WANG, S MILNE, GWA LEWIN, NE LIU, HL BLUMBERG, PM AF KAZANIETZ, MG WANG, S MILNE, GWA LEWIN, NE LIU, HL BLUMBERG, PM TI RESIDUES IN THE 2ND CYSTEINE-RICH REGION OF PROTEIN-KINASE-C-DELTA RELEVANT TO PHORBOL ESTER BINDING AS REVEALED BY SITE-DIRECTED MUTAGENESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAENORHABDITIS-ELEGANS; REGULATORY DOMAIN; UNC-13 GENE; RAT-BRAIN; DIACYLGLYCEROL; ZINC; EXPRESSION; INHIBITORS; CHIMAERIN; AFFINITY AB Phorbol esters bind with high affinity to protein kinase C (PKC) isozymes as well as to two novel receptors, n-chimaerin and Unc-13, The cysteine-rich regions present in these proteins were identified as the binding sites for the phorbol ester tumor promoters and the lipophilic second messenger sn-diacylglycerol. A 50-amino-acid peptide comprising the second cysteine-rich region of PKC delta, expressed in Escherichia coli as a glutathione S-transferase (GST)-fusion protein, bound [H-3]phorbol 12,13-dibutyrate (PDBu) with high affinity (K-d =0.8 nM). Using the cDNA of that cysteine-rich region as a template, a series of 37 point mutations was generated by site-directed mutagenesis, and the mutated proteins were analyzed quantitatively for binding of [H-3]PDBu and, as appropriate, for binding of the ultrapotent analog [3H]bryostatin 1. Mutants displayed one of three patterns of behavior: phorbol ester binding was completely abolished, binding affinity was reduced, or binding was not significantly modified, As expected, five of the six cysteines as well as the two histidines involved in Zn2+ coordination are critical for the interaction of the protein with the phorbol esters. In addition, mutations in several positions, including phenylalanine 3, tyrosine 8, proline 11, leucines 20, 21, and 24, tryptophan 21, glutamine 27, and valine 38 drastically reduced the interaction with the ligands, The effect of these mutations can be rationalized from the three-dimensional (NMR) structure of the cysteine-rich region. In particular, the C-terminal portion of the protein does not appear to be essential, and the loop comprising amino acids 20 to 28 is implicated in the binding activity. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 34 TC 150 Z9 151 U1 1 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 SEP 15 PY 1995 VL 270 IS 37 BP 21852 EP 21859 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700068 PM 7665608 ER PT J AU OSHIMA, H SZAPARY, D SIMONS, SS AF OSHIMA, H SZAPARY, D SIMONS, SS TI THE FACTOR-BINDING TO THE GLUCOCORTICOID MODULATORY ELEMENT OF THE TYROSINE AMINOTRANSFERASE GENE IS A NOVEL AND UBIQUITOUS HETEROMERIC COMPLEX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-A; TISSUE-SPECIFIC EXTINGUISHER; SEQUENCE-SPECIFIC BINDING; HEPATOMA-CELL LINES; TRANSCRIPTION FACTOR; AGONIST ACTIVITY; PROGESTERONE-RECEPTOR; DNA-BINDING; DEXAMETHASONE 21-MESYLATE; RESPONSIVE ELEMENTS AB Glucocorticoid induction of the tyrosine aminotransferase gene deviates from that of many glucocorticoid-responsive genes by having a lower EC(50) and displaying more agonist activity with a given antiglucocorticoid. A cis acting element, located 3646 base pairs upstream of the start of tyrosine aminotransferase gene transcription, has been found to be sufficient to reproduce these variations with heterologous genes and promoters (Oshima, H., and Simons, S. S., Jr. (1992) Mol. Endocrinol. 6, 416-428). This element has been called a glucocorticoid modulatory element, or GME. Others have called this sequence a cyclic AMP-responsive element (CRE) due to the binding of the cyclic AMP response element binding protein (CREB). We now report the partial purification and characterization of two new proteins (GMEB1 and -2) of 88 and 67 kDa that bind to the GME/ CRE as a heteromeric complex. This purification was followed by the formation of a previously characterized, biologically relevant band in gel shift assays. By several biochemical criteria, the GMEBs differed from many of the previously described CREB/CREM/ATF family members. Partial peptide sequencing revealed that the sequences of these two proteins have not yet been described. Size exclusion chromatography and molecular weight measurements of the gel-shifted band demonstrated that the GMEBs bound to the GME as a macromolecular complex of about 550 kDa that could be dissociated by deoxycholate. Similar experiments showed that CREB bound to the GME as heteromeric complexes of about 310 and 360 kDa. As determined from gel shift assays, GMEB1 and -2 are not restricted to rat liver cells but appear to be ubiquitous. Thus, these novel GMEBs may participate in a similar modulation of other glucocorticoid-inducible genes in a variety of cells. C1 NIDDK,CELLULAR & MOLEC BIOL LAB,STEROID HORMONES SECT,BETHESDA,MD 20892. NR 53 TC 41 Z9 44 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 SEP 15 PY 1995 VL 270 IS 37 BP 21893 EP 21901 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700073 PM 7665613 ER PT J AU SWIETER, M BERENSTEIN, EH SWAIM, WD SIRAGANIAN, RP AF SWIETER, M BERENSTEIN, EH SWAIM, WD SIRAGANIAN, RP TI AGGREGATION OF IGE RECEPTORS IN RAT BASOPHILIC LEUKEMIA 2H3 CELLS INDUCES TYROSINE PHOSPHORYLATION OF THE CYTOSOLIC PROTEIN-TYROSINE-PHOSPHATASE HEPTP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; HISTAMINE-RELEASE; PHOSPHOTYROSINE PHOSPHATASE; PHOSPHOLIPASE C-GAMMA-1; CALCIUM SIGNAL; ACTIVATION; CLONING; KINASE; IDENTIFICATION; STIMULATION AB The cDNA encoding the rat equivalent of the human hematopoietic tyrosine phosphatase, also known as leukocyte phosphatase, was isolated from a rat basophilic leukemia mast cell cDNA library. By two-dimensional electrophoresis, the protein expressed in the mast cells was of a size (40 kDa) and pI (6.9) predicted from the deduced amino acid sequence. Thus, although previously shown to be preferentially expressed in T cells and B cells, the phosphatase is also Pound in mast cells. By immunofluorescence microscopy, rat hematopoietic tyrosine phosphatase localized to discrete, globular compartments within the cytoplasm and was not found either in the nucleus or associated with the cell surface membrane. Aggregation of high affinity IgE receptors in the mast cells induced tyrosine phosphorylation of the phosphatase. The tyrosine phosphorylation was mimicked by stimulation with calcium ionophore A23187 but not by direct activation of protein kinase C. Since phosphorylation of the phosphatase was dramatically reduced when the cells were activated in Ca2+ free media, it is dependent on a rise in intracellular Ca2+. These data strongly suggest that hematopoietic tyrosine phosphatase may be involved in the IgE receptor-mediated signaling cascade. RP SWIETER, M (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N1-6,BETHESDA,MD 20892, USA. NR 46 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 SEP 15 PY 1995 VL 270 IS 37 BP 21902 EP 21906 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700074 PM 7545170 ER PT J AU FELLER, SE ZHANG, YH PASTOR, RW BROOKS, BR AF FELLER, SE ZHANG, YH PASTOR, RW BROOKS, BR TI CONSTANT-PRESSURE MOLECULAR-DYNAMICS SIMULATION - THE LANGEVIN PISTON METHOD SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article AB A new method for performing molecular dynamics simulations under constant pressure is presented. In the method, which is based on the extended system formalism introduced by Andersen, the deterministic equations of motion for the piston degree of freedom are replaced by a Langevin equation; a suitable choice of collision frequency then eliminates the unphysical ''ringing'' of the volume associated with the piston mass. In this way it is similar to the ''weak coupling algorithm'' developed by Berendsen and co-workers to perform molecular dynamics simulation without piston mass effects. It is shown, however, that the weak coupling algorithm induces artifacts into the simulation which can be quite severe for inhomogeneous systems such as aqueous biopolymers or liquid/liquid interfaces. C1 NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. RP FELLER, SE (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,ROCKVILLE,MD 20852, USA. NR 22 TC 1789 Z9 1799 U1 13 U2 140 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 15 PY 1995 VL 103 IS 11 BP 4613 EP 4621 DI 10.1063/1.470648 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA RU110 UT WOS:A1995RU11000023 ER PT J AU MURPHY, WJ RAZIUDDIN, A MASON, L KUMAR, V BENNETT, M LONGO, DL AF MURPHY, WJ RAZIUDDIN, A MASON, L KUMAR, V BENNETT, M LONGO, DL TI NK CELL SUBSETS IN THE REGULATION OF MURINE HEMATOPOIESIS .1. 5E6(+) NK CELLS PROMOTE HEMATOPOIETIC GROWTH IN H-2(D) STRAIN MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; BONE-MARROW TRANSPLANTATION; COMBINED IMMUNE-DEFICIENCY; RECEPTOR GENES; REJECTION; INVIVO; ENGRAFTMENT; SPECIFICITY; BIOLOGY AB NK cells are able to reject bone marrow allografts in lethally irradiated mice. 5E6 is a marker expressed on a subset of NK cells that is responsible for the rejection of H-2(d) homozygous bone marrow cell (BMC) allografts. This suggests that the 5E6(+) NK cell subset somehow recognizes and is deleterious for H-2(d) BMC. However, unlike Ly-49(+) NK cells, 5E6(+) cells are not deleted or even down-regulated in H-2(d)-homozygous mice. We wanted to determine, therefore, the role of the 5E6(+) and 5E6(-) NK cell subsets in the normal physiologic regulation of hematopoiesis in H-2(d) strains of mice. Surprisingly, both in vivo depletion studies of normal mice and studies in which the subsets were purified and cultured with syngeneic BMC in vitro demonstrated that in H-2(d) mice, the 5E6(+) subset of NK cells did not inhibit, but instead promoted, growth of H-2(d) BMC. Depletion of the 5E6(+) subset also resulted in decreased marrow engraftment after syngeneic bone marrow transplantation in H-2(d) mice. Analysis of the cell culture supernatants of the purified subsets indicated that the functional effects of the subsets on hematopoiesis correlated with the relative amounts of hematopoietic growth-promoting cytokines produced by the NK cells. These results demonstrate that physiologically relevant subsets of NK cells exist that are involved in the homeostatic regulation of hematopoiesis and that they can be distinguished on the basis of 5E6 expression. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,BLDG 567,ROOM 141,FREDERICK,MD 21702, USA. FU NCI NIH HHS [1-R01-CA36921, 1-R01-CA36922] NR 20 TC 27 Z9 27 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 SEP 15 PY 1995 VL 155 IS 6 BP 2911 EP 2917 PG 7 WC Immunology SC Immunology GA RU050 UT WOS:A1995RU05000014 PM 7673708 ER PT J AU SALKOWSKI, CA NETA, R WYNN, TA STRASSMANN, G VANROOIJEN, N VOGEL, SN AF SALKOWSKI, CA NETA, R WYNN, TA STRASSMANN, G VANROOIJEN, N VOGEL, SN TI EFFECT OF LIPOSOME-MEDIATED MACROPHAGE DEPLETION ON LPS-INDUCED CYTOKINE GENE-EXPRESSION AND RADIOPROTECTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE; COLONY-STIMULATING FACTOR; MESSENGER-RNA EXPRESSION; FACTOR-ALPHA; IFN-GAMMA; EXPERIMENTAL ENDOTOXEMIA; INTRAVENOUS-INJECTION; PHAGOCYTIC-CELLS; INVIVO AB Tissue-specific cytokine mRNA expression was examined in mice that received LPS. In the liver, IL-6, IL-10, IL-12 (p40), and TNF-alpha were induced by 30 min after injection with LPS. In the spleen, IL-6 and TNF-alpha were induced by 30 min after LPS challenge, while increases in IL-10 and IL-12 (p40) were delayed in onset. CM-CSF, IFN-gamma, and IL-12 (p35) were not induced in the liver or spleen until 60 to 90 min after LPS injection. Mice were depleted of macrophages in their liver and spleen by i.v. injection of liposome-ensapsulated dichloromethylene bisphosphonate (Cl(2)MBP). Induction of IL-1 beta, IL-6, IL-10, and IL-12 (p40) mRNA by LPS was reduced by >95% in the liver of macrophage-depleted mice, implicating macrophages as the primary producers of these cytokines. Macrophage depletion resulted in a 50 to 75% reduction in TNF-alpha mRNA in the liver. The results from Cl(2)MBP-liposome-treated mice also suggested that splenic macrophages were the primary producers of LPS-induced IL-1 beta, IL-6, IL-12 (p40), and IL-1 receptor antagonist (IL-1ra) mRNA, but not IL-10 and TNF-alpha mRNA. Mice treated with Cl(2)MBP-liposomes were more susceptible to ionizing irradiation than control mice, whether or not they were administered a radioprotective dose of LPS. These findings suggest that depletion of liver and splenic macrophages results in a dysregulation of basal and LPS-induced cytokine responses that can be associated with an altered biologic response. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. ARMED FORCES RADIOBIOL RES INST,DEPT EXPTL HEMATOL,BETHESDA,MD 20814. NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,HOST PARASITE SECT,BETHESDA,MD 20892. OTSUKA AMER PHARMACEUT INC,DEPT IMMUNOL,ROCKVILLE,MD 20850. FREE UNIV AMSTERDAM,DEPT CELL BIOL & IMMUNOL,DIV HISTOL,AMSTERDAM,NETHERLANDS. RI Wynn, Thomas/C-2797-2011 FU NIAID NIH HHS [AI-18797] NR 62 TC 100 Z9 100 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1995 VL 155 IS 6 BP 3168 EP 3179 PG 12 WC Immunology SC Immunology GA RU050 UT WOS:A1995RU05000040 PM 7673730 ER PT J AU DANG, H GEISER, AG LETTERIO, JJ NAKABAYASHI, T KONG, LP FERNANDES, G TALAL, N AF DANG, H GEISER, AG LETTERIO, JJ NAKABAYASHI, T KONG, LP FERNANDES, G TALAL, N TI SLE-LIKE AUTOANTIBODIES AND SJOGRENS SYNDROME-LIKE LYMPHOPROLIFERATION IN TGF-BETA KNOCKOUT MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CELL-PROLIFERATION; LYMPHOCYTES-B; FACTOR-BETA-1; EXPRESSION; DISEASE; MOUSE; DEATH AB Mice bearing the TGF-beta 1 null mutation (-/-) develop lymphoid infiltrates in the heart, lungs, salivary glands, and other organs similar to those seen in the pseudolymphoma of Sjogren's Syndrome. We studied sera from -/- mice and found elevated Ab levels to dsDNA, ssDNA, and Sm ribonucleoprotein. No Abs to SSA/Ro or SSB/La and no IgM rheumatoid factor were found. Serum autoantibodies were predominately Ige and were specific as shown by ELISA inhibition studies. Antinuclear Ab patterns on Western blots varied from one mouse to the next, indicating a random process responsible for the diversity. Wild-type and heterozygote mice had no autoantibodies. Ig glomerular deposits were found in -/- mice, indicating that these autoantibodies may be pathogenic. Treatment of -/- mice with dexamethasone or TGF-beta 1 failed to suppress autoantibody production. These mice represent an overlap combining the autoimmune serology of SLE with the tissue infiltrates of SS. Our results support the concept that TGF-beta 1 is an important naturally occurring immunosuppressive cytokine whose absence can lead to a systemic autoimmune disease. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,SAN ANTONIO,TX 78284. RP DANG, H (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [AG10531]; NIDCR NIH HHS [DE09311, DE10863] NR 32 TC 137 Z9 139 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1995 VL 155 IS 6 BP 3205 EP 3212 PG 8 WC Immunology SC Immunology GA RU050 UT WOS:A1995RU05000044 PM 7673733 ER PT J AU ANDERSON, WK KASLIWAL, R HOUSTON, DM WANG, YS NARAYANAN, VL HAUGWITZ, RD PLOWMAN, J AF ANDERSON, WK KASLIWAL, R HOUSTON, DM WANG, YS NARAYANAN, VL HAUGWITZ, RD PLOWMAN, J TI SYNTHESIS, ANTITUMOR-ACTIVITY, AND CHEMICAL-PROPERTIES OF SILAPLATIN AND RELATED PLATINUM(II) AND PLATINUM(IV) COMPLEXES DERIVED FROM BETA-SILYL AMINES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PHYSICAL-PROPERTIES; 1,2-DIAMINOCYCLOHEXANE; TETRAPLATIN AB Platinum(II) and platinum(TV) coordination complexes derived from beta-silyl-substituted amines were prepared. The solubility of selected complexes in water and physiological saline was measured, and the effect of the beta-silicon on the reactivity of the complex in aqueous solution was determined by HPLC. The stabilities of selected silyl complexes were compared to the carbon analogues. The cyclic complexes 2a (''silaplatin'') and its Pt(IV) analogue, 2b, were very active against L1210 leukemia in vivo. Both the platinum(LI) complex 2a and the platinum(IV) complex 2b produced a significant number of cures over the dose range 10-40 mg/kg. The platinum(II) complex 2a, silaplatin, was very active in vivo against an L1210 leukemia subline that was resistant to cisplatin; 2a was also active, when given ip, against ic implanted L1210. The cyclobutanedicarboxylic acid complex 3c was synthesized; this complex was active against both cisplatin sensitive and resistant L1210 leukemia but was less potent than the analogous dichloro compound 2a. The acyclic platinum(II) and platinum(IV) complexes 1a,b were synthesized and unexpectedly found to be inactive in vivo against L1210 leukemia. More lipophilic silaplatin analogues were prepared-Pt(II) complex 2c and Pt(IV) complex 2d have one additional methylene carbon compared to 2a,b, whereas Pt(II) complex 2e and Pt(IV) complex 2f have two additional methylene carbons. Cyclization of the alkyl groups attached to the silicon gave the spiro bicyclic Pt(II) complexes 10a and 11a and the Pt(TV) complexes 10b and 11b. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP ANDERSON, WK (reprint author), SUNY BUFFALO,SCH PHARM,DEPT MED CHEM,BUFFALO,NY 14260, USA. FU NCI NIH HHS [N01-CM-17569, N01-CM-67698] NR 22 TC 30 Z9 31 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 15 PY 1995 VL 38 IS 19 BP 3789 EP 3797 DI 10.1021/jm00019a008 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RW117 UT WOS:A1995RW11700008 PM 7562909 ER PT J AU YAGIL, E DORGAI, L WEISBERG, RA AF YAGIL, E DORGAI, L WEISBERG, RA TI IDENTIFYING DETERMINANTS OF RECOMBINATION SPECIFICITY - CONSTRUCTION AND CHARACTERIZATION OF CHIMERIC BACTERIOPHAGE INTEGRASES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RECOMBINATION SPECIFICITY; CHIMERIC INTEGRASES; LAMBDA; ATTACHMENT SITES ID SITE-SPECIFIC RECOMBINATION; FLP RECOMBINASE; ACTIVE-SITE; DNA-BINDING; COLIPHAGE-LAMBDA; ESCHERICHIA-COLI; 2-MU-M PLASMID; PROTEIN; IDENTIFICATION; MUTANTS AB Bacteriophage integrases are members of a family of structurally related enzymes that promote recombination between DNA molecules that carry specific sites. Phages lambda and HK022 encode closely related integrases that recognize different sets of sequences within the core regions of their respective attachment sites. To locate the amino acid residues that determine this difference in specificity, we isolated recombinant phages that produce chimeric integrases and measured the ability of these chimeras to promote recombination of lambda and HK022 sites in vivo. A chimera that is of lambda origin except for one HK022 residue at position 99 and 12 HK022 residues located between positions 279 and 329 had wild-type HK022 specificity and activity for both integrative and excisive recombination. Chimeras containing certain subsets of these 13 residues had incomplete specificity The region around position 99 is not well-conserved in other members of the integrase family, but the 279-329 segment includes residues that are highly conserved and believed to be directly involved in catalysis. Many chimeras were inactive in recombining either HK022 or lambda sites. Selection for mutants that restored activity to these chimeras revealed sets of residues that are likely to interact with each other. (C) 1995 Academic Press Limited C1 NICHHD,MOLEC GENET LAB,MICROBIAL GENET SECT,BETHESDA,MD 20892. TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NR 59 TC 45 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 15 PY 1995 VL 252 IS 2 BP 163 EP 177 DI 10.1006/jmbi.1995.0485 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU752 UT WOS:A1995RU75200002 PM 7674299 ER PT J AU DORGAI, L YAGIL, E WEISBERG, RA AF DORGAI, L YAGIL, E WEISBERG, RA TI IDENTIFYING DETERMINANTS OF RECOMBINATION SPECIFICITY - CONSTRUCTION AND CHARACTERIZATION OF MUTANT BACTERIOPHAGE INTEGRASES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE LAMBDA; INTEGRASE; RECOMBINATION SPECIFICITY; ATTACHMENT SITES ID SITE-SPECIFIC RECOMBINATION; GAMMA-DELTA RESOLVASE; PROTEIN-DNA COMPLEX; ATTACHMENT SITES; INT-H; LAMBDA; RECOGNITION; CLEAVAGE; GENE; ATTL AB The Integrases of bacteriophages lambda and HK022 promote recombination between DNA molecules that carry attachment sites. The two integrases are about 70 % identical in sequence and catalyze nearly identical reactions, but recognize different sets of sites. To identify the amino acids that determine this difference in specificity, we selected mutants of lambda integrase with increased ability to recombine HK022 sites. This selection yielded eleven different amino acid substitutions at eight different positions. Three of the positions belong to a larger set that were identified as important for the lambda/HK022 specificity difference by analysis of chimeric integrases. Substitution of the HK022 for the corresponding lambda residue at each of these three positions increased recombination of HK022 sites, and one double substitution, N99D-E319R, increased recombination to nearly wild-type HK022 levels. Mutations at the other five positions changed residues that are identical in the wild-type proteins or are at positions identified by chimera analysis as unimportant for the lambda/HK022 specificity difference. All of the mutants isolated by selection for increased recombination of HK022 sites retained considerable ability to recombine lambda sites. However, we found that substitution of HK022 for lambda residues at three additional positions, S282P, G283K, and R287X, specifically reduced recombination of lambda sites. These three substitutions when combined with N99D and E319R were sufficient to change the specificity of lambda to that of HK022 integrase. The first three substitutions act principally to prevent recombination of lambda sites, and the second two to remove a barrier to recombination of HK022 sites. We suggest that many natural alterations in the specificity of protein-DNA interactions occur by multi-step changes that first relax and then restrict specificity (C) 1995 Academic Press Limited C1 NICHHD,GENET MOLEC LAB,MICROBIAL GENET SECT,BETHESDA,MD 20892. TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NR 29 TC 56 Z9 56 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 15 PY 1995 VL 252 IS 2 BP 178 EP 188 DI 10.1006/jmbi.1995.0486 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU752 UT WOS:A1995RU75200003 PM 7674300 ER PT J AU NOREL, R LIN, SL WOLFSON, HJ NUSSINOV, R AF NOREL, R LIN, SL WOLFSON, HJ NUSSINOV, R TI MOLECULAR-SURFACE COMPLEMENTARITY AT PROTEIN-PROTEIN INTERFACES - THE CRITICAL ROLE PLAYED BY SURFACE NORMALS AT WELL PLACED, SPARSE, POINTS IN DOCKING SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DOCKING; PROTEIN-PROTEIN RECOGNITION; MOLECULAR SURFACE COMPLEMENTARITY; RIGID-BODY MATCHING; SURFACE NORMALS ID RECOGNITION; ALGORITHM AB Rigid-body docking of two molecules involves matching of their surfaces. A successful docking methodology considers two key issues: molecular surface representation, and matching. While approaches to the problem differ, they all employ certain surface geometric features. While surface normals are routinely created with molecular surfaces, their employment has surprisingly been almost completely overlooked. Here we show how the normals to the surface, at specific, well placed points, can play a critical role in molecular docking. If the points for which the normals are calculated represent faithfully and accurately the molecular surfaces, the normals can substantially ameliorate the efficiency of the docking in a number of ways. The normals can drastically reduce the combinatorial complexity of the receptor-ligand docking. Furthermore, they can serve as a powerful filter in screening for quality docked conformations. Below we show how deploying such a straight forward device, which is easy to calculate, large protein-protein molecules are docked with unparalleled short times and with a manageable number of potential solutions. Considering the facts that here we dock (1) two large protein molecules, including several large immunoglobulin-lysozyme complexes; (2) that we use the entire molecular surfaces, without a predefinition of the active sites, or of the epitopes, of neither the ligand nor the receptor; that (3) the docking is completely automated, without any labelling, or pre-specification, of the input structural database, and (4) with a single set of parameters, without any further tuning whatsoever, such results are highly desirable. This approach is specifically geared towards matching of the surfaces of large protein molecules and is not applicable to small molecule drugs. (C) 1995 Academic Press Limited C1 TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES FACIL,PRI DYNACORP,MATH BIOL LAB,FREDERICK,MD 21712. TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011; OI Norel, Raquel/0000-0001-7737-4172 FU NCI NIH HHS [1-CO-74102] NR 17 TC 93 Z9 93 U1 1 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 15 PY 1995 VL 252 IS 2 BP 263 EP 273 DI 10.1006/jmbi.1995.0493 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU752 UT WOS:A1995RU75200010 PM 7674306 ER PT J AU OLAH, Z FERRIER, A LEHEL, C ANDERSON, WB AF OLAH, Z FERRIER, A LEHEL, C ANDERSON, WB TI THE 33-KDA C-TERMINAL DOMAIN OF RAF-1 PROTEIN-KINASE EXHIBITS A RAS-DEPENDENT SERUM-INDUCED AND PHORBOL ESTER-INDUCED SHIFT IN GEL MOBILITY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SIGNAL-TRANSDUCTION; PHOSPHORYLATION; ACTIVATION; ASSOCIATION; RECEPTOR; MEMBRANE; P21(RAS) AB Experiments were carried out to determine Raf-1 protein kinase domain fragments which exhibit a characteristic electrophoretic mobility shift noted with Raf-1 protein kinase in response to serum and phorbol ester (PMA) treatment of serum-deprived NIH 3T3 cells. epsilon-epitope tagged 84 kDa Raf-1 holoenzyme (HR-epsilon), as well as the epsilon-epsilon pitope tagged 35 kDa N-terminal (RI-epsilon), 33 kDa mid-portion (RII-epsilon) and 33 kDa C-terminal (RIII-epsilon) fragments of Raf-1 were overexpressed in NIH 3T3 cells. The overexpressed HR-(e)psilon exhibited a serum- and PMA-induced shift in gel mobility similar to that noted with endogenous Raf-1. The C-terminal RIII-epsilon fragment exhibited a similar shift in gel mobility while the electrophoretic mobility of the N-terminal RI-epsilon fragment remained unchanged. These results suggest that modification(s) within the 33 kDa C-terminal portion of Raf-1 which occur independently of association with Ras may be responsible for the band shift observed with serum and PMA treatment of serum-deprived NIH 3T3 cells. (C) 1995 Academic Press, Inc. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 29 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 14 PY 1995 VL 214 IS 2 BP 340 EP 347 DI 10.1006/bbrc.1995.2293 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RW822 UT WOS:A1995RW82200006 PM 7545901 ER PT J AU KARNI, A MEYER, G JEZZARD, P ADAMS, MM TURNER, R UNGERLEIDER, LG AF KARNI, A MEYER, G JEZZARD, P ADAMS, MM TURNER, R UNGERLEIDER, LG TI FUNCTIONAL MRI EVIDENCE FOR ADULT MOTOR CORTEX PLASTICITY DURING MOTOR SKILL LEARNING SO NATURE LA English DT Article ID CEREBRAL BLOOD-FLOW; SENSORY STIMULATION; TIME-COURSE; REPRESENTATION; HABITUATION; TASK AB PERFORMANCE of complex motor tasks, such as rapid sequences of finger movements, can be improved in terms of speed and accuracy over several weeks by daily practice sessions, This improvement does not generalize to a matched sequence of identical component movements, nor to the contralateral hand, Here we report a study of the neural changes underlying this learning using functional magnetic resonance imaging (MRI) of local blood oxygenation level-dependent (BOLD)(1-4) signals evoked in primary motor cortex (Mi). Before training, a comparable extent of M1 was activated by both sequences, However, two ordering effects were observed: repeating a sequence within a brief time window initially resulted in a smaller area of activation (habituation), but later in a larger area of activation (enhancement), suggesting a switch in M1 processing mode within the first session (fast learning), By week 4 of training, concurrent with asymptotic performance, the extent of cortex activated by the practised sequence enlarged compared with the unpractised sequence, irrespective of order (slow learning), These changes persisted for several months, The results suggest a slowly evolving, long-term, experience-dependent reorganization of the adult M1, which may underlie the acquisition and retention of the motor skill. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RP KARNI, A (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008; Li, Chong/F-4265-2015; OI Jezzard, Peter/0000-0001-7912-2251 NR 25 TC 1063 Z9 1080 U1 4 U2 74 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 14 PY 1995 VL 377 IS 6545 BP 155 EP 158 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU754 UT WOS:A1995RU75400050 PM 7675082 ER PT J AU SUN, XJ WANG, LM ZHANG, YT YENUSH, L MYERS, MG GLASHEEN, E LANE, WS PIERCE, JH WHITE, MF AF SUN, XJ WANG, LM ZHANG, YT YENUSH, L MYERS, MG GLASHEEN, E LANE, WS PIERCE, JH WHITE, MF TI ROLE OF IRS-2 IN INSULIN AND CYTOKINE SIGNALING SO NATURE LA English DT Article ID HEMATOPOIETIC-CELLS; RECEPTOR; PROTEIN; PHOSPHORYLATION; TRANSMISSION; SEQUENCE AB THE protein IRS-1 acts as an interface between signalling proteins with Src-homology-2 domains (SH2 proteins) and the receptors for insulin, IGF-1, growth hormone, several interleukins (IL-4, IL-9, IL-13) and other cytokines(1-7). It regulates gene expression acid stimulates mitogenesis, and appears to mediate insulin/IGF-1-stimulated glucose transport(8). Thus, survival of the IRS-1(-/-) mouse with only mild resistance to insulin was surprising(9,10). This dilemma is provisionally resolved with our discovery of a second IRS-signalling protein, We purified and cloned a likely candidate called 4PS from myeloid progenitor cells and, because of its resemblance to IRS-1, we designate it IRS-2. Alignment of the sequences of IRS-2 acid IRS-1 revealed a highly conserved amino terminus containing a pleckstrin-homology domain and a phosphotyrosine-binding domain, and a poorly conserved carboxy terminus containing several tyrosine phosphorylation motifs. IRS-2 is expressed in many cells, including tissues from IRS-1(-/-) mice(11), and may be essential for signalling by several receptor systems. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. NIH,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,HARVARD MICROCHEM FACIL,CAMBRIDGE,MA 02138. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 NR 36 TC 700 Z9 711 U1 2 U2 19 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 14 PY 1995 VL 377 IS 6545 BP 173 EP 177 DI 10.1038/377173a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU754 UT WOS:A1995RU75400055 PM 7675087 ER PT J AU IRIBARREN, C SHARP, DS BURCHFIEL, CM PETROVITCH, H AF IRIBARREN, C SHARP, DS BURCHFIEL, CM PETROVITCH, H TI ASSOCIATION OF WEIGHT-LOSS AND WEIGHT FLUCTUATION WITH MORTALITY AMONG JAPANESE-AMERICAN MEN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; ALL-CAUSE MORTALITY; BODY-WEIGHT; METABOLIC-RATE; HEALTH; RISK; VARIABILITY; LONGEVITY; STROKE; HAWAII AB Background. Weight loss and fluctuations in weight have been associated with increased risks of death from cardiovascular disease and from all causes. The clinical and public health implications of these associations are unclear. Methods. We examined the long-term relation of weight change and fluctuation in weight with mortality over a 6-year period in 6537 middle-aged Japanese American men enrolled in the Honolulu Heart Program, a prospective study (mean follow-up, 14.5 years). Results. Men who had a weight loss of 4.5 kg or more or who had large fluctuations in weight (or both) over a six-year period were, on average, in poorer health than their peers whose weight was more stable. After the exclusion of subjects who died during the first five years of follow-up and after adjustment for confounding factors, a weight loss of more than 4.5 kg was associated with the risk of death from all causes, with the exception of death from cancer. The subjects whose weight fluctuated the most had a significantly higher risk of death from cardiovascular causes (relative risk, 1.41; 95 percent confidence interval, 1.03 to 1.93), death from noncardiovascular and noncancerous causes (relative risk, 1.53; 95 percent confidence interval, 1.12 to 2.10), and death from all causes (relative risk, 1.25; 95 percent confidence interval, 1.05 to 1.48). However, the associations of weight loss and variation in weight with death from cardiovascular causes and from noncardiovascular and noncancerous causes were not found among healthy men who had never smoked. Conclusions. The associations between weight loss or fluctuation and mortality were partially explained by confounding factors and by the presence of preexisting disease. However, weight loss and weight fluctuation were unrelated to death among healthy men who had never smoked. Thus, concern about the health hazards of weight loss and variation may not be applicable to otherwise healthy people. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,HONOLULU EPIDEMIOL RES UNIT,BETHESDA,MD 20892. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. RP IRIBARREN, C (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [N01-HC-02901, N01-HV-02901] NR 41 TC 85 Z9 85 U1 1 U2 1 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 SEP 14 PY 1995 VL 333 IS 11 BP 686 EP 692 DI 10.1056/NEJM199509143331102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RV227 UT WOS:A1995RV22700002 PM 7637745 ER PT J AU FAUCI, AS AF FAUCI, AS TI NEW SCIENCE AIMED AT AN ANCIENT KILLER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP FAUCI, AS (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 3 TC 2 Z9 2 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 SEP 13 PY 1995 VL 274 IS 10 BP 786 EP 786 DI 10.1001/jama.274.10.786 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RU324 UT WOS:A1995RU32400005 PM 7650787 ER PT J AU BALAGURUMOORTHY, P SAKAMOTO, H LEWIS, MS ZAMBRANO, N CLORE, GM GRONENBORN, AM APPELLA, E HARRINGTON, RE AF BALAGURUMOORTHY, P SAKAMOTO, H LEWIS, MS ZAMBRANO, N CLORE, GM GRONENBORN, AM APPELLA, E HARRINGTON, RE TI 4 P53 DNA-BINDING DOMAIN PEPTIDES BIND NATURAL P53-RESPONSE ELEMENTS AND BEND THE DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COOPERATIVE DNA BINDING; DNA BENDING; CYCLIZATION ID GEL-ELECTROPHORESIS; PROTEIN; SITE AB Recent structural studies of the minimal core DNA-binding domain of p53 (p53DBD) complexed to a single consensus pentamer sequence and of the isolated p53 tetramerization domain have provided valuable insights into their functions, but many questions about their interacting roles and synergism remain unanswered, To better understand these relationships, we have examined the binding of the p53DBD to two biologically important full-response elements (the WAF1 and ribosomal gene cluster sites) by using DNA circularization and analytical ultracentrifugation, We show that the p53DBD binds DNA strongly and cooperatively with p53DBD to DNA binding stoichiometries of 4:1. For the WAF1 element, the mean apparent K-d is (8.3 +/- 1.4) x 10(-8) M, and no intermediate species of lower stoichiometries can be detected, We show further that complex formation induces an axial bend of at least 60 degrees in both response elements. These results, taken collectively, demonstrate that p53DBD possesses the ability to direct the formation of a tight nucleoprotein complex having the same 4:1 DNA-binding stoichiometry as wild-type p53 which is accompanied by a substantial conformational change in the response-element DNA, This suggests that the p53DBD may play a role in the tetramerization function of p53, A possible role in this regard is proposed. C1 UNIV NEVADA,DEPT BIOCHEM,RENO,NV 89557. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NIDDKD,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008; Sakamoto, Hiroshi/A-3181-2011; Zambrano, Nicola/B-9352-2014 OI Clore, G. Marius/0000-0003-3809-1027; Zambrano, Nicola/0000-0001-9395-3481 FU NHGRI NIH HHS [1 R55 HG00656-01] NR 43 TC 98 Z9 99 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 SEP 12 PY 1995 VL 92 IS 19 BP 8591 EP 8595 DI 10.1073/pnas.92.19.8591 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900012 PM 7567980 ER PT J AU JOHNSTON, JA BACON, CM FINBLOOM, DS REES, RC KAPLAN, D SHIBUYA, K ORTALDO, JR GUPTA, S CHEN, YQ GIRI, JD OSHEA, JJ AF JOHNSTON, JA BACON, CM FINBLOOM, DS REES, RC KAPLAN, D SHIBUYA, K ORTALDO, JR GUPTA, S CHEN, YQ GIRI, JD OSHEA, JJ TI TYROSINE PHOSPHORYLATION AND ACTIVATION OF STAT5, STAT3, AND JANUS KINASES BY INTERLEUKIN-2 AND INTERLEUKIN-15 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR GAMMA-CHAIN; INTERFERON; PATHWAYS; ELEMENTS AB The cytokines interleukin 2 (IL-2) and IL-15 have similar biological effects on T cells and bind common hematopoietin receptor subunits. Pathways that involve Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have been shown to be important for hematopoietin receptor signaling. In this study we identify the STAT proteins activated by IL-2 and IL-15 in human T cells. IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and STAT5, and DNA-binding complexes containing STAT3 and STAT5 were rapidly activated by these cytokines in T cells. IL 4 induced tyrosine phosphorylation and activation of STAT3 but not STATS. JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. Hence, the JAK and STAT molecules that are activated in response to IL-2 and IL-15 are similar but differ from those induced by IL-4. These observations identify the STAT proteins activated by IL-2 and IL-15 and therefore define signaling pathways by which these T-cell growth factors may regulate gene transcription. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,FREDERICK,MD 21702. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. RP JOHNSTON, JA (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20892, USA. NR 38 TC 262 Z9 264 U1 2 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 SEP 12 PY 1995 VL 92 IS 19 BP 8705 EP 8709 DI 10.1073/pnas.92.19.8705 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900035 PM 7568001 ER PT J AU SMITH, MA MAKINO, S ALTEMUS, M MICHELSON, D HONG, SK KVETNANSKY, R POST, RM AF SMITH, MA MAKINO, S ALTEMUS, M MICHELSON, D HONG, SK KVETNANSKY, R POST, RM TI STRESS AND ANTIDEPRESSANTS DIFFERENTIALLY REGULATE NEUROTROPHIN-3 MESSENGER-RNA EXPRESSION IN THE LOCUS-COERULEUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NERVE GROWTH-FACTOR; HYDROXYLASE MESSENGER-RNA; TYROSINE-HYDROXYLASE; RAT-BRAIN; CERULEUS NEURONS; BIOCHEMICAL MANIFESTATIONS; INSITU HYBRIDIZATION; MOLECULAR-CLONING; FACTOR FAMILY; CYCLIC-AMP AB The mechanisms by which stress and antidepressants exert opposite effects on the course of clinical depression are not known. However, potential candidates might include neurotrophic factors that regulate the development, plasticity, and survival of neurons. To explore this hypothesis, we examined the effects of stress and antidepressants on neurotrophin expression in the locus coeruleus (LC), which modulates many of the behavioral and physiological responses to stress and has been implicated in mood disorders, Using iii situ hybridization, we demonstrate that neurotrophin 3 (NT-3) is expressed in noradrenergic neurons of the LC. Recurrent, but not acute, immobilization stress increased NT-3 mRNA levels in the LC, In contrast, chronic treatment with antidepressants decreased NT-3 mRNA levels. The effect occurred in response to antidepressants that blocked norepinephrine uptake, whereas serotonin-specific reuptake inhibitors did not alter NT-3 levels. Electroconvulsive seizures also decreased NT-3 expression in the LC as well as the hippocampus, Ntrk3 (neurotrophic tyrosine kinase receptor type 3; formerly TrkC), the receptor for NT-3, is expressed in the LC, but its mRNA levels did not change with stress or antidepressant treatments, Because NT-3 is known to be trophic for LC neurons, our results raise the possibility that some of the effects of stress and antidepressants on LC function and plasticity could be mediated through NT-3. Moreover, the coexpression of NT-3 and its receptor in the LC suggests the potential for autocrine mechanisms of action. C1 NIMH,CLIN SCI BRANCHES LAB,BETHESDA,MD 20892. SLOVAK ACAD SCI,INST EXPTL ENDOCRINOL,BRATISLAVA,SLOVAKIA. NR 47 TC 85 Z9 88 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 SEP 12 PY 1995 VL 92 IS 19 BP 8788 EP 8792 DI 10.1073/pnas.92.19.8788 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900052 PM 7568018 ER EF